Mobile monolithic polymer elements for flow control in microfluidic devices

DOEpatents

Hasselbrink, Jr., Ernest F.; Rehm, Jason E [Alameda, CA; Shepodd, Timothy J [Livermore, CA; Kirby, Brian J [San Francisco, CA

2005-11-11

A cast-in-place and lithographically shaped mobile, monolithic polymer element for fluid flow control in microfluidic devices and method of manufacture. Microfluid flow control devices, or microvalves that provide for control of fluid or ionic current flow can be made incorporating a cast-in-place, mobile monolithic polymer element, disposed within a microchannel, and driven by fluid pressure (either liquid or gas) against a retaining or sealing surface. The polymer elements are made by the application of lithographic methods to monomer mixtures formulated in such a way that the polymer will not bond to microchannel walls. The polymer elements can seal against pressures greater than 5000 psi, and have a response time on the order of milliseconds. By the use of energetic radiation it is possible to depolymerize selected regions of the polymer element to form shapes that cannot be produced by conventional lithographic patterning and would be impossible to machine.

Microfluidic devices for stem-cell cultivation, differentiation and toxicity testing

NASA Astrophysics Data System (ADS)

Becker, Holger; Hansen-Hagge, Thomas; Kurtz, Andreas; Mrowka, Ralf; Wölfl, Stefan; Gärtner, Claudia

2017-02-01

The development of new drugs is time-consuming, extremely expensive and often promising drug candidates fail in late stages of the development process due to the lack of suitable tools to either predict toxicological effects or to test drug candidates in physiologically relevant environments prior to clinical tests. We therefore try to develop diagnostic multiorgan microfluidic chips based on patient specific induced pluripotent stem cell (iPS) technology to explore liver dependent toxic effects of drugs on individual human tissues such as liver or kidney cells. Based initially on standardized microfluidic modules for cell culture, we have developed integrated microfluidic devices which contain different chambers for cell/tissue cultivation. The devices are manufactured using injection molding of thermoplastic polymers such as polystyrene or cyclo-olefin polymer. In the project, suitable surface modification methods of the used materials had to be explored. We have been able to successfully demonstrate the seeding, cultivation and further differentiation of modified iPS, as shown by the use of differentiation markers, thus providing a suitable platform for toxicity testing and potential tissue-tissue interactions.

Fabrication of polyimide based microfluidic channels for biosensor devices

NASA Astrophysics Data System (ADS)

Zulfiqar, Azeem; Pfreundt, Andrea; Svendsen, Winnie Edith; Dimaki, Maria

2015-03-01

The ever-increasing complexity of the fabrication process of Point-of-care (POC) devices, due to high demand of functional versatility, compact size and ease-of-use, emphasizes the need of multifunctional materials that can be used to simplify this process. Polymers, currently in use for the fabrication of the often needed microfluidic channels, have limitations in terms of their physicochemical properties. Therefore, the use of a multipurpose biocompatible material with better resistance to the chemical, thermal and electrical environment, along with capability of forming closed channel microfluidics is inevitable. This paper demonstrates a novel technique of fabricating microfluidic devices using polyimide (PI) which fulfills the aforementioned properties criteria. A fabrication process to pattern microfluidic channels, using partially cured PI, has been developed by using a dry etching method. The etching parameters are optimized and compared to those used for fully cured PI. Moreover, the formation of closed microfluidic channel on wafer level by bonding two partially cured PI layers or a partially cured PI to glass with high bond strength has been demonstrated. The reproducibility in uniformity of PI is also compared to the most commonly used SU8 polymer, which is a near UV sensitive epoxy resin. The potential applications of PI processing are POC and biosensor devices integrated with microelectronics.

Evanescent field-based optical fiber sensing device for measuring the refractive index of liquids in microfluidic channels.

PubMed

Polynkin, PaveL; Polynkin, Alexander; Peyghambarian, N; Mansuripur, Masud

2005-06-01

We report a simple optical sensing device capable of measuring the refractive index of liquids propagating in microfluidic channels. The sensor is based on a single-mode optical fiber that is tapered to submicrometer dimensions and immersed in a transparent curable soft polymer. A channel for liquid analyte is created in the immediate vicinity of the taper waist. Light propagating through the tapered section of the fiber extends into the channel, making the optical loss in the system sensitive to the refractive-index difference between the polymer and the liquid. The fabrication process and testing of the prototype sensing devices are described. The sensor can operate both as a highly responsive on-off device and in the continuous measurement mode, with an estimated accuracy of refractive-index measurement of approximately 5 x 10(-4).

High-speed droplet actuation on single-plate electrode arrays.

PubMed

Banerjee, Arghya Narayan; Qian, Shizhi; Joo, Sang Woo

2011-10-15

This paper reports a droplet-based microfluidic device composed of patterned co-planar electrodes in an all-in-a-single-plate arrangement and coated with dielectric layers for electrowetting-on-dielectric (EWOD) actuation of discrete droplets. The co-planar arrangement is preferred over conventional two-plate electrowetting devices because it provides simpler manufacturing process, reduced viscous drag, and easier liquid-handling procedures. These advantages lead to more versatile and efficient microfluidic devices capable of generating higher droplet speed and can incorporate various other droplet manipulation functions into the system for biological, sensing, and other microfluidic applications. We have designed, fabricated, and tested the devices using an insulating layer with materials having relatively high dielectric constant (SiO(2)) and compared the results with polymer coatings (Cytop) with low dielectric constant. Results show that the device with high dielectric layer generates more reproducible droplet transfer over a longer distance with a 25% reduction in the actuation voltage with respect to the polymer coatings, leading to more energy efficient microfluidic applications. We can generate droplet speeds as high as 26 cm/s using materials with high dielectric constant such as SiO(2). Copyright © 2011. Published by Elsevier Inc.

Microfluidics for High School Chemistry Students.

PubMed

Hemling, Melissa; Crooks, John A; Oliver, Piercen M; Brenner, Katie; Gilbertson, Jennifer; Lisensky, George C; Weibel, Douglas B

2014-01-14

We present a laboratory experiment that introduces high school chemistry students to microfluidics while teaching fundamental properties of acid-base chemistry. The procedure enables students to create microfluidic systems using nonspecialized equipment that is available in high school classrooms and reagents that are safe, inexpensive, and commercially available. The experiment is designed to ignite creativity and confidence about experimental design in a high school chemistry class. This experiment requires a computer program (e.g., PowerPoint), Shrinky Dink film, a readily available silicone polymer, weak acids, bases, and a colorimetric pH indicator. Over the span of five 45-min class periods, teams of students design and prepare devices in which two different pH solutions mix in a predictable way to create five different pH solutions. Initial device designs are instructive but rarely optimal. During two additional half-class periods, students have the opportunity to use their initial observations to redesign their microfluidic systems to optimize the outcome. The experiment exposes students to cutting-edge science and the design process, and solidifies introductory chemistry concepts including laminar flow, neutralization of weak acids-bases, and polymers.

Microfluidics for High School Chemistry Students

PubMed Central

Hemling, Melissa; Crooks, John A.; Oliver, Piercen M.; Brenner, Katie; Gilbertson, Jennifer; Lisensky, George C.; Weibel, Douglas B.

2014-01-01

We present a laboratory experiment that introduces high school chemistry students to microfluidics while teaching fundamental properties of acid–base chemistry. The procedure enables students to create microfluidic systems using nonspecialized equipment that is available in high school classrooms and reagents that are safe, inexpensive, and commercially available. The experiment is designed to ignite creativity and confidence about experimental design in a high school chemistry class. This experiment requires a computer program (e.g., PowerPoint), Shrinky Dink film, a readily available silicone polymer, weak acids, bases, and a colorimetric pH indicator. Over the span of five 45-min class periods, teams of students design and prepare devices in which two different pH solutions mix in a predictable way to create five different pH solutions. Initial device designs are instructive but rarely optimal. During two additional half-class periods, students have the opportunity to use their initial observations to redesign their microfluidic systems to optimize the outcome. The experiment exposes students to cutting-edge science and the design process, and solidifies introductory chemistry concepts including laminar flow, neutralization of weak acids–bases, and polymers. PMID:25584013

Batch fabrication of polymer microfluidic cartridges for QCM sensor packaging by direct bonding

NASA Astrophysics Data System (ADS)

Sandström, Niklas; Zandi Shafagh, Reza; Gylfason, Kristinn B.; Haraldsson, Tommy; van der Wijngaart, Wouter

2017-12-01

Quartz crystal microbalance (QCM) sensing is an established technique commonly used in laboratory based life-science applications. However, the relatively complex, multi-part design and multi-step fabrication and assembly of state-of-the-art QCM cartridges make them unsuited for disposable applications such as point-of-care (PoC) diagnostics. In this work, we present the uncomplicated manufacturing of QCMs in polymer microfluidic cartridges. Our novel approach comprises two key innovations: the batch reaction injection molding of microfluidic parts; and the integration of the cartridge components by direct, unassisted bonding. We demonstrate molding of batches of 12 off-stoichiometry thiol-ene epoxy polymer (OSTE+) polymer parts in a single molding cycle using an adapted reaction injection molding process; and the direct bonding of the OSTE+  parts to other OSTE+  substrates, to printed circuit boards, and to QCMs. The microfluidic QCM OSTE+  cartridges were successfully evaluated in terms of liquid sealing as well as electrical properties, and the sensor performance characteristics are on par with those of a commercially available QCM biosensor cartridge. The simplified manufacturing of QCM sensors with maintained performance potentializes novel application areas, e.g. as disposable devices in a point of care setting. Moreover, our results can be extended to simplifying the fabrication of other microfluidic devices with multiple heterogeneously integrated components.

Mobile Monolith Polymer Elements For Flow Control In Microfluidic Systems

DOEpatents

Hasselbrink, Jr., Ernest F.; Rehm, Jason E.; Shepodd, Timothy J.; Kirby, Brian J.

2006-01-24

A cast-in-place and lithographically shaped mobile, monolithic polymer element for fluid flow control in microfluidic devices and method of manufacture. Microfluid flow control devices, or microvalves that provide for control of fluid or ionic current flow can be made incorporating a cast-in-place, mobile monolithic polymer element, disposed within a microchannel, and driven by fluid pressure (either liquid or gas) against a retaining or sealing surface. The polymer elements are made by the application of lithographic methods to monomer mixtures formulated in such a way that the polymer will not bond to microchannel walls. The polymer elements can seal against pressures greater than 5000 psi, and have a response time on the order of milliseconds. By the use of energetic radiation it is possible to depolymerize selected regions of the polymer element to form shapes that cannot be produced by conventional lithographic patterning and would be impossible to machine.

PVDF Sensor Stimulated by Infrared Radiation for Temperature Monitoring in Microfluidic Devices.

PubMed

Pullano, Salvatore A; Mahbub, Ifana; Islam, Syed K; Fiorillo, Antonino S

2017-04-13

This paper presents a ferroelectric polymer-based temperature sensor designed for microfluidic devices. The integration of the sensor into a system-on-a-chip platform facilitates quick monitoring of localized temperature of a biological fluid, avoiding errors in the evaluation of thermal evolution of the fluid during analysis. The contact temperature sensor is fabricated by combining a thin pyroelectric film together with an infrared source, which stimulates the active element located on the top of the microfluidic channel. An experimental setup was assembled to validate the analytical model and to characterize the response rate of the device. The evaluation procedure and the operating range of the temperature also make this device suitable for applications where the localized temperature monitoring of biological samples is necessary. Additionally, ease of integration with standard microfluidic devices makes the proposed sensor an attractive option for in situ analysis of biological fluids.

Design, fabrication and characterization of an arrayable all-polymer microfluidic valve employing highly magnetic rare-earth composite polymer

NASA Astrophysics Data System (ADS)

Rahbar, Mona; Shannon, Lesley; Gray, Bonnie L.

2016-05-01

We present a new magnetically actuated microfluidic valve that employs a highly magnetic composite polymer (M-CP) containing rare-earth hard-magnetic powder for its actuating element and for its valve seat. The M-CP offers much higher magnetization compared to the soft-magnetic, ferrite-based composite polymers typically used in microfluidic applications. Each valve consists of a permanently magnetized M-CP flap and valve seat mounted on a microfluidic channel system fabricated in poly(dimethylsiloxane) (PDMS). Each valve is actuated under a relatively small external magnetic field of 80 mT provided by a small permanent magnet mounted on a miniature linear actuator. The performance of the valve with different flap thicknesses is characterized. In addition, the effect of the magnetic valve seat on the valve’s performance is also characterized. It is experimentally shown that a valve with a 2.3 mm flap thickness, actuated under an 80 mT magnetic field, is capable of completely blocking liquid flow at a flow rate of 1 ml min-1 for pressures up to 9.65 kPa in microfluidic channels 200 μm wide and 200 μm deep. The valve can also be fabricated into an array for flow switching between multiple microfluidic channels under continuous flow conditions. The performance of arrays of valves for flow routing is demonstrated for flow rates up to 5 ml min-1 with larger microfluidic channels of up to 1 mm wide and 500 μm deep. The design of the valves is compatible with other commonly used polymeric microfluidic components, as well as other components that use the same novel permanently magnetic composite polymer, such as our previously reported cilia-based mixing devices.

Irreversible, direct bonding of nanoporous polymer membranes to PDMS or glass microdevices.

PubMed

Aran, Kiana; Sasso, Lawrence A; Kamdar, Neal; Zahn, Jeffrey D

2010-03-07

A method for integrating porous polymer membranes such as polycarbonate, polyethersulfone and polyethylene terephthalate to microfluidic devices is described. The use of 3-aminopropyltriethoxysilane as a chemical crosslinking agent was extended to integrate membranes with PDMS and glass microfluidic channels. A strong, irreversible bond between the membranes and microfluidic structure was achieved. The bonding strength in the APTES treated devices was significantly greater than in devices fabricated using either a PDMS "glue" or two-part epoxy bonding method. Evaluation of a filtering microdevice and the pore structure via SEM indicates the APTES conjugation does not significantly alter the membrane transport function and pore morphology.

Fabrication of advanced particles and particle-based materials assisted by droplet-based microfluidics.

PubMed

Wang, Jing-Tao; Wang, Juan; Han, Jun-Jie

2011-07-04

Recent advances in the fabrication of complex particles and particle-based materials assisted by droplet-based microfluidics are reviewed. Monodisperse particles with expected internal structures, morphologies, and sizes in the range of nanometers to hundreds of micrometers have received a good deal of attention in recent years. Due to the capability of generating monodisperse emulsions and of executing precise control and operations on the suspended droplets inside the microchannels, droplet-based microfluidic devices have become powerful tools for fabricating complex particles with desired properties. Emulsions and multiple-emulsions generated in the microfluidic devices can be composed of a variety of materials including aqueous solutions, gels, polymers and solutions containing functional nanoparticles. They are ideal microreactors or fine templates for synthesizing advanced particles, such as polymer particles, microcapsules, nanocrystals, and photonic crystal clusters or beads by further chemical or physical operations. These particles are promising materials that may be applicable for many fields, such as photonic materials, drug delivery systems, and bio-analysis. From simple to complex, from spherical to nonspherical, from polymerization and reaction crystallization to self-assembly, this review aims to help readers be aware of the many aspects of this field. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Polymer dual ring resonators for label-free optical biosensing using microfluidics.

PubMed

Salleh, Muhammad H M; Glidle, Andrew; Sorel, Marc; Reboud, Julien; Cooper, Jonathan M

2013-04-18

We demonstrate a polymer resonator microfluidic biosensor that overcomes the complex manufacturing procedures required to fabricate traditional devices. In this new format, we show that a gapless light coupling photonic configuration, fabricated in SU8 polymer, can achieve high sensitivity, label-free chemical sensing in solution and high sensitivity biological sensing, at visible wavelengths.

Synthetic microfluidic paper: high surface area and high porosity polymer micropillar arrays.

PubMed

Hansson, Jonas; Yasuga, Hiroki; Haraldsson, Tommy; van der Wijngaart, Wouter

2016-01-21

We introduce Synthetic Microfluidic Paper, a novel porous material for microfluidic applications that consists of an OSTE polymer that is photostructured in a well-controlled geometry of slanted and interlocked micropillars. We demonstrate the distinct benefits of Synthetic Microfluidic Paper over other porous microfluidic materials, such as nitrocellulose, traditional paper and straight micropillar arrays: in contrast to straight micropillar arrays, the geometry of Synthetic Microfluidic Paper was miniaturized without suffering capillary collapse during manufacturing and fluidic operation, resulting in a six-fold increased internal surface area and a three-fold increased porous fraction. Compared to commercial nitrocellulose materials for capillary assays, Synthetic Microfluidic Paper shows a wider range of capillary pumping speed and four times lower device-to-device variation. Compared to the surfaces of the other porous microfluidic materials that are modified by adsorption, Synthetic Microfluidic Paper contains free thiol groups and has been shown to be suitable for covalent surface chemistry, demonstrated here for increasing the material hydrophilicity. These results illustrate the potential of Synthetic Microfluidic Paper as a porous microfluidic material with improved performance characteristics, especially for bioassay applications such as diagnostic tests.

All-polymer photonic sensing platform based on whispering-gallery mode microgoblet lasers.

PubMed

Wienhold, T; Kraemmer, S; Wondimu, S F; Siegle, T; Bog, U; Weinzierl, U; Schmidt, S; Becker, H; Kalt, H; Mappes, T; Koeber, S; Koos, C

2015-09-21

We present an all-polymer photonic sensing platform based on whispering-gallery mode microgoblet lasers integrated into a microfluidic chip. The chip is entirely made from polymers, enabling the use of the devices as low-cost disposables. The microgoblet cavities feature quality factors exceeding 10(5) and are fabricated from poly(methyl methacrylate) (PMMA) using spin-coating, mask-based optical lithography, wet chemical etching, and thermal reflow. In contrast to silica-based microtoroid resonators, this approach replaces technically demanding vacuum-based dry etching and serial laser-based reflow techniques by solution-based processing and parallel thermal reflow. This enables scaling to large-area substrates, and hence significantly reduces device costs. Moreover, the resonators can be fabricated on arbitrary substrate materials, e.g., on transparent and flexible polymer foils. Doping the microgoblets with the organic dye pyrromethene 597 transforms the passive resonators into lasers. Devices have lasing thresholds below 0.6 nJ per pulse and can be efficiently pumped via free-space optics using a compact and low-cost green laser diode. We demonstrate that arrays of microgoblet lasers can be readily integrated into a state-of-the-art microfluidic chip replicated via injection moulding. In a proof-of-principle experiment, we show the viability of the lab-on-a-chip via refractometric sensing, demonstrating a bulk refractive index sensitivity (BRIS) of 10.56 nm per refractive index unit.

Simulation of magnetic active polymers for versatile microfluidic devices

NASA Astrophysics Data System (ADS)

Gusenbauer, Markus; Özelt, Harald; Fischbacher, Johann; Reichel, Franz; Exl, Lukas; Bance, Simon; Kataeva, Nadezhda; Binder, Claudia; Brückl, Hubert; Schrefl, Thomas

2013-01-01

We propose to use a compound of magnetic nanoparticles (20-100 nm) embedded in a flexible polymer (Polydimethylsiloxane PDMS) to filter circulating tumor cells (CTCs). The analysis of CTCs is an emerging tool for cancer biology research and clinical cancer management including the detection, diagnosis and monitoring of cancer. The combination of experiments and simulations lead to a versatile microfluidic lab-on-chip device. Simulations are essential to understand the influence of the embedded nanoparticles in the elastic PDMS when applying a magnetic gradient field. It combines finite element calculations of the polymer, magnetic simulations of the embedded nanoparticles and the fluid dynamic calculations of blood plasma and blood cells. With the use of magnetic active polymers a wide range of tunable microfluidic structures can be created. The method can help to increase the yield of needed isolated CTCs.

Bright conjugated polymer nanoparticles containing a biodegradable shell produced at high yields and with tuneable optical properties by a scalable microfluidic device.

PubMed

Abelha, T F; Phillips, T W; Bannock, J H; Nightingale, A M; Dreiss, C A; Kemal, E; Urbano, L; deMello, J C; Green, M; Dailey, L A

2017-02-02

This study compares the performance of a microfluidic technique and a conventional bulk method to manufacture conjugated polymer nanoparticles (CPNs) embedded within a biodegradable poly(ethylene glycol) methyl ether-block-poly(lactide-co-glycolide) (PEG 5K -PLGA 55K ) matrix. The influence of PEG 5K -PLGA 55K and conjugated polymers cyano-substituted poly(p-phenylene vinylene) (CN-PPV) and poly(9,9-dioctylfluorene-2,1,3-benzothiadiazole) (F8BT) on the physicochemical properties of the CPNs was also evaluated. Both techniques enabled CPN production with high end product yields (∼70-95%). However, while the bulk technique (solvent displacement) under optimal conditions generated small nanoparticles (∼70-100 nm) with similar optical properties (quantum yields ∼35%), the microfluidic approach produced larger CPNs (140-260 nm) with significantly superior quantum yields (49-55%) and tailored emission spectra. CPNs containing CN-PPV showed smaller size distributions and tuneable emission spectra compared to F8BT systems prepared under the same conditions. The presence of PEG 5K -PLGA 55K did not affect the size or optical properties of the CPNs and provided a neutral net electric charge as is often required for biomedical applications. The microfluidics flow-based device was successfully used for the continuous preparation of CPNs over a 24 hour period. On the basis of the results presented here, it can be concluded that the microfluidic device used in this study can be used to optimize the production of bright CPNs with tailored properties with good reproducibility.

Smart monolithic integration of inkjet printed thermal flow sensors with fast prototyping polymer microfluidics

NASA Astrophysics Data System (ADS)

Etxebarria, Ikerne; Elizalde, Jorge; Pacios, Roberto

2016-08-01

There is an increasing demand for built-in flow sensors in order to effectively control microfluidic processes due to the high number of available microfluidic applications. The possible solutions should be inexpensive and easy to connect to both, the microscale features and the macro setup. In this paper, we present a novel approach to integrate a printed thermal flow sensor with polymeric microfluidic channels. This approach is focused on merging two high throughput production processes, namely inkjet printing and fast prototyping technologies, in order to produce trustworthy and low cost devices. These two technologies are brought together to obtain a sensor located outside the microfluidic device. This avoids the critical contact between the sensor material and the fluids through the microchannels that can seriously damage the conducting paths under continuous working regimes. In this way, we ensure reliable and stable operation modes. For this application, a silver nanoparticle based ink and cyclic olefin polymer were used. This flow sensor operates linearly in the range of 0-10 μl min-1 for water and 0-20 μl min-1 for ethanol in calorimetric mode. Switching to anemometric mode, the range can be expanded up to 40 μl min-1.

Additive manufacturing of microfluidic glass chips

NASA Astrophysics Data System (ADS)

Kotz, F.; Helmer, D.; Rapp, B. E.

2018-02-01

Additive manufacturing has gained great interest in the microfluidic community due to the numerous channel designs which can be tested in the early phases of a lab-on-a-chip device development. High resolution additive manufacturing like microstereolithography is largely associated with polymers. Polymers are at a disadvantage compared to other materials due to their softness and low chemical resistance. Whenever high chemical and thermal resistance combined with high optical transparency is needed, glasses become the material of choice. However, glasses are difficult to structure at the microscale requiring hazardous chemicals for etching processes. In this work we present additive manufacturing and high resolution patterning of microfluidic chips in transparent fused silica glass using stereolithography and microlithography. We print an amorphous silica nanocomposite at room temperature using benchtop stereolithography printers and a custom built microlithography system based on a digital mirror device. Using microlithography we printed structures with tens of micron resolution. The printed part is then converted to a transparent fused silica glass using thermal debinding and sintering. Printing of a microfluidic chip can be done within 30 minutes. The heat treatment can be done within two days.

Thermally driven microfluidic pumping via reversible shape memory polymers

NASA Astrophysics Data System (ADS)

Robertson, J. M.; Rodriguez, R. X.; Holmes, L. R., Jr.; Mather, P. T.; Wetzel, E. D.

2016-08-01

The need exists for autonomous microfluidic pumping systems that utilize environmental cues to transport fluid within a network of channels for such purposes as heat distribution, self-healing, or optical reconfiguration. Here, we report on reversible thermally driven microfluidic pumping enabled by two-way shape memory polymers. After developing a suitable shape memory polymer (SMP) through variation in the crosslink density, thin and flexible microfluidic devices were constructed by lamination of plastic films with channels defined by laser-cutting of double-sided adhesive film. SMP blisters integrated into the devices provide thermally driven pumping, while opposing elastic blisters are used to generate backpressure for reversible operation. Thermal cycling of the device was found to drive reversible fluid flow: upon heating to 60 °C, the SMP rapidly contracted to fill the surface channels with a transparent fluid, and upon cooling to 8 °C the flow reversed and the channel re-filled with black ink. Combined with a metallized backing layer, this device results in refection of incident light at high temperatures and absorption of light (at the portions covered with channels) at low temperatures. We discuss power-free, autonomous applications ranging from thermal regulation of structures to thermal indication via color change.

Microfluidic-based screening of resveratrol and drug-loading PLA/Gelatine nano-scaffold for the repair of cartilage defect.

PubMed

Ming, Li; Zhipeng, Yuan; Fei, Yu; Feng, Rao; Jian, Weng; Baoguo, Jiang; Yongqiang, Wen; Peixun, Zhang

2018-03-26

Cartilage defect is common in clinical but notoriously difficult to treat for low regenerative and migratory capacity of chondrocytes. Biodegradable tissue engineering nano-scaffold with a lot of advantages has been the direction of material to repair cartilage defect in recent years. The objective of our study is to establish a biodegradable drug-loading synthetic polymer (PLA) and biopolymer (Gelatine) composite 3D nano-scaffold to support the treatment of cartilage defect. We designed a microfluidic chip-based drug-screening device to select the optimum concentration of resveratrol, which has strong protective capability for chondrocyte. Then biodegradable resveratrol-loading PLA/Gelatine 3D nano-scaffolds were fabricated and used to repair the cartilage defects. As a result, we successfully cultured primary chondrocytes and screened the appropriate concentrations of resveratrol by the microfluidic device. We also smoothly obtained superior biodegradable resveratrol-loading PLA/Gelatine 3D nano-scaffolds and compared the properties and therapeutic effects of cartilage defect in rats. In summary, our microfluidic device is a simple but efficient platform for drug screening and resveratrol-loading PLA/Gelatine 3D nano-scaffolds could greatly promote the cartilage formation. It would be possible for materials and medical researchers to explore individualized pharmacotherapy and drug-loading synthetic polymer and biopolymer composite tissue engineering scaffolds for the repair of cartilage defect in future.

Biomarker detection for disease diagnosis using cost-effective microfluidic platforms.

PubMed

Sanjay, Sharma T; Fu, Guanglei; Dou, Maowei; Xu, Feng; Liu, Rutao; Qi, Hao; Li, XiuJun

2015-11-07

Early and timely detection of disease biomarkers can prevent the spread of infectious diseases, and drastically decrease the death rate of people suffering from different diseases such as cancer and infectious diseases. Because conventional diagnostic methods have limited application in low-resource settings due to the use of bulky and expensive instrumentation, simple and low-cost point-of-care diagnostic devices for timely and early biomarker diagnosis is the need of the hour, especially in rural areas and developing nations. The microfluidics technology possesses remarkable features for simple, low-cost, and rapid disease diagnosis. There have been significant advances in the development of microfluidic platforms for biomarker detection of diseases. This article reviews recent advances in biomarker detection using cost-effective microfluidic devices for disease diagnosis, with the emphasis on infectious disease and cancer diagnosis in low-resource settings. This review first introduces different microfluidic platforms (e.g. polymer and paper-based microfluidics) used for disease diagnosis, with a brief description of their common fabrication techniques. Then, it highlights various detection strategies for disease biomarker detection using microfluidic platforms, including colorimetric, fluorescence, chemiluminescence, electrochemiluminescence (ECL), and electrochemical detection. Finally, it discusses the current limitations of microfluidic devices for disease biomarker detection and future prospects.

Ionic electroactive polymer actuators as active microfluidic mixers

DOE PAGES

Meis, Catherine; Montazami, Reza; Hashemi, Nastaran

2015-11-06

On-chip sample processing is integral to the continued development of lab-on-a-chip devices for various applications. An active microfluidic mixer prototype is proposed using ionic electroactive polymer actuators (IEAPAs) as artificial cilia. A proof-of-concept experiment was performed in which the actuators were shown to produce localized flow pattern disruptions in the laminar flow regime. Suggestions for further engineering and optimization of a scaled-down, complete device are provided. Furthermore, the device in its current state of development necessitates further engineering, the use of IEAPAs addresses issues currently associated with the use of electromechanical actuators as active microfluidic mixers and may prove tomore » be a useful alternative to other similar materials.« less

A simple method of fabricating mask-free microfluidic devices for biological analysis

PubMed Central

Yi, Xin; Kodzius, Rimantas; Gong, Xiuqing; Xiao, Kang; Wen, Weijia

2010-01-01

We report a simple, low-cost, rapid, and mask-free method to fabricate two-dimensional (2D) and three-dimensional (3D) microfluidic chip for biological analysis researches. In this fabrication process, a laser system is used to cut through paper to form intricate patterns and differently configured channels for specific purposes. Bonded with cyanoacrylate-based resin, the prepared paper sheet is sandwiched between glass slides (hydrophilic) or polymer-based plates (hydrophobic) to obtain a multilayer structure. In order to examine the chip’s biocompatibility and applicability, protein concentration was measured while DNA capillary electrophoresis was carried out, and both of them show positive results. With the utilization of direct laser cutting and one-step gas-sacrificing techniques, the whole fabrication processes for complicated 2D and 3D microfluidic devices are shorten into several minutes which make it a good alternative of poly(dimethylsiloxane) microfluidic chips used in biological analysis researches. PMID:20890452

Single nanopore transport of synthetic and biological polyelectrolytes in three-dimensional hybrid microfluidic/nanofluidic devices

DOE PAGES

King, Travis L.; Gatimu, Enid N.; Bohn, Paul W.

2009-01-02

This paper presents a study of electrokinetic transport in single nanopores integrated into vertically-stacked three-dimensional hybrid microfluidic/nanofluidic structures. In these devices single nanopores, created by focused ion beam (FIB) milling in thin polymer films, provide fluidic connection between two vertically separated, perpendicular microfluidic channels. Experiments address both systems in which the nanoporous membrane is composed of the same (homojunction) or different (heterojunction) polymer as the microfluidic channels. These devices are then used to study the electrokinetic transport properties of synthetic (i.e., polystyrene sulfonate and polyallylamine) and biological (i.e.,DNA) polyelectrolytes across these nanopores. Single nanopore transport of polyelectrolytes across these nanoporesmore » using both electrical current measurements and confocal microscopy. Both optical and electrical measurements indicate that electroosmotic transport is predominant over electrophoresis in single nanopores with d > 180 nm, consistent with results obtained under similar conditions for nanocapillary array membranes.« less

Method for forming polymerized microfluidic devices

DOEpatents

Sommer, Gregory J.; Hatch, Anson V.; Wang, Ying-Chih; Singh, Anup K.; Renzi, Ronald F.; Claudnic, Mark R.

2013-03-12

Methods for making a microfluidic device according to embodiments of the present invention include defining.about.cavity. Polymer precursor solution is positioned in the cavity, and exposed to light to begin the polymerization process and define a microchannel. In some embodiments, after the polymerization process is partially complete, a solvent rinse is performed, or fresh polymer precursor introduced into the microchannel. This may promote removal of unpolymerized material from the microchannel and enable smaller feature sizes. The polymer precursor solution may contain an iniferter. Polymerized features therefore may be capped with the iniferter, which is photoactive. The iniferter may aid later binding of a polyacrylamide gel to the microchannel surface.

A microfluidic device for real-time monitoring of Bacillus subtilis bacterial spores during germination based on non-specific physicochemical interactions on the nanoscale level.

PubMed

Zabrocka, L; Langer, K; Michalski, A; Kocik, J; Langer, J J

2015-01-07

A microfluidic device for studies on the germination of bacterial spores (e.g. Bacillus subtilis) based on non-specific interactions on the nanoscale is presented. A decrease in the population of spores during germination followed by the appearance of transition forms and an increase in the number of vegetative cells can be registered directly and simultaneously by using the microfluidic device, which is equipped with a conductive polymer layer (polyaniline) in the form of a nano-network. The lab-on-a-chip-type device, operating in a continuous flow regime, allows monitoring of germination of bacterial spores and analysis of the process in detail. The procedure is fast and accurate enough for quantitative real-time monitoring of the main steps of germination, including final transformation of the spores into vegetative cells. All of this is done without the use of biomarkers or any bio-specific materials, such as enzymes, antibodies and aptamers, and is simply based on an analysis of physicochemical interactions on the nanoscale level.

Flexible fabrication and applications of polymer nanochannels and nanoslits

PubMed Central

Chantiwas, Rattikan; Kim, Byoung Choul; Sunkara, Vijaya; Hwang, Hyundoo

2016-01-01

Fluidic devices that employ nanoscale structures (<100 nm in one or two dimensions, slits or channels, respectively) are generating great interest due to the unique properties afforded by this size domain compared to their micro-scale counterparts. Examples of interesting nanoscale phenomena include the ability to preconcentrate ionic species at extremely high levels due to ion selective migration, unique molecular separation modalities, confined environments to allow biopolymer stretching and elongation and solid-phase bioreactions that are not constrained by mass transport artifacts. Indeed, many examples in the literature have demonstrated these unique opportunities, although predominately using glass, fused silica or silicon as the substrate material. Polymer microfluidics has established itself as an alternative to glass, fused silica, or silicon-based fluidic devices. The primary advantages arising from the use of polymers are the diverse fabrication protocols that can be used to produce the desired structures, the extensive array of physiochemical properties associated with different polymeric materials, and the simple and robust modification strategies that can be employed to alter the substrate's surface chemistry. However, while the strengths of polymer microfluidics is currently being realized, the evolution of polymer-based nanofluidics has only recently been reported. In this critical review, the opportunities afforded by polymer-based nanofluidics will be discussed using both elastomeric and thermoplastic materials. In particular, various fabrication modalities will be discussed along with the nanometre size domains that they can achieve for both elastomer and thermoplastic materials. Different polymer substrates that can be used for nanofluidics will be presented along with comparisons to inorganic nanodevices and the consequences of material differences on the fabrication and operation of nanofluidic devices (257 references). PMID:21442106

Microfluidic electrochemical reactors

DOEpatents

Nuzzo, Ralph G [Champaign, IL; Mitrovski, Svetlana M [Urbana, IL

2011-03-22

A microfluidic electrochemical reactor includes an electrode and one or more microfluidic channels on the electrode, where the microfluidic channels are covered with a membrane containing a gas permeable polymer. The distance between the electrode and the membrane is less than 500 micrometers. The microfluidic electrochemical reactor can provide for increased reaction rates in electrochemical reactions using a gaseous reactant, as compared to conventional electrochemical cells. Microfluidic electrochemical reactors can be incorporated into devices for applications such as fuel cells, electrochemical analysis, microfluidic actuation, pH gradient formation.

Microfluidics in the Undergraduate Laboratory: Device Fabrication and an Experiment to Mimic Intravascular Gas Embolism

ERIC Educational Resources Information Center

Jablonski, Erin L.; Vogel, Brandon M.; Cavanagh, Daniel P.; Beers, Kathryn L.

2010-01-01

A method to fabricate microfluidic devices and an experimental protocol to model intravascular gas embolism for undergraduate laboratories are presented. The fabrication process details how to produce masters on glass slides; these masters serve as molds to pattern channels in an elastomeric polymer that can be adhered to a substrate, resulting in…

Optothermally actuated capillary burst valve

NASA Astrophysics Data System (ADS)

Eriksen, Johan; Bilenberg, Brian; Kristensen, Anders; Marie, Rodolphe

2017-04-01

We demonstrate the optothermal actuation of individual capillary burst valves in an all-polymer microfluidic device. The capillary burst valves are realised in a planar design by introducing a fluidic constriction in a microfluidic channel of constant depth. We show that a capillary burst valve can be burst by raising the temperature due to the temperature dependence of the fluid surface tension. We address individual valves by using a local heating platform based on a thin film of near infrared absorber dye embedded in the lid used to seal the microfluidic device [L. H. Thamdrup et al., Nano Lett. 10, 826-832 (2010)]. An individual valve is burst by focusing the laser in its vicinity. We demonstrate the capture of single polystyrene 7 μm beads in the constriction triggered by the bursting of the valve.

Fabrication of robust tooling for mass production of polymeric microfluidic devices

NASA Astrophysics Data System (ADS)

Fu, G.; Tor, S. B.; Loh, N. H.; Hardt, D. E.

2010-08-01

Polymer microfluidic devices are gaining popularity for bio-applications. In both commonly used methods for the fabrication of polymer microfluidic devices, i.e. injection molding and hot-embossing, the quality of a mold insert is of high importance. Micro powder injection molding (μPIM) provides a suitable option for metal mold insert fabrication. In this paper, two mold inserts with micro-features of different patterns and sizes were produced using 316L stainless steel powder and an in-house binder system. The mold inserts were successfully used to produce cyclic olefin copolymer (COC, trade name TOPAS) micromixer plates with micro-channels of widths 100 µm and 50 µm. Compared with CNC-machined hot work steel mold inserts, the quality of the micro-channels is better as far as geometrical quality and dimensional tolerance are concerned. However, surface finish and flatness of the μPIM mold inserts are inferior to those of CNC-machined mold inserts.

PDMS-co-PVMS Copolymer Synthesis for Microfluidic Devices

NASA Astrophysics Data System (ADS)

Baiamonte, Arissa; Nguyen, Devin; Lwoya, Baraka; Kelly, Giovanni; Albert, Julie N. L.

Poly (dimethylsiloxane) (PDMS) is the predominant material used for the fabrication of microfluidic devices because it is an easily synthesized, biocompatible, and flexible material that forms a good seal with other surfaces. However, PDMS is chemically inert and therefore difficult to functionalize for targeted applications, it can swell in the presence of organic solvents, and it can contaminate microfluidic solutions with unreacted oligomers. Therefore, my research goal is to synthesize random copolymers of PDMS and poly (vinylmethylsiloxane) (PVMS) that retain the benefits of PDMS and can be functionalized easily via thiol-ene click reactions. In the first stage of this work, dichlorodimethylsilane and vinylmethyldichlorosilane were each reacted with water to produce n-membered dimethylsiloxane rings and n-membered vinylmethylsiloxane rings, respectively. In the next step, polymers are synthesized by reacting these rings with potassium hydroxide and heat to form PDMS, PVMS, and PDMS-co-PVMS copolymers. Several reaction conditions have been tested to determine the kinetics and to relate molecular weight of the polymer or copolymer to reaction time. The polymer is then cross-liked through hydroxyl end groups with vinylmethoxysiloxane homopolymer (PVMES) cross-linker, tin catalyst, and heat. Once the polymer is cross-linked, the surface can be modified via thiol-ene click reaction to provide a diversity of surface functionality for microfluidic device applications. In the present work, we functionalize with a fluorinated thiol to impart solvent resistance. Newcomb Tulane College Georges Lurcy Grant, National Academies Gulf Research Program Early Career Research Fellowship, Tulane CIF.

Preparation of Monodisperse Biodegradable Polymer Microparticles Using a Microfluidic Flow-focusing Device for Controlled Drug Delivery

PubMed Central

Xu, Qiaobing; Hashimoto, Michinao; Dang, Tram T.; Hoare, Todd; Kohane, Daniel S.; Whitesides, George M.; Langer, Robert; Anderson, Daniel G.

2009-01-01

Degradable microparticles have broad utility as vehicles for drug delivery and form the basis of several FDA-approved therapies. Conventional emulsion-based methods of manufacturing produce particles with a wide range of diameters (and thus kinetics of release) in each batch. This paper describes the fabrication of monodisperse, drug-loaded microparticles from biodegradable polymers using the microfluidic flow-focusing (FF) devices and the drug delivery properties of those particles. Particles were engineered with defined sizes, ranging from 10 μm to 50 μm. These particles were nearly monodisperse (polydispersity index = 3.9 %). We incorporated a model amphiphilic drug (bupivacaine) within the biodegradable matrix of the particles. Kinetic analysis showed that the release of drug from these monodisperse particles was slower than that from conventional methods of the same average size but a broader distribution of sizes and, most importantly, exhibited a significantly lower initial burst than that observed with conventional particles. The difference in the initial kinetics of drug release was attributed to the uniform distribution of drug inside the particles generated using the microfluidic methods. These results demonstrated the utility of microfluidic FF for the generation of homogenous systems of particles for the delivery of drugs. PMID:19296563

Microfluidic PMMA interfaces for rectangular glass capillaries

NASA Astrophysics Data System (ADS)

Evander, Mikael; Tenje, Maria

2014-02-01

We present the design and fabrication of a polymeric capillary fluidic interface fabricated by micro-milling. The design enables the use of glass capillaries with any kind of cross-section in complex microfluidic setups. We demonstrate two different designs of the interface; a double-inlet interface for hydrodynamic focusing and a capillary interface with integrated pneumatic valves. Both capillary interfaces are presented together with examples of practical applications. This communication shows the design optimization and presents details of the fabrication process. The capillary interface opens up for the use of complex microfluidic systems in single-use glass capillaries. They also enable simple fabrication of glass/polymer hybrid devices that can be beneficial in many research fields where a pure polymer chip negatively affects the device's performance, e.g. acoustofluidics.

Fabrication of zein nanostructure

NASA Astrophysics Data System (ADS)

Luecha, Jarupat

The concerns on the increase of polluting plastic wastes as well as the U.S. dependence on imported petrochemical products have driven an attention towards alternative biodegradable polymers from renewable resources. Zein protein, a co-product from ethanol production from corn, is a good candidate. This research project aims to increase zein value by adopting nanotechnology for fabricating advanced zein packaging films and zein microfluidic devices. Two nanotechnology approaches were focused: the polymer nanoclay nanocomposite technique where the nanocomposite structures were created in the zein matrix, and the soft lithography and the microfluidic devices where the micro and nanopatterns were created on the zein film surfaces. The polymer nanoclay nanocomposite technique was adopted in the commonly used zein film fabrication processes which were solvent casting and extrusion blowing methods. The two methods resulted in partially exfoliated nanocomposite structures. The impact of nanoclays on the physical properties of zein films strongly depended on the film preparation techniques. The impact of nanoclay concentration was more pronounced in the films made by extrusion blowing technique than by the solvent casting technique. As the processability limitation for the extrusion blowing technique of the zein sample containing hight nanoclay content, the effect of the nanoclay content on the rheological properties of zein hybrid resins at linear and nonlinear viscoelastic regions were further investigated. A pristine zein resin exhibited soft solid like behavior. On the other hand, the zein hybrid with nanoclay content greater than 5 wt.% showed more liquid like behavior, suggesting that the nanoclays interrupted the entangled zein network. There was good correspondence between the experimental data and the predictions of the Wagner model for the pristine zein resins. However, the model failed to predict the steady shear properties of the zein nanoclay nanocomposite resins. The soft lithography technique was mainly used to fabricate micro and nanostructures on zein films. Zein material well-replicated small structures with the smallest size at sub micrometer scale that resulted in interesting photonic properties. The bonding method was also developed for assembling portable zein microfluidic devices with small shape distortion. Zein-zein and zein-glass microfluidic devices demonstrated sufficient strength to facilitate fluid flow in a complex microfluidic design with no leakage. Aside from the fabrication technique development, several potential applications of this environmentally friendly microfluidic device were investigated. The concentration gradient manipulation of Rhodamine B solution in zein-glass microfluidic devices was demonstrated. The diffusion of small molecules such as fluorescent dye into the wall of the zein microfluidic channels was observed. However, with this formulation, zein microfluidic devices were not suitable for cell culture applications. This pioneer study covered a wide spectrum of the implementation of the two nanotechnology approaches to advance zein biomaterial which provided proof of fundamental concepts as well as presenting some limitations. The findings in this study can lead to several innovative research opportunities of advanced zein biomaterials with broad applications. The information from the study of zein nanocomposite structure allows the packaging industry to develop the low cost biodegradable materials with physical property improvement. The information from the study of the zein microfluidic devices allows agro-industry to develop the nanotechnology-enabled microfluidic sensors fabricated entirely from biodegradable polymer for on-site disease or contaminant detection in the fields of food and agriculture.

Lipid Microarray Biosensor for Biotoxin Detection.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Singh, Anup K.; Throckmorton, Daniel J.; Moran-Mirabal, Jose C.

2006-05-01

We present the use of micron-sized lipid domains, patterned onto planar substrates and within microfluidic channels, to assay the binding of bacterial toxins via total internal reflection fluorescence microscopy (TIRFM). The lipid domains were patterned using a polymer lift-off technique and consisted of ganglioside-populated DSPC:cholesterol supported lipid bilayers (SLBs). Lipid patterns were formed on the substrates by vesicle fusion followed by polymer lift-off, which revealed micron-sized SLBs containing either ganglioside GT1b or GM1. The ganglioside-populated SLB arrays were then exposed to either Cholera toxin subunit B (CTB) or Tetanus toxin fragment C (TTC). Binding was assayed on planar substrates bymore » TIRFM down to 1 nM concentration for CTB and 100 nM for TTC. Apparent binding constants extracted from three different models applied to the binding curves suggest that binding of a protein to a lipid-based receptor is strongly affected by the lipid composition of the SLB and by the substrate on which the bilayer is formed. Patterning of SLBs inside microfluidic channels also allowed the preparation of lipid domains with different compositions on a single device. Arrays within microfluidic channels were used to achieve segregation and selective binding from a binary mixture of the toxin fragments in one device. The binding and segregation within the microfluidic channels was assayed with epifluorescence as proof of concept. We propose that the method used for patterning the lipid microarrays on planar substrates and within microfluidic channels can be easily adapted to proteins or nucleic acids and can be used for biosensor applications and cell stimulation assays under different flow conditions. KEYWORDS. Microarray, ganglioside, polymer lift-off, cholera toxin, tetanus toxin, TIRFM, binding constant.4« less

Inexpensive, rapid fabrication of polymer-film microfluidic autoregulatory valve for disposable microfluidics.

PubMed

Zhang, Xinjie; Zhu, Zhixian; Ni, Zhonghua; Xiang, Nan; Yi, Hong

2017-06-01

This work presents the fabrication of a microfluidic autoregulatory valve which is composed of several layers of thin polymer films (i.e., polyvinyl chloride (PVC), polyethylene terephthalate (PET) double-sided tape, and polydimethylsiloxane (PDMS)). Briefly, pulsed UV laser is employed to cut the microstructures of through grooves or holes in the thermoplastic polymer films, and then the polymer-film valves are precisely assembled through laminating the PDMS membranes to the thermoplastic polymer films through the roll-lamination method. The effective bonding between the PVC film and the PDMS membrane is realized using the planar seal method, and the valve is sandwiched and compressed by a home-made housing to achieve the good seal effect. Then, the flow performances of the prototype valve are examined, and constant flow autoregulation is realized under the static or dynamic test pressures. The long-term response of the valve is also studied and minimum flow-rate decrements are found over a long actuation time. The fabrication method proposed in this work is successful for the low-cost and fast prototyping of the polymer-film valve. We believe our method will also be broadly applicable for fabrication of other low-cost and disposable polymer-film microfluidic devices.

Differentially photo-crosslinked polymers enable self-assembling microfluidics

PubMed Central

Jamal, Mustapha; Zarafshar, Aasiyeh M.; Gracias, David H.

2012-01-01

An important feature of naturally self-assembled systems such as leaves and tissues is that they are curved and have embedded fluidic channels that enable the transport of nutrients to, or removal of waste from, specific three-dimensional (3D) regions. Here, we report the self-assembly of photopatterned polymers, and consequently microfluidic devices, into curved geometries. We discovered that differentially photo-crosslinked SU-8 films spontaneously and reversibly curved upon film de-solvation and re-solvation. Photolithographic patterning of the SU-8 films enabled the self-assembly of cylinders, cubes, and bidirectionally folded sheets. We integrated polydimethylsiloxane (PDMS) microfluidic channels with these SU-8 films to self-assemble curved microfluidic networks. PMID:22068594

Smart and functional polymer materials for smart and functional microfluidic instruments

NASA Astrophysics Data System (ADS)

Gray, Bonnie L.

2014-04-01

As microfluidic systems evolve from "chip-in-the-lab" to true portable lab-on-a-chip (LoC) or lab-in-a-package (LiP) microinstrumentation, there is a need for increasingly miniaturized sensors, actuators, and integration/interconnect technologies with high levels of functionality and self-direction. Furthermore, as microfluidic instruments are increasingly realized in polymer-based rather than glass- or silicon- based platforms, there is a need to realize these highly functional components in materials that are polymer-compatible. Polymers that are altered to possess basic functionality, and even higher-functioning "smart" polymer materials, may help to realize high-functioning and selfdirecting portable microinstrumentation. Stimuli-responsive hydrogels have been recognized for over a decade as beneficial to the development of smart microfluidics systems and instrumentation. In addition, functional materials such as conductive and magnetic composite polymers are being increasingly employed to push microfluidics systems to greater degrees of functionality, portability, and/or flexibility for wearable/implantable systems. Functional and smart polymer materials can be employed to realize electrodes, electronic routing, heaters, mixers, valves, pumps, sensors, and interconnect structures in polymer-based microfluidic systems. Stimuli for such materials can be located on-chip or in a small package, thus greatly increasing the degree of portability and the potential for mechanical flexibility of such systems. This paper will examine the application of functional polymer materials to the development of high-functioning microfluidics instruments with a goal towards self-direction.

Microwave Dielectric Heating of Drops in Microfluidic Devices†

PubMed Central

Issadore, David; Humphry, Katherine J.; Brown, Keith A.; Sandberg, Lori; Weitz, David; Westervelt, Robert M.

2010-01-01

We present a technique to locally and rapidly heat water drops in microfluidic devices with microwave dielectric heating. Water absorbs microwave power more efficiently than polymers, glass, and oils due to its permanent molecular dipole moment that has a large dielectric loss at GHz frequencies. The relevant heat capacity of the system is a single thermally isolated picoliter drop of water and this enables very fast thermal cycling. We demonstrate microwave dielectric heating in a microfluidic device that integrates a flow-focusing drop maker, drop splitters, and metal electrodes to locally deliver microwave power from an inexpensive, commercially available 3.0 GHz source and amplifier. The temperature of the drops is measured by observing the temperature dependent fluorescence intensity of cadmium selenide nanocrystals suspended in the water drops. We demonstrate characteristic heating times as short as 15 ms to steady-state temperatures as large as 30°C above the base temperature of the microfluidic device. Many common biological and chemical applications require rapid and local control of temperature, such as PCR amplification of DNA, and can benefit from this new technique. PMID:19495453

Monodisperse Polyethylene Glycol Diacrylate Hydrogel Microsphere Formation by Oxygen-Controlled Photopolymerization in a Microfluidic Device

PubMed Central

Krutkramelis, K.; Xia, B.; Oakey, J.

2016-01-01

PEG-based hydrogels have become widely used as drug delivery and tissue scaffolding materials. Common among PEG hydrogel-forming polymers are photopolymerizable acrylates such as polyethylene glycol diacrylate (PEGDA). Microfluidics and microfabrication technologies have recently enabled the miniaturization of PEGDA structures, thus enabling many possible applications for nano- and micro- structured hydrogels. The presence of oxygen, however, dramatically inhibits the photopolymerization of PEGDA, which in turn frustrates hydrogel formation in environments of persistently high oxygen concentration. Using PEGDA that has been emulsified in fluorocarbon oil via microfluidic flow focusing within polydimethylsiloxane (PDMS) devices, we show that polymerization is completely inhibited below critical droplet diameters. By developing an integrated model incorporating reaction kinetics and oxygen diffusion, we demonstrate that the critical droplet diameter is largely determined by the oxygen transport rate, which is dictated by the oxygen saturation concentration of the continuous oil phase. To overcome this fundamental limitation, we present a nitrogen micro-jacketed microfluidic device to reduce oxygen within the droplet, enabling the continuous on-chip photopolymerization of microscale PEGDA particles. PMID:26987384

Development of a real-world direct interface for integrated DNA extraction and amplification in a microfluidic device.

PubMed

Shaw, Kirsty J; Joyce, Domino A; Docker, Peter T; Dyer, Charlotte E; Greenway, Gillian M; Greenman, John; Haswell, Stephen J

2011-02-07

Integrated DNA extraction and amplification have been carried out in a microfluidic device using electro-osmotic pumping (EOP) for fluidic control. All the necessary reagents for performing both DNA extraction and polymerase chain reaction (PCR) amplification were pre-loaded into the microfluidic device following encapsulation in agarose gel. Buccal cells were collected using OmniSwabs [Whatman™, UK] and manually added to a chaotropic binding/lysis solution pre-loaded into the microfluidic device. The released DNA was then adsorbed onto a silica monolith contained within the DNA extraction chamber and the microfluidic device sealed using polymer electrodes. The washing and elution steps for DNA extraction were carried out using EOP, resulting in transfer of the eluted DNA into the PCR chamber. Thermal cycling, achieved using a Peltier element, resulted in amplification of the Amelogenin locus as confirmed using conventional capillary gel electrophoresis. It was demonstrated that the PCR reagents could be stored in the microfluidic device for at least 8 weeks at 4 °C with no significant loss of activity. Such methodology lends itself to the production of 'ready-to-use' microfluidic devices containing all the necessary reagents for sample processing, with many obvious applications in forensics and clinical medicine.

Rapid wasted-free microfluidic fabrication based on ink-jet approach for microfluidic sensing applications

NASA Astrophysics Data System (ADS)

Jarujareet, Ungkarn; Amarit, Rattasart; Sumriddetchkajorn, Sarun

2016-11-01

Realizing that current microfluidic chip fabrication techniques are time consuming and labor intensive as well as always have material leftover after chip fabrication, this research work proposes an innovative approach for rapid microfluidic chip production. The key idea relies on a combination of a widely-used inkjet printing method and a heat-based polymer curing technique with an electronic-mechanical control, thus eliminating the need of masking and molds compared to typical microfluidic fabrication processes. In addition, as the appropriate amount of polymer is utilized during printing, there is much less amount of material wasted. Our inkjet-based microfluidic printer can print out the desired microfluidic chip pattern directly onto a heated glass surface, where the printed polymer is suddenly cured. Our proof-of-concept demonstration for widely-used single-flow channel, Y-junction, and T-junction microfluidic chips shows that the whole microfluidic chip fabrication process requires only 3 steps with a fabrication time of 6 minutes.

A temperature control method for shortening thermal cycling time to achieve rapid polymerase chain reaction (PCR) in a disposable polymer microfluidic device

NASA Astrophysics Data System (ADS)

Bu, Minqiang; Perch-Nielsen, Ivan R.; Sørensen, Karen S.; Skov, Julia; Sun, Yi; Duong Bang, Dang; Pedersen, Michael E.; Hansen, Mikkel F.; Wolff, Anders

2013-07-01

We present a temperature control method capable of effectively shortening the thermal cycling time of polymerase chain reaction (PCR) in a disposable polymer microfluidic device with an external heater and a temperature sensor. The method employs optimized temperature overshooting and undershooting steps to achieve a rapid ramping between the temperature steps for DNA denaturation, annealing and extension. The temperature dynamics within the microfluidic PCR chamber was characterized and the overshooting and undershooting parameters were optimized using the temperature-dependent fluorescence signal from Rhodamine B. The method was validated with the PCR amplification of mecA gene (162 bp) from methicillin-resistant Staphylococcus aureus bacterium (MRSA), where the time for 30 cycles was reduced from 50 min (without over- and undershooting) to 20 min.

Compact electrochemical sensor system and method for field testing for metals in saliva or other fluids

DOEpatents

Lin, Yuehe; Bennett, Wendy D.; Timchalk, Charles; Thrall, Karla D.

2004-03-02

Microanalytical systems based on a microfluidics/electrochemical detection scheme are described. Individual modules, such as microfabricated piezoelectrically actuated pumps and a microelectrochemical cell were integrated onto portable platforms. This allowed rapid change-out and repair of individual components by incorporating "plug and play" concepts now standard in PC's. Different integration schemes were used for construction of the microanalytical systems based on microfluidics/electrochemical detection. In one scheme, all individual modules were integrated in the surface of the standard microfluidic platform based on a plug-and-play design. Microelectrochemical flow cell which integrated three electrodes based on a wall-jet design was fabricated on polymer substrate. The microelectrochemical flow cell was then plugged directly into the microfluidic platform. Another integration scheme was based on a multilayer lamination method utilizing stacking modules with different functionality to achieve a compact microanalytical device. Application of the microanalytical system for detection of lead in, for example, river water and saliva samples using stripping voltammetry is described.

Design and fabrication of a multilayered polymer microfluidic chip with nanofluidic interconnects via adhesive contact printing.

PubMed

Flachsbart, Bruce R; Wong, Kachuen; Iannacone, Jamie M; Abante, Edward N; Vlach, Robert L; Rauchfuss, Peter A; Bohn, Paul W; Sweedler, Jonathan V; Shannon, Mark A

2006-05-01

The design and fabrication of a multilayered polymer micro-nanofluidic chip is described that consists of poly(methylmethacrylate) (PMMA) layers that contain microfluidic channels separated in the vertical direction by polycarbonate (PC) membranes that incorporate an array of nanometre diameter cylindrical pores. The materials are optically transparent to allow inspection of the fluids within the channels in the near UV and visible spectrum. The design architecture enables nanofluidic interconnections to be placed in the vertical direction between microfluidic channels. Such an architecture allows microchannel separations within the chip, as well as allowing unique operations that utilize nanocapillary interconnects: the separation of analytes based on molecular size, channel isolation, enhanced mixing, and sample concentration. Device fabrication is made possible by a transfer process of labile membranes and the development of a contact printing method for a thermally curable epoxy based adhesive. This adhesive is shown to have bond strengths that prevent leakage and delamination and channel rupture tests exceed 6 atm (0.6 MPa) under applied pressure. Channels 100 microm in width and 20 microm in depth are contact printed without the adhesive entering the microchannel. The chip is characterized in terms of resistivity measurements along the microfluidic channels, electroosmotic flow (EOF) measurements at different pH values and laser-induced-fluorescence (LIF) detection of green-fluorescent protein (GFP) plugs injected across the nanocapillary membrane and into a microfluidic channel. The results indicate that the mixed polymer micro-nanofluidic multilayer chip has electrical characteristics needed for use in microanalytical systems.

Fabrication of microfluidic architectures for optimal flow rate and concentration measurement for lab on chip application

NASA Astrophysics Data System (ADS)

Adam, Tijjani; Hashim, U.

2017-03-01

Optimum flow in micro channel for sensing purpose is challenging. In this study, The optimizations of the fluid sample flows are made through the design and characterization of the novel microfluidics' architectures to achieve the optimal flow rate in the micro channels. The biocompatibility of the Polydimetylsiloxane (Sylgard 184 silicon elastomer) polymer used to fabricate the device offers avenue for the device to be implemented as the universal fluidic delivery system for bio-molecules sensing in various bio-medical applications. The study uses the following methodological approaches, designing a novel microfluidics' architectures by integrating the devices on a single 4 inches silicon substrate, fabricating the designed microfluidic devices using low-cost solution soft lithography technique, characterizing and validating the flow throughput of urine samples in the micro channels by generating pressure gradients through the devices' inlets. The characterization on the urine samples flow in the micro channels have witnessed the constant flow throughout the devices.

Development of a Pressure Switched Microfluidic Cell Sorter

NASA Astrophysics Data System (ADS)

Ozbay, Baris; Jones, Alex; Gibson, Emily

2009-10-01

Lab on a chip technology allows for the replacement of traditional cell sorters with microfluidic devices which can be produced less expensively and are more compact. Additionally, the compact nature of microfluidic cell sorters may lead to the realization of their application in point-of-care medical devices. Though techniques have been demonstrated previously for sorting in microfluidic devices with optical or electro-osmotic switching, both of these techniques are expensive and more difficult to implement than pressure switching. This microfluidic cell sorter design also allows for easy integration with optical spectroscopy for identification of cell type. Our current microfluidic device was fabricated with polydimethylsiloxane (PDMS), a polymer that houses the channels, which is then chemically bonded to a glass slide. The flow of fluid through the device is controlled by pressure controllers, and the switching of the cells is accomplished with the use of a high performance pressure controller interfaced with a computer. The cells are fed through the channels with the use of hydrodynamic focusing techniques. Once the experimental setup is fully functional the objective will be to determine switching rates, explore techniques to optimize these rates, and experiment with sorting of other biomolecules including DNA.

Rapid and cheap prototyping of a microfluidic cell sorter.

PubMed

Islam, M Z; McMullin, J N; Tsui, Y Y

2011-05-01

Development of a microfluidic device is generally based on fabrication-design-fabrication loop, as, unlike the microelectronics design, there is no rigorous simulation-based verification of the chip before fabrication. This usually results in extremely long, and hence expensive, product development cycle if micro/nano fabrication facilities are used from the beginning of the cycle. Here, we illustrate a novel approach of device prototyping that is fast, cheap, reliable, and most importantly, this technique can be adopted even if no state-of-the-art microfabrication facility is available. A water-jet machine is used to cut the desired microfluidic channels into a thin steel plate which is then used as a template to cut the channels into a thin sheet of a transparent and cheap polymer material named Surlyn® by using a Hot Knife™. The feature-inscribed Surlyn sheet is bonded in between two microscope glass slides by utilizing the techniques which has been being used in curing polymer film between dual layer automotive glasses for years. Optical fibers are inserted from the sides of chip and are bonded by UV epoxy. To study the applicability of this prototyping approach, we made a basic microfluidic sorter and tested its functionalities. Sample containing microparticles is injected into the chip. Light from a 532-nm diode laser is coupled into the optical fiber that delivers light to the interrogation region in the channel. The emitted light from the particle is collected by a photodiode (PD) placed over the detection window. The device sorts the particles into the sorted or waste outlets depending on the level of the PD signal. We used fluorescent latex beads to test the detection and sorting functionalities of the device. We found that the system could detect all the beads that passed through its geometric observation region and could sort almost all the beads it detected. Copyright © 2011 International Society for Advancement of Cytometry.

Laser-bulge based ultrasonic bonding method for fabricating multilayer thermoplastic microfluidic devices

NASA Astrophysics Data System (ADS)

Liang, Chao; Liu, Chong; Liu, Ziyang; Meng, Fanjian; Li, Jingmin

2017-11-01

Ultrasonic bonding is a commonly-used method for fabrication of thermoplastic microfluidic devices. However, due to the existence of the energy director (a convex structure to concentrate the ultrasonic energy), it is difficult to control its molten polymer flow, which may result in a small gap between the bonding interface or microchannel clogging. In this paper, we present an approach to address these issues. Firstly, the microchannels were patterned onto the PMMA sheets using hot embossing with the wire electrical discharge machined molds. Then, a small bulge, which was formed at the edge of the laser-ablated groove (LG), was generated around the microchannel using a CO2 laser ablation system. By using the bulge to concentrate the ultrasonic energy, there was no need for fabricating the complicated and customized energy director. When the bulge was melted, it was able to flow into the LG which overcame the ‘gap’ and ‘clogging’ problems. Here, two types of two-layer microfluidic devices and a five-layer micromixer were fabricated to validate its performance. Our results showed that these thermoplastic microdevices can be successfully bonded by using this method. The liquid leakage was not observed in both the capillary-driven flowing test and the pressure-driven mixing experiments. It is a potential method for bonding the thermoplastic microfluidic devices.

Rapid prototyping of microchannels with surface patterns for fabrication of polymer fibers

DOE PAGES

Goodrich, Payton J.; Sharifi, Farrokh; Hashemi, Nastaran

2015-08-14

Microfluidic technology has provided innovative solutions to numerous problems, but the cost of designing and fabricating microfluidic channels is impeding its expansion. In this study, Shrinky-Dink thermoplastic sheets are used to create multilayered complex templates for microfluidic channels. We also used inkjet and laserjet printers to raise a predetermined microchannel geometry by depositing several layers of ink for each feature consecutively. We achieved feature heights over 100 μm, which were measured and compared with surface profilometry. Templates closest to the target geometry were then used to create microfluidic devices from soft-lithography with the molds as a template. These microfluidic devicesmore » were, futhermore used to fabricate polymer microfibers using the microfluidic focusing approach to demonstrate the potential that this process has for microfluidic applications. Finally, an economic analysis was conducted to compare the price of common microfluidic template manufacturing methods. We showed that multilayer microchannels can be created significantly quicker and cheaper than current methods for design prototyping and point-of-care applications in the biomedical area.« less

Microfluidic Cell-based Assays in Stem Cell and Other Rare Cell Type Research

DOE PAGES

Wu, Meiye

2015-03-23

Microfluidics is a technology defined by the engineered precise manipulation of minute amount of liquids through channels with dimensions in the micron scale. Much of microfluidic devices used for biomedical purposes are produced in the form of so called “lab-on-a-chip” format, where multiple steps of conventional biochemical analyses such as staining, washing, and signal collection are miniaturized and integrated into chips fabricated from polymer or glass. Cell-based microfluidic lab-on-achip technology provides some obvious advantages: 1) drastically reduced sample and reagent requirement, and 2) separation and detection with improved sensitivity due to fluid properties at the microscale, i.e. laminar flow. Basedmore » on these two advantages, the obvious place where microfluidic cell assays will provide the most benefit is wherescientists must gather much information from precious little sample. Stem cells and other precious cell types such as circulating tumor cells (CTCs), and rare immune subsets are the perfect match for microfluidic multiplex assays. The recent demonstration that multiple cellular changes such as surface receptor activation, protein translocation, long and short RNA, and DNA changes can all be extracted from intact single cells paves the way to systems level understanding of cellular states during development or disease. Finally, with the ability to preserve cell integrity in a microfluidic device during multiplexed analysis, one also preserves the single cell resolution, where information regarding the cell-to-cell heterogeneity during differentiation or response to stimuli is vitally important.« less

Optimal Control of Objects on the Micro- and Nano-Scale by Electrokinetic and Electromagnetic Manipulation: for Bio-Sample Preparation, Quantum Information Devices and Magnetic Drug Delivery

DTIC Science & Technology

2010-01-01

property variations. The system described here is a simple 4-electrode microfluidic device made of polydimethylsiloxane PDMS [50-53] which is reversibly...through the fluid and heat it.) A more detailed description and analysis of the physics of electroosmotic actuation can be found in [46, 83] In...a control algorithm on a standard personal computer. The micro-fluidic device is made out of a soft polymer ( polydimethylsiloxane (PDMS)) and is

A modular microfluidic platform for the synthesis of biopolymeric nanoparticles entrapping organic actives

NASA Astrophysics Data System (ADS)

Chronopoulou, Laura; Sparago, Carolina; Palocci, Cleofe

2014-11-01

Using a novel and versatile capillary microfluidic flow-focusing device we fabricated monodisperse drug-loaded nanoparticles from biodegradable polymers. A model amphiphilic drug (dexamethasone) was incorporated within the biodegradable matrix of the particles. The influence of flow rate ratio, polymer concentration, and microreactor-focusing channel dimensions on nanoparticles' size and drug loading has been investigated. The microfluidic approach resulted in the production of colloidal polymeric nanoparticles with a narrow size distribution (diameters ranging between 35 and 350 nm) and useful morphological characteristics. This technique allows the fast, low cost, easy, and automated synthesis of polymeric nanoparticles, therefore it may become a useful approach in the progression from laboratory scale to pilot-line scale processes.

High-sensitivity microfluidic calorimeters for biological and chemical applications.

PubMed

Lee, Wonhee; Fon, Warren; Axelrod, Blake W; Roukes, Michael L

2009-09-08

High-sensitivity microfluidic calorimeters raise the prospect of achieving high-throughput biochemical measurements with minimal sample consumption. However, it has been challenging to realize microchip-based calorimeters possessing both high sensitivity and precise sample-manipulation capabilities. Here, we report chip-based microfluidic calorimeters capable of characterizing the heat of reaction of 3.5-nL samples with 4.2-nW resolution. Our approach, based on a combination of hard- and soft-polymer microfluidics, provides both exceptional thermal response and the physical strength necessary to construct high-sensitivity calorimeters that can be scaled to automated, highly multiplexed array architectures. Polydimethylsiloxane microfluidic valves and pumps are interfaced to parylene channels and reaction chambers to automate the injection of analyte at 1 nL and below. We attained excellent thermal resolution via on-chip vacuum encapsulation, which provides unprecedented thermal isolation of the minute microfluidic reaction chambers. We demonstrate performance of these calorimeters by resolving measurements of the heat of reaction of urea hydrolysis and the enthalpy of mixing of water with methanol. The device structure can be adapted easily to enable a wide variety of other standard calorimeter operations; one example, a flow calorimeter, is described.

Comparison of roll-to-roll replication approaches for microfluidic and optical functions in lab-on-a-chip diagnostic devices

NASA Astrophysics Data System (ADS)

Brecher, Christian; Baum, Christoph; Bastuck, Thomas

2015-03-01

Economically advantageous microfabrication technologies for lab-on-a-chip diagnostic devices substituting commonly used glass etching or injection molding processes are one of the key enablers for the emerging market of microfluidic devices. On-site detection in fields of life sciences, point of care diagnostics and environmental analysis requires compact, disposable and highly functionalized systems. Roll-to-roll production as a high volume process has become the emerging fabrication technology for integrated, complex high technology products within recent years (e.g. fuel cells). Differently functionalized polymer films enable researchers to create a new generation of lab-on-a-chip devices by combining electronic, microfluidic and optical functions in multilayer architecture. For replication of microfluidic and optical functions via roll-to-roll production process competitive approaches are available. One of them is to imprint fluidic channels and optical structures of micro- or nanometer scale from embossing rollers into ultraviolet (UV) curable lacquers on polymer substrates. Depending on dimension, shape and quantity of those structures there are alternative manufacturing technologies for the embossing roller. Ultra-precise diamond turning, electroforming or casting polymer materials are used either for direct structuring or manufacturing of roller sleeves. Mastering methods are selected for application considering replication quality required and structure complexity. Criteria for the replication quality are surface roughness and contour accuracy. Structure complexity is evaluated by shapes producible (e.g. linear, circular) and aspect ratio. Costs for the mastering process and structure lifetime are major cost factors. The alternative replication approaches are introduced and analyzed corresponding to the criteria presented. Advantages and drawbacks of each technology are discussed and exemplary applications are presented.

Protein patterning in polycarbonate microfluidic channels

NASA Astrophysics Data System (ADS)

Thomson, David A.; Hayes, Jason P.; Thissen, Helmut

2004-03-01

In this work protein patterning has been achieved within a polycarbonate microfluidic device. Channel structures were first coated with plasma polymerized allylamine (ALAPP) followed by the "cloud point" deposition of polyethylene oxide (PEO), a protein repellent molecule. Excimer laser micromachining was used to pattern the PEO to control protein localization. Subsequent removal of a sacrificial layer of polycarbonate resulted in the patterned polymer coating only in the channels of a simple fluidic device. Following a final diffusion bonding fabrication step the devices were filled with a buffer containing Streptavidin conjugated with fluorescein, and visualized under a confocal fluorescent microscope. This confirmed that protein adhesion occurred only in laser patterned areas. The ability to control protein adhesion in microfludic channels leads to the possibility of generating arrays of proteins or cells within polymer microfludics for cheap automated biosensors and synthesis systems.

Targeted cell adhesion on selectively micropatterned polymer arrays on a poly(dimethylsiloxane) surface.

PubMed

Tang, Linzhi; Min, Junhong; Lee, Eun-Cheol; Kim, Jong Sung; Lee, Nae Yoon

2010-02-01

Herein, we introduce the fabrication of polymer micropattern arrays on a chemically inert poly(dimethylsiloxane) (PDMS) surface and employ them for the selective adhesion of cells. To fabricate the micropattern arrays, a mercapto-ester-based photocurable adhesive was coated onto a mercaptosilane-coated PDMS surface and photopolymerized using a photomask to obtain patterned arrays at the microscale level. Robust polymer patterns, 380 microm in diameter, were successfully fabricated onto a PDMS surface, and cells were selectively targeted toward the patterned regions. Next, the performance of the cell adhesion was observed by anchoring cell adhesive linker, an RGD oligopeptide, on the surface of the mercapto-ester-based adhesive-cured layer. The successful anchoring of the RGD linker was confirmed through various surface characterizations such as water contact angle measurement, XPS analysis, FT-IR analysis, and AFM measurement. The micropatterning of a photocurable adhesive onto a PDMS surface can provide high structural rigidity, a highly-adhesive surface, and a physical pathway for selective cell adhesion, while the incorporated polymer micropattern arrays inside a PDMS microfluidic device can serve as a microfluidic platform for disease diagnoses and high-throughput drug screening.

Nature-inspired polymer actuators for micro-fluidic mixing.

NASA Astrophysics Data System (ADS)

den Toonder, Jaap M. J.; Bos, Femke; de Goede, Judith; Anderson, Patrick

2007-11-01

One particular micro-fluidics manipulation mechanism ``designed'' by nature is that due to a covering of beating cilia over the external surface of micro-organisms (e.g. Paramecium). A cilium can be viewed as a small hair or flexible rod (in protozoa: typical length 10 microns and diameter 0.1 microns) which is attached to the surface. We have developed polymer micro-actuators, made with standard micro-technology processing, which respond to an applied electrical or magnetic field by changing their shape. The shape and size of the polymer actuators mimics that of cilia occurring in nature. Flow visualization experiments show that the cilia can generate substantial fluid velocities, in the order of 1 mm/s. In addition, using specially designed geometrical configurations of the cilia, very efficient mixing is obtained. Since the artificial cilia can be actively controlled using electrical signals, they have exciting applications in micro-fluidic devices.

Recent developments in microfluidics-based chemotaxis studies.

PubMed

Wu, Jiandong; Wu, Xun; Lin, Francis

2013-07-07

Microfluidic devices can better control cellular microenvironments compared to conventional cell migration assays. Over the past few years, microfluidics-based chemotaxis studies showed a rapid growth. New strategies were developed to explore cell migration in manipulated chemical gradients. In addition to expanding the use of microfluidic devices for a broader range of cell types, microfluidic devices were used to study cell migration and chemotaxis in complex environments. Furthermore, high-throughput microfluidic chemotaxis devices and integrated microfluidic chemotaxis systems were developed for medical and commercial applications. In this article, we review recent developments in microfluidics-based chemotaxis studies and discuss the new trends in this field observed over the past few years.

Photopatterned materials in bioanalytical microfluidic technology

PubMed Central

Tentori, Augusto M.; Herr, Amy E.

2011-01-01

Microfluidic technologies are playing an increasingly important role in biological inquiry. Sophisticated approaches to the microanalysis of biological specimens rely, in part, on the fine fluid and material control offered by microtechnology, as well as a sufficient capacity for systems integration. A suite of techniques that utilize photopatterning of polymers on fluidic surfaces, within fluidic volumes, and as primary device structures underpins recent technological innovation in bioanalysis. Well-characterized photopatterning approaches enable previously fabricated or commercially fabricated devices to be customized by the user in a straight-forward manner, making the tools accessible to laboratories that do not focus on microfabrication technology innovation. In this review of recent advances, we summarize reported microfluidic devices with photopatterned structures and regions as platforms for a diverse set of biological measurements and assays. PMID:21857772

Polymer microfluidic device replacing fluids using only capillary force

NASA Astrophysics Data System (ADS)

Chung, Kwang Hyo; Lee, Dae Sik; Yang, Haesik; Kim, Sung Jin; Pyo, Hyun Bong

2005-02-01

A novel polymer microfluidic device for self-wash using only capillary force is presented. A liquid filled in a reaction chamber is replaced by another liquid with no external actuation. All the fluidic actuations in the device is pre-programmed about time and sequence, and accomplished by capillary force naturally. Careful design is necessary for exact actions. The fluidic conduits were designed by the newly derived theoretical equations about the capillary stop pressure and flow time. Simulations using CFD-ACE+ were conducted to check the validity of theory and the performance of the chip. These analytic results were consistent with experimental ones. The chip was made of polymers for the purpose of single use and low price. It was fabricated by sealing the hot-embossed PMMA substrate with a PET film. For simpler fabrication, the chip was of a single height. The embossing master was produced from a nickel-electroplating on a SU8-patterned Ni-plate followed by CMP. The contact angles of liquids on substrates were manipulated through the mixing of surfactants, and the temporal variations were monitored for a more exact design. The real actuation steps in experiment revealed the stable performance of selfwash, and coincided well with the designed ones. The presented microfluidic method can be applicable to other LOCs of special purposes through simple modification. For example, array or serial types would be possible for multiple selfwashes.

Microfluidic paper-based biomolecule preconcentrator based on ion concentration polarization.

PubMed

Han, Sung Il; Hwang, Kyo Seon; Kwak, Rhokyun; Lee, Jeong Hoon

2016-06-21

Microfluidic paper-based analytical devices (μPADs) for molecular detection have great potential in the field of point-of-care diagnostics. Currently, a critical problem being faced by μPADs is improving their detection sensitivity. Various preconcentration processes have been developed, but they still have complicated structures and fabrication processes to integrate into μPADs. To address this issue, we have developed a novel paper-based preconcentrator utilizing ion concentration polarization (ICP) with minimal addition on lateral-flow paper. The cation selective membrane (i.e., Nafion) is patterned on adhesive tape, and this tape is then attached to paper-based channels. When an electric field is applied across the Nafion, ICP is initiated to preconcentrate the biomolecules in the paper channel. Departing from previous paper-based preconcentrators, we maintain steady lateral fluid flow with the separated Nafion layer; as a result, fluorescent dyes and proteins (FITC-albumin and bovine serum albumin) are continuously delivered to the preconcentration zone, achieving high preconcentration performance up to 1000-fold. In addition, we demonstrate that the Nafion-patterned tape can be integrated with various geometries (multiplexed preconcentrator) and platforms (string and polymer microfluidic channel). This work would facilitate integration of various ICP devices, including preconcentrators, pH/concentration modulators, and micro mixers, with steady lateral flows in paper-based platforms.

A fluorescence-based centrifugal microfluidic system for parallel detection of multiple allergens

NASA Astrophysics Data System (ADS)

Chen, Q. L.; Ho, H. P.; Cheung, K. L.; Kong, S. K.; Suen, Y. K.; Kwan, Y. W.; Li, W. J.; Wong, C. K.

2010-02-01

This paper reports a robust polymer based centrifugal microfluidic analysis system that can provide parallel detection of multiple allergens in vitro. Many commercial food products (milk, bean, pollen, etc.) may introduce allergy to people. A low-cost device for rapid detection of allergens is highly desirable. With this as the objective, we have studied the feasibility of using a rotating disk device incorporating centrifugal microfluidics for performing actuationfree and multi-analyte detection of different allergen species with minimum sample usage and fast response time. Degranulation in basophils or mast cells is an indicator to demonstrate allergic reaction. In this connection, we used acridine orange (AO) to demonstrate degranulation in KU812 human basophils. It was found that the AO was released from granules when cells were stimulated by ionomycin, thus signifying the release of histamine which accounts for allergy symptoms [1-2]. Within this rotating optical platform, major microfluidic components including sample reservoirs, reaction chambers, microchannel and flow-control compartments are integrated into a single bio-compatible polydimethylsiloxane (PDMS) substrate. The flow sequence and reaction time can be controlled precisely. Sequentially through varying the spinning speed, the disk may perform a variety of steps on sample loading, reaction and detection. Our work demonstrates the feasibility of using centrifugation as a possible immunoassay system in the future.

Femtosecond laser direct-write of optofluidics in polymer-coated optical fiber

NASA Astrophysics Data System (ADS)

Joseph, Kevin A. J.; Haque, Moez; Ho, Stephen; Aitchison, J. Stewart; Herman, Peter R.

2017-03-01

Multifunctional lab in fiber technology seeks to translate the accomplishments of optofluidic, lab on chip devices into silica fibers. a robust, flexible, and ubiquitous optical communication platform that can underpin the `Internet of Things' with distributed sensors, or enable lab on chip functions deep inside our bodies. Femtosecond lasers have driven significant advances in three-dimensional processing, enabling optical circuits, microfluidics, and micro-mechanical structures to be formed around the core of the fiber. However, such processing typically requires the stripping and recoating of the polymer buffer or jacket, increasing processing time and mechanically weakening the device. This paper reports on a comprehensive assessment of laser damage in urethane-acrylate-coated fiber. The results show a sufficient processing window is available for femtosecond laser processing of the fiber without damaging the polymer jacket. The fiber core, cladding, and buffer could be simultaneously processed without removal of the buffer jacket. Three-dimensional lab in fiber devices were successfully fabricated by distortion-free immersionlens focusing, presenting fiber-cladding optical circuits and progress towards chemically-etched channels, microfluidic cavities, and MEMS structure inside buffer-coated fiber.

Fully solution-processed organic light-emitting electrochemical cells (OLEC) with inkjet-printed micro-lenses for disposable lab-on-chip applications at ambient conditions

NASA Astrophysics Data System (ADS)

Shu, Zhe; Pabst, Oliver; Beckert, Erik; Eberhardt, Ramona; Tünnermann, Andreas

2016-02-01

Microfluidic lab-on-chip devices can be used for chemical and biological analyses such as DNA tests or environmental monitoring. Such devices integrate most of the basic functionalities needed for scientific analysis on a microfluidic chip. When using such devices, cost and space-intensive lab equipment is no longer necessary. However, in order to make a monolithic and cost-efficient/disposable microfluidic sensing device, direct integration of the excitation light source for fluorescent sensing is often required. To achieve this, we introduce a fully solution processable deviation of OLEDs, organic light-emitting electrochemical cells (OLECs), as a low-cost excitation light source for a disposable microfluidic sensing platform. By mixing metal ions and a solid electrolyte with light-emitting polymers as active materials, an in-situ doping and in-situ PN-junction can be generated within a three layer sandwich device. Thanks to this doping effect, work function adaptation is not necessary and air-stable electrode can be used. An ambient manufacturing process for fully solution-processed OLECs is presented, which consist of a spin-coated blue light-emitting polymer plus dopants on an ITO cathode and an inkjet-printed PEDOT:PSS transparent top anode. A fully transparent blue OLEC is able to obtain light intensity > 2500 cd/m2 under pulsed driving mode and maintain stable after 1000 cycles, which fulfils requirements for simple fluorescent on-chip sensing applications. However, because of the large refractive index difference between substrates and air, about 80% of emitted light is trapped inside the device. Therefore, inkjet printed micro-lenses on the rear side are introduced here to further increase light-emitting brightness.

Microfluidic systems with ion-selective membranes.

PubMed

Slouka, Zdenek; Senapati, Satyajyoti; Chang, Hsueh-Chia

2014-01-01

When integrated into microfluidic chips, ion-selective nanoporous polymer and solid-state membranes can be used for on-chip pumping, pH actuation, analyte concentration, molecular separation, reactive mixing, and molecular sensing. They offer numerous functionalities and are hence superior to paper-based devices for point-of-care biochips, with only slightly more investment in fabrication and material costs required. In this review, we first discuss the fundamentals of several nonequilibrium ion current phenomena associated with ion-selective membranes, many of them revealed by studies with fabricated single nanochannels/nanopores. We then focus on how the plethora of phenomena has been applied for transport, separation, concentration, and detection of biomolecules on biochips.

Microfluidic Systems with Ion-Selective Membranes

NASA Astrophysics Data System (ADS)

Slouka, Zdenek; Senapati, Satyajyoti; Chang, Hsueh-Chia

2014-06-01

When integrated into microfluidic chips, ion-selective nanoporous polymer and solid-state membranes can be used for on-chip pumping, pH actuation, analyte concentration, molecular separation, reactive mixing, and molecular sensing. They offer numerous functionalities and are hence superior to paper-based devices for point-of-care biochips, with only slightly more investment in fabrication and material costs required. In this review, we first discuss the fundamentals of several nonequilibrium ion current phenomena associated with ion-selective membranes, many of them revealed by studies with fabricated single nanochannels/nanopores. We then focus on how the plethora of phenomena has been applied for transport, separation, concentration, and detection of biomolecules on biochips.

Chromatographic Separation and Visual Detection on Wicking Microfluidic Devices: Quantitation of Cu2+ in Surface, Ground, and Drinking Water.

PubMed

Bandara, Gayan C; Heist, Christopher A; Remcho, Vincent T

2018-02-20

Copper is widely applied in industrial and technological applications and is an essential micronutrient for humans and animals. However, exposure to high environmental levels of copper, especially through drinking water, can lead to copper toxicity, resulting in severe acute and chronic health effects. Therefore, regular monitoring of aqueous copper ions has become necessary as recent anthropogenic activities have led to elevated environmental concentrations of copper. On-site monitoring processes require an inexpensive, simple, and portable analytical approach capable of generating reliable qualitative and quantitative data efficiently. Membrane-based lateral flow microfluidic devices are ideal candidates as they facilitate rapid, inexpensive, and portable measurements. Here we present a simple, chromatographic separation approach in combination with a visual detection method for Cu 2+ quantitation, performed in a lateral flow microfluidic channel. This method appreciably minimizes interferences by incorporating a nonspecific polymer inclusion membrane (PIM) based assay with a "dot-counting" approach to quantification. In this study, hydrophobic polycaprolactone (PCL)-filled glass microfiber (GMF) membranes were used as the base substrate onto which the PIM was evenly dispensed as an array of dots. The devices thus prepared were then selectively exposed to oxygen radicals through a mask to generate a hydrophilic surface path along which the sample was wicked. Using this approach, copper concentrations from 1 to 20 ppm were quantified from 5 μL samples using only visual observation of the assay device.

Parallel affinity-based isolation of leukocyte subsets using microfluidics: application for stroke diagnosis.

PubMed

Pullagurla, Swathi R; Witek, Małgorzata A; Jackson, Joshua M; Lindell, Maria A M; Hupert, Mateusz L; Nesterova, Irina V; Baird, Alison E; Soper, Steven A

2014-04-15

We report the design and performance of a polymer microfluidic device that can affinity select multiple types of biological cells simultaneously with sufficient recovery and purity to allow for the expression profiling of mRNA isolated from these cells. The microfluidic device consisted of four independent selection beds with curvilinear channels that were 25 μm wide and 80 μm deep and were modified with antibodies targeting antigens specifically expressed by two different cell types. Bifurcated and Z-configured device geometries were evaluated for cell selection. As an example of the performance of these devices, CD4+ T-cells and neutrophils were selected from whole blood as these cells are known to express genes found in stroke-related expression profiles that can be used for the diagnosis of this disease. CD4+ T-cells and neutrophils were simultaneously isolated with purities >90% using affinity-based capture in cyclic olefin copolymer (COC) devices with a processing time of ∼3 min. In addition, sufficient quantities of the cells could be recovered from a 50 μL whole blood input to allow for reverse transcription-polymerase chain reaction (RT-PCR) following cell lysis. The expression of genes from isolated T-cells and neutrophils, such as S100A9, TCRB, and FPR1, was evaluated using RT-PCR. The modification and isolation procedures demonstrated here can also be used to analyze other cell types as well where multiple subsets must be interrogated.

[Advances on enzymes and enzyme inhibitors research based on microfluidic devices].

PubMed

Hou, Feng-Hua; Ye, Jian-Qing; Chen, Zuan-Guang; Cheng, Zhi-Yi

2010-06-01

With the continuous development in microfluidic fabrication technology, microfluidic analysis has evolved from a concept to one of research frontiers in last twenty years. The research of enzymes and enzyme inhibitors based on microfluidic devices has also made great progress. Microfluidic technology improved greatly the analytical performance of the research of enzymes and enzyme inhibitors by reducing the consumption of reagents, decreasing the analysis time, and developing automation. This review focuses on the development and classification of enzymes and enzyme inhibitors research based on microfluidic devices.

Rapid prototyping polymers for microfluidic devices and high pressure injections.

PubMed

Sollier, Elodie; Murray, Coleman; Maoddi, Pietro; Di Carlo, Dino

2011-11-21

Multiple methods of fabrication exist for microfluidic devices, with different advantages depending on the end goal of industrial mass production or rapid prototyping for the research laboratory. Polydimethylsiloxane (PDMS) has been the mainstay for rapid prototyping in the academic microfluidics community, because of its low cost, robustness and straightforward fabrication, which are particularly advantageous in the exploratory stages of research. However, despite its many advantages and its broad use in academic laboratories, its low elastic modulus becomes a significant issue for high pressure operation as it leads to a large alteration of channel geometry. Among other consequences, such deformation makes it difficult to accurately predict the flow rates in complex microfluidic networks, change flow speed quickly for applications in stop-flow lithography, or to have predictable inertial focusing positions for cytometry applications where an accurate alignment of the optical system is critical. Recently, other polymers have been identified as complementary to PDMS, with similar fabrication procedures being characteristic of rapid prototyping but with higher rigidity and better resistance to solvents; Thermoset Polyester (TPE), Polyurethane Methacrylate (PUMA) and Norland Adhesive 81 (NOA81). In this review, we assess these different polymer alternatives to PDMS for rapid prototyping, especially in view of high pressure injections with the specific example of inertial flow conditions. These materials are compared to PDMS, for which magnitudes of deformation and dynamic characteristics are also characterized. We provide a complete and systematic analysis of these materials with side-by-side experiments conducted in our lab that also evaluate other properties, such as biocompatibility, solvent compatibility, and ease of fabrication. We emphasize that these polymer alternatives, TPE, PUMA and NOA, have some considerable strengths for rapid prototyping when bond strength, predictable operation at high pressure, or transitioning to commercialization are considered important for the application.

An investigation of paper based microfluidic devices for size based separation and extraction applications.

PubMed

Zhong, Z W; Wu, R G; Wang, Z P; Tan, H L

2015-09-01

Conventional microfluidic devices are typically complex and expensive. The devices require the use of pneumatic control systems or highly precise pumps to control the flow in the devices. This work investigates an alternative method using paper based microfluidic devices to replace conventional microfluidic devices. Size based separation and extraction experiments conducted were able to separate free dye from a mixed protein and dye solution. Experimental results showed that pure fluorescein isothiocyanate could be separated from a solution of mixed fluorescein isothiocyanate and fluorescein isothiocyanate labeled bovine serum albumin. The analysis readings obtained from a spectrophotometer clearly show that the extracted tartrazine sample did not contain any amount of Blue-BSA, because its absorbance value was 0.000 measured at a wavelength of 590nm, which correlated to Blue-BSA. These demonstrate that paper based microfluidic devices, which are inexpensive and easy to implement, can potentially replace their conventional counterparts by the use of simple geometry designs and the capillary action. These findings will potentially help in future developments of paper based microfluidic devices. Copyright © 2015 Elsevier B.V. All rights reserved.

Fabrication of Glass Microchannel via Glass Imprinting using a Vitreous Carbon Stamp for Flow Focusing Droplet Generator

PubMed Central

Refatul Haq, Muhammad; Kim, Youngkyu; Kim, Jun; Oh, Pyoung-hwa; Ju, Jonghyun; Kim, Seok-Min; Lim, Jiseok

2017-01-01

This study reports a cost-effective method of replicating glass microfluidic chips using a vitreous carbon (VC) stamp. A glass replica with the required microfluidic microstructures was synthesized without etching. The replication method uses a VC stamp fabricated by combining thermal replication using a furan-based, thermally-curable polymer with carbonization. To test the feasibility of this method, a flow focusing droplet generator with flow-focusing and channel widths of 50 µm and 100 µm, respectively, was successfully fabricated in a soda-lime glass substrate. Deviation between the geometries of the initial shape and the vitreous carbon mold occurred because of shrinkage during the carbonization process, however this effect could be predicted and compensated for. Finally, the monodispersity of the droplets generated by the fabricated microfluidic device was evaluated. PMID:29286341

Field-Effect Flow Control for 2-D and 3-D Microfluidics

DTIC Science & Technology

2006-02-13

goal of achieving 75% transfer efficiency. The test devices with 3-D channels were fabricated in PDMS polymer (Figure la & lb) and the pumping...properties of a variety of polymer substrate materials were investigated to determine the material that was most amenable to the laser-induced...fluorescence detection employed in this project. Different polymer samples were obtained from different companies and are listed in Table 1 below. Field

Highly efficient circulating tumor cell isolation from whole blood and label-free enumeration using polymer-based microfluidics with an integrated conductivity sensor.

PubMed

Adams, André A; Okagbare, Paul I; Feng, Juan; Hupert, Matuesz L; Patterson, Don; Göttert, Jost; McCarley, Robin L; Nikitopoulos, Dimitris; Murphy, Michael C; Soper, Steven A

2008-07-09

A novel microfluidic device that can selectively and specifically isolate exceedingly small numbers of circulating tumor cells (CTCs) through a monoclonal antibody (mAB) mediated process by sampling large input volumes (>/=1 mL) of whole blood directly in short time periods (<37 min) was demonstrated. The CTCs were concentrated into small volumes (190 nL), and the number of cells captured was read without labeling using an integrated conductivity sensor following release from the capture surface. The microfluidic device contained a series (51) of high-aspect ratio microchannels (35 mum width x 150 mum depth) that were replicated in poly(methyl methacrylate), PMMA, from a metal mold master. The microchannel walls were covalently decorated with mABs directed against breast cancer cells overexpressing the epithelial cell adhesion molecule (EpCAM). This microfluidic device could accept inputs of whole blood, and its CTC capture efficiency was made highly quantitative (>97%) by designing capture channels with the appropriate widths and heights. The isolated CTCs were readily released from the mAB capturing surface using trypsin. The released CTCs were then enumerated on-device using a novel, label-free solution conductivity route capable of detecting single tumor cells traveling through the detection electrodes. The conductivity readout provided near 100% detection efficiency and exquisite specificity for CTCs due to scaling factors and the nonoptimal electrical properties of potential interferences (erythrocytes or leukocytes). The simplicity in manufacturing the device and its ease of operation make it attractive for clinical applications requiring one-time use operation.

Highly Efficient Circulating Tumor Cell Isolation from Whole Blood and Label-Free Enumeration Using Polymer-Based Microfluidics with an Integrated Conductivity Sensor

PubMed Central

Adams, André A.; Okagbare, Paul I.; Feng, Juan; Hupert, Matuesz L.; Patterson, Don; Göttert, Jost; McCarley, Robin L.; Nikitopoulos, Dimitris; Murphy, Michael C.; Soper, Steven A.

2008-01-01

A novel microfluidic device that can selectively and specifically isolate exceedingly small numbers of circulating tumor cells (CTCs) through a monoclonal antibody (mAB) mediated process by sampling large input volumes (≥1 mL) of whole blood directly in short time periods (<37 min) was demonstrated. The CTCs were concentrated into small volumes (190 nL), and the number of cells captured was read without labeling using an integrated conductivity sensor following release from the capture surface. The microfluidic device contained a series (51) of high-aspect ratio microchannels (35 μm width × 150 μm depth) that were replicated in poly(methyl methacrylate), PMMA, from a metal mold master. The microchannel walls were covalently decorated with mABs directed against breast cancer cells overexpressing the epithelial cell adhesion molecule (EpCAM). This microfluidic device could accept inputs of whole blood, and its CTC capture efficiency was made highly quantitative (>97%) by designing capture channels with the appropriate widths and heights. The isolated CTCs were readily released from the mAB capturing surface using trypsin. The released CTCs were then enumerated on-device using a novel, label-free solution conductivity route capable of detecting single tumor cells traveling through the detection electrodes. The conductivity readout provided near 100% detection efficiency and exquisite specificity for CTCs due to scaling factors and the nonoptimal electrical properties of potential interferences (erythrocytes or leukocytes). The simplicity in manufacturing the device and its ease of operation make it attractive for clinical applications requiring one-time use operation. PMID:18557614

Comparison of biocompatibility and adsorption properties of different plastics for advanced microfluidic cell and tissue culture models.

PubMed

van Midwoud, Paul M; Janse, Arnout; Merema, Marjolijn T; Groothuis, Geny M M; Verpoorte, Elisabeth

2012-05-01

Microfluidic technology is providing new routes toward advanced cell and tissue culture models to better understand human biology and disease. Many advanced devices have been made from poly(dimethylsiloxane) (PDMS) to enable experiments, for example, to study drug metabolism by use of precision-cut liver slices, that are not possible with conventional systems. However, PDMS, a silicone rubber material, is very hydrophobic and tends to exhibit significant adsorption and absorption of hydrophobic drugs and their metabolites. Although glass could be used as an alternative, thermoplastics are better from a cost and fabrication perspective. Thermoplastic polymers (plastics) allow easy surface treatment and are generally transparent and biocompatible. This study focuses on the fabrication of biocompatible microfluidic devices with low adsorption properties from the thermoplastics poly(methyl methacrylate) (PMMA), polystyrene (PS), polycarbonate (PC), and cyclic olefin copolymer (COC) as alternatives for PDMS devices. Thermoplastic surfaces were oxidized using UV-generated ozone or oxygen plasma to reduce adsorption of hydrophobic compounds. Surface hydrophilicity was assessed over 4 weeks by measuring the contact angle of water on the surface. The adsorption of 7-ethoxycoumarin, testosterone, and their metabolites was also determined after UV-ozone treatment. Biocompatibility was assessed by culturing human hepatoma (HepG2) cells on treated surfaces. Comparison of the adsorption properties and biocompatibility of devices in different plastics revealed that only UV-ozone-treated PC and COC devices satisfied both criteria. This paper lays an important foundation that will help researchers make informed decisions with respect to the materials they select for microfluidic cell-based culture experiments.

Polymer-based platform for microfluidic systems

DOEpatents

Benett, William [Livermore, CA; Krulevitch, Peter [Pleasanton, CA; Maghribi, Mariam [Livermore, CA; Hamilton, Julie [Tracy, CA; Rose, Klint [Boston, MA; Wang, Amy W [Oakland, CA

2009-10-13

A method of forming a polymer-based microfluidic system platform using network building blocks selected from a set of interconnectable network building blocks, such as wire, pins, blocks, and interconnects. The selected building blocks are interconnectably assembled and fixedly positioned in precise positions in a mold cavity of a mold frame to construct a three-dimensional model construction of a microfluidic flow path network preferably having meso-scale dimensions. A hardenable liquid, such as poly (dimethylsiloxane) is then introduced into the mold cavity and hardened to form a platform structure as well as to mold the microfluidic flow path network having channels, reservoirs and ports. Pre-fabricated elbows, T's and other joints are used to interconnect various building block elements together. After hardening the liquid the building blocks are removed from the platform structure to make available the channels, cavities and ports within the platform structure. Microdevices may be embedded within the cast polymer-based platform, or bonded to the platform structure subsequent to molding, to create an integrated microfluidic system. In this manner, the new microfluidic platform is versatile and capable of quickly generating prototype systems, and could easily be adapted to a manufacturing setting.

Passive non-linear microrheology for determining extensional viscosity

NASA Astrophysics Data System (ADS)

Hsiao, Kai-Wen; Dinic, Jelena; Ren, Yi; Sharma, Vivek; Schroeder, Charles M.

2017-12-01

Extensional viscosity is a key property of complex fluids that greatly influences the non-equilibrium behavior and processing of polymer solutions, melts, and colloidal suspensions. In this work, we use microfluidics to determine steady extensional viscosity for polymer solutions by directly observing particle migration in planar extensional flow. Tracer particles are suspended in semi-dilute solutions of DNA and polyethylene oxide, and a Stokes trap is used to confine single particles in extensional flows of polymer solutions in a cross-slot device. Particles are observed to migrate in the direction transverse to flow due to normal stresses, and particle migration is tracked and quantified using a piezo-nanopositioning stage during the microfluidic flow experiment. Particle migration trajectories are then analyzed using a second-order fluid model that accurately predicts that migration arises due to normal stress differences. Using this analytical framework, extensional viscosities can be determined from particle migration experiments, and the results are in reasonable agreement with bulk rheological measurements of extensional viscosity based on a dripping-onto-substrate method. Overall, this work demonstrates that non-equilibrium properties of complex fluids can be determined by passive yet non-linear microrheology.

Microfluidic devices fabricated in poly(methyl methacrylate) using hot-embossing with integrated sampling capillary and fiber optics for fluorescence detection.

PubMed

Qi, Shize; Liu, Xuezhu; Ford, Sean; Barrows, James; Thomas, Gloria; Kelly, Kevin; McCandless, Andrew; Lian, Kun; Goettert, Jost; Soper, Steven A

2002-05-01

High-aspect-ratio microstructures have been prepared using hot-embossing techniques in poly(methyl methacrylate) (PMMA) from Ni-based molding dies prepared using LIGA (Lithographie, Galvanoformung, Abformung). Due to the small amount of mask undercutting associated with X-ray lithography and the high energy X-ray beam used during photoresist patterning, deep structures with sharp and smooth sidewalls have been prepared. The Ni-electroforms produced devices with minimal replication errors using hot-embossing at a turn around time of approximately 5 min per device. In addition, several different polymers (with different glass transition temperatures) could be effectively molded with these Ni-electroforms and many devices (>300) molded with the same master without any noticeable degradation. The PMMA devices consisted of deep and narrow channels for insertion of a capillary for the automated electrokinetic loading of sample into the microfluidic device and also, a pair of optical fibers for shuttling laser light to the detection zone and collecting the resulting emission for fluorescence analysis. Electrophoretic separations of double-stranded DNA ladders Phi X174 digested with Hae III) were performed with fluorescence detection accomplished using near-IR excitation. It was found that the narrow width of the channels did not contribute significantly to electrophoretic zone broadening and the plate numbers generated in the extended length separation channel allowed sorting of the 271/281 base pair fragments associated with this sizing ladder when electrophoresed in methylcellulose entangled polymer solutions. The dual fiber detector produced sub-attomole detection limits with the entire detector, including laser source, electronics and photon transducer, situated in a single box measuring 3'' x 10" x 14".

Flexible manipulation of microfluids using optically regulated adsorption/desorption of hydrophobic materials.

PubMed

Nagai, Hidenori; Irie, Takashi; Takahashi, Junko; Wakida, Shin-ichi

2007-04-15

To realize highly integrated micro total analysis systems (microTAS), a simply controlled miniaturized valve should be utilized on microfluidic device. In this paper, we describe the application of photo-induced super-hydrophilicity of titanium dioxide (TiO2) to microfluidic manipulation. In addition, we found a new phenomenon for reversibly converting the surface wettability using a polydimethylsiloxane (PDMS) matrix and the photocatalytic properties of TiO2. While PDMS polymer was irradiated with UV, it was confirmed that hydrophobic material was released from the polymer to air. Several prepolymers were identified as the hydrophobic material with a gas chromatograph and mass spectrometer (GC/MS). Here, we successfully demonstrated the flexible manipulation of microfluid in a branched microchannel using the reversible wettability as micro opto-switching valve (MOS/V). The simultaneous control of MOS/Vs was also demonstrated on a 256-MOS/V integrated disk. The MOS/V promises to be one of the most effective flow switching valves for advanced applications in highly integrated micro/nano fluidics.

Ultrasonic alignment of microparticles in nozzle-like geometries

NASA Astrophysics Data System (ADS)

Whittaker, Molly A.; Dauson, Erin R.; Parra-Raad, Jaime; Heard, Robert A.; Oppenheim, Irving J.

2018-03-01

Additive manufacturing (3-D printing) is presently limited by the mechanical properties of the materials, such as polymer resins, that are otherwise efficient and economical for part-forming. Reinforcing the resin with microscale fibers and/or particles would be an effective mechanism to achieve desired mechanical properties such as strength and ductility. Our work combines standing wave ultrasonics and microfluidics to align microparticles in devices that can act as print nozzles, based in part on our prior work with cell sorting. In this paper three different approaches are presented illustrating different engineering tradeoffs, and demonstrating laboratory results of particle alignment. First acoustic resonators are discussed, in which the ultrasonic standing waves result mostly from the mechanical properties of the microfluidic structure, excited by a piezoceramic transducer. Next non-resonant microfluidic structures are discussed, in which ultrasonic standing waves are produced directly by symmetrical transducer deployment. Finally, devices that combine nozzle-like structures, which themselves are suitable acoustic resonators, subjected to symmetrical ultrasonic excitation are presented. We will show that all three configurations will align microparticles, and discuss the tradeoffs among them for subsequent configuration of a print nozzle.

Accurate, predictable, repeatable micro-assembly technology for polymer, microfluidic modules.

PubMed

Lee, Tae Yoon; Han, Kyudong; Barrett, Dwhyte O; Park, Sunggook; Soper, Steven A; Murphy, Michael C

2018-01-01

A method for the design, construction, and assembly of modular, polymer-based, microfluidic devices using simple micro-assembly technology was demonstrated to build an integrated fluidic system consisting of vertically stacked modules for carrying out multi-step molecular assays. As an example of the utility of the modular system, point mutation detection using the ligase detection reaction (LDR) following amplification by the polymerase chain reaction (PCR) was carried out. Fluid interconnects and standoffs ensured that temperatures in the vertically stacked reactors were within ± 0.2 C° at the center of the temperature zones and ± 1.1 C° overall. The vertical spacing between modules was confirmed using finite element models (ANSYS, Inc., Canonsburg, PA) to simulate the steady-state temperature distribution for the assembly. Passive alignment structures, including a hemispherical pin-in-hole, a hemispherical pin-in-slot, and a plate-plate lap joint, were developed using screw theory to enable accurate exactly constrained assembly of the microfluidic reactors, cover sheets, and fluid interconnects to facilitate the modular approach. The mean mismatch between the centers of adjacent through holes was 64 ± 7.7 μm, significantly reducing the dead volume necessary to accommodate manufacturing variation. The microfluidic components were easily assembled by hand and the assembly of several different configurations of microfluidic modules for executing the assay was evaluated. Temperatures were measured in the desired range in each reactor. The biochemical performance was comparable to that obtained with benchtop instruments, but took less than 45 min to execute, half the time.

Polymeric salt bridges for conducting electric current in microfluidic devices

DOEpatents

Shepodd, Timothy J [Livermore, CA; Tichenor, Mark S [San Diego, CA; Artau, Alexander [Humacao, PR

2009-11-17

A "cast-in-place" monolithic microporous polymer salt bridge for conducting electrical current in microfluidic devices, and methods for manufacture thereof is disclosed. Polymeric salt bridges are formed in place in capillaries or microchannels. Formulations are prepared with monomer, suitable cross-linkers, solvent, and a thermal or radiation responsive initiator. The formulation is placed in a desired location and then suitable radiation such as UV light is used to polymerize the salt bridge within a desired structural location. Embodiments are provided wherein the polymeric salt bridges have sufficient porosity to allow ionic migration without bulk flow of solvents therethrough. The salt bridges form barriers that seal against fluid pressures in excess of 5000 pounds per square inch. The salt bridges can be formulated for carriage of suitable amperage at a desired voltage, and thus microfluidic devices using such salt bridges can be specifically constructed to meet selected analytical requirements.

Direct observation of single flexible polymers using single stranded DNA†

PubMed Central

Brockman, Christopher; Kim, Sun Ju

2012-01-01

Over the last 15 years, double stranded DNA (dsDNA) has been used as a model polymeric system for nearly all single polymer dynamics studies. However, dsDNA is a semiflexible polymer with markedly different molecular properties compared to flexible chains, including synthetic organic polymers. In this work, we report a new system for single polymer studies of flexible chains based on single stranded DNA (ssDNA). We developed a method to synthesize ssDNA for fluorescence microscopy based on rolling circle replication, which generates long strands (>65 kb) of ssDNA containing “designer” sequences, thereby preventing intramolecular base pair interactions. Polymers are synthesized to contain amine-modified bases randomly distributed along the backbone, which enables uniform labelling of polymer chains with a fluorescent dye to facilitate fluorescence microscopy and imaging. Using this approach, we synthesized ssDNA chains with long contour lengths (>30 μm) and relatively low dye loading ratios (~1 dye per 100 bases). In addition, we used epifluorescence microscopy to image single ssDNA polymer molecules stretching in flow in a microfluidic device. Overall, we anticipate that ssDNA will serve as a useful model system to probe the dynamics of polymeric materials at the molecular level. PMID:22956981

New valve and bonding designs for microfluidic biochips containing proteins.

PubMed

Lu, Chunmeng; Xie, Yubing; Yang, Yong; Cheng, Mark M-C; Koh, Chee-Guan; Bai, Yunling; Lee, L James; Juang, Yi-Je

2007-02-01

Two major concerns in the design and fabrication of microfluidic biochips are protein binding on the channel surface and protein denaturing during device assembly. In this paper, we describe new methods to solve these problems. A "fishbone" microvalve design based on the concept of superhydrophobicity was developed to replace the capillary valve in applications where the chip surface requires protein blocking to prevent nonspecific binding. Our experimental results show that the valve functions well in a CD-like ELISA device. The packaging of biochips containing pre-loaded proteins is also a challenging task since conventional sealing methods often require the use of high temperatures, electric voltages, or organic solvents that are detrimental to the protein activity. Using CO2 gas to enhance the diffusion of polymer molecules near the device surface can result in good bonding at low temperatures and low pressure. This bonding method has little influence on the activity of the pre-loaded proteins after bonding.

Small molecule absorption by PDMS in the context of drug response bioassays.

PubMed

van Meer, B J; de Vries, H; Firth, K S A; van Weerd, J; Tertoolen, L G J; Karperien, H B J; Jonkheijm, P; Denning, C; IJzerman, A P; Mummery, C L

2017-01-08

The polymer polydimethylsiloxane (PDMS) is widely used to build microfluidic devices compatible with cell culture. Whilst convenient in manufacture, PDMS has the disadvantage that it can absorb small molecules such as drugs. In microfluidic devices like "Organs-on-Chip", designed to examine cell behavior and test the effects of drugs, this might impact drug bioavailability. Here we developed an assay to compare the absorption of a test set of four cardiac drugs by PDMS based on measuring the residual non-absorbed compound by High Pressure Liquid Chromatography (HPLC). We showed that absorption was variable and time dependent and not determined exclusively by hydrophobicity as claimed previously. We demonstrated that two commercially available lipophilic coatings and the presence of cells affected absorption. The use of lipophilic coatings may be useful in preventing small molecule absorption by PDMS. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Hybrid membrane-microfluidic components using a novel ceramic MEMS technology

NASA Astrophysics Data System (ADS)

Lutz, Brent J.; Polyakov, Oleg; Rinaldo, Chris

2012-03-01

A novel hybrid nano/microfabrication technology has been employed to produce unique MEMS and microfluidic components that integrate nanoporous membranes. The components are made by micromachining a self-organized nanostructured ceramic material that is biocompatible and amenable to surface chemistry modification. Microfluidic structures, such as channels and wells, can be made with a precision of <2 microns. Thin-film membranes can be integrated into the bottom of these structures, featuring a wide range of possible thicknesses, from 100 micron to <50 nm. Additionally, these membranes may be non-porous or porous (with controllable pore sizes from 200 nm to <5 nm), for sophisticated size-based separations. With previous and current support from the NIH SBIR program, we have built several unique devices, and demonstrated improved separations, cell culturing, and imaging (optical and electron microscopy) versus standard products. Being ceramic, the material is much more robust to demanding environments (e.g. high and low temperatures and organic solvents), compared to polymer-based devices. Additionally, we have applied multiple surface modification techniques, including atomic layer deposition, to manipulate properties such as electrical conductivity. This microfabrication technology is highly scaleable, and thus can yield low-cost, reliable, disposable microcomponents and devices. Specific applications that can benefit from this technology includes cell culturing and assays, imaging by cryo-electron tomography, environmental sample processing, as well as many others.

Localized, stepwise template growth of functional nanowires from an amino acid-supported framework in a microfluidic chip.

PubMed

Puigmartí-Luis, Josep; Rubio-Martínez, Marta; Imaz, Inhar; Cvetković, Benjamin Z; Abad, Llibertat; Pérez Del Pino, Angel; Maspoch, Daniel; Amabilino, David B

2014-01-28

A spatially controlled synthesis of nanowire bundles of the functional crystalline coordination polymer (CP) Ag(I)TCNQ (tetracyanoquinodimethane) from previously fabricated and trapped monovalent silver CP (Ag(I)Cys (cysteine)) using a room-temperature microfluidic-assisted templated growth method is demonstrated. The incorporation of microengineered pneumatic clamps in a two-layer polydimethylsiloxane-based (PDMS) microfluidic platform was used. Apart from guiding the formation of the Ag(I)Cys coordination polymer, this microfluidic approach enables a local trapping of the in situ synthesized structures with a simple pneumatic clamp actuation. This method not only enables continuous and multiple chemical events to be conducted upon the trapped structures, but the excellent fluid handling ensures a precise chemical activation of the amino acid-supported framework in a position controlled by interface and clamp location that leads to a site-specific growth of Ag(I)TCNQ nanowire bundles. The synthesis is conducted stepwise starting with Ag(I)Cys CPs, going through silver metal, and back to a functional CP (Ag(I)TCNQ); that is, a novel microfluidic controlled ligand exchange (CP → NP → CP) is presented. Additionally, the pneumatic clamps can be employed further to integrate the conductive Ag(I)TCNQ nanowire bundles onto electrode arrays located on a surface, hence facilitating the construction of the final functional interfaced systems from solution specifically with no need for postassembly manipulation. This localized self-supported growth of functional matter from an amino acid-based CP shows how sequential localized chemistry in a fluid cell can be used to integrate molecular systems onto device platforms using a chip incorporating microengineered pneumatic tools. The control of clamp pressure and in parallel the variation of relative flow rates of source solutions permit deposition of materials at different locations on a chip that could be useful for device array preparation. The in situ reaction and washing procedures make this approach a powerful one for the fabrication of multicomponent complex nanomaterials using a soft bottom-up approach.

Method for forming polymerized microfluidic devices

DOEpatents

Sommer, Gregory J [Livermore, CA; Hatch, Anson V [Tracy, CA; Wang, Ying-Chih [Pleasanton, CA; Singh, Anup K [Danville, CA; Renzi, Ronald F [Tracy, CA; Claudnic, Mark R [Livermore, CA

2011-11-01

Methods for making a micofluidic device according to embodiments of the present invention include defining a cavity. Polymer precursor solution is positioned in the cavity, and exposed to light to begin the polymerization process and define a microchannel. In some embodiments, after the polymerization process is partially complete, a solvent rinse is performed, or fresh polymer precursor introduced into the microchannel. This may promote removal of unpolymerized material from the microchannel and enable smaller feature sizes. The polymer precursor solution may contain an iniferter. Polymerized features therefore may be capped with the iniferter, which is photoactive. The iniferter may aid later binding of a polyacrylamide gel to the microchannel surface.

Automated microfluidic devices integrating solid-phase extraction, fluorescent labeling, and microchip electrophoresis for preterm birth biomarker analysis.

PubMed

Sahore, Vishal; Sonker, Mukul; Nielsen, Anna V; Knob, Radim; Kumar, Suresh; Woolley, Adam T

2018-01-01

We have developed multichannel integrated microfluidic devices for automated preconcentration, labeling, purification, and separation of preterm birth (PTB) biomarkers. We fabricated multilayer poly(dimethylsiloxane)-cyclic olefin copolymer (PDMS-COC) devices that perform solid-phase extraction (SPE) and microchip electrophoresis (μCE) for automated PTB biomarker analysis. The PDMS control layer had a peristaltic pump and pneumatic valves for flow control, while the PDMS fluidic layer had five input reservoirs connected to microchannels and a μCE system. The COC layers had a reversed-phase octyl methacrylate porous polymer monolith for SPE and fluorescent labeling of PTB biomarkers. We determined μCE conditions for two PTB biomarkers, ferritin (Fer) and corticotropin-releasing factor (CRF). We used these integrated microfluidic devices to preconcentrate and purify off-chip-labeled Fer and CRF in an automated fashion. Finally, we performed a fully automated on-chip analysis of unlabeled PTB biomarkers, involving SPE, labeling, and μCE separation with 1 h total analysis time. These integrated systems have strong potential to be combined with upstream immunoaffinity extraction, offering a compact sample-to-answer biomarker analysis platform. Graphical abstract Pressure-actuated integrated microfluidic devices have been developed for automated solid-phase extraction, fluorescent labeling, and microchip electrophoresis of preterm birth biomarkers.

Integration of Multiplexed Microfluidic Electrokinetic Concentrators with a Morpholino Microarray via Reversible Surface Bonding for Enhanced DNA Hybridization.

PubMed

Martins, Diogo; Wei, Xi; Levicky, Rastislav; Song, Yong-Ak

2016-04-05

We describe a microfluidic concentration device to accelerate the surface hybridization reaction between DNA and morpholinos (MOs) for enhanced detection. The microfluidic concentrator comprises a single polydimethylsiloxane (PDMS) microchannel onto which an ion-selective layer of conductive polymer poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) ( PSS) was directly printed and then reversibly surface bonded onto a morpholino microarray for hybridization. Using this electrokinetic trapping concentrator, we could achieve a maximum concentration factor of ∼800 for DNA and a limit of detection of 10 nM within 15 min. In terms of the detection speed, it enabled faster hybridization by around 10-fold when compared to conventional diffusion-based hybridization. A significant advantage of our approach is that the fabrication of the microfluidic concentrator is completely decoupled from the microarray; by eliminating the need to deposit an ion-selective layer on the microarray surface prior to device integration, interfacing between both modules, the PDMS chip for electrokinetic concentration and the substrate for DNA sensing are easier and applicable to any microarray platform. Furthermore, this fabrication strategy facilitates a multiplexing of concentrators. We have demonstrated the proof-of-concept for multiplexing by building a device with 5 parallel concentrators connected to a single inlet/outlet and applying it to parallel concentration and hybridization. Such device yielded similar concentration and hybridization efficiency compared to that of a single-channel device without adding any complexity to the fabrication and setup. These results demonstrate that our concentrator concept can be applied to the development of a highly multiplexed concentrator-enhanced microarray detection system for either genetic analysis or other diagnostic assays.

Simple and inexpensive microfluidic devices for the generation of monodisperse multiple emulsions

NASA Astrophysics Data System (ADS)

Li, Er Qiang; Zhang, Jia Ming; Thoroddsen, Sigurdur T.

2014-01-01

Droplet-based microfluidic devices have become a preferred versatile platform for various fields in physics, chemistry and biology. Polydimethylsiloxane soft lithography, the mainstay for fabricating microfluidic devices, usually requires the usage of expensive apparatus and a complex manufacturing procedure. Here, we report the design and fabrication of simple and inexpensive microfluidic devices based on microscope glass slides and pulled glass capillaries, for generating monodisperse multiple emulsions. The advantages of our method lie in a simple manufacturing procedure, inexpensive processing equipment and flexibility in the surface modification of the designed microfluidic devices. Different types of devices have been designed and tested and the experimental results demonstrated their robustness for preparing monodisperse single, double, triple and multi-component emulsions.

Pumps for microfluidic cell culture.

PubMed

Byun, Chang Kyu; Abi-Samra, Kameel; Cho, Yoon-Kyoung; Takayama, Shuichi

2014-02-01

In comparison to traditional in vitro cell culture in Petri dishes or well plates, cell culture in microfluidic-based devices enables better control over chemical and physical environments, higher levels of experimental automation, and a reduction in experimental materials. Over the past decade, the advantages associated with cell culturing in microfluidic-based platforms have garnered significant interest and have led to a plethora of studies for high throughput cell assays, organs-on-a-chip applications, temporal signaling studies, and cell sorting. A clear concern for performing cell culture in microfluidic-based devices is deciding on a technique to deliver and pump media to cells that are encased in a microfluidic device. In this review, we summarize recent advances in pumping techniques for microfluidic cell culture and discuss their advantages and possible drawbacks. The ultimate goal of our review is to distill the large body of information available related to pumps for microfluidic cell culture in an effort to assist current and potential users of microfluidic-based devices for advanced in vitro cellular studies. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Hybrid Integrated Silicon Microfluidic Platform for Fluorescence Based Biodetection.

PubMed

Chandrasekaran, Arvind; Acharya, Ashwin; You, Jian Liang; Soo, Kim Young; Packirisamy, Muthukumaran; Stiharu, Ion; Darveau, André

2007-09-11

The desideratum to develop a fully integrated Lab-on-a-chip device capable ofrapid specimen detection for high throughput in-situ biomedical diagnoses and Point-of-Care testing applications has called for the integration of some of the novel technologiessuch as the microfluidics, microphotonics, immunoproteomics and Micro ElectroMechanical Systems (MEMS). In the present work, a silicon based microfluidic device hasbeen developed for carrying out fluorescence based immunoassay. By hybrid attachment ofthe microfluidic device with a Spectrometer-on-chip, the feasibility of synthesizing anintegrated Lab-on-a-chip type device for fluorescence based biosensing has beendemonstrated. Biodetection using the microfluidic device has been carried out usingantigen sheep IgG and Alexafluor-647 tagged antibody particles and the experimentalresults prove that silicon is a compatible material for the present application given thevarious advantages it offers such as cost-effectiveness, ease of bulk microfabrication,superior surface affinity to biomolecules, ease of disposability of the device etc., and is thussuitable for fabricating Lab-on-a-chip type devices.

Optical biosensor system with integrated microfluidic sample preparation and TIRF based detection

NASA Astrophysics Data System (ADS)

Gilli, Eduard; Scheicher, Sylvia R.; Suppan, Michael; Pichler, Heinz; Rumpler, Markus; Satzinger, Valentin; Palfinger, Christian; Reil, Frank; Hajnsek, Martin; Köstler, Stefan

2013-05-01

There is a steadily growing demand for miniaturized bioanalytical devices allowing for on-site or point-of-care detection of biomolecules or pathogens in applications like diagnostics, food testing, or environmental monitoring. These, so called labs-on-a-chip or micro-total analysis systems (μ-TAS) should ideally enable convenient sample-in - result-out type operation. Therefore, the entire process from sample preparation, metering, reagent incubation, etc. to detection should be performed on a single disposable device (on-chip). In the early days such devices were mainly fabricated using glass or silicon substrates and adapting established fabrication technologies from the electronics and semiconductor industry. More recently, the development focuses on the use of thermoplastic polymers as they allow for low-cost high volume fabrication of disposables. One of the most promising materials for the development of plastic based lab-on-achip systems are cyclic olefin polymers and copolymers (COP/COC) due to their excellent optical properties (high transparency and low autofluorescence) and ease of processing. We present a bioanalytical system for whole blood samples comprising a disposable plastic chip based on TIRF (total internal reflection fluorescence) optical detection. The chips were fabricated by compression moulding of COP and microfluidic channels were structured by hot embossing. These microfluidic structures integrate several sample pretreatment steps. These are the separation of erythrocytes, metering of sample volume using passive valves, and reagent incubation for competitive bioassays. The surface of the following optical detection zone is functionalized with specific capture probes in an array format. The plastic chips comprise dedicated structures for simple and effective coupling of excitation light from low-cost laser diodes. This enables TIRF excitation of fluorescently labeled probes selectively bound to detection spots at the microchannel surface. The fluorescence of these detection arrays is imaged using a simple set-up based on a digital consumer camera. Image processing for spot detection and intensity calculation is accomplished using customized software. Using this combined TIRF excitation and imaging based detection approach allowes for effective suppression of background fluorescence from the sample, multiplexed detection in an array format, as well as internal calibration and background correction.

Direct coupling of polymer-based microchip electrophoresis to online MALDI-MS using a rotating ball inlet.

PubMed

Musyimi, Harrison K; Guy, Jason; Narcisse, Damien A; Soper, Steven A; Murray, Kermit K

2005-12-01

We report on the coupling of a polymer-based microfluidic chip to a MALDI-TOF MS using a rotating ball interface. The microfluidic chips were fabricated by micromilling a mold insert into a brass plate, which was then used for replicating polymer microparts via hot embossing. Assembly of the chip was accomplished by thermally annealing a cover slip to the embossed substrate to enclose the channels. The linear separation channel was 50 microm wide, 100 microm deep, and possessed an 8 cm effective length separation channel with a double-T injector (V(inj) = 10 nL). The exit of the separation channel was machined to allow direct contact deposition of effluent onto a specially constructed rotating ball inlet to the mass spectrometer. Matrix addition was accomplished in-line on the surface of the ball. The coupling utilized the ball as the cathode transfer electrode to transport sample into the vacuum for desorption with a 355 nm Nd:YAG laser and analyzed on a TOF mass spectrometer. The ball was cleaned online after every rotation. The ability to couple poly(methylmethacrylate) microchip electrophoresis devices for the separation of peptides and peptide fragments produced from a protein digest with subsequent online MALDI MS detection was demonstrated.

Controlled and tunable polymer particles' production using a single microfluidic device

NASA Astrophysics Data System (ADS)

Amoyav, Benzion; Benny, Ofra

2018-04-01

Microfluidics technology offers a new platform to control liquids under flow in small volumes. The advantage of using small-scale reactions for droplet generation along with the capacity to control the preparation parameters, making microfluidic chips an attractive technology for optimizing encapsulation formulations. However, one of the drawback in this methodology is the ability to obtain a wide range of droplet sizes, from sub-micron to microns using a single chip design. In fact, typically, droplet chips are used for micron-dimension particles, while nanoparticles' synthesis requires complex chips design (i.e., microreactors and staggered herringbone micromixer). Here, we introduce the development of a highly tunable and controlled encapsulation technique, using two polymer compositions, for generating particles ranging from microns to nano-size using the same simple single microfluidic chip design. Poly(lactic-co-glycolic acid) (PLGA 50:50) or PLGA/polyethylene glycol polymeric particles were prepared with focused-flow chip, yielding monodisperse particle batches. We show that by varying flow rate, solvent, surfactant and polymer composition, we were able to optimize particles' size and decrease polydispersity index, using simple chip designs with no further related adjustments or costs. Utilizing this platform, which offers tight tuning of particle properties, could offer an important tool for formulation development and can potentially pave the way towards a better precision nanomedicine.

How to fabricate robust microfluidic systems for a dollar

NASA Astrophysics Data System (ADS)

Lapierre, Florian; Cameron, Neil R.; Oakeshott, John; Peat, Thomas; Zhu, Yonggang

2013-12-01

Since the past decade, the interest towards microfluidic devices has sensibly grown due to the wide variety of multidisciplinary applications. One branch of the microfluidic domain consists in the synthesis of various types of emulsions requested by cosmetic, food and biotechnological industries In particular, monodisperse water-in-oil microemulsion synthetised in microfluidic devices are quickly becoming the new generation of emulsions for precise bead control and high surface area. These microemulsions are generally aqueous bioreactors in the form of droplets from 500 nm to 10 μm in diameter, enclosed in an oil environment. An increasing demand for bigger emulsions has led us to investigate new techniques for fabricating fluidic devices allowing a better control over the final size of the droplets. An easy, cheap, reproducible and fast technology for generating emulsions in the range of 100s μm with high throughout (up to mL/h) is reported. Simply using pipette tips and tubing, an innovative microfluidic device was fabricated, able to synthetise water-in-oil emulsions within the range 50 - 500 _μm and double emulsions. These new emulsions are currently used for the synthesis of highly porous polymers beads from High Internal Phase Emulsion (HIPE). These beads will find high potential in 3D cell culture due to their high porosity (up to 90%) and pore size (from 5 to 30μm).

Thiolene and SIFEL-based Microfluidic Platforms for Liquid-Liquid Extraction

PubMed Central

Goyal, Sachit; Desai, Amit V.; Lewis, Robert W.; Ranganathan, David R.; Li, Hairong; Zeng, Dexing; Reichert, David E.; Kenis, Paul J.A.

2014-01-01

Microfluidic platforms provide several advantages for liquid-liquid extraction (LLE) processes over conventional methods, for example with respect to lower consumption of solvents and enhanced extraction efficiencies due to the inherent shorter diffusional distances. Here, we report the development of polymer-based parallel-flow microfluidic platforms for LLE. To date, parallel-flow microfluidic platforms have predominantly been made out of silicon or glass due to their compatibility with most organic solvents used for LLE. Fabrication of silicon and glass-based LLE platforms typically requires extensive use of photolithography, plasma or laser-based etching, high temperature (anodic) bonding, and/or wet etching with KOH or HF solutions. In contrast, polymeric microfluidic platforms can be fabricated using less involved processes, typically photolithography in combination with replica molding, hot embossing, and/or bonding at much lower temperatures. Here we report the fabrication and testing of microfluidic LLE platforms comprised of thiolene or a perfluoropolyether-based material, SIFEL, where the choice of materials was mainly guided by the need for solvent compatibility and fabrication amenability. Suitable designs for polymer-based LLE platforms that maximize extraction efficiencies within the constraints of the fabrication methods and feasible operational conditions were obtained using analytical modeling. To optimize the performance of the polymer-based LLE platforms, we systematically studied the effect of surface functionalization and of microstructures on the stability of the liquid-liquid interface and on the ability to separate the phases. As demonstrative examples, we report (i) a thiolene-based platform to determine the lipophilicity of caffeine, and (ii) a SIFEL-based platform to extract radioactive copper from an acidic aqueous solution. PMID:25246730

Exploration of microfluidic devices based on multi-filament threads and textiles: A review

PubMed Central

Nilghaz, A.; Ballerini, D. R.; Shen, W.

2013-01-01

In this paper, we review the recent progress in the development of low-cost microfluidic devices based on multifilament threads and textiles for semi-quantitative diagnostic and environmental assays. Hydrophilic multifilament threads are capable of transporting aqueous and non-aqueous fluids via capillary action and possess desirable properties for building fluid transport pathways in microfluidic devices. Thread can be sewn onto various support materials to form fluid transport channels without the need for the patterned hydrophobic barriers essential for paper-based microfluidic devices. Thread can also be used to manufacture fabrics which can be patterned to achieve suitable hydrophilic-hydrophobic contrast, creating hydrophilic channels which allow the control of fluids flow. Furthermore, well established textile patterning methods and combination of hydrophilic and hydrophobic threads can be applied to fabricate low-cost microfluidic devices that meet the low-cost and low-volume requirements. In this paper, we review the current limitations and shortcomings of multifilament thread and textile-based microfluidics, and the research efforts to date on the development of fluid flow control concepts and fabrication methods. We also present a summary of different methods for modelling the fluid capillary flow in microfluidic thread and textile-based systems. Finally, we summarized the published works of thread surface treatment methods and the potential of combining multifilament thread with other materials to construct devices with greater functionality. We believe these will be important research focuses of thread- and textile-based microfluidics in future. PMID:24086179

Preparation Details for Making Silicones: Influence of Molecular Network Architecture on Mechanical and Surface Properties of PDMS Elastomers

NASA Astrophysics Data System (ADS)

Melillo, Matthew; Walker, Edwin; Klein, Zoe; Efimenko, Kirill; Genzer, Jan

Poly(dimethylsiloxane) (PDMS) is one of the most common elastomers, with applications ranging from medical devices to absorbents for water treatment. Fundamental understanding of how liquids spread on the surface of and absorb into PDMS networks is of critical importance for the design and use of another application - microfluidic devices. We have systematically studied the effects of polymer molecular weight, loading of tetra-functional crosslinker, end-group chemical functionality, the extent of dilution of the curing mixture, and gelation kinetics on the mechanical and surface properties of end-linked PDMS networks. The gel and sol fractions, storage and loss moduli, liquid swelling ratios, and water contact angles have all been shown to vary greatly based on the aforementioned variables. Similar trends were observed for the commercial PDMS material, Sylgard-184. Our results have confirmed theories predicting the relationships between modulus and swelling and we've also applied the theory of Macosko-Miller to estimate extent of reaction of crosslinker and polymer groups. Methods for determining the molecular weight between crosslinks from swelling, mechanical, and gelation theories were applied to ascertain their similarities and differences in an effort to identify the most accurate method. These findings will aid in the design and implementation of efficient microfluidics and other PDMS-based materials that involve the transport of liquids.

Surfactant-induced electroosmotic flow in microfluidic capillaries.

PubMed

Azadi, Glareh; Tripathi, Anubhav

2012-07-01

Control of EOF in microfluidic devices is essential in applications such as protein/DNA sizing and high-throughput drug screening. With the growing popularity of poly(methyl methacrylate) (PMMA) as the substrate for polymeric-based microfludics, it is important to understand the effect of surfactants on EOF in these devices. In this article, we present an extensive investigation exploring changes in EOF rate induced by SDS, polyoxyethylene lauryl ether (Brij35) and CTAB in PMMA microfluidic capillaries. In a standard protein buffer (Tris-Glycine), PMMA capillaries exhibited a cathodic EOF with measured mobility of 1.54 ± 0.1 (× 10⁻⁴ cm²/V.s). In the presence of surfactant below a critical concentration, EOF was independent of surfactant concentration. At high concentrations of surfactants, the electroosmotic mobility was found to linearly increase/decrease as the logarithm of concentration before reaching a constant value. With SDS, the EOF increased by 257% (compared to buffer), while it was decreased by 238% with CTAB. In the case of Brij35, the electroosmotic mobility was reduced by 70%. In a binary surfactant system of SDS/CTAB and SDS/Brij35, addition of oppositely charged CTAB reduced the SDS-induced EOF more effectively compared to nonionic Brij35. We propose possible mechanisms that explain the observed changes in EOF and zeta potential values. Use of neutral polymer coatings in combination with SDS resulted in 50% reduction in the electroosmotic mobility with 0.1% hydroxypropyl methyl cellulose (HPMC), while including 2% poly (N,N-dimethylacrylamide) (PDMA) had no effect. These results will potentially contribute to the development of PMMA-based microfluidic devices. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Advances in three-dimensional rapid prototyping of microfluidic devices for biological applications

PubMed Central

O'Neill, P. F.; Ben Azouz, A.; Vázquez, M.; Liu, J.; Marczak, S.; Slouka, Z.; Chang, H. C.; Diamond, D.; Brabazon, D.

2014-01-01

The capability of 3D printing technologies for direct production of complex 3D structures in a single step has recently attracted an ever increasing interest within the field of microfluidics. Recently, ultrafast lasers have also allowed developing new methods for production of internal microfluidic channels within the bulk of glass and polymer materials by direct internal 3D laser writing. This review critically summarizes the latest advances in the production of microfluidic 3D structures by using 3D printing technologies and direct internal 3D laser writing fabrication methods. Current applications of these rapid prototyped microfluidic platforms in biology will be also discussed. These include imaging of cells and living organisms, electrochemical detection of viruses and neurotransmitters, and studies in drug transport and induced-release of adenosine triphosphate from erythrocytes. PMID:25538804

Ultrathin Polymer Membranes with Patterned, Micrometric Pores for Organs-on-Chips.

PubMed

Pensabene, Virginia; Costa, Lino; Terekhov, Alexander Y; Gnecco, Juan S; Wikswo, John P; Hofmeister, William H

2016-08-31

The basal lamina or basement membrane (BM) is a key physiological system that participates in physicochemical signaling between tissue types. Its formation and function are essential in tissue maintenance, growth, angiogenesis, disease progression, and immunology. In vitro models of the BM (e.g., Boyden and transwell chambers) are common in cell biology and lab-on-a-chip devices where cells require apical and basolateral polarization. Extravasation, intravasation, membrane transport of chemokines, cytokines, chemotaxis of cells, and other key functions are routinely studied in these models. The goal of the present study was to integrate a semipermeable ultrathin polymer membrane with precisely positioned pores of 2 μm diameter in a microfluidic device with apical and basolateral chambers. We selected poly(l-lactic acid) (PLLA), a transparent biocompatible polymer, to prepare the semipermeable ultrathin membranes. The pores were generated by pattern transfer using a three-step method coupling femtosecond laser machining, polymer replication, and spin coating. Each step of the fabrication process was characterized by scanning electron microscopy to investigate reliability of the process and fidelity of pattern transfer. In order to evaluate the compatibility of the fabrication method with organs-on-a-chip technology, porous PLLA membranes were embedded in polydimethylsiloxane (PDMS) microfluidic devices and used to grow human umbilical vein endothelial cells (HUVECS) on top of the membrane with perfusion through the basolateral chamber. Viability of cells, optical transparency of membranes and strong adhesion of PLLA to PDMS were observed, thus confirming the suitability of the prepared membranes for use in organs-on-a-chip devices.

Femtosecond laser three-dimensional micro- and nanofabrication

NASA Astrophysics Data System (ADS)

Sugioka, Koji; Cheng, Ya

2014-12-01

The rapid development of the femtosecond laser has revolutionized materials processing due to its unique characteristics of ultrashort pulse width and extremely high peak intensity. The short pulse width suppresses the formation of a heat-affected zone, which is vital for ultrahigh precision fabrication, whereas the high peak intensity allows nonlinear interactions such as multiphoton absorption and tunneling ionization to be induced in transparent materials, which provides versatility in terms of the materials that can be processed. More interestingly, irradiation with tightly focused femtosecond laser pulses inside transparent materials makes three-dimensional (3D) micro- and nanofabrication available due to efficient confinement of the nonlinear interactions within the focal volume. Additive manufacturing (stereolithography) based on multiphoton absorption (two-photon polymerization) enables the fabrication of 3D polymer micro- and nanostructures for photonic devices, micro- and nanomachines, and microfluidic devices, and has applications for biomedical and tissue engineering. Subtractive manufacturing based on internal modification and fabrication can realize the direct fabrication of 3D microfluidics, micromechanics, microelectronics, and photonic microcomponents in glass. These microcomponents can be easily integrated in a single glass microchip by a simple procedure using a femtosecond laser to realize more functional microdevices, such as optofluidics and integrated photonic microdevices. The highly localized multiphoton absorption of a tightly focused femtosecond laser in glass can also induce strong absorption only at the interface of two closely stacked glass substrates. Consequently, glass bonding can be performed based on fusion welding with femtosecond laser irradiation, which provides the potential for applications in electronics, optics, microelectromechanical systems, medical devices, microfluidic devices, and small satellites. This review paper describes the concepts and principles of femtosecond laser 3D micro- and nanofabrication and presents a comprehensive review on the state-of-the-art, applications, and the future prospects of this technology.

Femtosecond laser three-dimensional micro- and nanofabrication

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sugioka, Koji, E-mail: ksugioka@riken.jp; Cheng, Ya, E-mail: ya.cheng@siom.ac.cn

2014-12-15

The rapid development of the femtosecond laser has revolutionized materials processing due to its unique characteristics of ultrashort pulse width and extremely high peak intensity. The short pulse width suppresses the formation of a heat-affected zone, which is vital for ultrahigh precision fabrication, whereas the high peak intensity allows nonlinear interactions such as multiphoton absorption and tunneling ionization to be induced in transparent materials, which provides versatility in terms of the materials that can be processed. More interestingly, irradiation with tightly focused femtosecond laser pulses inside transparent materials makes three-dimensional (3D) micro- and nanofabrication available due to efficient confinement ofmore » the nonlinear interactions within the focal volume. Additive manufacturing (stereolithography) based on multiphoton absorption (two-photon polymerization) enables the fabrication of 3D polymer micro- and nanostructures for photonic devices, micro- and nanomachines, and microfluidic devices, and has applications for biomedical and tissue engineering. Subtractive manufacturing based on internal modification and fabrication can realize the direct fabrication of 3D microfluidics, micromechanics, microelectronics, and photonic microcomponents in glass. These microcomponents can be easily integrated in a single glass microchip by a simple procedure using a femtosecond laser to realize more functional microdevices, such as optofluidics and integrated photonic microdevices. The highly localized multiphoton absorption of a tightly focused femtosecond laser in glass can also induce strong absorption only at the interface of two closely stacked glass substrates. Consequently, glass bonding can be performed based on fusion welding with femtosecond laser irradiation, which provides the potential for applications in electronics, optics, microelectromechanical systems, medical devices, microfluidic devices, and small satellites. This review paper describes the concepts and principles of femtosecond laser 3D micro- and nanofabrication and presents a comprehensive review on the state-of-the-art, applications, and the future prospects of this technology.« less

Fabrication of a Paper-Based Microfluidic Device to Readily Determine Nitrite Ion Concentration by Simple Colorimetric Assay

ERIC Educational Resources Information Center

Wang, Bo; Lin, Zhiqiang; Wang, Min

2015-01-01

Paper-based microfluidic devices (µPAD) are a burgeoning platform of microfluidic analysis technology. The method described herein is for use in undergraduate and high school chemistry laboratories. A simple and convenient µPAD was fabricated by easy patterning of filter paper using a permanent marker pen. The usefulness of the device was…

Microfluidics: a transformational tool for nanomedicine development and production.

PubMed

Garg, Shyam; Heuck, Gesine; Ip, Shell; Ramsay, Euan

2016-11-01

Microfluidic devices are mircoscale fluidic circuits used to manipulate liquids at the nanoliter scale. The ability to control the mixing of fluids and the continuous nature of the process make it apt for solvent/antisolvent precipitation of drug-delivery nanoparticles. This review describes the use of numerous microfluidic designs for the formulation and production of lipid nanoparticles, liposomes and polymer nanoparticles to encapsulate and deliver small molecule or genetic payloads. The advantages of microfluidics are illustrated through examples from literature comparing conventional processes such as beaker and T-tube mixing to microfluidic approaches. Particular emphasis is placed on examples of microfluidic nanoparticle formulations that have been tested in vitro and in vivo. Fine control of process parameters afforded by microfluidics, allows unprecedented optimization of nanoparticle quality and encapsulation efficiency. Automation improves the reproducibility and optimization of formulations. Furthermore, the continuous nature of the microfluidic process is inherently scalable, allowing optimization at low volumes, which is advantageous with scarce or costly materials, as well as scale-up through process parallelization. Given these advantages, microfluidics is poised to become the new paradigm for nanomedicine formulation and production.

Design and fabricate multi channel microfluidic mold on top of glass slide using SU-8

NASA Astrophysics Data System (ADS)

Azman, N. A. N.; Rajapaksha, R. D. A. A.; Uda, M. N. A.; Hashim, U.

2017-09-01

Microfluidic is the study of fluid in microscale. Microfluidics provides miniaturized fluidic networks for processing and analyzing liquids in the nanoliter to milliliter range. Microfluidic device comprises of some essential segments or structure that are micromixer, microchannel and microchamber. The SU-8 mold is known as the most used technique in microfluidic fabrication due to the characteristic of very gooey polymer that can be spread over a thickness. In this study, in order to reduce the fabrication cost, the development and fabrication of SU-8 mold is replace by using a glass plate instead of silicon wafer which is used in the previous research. We designed a microfluidic chip for use with an IDE sensors to conduct multiplex detection of multiple channels. The microfluidic chip was designed to include multiplex detection for pathogen that consists of multiple channels of simultaneous results. The multi-channel microfluidic chip was designed, including the fluid outlet and inlet. A multi-channel microfluidic chip was used for pathogen detection. This paper sum up the fabrication of lab SU-8 mold using glass slide.

Combined surface-enhanced Raman spectroscopy biotags and microfluidic platform for quantitative ratiometric discrimination between noncancerous and cancerous cells in flow

NASA Astrophysics Data System (ADS)

Pallaoro, Alessia; Hoonejani, Mehran R.; Braun, Gary B.; Meinhart, Carl; Moskovits, Martin

2013-01-01

Surface-enhanced Raman spectroscopy (SERS) biotags (SBTs) that carry peptides as cell recognition moieties were made from polymer-encapsulated silver nanoparticle dimers, infused with unique Raman reporter molecules. We previously demonstrated their potential use for identification of malignant cells, a central goal in cancer research, through a multiplexed, ratiometric method that can confidently distinguish between cancerous and noncancerous epithelial prostate cells in vitro based on receptor overexpression. Progress has been made toward the application of this quantitative methodology for the identification of cancer cells in a microfluidic flow-focusing device. Beads are used as cell mimics to evaluate the devices. Cells (and beads) are simultaneously incubated with two sets of SBTs while in suspension, then injected into the device for laser interrogation under flow. Each cell event is characterized by a composite Raman spectrum, deconvoluted into its single components to ultimately determine their relative contribution. We have found that using SBTs ratiometrically can provide cell identification in flow, insensitive to normal causes of uncertainty in optical measurements such as variations in focal plane, cell concentration, autofluorescence, and turbidity.

Hot embossing and thermal bonding of poly(methyl methacrylate) microfluidic chips using positive temperature coefficient ceramic heater.

PubMed

Wang, Xia; Zhang, Luyan; Chen, Gang

2011-11-01

As a self-regulating heating device, positive temperature coefficient ceramic heater was employed for hot embossing and thermal bonding of poly(methyl methacrylate) microfluidic chip because it supplied constant-temperature heating without electrical control circuits. To emboss a channel plate, a piece of poly(methyl methacrylate) plate was sandwiched between a template and a microscopic glass slide on a positive temperature coefficient ceramic heater. All the assembled components were pressed between two elastic press heads of a spring-driven press while a voltage was applied to the heater for 10 min. Subsequently, the embossed poly(methyl methacrylate) plate bearing negative relief of channel networks was bonded with a piece of poly(methyl methacrylate) cover sheet to obtain a complete microchip using a positive temperature coefficient ceramic heater and a spring-driven press. High quality microfluidic chips fabricated by using the novel embossing/bonding device were successfully applied in the electrophoretic separation of three cations. Positive temperature coefficient ceramic heater indicates great promise for the low-cost production of poly(methyl methacrylate) microchips and should find wide applications in the fabrication of other thermoplastic polymer microfluidic devices.

A "place n play" modular pump for portable microfluidic applications.

PubMed

Li, Gang; Luo, Yahui; Chen, Qiang; Liao, Lingying; Zhao, Jianlong

2012-03-01

This paper presents an easy-to-use, power-free, and modular pump for portable microfluidic applications. The pump module is a degassed particle desorption polydimethylsiloxane (PDMS) slab with an integrated mesh-shaped chamber, which can be attached on the outlet port of microfluidic device to absorb the air in the microfluidic system and then to create a negative pressure for driving fluid. Different from the existing monolithic degassed PDMS pumps that are generally restricted to limited pumping capacity and are only compatible with PDMS-based microfluidic devices, this pump can offer various possible configures of pumping power by varying the geometries of the pump or by combining different pump modules and can also be employed in any material microfluidic devices. The key advantage of this pump is that its operation only requires the user to place the degassed PDMS slab on the outlet ports of microfluidic devices. To help design pumps with a suitable pumping performance, the effect of pump module geometry on its pumping capacity is also investigated. The results indicate that the performance of the degassed PDMS pump is strongly dependent on the surface area of the pump chamber, the exposure area and the volume of the PDMS pump slab. In addition, the initial volume of air in the closed microfluidic system and the cross-linking degree of PDMS also affect the performance of the degassed PDMS pump. Finally, we demonstrated the utility of this modular pumping method by applying it to a glass-based microfluidic device and a PDMS-based protein crystallization microfluidic device.

A “place n play” modular pump for portable microfluidic applications

PubMed Central

Li, Gang; Luo, Yahui; Chen, Qiang; Liao, Lingying; Zhao, Jianlong

2012-01-01

This paper presents an easy-to-use, power-free, and modular pump for portable microfluidic applications. The pump module is a degassed particle desorption polydimethylsiloxane (PDMS) slab with an integrated mesh-shaped chamber, which can be attached on the outlet port of microfluidic device to absorb the air in the microfluidic system and then to create a negative pressure for driving fluid. Different from the existing monolithic degassed PDMS pumps that are generally restricted to limited pumping capacity and are only compatible with PDMS-based microfluidic devices, this pump can offer various possible configures of pumping power by varying the geometries of the pump or by combining different pump modules and can also be employed in any material microfluidic devices. The key advantage of this pump is that its operation only requires the user to place the degassed PDMS slab on the outlet ports of microfluidic devices. To help design pumps with a suitable pumping performance, the effect of pump module geometry on its pumping capacity is also investigated. The results indicate that the performance of the degassed PDMS pump is strongly dependent on the surface area of the pump chamber, the exposure area and the volume of the PDMS pump slab. In addition, the initial volume of air in the closed microfluidic system and the cross-linking degree of PDMS also affect the performance of the degassed PDMS pump. Finally, we demonstrated the utility of this modular pumping method by applying it to a glass-based microfluidic device and a PDMS-based protein crystallization microfluidic device. PMID:22685507

Microfluidic routing of aqueous and organic flows at high pressures: fabrication and characterization of integrated polymer microvalve elements.

PubMed

Kirby, Brian J; Reichmuth, David S; Renzi, Ronald F; Shepodd, Timothy J; Wiedenman, Boyd J

2005-02-01

This paper presents the first systematic engineering study of the impact of chemical formulation and surface functionalization on the performace of free-standing microfluidic polymer elements used for high-pressure fluid control in glass microsystems. System design, chemical wet-etch processes, and laser-induced polymerization techniques are described, and parametric studies illustrate the effects of polymer formulation, glass surface modification, and geometric constraints on system performance parameters. In particular, this study shows that highly crosslinked and fluorinated polymers can overcome deficiencies in previously-reported microvalve architectures, particularly limited solvent compatibility. Substrate surface modification is shown effective in reducing the friction of the polymer-glass interface and thereby facilitating valve actuation. A microchip one-way valve constructed using this architecture shows a 2 x 10(8) ratio of forward and backward flow rates at 7 MPa. This valve architecture is integrated on chip with minimal dead volumes (70 pl), and should be applicable to systems (including chromatography and chemical synthesis devices) requiring high pressures and solvents of varying polarity.

How does the molecular network structure influence PDMS elastomer wettability?

NASA Astrophysics Data System (ADS)

Melillo, Matthew; Genzer, Jan

Poly(dimethylsiloxane) (PDMS) is one of the most common elastomers, with applications ranging from medical devices to absorbents for water treatment. Fundamental understanding of how liquids spread on the surface of and absorb into PDMS networks is of critical importance for the design and use of another application - microfluidic devices. We have systematically studied the effects of polymer molecular weight, loading of tetra-functional crosslinker, end-group chemical functionality, and the extent of dilution of the curing mixture on the mechanical and surface properties of end-linked PDMS networks. The gel and sol fractions, storage and loss moduli, liquid swelling ratios, and water contact angles have all been shown to vary greatly based on the aforementioned variables. Similar trends were observed for the commercial PDMS material, Sylgard-184. Our results have confirmed theories predicting the relationships between modulus and swelling. Furthermore, we have provided new evidence for the strong influence that substrate modulus and molecular network structure have on the wettability of PDMS elastomers. These findings will aid in the design and implementation of efficient microfluidics and other PDMS-based materials that involve the transport of liquids.

Optofluidic bioimaging platform for quantitative phase imaging of lab on a chip devices using digital holographic microscopy.

PubMed

Pandiyan, Vimal Prabhu; John, Renu

2016-01-20

We propose a versatile 3D phase-imaging microscope platform for real-time imaging of optomicrofluidic devices based on the principle of digital holographic microscopy (DHM). Lab-on-chip microfluidic devices fabricated on transparent polydimethylsiloxane (PDMS) and glass substrates have attained wide popularity in biological sensing applications. However, monitoring, visualization, and characterization of microfluidic devices, microfluidic flows, and the biochemical kinetics happening in these devices is difficult due to the lack of proper techniques for real-time imaging and analysis. The traditional bright-field microscopic techniques fail in imaging applications, as the microfluidic channels and the fluids carrying biological samples are transparent and not visible in bright light. Phase-based microscopy techniques that can image the phase of the microfluidic channel and changes in refractive indices due to the fluids and biological samples present in the channel are ideal for imaging the fluid flow dynamics in a microfluidic channel at high resolutions. This paper demonstrates three-dimensional imaging of a microfluidic device with nanometric depth precisions and high SNR. We demonstrate imaging of microelectrodes of nanometric thickness patterned on glass substrate and the microfluidic channel. Three-dimensional imaging of a transparent PDMS optomicrofluidic channel, fluid flow, and live yeast cell flow in this channel has been demonstrated using DHM. We also quantify the average velocity of fluid flow through the channel. In comparison to any conventional bright-field microscope, the 3D depth information in the images illustrated in this work carry much information about the biological system under observation. The results demonstrated in this paper prove the high potential of DHM in imaging optofluidic devices; detection of pathogens, cells, and bioanalytes on lab-on-chip devices; and in studying microfluidic dynamics in real time based on phase changes.

Electrodes for microfluidic applications

DOEpatents

Crocker, Robert W [Fremont, CA; Harnett, Cindy K [Livermore, CA; Rognlien, Judith L [Livermore, CA

2006-08-22

An electrode device for high pressure applications. These electrodes, designed to withstand pressure of greater than 10,000 psi, are adapted for use in microfluidic devices that employ electrokinetic or electrophoretic flow. The electrode is composed, generally, of an outer electrically insulating tubular body having a porous ceramic frit material disposed in one end of the outer body. The pores of the porous ceramic material are filled with an ion conductive polymer resin. A conductive material situated on the upper surface of the porous ceramic frit material and, thus isolated from direct contact with the electrolyte, forms a gas diffusion electrode. A metal current collector, in contact with the gas diffusion electrode, provides connection to a voltage source.

Development of a Mechatronic Syringe Pump to Control Fluid Flow in a Microfluidic Device Based on Polyimide Film

NASA Astrophysics Data System (ADS)

Sek Tee, Kian; Sharil Saripan, Muhammad; Yap, Hiung Yin; Fhong Soon, Chin

2017-08-01

With the advancement in microfluidic technology, fluid flow control for syringe pump is always essential. In this paper, a mechatronic syringe pump will be developed and customized to control the fluid flow in a poly-dimethylsiloxane (PDMS) microfluidic device based on a polyimide laminating film. The syringe pump is designed to drive fluid with flow rates of 100 and 1000 μl/min which intended to drive continuous fluid in a polyimide based microfluidic device. The electronic system consists of an Arduino microcontroller board and a uni-polar stepper motor. In the system, the uni-polar stepper motor was coupled to a linear slider attached to the plunger of a syringe pump. As the motor rotates, the plunger pumps the liquid out of the syringe. The accuracy of the fluid flow rate was determined by adjusting the number of micro-step/revolution to drive the stepper motor to infuse fluid into the microfluidic device. With the precise control of the electronic system, the syringe pump could accurately inject fluid volume at 100 and 1000 μl/min into a microfluidic device.

Mass-manufacturable polymer microfluidic device for dual fiber optical trapping.

PubMed

De Coster, Diane; Ottevaere, Heidi; Vervaeke, Michael; Van Erps, Jürgen; Callewaert, Manly; Wuytens, Pieter; Simpson, Stephen H; Hanna, Simon; De Malsche, Wim; Thienpont, Hugo

2015-11-30

We present a microfluidic chip in Polymethyl methacrylate (PMMA) for optical trapping of particles in an 80µm wide microchannel using two counterpropagating single-mode beams. The trapping fibers are separated from the sample fluid by 70µm thick polymer walls. We calculate the optical forces that act on particles flowing in the microchannel using wave optics in combination with non-sequential ray-tracing and further mathematical processing. Our results are compared with a theoretical model and the Mie theory. We use a novel fabrication process that consists of a premilling step and ultraprecision diamond tooling for the manufacturing of the molds and double-sided hot embossing for replication, resulting in a robust microfluidic chip for optical trapping. In a proof-of-concept demonstration, we show the trapping capabilities of the hot embossed chip by trapping spherical beads with a diameter of 6µm, 8µm and 10µm and use the power spectrum analysis of the trapped particle displacements to characterize the trap strength.

All-organic electrostrictive polymer composites with low driving electrical voltages for micro-fluidic pump applications

PubMed Central

Le, Minh Quyen; Capsal, Jean-Fabien; Galineau, Jérémy; Ganet, Florent; Yin, Xunqian; Yang, Mingchia (Dawn); Chateaux, Jean-François; Renaud, Louis; Malhaire, Christophe; Cottinet, Pierre-Jean; Liang, Richard

2015-01-01

This paper focuses on the improvement of a relaxor ferroelectric terpolymer, i.e., poly (vinylidene fluoride-trifluoroethylene-chlorofluoroethylene) [P(VDF-TrFE-CFE)], filled with a bis(2-ethylhexyl) phthalate (DEHP). The developed material gave rise to a significantly increased longitudinal electrostrictive strain, as well as an increased mechanical energy density under a relatively low electric field. These features were attributed to the considerably enhanced dielectric permittivity and a decreased Young modulus as a result of the introduction of only small DEHP plasticizer molecules. In addition, the plasticizer-filled terpolymer only exhibited a slight decrease of the dielectric breakdown strength, which was a great advantage with respect to the traditional polymer-based electrostrictive composites. More importantly, the approach proposed herein is promising for the future development and scale-up of new high-performance electrostrictive dielectrics under low applied electrical fields through modification simply by blending with a low-cost plasticizer. An experimental demonstration based on a flexible micro-fluidic application is described at the end of this paper, confirming the attractive characteristics of the proposed materials as well as the feasibility of integrating them as micro-actuators in small-scale devices. PMID:26139015

Appendix C: Automated Vitrification of Mammalian Embryos on a Digital Microfluidic Device.

PubMed

Liu, Jun; Pyne, Derek G; Abdelgawad, Mohamed; Sun, Yu

2017-01-01

This chapter introduces a digital microfluidic device that automates sample preparation for mammalian embryo vitrification. Individual microdroplets manipulated on the microfluidic device were used as microvessels to transport a single mouse embryo through a complete vitrification procedure. Advantages of this approach, compared to manual operation and channel-based microfluidic vitrification, include automated operation, cryoprotectant concentration gradient generation, and feasibility of loading and retrieval of embryos.

Microfluidic Droplet Dehydration for Concentrating Processes in Biomolecules

NASA Astrophysics Data System (ADS)

Anna, Shelley

2014-03-01

Droplets in microfluidic devices have proven useful as picoliter reactors for biochemical processing operations such as polymerase chain reaction, protein crystallization, and the study of enzyme kinetics. Although droplets are typically considered to be self-contained, constant volume reactors, there can be significant transport between the dispersed and continuous phases depending on solubility and other factors. In the present talk, we show that water droplets trapped within a microfluidic device for tens of hours slowly dehydrate, concentrating the contents encapsulated within. We use this slow dehydration along with control of the initial droplet composition to influence gellation, crystallization, and phase separation processes. By examining these concentrating processes in many trapped drops at once we gain insight into the stochastic nature of the events. In one example, we show that dehydration rate impacts the probability of forming a specific crystal habit in a crystallizing amino acid. In another example, we phase separate a common aqueous two-phase system within droplets and use the ensuing two phases to separate DNA from an initial mixture. We further influence wetting conditions between the two aqueous polymer phases and the continuous oil, promoting complete de-wetting and physical separation of the polymer phases. Thus, controlled dehydration of droplets allows for concentration, separation, and purification of important biomolecules on a chip.

Paper-based chemical and biological sensors: Engineering aspects.

PubMed

Ahmed, Snober; Bui, Minh-Phuong Ngoc; Abbas, Abdennour

2016-03-15

Remarkable efforts have been dedicated to paper-based chemosensors and biosensors over the last few years, mainly driven by the promise of reaching the best trade-off between performance, affordability and simplicity. Because of the low-cost and rapid prototyping of these sensors, recent research has been focused on providing affordable diagnostic devices to the developing world. The recent progress in sensitivity, multi-functionality and integration of microfluidic paper-based analytical devices (µPADs), increasingly suggests that this technology is not only attractive in resource-limited environments but it also represents a serious challenger to silicon, glass and polymer-based biosensors. This review discusses the design, chemistry and engineering aspects of these developments, with a focus on the past few years. Copyright © 2015 Elsevier B.V. All rights reserved.

Finger-triggered portable PDMS suction cup for equipment-free microfluidic pumping

NASA Astrophysics Data System (ADS)

Lee, Sanghyun; Kim, Hojin; Lee, Wonhyung; Kim, Joonwon

2018-12-01

This study presents a finger-triggered portable polydimethylsiloxane suction cup that enables equipment-free microfluidic pumping. The key feature of this method is that its operation only involves a "pressing-and-releasing" action for the cup placed at the outlet of a microfluidic device, which transports the fluid at the inlet toward the outlet through a microchannel. This method is simple, but effective and powerful. The cup is portable and can easily be fabricated from a three-dimensional printed mold, used without any pre-treatment, reversibly bonded to microfluidic devices without leakage, and applied to various material-based microfluidic devices. The effect of the suction cup geometry and fabrication conditions on the pumping performance was investigated. Furthermore, we demonstrated the practical applications of the suction cup by conducting an equipment-free pumping of thermoplastic-based microfluidic devices and water-in-oil droplet generation.

Particle-Based Microfluidic Device for Providing High Magnetic Field Gradients

NASA Technical Reports Server (NTRS)

Wong, Tak S. (Inventor); Lin, Adam Y. (Inventor)

2013-01-01

A microfluidic device for manipulating particles in a fluid has a device body that defines a main channel therein, in which the main channel has an inlet and an outlet. The device body further defines a particulate diverting channel therein, the particulate diverting channel being in fluid connection with the main channel between the inlet and the outlet of the main channel and having a particulate outlet. The microfluidic device also has a plurality of microparticles arranged proximate or in the main channel between the inlet of the main channel and the fluid connection of the particulate diverting channel to the main channel. The plurality of microparticles each comprises a material in a composition thereof having a magnetic susceptibility suitable to cause concentration of magnetic field lines of an applied magnetic field while in operation. A microfluidic particle-manipulation system has a microfluidic particle-manipulation device and a magnet disposed proximate the microfluidic particle-manipulation device.

Fabrication and Evaluation of Microfluidic Immunoassay Devices with Antibody-Immobilized Microbeads Retained in Porous Hydrogel Micropillars.

PubMed

Kasama, Toshihiro; Kaji, Noritada; Tokeshi, Manabu; Baba, Yoshinobu

2017-01-01

Due to the inherent characteristics including confinement of molecular diffusion and high surface-to-volume ratio, microfluidic device-based immunoassay has great advantages in cost, speed, sensitivity, and so on, compared with conventional techniques such as microtiter plate-based ELISA, latex agglutination method, and lateral flow immunochromatography. In this paper, we explain the detection of C-reactive protein as a model antigen by using our microfluidic immunoassay device, so-called immuno-pillar device. We describe in detail how we fabricated and used the immuno-pillar devices.

Desktop aligner for fabrication of multilayer microfluidic devices.

PubMed

Li, Xiang; Yu, Zeta Tak For; Geraldo, Dalton; Weng, Shinuo; Alve, Nitesh; Dun, Wu; Kini, Akshay; Patel, Karan; Shu, Roberto; Zhang, Feng; Li, Gang; Jin, Qinghui; Fu, Jianping

2015-07-01

Multilayer assembly is a commonly used technique to construct multilayer polydimethylsiloxane (PDMS)-based microfluidic devices with complex 3D architecture and connectivity for large-scale microfluidic integration. Accurate alignment of structure features on different PDMS layers before their permanent bonding is critical in determining the yield and quality of assembled multilayer microfluidic devices. Herein, we report a custom-built desktop aligner capable of both local and global alignments of PDMS layers covering a broad size range. Two digital microscopes were incorporated into the aligner design to allow accurate global alignment of PDMS structures up to 4 in. in diameter. Both local and global alignment accuracies of the desktop aligner were determined to be about 20 μm cm(-1). To demonstrate its utility for fabrication of integrated multilayer PDMS microfluidic devices, we applied the desktop aligner to achieve accurate alignment of different functional PDMS layers in multilayer microfluidics including an organs-on-chips device as well as a microfluidic device integrated with vertical passages connecting channels located in different PDMS layers. Owing to its convenient operation, high accuracy, low cost, light weight, and portability, the desktop aligner is useful for microfluidic researchers to achieve rapid and accurate alignment for generating multilayer PDMS microfluidic devices.

Desktop aligner for fabrication of multilayer microfluidic devices

PubMed Central

Li, Xiang; Yu, Zeta Tak For; Geraldo, Dalton; Weng, Shinuo; Alve, Nitesh; Dun, Wu; Kini, Akshay; Patel, Karan; Shu, Roberto; Zhang, Feng; Li, Gang; Jin, Qinghui; Fu, Jianping

2015-01-01

Multilayer assembly is a commonly used technique to construct multilayer polydimethylsiloxane (PDMS)-based microfluidic devices with complex 3D architecture and connectivity for large-scale microfluidic integration. Accurate alignment of structure features on different PDMS layers before their permanent bonding is critical in determining the yield and quality of assembled multilayer microfluidic devices. Herein, we report a custom-built desktop aligner capable of both local and global alignments of PDMS layers covering a broad size range. Two digital microscopes were incorporated into the aligner design to allow accurate global alignment of PDMS structures up to 4 in. in diameter. Both local and global alignment accuracies of the desktop aligner were determined to be about 20 μm cm−1. To demonstrate its utility for fabrication of integrated multilayer PDMS microfluidic devices, we applied the desktop aligner to achieve accurate alignment of different functional PDMS layers in multilayer microfluidics including an organs-on-chips device as well as a microfluidic device integrated with vertical passages connecting channels located in different PDMS layers. Owing to its convenient operation, high accuracy, low cost, light weight, and portability, the desktop aligner is useful for microfluidic researchers to achieve rapid and accurate alignment for generating multilayer PDMS microfluidic devices. PMID:26233409

Magnet-assisted device-level alignment for the fabrication of membrane-sandwiched polydimethylsiloxane microfluidic devices

NASA Astrophysics Data System (ADS)

Lu, J.-C.; Liao, W.-H.; Tung, Y.-C.

2012-07-01

Polydimethylsiloxane (PDMS) microfluidic device is one of the most essential techniques that advance microfluidics research in recent decades. PDMS is broadly exploited to construct microfluidic devices due to its unique and advantageous material properties. To realize more functionalities, PDMS microfluidic devices with multi-layer architectures, especially those with sandwiched membranes, have been developed for various applications. However, existing alignment methods for device fabrication are mainly based on manual observations, which are time consuming, inaccurate and inconsistent. This paper develops a magnet-assisted alignment method to enhance device-level alignment accuracy and precision without complicated fabrication processes. In the developed alignment method, magnets are embedded into PDMS layers at the corners of the device. The paired magnets are arranged in symmetric positions at each PDMS layer, and the magnetic attraction force automatically pulls the PDMS layers into the aligned position during assembly. This paper also applies the method to construct a practical microfluidic device, a tunable chaotic micromixer. The results demonstrate the successful operation of the device without failure, which suggests the accurate alignment and reliable bonding achieved by the method. Consequently, the fabrication method developed in this paper is promising to be exploited to construct various membrane-sandwiched PDMS microfluidic devices with more integrated functionalities to advance microfluidics research.

QR-on-a-chip: a computer-recognizable micro-pattern engraved microfluidic device for high-throughput image acquisition.

PubMed

Yun, Kyungwon; Lee, Hyunjae; Bang, Hyunwoo; Jeon, Noo Li

2016-02-21

This study proposes a novel way to achieve high-throughput image acquisition based on a computer-recognizable micro-pattern implemented on a microfluidic device. We integrated the QR code, a two-dimensional barcode system, onto the microfluidic device to simplify imaging of multiple ROIs (regions of interest). A standard QR code pattern was modified to arrays of cylindrical structures of polydimethylsiloxane (PDMS). Utilizing the recognition of the micro-pattern, the proposed system enables: (1) device identification, which allows referencing additional information of the device, such as device imaging sequences or the ROIs and (2) composing a coordinate system for an arbitrarily located microfluidic device with respect to the stage. Based on these functionalities, the proposed method performs one-step high-throughput imaging for data acquisition in microfluidic devices without further manual exploration and locating of the desired ROIs. In our experience, the proposed method significantly reduced the time for the preparation of an acquisition. We expect that the method will innovatively improve the prototype device data acquisition and analysis.

Optofluidic platforms based on surface-enhanced Raman scattering.

PubMed

Lim, Chaesung; Hong, Jongin; Chung, Bong Geun; deMello, Andrew J; Choo, Jaebum

2010-05-01

We report recent progress in the development of surface-enhanced Raman scattering (SERS)-based optofluidic platforms for the fast and sensitive detection of chemical and biological analytes. In the current context, a SERS-based optofluidic platform is defined as an integrated analytical device composed of a microfluidic element and a sensitive Raman spectrometer. Optofluidic devices for SERS detection normally involve nanocolloid-based microfluidic systems or metal nanostructure-embedded microfluidic systems. In the current review, recent advances in both approaches are surveyed and assessed. Additionally, integrated real-time sensing systems that combine portable Raman spectrometers with microfluidic devices are also reviewed. Such real-time sensing systems have significant utility in environmental monitoring, forensic science and homeland defense applications.

Super-Absorbent Polymer Valves and Colorimetric Chemistries for Time-Sequenced Discrete Sampling and Chloride Analysis of Sweat via Skin-Mounted Soft Microfluidics.

PubMed

Kim, Sung Bong; Zhang, Yi; Won, Sang Min; Bandodkar, Amay J; Sekine, Yurina; Xue, Yeguang; Koo, Jahyun; Harshman, Sean W; Martin, Jennifer A; Park, Jeong Min; Ray, Tyler R; Crawford, Kaitlyn E; Lee, Kyu-Tae; Choi, Jungil; Pitsch, Rhonda L; Grigsby, Claude C; Strang, Adam J; Chen, Yu-Yu; Xu, Shuai; Kim, Jeonghyun; Koh, Ahyeon; Ha, Jeong Sook; Huang, Yonggang; Kim, Seung Wook; Rogers, John A

2018-03-01

This paper introduces super absorbent polymer valves and colorimetric sensing reagents as enabling components of soft, skin-mounted microfluidic devices designed to capture, store, and chemically analyze sweat released from eccrine glands. The valving technology enables robust means for guiding the flow of sweat from an inlet location into a collection of isolated reservoirs, in a well-defined sequence. Analysis in these reservoirs involves a color responsive indicator of chloride concentration with a formulation tailored to offer stable operation with sensitivity optimized for the relevant physiological range. Evaluations on human subjects with comparisons against ex situ analysis illustrate the practical utility of these advances. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Multilayer based lab-on-a-chip-systems for substance testing

NASA Astrophysics Data System (ADS)

Sonntag, Frank; Grünzner, Stefan; Schmieder, Florian; Busek, Mathias; Klotzbach, Udo; Franke, Volker

2015-03-01

An integrated technology chain for laser-microstructuring and bonding of polymer foils for fast, flexible and low-cost manufacturing of multilayer lab-on-a-chip devices especially for complex cell and tissue culture applications, which provides pulsatile fluid flow within physiological ranges at low media-to-cells ratio, was developed and established. Initially the microfluidic system is constructively divided into individual layers which are formed by separate foils or plates. Based on the functional boundary conditions and the necessary properties of each layer the corresponding foils and plates are chosen. In the third step the foils and plates are laser microstructured and functionalized from both sides. In the fourth and last manufacturing step the multiple plates and foils are joined using thermal diffusion bonding. Membranes for pneumatically driven valves and micropumps where bonded via chemical surface modification. Based on the established lab-on-a-chip platform for perfused cell-based assays, a multilayer microfluidic system with two parallel connected cell culture chambers was successfully implemented.

Bio-Magnetics Interfacing Concepts: A Microfluidic System Using Magnetic Nanoparticles for Quantitative Detection of Biological Species

DTIC Science & Technology

2004-09-30

nanoparticles that consist of a polymer coated ?-Fe2O3 superparamagnetic core and CdSe/ZnS quantum dots (QDs) shell. A single layer of QDs was bound to the...Fe2O3) with polymer coating, the scale bar is 20 nm; b) A TEM image of QDs magnetic beads core-shell nanoparticles. The scale bar is 20 nm. c) A High...common practice in microfluidic/GMR sensor integration is using hybrid approaches by adding-on polymer based fluidic structures (such as PDMS fluidic

On-demand acoustic droplet splitting and steering in a disposable microfluidic chip.

PubMed

Park, Jinsoo; Jung, Jin Ho; Park, Kwangseok; Destgeer, Ghulam; Ahmed, Husnain; Ahmad, Raheel; Sung, Hyung Jin

2018-01-30

On-chip droplet splitting is one of the fundamental droplet-based microfluidic unit operations to control droplet volume after production and increase operational capability, flexibility, and throughput. Various droplet splitting methods have been proposed, and among them the acoustic droplet splitting method is promising because of its label-free operation without any physical or thermal damage to droplets. Previous acoustic droplet splitting methods faced several limitations: first, they employed a cross-type acoustofluidic device that precluded multichannel droplet splitting; second, they required irreversible bonding between a piezoelectric substrate and a microfluidic chip, such that the fluidic chip was not replaceable. Here, we present a parallel-type acoustofluidic device with a disposable microfluidic chip to address the limitations of previous acoustic droplet splitting devices. In the proposed device, an acoustic field is applied in the direction opposite to the flow direction to achieve multichannel droplet splitting and steering. A disposable polydimethylsiloxane microfluidic chip is employed in the developed device, thereby removing the need for permanent bonding and improving the flexibility of the droplet microfluidic device. We experimentally demonstrated on-demand acoustic droplet bi-splitting and steering with precise control over the droplet splitting ratio, and we investigated the underlying physical mechanisms of droplet splitting and steering based on Laplace pressure and ray acoustics analyses, respectively. We also demonstrated droplet tri-splitting to prove the feasibility of multichannel droplet splitting. The proposed on-demand acoustic droplet splitting device enables on-chip droplet volume control in various droplet-based microfluidic applications.

Topological and thermal properties of polypropylene composites based on oil palm biomass

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bhat, A. H., E-mail: aamir.bhat@petronas.com.my, E-mail: anie-yal88@yahoo.com; Dasan, Y. K., E-mail: aamir.bhat@petronas.com.my, E-mail: anie-yal88@yahoo.com

Roughness on pristine and polymer composite surfaces is of enormous practical importance for polymer applications. This study deals with the use of varying quantity of oil palm ash as a nanofiller in a polypropylene based matrix. The oil palm ash sample was preprocessed to break the particles into small diameter by using ultra sonication before using microfluidizer for further deduction in size and homogenization. The oil palm ash was made to undergo many passes through the microfluidizer for fine distribution of particles. Polypropylene based composites containing different loading percentage oil palm ash was granulated by twin screw extruder and thenmore » injection molded. The surface morphology of the OPA passed through microfluidizer was analyzed by Tapping Mode - Atomic Force Microscopy (TMAFM). Thermal analysis results showed an increase in the activation energy values. The thermal stability of the composite samples showed improvement as compared to the virgin polymer as corroborated by the on-set degradation temperatures and the temperatures at which 50% degradation occurred.« less

Simple Check Valves for Microfluidic Devices

NASA Technical Reports Server (NTRS)

Willis, Peter A.; Greer, Harold F.; Smith, J. Anthony

2010-01-01

A simple design concept for check valves has been adopted for microfluidic devices that consist mostly of (1) deformable fluorocarbon polymer membranes sandwiched between (2) borosilicate float glass wafers into which channels, valve seats, and holes have been etched. The first microfluidic devices in which these check valves are intended to be used are micro-capillary electrophoresis (microCE) devices undergoing development for use on Mars in detecting compounds indicative of life. In this application, it will be necessary to store some liquid samples in reservoirs in the devices for subsequent laboratory analysis, and check valves are needed to prevent cross-contamination of the samples. The simple check-valve design concept is also applicable to other microfluidic devices and to fluidic devices in general. These check valves are simplified microscopic versions of conventional rubber- flap check valves that are parts of numerous industrial and consumer products. These check valves are fabricated, not as separate components, but as integral parts of microfluidic devices. A check valve according to this concept consists of suitably shaped portions of a deformable membrane and the two glass wafers between which the membrane is sandwiched (see figure). The valve flap is formed by making an approximately semicircular cut in the membrane. The flap is centered over a hole in the lower glass wafer, through which hole the liquid in question is intended to flow upward into a wider hole, channel, or reservoir in the upper glass wafer. The radius of the cut exceeds the radius of the hole by an amount large enough to prevent settling of the flap into the hole. As in a conventional rubber-flap check valve, back pressure in the liquid pushes the flap against the valve seat (in this case, the valve seat is the adjacent surface of the lower glass wafer), thereby forming a seal that prevents backflow.

Biological implications of lab-on-a-chip devices fabricated using multi-jet modelling and stereolithography processes

NASA Astrophysics Data System (ADS)

Zhu, Feng; Macdonald, Niall; Skommer, Joanna; Wlodkowic, Donald

2015-06-01

Current microfabrication methods are often restricted to two-dimensional (2D) or two and a half dimensional (2.5D) structures. Those fabrication issues can be potentially addressed by emerging additive manufacturing technologies. Despite rapid growth of additive manufacturing technologies in tissue engineering, microfluidics has seen relatively little developments with regards to adopting 3D printing for rapid fabrication of complex chip-based devices. This has been due to two major factors: lack of sufficient resolution of current rapid-prototyping methods (usually >100 μm ) and optical transparency of polymers to allow in vitro imaging of specimens. We postulate that adopting innovative fabrication processes can provide effective solutions for prototyping and manufacturing of chip-based devices with high-aspect ratios (i.e. above ration of 20:1). This work provides a comprehensive investigation of commercially available additive manufacturing technologies as an alternative for rapid prototyping of complex monolithic Lab-on-a-Chip devices for biological applications. We explored both multi-jet modelling (MJM) and several stereolithography (SLA) processes with five different 3D printing resins. Compared with other rapid prototyping technologies such as PDMS soft lithography and infrared laser micromachining, we demonstrated that selected SLA technologies had superior resolution and feature quality. We also for the first time optimised the post-processing protocols and demonstrated polymer features under scanning electronic microscope (SEM). Finally we demonstrate that selected SLA polymers have optical properties enabling high-resolution biological imaging. A caution should be, however, exercised as more work is needed to develop fully bio-compatible and non-toxic polymer chemistries.

Rapid and low-cost hot-embossing of polycaprolactone microfluidic devices

NASA Astrophysics Data System (ADS)

Fan, Yiqiang; Liu, Shicheng; He, Jianyun; Gao, Kexin; Zhang, Yajun

2018-01-01

Polycaprolactone (PCL) is a low-cost biocompatible and biodegradable material which is highly suitable for the short-live applications like microfluidics in the biological and medical field. In this study, a rapid and low-cost microfabrication technique for PCL-based microfluidic devices is proposed, the SU-8 mold fabricated on the silicon substrate was used for the hot-embossing of microstructures on PCL. Since PCL after the molding process is optically non-transparent, to improve the visibility of the fluid in the microfluidic device and enclosing the microchannel, a transparency adhesive film which originally used for the sealing of PCR well-plate is used for the sealing of the microchannels embossed on PCL substrate. The profile of the fabricated microchannels was carefully characterized, the bonding strength is tested and several PCL-based microfluidic devices were also fabricated and tested for demonstration.

Surface engineered biosensors for the early detection of cancer

NASA Astrophysics Data System (ADS)

Islam, Muhymin

Cancer commences in the building block of human body which is cells and in most of the cases remains silent at early stage. Diseases are only expressed at molecular and cellular level at primary stages. Recognition of diseases at this micro and nano level might reduce the mortality rate of cancer significantly. This research work aimed to introduce novel electronic biosensors for for identification of cancer at cellular level. The dissertation study focuses on 1) Label-Free Isolation of Metastatic Tumor Cells Using Filter Based Microfluidic device; 2) Nanotextured Polymer Substrates for Enhanced Cancer Cell Isolation and Cell Growth; 3) Nanotextured Microfluidic Channel for Electrical Profiling and Detection of Tumor Cells from Blood; and 4) Single Biochip for the Detection of Tumor Cells by Electrical Profile and Surface Immobilized Aptamer. Standard silicon processing techniques were followed to fabricate all of the biosensors. Nantoextruing and surface functionalizon were also incorporated to elevate the efficiency of the devices. The first approach aimed to detect cancer cells from blood based on their mechanophysical properties. Cancer cells are larger than blood cells but highly elastic in nature. These cells can squeeze through small microchannels much smaller than their size. The cross sectional area of the microchannels was optimized to isolate tumor cells from blood. Nanotextured polymer substrates, a platform inspired from the natural basement membrane was used to enhance the isolation and growth of tumor cells. Micro reactive ion etching was performed to have better control on features of nantoxtured surfaces and did not require any template. Next, electrical measurement of ionic current was performed across single microchannel to detect tumor cells from blood. Later, nanotexturing enhanced the efficiency of the device by selectively altering the translocation profile of cancer cells. Eventually aptamer functionalized nanotextured polymer surface was integrated with current measurement facilities in a single biochip to discriminate tumor cells from blood with higher efficiency and selectivity. This biochip can be an implemented as a point-of-care device for the early detection of cancer at cellular level.

Additive manufacturing of three-dimensional (3D) microfluidic-based microelectromechanical systems (MEMS) for acoustofluidic applications.

PubMed

Cesewski, Ellen; Haring, Alexander P; Tong, Yuxin; Singh, Manjot; Thakur, Rajan; Laheri, Sahil; Read, Kaitlin A; Powell, Michael D; Oestreich, Kenneth J; Johnson, Blake N

2018-06-13

Three-dimensional (3D) printing now enables the fabrication of 3D structural electronics and microfluidics. Further, conventional subtractive manufacturing processes for microelectromechanical systems (MEMS) relatively limit device structure to two dimensions and require post-processing steps for interface with microfluidics. Thus, the objective of this work is to create an additive manufacturing approach for fabrication of 3D microfluidic-based MEMS devices that enables 3D configurations of electromechanical systems and simultaneous integration of microfluidics. Here, we demonstrate the ability to fabricate microfluidic-based acoustofluidic devices that contain orthogonal out-of-plane piezoelectric sensors and actuators using additive manufacturing. The devices were fabricated using a microextrusion 3D printing system that contained integrated pick-and-place functionality. Additively assembled materials and components included 3D printed epoxy, polydimethylsiloxane (PDMS), silver nanoparticles, and eutectic gallium-indium as well as robotically embedded piezoelectric chips (lead zirconate titanate (PZT)). Electrical impedance spectroscopy and finite element modeling studies showed the embedded PZT chips exhibited multiple resonant modes of varying mode shape over the 0-20 MHz frequency range. Flow visualization studies using neutrally buoyant particles (diameter = 0.8-70 μm) confirmed the 3D printed devices generated bulk acoustic waves (BAWs) capable of size-selective manipulation, trapping, and separation of suspended particles in droplets and microchannels. Flow visualization studies in a continuous flow format showed suspended particles could be moved toward or away from the walls of microfluidic channels based on selective actuation of in-plane or out-of-plane PZT chips. This work suggests additive manufacturing potentially provides new opportunities for the design and fabrication of acoustofluidic and microfluidic devices.

Dehydration induced phase transitions in a microfluidic droplet array for the separation of biomolecules

NASA Astrophysics Data System (ADS)

Nelson, Chris; Anna, Shelley

2013-11-01

Droplet-based strategies for fluid manipulation have seen significant application in microfluidics due to their ability to compartmentalize solutions and facilitate highly parallelized reactions. Functioning as micro-scale reaction vessels, droplets have been used to study protein crystallization, enzyme kinetics, and to encapsulate whole cells. Recently, the mass transport out of droplets has been used to concentrate solutions and induce phase transitions. Here, we show that droplets trapped in a microfluidic array will spontaneously dehydrate over the course of several hours. By loading these devices with an initially dilute aqueous polymer solution, we use this slow dehydration to observe phase transitions and the evolution of droplet morphology in hundreds of droplets simultaneously. As an example, we trap and dehydrate droplets of a model aqueous two-phase system consisting of polyethylene glycol and dextran. Initially the drops are homogenous, then after some time the polymer concentration reaches a critical point and two phases form. As water continues to leave the system, the drops transition from a microemulsion of DEX in PEG to a core-shell configuration. Eventually, changes in interfacial tension, driven by dehydration, cause the DEX core to completely de-wet from the PEG shell. Since aqueous two phase systems are able to selectively separate a variety of biomolecules, this core shedding behavior has the potential to provide selective, on-chip separation and concentration.

Tailoring microfluidic systems for organ-like cell culture applications using multiphysics simulations

NASA Astrophysics Data System (ADS)

Hagmeyer, Britta; Schütte, Julia; Böttger, Jan; Gebhardt, Rolf; Stelzle, Martin

2013-03-01

Replacing animal testing with in vitro cocultures of human cells is a long-term goal in pre-clinical drug tests used to gain reliable insight into drug-induced cell toxicity. However, current state-of-the-art 2D or 3D cell cultures aiming at mimicking human organs in vitro still lack organ-like morphology and perfusion and thus organ-like functions. To this end, microfluidic systems enable construction of cell culture devices which can be designed to more closely resemble the smallest functional unit of organs. Multiphysics simulations represent a powerful tool to study the various relevant physical phenomena and their impact on functionality inside microfluidic structures. This is particularly useful as it allows for assessment of system functions already during the design stage prior to actual chip fabrication. In the HepaChip®, dielectrophoretic forces are used to assemble human hepatocytes and human endothelial cells in liver sinusoid-like structures. Numerical simulations of flow distribution, shear stress, electrical fields and heat dissipation inside the cell assembly chambers as well as surface wetting and surface tension effects during filling of the microchannel network supported the design of this human-liver-on-chip microfluidic system for cell culture applications. Based on the device design resulting thereof, a prototype chip was injection-moulded in COP (cyclic olefin polymer). Functional hepatocyte and endothelial cell cocultures were established inside the HepaChip® showing excellent metabolic and secretory performance.

3D printed conformal microfluidics for isolation and profiling of biomarkers from whole organs.

PubMed

Singh, Manjot; Tong, Yuxin; Webster, Kelly; Cesewski, Ellen; Haring, Alexander P; Laheri, Sahil; Carswell, Bill; O'Brien, Timothy J; Aardema, Charles H; Senger, Ryan S; Robertson, John L; Johnson, Blake N

2017-07-25

The ability to interface microfluidic devices with native complex biological architectures, such as whole organs, has the potential to shift the paradigm for the study and analysis of biological tissue. Here, we show 3D printing can be used to fabricate bio-inspired conformal microfluidic devices that directly interface with the surface of whole organs. Structured-light scanning techniques enabled the 3D topographical matching of microfluidic device geometry to porcine kidney anatomy. Our studies show molecular species are spontaneously transferred from the organ cortex to the conformal microfluidic device in the presence of fluid flow through the organ-conforming microchannel. Large animal studies using porcine kidneys (n = 32 organs) revealed the profile of molecular species in the organ-conforming microfluidic stream was dependent on the organ preservation conditions. Enzyme-linked immunosorbent assay (ELISA) studies revealed conformal microfluidic devices isolate clinically relevant metabolic and pathophysiological biomarkers from whole organs, including heat shock protein 70 (HSP-70) and kidney injury molecule-1 (KIM-1), which were detected in the microfluidic device as high as 409 and 12 pg mL -1 , respectively. Overall, these results show conformal microfluidic devices enable a novel minimally invasive 'microfluidic biopsy' technique for isolation and profiling of biomarkers from whole organs within a clinically relevant interval. This achievement could shift the paradigm for whole organ preservation and assessment, thereby helping to relieve the organ shortage crisis through increased availability and quality of donor organs. Ultimately, this work provides a major advance in microfluidics through the design and manufacturing of organ-conforming microfluidic devices and a novel technique for microfluidic-based analysis of whole organs.

Microfluidic method for measuring viscosity using images from smartphone

NASA Astrophysics Data System (ADS)

Kim, Sooyeong; Kim, Kyung Chun; Yeom, Eunseop

2018-05-01

The viscosity of a fluid is the most important characteristic in fluid rheology. Many microfluidic devices have been proposed for easily measuring the fluid viscosity of small samples. A hybrid system consisting of a smartphone and microfluidic device can offer a mobile laboratory for performing a wide range of detection and analysis functions related to healthcare. In this study, a new mobile sensing method based on a microfluidic device was proposed for fluid viscosity measurements. By separately delivering sample and reference fluids into the two inlets of a Y-shaped microfluidic device, an interfacial line is induced at downstream of the device. Because the interfacial width (W) between the sample and reference fluid flows was determined by their pressure ratio, the viscosity (μ) of the sample could be estimated by measuring the interfacial width. To distinguish the interfacial width of a sample, optical images of the flows at downstream of the Y-shaped microfluidic device were acquired using a smartphone. To check the measurement accuracy of the proposed method, the viscosities of glycerol mixtures were compared with those measured by a conventional viscometer. The proposed technique was applied to monitor the variations in blood and oil samples depending on storage or rancidity. We expect that this mobile sensing method based on a microfluidic device could be utilized as a viscometer with significant advantages in terms of mobility, ease-of-operation, and data management.

Integrated Microfluidic Devices for Automated Microarray-Based Gene Expression and Genotyping Analysis

NASA Astrophysics Data System (ADS)

Liu, Robin H.; Lodes, Mike; Fuji, H. Sho; Danley, David; McShea, Andrew

Microarray assays typically involve multistage sample processing and fluidic handling, which are generally labor-intensive and time-consuming. Automation of these processes would improve robustness, reduce run-to-run and operator-to-operator variation, and reduce costs. In this chapter, a fully integrated and self-contained microfluidic biochip device that has been developed to automate the fluidic handling steps for microarray-based gene expression or genotyping analysis is presented. The device consists of a semiconductor-based CustomArray® chip with 12,000 features and a microfluidic cartridge. The CustomArray was manufactured using a semiconductor-based in situ synthesis technology. The micro-fluidic cartridge consists of microfluidic pumps, mixers, valves, fluid channels, and reagent storage chambers. Microarray hybridization and subsequent fluidic handling and reactions (including a number of washing and labeling steps) were performed in this fully automated and miniature device before fluorescent image scanning of the microarray chip. Electrochemical micropumps were integrated in the cartridge to provide pumping of liquid solutions. A micromixing technique based on gas bubbling generated by electrochemical micropumps was developed. Low-cost check valves were implemented in the cartridge to prevent cross-talk of the stored reagents. Gene expression study of the human leukemia cell line (K562) and genotyping detection and sequencing of influenza A subtypes have been demonstrated using this integrated biochip platform. For gene expression assays, the microfluidic CustomArray device detected sample RNAs with a concentration as low as 0.375 pM. Detection was quantitative over more than three orders of magnitude. Experiment also showed that chip-to-chip variability was low indicating that the integrated microfluidic devices eliminate manual fluidic handling steps that can be a significant source of variability in genomic analysis. The genotyping results showed that the device identified influenza A hemagglutinin and neuraminidase subtypes and sequenced portions of both genes, demonstrating the potential of integrated microfluidic and microarray technology for multiple virus detection. The device provides a cost-effective solution to eliminate labor-intensive and time-consuming fluidic handling steps and allows microarray-based DNA analysis in a rapid and automated fashion.

Low-cost bioanalysis on paper-based and its hybrid microfluidic platforms.

PubMed

Dou, Maowei; Sanjay, Sharma Timilsina; Benhabib, Merwan; Xu, Feng; Li, XiuJun

2015-12-01

Low-cost assays have broad applications ranging from human health diagnostics and food safety inspection to environmental analysis. Hence, low-cost assays are especially attractive for rural areas and developing countries, where financial resources are limited. Recently, paper-based microfluidic devices have emerged as a low-cost platform which greatly accelerates the point of care (POC) analysis in low-resource settings. This paper reviews recent advances of low-cost bioanalysis on paper-based microfluidic platforms, including fully paper-based and paper hybrid microfluidic platforms. In this review paper, we first summarized the fabrication techniques of fully paper-based microfluidic platforms, followed with their applications in human health diagnostics and food safety analysis. Then we highlighted paper hybrid microfluidic platforms and their applications, because hybrid platforms could draw benefits from multiple device substrates. Finally, we discussed the current limitations and perspective trends of paper-based microfluidic platforms for low-cost assays. Copyright © 2015 Elsevier B.V. All rights reserved.

Silicon microfluidic flow focusing devices for the production of size-controlled PLGA based drug loaded microparticles.

PubMed

Keohane, Kieran; Brennan, Des; Galvin, Paul; Griffin, Brendan T

2014-06-05

The increasing realisation of the impact of size and surface properties on the bio-distribution of drug loaded colloidal particles has driven the application of micro fabrication technologies for the precise engineering of drug loaded microparticles. This paper demonstrates an alternative approach for producing size controlled drug loaded PLGA based microparticles using silicon Microfluidic Flow Focusing Devices (MFFDs). Based on the precise geometry and dimensions of the flow focusing channel, microparticle size was successfully optimised by modifying the polymer type, disperse phase (Qd) flow rate, and continuous phase (Qc) flow rate. The microparticles produced ranged in sizes from 5 to 50 μm and were highly monodisperse (coefficient of variation <5%). A comparison of Ciclosporin (CsA) loaded PLGA microparticles produced by MFFDs vs conventional production techniques was also performed. MFFDs produced microparticles with a narrower size distribution profile, relative to the conventional approaches. In-vitro release kinetics of CsA was found to be influenced by the production technique, with the MFFD approach demonstrating the slowest rate of release over 7 days (4.99 ± 0.26%). Finally, MFFDs were utilised to produce pegylated microparticles using the block co-polymer, PEG-PLGA. In contrast to the smooth microparticles produced using PLGA, PEG-PLGA microparticles displayed a highly porous surface morphology and rapid CsA release, with 85 ± 6.68% CsA released after 24h. The findings from this study demonstrate the utility of silicon MFFDs for the precise control of size and surface morphology of PLGA based microparticles with potential drug delivery applications. Copyright © 2014 Elsevier B.V. All rights reserved.

Patterned Electrode-Based Amperometric Gas Sensor for Direct Nitric Oxide Detection within Microfluidic Devices

PubMed Central

Cha, Wansik; Tung, Yi-Chung; Meyerhoff, Mark E.; Takayama, Shuichi

2010-01-01

This manuscript describes a thin amperometric nitric oxide (NO) sensor that can be microchannel embedded to enable direct real-time detection of NO produced by cells cultured within the microdevice. A key for achieving the thin (~ 1 mm) planar sensor configuration required for sensor-channel integration is the use of gold/indium-tin oxide patterned electrode directly on a porous polymer membrane (pAu/ITO) as the base working electrode. Electrochemically deposited Au-hexacyanoferrate layer on pAu/ITO is used to catalyze NO oxidation to nitrite at lower applied potentials (0.65 ~ 0.75 V vs. Ag/AgCl) and stabilize current output. Furthermore, use of a gas-permeable membrane to separate internal sensor compartments from the sample phase imparts excellent NO selectivity over common interferents (e.g., nitrite, ascorbate, ammonia, etc.) present in culture media and biological fluids. The optimized sensor design reversibly detects NO down to ~1 nM level in stirred buffer and <10 nM in flowing buffer when integrated within a polymeric microfluidic device. We demonstrate utility of the channel-embedded sensor by monitoring NO generation from macrophages cultured within non-gas permeable microchannels, as they are stimulated with endotoxin. PMID:20329749

Getting the most from microfluidic platforms for biomedical applications (Conference Presentation)

NASA Astrophysics Data System (ADS)

Shen, Amy

2016-03-01

Microfluidics has emerged in recent years as a versatile method of manipulating fluids at small length-scales, and in particular, for generating and manipulating micron size droplets with controllable size and functionality. For example, many research groups developed microfluidics devices for cell encapsulation, and synthesizing functionalized polymer microspheres and inorganic nanoparticles with precise control over their shapes and sizes. In this talk, I will showcase 2 microfluidic platforms to highlight their versatility and potential biomedical applications. (1) Droplet microfluidic platforms (a) A droplet microfluidics method to fabricate alginate microspheres while simultaneously immobilizing anti-Mycobacterium tuberculosis complex IgY and anti-Escherichia coli IgG antibodies primarily on the porous alginate carriers for specific binding and binding affinity tests. The binding affinity of antibodies is directly measured by fluorescence intensity of stained target bacteria on the microspheres. We demonstrate that the functionalized alginate microspheres yield specificity comparable with an enzyme-linked immunosorbent assay. We can easily modify the size and shape of alginate microspheres, and increase the concentration of functionalized alginate microspheres to further enhance binding kinetics and enable multiplexing. (b) A novel droplet microfluidics method to image oxygen in single islets (pancreatic cells) for glucose sensing. Individual islets and a fluorescent oxygen-sensitive dye were encased within a thin alginate polymer microcapsule for insulin secretion monitoring. The sensing system operated similarly from 2-48 hours following encapsulation, and viability and function of the islets were not significantly affected by the encapsulation process. This approach should be applicable to other cell types and dyes sensitive to other biologically important molecules. (2) A microfluidic chamber to perform uniform electric field stimulation in circular shaped culturewares A 3D computer-aided designed (CAD) polymeric insert is designed and retrofitted to circular shaped culturewares in an integrated microfluidic electrical stimulation platform to generate uniform EF with higher cell yields. In particular, NIH/3T3 mouse embryonic fibroblast cells are used to validate the performance of the 3D designed Poly(methyl methacrylate) (PMMA) inserts in a circular-shaped 6-well plate. The CAD based inserts can be easily scaled up to further increase effective stimulation area percentages, and also be implemented in commercially available culturewares for a wide variety of EF-related research such as EF-cell interaction and tissue regeneration studies.

Formation of Cucurbit[8]uril-Based Supramolecular Hydrogel Beads Using Droplet-Based Microfluidics.

PubMed

Xu, Xuejiao; Appel, Eric A; Liu, Xin; Parker, Richard M; Scherman, Oren A; Abell, Chris

2015-09-14

Herein we describe the use of microdroplets as templates for the fabrication of uniform-sized supramolecular hydrogel beads, assembled by supramolecular cross-linking of functional biopolymers with the macrocyclic host molecule, cucurbit[8]uril (CB[8]). The microdroplets were formed containing diluted hydrogel precursors in solution, including the functional polymers and CB[8], in a microfluidic device. Subsequent evaporation of water from collected microdroplets concentrated the contents, driving the formation of the CB[8]-mediated host-guest ternary complex interactions and leading to the assembly of condensed three-dimensional polymeric scaffolds. Rehydration of the dried particles gave monodisperse hydrogel beads. Their equilibrium size was shown to be dependent on both the quantity of material loaded and the dimensions of the microfluidic flow focus. Fluorescein-labeled dextran was used to evaluate the efficacy of the hydrogel beads as a vector for controlled cargo release. Both passive, sustained release (hours) and triggered, fast release (minutes) of the FITC-dextran was observed, with the rate of sustained release dependent on the formulation. The kinetics of release was fitted to the Ritger-Peppas controlled release equation and shown to follow an anomalous (non-Fickian) transport mechanism.

Advantages and challenges of microfluidic cell culture in polydimethylsiloxane devices.

PubMed

Halldorsson, Skarphedinn; Lucumi, Edinson; Gómez-Sjöberg, Rafael; Fleming, Ronan M T

2015-01-15

Culture of cells using various microfluidic devices is becoming more common within experimental cell biology. At the same time, a technological radiation of microfluidic cell culture device designs is currently in progress. Ultimately, the utility of microfluidic cell culture will be determined by its capacity to permit new insights into cellular function. Especially insights that would otherwise be difficult or impossible to obtain with macroscopic cell culture in traditional polystyrene dishes, flasks or well-plates. Many decades of heuristic optimization have gone into perfecting conventional cell culture devices and protocols. In comparison, even for the most commonly used microfluidic cell culture devices, such as those fabricated from polydimethylsiloxane (PDMS), collective understanding of the differences in cellular behavior between microfluidic and macroscopic culture is still developing. Moving in vitro culture from macroscopic culture to PDMS based devices can come with unforeseen challenges. Changes in device material, surface coating, cell number per unit surface area or per unit media volume may all affect the outcome of otherwise standard protocols. In this review, we outline some of the advantages and challenges that may accompany a transition from macroscopic to microfluidic cell culture. We focus on decisive factors that distinguish macroscopic from microfluidic cell culture to encourage a reconsideration of how macroscopic cell culture principles might apply to microfluidic cell culture. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

Ceramic microparticles and capsules via microfluidic processing of a preceramic polymer

PubMed Central

Ye, Congwang; Chen, Anthony; Colombo, Paolo; Martinez, Carlos

2010-01-01

We have developed a robust technique to fabricate monodispersed solid and porous ceramic particles and capsules from single and double emulsion drops composed of silsesquioxane preceramic polymer. A microcapillary microfluidic device was used to generate the monodispersed drops. In this device, two round capillaries are aligned facing each other inside a square capillary. Three fluids are needed to generate the double emulsions. The inner fluid, which flows through the input capillary, and the middle fluid, which flows through the void space between the square and inner fluid capillaries, form a coaxial co-flow in a direction that is opposite to the flow of the outer fluid. As the three fluids are forced through the exit capillary, the inner and middle fluids break into monodispersed double emulsion drops in a single-step process, at rates of up to 2000 drops s−1. Once the drops are generated, the silsesquioxane is cross-linked in solution and the cross-linked particles are dried and pyrolysed in an inert atmosphere to form oxycarbide glass particles. Particles with diameters ranging from 30 to 180 µm, shell thicknesses ranging from 10 to 50 µm and shell pore diameters ranging from 1 to 10 µm were easily prepared by changing fluid flow rates, device dimensions and fluid composition. The produced particles and capsules can be used in their polymeric state or pyrolysed to ceramic. This technique can be extended to other preceramic polymers and can be used to generate unique core–shell multimaterial particles. PMID:20484226

Ceramic microparticles and capsules via microfluidic processing of a preceramic polymer.

PubMed

Ye, Congwang; Chen, Anthony; Colombo, Paolo; Martinez, Carlos

2010-08-06

We have developed a robust technique to fabricate monodispersed solid and porous ceramic particles and capsules from single and double emulsion drops composed of silsesquioxane preceramic polymer. A microcapillary microfluidic device was used to generate the monodispersed drops. In this device, two round capillaries are aligned facing each other inside a square capillary. Three fluids are needed to generate the double emulsions. The inner fluid, which flows through the input capillary, and the middle fluid, which flows through the void space between the square and inner fluid capillaries, form a coaxial co-flow in a direction that is opposite to the flow of the outer fluid. As the three fluids are forced through the exit capillary, the inner and middle fluids break into monodispersed double emulsion drops in a single-step process, at rates of up to 2000 drops s(-1). Once the drops are generated, the silsesquioxane is cross-linked in solution and the cross-linked particles are dried and pyrolysed in an inert atmosphere to form oxycarbide glass particles. Particles with diameters ranging from 30 to 180 microm, shell thicknesses ranging from 10 to 50 microm and shell pore diameters ranging from 1 to 10 microm were easily prepared by changing fluid flow rates, device dimensions and fluid composition. The produced particles and capsules can be used in their polymeric state or pyrolysed to ceramic. This technique can be extended to other preceramic polymers and can be used to generate unique core-shell multimaterial particles.

Generation of colloidal granules and capsules from double emulsion drops

NASA Astrophysics Data System (ADS)

Hess, Kathryn S.

Assemblies of colloidal particles are extensively used in ceramic processing, pharmaceuticals, inks and coatings. In this project, the aim was to develop a new technique to fabricate monodispersed colloidal assemblies. The use of microfluidic devices and emulsion processing allows for the fabrication of complex materials that can be used in a variety of applications. A microfluidic device is used to create monodispersed water/oil/water (w/o/w) double emulsions with interior droplets of colloidal silica suspension ranging in size from tens to hundreds of microns. By tailoring the osmotic pressure using glycerol as a solute in the continuous and inner phases of the emulsion, we can control the final volume size of the monodispersed silica colloidal crystals that form in the inner droplets of the double emulsion. Modifying the ionic strength in the colloidal dispersion can be used to affect the particle-particle interactions and crystal formation of the final colloidal particle. This w/o/w technique has been used with other systems of metal oxide colloids and cellulose nanocrystals. Encapsulation of the colloidal suspension in a polymer shell for the generation of ceramic-polymer core-shell particles has also been developed. These core-shell particles have spawned new research in the field of locally resonant acoustic metamaterials. Systems and chemistries for creating cellulose hydrogels within the double emulsions have also been researched. Water in oil single emulsions and double emulsions have been used to create cellulose hydrogel spheres in the sub-100 micron diameter range. Oil/water/oil double emulsions allow us to create stable cellulose capsules. The addition of a second hydrogel polymer, such as acrylate or alginate, further strengthens the cellulose gel network and can also be processed into capsules and particles using the microfluidic device. This work could have promising applications in acoustic metamaterials, personal care products, pharmaceuticals, and agricultural applications, among others.

An instrument-free, screen-printed paper microfluidic device that enables bio and chemical sensing.

PubMed

Mohammadi, Saeed; Maeki, Masatoshi; Mohamadi, Reza M; Ishida, Akihiko; Tani, Hirofumi; Tokeshi, Manabu

2015-10-07

This paper describes a simple and instrument-free screen-printing method to fabricate hydrophilic channels by patterning polydimethylsiloxane (PDMS) onto chromatography paper. Clearly recognizable border lines were formed between hydrophilic and hydrophobic areas. The minimum width of the printed channel to deliver an aqueous sample was 600 μm, as obtained by this method. Fabricated microfluidic paper-based analytical devices (μPADs) were tested for several colorimetric assays of pH, glucose, and protein in both buffer and artificial urine samples and results were obtained in less than 30 min. The limits of detection (LODs) for glucose and bovine serum albumin (BSA) were 5 mM and 8 μM, respectively. Furthermore, the pH values of different solutions were visually recognised with the naked eye by using a sensitive ink. Ultimately, it is expected that this PDMS-screen-printing (PSP) methodology for μPADs can be readily translated to other colorimetric detection and hydrophilic channels surrounded by a hydrophobic polymer can be formed to transport fluids toward target zones.

Biological implications of polydimethylsiloxane-based microfluidic cell culture†

PubMed Central

Regehr, Keil J.; Domenech, Maribella; Koepsel, Justin T.; Carver, Kristopher C.; Ellison-Zelski, Stephanie J.; Murphy, William L.; Schuler, Linda A.; Alarid, Elaine T.; Beebe, David J.

2009-01-01

Polydimethylsiloxane (PDMS) has become a staple of the microfluidics community by virtue of its simple fabrication process and material attributes, such as gas permeability, optical transparency, and flexibility. As microfluidic systems are put toward biological problems and increasingly utilized as cell culture platforms, the material properties of PDMS must be considered in a biological context. Two properties of PDMS were addressed in this study: the leaching of uncured oligomers from the polymer network into microchannel media, and the absorption of small, hydrophobic molecules (i.e. estrogen) from serum-containing media into the polymer bulk. Uncured PDMS oligomers were detectable via MALDI-MS in microchannel media both before and after Soxhlet extraction of PDMS devices in ethanol. Additionally, PDMS oligomers were identified in the plasma membranes of NMuMG cells cultured in PDMS microchannels for 24 hours. Cells cultured in extracted microchannels also contained a detectable amount of uncured PDMS. It was shown that MCF-7 cells seeded directly on PDMS inserts were responsive to hydrophilic prolactin but not hydrophobic estrogen, reflecting its specificity for absorbing small, hydrophobic molecules; and the presence of PDMS floating in wells significantly reduced cellular response to estrogen in a serum-dependent manner. Quantification of estrogen via ELISA revealed that microchannel estrogen partitioned rapidly into the surrounding PDMS to a ratio of approximately 9:1. Pretreatments such as blocking with serum or pre-absorbing estrogen for 24 hours did not affect estrogen loss from PDMS-based microchannels. These findings highlight the importance of careful consideration of culture system properties when determining an appropriate environment for biological experiments. PMID:19606288

PDMS Network Structure-Property Relationships: Influence of Molecular Architecture on Mechanical and Wetting Properties

NASA Astrophysics Data System (ADS)

Melillo, Matthew Joseph

Poly(dimethylsiloxane) (PDMS) is one of the most common elastomers, with applications ranging from sealants and marine-antifouling coatings to medical devices and absorbents for water treatment. Fundamental understanding of how liquids spread on the surface of and absorb into and leach out of PDMS networks is of critical importance for the design and use in another application - microfluidic devices. The growing use of PDMS in microfluidic devices raises the concern that some researchers may use this material without fully understanding all of its advantages, drawbacks, and intricacies. The primary goal of this Ph.D. dissertation is to elucidate PDMS network molecular structure to macroscopic property relationships and to demonstrate how molecular architecture can alter dynamic mechanical and wetting characteristics. We prepare PDMS materials by using vinyl/ tetrakis(dimethylsiloxy)silane (TDSS) and silanol/ tetraethylorthosilicate (TEOS) combinations of PDMS end-groups and crosslinkers as two model systems. Under constant curing conditions, we systematically study the effects of polymer molecular weight, loading of crosslinker, and end-group chemical functionality on the extent of gelation and the dynamic mechanical and water wetting properties of end-linked PDMS networks. The extent of the gelation reaction is determined using the Soxhlet extraction to quantify the amount of material that did and did not participate in the crosslinking reactions, termed the gel and sol fractions, respectively. We use the Miller-Macosko model in conjunction with the gel fraction and precise chemical composition (i.e., stoichiometric ratio and molecular weight) to determine the fractions of elastic and pendant material, the molecular weight between chemical crosslinks, and the average effective functionality of the crosslinker molecule. Based on dynamic mechanical testing, we find that the maximum storage moduli are achieved at optimal stoichiometric conditions in the vinyl/TDSS and commercial PDMS-based Sylgard 184 composite, but only keep improving with additional crosslinker in the silanol/TEOS systems due to in situ TEOS aggregation. We relate molecular network topology to mechanical properties using outputs from the Miller-Macosko model in the vinyl/TDSS system. The elastic fraction and storage modulus correlate well, as do the pendant fraction and the loss tangent, demonstrating the importance of each fraction in bulk mechanical properties. By studying the dynamic behavior of water droplets wetting PDMS substrates, we observe non-linear wetting behaviors that are markedly different from linear behaviors seen on glassy polymer substrates. The non-linear behavior is only observed prior to extraction, while after extraction, both systems demonstrate behavior similar to glassy polymers. This reveals the dramatic role small amounts of uncrosslinked materials present in the sol fraction play in the surface wetting dynamics of PDMS materials. We further demonstrate the role of uncrosslinked material by adding silicone oils into otherwise fully crosslinked PDMS networks and study their wetting properties. Through careful formulation and preparation of PDMS materials, compared to simply mixing two formulations present in Sylgard 184, one can apply polymer network models to glean useful information about network topology. The benefits of doing so outweigh the costs. We stress the importance of performing Soxhlet extraction to remove unreacted components from PDMS materials, even when using optimal stoichiometry. These mobile molecules that remain after crosslinking can alter significantly wetting behavior and readily leach into liquid environments. However, it is equally important to stress that Soxhlet extraction will not remove all unreacted material. Some will always remain in PDMS, which is often the practice in preparing microfluidic devices. While Sylgard 184 is very well suited for some applications, the results presented in this dissertation demonstrate to researchers that the material does have its limitations and that other options are available. These findings will aid in the design and implementation of reliable microfluidic devices and other PDMS-based materials that encounter liquid interfaces.

Laser micromachining as a metallization tool for microfluidic polymer stacks

NASA Astrophysics Data System (ADS)

Brettschneider, T.; Dorrer, C.; Czurratis, D.; Zengerle, R.; Daub, M.

2013-03-01

A novel assembly approach for the integration of metal structures into polymeric microfluidic systems is described. The presented production process is completely based on a single solid-state laser source, which is used to incorporate metal foils into a polymeric multi-layer stack by laser bonding and ablation processes. Chemical reagents or glues are not required. The polymer stack contains a flexible membrane which can be used for realizing microfluidic valves and pumps. The metal-to-polymer bond was investigated for different metal foils and plasma treatments, yielding a maximum peel strength of Rps = 1.33 N mm-1. A minimum structure size of 10 µm was determined by 3D microscopy of the laser cut line. As an example application, two different metal foils were used in combination to micromachine a standardized type-T thermocouple on a polymer substrate. An additional laser process was developed which allows metal-to-metal welding in close vicinity to the polymer substrate. With this process step, the reliability of the electrical contact could be increased to survive at least 400 PCR temperature cycles at very low contact resistances.

Tunable Microfluidic Devices for Hydrodynamic Fractionation of Cells and Beads: A Review

PubMed Central

Alvankarian, Jafar; Majlis, Burhanuddin Yeop

2015-01-01

The adjustable microfluidic devices that have been developed for hydrodynamic-based fractionation of beads and cells are important for fast performance tunability through interaction of mechanical properties of particles in fluid flow and mechanically flexible microstructures. In this review, the research works reported on fabrication and testing of the tunable elastomeric microfluidic devices for applications such as separation, filtration, isolation, and trapping of single or bulk of microbeads or cells are discussed. Such microfluidic systems for rapid performance alteration are classified in two groups of bulk deformation of microdevices using external mechanical forces, and local deformation of microstructures using flexible membrane by pneumatic pressure. The main advantage of membrane-based tunable systems has been addressed to be the high capability of integration with other microdevice components. The stretchable devices based on bulk deformation of microstructures have in common advantage of simplicity in design and fabrication process. PMID:26610519

Micro Electromechanical Systems (MEMS) Based Microfluidic Devices for Biomedical Applications

PubMed Central

Ashraf, Muhammad Waseem; Tayyaba, Shahzadi; Afzulpurkar, Nitin

2011-01-01

Micro Electromechanical Systems (MEMS) based microfluidic devices have gained popularity in biomedicine field over the last few years. In this paper, a comprehensive overview of microfluidic devices such as micropumps and microneedles has been presented for biomedical applications. The aim of this paper is to present the major features and issues related to micropumps and microneedles, e.g., working principles, actuation methods, fabrication techniques, construction, performance parameters, failure analysis, testing, safety issues, applications, commercialization issues and future prospects. Based on the actuation mechanisms, the micropumps are classified into two main types, i.e., mechanical and non-mechanical micropumps. Microneedles can be categorized according to their structure, fabrication process, material, overall shape, tip shape, size, array density and application. The presented literature review on micropumps and microneedles will provide comprehensive information for researchers working on design and development of microfluidic devices for biomedical applications. PMID:21747700

Engineering and evaluating drug delivery particles in microfluidic devices.

PubMed

Björnmalm, Mattias; Yan, Yan; Caruso, Frank

2014-09-28

The development of new and improved particle-based drug delivery is underpinned by an enhanced ability to engineer particles with high fidelity and integrity, as well as increased knowledge of their biological performance. Microfluidics can facilitate these processes through the engineering of spatiotemporally highly controlled environments using designed microstructures in combination with physical phenomena present at the microscale. In this review, we discuss microfluidics in the context of addressing key challenges in particle-based drug delivery. We provide an overview of how microfluidic devices can: (i) be employed to engineer particles, by providing highly controlled interfaces, and (ii) be used to establish dynamic in vitro models that mimic in vivo environments for studying the biological behavior of engineered particles. Finally, we discuss how the flexible and modular nature of microfluidic devices provides opportunities to create increasingly realistic models of the in vivo milieu (including multi-cell, multi-tissue and even multi-organ devices), and how ongoing developments toward commercialization of microfluidic tools are opening up new opportunities for the engineering and evaluation of drug delivery particles. Copyright © 2014 Elsevier B.V. All rights reserved.

Design of pressure-driven microfluidic networks using electric circuit analogy.

PubMed

Oh, Kwang W; Lee, Kangsun; Ahn, Byungwook; Furlani, Edward P

2012-02-07

This article reviews the application of electric circuit methods for the analysis of pressure-driven microfluidic networks with an emphasis on concentration- and flow-dependent systems. The application of circuit methods to microfluidics is based on the analogous behaviour of hydraulic and electric circuits with correlations of pressure to voltage, volumetric flow rate to current, and hydraulic to electric resistance. Circuit analysis enables rapid predictions of pressure-driven laminar flow in microchannels and is very useful for designing complex microfluidic networks in advance of fabrication. This article provides a comprehensive overview of the physics of pressure-driven laminar flow, the formal analogy between electric and hydraulic circuits, applications of circuit theory to microfluidic network-based devices, recent development and applications of concentration- and flow-dependent microfluidic networks, and promising future applications. The lab-on-a-chip (LOC) and microfluidics community will gain insightful ideas and practical design strategies for developing unique microfluidic network-based devices to address a broad range of biological, chemical, pharmaceutical, and other scientific and technical challenges.

Design and fabrication of chemically robust three-dimensional microfluidic valves.

PubMed

Maltezos, George; Garcia, Erika; Hanrahan, Grady; Gomez, Frank A; Vyawahare, Saurabh; Vyawhare, Saurabh; van Dam, R Michael; Chen, Yan; Scherer, Axel

2007-09-01

A current problem in microfluidics is that poly(dimethylsiloxane) (PDMS), used to fabricate many microfluidic devices, is not compatible with most organic solvents. Fluorinated compounds are more chemically robust than PDMS but, historically, it has been nearly impossible to construct valves out of them by multilayer soft lithography (MSL) due to the difficulty of bonding layers made of "non-stick" fluoropolymers necessary to create traditional microfluidic valves. With our new three-dimensional (3D) valve design we can fabricate microfluidic devices from fluorinated compounds in a single monolithic layer that is resistant to most organic solvents with minimal swelling. This paper describes the design and development of 3D microfluidic valves by molding of a perfluoropolyether, termed Sifel, onto printed wax molds. The fabrication of Sifel-based microfluidic devices using this technique has great potential in chemical synthesis and analysis.

Mitigated reactive oxygen species generation leads to an improvement of cell proliferation on poly[glycidyl methacrylate-co-poly(ethylene glycol) methacrylate] functionalized polydimethylsiloxane surfaces.

PubMed

Yu, Ling; Shi, ZhuanZhuan; Gao, LiXia; Li, ChangMing

2015-09-01

In vitro cell-based analysis is strongly affected by material's surface chemical properties. The cell spreading, migration, and proliferation on a substrate surface are initiated and controlled by successful adhesion, particularly for anchor-dependent cells. Unfortunately, polydimethylsiloxane (PDMS), one of the most used polymeric materials for construction of microfluidic and miniaturized biomedical analytic devices, is not a cell-friendly surface because of its inherent hydrophobic property. Herein, a poly[glycidyl methacrylate-co-poly(ethylene glycol) methacrylate] (poly(GMA-co-pEGMA)) polymer brush was synthesized on a PDMS surface through a surface-initiated atom-transfer radical polymerization method. Contact angle and Fourier transform infrared characterization show that the poly (GMA-co-pEGMA) polymer brush functionalization can increase wettability of PDMS and introduce epoxy, hydroxyl, and ether groups into PDMS surface. In vitro cell growth assay demonstrates that cell adhesion and proliferation on poly(GMA-co-pEGMA) polymer brush-functionalized PDMS (poly(GMA-co-pEGMA)@PDMS) are better than on pristine PDMS. Additionally, immobilization of collagen type I (CI) and fibronectin (FN) on poly(GMA-co-pEGMA)@PDMS is better than direct coating of CI and FN on pristine PDMS to promote cell adhesion. Furthermore, increased intracellular reactive oxygen species and cell mitochondrial membrane depolarization, two indicators of cell oxidative stress, are observed from cells growing on pristine PDMS, but not from those on poly(GMA-co-pEGMA)@PDMS. Collectively, we demonstrate that poly(GMA-co-pEGMA) functionalization can enhance cell adhesion and proliferation on PDMS, and thus can be potentially used for microfluidic cell assay devices for cellular physiology study or drug screening. © 2015 Wiley Periodicals, Inc.

Single polymer dynamics in semi-dilute unentangled and entangled solutions: from molecular conformation to normal stress

NASA Astrophysics Data System (ADS)

Schroeder, Charles

Semi-dilute polymer solutions are encountered in a wide array of applications such as advanced 3D printing technologies. Semi-dilute solutions are characterized by large fluctuations in concentration, such that hydrodynamic interactions, excluded volume interactions, and transient chain entanglements may be important, which greatly complicates analytical modeling and theoretical treatment. Despite recent progress, we still lack a complete molecular-level understanding of polymer dynamics in these systems. In this talk, I will discuss three recent projects in my group to study semi-dilute solutions that focus on single molecule studies of linear and ring polymers and a new method to measure normal stresses in microfluidic devices based on the Stokes trap. In the first effort, we use single polymer techniques to investigate the dynamics of semi-dilute unentangled and semi-dilute entangled DNA solutions in extensional flow, including polymer relaxation from high stretch, transient stretching dynamics in step-strain experiments, and steady-state stretching in flow. In the semi-dilute unentangled regime, our results show a power-law scaling of the longest polymer relaxation time that is consistent with scaling arguments based on the double cross-over regime. Upon increasing concentration, we observe a transition region in dynamics to the entangled regime. We also studied the transient and steady-state stretching dynamics in extensional flow using the Stokes trap, and our results show a decrease in transient polymer stretch and a milder coil-to-stretch transition for semi-dilute polymer solutions compared to dilute solutions, which is interpreted in the context of a critical Weissenberg number Wi at the coil-to-stretch transition. Interestingly, we observe a unique set of polymer conformations in semi-dilute unentangled solutions that are highly suggestive of transient topological entanglements in solutions that are nominally unentangled at equilibrium. Taken together, these results suggest that the transient stretching pathways in semi-dilute solution extensional flows are qualitatively different than for both dilute solutions and for semi-dilute solutions in shear flow. In a second effort, we studied the dynamics of ring polymers in background solutions of semi-dilute linear polymers. Interestingly, we observe strikingly large fluctuations in steady-state polymer extension for ring polymers in flow, which occurs due to the interplay between polymer topology and concentration leading to chain `threading' in flow. In a third effort, we developed a new microfluidic method to measure normal stress and extensional viscosity that can be loosely described as passive yet non-linear microrheology. In particular, we incorporated 3-D particle imaging velocimetry (PIV) with the Stokes trap to study extensional flow-induced particle migration in semi-dilute polymer solutions. Experimental results are analyzed using the framework of a second-order-fluid model, which allows for measurement of normal stress and extensional viscosity in semi-dilute polymer solutions, all of which is a first-of-its-kind demonstration. Microfluidic measurements of extensional viscosity are directly compared to the dripping-onto-substrate or DOS method, and good agreement is generally observed. Overall, our work aims to provide a molecular-level understanding of the role of polymer topology and concentration on bulk rheological properties by using single polymer techniques.

Modelling of capillary-driven flow for closed paper-based microfluidic channels

NASA Astrophysics Data System (ADS)

Songok, Joel; Toivakka, Martti

2017-06-01

Paper-based microfluidics is an emerging field focused on creating inexpensive devices, with simple fabrication methods for applications in various fields including healthcare, environmental monitoring and veterinary medicine. Understanding the flow of liquid is important in achieving consistent operation of the devices. This paper proposes capillary models to predict flow in paper-based microfluidic channels, which include a flow accelerating hydrophobic top cover. The models, which consider both non-absorbing and absorbing substrates, are in good agreement with the experimental results.

Surface-Controlled Properties of Myosin Studied by Electric Field Modulation.

PubMed

van Zalinge, Harm; Ramsey, Laurence C; Aveyard, Jenny; Persson, Malin; Mansson, Alf; Nicolau, Dan V

2015-08-04

The efficiency of dynamic nanodevices using surface-immobilized protein molecular motors, which have been proposed for diagnostics, drug discovery, and biocomputation, critically depends on the ability to precisely control the motion of motor-propelled, individual cytoskeletal filaments transporting cargo to designated locations. The efficiency of these devices also critically depends on the proper function of the propelling motors, which is controlled by their interaction with the surfaces they are immobilized on. Here we use a microfluidic device to study how the motion of the motile elements, i.e., actin filaments propelled by heavy mero-myosin (HMM) motor fragments immobilized on various surfaces, is altered by the application of electrical loads generated by an external electric field with strengths ranging from 0 to 8 kVm(-1). Because the motility is intimately linked to the function of surface-immobilized motors, the study also showed how the adsorption properties of HMM on various surfaces, such as nitrocellulose (NC), trimethylclorosilane (TMCS), poly(methyl methacrylate) (PMMA), poly(tert-butyl methacrylate) (PtBMA), and poly(butyl methacrylate) (PBMA), can be characterized using an external field. It was found that at an electric field of 5 kVm(-1) the force exerted on the filaments is sufficient to overcome the frictionlike resistive force of the inactive motors. It was also found that the effect of assisting electric fields on the relative increase in the sliding velocity was markedly higher for the TMCS-derivatized surface than for all other polymer-based surfaces. An explanation of this behavior, based on the molecular rigidity of the TMCS-on-glass surfaces as opposed to the flexibility of the polymer-based ones, is considered. To this end, the proposed microfluidic device could be used to select appropriate surfaces for future lab-on-a-chip applications as illustrated here for the almost ideal TMCS surface. Furthermore, the proposed methodology can be used to gain fundamental insights into the functioning of protein molecular motors, such as the force exerted by the motors under different operational conditions.

Manufacture of micro fluidic devices by laser welding using thermal transfer printing techniques

NASA Astrophysics Data System (ADS)

Klein, R.; Klein, K. F.; Tobisch, T.; Thoelken, D.; Belz, M.

2016-03-01

Micro-fluidic devices are widely used today in the areas of medical diagnostics and drug research, as well as for applications within the process, electronics and chemical industry. Microliters of fluids or single cell to cell interactions can be conveniently analyzed with such devices using fluorescence imaging, phase contrast microscopy or spectroscopic techniques. Typical micro-fluidic devices consist of a thermoplastic base component with chambers and channels covered by a hermetic fluid and gas tight sealed lid component. Both components are usually from the same or similar thermoplastic material. Different mechanical, adhesive or thermal joining processes can be used to assemble base component and lid. Today, laser beam welding shows the potential to become a novel manufacturing opportunity for midsize and large scale production of micro-fluidic devices resulting in excellent processing quality by localized heat input and low thermal stress to the device during processing. For laser welding, optical absorption of the resin and laser wavelength has to be matched for proper joining. This paper will focus on a new approach to prepare micro-fluidic channels in such devices using a thermal transfer printing process, where an optical absorbing layer absorbs the laser energy. Advantages of this process will be discussed in combination with laser welding of optical transparent micro-fluidic devices.

Fabrication of Three-dimensional Paper-based Microfluidic Devices for Immunoassays.

PubMed

Fernandes, Syrena C; Wilson, Daniel J; Mace, Charles R

2017-03-09

Paper wicks fluids autonomously due to capillary action. By patterning paper with hydrophobic barriers, the transport of fluids can be controlled and directed within a layer of paper. Moreover, stacking multiple layers of patterned paper creates sophisticated three-dimensional microfluidic networks that can support the development of analytical and bioanalytical assays. Paper-based microfluidic devices are inexpensive, portable, easy to use, and require no external equipment to operate. As a result, they hold great promise as a platform for point-of-care diagnostics. In order to properly evaluate the utility and analytical performance of paper-based devices, suitable methods must be developed to ensure their manufacture is reproducible and at a scale that is appropriate for laboratory settings. In this manuscript, a method to fabricate a general device architecture that can be used for paper-based immunoassays is described. We use a form of additive manufacturing (multi-layer lamination) to prepare devices that comprise multiple layers of patterned paper and patterned adhesive. In addition to demonstrating the proper use of these three-dimensional paper-based microfluidic devices with an immunoassay for human chorionic gonadotropin (hCG), errors in the manufacturing process that may result in device failures are discussed. We expect this approach to manufacturing paper-based devices will find broad utility in the development of analytical applications designed specifically for limited-resource settings.

Castable three-dimensional stationary phase for electric field-driven applications

DOEpatents

Shepodd, Timothy J.; Whinnery, Jr., Leroy; Even, Jr., William R.

2005-01-25

A polymer material useful as the porous dielectric medium for microfluidic devices generally and electrokinetic pumps in particular. The polymer material is produced from an inverse (water-in-oil) emulsion that creates a 3-dimensional network characterized by small pores and high internal volume, characteristics that are particularly desirable for the dielectric medium for electrokinetic pumps. Further, the material can be cast-to-shape inside a microchannel. The use of bifunctional monomers provides for charge density within the polymer structure sufficient to support electroosmotic flow. The 3-dimensional polymeric material can also be covalently bound to the channel walls thereby making it suitable for high-pressure applications.

Castable three-dimensional stationary phase for electric field-driven applications

DOEpatents

Shepodd, Timothy J [Livermore, CA; Whinnery, Jr., Leroy; Even, Jr., William R.

2009-02-10

A polymer material useful as the porous dielectric medium for microfluidic devices generally and electrokinetic pumps in particular. The polymer material is produced from an inverse (water-in-oil) emulsion that creates a 3-dimensional network characterized by small pores and high internal volume, characteristics that are particularly desirable for the dielectric medium for electrokinetic pumps. Further, the material can be cast-to-shape inside a microchannel. The use of bifunctional monomers provides for charge density within the polymer structure sufficient to support electroosmotic flow. The 3-dimensional polymeric material can also be covalently bound to the channel walls thereby making it suitable for high-pressure applications.

Continuous microfluidic assembly of biodegradable poly(beta-amino ester)/DNA nanoparticles for enhanced gene delivery.

PubMed

Wilson, David R; Mosenia, Arman; Suprenant, Mark P; Upadhya, Rahul; Routkevitch, Denis; Meyer, Randall A; Quinones-Hinojosa, Alfredo; Green, Jordan J

2017-06-01

Translation of biomaterial-based nanoparticle formulations to the clinic faces significant challenges including efficacy, safety, consistency and scale-up of manufacturing, and stability during long-term storage. Continuous microfluidic fabrication of polymeric nanoparticles has the potential to alleviate the challenges associated with manufacture, while offering a scalable solution for clinical level production. Poly(beta-amino esters) (PBAE)s are a class of biodegradable cationic polymers that self-assemble with anionic plasmid DNA to form polyplex nanoparticles that have been shown to be effective for transfecting cancer cells specifically in vitro and in vivo. Here, we demonstrate the use of a microfluidic device for the continuous and scalable production of PBAE/DNA nanoparticles followed by lyophilization and long term storage that results in improved in vitro efficacy in multiple cancer cell lines compared to nanoparticles produced by bulk mixing as well as in comparison to widely used commercially available transfection reagents polyethylenimine and Lipofectamine® 2000. We further characterized the nanoparticles using nanoparticle tracking analysis (NTA) to show that microfluidic mixing resulted in fewer DNA-free polymeric nanoparticles compared to those produced by bulk mixing. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1813-1825, 2017. © 2017 Wiley Periodicals, Inc.

Ice matrix in reconfigurable microfluidic systems

NASA Astrophysics Data System (ADS)

Bossi, A. M.; Vareijka, M.; Piletska, E. V.; Turner, A. P. F.; Meglinski, I.; Piletsky, S. A.

2013-07-01

Microfluidic devices find many applications in biotechnologies. Here, we introduce a flexible and biocompatible microfluidic ice-based platform with tunable parameters and configuration of microfluidic patterns that can be changed multiple times during experiments. Freezing and melting of cavities, channels and complex relief structures created and maintained in the bulk of ice by continuous scanning of an infrared laser beam are used as a valve action in microfluidic systems. We demonstrate that pre-concentration of samples and transport of ions and dyes through the open channels created can be achieved in ice microfluidic patterns by IR laser-assisted zone melting. The proposed approach can be useful for performing separation and sensing processes in flexible reconfigurable microfluidic devices.

Novel concept of washing for microfluidic paper-based analytical devices based on capillary force of paper substrates.

PubMed

Mohammadi, Saeed; Busa, Lori Shayne Alamo; Maeki, Masatoshi; Mohamadi, Reza M; Ishida, Akihiko; Tani, Hirofumi; Tokeshi, Manabu

2016-11-01

A novel washing technique for microfluidic paper-based analytical devices (μPADs) that is based on the spontaneous capillary action of paper and eliminates unbound antigen and antibody in a sandwich immunoassay is reported. Liquids can flow through a porous medium (such as paper) in the absence of external pressure as a result of capillary action. Uniform results were achieved when washing a paper substrate in a PDMS holder which was integrated with a cartridge absorber acting as a porous medium. Our study demonstrated that applying this washing technique would allow μPADs to become the least expensive microfluidic device platform with high reproducibility and sensitivity. In a model μPAD assay that utilized this novel washing technique, C-reactive protein (CRP) was detected with a limit of detection (LOD) of 5 μg mL -1 . Graphical Abstract A novel washing technique for microfluidic paper-based analytical devices (μPADs) that is based on the spontaneous capillary action of paper and eliminates unbound antigen and antibody in a sandwich immunoassay is reported.

Finger-Powered Electro-Digital-Microfluidics.

PubMed

Peng, Cheng; Ju, Y Sungtaek

2017-01-01

Portable microfluidic devices are promising for point-of-care (POC) diagnosis and bio- and environmental surveillance in resource-constrained or non-laboratory environments. Lateral-flow devices, some built off paper or strings, have been widely developed but the fixed layouts of their underlying wicking/microchannel structures limit their flexibility and present challenges in implementing multistep reactions. Digital microfluidics can circumvent these difficulties by addressing discrete droplets individually. Existing approaches to digital microfluidics, however, often require bulky power supplies/batteries and high voltage circuits. We present a scheme to drive digital microfluidic devices by converting mechanical energy of human fingers to electrical energy using an array of piezoelectric elements. We describe the integration our scheme into two promising digital microfluidics platforms: one based on the electro-wetting-on-dielectric (EWOD) phenomenon and the other on the electrophoretic control of droplet (EPD). Basic operations of droplet manipulations, such as droplet transport, merging and splitting, are demonstrated using the finger-powered digital-microfluidics.

Cost Effective Paper-Based Colorimetric Microfluidic Devices and Mobile Phone Camera Readers for the Classroom

ERIC Educational Resources Information Center

Koesdjojo, Myra T.; Pengpumkiat, Sumate; Wu, Yuanyuan; Boonloed, Anukul; Huynh, Daniel; Remcho, Thomas P.; Remcho, Vincent T.

2015-01-01

We have developed a simple and direct method to fabricate paper-based microfluidic devices that can be used for a wide range of colorimetric assay applications. With these devices, assays can be performed within minutes to allow for quantitative colorimetric analysis by use of a widely accessible iPhone camera and an RGB color reader application…

Encapsulation of cell into monodispersed hydrogels on microfluidic device

NASA Astrophysics Data System (ADS)

Choi, Chang-Hyoung; Lee, Ji-Hye; Shim, Hyun-Woo; Lee, Nae-Rym; Jung, Jae-Hoon; Yoon, Tae-Ho; Kim, Dong-Pyo; Lee, Chang-Soo

2007-12-01

In here, we present the microfluidic approach to produce monodispersed microbeads that will contain viable cells. The utilization of microfludics is helpful to synthesize monodispersed alginate hydrogels and in situ encapsulate cell into the generating hydrogels in microfludic device. First, the condition of formation of hydrogels in multiphase flows including oil, CaCl II, and alginate was optimized. Based on the preliminary survey, microfludic device could easily manipulate the size of alginate beads having narrow size distribution. The microfluidic method manipulates the size of hydrogel microbeads from 30 to 200um with a variation less than 2%. For the proof of concept of cell entrapment, the live yeast expressing green fluorescence protein is successfully encapsulated in microfluidic device.

Femtosecond laser microfabrication in polymers towards memory devices and microfluidic applications

NASA Astrophysics Data System (ADS)

Deepak, K. L. N.; Venugopal Rao, S.; Narayana Rao, D.

2011-12-01

We have investigated femtosecond laser induced microstructures, gratings, and craters in four different polymers: poly methyl methacrylate (PMMA), poly dimethyl siloxane (PDMS), polystyrene (PS) and poly vinyl alcohol (PVA) using Ti:sapphire laser delivering 800 nm, 100 femtosecond (fs) pulses at 1 kHz repetition rate with a maximum pulse energy of 1 mJ. Local chemical modifications leading to the formation of optical centers and peroxide radicals which were studied using UV-Visible absorption and emission, confocal micro-Raman and Electron Spin Resonance (ESR) spectroscopic techniques.

Additive manufacturing of lab-on-a-chip devices: promises and challenges

NASA Astrophysics Data System (ADS)

Zhu, Feng; Macdonald, Niall P.; Cooper, Jonathan M.; Wlodkowic, Donald

2013-12-01

This work describes a preliminary investigation of commercially available 3D printing technologies for rapid prototyping and low volume fabrication of Lab-on-a-Chip devices. The main motivation of the work was to use off-the-shelf 3D printing methods in order to rapidly and inexpensively build microfluidic devices with complex geometric features and reduce the need to use clear room environment and conventional microfabrication techniques. Both multi-jet modelling (MJM) and stereolithography (SLA) processes were explored. MJM printed devices were fabricated using a HD3500+ (3D Systems) high-definition printer using a thermo-polymer VisiJet Crystal (3D Systems) substratum that allows for a z-axis resolution of 16 μm and 25 μm x-y accuracy. SLA printed devices were produced using a Viper Pro (3D Systems) stereolithography system using Watershed 11122XC (DSM Somos) and Dreve Fototec 7150 Clear (Dreve Otoplastik GmbH) resins which allow for a z-axis resolution of 50 μm and 25 μm x-y accuracy. Fabrication results compared favourably with other forms of rapid prototyping such as laser cut PMMA devices and PDMS moulded microfluidic devices of the same design. Both processes allowed for fabrication of monolithic, optically transparent devices with features in the 100 μm range requiring minimal post-processing. Optical polymer qualities following different post-processing methods were also tested in both brightfield and fluorescence imaging of transgenic zebrafish embryos. Finally, we show that only ethanol-treated Dreve Fototec 7150 Clear resign proved to be non-toxic to human cell lines and fish embryos in fish toxicity assays (FET) requiring further investigation of 3D printing materials.

Ionic current devices-Recent progress in the merging of electronic, microfluidic, and biomimetic structures.

PubMed

Koo, Hyung-Jun; Velev, Orlin D

2013-05-09

We review the recent progress in the emerging area of devices and circuits operating on the basis of ionic currents. These devices operate at the intersection of electrochemistry, electronics, and microfluidics, and their potential applications are inspired by essential biological processes such as neural transmission. Ionic current rectification has been demonstrated in diode-like devices containing electrolyte solutions, hydrogel, or hydrated nanofilms. More complex functions have been realized in ionic current based transistors, solar cells, and switching memory devices. Microfluidic channels and networks-an intrinsic component of the ionic devices-could play the role of wires and circuits in conventional electronics.

Detection of heavy metal by paper-based microfluidics.

PubMed

Lin, Yang; Gritsenko, Dmitry; Feng, Shaolong; Teh, Yi Chen; Lu, Xiaonan; Xu, Jie

2016-09-15

Heavy metal pollution has shown great threat to the environment and public health worldwide. Current methods for the detection of heavy metals require expensive instrumentation and laborious operation, which can only be accomplished in centralized laboratories. Various microfluidic paper-based analytical devices have been developed recently as simple, cheap and disposable alternatives to conventional ones for on-site detection of heavy metals. In this review, we first summarize current development of paper-based analytical devices and discuss the selection of paper substrates, methods of device fabrication, and relevant theories in these devices. We then compare and categorize recent reports on detection of heavy metals using paper-based microfluidic devices on the basis of various detection mechanisms, such as colorimetric, fluorescent, and electrochemical methods. To finalize, the future development and trend in this field are discussed. Copyright © 2016 Elsevier B.V. All rights reserved.

Three-dimensional ordered titanium dioxide-zirconium dioxide film-based microfluidic device for efficient on-chip phosphopeptide enrichment.

PubMed

Zhao, De; He, Zhongyuan; Wang, Gang; Wang, Hongzhi; Zhang, Qinghong; Li, Yaogang

2016-09-15

Microfluidic technology plays a significant role in separating biomolecules, because of its miniaturization, integration, and automation. Introducing micro/nanostructured functional materials can improve the properties of microfluidic devices, and extend their application. Inverse opal has a three-dimensional ordered net-like structure. It possesses a large surface area and exhibits good mass transport, making it a good candidate for bio-separation. This study exploits inverse opal titanium dioxide-zirconium dioxide films for on-chip phosphopeptide enrichment. Titanium dioxide-zirconium dioxide inverse opal film-based microfluidic devices were constructed from templates of 270-, 340-, and 370-nm-diameter poly(methylmethacrylate) spheres. The phosphopeptide enrichments of these devices were determined by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. The device constructed from the 270-nm-diameter sphere template exhibited good comprehensive phosphopeptide enrichment, and was the best among these three devices. Because the size of opal template used in construction was the smallest, the inverse opal film therefore had the smallest pore sizes and the largest surface area. Enrichment by this device was also better than those of similar devices based on nanoparticle films and single component films. The titanium dioxide-zirconium dioxide inverse opal film-based device provides a promising approach for the efficient separation of various biomolecules. Copyright © 2016 Elsevier Inc. All rights reserved.

Automated Long-Term Monitoring of Parallel Microfluidic Operations Applying a Machine Vision-Assisted Positioning Method

PubMed Central

Yip, Hon Ming; Li, John C. S.; Cui, Xin; Gao, Qiannan; Leung, Chi Chiu

2014-01-01

As microfluidics has been applied extensively in many cell and biochemical applications, monitoring the related processes is an important requirement. In this work, we design and fabricate a high-throughput microfluidic device which contains 32 microchambers to perform automated parallel microfluidic operations and monitoring on an automated stage of a microscope. Images are captured at multiple spots on the device during the operations for monitoring samples in microchambers in parallel; yet the device positions may vary at different time points throughout operations as the device moves back and forth on a motorized microscopic stage. Here, we report an image-based positioning strategy to realign the chamber position before every recording of microscopic image. We fabricate alignment marks at defined locations next to the chambers in the microfluidic device as reference positions. We also develop image processing algorithms to recognize the chamber positions in real-time, followed by realigning the chambers to their preset positions in the captured images. We perform experiments to validate and characterize the device functionality and the automated realignment operation. Together, this microfluidic realignment strategy can be a platform technology to achieve precise positioning of multiple chambers for general microfluidic applications requiring long-term parallel monitoring of cell and biochemical activities. PMID:25133248

Biologically Inspired Electronic, Photovoltaic and Microfluidic Devices Based on Aqueous Soft Matter

NASA Astrophysics Data System (ADS)

Koo, Hyung Jun

Hydrogels are a water-based soft material where three dimensional networks of hydrophilic polymer retain large amounts of water. We developed hydrogel based devices with new functionalities inspired by materials, structures and processes in nature. The advantages, such as softness, biocompatibility and high ionic conductivity, could enable hydrogels to be novel materials for biomimetic devices operated by ionic current. Moreover, microfluidic patterns are easily embedded in moldable hydrogels and allow for unique convective/diffusive transport mechanism in porous gel to be used for uniform delivery of reagent solution. We first developed and characterized a device with unidirectional ionic current flow across a SiO2/Gel junction, which showed highly efficient rectification of the ionic current by non-linear conductivity of SiO2 films. Addition of polyelectrolytes and salt to the gel layer significantly improved the performance of the new diode device because of the enhanced gel conductance. A soft matter based diode composed of hydrogel and liquid metal (eutectic gallium indium, EGaIn) was also presented. The ability to control the thickness, and thus resistivity, of an insulating oxide skin on the metal enables the current rectification. The effect of ionic conductivity and pH on the formation of the insulating oxide was investigated in a simple model system with liquid metal/electrolyte solution or hydrogel/Pt interfaces. Finally, we present a diode composed entirely of soft materials by replacing the platinum electrode with a second liquid metal electrode. A new type of hydrogel-based photovoltaic systems (HGPVs) was constructed. Two photosensitive ionized molecules embedded in aqueous gel served as photoactive species. The HGPVs showed performance comparable with or higher than those of some other biomimetic or ionic photovoltaic systems reported recently. We suggest a provisional mechanism of the device operation, based on a synergetic effect of the two dye molecules. To reduce the fabrication cost without efficiency loss, we found an inexpensive replacement of the expensive Pt counter-electrode with copper coated with carbon materials. Biologically derived photoactive molecules, such as Chlorophyll and Photosystem II, were successfully operated in the aqueous gel of such HGPVs. As a proof of demonstration of biomimetic structures, a light driven biomimetic reactor was developed by using hydrogel media with embedded photocatalytic TiO2 nanoparticles. Uniform supply of the reactants and extraction of the products was accomplished via a microfluidic channel network, broadly similar to the vein structure of live leaves. The dyes were transported in the gel between the microchannels and degraded by photocatalytic oxidation by the illuminated TiO2 particles. Quantitative analysis of the photocatalytic degradation rate of the injected dyes revealed that the microvascular reactor has high quantum efficiency per catalyst mass. Numerical modeling was performed to explore how a soluble reagent could be supplied rapidly and efficiently through microfluidic channel networks embedded in hydrogels. The computational model takes into account the fluid transport in porous media and the solute convection and diffusion, to simulate the solute distribution and outflux with time in microfluidic hydrogel media. The effect of the channel dimensions and shapes on mass transport rapidity and efficiency was quantitatively evaluated. Experimental data proved the validity of the time dependent concentration profile calculated by the simulation. Lastly, a microfluidic hydrogel solar cell with biomimetic regeneration functionality was demonstrated as a result of the above experimental and modeling studies. A new concept of open and replenishable photovoltaics was constructed on the basis of dye-sensitized solar cells. Photovoltaic reagents, dyes and redox electrolytes, were uniformly delivered via microfluidic networks embedded in a hydrogel, resulting in increase of photocurrent generation. The regeneration process was established, based on the pH dependence of adsorption/desorption kinetics of the dye molecules on a TiO2 photoanode. Complete and reliable recovery of the photocurrent after an accelerated photodegradation in the biomimetic photovoltaics was demonstrated.

Three-Dimensional Printing Based Hybrid Manufacturing of Microfluidic Devices.

PubMed

Alapan, Yunus; Hasan, Muhammad Noman; Shen, Richang; Gurkan, Umut A

2015-05-01

Microfluidic platforms offer revolutionary and practical solutions to challenging problems in biology and medicine. Even though traditional micro/nanofabrication technologies expedited the emergence of the microfluidics field, recent advances in advanced additive manufacturing hold significant potential for single-step, stand-alone microfluidic device fabrication. One such technology, which holds a significant promise for next generation microsystem fabrication is three-dimensional (3D) printing. Presently, building 3D printed stand-alone microfluidic devices with fully embedded microchannels for applications in biology and medicine has the following challenges: (i) limitations in achievable design complexity, (ii) need for a wider variety of transparent materials, (iii) limited z-resolution, (iv) absence of extremely smooth surface finish, and (v) limitations in precision fabrication of hollow and void sections with extremely high surface area to volume ratio. We developed a new way to fabricate stand-alone microfluidic devices with integrated manifolds and embedded microchannels by utilizing a 3D printing and laser micromachined lamination based hybrid manufacturing approach. In this new fabrication method, we exploit the minimized fabrication steps enabled by 3D printing, and reduced assembly complexities facilitated by laser micromachined lamination method. The new hybrid fabrication method enables key features for advanced microfluidic system architecture: (i) increased design complexity in 3D, (ii) improved control over microflow behavior in all three directions and in multiple layers, (iii) transverse multilayer flow and precisely integrated flow distribution, and (iv) enhanced transparency for high resolution imaging and analysis. Hybrid manufacturing approaches hold great potential in advancing microfluidic device fabrication in terms of standardization, fast production, and user-independent manufacturing.

Three-Dimensional Printing Based Hybrid Manufacturing of Microfluidic Devices

PubMed Central

Shen, Richang; Gurkan, Umut A.

2016-01-01

Microfluidic platforms offer revolutionary and practical solutions to challenging problems in biology and medicine. Even though traditional micro/nanofabrication technologies expedited the emergence of the microfluidics field, recent advances in advanced additive manufacturing hold significant potential for single-step, stand-alone microfluidic device fabrication. One such technology, which holds a significant promise for next generation microsystem fabrication is three-dimensional (3D) printing. Presently, building 3D printed stand-alone microfluidic devices with fully embedded microchannels for applications in biology and medicine has the following challenges: (i) limitations in achievable design complexity, (ii) need for a wider variety of transparent materials, (iii) limited z-resolution, (iv) absence of extremely smooth surface finish, and (v) limitations in precision fabrication of hollow and void sections with extremely high surface area to volume ratio. We developed a new way to fabricate stand-alone microfluidic devices with integrated manifolds and embedded microchannels by utilizing a 3D printing and laser micromachined lamination based hybrid manufacturing approach. In this new fabrication method, we exploit the minimized fabrication steps enabled by 3D printing, and reduced assembly complexities facilitated by laser micromachined lamination method. The new hybrid fabrication method enables key features for advanced microfluidic system architecture: (i) increased design complexity in 3D, (ii) improved control over microflow behavior in all three directions and in multiple layers, (iii) transverse multilayer flow and precisely integrated flow distribution, and (iv) enhanced transparency for high resolution imaging and analysis. Hybrid manufacturing approaches hold great potential in advancing microfluidic device fabrication in terms of standardization, fast production, and user-independent manufacturing. PMID:27512530

Soft materials with recoverable shape factors from extreme distortion states

DOE PAGES

Goff, Jonathan; Sulaiman, Santy; Arkles, Barry; ...

2016-01-20

We present elastomeric polysiloxane nanocomposites with elongations of >5000% (more than 3× greater than any previously reported material) with excellent shape recovery. Highly deformable materials are desirable for the fabrication of stretchable implants and microfluidic devices. No crosslinking or domain formation is observed by a variety of analytical techniques, suggesting that their elastomeric behavior is caused by polymer chain entanglements.

Paper-based enzymatic microfluidic fuel cell: From a two-stream flow device to a single-stream lateral flow strip

NASA Astrophysics Data System (ADS)

González-Guerrero, Maria José; del Campo, F. Javier; Esquivel, Juan Pablo; Giroud, Fabien; Minteer, Shelley D.; Sabaté, Neus

2016-09-01

This work presents a first approach towards the development of a cost-effective enzymatic paper-based glucose/O2 microfluidic fuel cell in which fluid transport is based on capillary action. A first fuel cell configuration consists of a Y-shaped paper device with the fuel and the oxidant flowing in parallel over carbon paper electrodes modified with bioelectrocatalytic enzymes. The anode consists of a ferrocenium-based polyethyleneimine polymer linked to glucose oxidase (GOx/Fc-C6-LPEI), while the cathode contains a mixture of laccase, anthracene-modified multiwall carbon nanotubes, and tetrabutylammonium bromide-modified Nafion (MWCNTs/laccase/TBAB-Nafion). Subsequently, the Y-shaped configuration is improved to use a single solution containing both, the anolyte and the catholyte. Thus, the electrolytes pHs of the fuel and the oxidant solutions are adapted to an intermediate pH of 5.5. Finally, the fuel cell is run with this single solution obtaining a maximum open circuit of 0.55 ± 0.04 V and a maximum current and power density of 225 ± 17 μA cm-2 and 24 ± 5 μW cm-2, respectively. Hence, a power source closer to a commercial application (similar to conventional lateral flow test strips) is developed and successfully operated. This system can be used to supply the energy required to power microelectronics demanding low power consumption.

Fast pesticide detection inside microfluidic device with integrated optical pH, oxygen sensors and algal fluorescence.

PubMed

Tahirbegi, Islam Bogachan; Ehgartner, Josef; Sulzer, Philipp; Zieger, Silvia; Kasjanow, Alice; Paradiso, Mirco; Strobl, Martin; Bouwes, Dominique; Mayr, Torsten

2017-02-15

The necessities of developing fast, portable, cheap and easy to handle pesticide detection platforms are getting attention of scientific and industrial communities. Although there are some approaches to develop microchip based pesticide detection platforms, there is no compact microfluidic device for the complementary, fast, cheap, reusable and reliable analysis of different pesticides. In this work, a microfluidic device is developed for in-situ analysis of pesticide concentration detected via metabolism/photosynthesis of Chlamydomonas reinhardtii algal cells (algae) in tap water. Algae are grown in glass based microfluidic chip, which contains integrated optical pH and oxygen sensors in a portable system for on-site detection. In addition, intrinsic algal fluorescence is detected to analyze the pesticide concentration in parallel to pH and oxygen sensors with integrated fluorescence detectors. The response of the algae under the effect of different concentrations of pesticides is evaluated and complementary inhibition effects depending on the pesticide concentration are demonstrated. The three different sensors allow the determination of various pesticide concentrations in the nanomolar concentration range. The miniaturized system provides the fast quantification of pesticides in less than 10min and enables the study of toxic effects of different pesticides on Chlamydomonas reinhardtii green algae. Consequently, the microfluidic device described here provides fast and complementary detection of different pesticides with algae in a novel glass based microfluidic device with integrated optical pH, oxygen sensors and algal fluorescence. Copyright © 2016 Elsevier B.V. All rights reserved.

Novel developments in mobile sensing based on the integration of microfluidic devices and smartphones.

PubMed

Yang, Ke; Peretz-Soroka, Hagit; Liu, Yong; Lin, Francis

2016-03-21

Portable electronic devices and wireless communication systems enable a broad range of applications such as environmental and food safety monitoring, personalized medicine and healthcare management. Particularly, hybrid smartphone and microfluidic devices provide an integrated solution for the new generation of mobile sensing applications. Such mobile sensing based on microfluidic devices (broadly defined) and smartphones (MS(2)) offers a mobile laboratory for performing a wide range of bio-chemical detection and analysis functions such as water and food quality analysis, routine health tests and disease diagnosis. MS(2) offers significant advantages over traditional platforms in terms of test speed and control, low cost, mobility, ease-of-operation and data management. These improvements put MS(2) in a promising position in the fields of interdisciplinary basic and applied research. In particular, MS(2) enables applications to remote in-field testing, homecare, and healthcare in low-resource areas. The marriage of smartphones and microfluidic devices offers a powerful on-chip operating platform to enable various bio-chemical tests, remote sensing, data analysis and management in a mobile fashion. The implications of such integration are beyond telecommunication and microfluidic-related research and technology development. In this review, we will first provide the general background of microfluidic-based sensing, smartphone-based sensing, and their integration. Then, we will focus on several key application areas of MS(2) by systematically reviewing the important literature in each area. We will conclude by discussing our perspectives on the opportunities, issues and future directions of this emerging novel field.

Novel Developments of Mobile Sensing Based on the Integration of Microfluidic Devices and Smartphone

PubMed Central

Yang, Ke; Peretz-Soroka, Hagit; Liu, Yong; Lin, Francis

2016-01-01

Portable electronic devices and wireless communication systems enable a broad range of applications such as environmental and food safety monitoring, personalized medicine and healthcare management. Particularly, hybrid smartphone and microfluidic devices provide an integrated solution for the new generation of mobile sensing applications. Such mobile sensing based on microfluidic devices (broadly defined) and smartphones (MS2) offers a mobile laboratory for performing a wide range of bio-chemical detection and analysis functions such as water and food quality analysis, routine health tests and disease diagnosis. MS2 offers significant advantages over traditional platforms in terms of test speed and control, low cost, mobility, ease-of-operation and data management. These improvements put MS2 in a promising position in the fields of interdisciplinary basic and applied research. In particular, MS2 enables applications to remote infield testing, homecare, and healthcare in low-resource areas. The marriage of smartphones and microfluidic devices offers a powerful on-chip operating platform to enable various bio-chemical tests, remote sensing, data analysis and management in a mobile fashion. The implications of such integration are beyond telecommunication and microfluidic-related research and technology development. In this review, we will first provide the general background of microfluidic-based sensing, smartphone-based sensing, and their integration. Then, we will focus on several key application areas of MS2 by systematically reviewing the important literature in each area. We will conclude by discussing our perspectives on the opportunities, issues and future directions of this emerging novel field. PMID:26899264

Efficient gas-liquid contact using microfluidic membrane devices with staggered herringbone mixers.

PubMed

Femmer, Tim; Eggersdorfer, Max L; Kuehne, Alexander J C; Wessling, Matthias

2015-08-07

We describe a novel membrane based gas-liquid-contacting device with increased mass transport and reduced pressure loss by combining a membrane with a staggered herringbone static mixer. Herringbone structures are imposed on the microfluidic channel geometry via soft lithography, acting as mixers which introduce secondary flows at the membrane interface. Such flows include Dean vortices and Taylor flows generating effective mixing while improving mass transport and preventing concentration polarization in microfluidic channels. Furthermore, our static herringbone mixer membranes effectively reduce pressure losses leading to devices with enhanced transfer properties for microfluidic gas-liquid contact. We investigate the red blood cell distribution to tailor our devices towards miniaturised extracorporeal membrane oxygenation and improved comfort of patients with lung insufficiencies.

ZnO-Based Microfluidic pH Sensor: A Versatile Approach for Quick Recognition of Circulating Tumor Cells in Blood.

PubMed

Mani, Ganesh Kumar; Morohoshi, Madoka; Yasoda, Yutaka; Yokoyama, Sho; Kimura, Hiroshi; Tsuchiya, Kazuyoshi

2017-02-15

The present study is concerned about the development of highly sensitive and stable microfluidic pH sensor for possible identification of circulating tumor cells (CTCs) in blood. The precise pH measurements between silver-silver chloride (Ag/AgCl) reference electrode and zinc oxide (ZnO) working electrode have been investigated in the microfluidic device. Since there is a direct link between pH and cancer cells, the developed device is one of the valuable tools to examine circulating tumor cells (CTCs) in blood. The ZnO-based working electrode was deposited by radio frequency (rf) sputtering technique. The potential voltage difference between the working and reference electrodes (Ag/AgCl) is evaluated on the microfluidic device. The ideal Nernstian response of -43.71165 mV/pH was achieved along with high stability and quick response time. Finally, to evaluate the real time capability of the developed microfluidic device, in vitro testing was done with A549, A7r5, and MDCK cells.

Progress in the development and integration of fluid flow control tools in paper microfluidics.

PubMed

Fu, Elain; Downs, Corey

2017-02-14

Paper microfluidics is a rapidly growing subfield of microfluidics in which paper-like porous materials are used to create analytical devices. There is a need for higher performance field-use tests for many application domains including human disease diagnosis, environmental monitoring, and veterinary medicine. A key factor in creating high performance paper-based devices is the ability to manipulate fluid flow within the devices. This critical review is focused on the progress that has been made in (i) the development of fluid flow control tools and (ii) the integration of those tools into paper microfluidic devices. Further, we strive to be comprehensive in our presentation and provide historical context through discussion and performance comparisons, when possible, of both relevant earlier work and recent work. Finally, we discuss the major areas of focus for fluid flow methods development to advance the potential of paper microfluidics for high-performance field applications.

Isolation of Circulating Plasma Cells in Multiple Myeloma Using CD138 Antibody-Based Capture in a Microfluidic Device

NASA Astrophysics Data System (ADS)

Qasaimeh, Mohammad A.; Wu, Yichao C.; Bose, Suman; Menachery, Anoop; Talluri, Srikanth; Gonzalez, Gabriel; Fulciniti, Mariateresa; Karp, Jeffrey M.; Prabhala, Rao H.; Karnik, Rohit

2017-04-01

The necessity for bone marrow aspiration and the lack of highly sensitive assays to detect residual disease present challenges for effective management of multiple myeloma (MM), a plasma cell cancer. We show that a microfluidic cell capture based on CD138 antigen, which is highly expressed on plasma cells, permits quantitation of rare circulating plasma cells (CPCs) in blood and subsequent fluorescence-based assays. The microfluidic device is based on a herringbone channel design, and exhibits an estimated cell capture efficiency of ~40-70%, permitting detection of <10 CPCs/mL using 1-mL sample volumes, which is difficult using existing techniques. In bone marrow samples, the microfluidic-based plasma cell counts exhibited excellent correlation with flow cytometry analysis. In peripheral blood samples, the device detected a baseline of 2-5 CD138+ cells/mL in healthy donor blood, with significantly higher numbers in blood samples of MM patients in remission (20-24 CD138+ cells/mL), and yet higher numbers in MM patients exhibiting disease (45-184 CD138+ cells/mL). Analysis of CPCs isolated using the device was consistent with serum immunoglobulin assays that are commonly used in MM diagnostics. These results indicate the potential of CD138-based microfluidic CPC capture as a useful ‘liquid biopsy’ that may complement or partially replace bone marrow aspiration.

Diffusion phenomena of cells and biomolecules in microfluidic devices.

PubMed

Yildiz-Ozturk, Ece; Yesil-Celiktas, Ozlem

2015-09-01

Biomicrofluidics is an emerging field at the cross roads of microfluidics and life sciences which requires intensive research efforts in terms of introducing appropriate designs, production techniques, and analysis. The ultimate goal is to deliver innovative and cost-effective microfluidic devices to biotech, biomedical, and pharmaceutical industries. Therefore, creating an in-depth understanding of the transport phenomena of cells and biomolecules becomes vital and concurrently poses significant challenges. The present article outlines the recent advancements in diffusion phenomena of cells and biomolecules by highlighting transport principles from an engineering perspective, cell responses in microfluidic devices with emphases on diffusion- and flow-based microfluidic gradient platforms, macroscopic and microscopic approaches for investigating the diffusion phenomena of biomolecules, microfluidic platforms for the delivery of these molecules, as well as the state of the art in biological applications of mammalian cell responses and diffusion of biomolecules.

Diffusion phenomena of cells and biomolecules in microfluidic devices

PubMed Central

Yildiz-Ozturk, Ece; Yesil-Celiktas, Ozlem

2015-01-01

Biomicrofluidics is an emerging field at the cross roads of microfluidics and life sciences which requires intensive research efforts in terms of introducing appropriate designs, production techniques, and analysis. The ultimate goal is to deliver innovative and cost-effective microfluidic devices to biotech, biomedical, and pharmaceutical industries. Therefore, creating an in-depth understanding of the transport phenomena of cells and biomolecules becomes vital and concurrently poses significant challenges. The present article outlines the recent advancements in diffusion phenomena of cells and biomolecules by highlighting transport principles from an engineering perspective, cell responses in microfluidic devices with emphases on diffusion- and flow-based microfluidic gradient platforms, macroscopic and microscopic approaches for investigating the diffusion phenomena of biomolecules, microfluidic platforms for the delivery of these molecules, as well as the state of the art in biological applications of mammalian cell responses and diffusion of biomolecules. PMID:26180576

Microfluidic cell chips for high-throughput drug screening

PubMed Central

Chi, Chun-Wei; Ahmed, AH Rezwanuddin; Dereli-Korkut, Zeynep; Wang, Sihong

2016-01-01

The current state of screening methods for drug discovery is still riddled with several inefficiencies. Although some widely used high-throughput screening platforms may enhance the drug screening process, their cost and oversimplification of cell–drug interactions pose a translational difficulty. Microfluidic cell-chips resolve many issues found in conventional HTS technology, providing benefits such as reduced sample quantity and integration of 3D cell culture physically more representative of the physiological/pathological microenvironment. In this review, we introduce the advantages of microfluidic devices in drug screening, and outline the critical factors which influence device design, highlighting recent innovations and advances in the field including a summary of commercialization efforts on microfluidic cell chips. Future perspectives of microfluidic cell devices are also provided based on considerations of present technological limitations and translational barriers. PMID:27071838

An integrated optics microfluidic device for detecting single DNA molecules.

PubMed

Krogmeier, Jeffrey R; Schaefer, Ian; Seward, George; Yantz, Gregory R; Larson, Jonathan W

2007-12-01

A fluorescence-based integrated optics microfluidic device is presented, capable of detecting single DNA molecules in a high throughput and reproducible manner. The device integrates microfluidics for DNA stretching with two optical elements for single molecule detection (SMD): a plano-aspheric refractive lens for fluorescence excitation (illuminator) and a solid parabolic reflective mirror for fluorescence collection (collector). Although miniaturized in size, both optical components were produced and assembled onto the microfluidic device by readily manufacturable fabrication techniques. The optical resolution of the device is determined by the small and relatively low numerical aperture (NA) illuminator lens (0.10 effective NA, 4.0 mm diameter) that delivers excitation light to a diffraction limited 2.0 microm diameter spot at full width half maximum within the microfluidic channel. The collector (0.82 annular NA, 15 mm diameter) reflects the fluorescence over a large collection angle, representing 71% of a hemisphere, toward a single photon counting module in an infinity-corrected scheme. As a proof-of-principle experiment for this simple integrated device, individual intercalated lambda-phage DNA molecules (48.5 kb) were stretched in a mixed elongational-shear microflow, detected, and sized with a fluorescence signal to noise ratio of 9.9 +/-1.0. We have demonstrated that SMD does not require traditional high numerical aperture objective lenses and sub-micron positioning systems conventionally used in many applications. Rather, standard manufacturing processes can be combined in a novel way that promises greater accessibility and affordability for microfluidic-based single molecule applications.

Creating compact and microscale features in paper-based devices by laser cutting.

PubMed

Mahmud, Md Almostasim; Blondeel, Eric J M; Kaddoura, Moufeed; MacDonald, Brendan D

2016-11-14

In this work we describe a fabrication method to create compact and microscale features in paper-based microfluidic devices using a CO 2 laser cutting/engraving machine. Using this method we are able to produce the smallest features with the narrowest barriers yet reported for paper-based microfluidic devices. The method uses foil backed paper as the base material and yields inexpensive paper-based devices capable of using small fluid sample volumes and thus small reagent volumes, which is also suitable for mass production. The laser parameters (power and laser head speed) were adjusted to minimize the width of hydrophobic barriers and we were able to create barriers with a width of 39 ± 15 μm that were capable of preventing cross-barrier bleeding. We generated channels with a width of 128 ± 30 μm, which we found to be the physical limit for small features in the chromatography paper we used. We demonstrate how miniaturizing of paper-based microfluidic devices enables eight tests on a single bioassay device using only 2 μL of sample fluid volume.

Microfluidic Preparation of Polymer-Nucleic Acid Nanocomplexes Improves Nonviral Gene Transfer

NASA Astrophysics Data System (ADS)

Grigsby, Christopher L.; Ho, Yi-Ping; Lin, Chao; Engbersen, Johan F. J.; Leong, Kam W.

2013-11-01

As the designs of polymer systems used to deliver nucleic acids continue to evolve, it is becoming increasingly apparent that the basic bulk manufacturing techniques of the past will be insufficient to produce polymer-nucleic acid nanocomplexes that possess the uniformity, stability, and potency required for their successful clinical translation and widespread commercialization. Traditional bulk-prepared products are often physicochemically heterogeneous and may vary significantly from one batch to the next. Here we show that preparation of bioreducible nanocomplexes with an emulsion-based droplet microfluidic system produces significantly improved nanoparticles that are up to fifty percent smaller, more uniform, and are less prone to aggregation. The intracellular integrity of nanocomplexes prepared with this microfluidic method is significantly prolonged, as detected using a high-throughput flow cytometric quantum dot Förster resonance energy transfer nanosensor system. These physical attributes conspire to consistently enhance the delivery of both plasmid DNA and messenger RNA payloads in stem cells, primary cells, and human cell lines. Innovation in processing is necessary to move the field toward the broader clinical implementation of safe and effective nonviral nucleic acid therapeutics, and preparation with droplet microfluidics represents a step forward in addressing the critical barrier of robust and reproducible nanocomplex production.

Making the invisible visible: a microfluidic chip using a low refractive index polymer.

PubMed

Hanada, Yasutaka; Ogawa, Tatsuya; Koike, Kazuhiko; Sugioka, Koji

2016-07-07

Microfluidic frameworks known as micro-total-analysis-systems or lab-on-a-chip have become versatile tools in cell biology research, since functional biochips are able to streamline dynamic observations of various cells. Glass or polymers are generally used as the substrate due to their high transparency, chemical stability and cost-effectiveness. However, these materials are not well suited for the microscopic observation of cell migration at the fluid boundary due to the refractive index mismatch between the medium and the biochip material. For this reason, we have developed a new method of fabricating three-dimensional (3D) microfluidic chips made of the low refractive index fluoric polymer CYTOP. This novel fabrication procedure involves the use of a femtosecond laser for direct writing, followed by wet etching with a dilute fluorinated solvent and annealing, to create high-quality 3D microfluidic chips inside a polymer substrate. A microfluidic chip made in this manner enabled us to more clearly observe the flagellum motion of a Dinoflagellate moving in circles near the fluid surface compared to the observations possible using conventional microfluidic chips. We believe that CYTOP microfluidic chips made using this new method may allow more detailed analysis of various cell migrations near solid boundaries.

Recent advances in enzyme extraction strategies: A comprehensive review.

PubMed

Nadar, Shamraja S; Pawar, Rohini G; Rathod, Virendra K

2017-08-01

The increasing interest of industrial enzymes demands for development of new downstream strategies for maximizing enzyme recovery. The significant efforts have been focused on the development of newly adapted technologies to purify enzymes in catalytically active form. Recently, an aqueous two phase system (ATPS) is emerged as powerful tools for efficient extraction and purification of enzymes due to their versatility, lower cost, process integration capability and easy scale-up. The present review gives an overview of effect of parameters such as tie line length, pH, neutral salts, properties of polymer and salt involved in traditional polymer/polymer and polymer/salt ATPS for enzyme recovery. Further, advanced ATPS have been developed based on alcohols, surfactants, micellar compounds to avoid tedious recovery steps for getting desired enzyme. In order to improve the selectivity and efficiency of ATPS, recent approaches of conventional ATPS combined with different techniques like affinity ligands, ionic liquids, thermoseparating polymers and microfluidic device based ATPS have been reviewed. Moreover, three phase partitioning is also highlighted for enzymes enrichment as a blooming technology for efficiently integrated bioseparation techniques. At the end, it includes an overview of CLEAs technology and organic-inorganic nanoflowers preparation as novel strategies for simultaneous extraction, purification and immobilization of enzymes. Copyright © 2017 Elsevier B.V. All rights reserved.

Low cost microfluidic device based on cotton threads for electroanalytical application.

PubMed

Agustini, Deonir; Bergamini, Márcio F; Marcolino-Junior, Luiz Humberto

2016-01-21

Microfluidic devices are an interesting alternative for performing analytical assays, due to the speed of analyses, reduced sample, reagent and solvent consumption and less waste generation. However, the high manufacturing costs still prevent the massive use of these devices worldwide. Here, we present the construction of a low cost microfluidic thread-based electroanalytical device (μTED), employing extremely cheap materials and a manufacturing process free of equipment. The microfluidic channels were built with cotton threads and the estimated cost per device was only $0.39. The flow of solutions (1.12 μL s(-1)) is generated spontaneously due to the capillary forces, eliminating the use of any pumping system. To demonstrate the analytical performance of the μTED, a simultaneous determination of acetaminophen (ACT) and diclofenac (DCF) was performed by multiple pulse amperometry (MPA). A linear dynamic range (LDR) of 10 to 320 μmol L(-1) for both species, a limit of detection (LOD) and a limit of quantitation (LOQ) of 1.4 and 4.7 μmol L(-1) and 2.5 and 8.3 μmol L(-1) for ACT and DCF, respectively, as well as an analytical frequency of 45 injections per hour were reached. Thus, the proposed device has shown potential to extend the use of microfluidic analytical devices, due to its simplicity, low cost and good analytical performance.

High process yield rates of thermoplastic nanofluidic devices using a hybrid thermal assembly technique.

PubMed

Uba, Franklin I; Hu, Bo; Weerakoon-Ratnayake, Kumuditha; Oliver-Calixte, Nyote; Soper, Steven A

2015-02-21

Over the past decade, thermoplastics have been used as alternative substrates to glass and Si for microfluidic devices because of the diverse and robust fabrication protocols available for thermoplastics that can generate high production rates of the desired structures at low cost and with high replication fidelity, the extensive array of physiochemical properties they possess, and the simple surface activation strategies that can be employed to tune their surface chemistry appropriate for the intended application. While the advantages of polymer microfluidics are currently being realized, the evolution of thermoplastic-based nanofluidic devices is fraught with challenges. One challenge is assembly of the device, which consists of sealing a cover plate to the patterned fluidic substrate. Typically, channel collapse or substrate dissolution occurs during assembly making the device inoperable resulting in low process yield rates. In this work, we report a low temperature hybrid assembly approach for the generation of functional thermoplastic nanofluidic devices with high process yield rates (>90%) and with a short total assembly time (16 min). The approach involves thermally sealing a high T(g) (glass transition temperature) substrate containing the nanofluidic structures to a cover plate possessing a lower T(g). Nanofluidic devices with critical feature sizes ranging between 25-250 nm were fabricated in a thermoplastic substrate (T(g) = 104 °C) and sealed with a cover plate (T(g) = 75 °C) at a temperature significantly below the T(g) of the substrate. Results obtained from sealing tests revealed that the integrity of the nanochannels remained intact after assembly and devices were useful for fluorescence imaging at high signal-to-noise ratios. The functionality of the assembled devices was demonstrated by studying the stretching and translocation dynamics of dsDNA in the enclosed thermoplastic nanofluidic channels.

Thermally induced light-driven microfluidics using a MOEMS-based laser scanner for particle manipulation

NASA Astrophysics Data System (ADS)

Kremer, Matthias P.; Tortschanoff, Andreas

2014-03-01

One key challenge in the field of microfluidics and lab-on-a-chip experiments for biological or chemical applications is the remote manipulation of fluids, droplets and particles. These can be volume elements of reactants, particles coated with markers, cells or many others. Light-driven microfluidics is one way of accomplishing this challenge. In our work, we manipulated micrometre sized polystyrene beads in a microfluidic environment by inducing thermal flows. Therefore, the beads were held statically in an unstructured microfluidic chamber, containing a dyed watery solution. Inside this chamber, the beads were moved along arbitrary trajectories on a micrometre scale. The experiments were performed, using a MOEMS (micro-opto-electro-mechanical-systems)-based laser scanner with a variable focal length. This scanner system is integrated in a compact device, which is flexibly applicable to various microscope setups. The device utilizes a novel approach for varying the focal length, using an electrically tunable lens. A quasi statically driven MOEMS mirror is used for beam steering. The combination of a tunable lens and a dual axis micromirror makes the device very compact and robust and is capable of positioning the laser focus at any arbitrary location within a three dimensional working space. Hence, the developed device constitutes a valuable extension to manually executed microfluidic lab-on-chip experiments.

Microfluidics and photonics for Bio-System-on-a-Chip: a review of advancements in technology towards a microfluidic flow cytometry chip.

PubMed

Godin, Jessica; Chen, Chun-Hao; Cho, Sung Hwan; Qiao, Wen; Tsai, Frank; Lo, Yu-Hwa

2008-10-01

Microfluidics and photonics come together to form a field commonly referred to as 'optofluidics'. Flow cytometry provides the field with a technology base from which both microfluidic and photonic components be developed and integrated into a useful device. This article reviews some of the more recent developments to familiarize a reader with the current state of the technologies and also highlights the requirements of the device and how researchers are working to meet these needs.

Embellishment of microfluidic devices via femtosecond laser micronanofabrication for chip functionalization.

PubMed

Wang, Juan; He, Yan; Xia, Hong; Niu, Li-Gang; Zhang, Ran; Chen, Qi-Dai; Zhang, Yong-Lai; Li, Yan-Feng; Zeng, Shao-Jiang; Qin, Jian-Hua; Lin, Bing-Cheng; Sun, Hong-Bo

2010-08-07

This paper demonstrates the embellishment of existing microfluidic devices with integrated three dimensional (3D) micronanostructures via femtosecond laser micronanofabrication, which, for the first time, proves two-photon photopolymerization (TPP) to be a powerful technology for chip functionalization. As representative examples, microsieves with various pore shape and adjustable pore size were successfully fabricated inside a conventional glass-based microfluidic channel prepared by wet etching for microparticle separation. Moreover, a fish scale like microfilter was also fabricated and appointed as a one-way valve, which showed excellent performance as we expected. These results indicate that such embellishment of microfluidic devices is simple, low cost, flexible and easy to access. We believe that, combined with TPP, the application of lab-on-chip devices would be further extended.

Versatile fabrication of paper-based microfluidic devices with high chemical resistance using scholar glue and magnetic masks.

PubMed

Cardoso, Thiago M G; de Souza, Fabrício R; Garcia, Paulo T; Rabelo, Denilson; Henry, Charles S; Coltro, Wendell K T

2017-06-29

Simple methods have been developed for fabricating microfluidic paper-based analytical devices (μPADs) but few of these devices can be used with organic solvents and/or aqueous solutions containing surfactants. This study describes a simple fabrication strategy for μPADs that uses readily available scholar glue to create the hydrophobic flow barriers that are resistant to surfactants and organic solvents. Microfluidic structures were defined by magnetic masks designed with either neodymium magnets or magnetic sheets to define the patter, and structures were created by spraying an aqueous solution of glue on the paper surface. The glue-coated paper was then exposed to UV/Vis light for cross-linking to maximize chemical resistance. Examples of microzone arrays and microfluidic devices are demonstrated. μPADs fabricated with scholar glue retained their barriers when used with surfactants, organic solvents, and strong/weak acids and bases unlike common wax-printed barriers. Paper microzones and microfluidic devices were successfully used for colorimetric assays of clinically relevant analytes commonly detected in urinalysis to demonstrate the low background of the barrier material and generally applicability to sensing. The proposed fabrication method is attractive for both its ability to be used with diverse chemistries and the low cost and simplicity of the materials and process. Copyright © 2017 Elsevier B.V. All rights reserved.

A new UV-curing elastomeric substrate for rapid prototyping of microfluidic devices

NASA Astrophysics Data System (ADS)

Alvankarian, Jafar; Yeop Majlis, Burhanuddin

2012-03-01

Rapid prototyping in the design cycle of new microfluidic devices is very important for shortening time-to-market. Researchers are facing the challenge to explore new and suitable substrates with simple and efficient microfabrication techniques. In this paper, we introduce and characterize a UV-curing elastomeric polyurethane methacrylate (PUMA) for rapid prototyping of microfluidic devices. The swelling and solubility of PUMA in different chemicals is determined. Time-dependent measurements of water contact angle show that the native PUMA is hydrophilic without surface treatment. The current monitoring method is used for measurement of the electroosmotic flow mobility in the microchannels made from PUMA. The optical, physical, thermal and mechanical properties of PUMA are evaluated. The UV-lithography and molding process is used for making micropillars and deep channel microfluidic structures integrated to the supporting base layer. Spin coating is characterized for producing different layer thicknesses of PUMA resin. A device is fabricated and tested for examining the strength of different bonding techniques such as conformal, corona treating and semi-curing of two PUMA layers in microfluidic application and the results show that the bonding strengths are comparable to that of PDMS. We also report fabrication and testing of a three-layer multi inlet/outlet microfluidic device including a very effective fluidic interconnect for application demonstration of PUMA as a promising new substrate. A simple micro-device is developed and employed for observing the pressure deflection of membrane made from PUMA as a very effective elastomeric valve in microfluidic devices.

Fully Integrated Microfluidic Device for Direct Sample-to-Answer Genetic Analysis

NASA Astrophysics Data System (ADS)

Liu, Robin H.; Grodzinski, Piotr

Integration of microfluidics technology with DNA microarrays enables building complete sample-to-answer systems that are useful in many applications such as clinic diagnostics. In this chapter, a fully integrated microfluidic device [1] that consists of microfluidic mixers, valves, pumps, channels, chambers, heaters, and a DNA microarray sensor to perform DNA analysis of complex biological sample solutions is present. This device can perform on-chip sample preparation (including magnetic bead-based cell capture, cell preconcentration and purification, and cell lysis) of complex biological sample solutions (such as whole blood), polymerase chain reaction, DNA hybridization, and electrochemical detection. A few novel microfluidic techniques were developed and employed. A micromix-ing technique based on a cavitation microstreaming principle was implemented to enhance target cell capture from whole blood samples using immunomagnetic beads. This technique was also employed to accelerate DNA hybridization reaction. Thermally actuated paraffin-based microvalves were developed to regulate flows. Electrochemical pumps and thermopneumatic pumps were integrated on the chip to provide pumping of liquid solutions. The device is completely self-contained: no external pressure sources, fluid storage, mechanical pumps, or valves are necessary for fluid manipulation, thus eliminating possible sample contamination and simplifying device operation. Pathogenic bacteria detection from ~mL whole blood samples and single-nucleotide polymorphism analysis directly from diluted blood were demonstrated. The device provides a cost-effective solution to direct sample-to-answer genetic analysis, and thus has a potential impact in the fields of point-of-care genetic analysis, environmental testing, and biological warfare agent detection.

Two-photon excitation in chip electrophoresis enabling label-free fluorescence detection in non-UV transparent full-body polymer chips.

PubMed

Geissler, David; Belder, Detlev

2015-12-01

One of the most commonly employed detection methods in microfluidic research is fluorescence detection, due to its ease of integration and excellent sensitivity. Many analytes though do not show luminescence when excited in the visible light spectrum, require suitable dyes. Deep-ultraviolet (UV) excitation (<300 nm) allows label-free detection of a broader range of analytes but also mandates the use of expensive fused silica glass, which is transparent to UV light. Herein, we report the first application of label-free deep UV fluorescence detection in non-UV transparent full-body polymer microfluidic devices. This was achieved by means of two-photon excitation in the visible range (λex = 532 nm). Issues associated with the low optical transmittance of plastics in the UV range were successfully circumvented in this way. The technique was investigated by application to microchip electrophoresis of small aromatic compounds. Various polymers, such as poly(methyl methacrylate), cyclic olefin polymer, and copolymer as well as poly(dimethylsiloxane) were investigated and compared with respect to achievable LOD and ruggedness against photodamage. To demonstrate the applicability of the technique, the method was also applied to the determination of serotonin and tryptamine in fruit samples. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Lagrangian 3D tracking of fluorescent microscopic objects in motion

NASA Astrophysics Data System (ADS)

Darnige, T.; Figueroa-Morales, N.; Bohec, P.; Lindner, A.; Clément, E.

2017-05-01

We describe the development of a tracking device, mounted on an epi-fluorescent inverted microscope, suited to obtain time resolved 3D Lagrangian tracks of fluorescent passive or active micro-objects in microfluidic devices. The system is based on real-time image processing, determining the displacement of a x, y mechanical stage to keep the chosen object at a fixed position in the observation frame. The z displacement is based on the refocusing of the fluorescent object determining the displacement of a piezo mover keeping the moving object in focus. Track coordinates of the object with respect to the microfluidic device as well as images of the object are obtained at a frequency of several tenths of Hertz. This device is particularly well adapted to obtain trajectories of motile micro-organisms in microfluidic devices with or without flow.

Lagrangian 3D tracking of fluorescent microscopic objects in motion.

PubMed

Darnige, T; Figueroa-Morales, N; Bohec, P; Lindner, A; Clément, E

2017-05-01

We describe the development of a tracking device, mounted on an epi-fluorescent inverted microscope, suited to obtain time resolved 3D Lagrangian tracks of fluorescent passive or active micro-objects in microfluidic devices. The system is based on real-time image processing, determining the displacement of a x, y mechanical stage to keep the chosen object at a fixed position in the observation frame. The z displacement is based on the refocusing of the fluorescent object determining the displacement of a piezo mover keeping the moving object in focus. Track coordinates of the object with respect to the microfluidic device as well as images of the object are obtained at a frequency of several tenths of Hertz. This device is particularly well adapted to obtain trajectories of motile micro-organisms in microfluidic devices with or without flow.

Microfluidic Diatomite Analytical Devices for Illicit Drug Sensing with ppb-Level Sensitivity.

PubMed

Kong, Xianming; Chong, Xinyuan; Squire, Kenny; Wang, Alan X

2018-04-15

The escalating research interests in porous media microfluidics, such as microfluidic paper-based analytical devices, have fostered a new spectrum of biomedical devices for point-of-care (POC) diagnosis and biosensing. In this paper, we report microfluidic diatomite analytical devices (μDADs), which consist of highly porous photonic crystal biosilica channels, as an innovative lab-on-a-chip platform to detect illicit drugs. The μDADs in this work are fabricated by spin-coating and tape-stripping diatomaceous earth on regular glass slides with cross section of 400×30µm 2 . As the most unique feature, our μDADs can simultaneously perform on-chip chromatography to separate small molecules from complex biofluidic samples and acquire the surface-enhanced Raman scattering spectra of the target chemicals with high specificity. Owing to the ultra-small dimension of the diatomite microfluidic channels and the photonic crystal effect from the fossilized diatom frustules, we demonstrate unprecedented sensitivity down to part-per-billion (ppb) level when detecting pyrene (1ppb) from mixed sample with Raman dye and cocaine (10 ppb) from human plasma. This pioneering work proves the exclusive advantage of μDADs as emerging microfluidic devices for chemical and biomedical sensing, especially for POC drug screening.

Silicon insulator-based dielectrophoresis devices for minimized heating effects.

PubMed

Zellner, Phillip; Agah, Masoud

2012-08-01

Concentration of biological specimens that are extremely dilute in a solution is of paramount importance for their detection. Microfluidic chips based on insulator-based DEP (iDEP) have been used to selectively concentrate bacteria and viruses. iDEP biochips are currently fabricated with glass or polymer substrates to allow for high electric fields within the channels. Joule heating is a well-known problem in these substrates and can lead to decreased throughput and even device failure. In this work, we present, for the first time, highly efficient trapping and separation of particles in DC iDEP devices that are fabricated on silicon using a single-etch-step three-dimensional microfabrication process with greatly improved heat dissipation properties. Fabrication in silicon allows for greater heat dissipation for identical geometries and operating conditions. The 3D fabrication allows for higher performance at lower applied potentials. Thermal measurements were performed on both the presented silicon chips and previously published PDMS devices comprised of microposts. Trapping and separation of 1 and 2 μm polystyrene particles was demonstrated. These results demonstrate the feasibility of high-performance silicon iDEP devices for the next generation of sorting and concentration microsystems. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Method for producing high dielectric strength microvalves

DOEpatents

Kirby, Brian J [San Francisco, CA; Reichmuth, David S [Oakland, CA; Shepodd, Timothy J [Livermore, CA

2006-04-04

A microvalve having a cast-in-place and lithographically shaped mobile, polymer monolith for fluid flow control in microfluidic devices and method of manufacture. The microvalve contains a porous fluorinated polymer monolithic element whose pores are filled with an electrically insulating, high dielectric strength fluid, typically a perfluorinated liquid. This combination provides a microvalve that combines high dielectric strength with extremely low electrical conductivity. These microvalves have been shown to have resistivities of at least 100 G.OMEGA. and are compatible with solvents such as water at a pH between 2.7 and 9.0, 1-1 propanol, acetonitrile, and acetone.

Microfluidic CODES: a scalable multiplexed electronic sensor for orthogonal detection of particles in microfluidic channels.

PubMed

Liu, Ruxiu; Wang, Ningquan; Kamili, Farhan; Sarioglu, A Fatih

2016-04-21

Numerous biophysical and biochemical assays rely on spatial manipulation of particles/cells as they are processed on lab-on-a-chip devices. Analysis of spatially distributed particles on these devices typically requires microscopy negating the cost and size advantages of microfluidic assays. In this paper, we introduce a scalable electronic sensor technology, called microfluidic CODES, that utilizes resistive pulse sensing to orthogonally detect particles in multiple microfluidic channels from a single electrical output. Combining the techniques from telecommunications and microfluidics, we route three coplanar electrodes on a glass substrate to create multiple Coulter counters producing distinct orthogonal digital codes when they detect particles. We specifically design a digital code set using the mathematical principles of Code Division Multiple Access (CDMA) telecommunication networks and can decode signals from different microfluidic channels with >90% accuracy through computation even if these signals overlap. As a proof of principle, we use this technology to detect human ovarian cancer cells in four different microfluidic channels fabricated using soft lithography. Microfluidic CODES offers a simple, all-electronic interface that is well suited to create integrated, low-cost lab-on-a-chip devices for cell- or particle-based assays in resource-limited settings.

Microfluidic multiplexing of solid-state nanopores

NASA Astrophysics Data System (ADS)

Jain, Tarun; Rasera, Benjamin C.; Guerrero, Ricardo Jose S.; Lim, Jong-Min; Karnik, Rohit

2017-12-01

Although solid-state nanopores enable electronic analysis of many clinically and biologically relevant molecular structures, there are few existing device architectures that enable high-throughput measurement of solid-state nanopores. Herein, we report a method for microfluidic integration of multiple solid-state nanopores at a high density of one nanopore per (35 µm2). By configuring microfluidic devices with microfluidic valves, the nanopores can be rinsed from a single fluid input while retaining compatibility for multichannel electrical measurements. The microfluidic valves serve the dual purpose of fluidic switching and electric switching, enabling serial multiplexing of the eight nanopores with a single pair of electrodes. Furthermore, the device architecture exhibits low noise and is compatible with electroporation-based in situ nanopore fabrication, providing a scalable platform for automated electronic measurement of a large number of integrated solid-state nanopores.

Design and characterization of hydrogel-based microfluidic devices with biomimetic solute transport networks

PubMed Central

Koo, Hyung-Jun

2017-01-01

Hydrogel could serve as a matrix material of new classes of solar cells and photoreactors with embedded microfluidic networks. These devices mimic the structure and function of plant leaves, which are a natural soft matter based microfluidic system. These unusual microfluidic-hydrogel devices with fluid-penetrable medium operate on the basis of convective-diffusive mechanism, where the liquid is transported between the non-connected channels via molecular permeation through the hydrogel. We define three key designs of such hydrogel devices, having linear, T-shaped, and branched channels and report results of numerical simulation of the process of their infusion with solute carried by the incoming fluid. The computational procedure takes into account both pressure-driven convection and concentration gradient-driven diffusion in the permeable gel matrix. We define the criteria for evaluation of the fluid infusion rate, uniformity, solute loss by outflow and overall performance. The T-shaped channel network was identified as the most efficient one and was improved further by investigating the effect of the channel-end secondary branches. Our parallel experimental data on the pattern of solute infusions are in excellent agreement with the simulation. These network designs can be applied to a broad range of novel microfluidic materials and soft matter devices with distributed microchannel networks. PMID:28396708

Flexible microfluidic devices with three-dimensional interconnected microporous walls for gas and liquid applications.

PubMed

Yuen, Po Ki; DeRosa, Michael E

2011-10-07

This article presents a simple, low-cost method of fabrication and the applications of flexible polystyrene microfluidic devices with three-dimensional (3D) interconnected microporous walls based on treatment using a solvent/non-solvent mixture at room temperature. The complete fabrication process from device design concept to working device can be completed in less than an hour in a regular laboratory setting, without the need for expensive equipment. Microfluidic devices were used to demonstrate gas generation and absorption reactions by acidifying water with carbon dioxide (CO(2)) gas. By selectively treating the microporous structures with oxygen plasma, acidification of water by acetic acid (distilled white vinegar) perfusion was also demonstrated with the same device design.

3D microfluidic fabrication using a low refractive index polymer for clear microscopic observation at the fluid boundary

NASA Astrophysics Data System (ADS)

Hanada, Y.

2018-02-01

Microfluidic chips known as μ-TAS or LoC have become versatile tools in cell research, since functional biochips are able to streamline dynamic observations of various cells. Glass or polymers are generally used as the substrate due to their high transparency, chemical stability and cost-effectiveness. However, these materials are not well suited to the microscopic observation at the fluid boundary due to the refractive index mismatch between the medium and the biochip material. For this reason, we have developed a method of fabricating three-dimensional (3D) microfluidic chips made of a low refractive index fluoric polymer CYTOP. CYTOP has a refractive index of 1.34, a value that is almost equivalent to that of water. This optical property is very important for clear 3D microscopic observations of cell motion near the solid boundary, due to the minimal mismatch between the refractive index values of the medium and the CYTOP substrate. Therefore, CYTOP microfluidics are expected to allow the generation of clear images of unique cell migratory processes near the microfluidic sidewall. Therefore, we established the fabrication procedure involving the use of femtosecond laser direct writing, followed by wet etching and annealing, to create high-quality 3D microfluidics inside a polymer substrate. A microfluidic chip made in this manner enables us to more clearly observe areas near the fluid surface, compared to the observations possible using conventional microfluidic chips.

Dual-nozzle microfluidic droplet generator

NASA Astrophysics Data System (ADS)

Choi, Ji Wook; Lee, Jong Min; Kim, Tae Hyun; Ha, Jang Ho; Ahrberg, Christian D.; Chung, Bong Geun

2018-05-01

The droplet-generating microfluidics has become an important technique for a variety of applications ranging from single cell analysis to nanoparticle synthesis. Although there are a large number of methods for generating and experimenting with droplets on microfluidic devices, the dispensing of droplets from these microfluidic devices is a challenge due to aggregation and merging of droplets at the interface of microfluidic devices. Here, we present a microfluidic dual-nozzle device for the generation and dispensing of uniform-sized droplets. The first nozzle of the microfluidic device is used for the generation of the droplets, while the second nozzle can accelerate the droplets and increase the spacing between them, allowing for facile dispensing of droplets. Computational fluid dynamic simulations were conducted to optimize the design parameters of the microfluidic device.

Mutual capacitance of liquid conductors in deformable tactile sensing arrays

NASA Astrophysics Data System (ADS)

Li, Bin; Fontecchio, Adam K.; Visell, Yon

2016-01-01

Advances in highly deformable electronics are needed in order to enable emerging categories of soft computing devices ranging from wearable electronics, to medical devices, and soft robotic components. The combination of highly elastic substrates with intrinsically stretchable conductors holds the promise of enabling electronic sensors that can conform to curved objects, reconfigurable displays, or soft biological tissues, including the skin. Here, we contribute sensing principles for tactile (mechanical image) sensors based on very low modulus polymer substrates with embedded liquid metal microfluidic arrays. The sensors are fabricated using a single-step casting method that utilizes fine nylon filaments to produce arrays of cylindrical channels on two layers. The liquid metal (gallium indium alloy) conductors that fill these channels readily adopt the shape of the embedding membrane, yielding levels of deformability greater than 400%, due to the use of soft polymer substrates. We modeled the sensor performance using electrostatic theory and continuum mechanics, yielding excellent agreement with experiments. Using a matrix-addressed capacitance measurement technique, we are able to resolve strain distributions with millimeter resolution over areas of several square centimeters.

Mutual capacitance of liquid conductors in deformable tactile sensing arrays

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Bin; Fontecchio, Adam K.; Visell, Yon

2016-01-04

Advances in highly deformable electronics are needed in order to enable emerging categories of soft computing devices ranging from wearable electronics, to medical devices, and soft robotic components. The combination of highly elastic substrates with intrinsically stretchable conductors holds the promise of enabling electronic sensors that can conform to curved objects, reconfigurable displays, or soft biological tissues, including the skin. Here, we contribute sensing principles for tactile (mechanical image) sensors based on very low modulus polymer substrates with embedded liquid metal microfluidic arrays. The sensors are fabricated using a single-step casting method that utilizes fine nylon filaments to produce arraysmore » of cylindrical channels on two layers. The liquid metal (gallium indium alloy) conductors that fill these channels readily adopt the shape of the embedding membrane, yielding levels of deformability greater than 400%, due to the use of soft polymer substrates. We modeled the sensor performance using electrostatic theory and continuum mechanics, yielding excellent agreement with experiments. Using a matrix-addressed capacitance measurement technique, we are able to resolve strain distributions with millimeter resolution over areas of several square centimeters.« less

A microfluidic platform for 3-dimensional cell culture and cell-based assays.

PubMed

Kim, Minseok S; Yeon, Ju Hun; Park, Je-Kyun

2007-02-01

This paper reports a novel microfluidic platform introducing peptide hydrogel to make biocompatible microenvironment as well as realizing in situ cell-based assays. Collagen composite, OPLA and Puramatrix scaffolds are compared to select good environment for human hepatocellular carcinoma cells (HepG2) by albumin measurement. The selected biocompatible self-assembling peptide hydrogel, Puramatrix, is hydrodynamically focused in the middle of main channel of a microfluidic device, and at the same time the cells are 3-dimensionally immobilized and encapsulated without any additional surface treatment. HepG2 cells have been 3-dimensionally cultured in a poly(dimethylsiloxane) (PDMS) microfluidic device for 4 days. The cells cultured in micro peptide scaffold are compared with those cultured by conventional petri dish in morphology and the rate of albumin secretion. By injection of different reagents into either side of the peptide scaffold, the microfluidic device also forms a linear concentration gradient profile across the peptide scaffold due to molecular diffusion. Based on this characteristic, toxicity tests are performed by Triton X-100. As the higher toxicant concentration gradient forms, the wider dead zone of cells in the peptide scaffold represents. This microfluidic platform facilitates in vivo-like 3-dimensional microenvironment, and have a potential for the applications of reliable cell-based screening and assays including cytotoxicity test, real-time cell viability monitoring, and continuous dose-response assay.

Microfluidic paper-based analytical devices for potential use in quantitative and direct detection of disease biomarkers in clinical analysis.

PubMed

Lim, Wei Yin; Goh, Boon Tong; Khor, Sook Mei

2017-08-15

Clinicians, working in the health-care diagnostic systems of developing countries, currently face the challenges of rising costs, increased number of patient visits, and limited resources. A significant trend is using low-cost substrates to develop microfluidic devices for diagnostic purposes. Various fabrication techniques, materials, and detection methods have been explored to develop these devices. Microfluidic paper-based analytical devices (μPADs) have gained attention for sensing multiplex analytes, confirming diagnostic test results, rapid sample analysis, and reducing the volume of samples and analytical reagents. μPADs, which can provide accurate and reliable direct measurement without sample pretreatment, can reduce patient medical burden and yield rapid test results, aiding physicians in choosing appropriate treatment. The objectives of this review are to provide an overview of the strategies used for developing paper-based sensors with enhanced analytical performances and to discuss the current challenges, limitations, advantages, disadvantages, and future prospects of paper-based microfluidic platforms in clinical diagnostics. μPADs, with validated and justified analytical performances, can potentially improve the quality of life by providing inexpensive, rapid, portable, biodegradable, and reliable diagnostics. Copyright © 2017 Elsevier B.V. All rights reserved.

Microfluidics Meets Dilute Solution Viscometry: An Undergraduate Laboratory to Determine Polymer Molecular Weight Using a Microviscometer

ERIC Educational Resources Information Center

Pety, Stephen J.; Lu, Hang; Thio, Yonathan S.

2011-01-01

This paper describes a student laboratory experiment to determine the molecular weight of a polymer sample by measuring the viscosity of dilute polymer solutions in a PDMS microfluidic viscometer. Sample data are given for aqueous solutions of poly(ethylene oxide) (PEO). A demonstration of shear thinning behavior using the microviscometer is…

Microfluidic devices for the isolation of circulating rare cells: a focus on affinity-based, dielectrophoresis, and hydrophoresis.

PubMed

Hyun, Kyung-A; Jung, Hyo-Il

2013-04-01

Circulating rare cells have attracted interest because they can be good indicators of various types of diseases. For example, enumeration of circulating tumor cells is used for cancer diagnosis and prognosis, while DNA analysis or enumeration of nucleated red blood cells is useful for prenatal diagnosis or hypoxic anemia, and that of circulating stem cells to diagnose cancer metastasis. Isolation of these cells and their downstream analyses can provide significant information such as the origin and characteristics of a disease. Novel approaches based on microfluidics have many advantages, including the continuous process and integration with other components for analysis. For these reasons, a variety of microfluidic devices have been developed to isolate and characterize rare cells. In this article, we review several microfluidic devices, with a focus on affinity-based isolation (e.g. antigen-antibody reaction) and label-free separation (DEP and hydrophoresis). © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Geometrical effect characterization of femtosecond-laser manufactured glass microfluidic chips based on optical manipulation of submicroparticles

NASA Astrophysics Data System (ADS)

Kotsifaki, Domna G.; Mackenzie, Mark D.; Polydefki, Georgia; Kar, Ajoy K.; Makropoulou, Mersini; Serafetinides, Alexandros A.

2017-12-01

Microfluidic devices provide a platform with wide ranging applications from environmental monitoring to disease diagnosis. They offer substantive advantages but are often not optimized or designed to be used by nonexpert researchers. Microchannels of a microanalysis platform and their geometrical characterization are of eminent importance when designing such devices. We present a method that is used to optimize each microchannel within a device using high-throughput particle manipulation. For this purpose, glass-based microfluidic devices, with three-dimensional channel networks of several geometrical sizes, were fabricated by employing laser fabrication techniques. The effect of channel geometry was investigated by employing an optical tweezer. The optical trapping force depends on the flow velocity that is associated with the dimensions of the microchannel. We observe a linear dependence of the trapping efficiency and of the fluid flow velocity, with the channel dimensions. We determined that the highest trapping efficiency was achieved for microchannels with aspect ratio equal to one. Numerical simulation validated the impact of the device design dimensions on the trapping efficiency. This investigation indicates that the geometrical characteristics, the flow velocity, and trapping efficiency are crucial and should be considered when fabricating microfluidic devices for cell studies.

Cost-effective rapid prototyping and assembly of poly(methyl methacrylate) microfluidic devices.

PubMed

Matellan, Carlos; Del Río Hernández, Armando E

2018-05-03

The difficulty in translating conventional microfluidics from laboratory prototypes to commercial products has shifted research efforts towards thermoplastic materials for their higher translational potential and amenability to industrial manufacturing. Here, we present an accessible method to fabricate and assemble polymethyl methacrylate (PMMA) microfluidic devices in a "mask-less" and cost-effective manner that can be applied to manufacture a wide range of designs due to its versatility. Laser micromachining offers high flexibility in channel dimensions and morphology by controlling the laser properties, while our two-step surface treatment based on exposure to acetone vapour and low-temperature annealing enables improvement of the surface quality without deformation of the device. Finally, we demonstrate a capillarity-driven adhesive delivery bonding method that can produce an effective seal between PMMA devices and a variety of substrates, including glass, silicon and LiNbO 3 . We illustrate the potential of this technique with two microfluidic devices, an H-filter and a droplet generator. The technique proposed here offers a low entry barrier for the rapid prototyping of thermoplastic microfluidics, enabling iterative design for laboratories without access to conventional microfabrication equipment.

Plasma extraction rate enhancement scheme for a real-time and continuous blood plasma separation device using a sheathless cell concentrator

NASA Astrophysics Data System (ADS)

Kang, Dong-Hyun; Kim, Kyongtae; Kim, Yong-Jun

2018-02-01

Microfluidic devices for plasma extraction are popular because they offer the advantage of smaller reagent consumption compared to conventional centrifugations. The plasma yield (volume percentage of plasma that can be extracted) is an important factor for diagnoses in microdevices with small reagent consumptions. However, recently designed microfluidic devices tend to have a low plasma yield because they have been optimized to improve the purity of extracted plasma. Thus, these devices require large amounts of reagents, and this complexity has eliminated the advantage of microfluidic devices that can operate with only small amounts of reagents. We therefore propose a continuous, real-time, blood plasma separation device, for plasma extraction rate enhancements. Moreover, a blood plasma separation device was designed to achieve improved plasma yields with high-purity efficiency. To obtain a high plasma yield, microstructures were placed on the bottom side of the channel to increase the concentration of blood cells. Plasma separation was then accomplished via microfluidic networks based on the Zweifach-Fung effect. The proposed device was fabricated based on the polydimethylsiloxane molding process using the SU-8 microfluidic channel for the fabrication of the mold and bottom structures. Human blood diluted in a phosphate buffered saline solution (25% hematocrit) was injected into the inlet of the device. The purity efficiencies were approximately equal to 96% with a maximum of 96.75% at a flow rate of 2 µl min-1, while the plasma yield was approximately 59% with a maximum of 59.92% at a flow rate of 4 µl min-1. Compared to results obtained using other devices, our proposed device could obtain comparable or higher plasma purity and a high plasma yield.

Microfluidics-Based Lab-on-Chip Systems in DNA-Based Biosensing: An Overview

PubMed Central

Dutse, Sabo Wada; Yusof, Nor Azah

2011-01-01

Microfluidics-based lab-on-chip (LOC) systems are an active research area that is revolutionising high-throughput sequencing for the fast, sensitive and accurate detection of a variety of pathogens. LOCs also serve as portable diagnostic tools. The devices provide optimum control of nanolitre volumes of fluids and integrate various bioassay operations that allow the devices to rapidly sense pathogenic threat agents for environmental monitoring. LOC systems, such as microfluidic biochips, offer advantages compared to conventional identification procedures that are tedious, expensive and time consuming. This paper aims to provide a broad overview of the need for devices that are easy to operate, sensitive, fast, portable and sufficiently reliable to be used as complementary tools for the control of pathogenic agents that damage the environment. PMID:22163925

Integrated microfluidic system with simultaneous emulsion generation and concentration.

PubMed

Koppula, Karuna S; Fan, Rong; Veerapalli, Kartik R; Wan, Jiandi

2016-03-15

Because the size, size distribution, and concentration of emulsions play an important role in most of the applications, controlled emulsion generation and effective concentration are of great interest in fundamental and applied studies. While microfluidics has been demonstrated to be able to produce emulsion drops with controlled size, size distribution, and hierarchical structures, progress of controlled generation of concentrated emulsions is limited. Here, we present an effective microfluidic emulsion generation system integrated with an orifice structure to separate aqueous droplets from the continuous oil phase, resulting in concentrated emulsion drops in situ. Both experimental and simulation results show that the efficiency of separation is determined by a balance between pressure drop and droplet accumulation near the orifice. By manipulating this balance via changing flow rates and microfluidic geometry, we can achieve monodisperse droplets on chip that have a concentration as high as 80,000 drops per microliter (volume fraction of 66%). The present approach thus provides insights to the design of microfluidic device that can be used to concentrate emulsions (drops and bubbles), colloidal particles (drug delivery polymer particles), and biological particles (cells and bacteria) when volume fractions as high as 66% are necessary. Copyright © 2015 Elsevier Inc. All rights reserved.

Microfluidic electronics.

PubMed

Cheng, Shi; Wu, Zhigang

2012-08-21

Microfluidics, a field that has been well-established for several decades, has seen extensive applications in the areas of biology, chemistry, and medicine. However, it might be very hard to imagine how such soft microfluidic devices would be used in other areas, such as electronics, in which stiff, solid metals, insulators, and semiconductors have previously dominated. Very recently, things have radically changed. Taking advantage of native properties of microfluidics, advances in microfluidics-based electronics have shown great potential in numerous new appealing applications, e.g. bio-inspired devices, body-worn healthcare and medical sensing systems, and ergonomic units, in which conventional rigid, bulky electronics are facing insurmountable obstacles to fulfil the demand on comfortable user experience. Not only would the birth of microfluidic electronics contribute to both the microfluidics and electronics fields, but it may also shape the future of our daily life. Nevertheless, microfluidic electronics are still at a very early stage, and significant efforts in research and development are needed to advance this emerging field. The intention of this article is to review recent research outcomes in the field of microfluidic electronics, and address current technical challenges and issues. The outlook of future development in microfluidic electronic devices and systems, as well as new fabrication techniques, is also discussed. Moreover, the authors would like to inspire both the microfluidics and electronics communities to further exploit this newly-established field.

Microfluidic opportunities in the field of nutrition

PubMed Central

Li, Sixing; Kiehne, Justin; Sinoway, Lawrence I.; Cameron, Craig E.

2013-01-01

Nutrition has always been closely related to human health, which is a constant motivational force driving research in a variety of disciplines. Over the years, the rapidly emerging field of microfluidics has been pushing forward the healthcare industry with the development of microfluidic-based, point-of-care (POC) diagnostic devices. Though a great deal of work has been done in developing microfluidic platforms for disease diagnoses, potential microfluidic applications in the field of nutrition remain largely unexplored. In this Focus article, we would like to investigate the potential chances for microfluidics in the field of nutrition. We will first highlight some of the recent advances in microfluidic blood analysis systems that have the capacity to detect biomarkers of nutrition. Then we will examine existing examples of microfluidic devices for the detection of specific biomarkers of nutrition or nutrient content in food. Finally, we will discuss the challenges in this field and provide some insight into the future of applied microfluidics in nutrition. PMID:24056522

Controlled evaporative self-assembly of confined microfluids: A route to complex ordered structures

NASA Astrophysics Data System (ADS)

Byun, Myunghwan

The evaporative self-assembly of nonvolatile solutes such as polymers, nanocrystals, and carbon nanotubes has been widely recognized as a non-lithographic means of producing a diverse range of intriguing complex structures. Due to the spatial variation of evaporative flux and possible convection, however, these non-equilibrium dissipative structures (e.g., fingering patterns and polygonal network structures) are often irregularly and stochastically organized. Yet for many applications in microelectronics, data storage devices, and biotechnology, it is highly desirable to achieve surface patterns having a well-controlled spatial arrangement. To date, only a few elegant studies have centered on precise control over the evaporation process to produce ordered structures. In a remarked comparison with conventional lithography techniques, surface patterning by controlled solvent evaporation is simple and cost-effective, offering a lithography- and external field-free means to organize nonvolatile materials into ordered microscopic structures over large surface areas. The ability to engineer an evaporative self-assembly process that yields a wide range of complex, self-organizing structures over large areas offers tremendous potential for applications in electronics, optoelectronics, and bio- or chemical sensors. We developed a facile, robust tool for evaporating polymer, nanoparticle, or DNA solutions in curve-on-flat geometries to create versatile, highly regular microstructures, including hierarchically structured polymer blend rings, conjugated polymer "snake-skins", block copolymer stripes, and punch-hole-like meshes, biomolecular microring arrays, etc. The mechanism of structure formation was elucidated both experimentally and theoretically. Our method further enhances current fabrication approaches to creating highly ordered structures in a simple and cost-effective manner, envisioning the potential to be tailored for use in photonics, optoelectronics, microfluidic devices, nanotechnology and biotechnology, etc.

Protein immobilization on the surface of polydimethylsiloxane and polymethyl methacrylate microfluidic devices.

PubMed

Khnouf, Ruba; Karasneh, Dina; Albiss, Borhan Aldeen

2016-02-01

PDMS and PMMA are two of the most used polymers in the fabrication of lab-on-chip or microfluidic devices. In order to use these polymers in biological applications, it is sometimes essential to be able to bind biomolecules such as proteins and DNA to the surface of these materials. In this work, we have evaluated a number of processes that have been developed to bind protein to PDMS surfaces which include passive adsorption, passive adsorption with glutaraldehyde cross-linking, (3-aminopropyl) triethoxysilane functionalization followed by glutaraldehyde or 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride cross-linkers. It has been shown that the latter technique--using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride--results in more than twice the bonding of protein to the surface of PDMS microchannels than proteins binding passively. We have also evaluated a few techniques that have been tested for the functionalization of PMMA microchannels where we have found that the use of polyethyleneimine (PEI) has led to the strongest protein-PMMA microchannel bond. We finally demonstrated the effect of PDMS curing methodology on protein adsorption to its surface, and showed that increased curing time is the factor that reduces passive adsorption the most. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Fully-Polymeric pH Sensor Realized by Means of a Single-Step Soft Embossing Technique

PubMed Central

Fanzio, Paola; Chang, Chi-Tung; Skolimowski, Maciej; Tanzi, Simone; Sasso, Luigi

2017-01-01

We present here an electrochemical sensor microsystem for the monitoring of pH. The all-polymeric device is comprised of a cyclic olefin copolymer substrate, a 200 nm-thin patterned layer of conductive polymer (PEDOT), and a 70 nm electropolymerized layer of a pH sensitive conductive polymer (polyaniline). The patterning of the fluidic (microfluidic channels) and conductive (wiring and electrodes) functional elements was achieved with a single soft PDMS mold via a single embossing step process. A post-processing treatment with ethylene glycol assured the functional enhancement of the electrodes, as demonstrated via an electrical and electrochemical characterization. A surface modification of the electrodes was carried out, based on voltammetric electropolymerization, to obtain a thin layer of polyaniline. The mechanism for pH sensing is based on the redox reactions of the polyaniline layer caused by protonation. The sensing performance of the microsystem was finally validated by monitoring its potentiometric response upon exposure to a relevant range of pH. PMID:28531106

Fully-Polymeric pH Sensor Realized by Means of a Single-Step Soft Embossing Technique.

PubMed

Fanzio, Paola; Chang, Chi-Tung; Skolimowski, Maciej; Tanzi, Simone; Sasso, Luigi

2017-05-20

We present here an electrochemical sensor microsystem for the monitoring of pH. The all-polymeric device is comprised of a cyclic olefin copolymer substrate, a 200 nm-thin patterned layer of conductive polymer (PEDOT), and a 70 nm electropolymerized layer of a pH sensitive conductive polymer (polyaniline). The patterning of the fluidic (microfluidic channels) and conductive (wiring and electrodes) functional elements was achieved with a single soft PDMS mold via a single embossing step process. A post-processing treatment with ethylene glycol assured the functional enhancement of the electrodes, as demonstrated via an electrical and electrochemical characterization. A surface modification of the electrodes was carried out, based on voltammetric electropolymerization, to obtain a thin layer of polyaniline. The mechanism for pH sensing is based on the redox reactions of the polyaniline layer caused by protonation. The sensing performance of the microsystem was finally validated by monitoring its potentiometric response upon exposure to a relevant range of pH.

Automated Microfluidic Instrument for Label-Free and High-Throughput Cell Separation.

PubMed

Zhang, Xinjie; Zhu, Zhixian; Xiang, Nan; Long, Feifei; Ni, Zhonghua

2018-03-20

Microfluidic technologies for cell separation were reported frequently in recent years. However, a compact microfluidic instrument enabling thoroughly automated cell separation is still rarely reported until today due to the difficult hybrid between the macrosized fluidic control system and the microsized microfluidic device. In this work, we propose a novel and automated microfluidic instrument to realize size-based separation of cancer cells in a label-free and high-throughput manner. Briefly, the instrument is equipped with a fully integrated microfluidic device and a set of robust fluid-driven and control units, and the instrument functions of precise fluid infusion and high-throughput cell separation are guaranteed by a flow regulatory chip and two cell separation chips which are the key components of the microfluidic device. With optimized control programs, the instrument is successfully applied to automatically sort human breast adenocarcinoma cell line MCF-7 from 5 mL of diluted human blood with a high recovery ratio of ∼85% within a rapid processing time of ∼23 min. We envision that our microfluidic instrument will be potentially useful in many biomedical applications, especially cell separation, enrichment, and concentration for the purpose of cell culture and analysis.

IFSA: a microfluidic chip-platform for frit-based immunoassay protocols

NASA Astrophysics Data System (ADS)

Hlawatsch, Nadine; Bangert, Michael; Miethe, Peter; Becker, Holger; Gärtner, Claudia

2013-03-01

Point-of-care diagnostics (POC) is one of the key application fields for lab-on-a-chip devices. While in recent years much of the work has concentrated on integrating complex molecular diagnostic assays onto a microfluidic device, there is a need to also put comparatively simple immunoassay-type protocols on a microfluidic platform. In this paper, we present the development of a microfluidic cartridge using an immunofiltration approach. In this method, the sandwich immunoassay takes place in a porous frit on which the antibodies have immobilized. The device is designed to be able to handle three samples in parallel and up to four analytical targets per sample. In order to meet the critical cost targets for the diagnostic market, the microfluidic chip has been designed and manufactured using high-volume manufacturing technologies in mind. Validation experiments show comparable sensitivities in comparison with conventional immunofiltration kits.

Dynamical formation of spatially localized arrays of aligned nanowires in plastic films with magnetic anisotropy.

PubMed

Fragouli, Despina; Buonsanti, Raffaella; Bertoni, Giovanni; Sangregorio, Claudio; Innocenti, Claudia; Falqui, Andrea; Gatteschi, Dante; Cozzoli, Pantaleo Davide; Athanassiou, Athanassia; Cingolani, Roberto

2010-04-27

We present a simple technique for magnetic-field-induced formation, assembling, and positioning of magnetic nanowires in a polymer film. Starting from a polymer/iron oxide nanoparticle casted solution that is allowed to dry along with the application of a weak magnetic field, nanocomposite films incorporating aligned nanocrystal-built nanowire arrays are obtained. The control of the dimensions of the nanowires and of their localization across the polymer matrix is achieved by varying the duration of the applied magnetic field, in combination with the evaporation dynamics. These multifunctional anisotropic free-standing nanocomposite films, which demonstrate high magnetic anisotropy, can be used in a wide field of technological applications, ranging from sensors to microfluidics and magnetic devices.

A microfluidic device for dry sample preservation in remote settings.

PubMed

Begolo, Stefano; Shen, Feng; Ismagilov, Rustem F

2013-11-21

This paper describes a microfluidic device for dry preservation of biological specimens at room temperature that incorporates chemical stabilization matrices. Long-term stabilization of samples is crucial for remote medical analysis, biosurveillance, and archiving, but the current paradigm for transporting remotely obtained samples relies on the costly "cold chain" to preserve analytes within biospecimens. We propose an alternative approach that involves the use of microfluidics to preserve samples in the dry state with stabilization matrices, developed by others, that are based on self-preservation chemistries found in nature. We describe a SlipChip-based device that allows minimally trained users to preserve samples with the three simple steps of placing a sample at an inlet, closing a lid, and slipping one layer of the device. The device fills automatically, and a pre-loaded desiccant dries the samples. Later, specimens can be rehydrated and recovered for analysis in a laboratory. This device is portable, compact, and self-contained, so it can be transported and operated by untrained users even in limited-resource settings. Features such as dead-end and sequential filling, combined with a "pumping lid" mechanism, enable precise quantification of the original sample's volume while avoiding overfilling. In addition, we demonstrated that the device can be integrated with a plasma filtration module, and we validated device operations and capabilities by testing the stability of purified RNA solutions. These features and the modularity of this platform (which facilitates integration and simplifies operation) would be applicable to other microfluidic devices beyond this application. We envision that as the field of stabilization matrices develops, microfluidic devices will be useful for cost-effectively facilitating remote analysis and biosurveillance while also opening new opportunities for diagnostics, drug development, and other medical fields.

Microfluidic device for acoustic cell lysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Branch, Darren W.; Cooley, Erika Jane; Smith, Gennifer Tanabe

2015-08-04

A microfluidic acoustic-based cell lysing device that can be integrated with on-chip nucleic acid extraction. Using a bulk acoustic wave (BAW) transducer array, acoustic waves can be coupled into microfluidic cartridges resulting in the lysis of cells contained therein by localized acoustic pressure. Cellular materials can then be extracted from the lysed cells. For example, nucleic acids can be extracted from the lysate using silica-based sol-gel filled microchannels, nucleic acid binding magnetic beads, or Nafion-coated electrodes. Integration of cell lysis and nucleic acid extraction on-chip enables a small, portable system that allows for rapid analysis in the field.

Visual Estimation of Bacterial Growth Level in Microfluidic Culture Systems.

PubMed

Kim, Kyukwang; Kim, Seunggyu; Jeon, Jessie S

2018-02-03

Microfluidic devices are an emerging platform for a variety of experiments involving bacterial cell culture, and has advantages including cost and convenience. One inevitable step during bacterial cell culture is the measurement of cell concentration in the channel. The optical density measurement technique is generally used for bacterial growth estimation, but it is not applicable to microfluidic devices due to the small sample volumes in microfluidics. Alternately, cell counting or colony-forming unit methods may be applied, but these do not work in situ; nor do these methods show measurement results immediately. To this end, we present a new vision-based method to estimate the growth level of the bacteria in microfluidic channels. We use Fast Fourier transform (FFT) to detect the frequency level change of the microscopic image, focusing on the fact that the microscopic image becomes rough as the number of cells in the field of view increases, adding high frequencies to the spectrum of the image. Two types of microfluidic devices are used to culture bacteria in liquid and agar gel medium, and time-lapsed images are captured. The images obtained are analyzed using FFT, resulting in an increase in high-frequency noise proportional to the time passed. Furthermore, we apply the developed method in the microfluidic antibiotics susceptibility test by recognizing the regional concentration change of the bacteria that are cultured in the antibiotics gradient. Finally, a deep learning-based data regression is performed on the data obtained by the proposed vision-based method for robust reporting of data.

Generation of monodisperse cell-sized microdroplets using a centrifuge-based axisymmetric co-flowing microfluidic device.

PubMed

Yamashita, Hitoyoshi; Morita, Masamune; Sugiura, Haruka; Fujiwara, Kei; Onoe, Hiroaki; Takinoue, Masahiro

2015-04-01

We report an easy-to-use generation method of biologically compatible monodisperse water-in-oil microdroplets using a glass-capillary-based microfluidic device in a tabletop mini-centrifuge. This device does not require complicated microfabrication; furthermore, only a small sample volume is required in experiments. Therefore, we believe that this method will assist biochemical and cell-biological experiments. Copyright © 2014 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Microfluidic preparation of polymer nanospheres

NASA Astrophysics Data System (ADS)

Kucuk, Israfil; Edirisinghe, Mohan

2014-12-01

In this work, solid polymer nanospheres with their surface tailored for drug adhesion were prepared using a V-shaped microfluidic junction. The biocompatible polymer solutions were infused using two channels of the microfluidic junction which was also simultaneously fed with a volatile liquid, perfluorohexane using the other channel. The mechanism by which the nanospheres are generated is explained using high speed camera imaging. The polymer concentration (5-50 wt%) and flow rates of the feeds (50-300 µl min-1) were important parameters in controlling the nanosphere diameter. The diameter of the polymer nanospheres was found to be in the range of 80-920 nm with a polydispersity index of 11-19 %. The interior structure and surfaces of the nanospheres prepared were studied using advanced microscopy and showed the presence of fine pores and cracks on surface which can be used as drug entrapment locations.

Multiphase flows with digital and traditional microfluidics

NASA Astrophysics Data System (ADS)

Nilsson, Michael A.

Multi-phase fluid systems are an important concept in fluid mechanics, seen every day in how fluids interact with solids, gases, and other fluids in many industrial, medical, agricultural, and other regimes. In this thesis, the development of a two-dimensional digital microfluidic device is presented, followed by the development of a two-phase microfluidic diagnostic tool designed to simulate sandstone geometries in oil reservoirs. In both instances, it is possible to take advantage of the physics involved in multiphase flows to affect positive outcomes in both. In order to make an effective droplet-based digital microfluidic device, one must be able to precisely control a number of key processes including droplet positioning, motion, coalescence, mixing, and sorting. For planar or open microfluidic devices, many of these processes have yet to be demonstrated. A suitable platform for an open system is a superhydrophobic surface, as suface characteristics are critical. Great efforts have been spent over the last decade developing hydrophobic surfaces exhibiting very large contact angles with water, and which allow for high droplet mobility. We demonstrate that sanding Teflon can produce superhydrophobic surfaces with advancing contact angles of up to 151° and contact angle hysteresis of less than 4°. We use these surfaces to characterize droplet coalescence, mixing, motion, deflection, positioning, and sorting. This research culminates with the presentation of two digital microfluidic devices: a droplet reactor/analyzer and a droplet sorter. As global energy usage increases, maximizing oil recovery from known reserves becomes a crucial multiphase challenge in order to meet the rising demand. This thesis presents the development of a microfluidic sandstone platform capable of quickly and inexpensively testing the performance of fluids with different rheological properties on the recovery of oil. Specifically, these microfluidic devices are utilized to examine how shear-thinning, shear-thickening, and viscoelastic fluids affect oil recovery. This work begins by looking at oil displacement from a microfluidic sandstone device, then investigates small-scale oil recovery from a single pore, and finally investigates oil displacement from larger scale, more complex microfluidic sandstone devices of varying permeability. The results demonstrate that with careful fluid design, it is possible to outperform current commercial additives using the patent-pending fluid we developed. Furthermore, the resulting microfluidic sandstone devices can reduce the time and cost of developing and testing of current and new enhanced oil recovery fluids.

Bio-functionalized silk hydrogel microfluidic systems.

PubMed

Zhao, Siwei; Chen, Ying; Partlow, Benjamin P; Golding, Anne S; Tseng, Peter; Coburn, Jeannine; Applegate, Matthew B; Moreau, Jodie E; Omenetto, Fiorenzo G; Kaplan, David L

2016-07-01

Bio-functionalized microfluidic systems were developed based on a silk protein hydrogel elastomeric materials. A facile multilayer fabrication method using gelatin sacrificial molding and layer-by-layer assembly was implemented to construct interconnected, three dimensional (3D) microchannel networks in silk hydrogels at 100 μm minimum feature resolution. Mechanically activated valves were implemented to demonstrate pneumatic control of microflow. The silk hydrogel microfluidics exhibit controllable mechanical properties, long-term stability in various environmental conditions, tunable in vitro and in vivo degradability in addition to optical transparency, providing unique features for cell/tissue-related applications than conventional polydimethylsiloxane (PDMS) and existing hydrogel-based microfluidic options. As demonstrated in the work here, the all aqueous-based fabrication process at ambient conditions enabled the incorporation of active biological substances in the bulk phase of these new silk microfluidic systems during device fabrication, including enzymes and living cells, which are able to interact with the fluid flow in the microchannels. These silk hydrogel-based microfluidic systems offer new opportunities in engineering active diagnostic devices, tissues and organs that could be integrated in vivo, and for on-chip cell sensing systems. Copyright © 2016 Elsevier Ltd. All rights reserved.

Two-ply channels for faster wicking in paper-based microfluidic devices.

PubMed

Camplisson, Conor K; Schilling, Kevin M; Pedrotti, William L; Stone, Howard A; Martinez, Andres W

2015-12-07

This article describes the development of porous two-ply channels for paper-based microfluidic devices that wick fluids significantly faster than conventional, porous, single-ply channels. The two-ply channels were made by stacking two single-ply channels on top of each other and were fabricated entirely out of paper, wax and toner using two commercially available printers, a convection oven and a thermal laminator. The wicking in paper-based channels was studied and modeled using a modified Lucas-Washburn equation to account for the effect of evaporation, and a paper-based titration device incorporating two-ply channels was demonstrated.

Frontal photopolymerization for microfluidic applications.

PubMed

Cabral, João T; Hudson, Steven D; Harrison, Christopher; Douglas, Jack F

2004-11-09

Frontal photopolymerization (FPP) offers numerous advantages for the rapid prototyping of microfluidic devices. Quantitative utilization of this method, however, requires a control of the vertical dimensions of the patterned resist material. To address this fundamental problem, we study the ultraviolet (UV) photopolymerization of a series of multifunctional thiolene resists through a combination of experiments and analytical modeling of the polymerization fronts. We describe this nonlinear spatio-temporal growth process in terms of a "minimal" model involving an order parameter phi(x, t) characterizing the extent of monomer-to-polymer conversion, the optical attenuation T(x, t), and the solid front position h(t). The latter exhibits an induction time (or equivalent critical UV dose) characterizing the onset of frontal propagation. We also observe a novel transition between two logarithmic rates of growth, determined by the Beer-Lambert attenuation constants mu(0) and mu(infinity) of the monomer and fully polymerized material, respectively. The measured frontal kinetics and optical transmission of the thiolene resist materials are consistent with our photopolymerization model, exhibiting both "photodarkening" and "photoinvariant" polymerization. This is apparently the first observation of photodarkening reported in FPP. On the basis of these results, multilevel fluidic devices with controlled height are readily fabricated with modulated illumination. A representative two-level microfluidic device, incorporating a chaotic mixer, a T junction, and a series of controlled flow constrictions, illustrates the practical versatility of this fabrication method.

SAXS on a chip: from dynamics of phase transitions to alignment phenomena at interfaces studied with microfluidic devices.

PubMed

Silva, Bruno F B

2017-09-13

The field of microfluidics offers attractive possibilities to perform novel experiments that are difficult (or even impossible) to perform using conventional bulk and surface-based methods. Such attractiveness comes from several important aspects inherent to these miniaturized devices. First, the flow of fluids under submillimeter confinement typically leads to a drop of inertial forces, meaning that turbulence is practically suppressed. This leads to predictable and controllable flow profiles, along with well-defined chemical gradients and stress fields that can be used for controlled mixing and actuation on the micro and nanoscale. Secondly, intricate microfluidic device designs can be fabricated using cleanroom standard procedures. Such intricate geometries can take diverse forms, designed by researchers to perform complex tasks, that require exquisite control of flow of several components and gradients, or to mimic real world examples, facilitating the establishment of more realistic models. Thirdly, microfluidic devices are usually compatible with in situ or integrated characterization methods that allow constant real-time monitoring of the processes occurring inside the microchannels. This is very different from typical bulk-based methods, where usually one can only observe the final result, or otherwise, take quick snapshots of the evolving process or take aliquots to be analyzed separately. Altogether, these characteristics inherent to microfluidic devices provide researchers with a set of tools that allow not only exquisite control and manipulation of materials at the micro and nanoscale, but also observation of these effects. In this review, we will focus on the use and prospects of combining microfluidic devices with in situ small-angle X-ray scattering (and related techniques such as small-angle neutron scattering and X-ray photon correlation spectroscopy), and their enormous potential for physical-chemical research, mainly in self-assembly and phase-transitions, and surface characterization.

Bead mediated separation of microparticles in droplets.

PubMed

Wang, Sida; Sung, Ki-Joo; Lin, Xiaoxia Nina; Burns, Mark A

2017-01-01

Exchange of components such as particles and cells in droplets is important and highly desired in droplet microfluidic assays, and many current technologies use electrical or magnetic fields to accomplish this process. Bead-based microfluidic techniques offer an alternative approach that uses the bead's solid surface to immobilize targets like particles or biological material. In this paper, we demonstrate a bead-based technique for exchanging droplet content by separating fluorescent microparticles in a microfluidic device. The device uses posts to filter surface-functionalized beads from a droplet and re-capture the filtered beads in a new droplet. With post spacing of 7 μm, beads above 10 μm had 100% capture efficiency. We demonstrate the efficacy of this system using targeted particles that bind onto the functionalized beads and are, therefore, transferred from one solution to another in the device. Binding capacity tests performed in the bulk phase showed an average binding capacity of 5 particles to each bead. The microfluidic device successfully separated the targeted particles from the non-targeted particles with up to 98% purity and 100% yield.

Bead mediated separation of microparticles in droplets

PubMed Central

Sung, Ki-Joo; Lin, Xiaoxia Nina; Burns, Mark A.

2017-01-01

Exchange of components such as particles and cells in droplets is important and highly desired in droplet microfluidic assays, and many current technologies use electrical or magnetic fields to accomplish this process. Bead-based microfluidic techniques offer an alternative approach that uses the bead’s solid surface to immobilize targets like particles or biological material. In this paper, we demonstrate a bead-based technique for exchanging droplet content by separating fluorescent microparticles in a microfluidic device. The device uses posts to filter surface-functionalized beads from a droplet and re-capture the filtered beads in a new droplet. With post spacing of 7 μm, beads above 10 μm had 100% capture efficiency. We demonstrate the efficacy of this system using targeted particles that bind onto the functionalized beads and are, therefore, transferred from one solution to another in the device. Binding capacity tests performed in the bulk phase showed an average binding capacity of 5 particles to each bead. The microfluidic device successfully separated the targeted particles from the non-targeted particles with up to 98% purity and 100% yield. PMID:28282412

Hot embossed polyethylene through-hole chips for bead-based microfluidic devices

PubMed Central

Chou, Jie; Du, Nan; Ou, Tina; Floriano, Pierre N.; Christodoulides, Nicolaos; McDevitt, John T.

2013-01-01

Over the past decade, there has been a growth of interest in the translation of microfluidic systems into real-world clinical practice, especially for use in point-of-care or near patient settings. While initial fabrication advances in microfluidics involved mainly the etching of silicon and glass, the economics of scaling of these materials is not amendable for point-of-care usage where single-test applications forces cost considerations to be kept low and throughput high. As such, a materials base more consistent with point-of-care needs is required. In this manuscript, the fabrication of a hot embossed, through-hole low-density polyethylene ensembles derived from an anisotropically etched silicon wafer is discussed. This semi-opaque polymer that can be easily sterilized and recycled provides low background noise for fluorescence measurements and yields more affordable cost than other thermoplastics commonly used for microfluidic applications such as cyclic olefin copolymer (COC). To fabrication through-hole microchips from this alternative material for microfluidics, a fabrication technique that uses a high-temperature, high-pressure resistant mold is described. This aluminum-based epoxy mold, serving as the positive master mold for embossing, is casted over etched arrays of pyramidal pits in a silicon wafer. Methods of surface treatment of the wafer prior to casting and PDMS casting of the epoxy are discussed to preserve the silicon wafer for future use. Changes in the thickness of polyethylene are observed for varying embossing temperatures. The methodology described herein can quickly fabricate 20 disposable, single use chips in less than 30 minutes with the ability to scale up 4x by using multiple molds simultaneously. When coupled as a platform supporting porous bead sensors, as in the recently developed Programmable Bio-Nano-Chip, this bead chip system can achieve limits of detection, for the cardiac biomarker C-reactive protein, of 0.3 ng/mL, thereby demonstrating the approach is compatible with high performance, real-world clinical measurements in the context of point-of-care testing. PMID:23183187

Paper microfluidic-based enzyme catalyzed double microreactor.

PubMed

Ferrer, Ivonne M; Valadez, Hector; Estala, Lissette; Gomez, Frank A

2014-08-01

We describe a paper microfluidic-based enzyme catalyzed double microreactor assay using fluorescent detection. Here, solutions of lactate dehydrogenase (LDH) and diaphorase (DI) were directly spotted onto the microfluidic paper-based analytical device (μPAD). Samples containing lactic acid, resazurin, and nicotinamide adenine dinucleotide oxidized form (NAD(+) ), potassium chloride (KCl), and BSA, in MES buffer were separately spotted onto the μPAD and MES buffer flowed through the device. A cascade reaction occurs upon the sample spot overlapping with LDH to form pyruvate and nicotinamide adenine dinucleotide reduced form (NADH). Subsequently, NADH is used in the conversion of resazurin to fluorescent resorufin by DI. The μPAD avoids the need of surface functionalization or enzyme immobilization steps. These microreactor devices are low cost and easy to fabricate and effect reaction based solely on buffer capillary action. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A Two-Stage Microfluidic Device for the Isolation and Capture of Circulating Tumor Cells

NASA Astrophysics Data System (ADS)

Cook, Andrew; Belsare, Sayali; Giorgio, Todd; Mu, Richard

2014-11-01

Analysis of circulating tumor cells (CTCs) can be critical for studying how tumors grow and metastasize, in addition to personalizing treatment for cancer patients. CTCs are rare events in blood, making it difficult to remove CTCs from the blood stream. Two microfluidic devices have been developed to separate CTCs from blood. The first is a double spiral device that focuses cells into streams, the positions of which are determined by cell diameter. The second device uses ligand-coated magnetic nanoparticles that selectively attach to CTCs. The nanoparticles then pull CTCs out of solution using a magnetic field. These two devices will be combined into a single 2-stage microfluidic device that will capture CTCs more efficiently than either device on its own. The first stage depletes the number of blood cells in the sample by size-based separation. The second stage will magnetically remove CTCs from solution for study and culturing. Thus far, size-based separation has been achieved. Research will also focus on understanding the equations that govern fluid dynamics and magnetic fields in order to determine how the manipulation of microfluidic parameters, such as dimensions and flow rate, will affect integration and optimization of the 2-stage device. NSF-CREST: Center for Physics and Chemistry of Materials. HRD-0420516; Department of Defense, Peer Reviewed Medical Research Program Award W81XWH-13-1-0397.

Integrated single-walled carbon nanotube/microfluidic devices for the study of the sensing mechanism of nanotube sensors.

PubMed

Fu, Qiang; Liu, Jie

2005-07-21

A method to fabricate integrated single-walled carbon nanotube/microfluidic devices was developed. This simple process could be used to directly prepare nanotube thin film transistors within the microfluidic channel and to register SWNT devices with the microfludic channel without the need of an additional alignment step. The microfluidic device was designed to have several inlets that deliver multiple liquid flows to a single main channel. The location and width of each flow in the main channel could be controlled by the relative flow rates. This capability enabled us to study the effect of the location and the coverage area of the liquid flow that contained charged molecules on the conduction of the nanotube devices, providing important information on the sensing mechanism of carbon nanotube sensors. The results showed that in a sensor based on a nanotube thin film field effect transistor, the sensing signal came from target molecules absorbed on or around the nanotubes. The effect from adsorption on metal electrodes was weak.

Transfection in perfused microfluidic cell culture devices: A case study.

PubMed

Raimes, William; Rubi, Mathieu; Super, Alexandre; Marques, Marco P C; Veraitch, Farlan; Szita, Nicolas

2017-08-01

Automated microfluidic devices are a promising route towards a point-of-care autologous cell therapy. The initial steps of induced pluripotent stem cell (iPSC) derivation involve transfection and long term cell culture. Integration of these steps would help reduce the cost and footprint of micro-scale devices with applications in cell reprogramming or gene correction. Current examples of transfection integration focus on maximising efficiency rather than viable long-term culture. Here we look for whole process compatibility by integrating automated transfection with a perfused microfluidic device designed for homogeneous culture conditions. The injection process was characterised using fluorescein to establish a LabVIEW-based routine for user-defined automation. Proof-of-concept is demonstrated by chemically transfecting a GFP plasmid into mouse embryonic stem cells (mESCs). Cells transfected in the device showed an improvement in efficiency (34%, n = 3) compared with standard protocols (17.2%, n = 3). This represents a first step towards microfluidic processing systems for cell reprogramming or gene therapy.

Microencapsulation of Clostridium difficile specific bacteriophages using microfluidic glass capillary devices for colon delivery using pH triggered release

PubMed Central

Vinner, Gurinder K.; Vladisavljević, Goran T.; Clokie, Martha R. J.

2017-01-01

The prevalence of pathogenic bacteria acquiring multidrug antibiotic resistance is a global health threat to mankind. This has motivated a renewed interest in developing alternatives to conventional antibiotics including bacteriophages (viruses) as therapeutic agents. The bacterium Clostridium difficile causes colon infection and is particularly difficult to treat with existing antibiotics; phage therapy may offer a viable alternative. The punitive environment within the gastrointestinal tract can inactivate orally delivered phages. C. difficile specific bacteriophage, myovirus CDKM9 was encapsulated in a pH responsive polymer (Eudragit® S100 with and without alginate) using a flow focussing glass microcapillary device. Highly monodispersed core-shell microparticles containing phages trapped within the particle core were produced by in situ polymer curing using 4-aminobenzoic acid dissolved in the oil phase. The size of the generated microparticles could be precisely controlled in the range 80 μm to 160 μm through design of the microfluidic device geometry and by varying flow rates of the dispersed and continuous phase. In contrast to free ‘naked’ phages, those encapsulated within the microparticles could withstand a 3 h exposure to simulated gastric fluid at pH 2 and then underwent a subsequent pH triggered burst release at pH 7. The significance of our research is in demonstrating that C. difficile specific phage can be formulated and encapsulated in highly uniform pH responsive microparticles using a microfluidic system. The microparticles were shown to afford significant protection to the encapsulated phage upon prolonged exposure to an acid solution mimicking the human stomach environment. Phage encapsulation and subsequent release kinetics revealed that the microparticles prepared using Eudragit® S100 formulations possess pH responsive characteristics with phage release triggered in an intestinal pH range suitable for therapeutic purposes. The results reported here provide proof-of-concept data supporting the suitability of our approach for colon targeted delivery of phages for therapeutic purposes. PMID:29023522

Open-Source Wax RepRap 3-D Printer for Rapid Prototyping Paper-Based Microfluidics.

PubMed

Pearce, J M; Anzalone, N C; Heldt, C L

2016-08-01

The open-source release of self-replicating rapid prototypers (RepRaps) has created a rich opportunity for low-cost distributed digital fabrication of complex 3-D objects such as scientific equipment. For example, 3-D printable reactionware devices offer the opportunity to combine open hardware microfluidic handling with lab-on-a-chip reactionware to radically reduce costs and increase the number and complexity of microfluidic applications. To further drive down the cost while improving the performance of lab-on-a-chip paper-based microfluidic prototyping, this study reports on the development of a RepRap upgrade capable of converting a Prusa Mendel RepRap into a wax 3-D printer for paper-based microfluidic applications. An open-source hardware approach is used to demonstrate a 3-D printable upgrade for the 3-D printer, which combines a heated syringe pump with the RepRap/Arduino 3-D control. The bill of materials, designs, basic assembly, and use instructions are provided, along with a completely free and open-source software tool chain. The open-source hardware device described here accelerates the potential of the nascent field of electrochemical detection combined with paper-based microfluidics by dropping the marginal cost of prototyping to nearly zero while accelerating the turnover between paper-based microfluidic designs. © 2016 Society for Laboratory Automation and Screening.

Bio-microfluidics: biomaterials and biomimetic designs.

PubMed

Domachuk, Peter; Tsioris, Konstantinos; Omenetto, Fiorenzo G; Kaplan, David L

2010-01-12

Bio-microfluidics applies biomaterials and biologically inspired structural designs (biomimetics) to microfluidic devices. Microfluidics, the techniques for constraining fluids on the micrometer and sub-micrometer scale, offer applications ranging from lab-on-a-chip to optofluidics. Despite this wealth of applications, the design of typical microfluidic devices imparts relatively simple, laminar behavior on fluids and is realized using materials and techniques from silicon planar fabrication. On the other hand, highly complex microfluidic behavior is commonplace in nature, where fluids with nonlinear rheology flow through chaotic vasculature composed from a range of biopolymers. In this Review, the current state of bio-microfluidic materials, designs and applications are examined. Biopolymers enable bio-microfluidic devices with versatile functionalization chemistries, flexibility in fabrication, and biocompatibility in vitro and in vivo. Polymeric materials such as alginate, collagen, chitosan, and silk are being explored as bulk and film materials for bio-microfluidics. Hydrogels offer options for mechanically functional devices for microfluidic systems such as self-regulating valves, microlens arrays and drug release systems, vital for integrated bio-microfluidic devices. These devices including growth factor gradients to study cell responses, blood analysis, biomimetic capillary designs, and blood vessel tissue culture systems, as some recent examples of inroads in the field that should lead the way in a new generation of microfluidic devices for bio-related needs and applications. Perhaps one of the most intriguing directions for the future will be fully implantable microfluidic devices that will also integrate with existing vasculature and slowly degrade to fully recapitulate native tissue structure and function, yet serve critical interim functions, such as tissue maintenance, drug release, mechanical support, and cell delivery.

Arrays of High-Aspect Ratio Microchannels for High-Throughput Isolation of Circulating Tumor Cells (CTCs).

PubMed

Hupert, Mateusz L; Jackson, Joshua M; Wang, Hong; Witek, Małgorzata A; Kamande, Joyce; Milowsky, Matthew I; Whang, Young E; Soper, Steven A

2014-10-01

Microsystem-based technologies are providing new opportunities in the area of in vitro diagnostics due to their ability to provide process automation enabling point-of-care operation. As an example, microsystems used for the isolation and analysis of circulating tumor cells (CTCs) from complex, heterogeneous samples in an automated fashion with improved recoveries and selectivity are providing new opportunities for this important biomarker. Unfortunately, many of the existing microfluidic systems lack the throughput capabilities and/or are too expensive to manufacture to warrant their widespread use in clinical testing scenarios. Here, we describe a disposable, all-polymer, microfluidic system for the high-throughput (HT) isolation of CTCs directly from whole blood inputs. The device employs an array of high aspect ratio (HAR), parallel, sinusoidal microchannels (25 µm × 150 µm; W × D; AR = 6.0) with walls covalently decorated with anti-EpCAM antibodies to provide affinity-based isolation of CTCs. Channel width, which is similar to an average CTC diameter (12-25 µm), plays a critical role in maximizing the probability of cell/wall interactions and allows for achieving high CTC recovery. The extended channel depth allows for increased throughput at the optimized flow velocity (2 mm/s in a microchannel); maximizes cell recovery, and prevents clogging of the microfluidic channels during blood processing. Fluidic addressing of the microchannel array with a minimal device footprint is provided by large cross-sectional area feed and exit channels poised orthogonal to the network of the sinusoidal capillary channels (so-called Z-geometry). Computational modeling was used to confirm uniform addressing of the channels in the isolation bed. Devices with various numbers of parallel microchannels ranging from 50 to 320 have been successfully constructed. Cyclic olefin copolymer (COC) was chosen as the substrate material due to its superior properties during UV-activation of the HAR microchannels surfaces prior to antibody attachment. Operation of the HT-CTC device has been validated by isolation of CTCs directly from blood secured from patients with metastatic prostate cancer. High CTC sample purities (low number of contaminating white blood cells, WBCs) allowed for direct lysis and molecular profiling of isolated CTCs.

Microfluidic-Based Generation of Size-Controlled, Biofunctionalized Synthetic Polymer Microgels for Cell Encapsulation

PubMed Central

Headen, Devon M.; Aubry, Guillaume; Lu, Hang

2014-01-01

Cell and islet microencapsulation in synthetic hydrogels provide an immunoprotective and cell-supportive microenvironment. A microfluidic strategy for the genaration of biofunctionalized, synthetic microgel particles with precise control over particle size and molecular permeability for cell and protein delivery is presented. These engineered capsules support high cell viability and function of encapsulated human stem cells and islets. PMID:24615922

Rapid detection of Cu(2+) by a paper-based microfluidic device coated with bovine serum albumin (BSA)-Au nanoclusters.

PubMed

Fang, Xueen; Zhao, Qianqian; Cao, Hongmei; Liu, Juan; Guan, Ming; Kong, Jilie

2015-11-21

In this work, bovine serum albumin (BSA)-Au nanoclusters were used to coat a paper-based microfluidic device. This device acted as a Cu(2+) biosensor that showed fluorescence quenching on detection of copper ions. The detection limit of this sensor could be adjusted by altering the water absorbing capacity of the device. Qualitative and semi-quantitative results could be obtained visually without the aid of any advanced instruments. This sensor could test Cu(2+) rapidly with high specificity and sensitivity, which would be useful for point-of-care testing (POCT).

Simple and inexpensive micromachined aluminum microfluidic devices for acoustic focusing of particles and cells.

PubMed

Gautam, Gayatri P; Burger, Tobias; Wilcox, Andrew; Cumbo, Michael J; Graves, Steven W; Piyasena, Menake E

2018-05-01

We introduce a new method to construct microfluidic devices especially useful for bulk acoustic wave (BAW)-based manipulation of cells and microparticles. To obtain efficient acoustic focusing, BAW devices require materials that have high acoustic impedance mismatch relative to the medium in which the cells/microparticles are suspended and materials with a high-quality factor. To date, silicon and glass have been the materials of choice for BAW-based acoustofluidic channel fabrication. Silicon- and glass-based fabrication is typically performed in clean room facilities, generates hazardous waste, and can take several hours to complete the microfabrication. To address some of the drawbacks in fabricating conventional BAW devices, we explored a new approach by micromachining microfluidic channels in aluminum substrates. Additionally, we demonstrate plasma bonding of poly(dimethylsiloxane) (PDMS) onto micromachined aluminum substrates. Our goal was to achieve an approach that is both low cost and effective in BAW applications. To this end, we micromachined aluminum 6061 plates and enclosed the systems with a thin PDMS cover layer. These aluminum/PDMS hybrid microfluidic devices use inexpensive materials and are simply constructed outside a clean room environment. Moreover, these devices demonstrate effectiveness in BAW applications as demonstrated by efficient acoustic focusing of polystyrene microspheres, bovine red blood cells, and Jurkat cells and the generation of multiple focused streams in flow-through systems. Graphical abstract The aluminum acoustofluidic device and the generation of multinode focusing of particles.

Microfluidics-Based PCR for Fusion Transcript Detection.

PubMed

Chen, Hui

2016-01-01

The microfluidic technology allows the production of network of submillimeter-size fluidic channels and reservoirs in a variety of material systems. The microfluidic-based polymerase chain reaction (PCR) allows automated multiplexing of multiple samples and multiple assays simultaneously within a network of microfluidic channels and chambers that are co-ordinated in controlled fashion by the valves. The individual PCR reaction is performed in nanoliter volume, which allows testing on samples with limited DNA and RNA. The microfluidics devices are used in various types of PCR such as digital PCR and single molecular emulsion PCR for genotyping, gene expression, and miRNA expression. In this chapter, the use of a microfluidics-based PCR for simultaneous screening of 14 known fusion transcripts in patients with leukemia is described.

Ultrafast STR Separations on Short-Channel Microfluidic Systems for Forensic Screening and Genotyping.

PubMed

Aboud, Maurice J; Gassmann, Marcus; McCord, Bruce

2015-09-01

There are situations in which it is important to quickly and positively identify an individual. Examples include suspects detained in the neighborhood of a bombing or terrorist incident, individuals detained attempting to enter or leave the country, and victims of mass disasters. Systems utilized for these purposes must be fast, portable, and easy to maintain. DNA typing methods provide the best biometric information yielding identity, kinship, and geographical origin, but they are not portable and rapid. This study details the development of a portable short-channel microfluidic device based on a modified Agilent 2100 bioanalyzer for applications in forensic genomics. The system utilizes a denaturing polymer matrix with dual-channel laser-induced fluorescence and is capable of producing a genotype in 80 sec. The device was tested for precision and resolution using an allelic ladder created from 6 short tandem repeat (STR) loci and a sex marker (amelogenin). The results demonstrated a precision of 0.09-0.21 bp over the entire size range and resolution values from 2.5 to 4.1 bp. Overall, the results demonstrate the chip provides a portable, rapid, and precise method for screening amplified short tandem repeats and human identification screening. © 2015 American Academy of Forensic Sciences.

Fabrication of PDMS-Based Microfluidic Devices: Application for Synthesis of Magnetic Nanoparticles

NASA Astrophysics Data System (ADS)

Thu, Vu Thi; Mai, An Ngoc; Le The Tam; Van Trung, Hoang; Thu, Phung Thi; Tien, Bui Quang; Thuat, Nguyen Tran; Lam, Tran Dai

2016-05-01

In this work, we have developed a convenient approach to synthesize magnetic nanoparticles with relatively high magnetization and controllable sizes. This was realized by combining the traditional co-precipitation method and microfluidic techniques inside microfluidic devices. The device was first designed, and then fabricated using simplified soft-lithography techniques. The device was utilized to synthesize magnetite nanoparticles. The synthesized nanomaterials were thoroughly characterized using field emission scanning electron microscopy and a vibrating sample magnetometer. The results demonstrated that the as-prepared device can be utilized as a simple and effective tool to synthesize magnetic nanoparticles with the sizes less than 10 nm and magnetization more than 50 emu/g. The development of these devices opens new strategies to synthesize nanomaterials with more precise dimensions at narrow size-distribution and with controllable behaviors.

Note: A microfluidic freezer based on evaporative cooling of atomized aqueous microdroplets

DOE Office of Scientific and Technical Information (OSTI.GOV)

Song, Jin; Kim, Dohyun, E-mail: dohyun.kim@mju.ac.kr; Chung, Minsub

2015-01-15

We report for the first time water-based evaporative cooling integrated into a microfluidic chip for temperature control and freezing of biological solution. We opt for water as a nontoxic, effective refrigerant. Aqueous solutions are atomized in our device and evaporation of microdroplets under vacuum removes heat effectively. We achieve rapid cooling (−5.1 °C/s) and a low freezing temperature (−14.1 °C). Using this approach, we demonstrate freezing of deionized water and protein solution. Our simple, yet effective cooling device may improve many microfluidic applications currently relying on external power-hungry instruments for cooling and freezing.

A laser-based technology for fabricating a soda-lime glass based microfluidic device for circulating tumour cell capture.

PubMed

Nieto, Daniel; Couceiro, Ramiro; Aymerich, Maria; Lopez-Lopez, Rafael; Abal, Miguel; Flores-Arias, María Teresa

2015-10-01

We developed a laser-based technique for fabricating microfluidic microchips on soda-lime glass substrates. The proposed methodology combines a laser direct writing, as a manufacturing tool for the fabrication of the microfluidics structures, followed by a post-thermal treatment with a CO2 laser. This treatment will allow reshaping and improving the morphological (roughness) and optical qualities (transparency) of the generated microfluidics structures. The use of lasers commonly implemented for material processing makes this technique highly competitive when compared with other glass microstructuring approaches. The manufactured chips were tested with tumour cells (Hec 1A) after being functionalized with an epithelial cell adhesion molecule (EpCAM) antibody coating. Cells were successfully arrested on the pillars after being flown through the device giving our technology a translational application in the field of cancer research. Copyright © 2015 Elsevier B.V. All rights reserved.

Single cell Enrichment with High Throughput Microfluidic Devices

NASA Astrophysics Data System (ADS)

Pakjesm Pourfard, Pedram

Microfluidics is a rapidly growing field of biomedical engineering with numerous applications such as diagnostic testing, therapeutics, and research preparation. Cell enrichment for automated diagnostic is often assayed through measurement of biochemical and biophysical markers. Although biochemical markers have been widely used, intrinsic biophysical markers, such as, Shear migration, Lift force, Dean force, and many other label-free techniques, are advantageous since they don't require costly labeling or sample preparation. However, current passive techniques for enrichment had limited adoption in clinical and cell biology research applications. They generally require low flow rate and low cell volume fraction for high efficiency. The Control increment filtration, T-shaped microfluidic device, and spiral-shaped microfluidic devices will be studied for single-cell separation from aggregates. Control increment filtration works like the tangential filter; however, cells are separated based off of same amount of flow rate passing through large space gaps. Main microchannel of T-Shaped is connected to two perpendicular side channels. Based off Shear-modulated inertial migration, this device will enable selective enrichment of cells. The spiral shaped microfluidic device depends on different Dean and lift forces acting on cells to separate them based off different sizes. The spiral geometry of the microchannel will enable dominant inertial forces and the Dean Rotation force to cause larger cells to migrate to the inner side of the microchannel. Because manipulation of microchannel dimensions correlates to the degree of cell separation, versatility in design exists. Cell mixture samples will contain cells of different sizes and therefore design strategies could be utilized to maximize the effectiveness of single-cell separation.

Biodegradable microsphere-mediated cell perforation in microfluidic channel using femtosecond laser

NASA Astrophysics Data System (ADS)

Ishii, Atsuhiro; Ariyasu, Kazumasa; Mitsuhashi, Tatsuki; Heinemann, Dag; Heisterkamp, Alexander; Terakawa, Mitsuhiro

2016-05-01

The use of small particles has expanded the capability of ultrashort pulsed laser optoinjection technology toward simultaneous treatment of multiple cells. The microfluidic platform is one of the attractive systems that has obtained synergy with laser-based technology for cell manipulation, including optoinjection. We have demonstrated the delivery of molecules into suspended-flowing cells in a microfluidic channel by using biodegradable polymer microspheres and a near-infrared femtosecond laser pulse. The use of polylactic-co-glycolic acid microspheres realized not only a higher optoinjection ratio compared to that with polylactic acid microspheres but also avoids optical damage to the microfluidic chip, which is attributable to its higher optical intensity enhancement at the localized spot under a microsphere. Interestingly, optoinjection ratios to nucleus showed a difference for adhered cells and suspended cells. The use of biodegradable polymer microspheres provides high throughput optoinjection; i.e., multiple cells can be treated in a short time, which is promising for various applications in cell analysis, drug delivery, and ex vivo gene transfection to bone marrow cells and stem cells without concerns about residual microspheres.

Fabrication, measurement, and modeling of electro-osmotic flow in micromachined polymer microchannels

NASA Astrophysics Data System (ADS)

Suriyage, Nihal U.; Ghantasala, Muralidhar K.; Iovenitti, Pio; Harvey, Erol C.

2004-03-01

Electroosmotic pumping in the microchannels fabricated in polycarbonate (PC), polyethyleneterephthalate (PET) and SU-8 polymer substrates was investigated and species transportation was modeled, in an attempt to show the suitability of low cost polymer materials for the development of disposable microfluidic devices. Microchannels and the fluid reservoirs were fabricated using excimer laser ablation and hot embossing techniques. Typical dimensions of the microchannels were 60μm (width) x 50μm (depth) x 45mm (length). Species transportation in the microchannels under electroosmosis was modeled by finite element method (FEM) with the help of NetFlow module of the CoventorWareTM computational fluid dynamics (CFD) package. In particular, electroosmosis and electrophoresis in a crossed microfluidic channel was modeled to calculate the percentage species mass transportation when the concentration shape of the Gaussian input species plug and the location of the injection point are varied. Change in the concentration shape of the initial species plug while it is electroosmotically transported along the crossed fluidic channel was visualized. Results indicated that Excimer laser ablated PC and PET devices have electroosmotic mobility in the range 2 to 5 x10-4 cm2/V.s, zeta potential 30 to 70 mV and flow rates of the order of 1 to 3 nL/s under an electric field of 200 V/cm. With the electroosmotic mobility value of PC the simulation results show that a crossed fluidic channel is electroosmotically pumping about 91% of the species mass injected along one of its straight channels.

Silanization of boron nitride nanosheets (BNNSs) through microfluidization and their use for producing thermally conductive and electrically insulating polymer nanocomposites

DOE Office of Scientific and Technical Information (OSTI.GOV)

Seyhan, A.Tuğrul, E-mail: atseyhan@anadolu.edu.tr; Composite Materials Manufacturing Science Laboratory; Göncü, Yapıncak

Chemical exfoliation of boron nitride nanosheets (BNNSs) from large flakes of specially synthesized micro-sized hexagonal boron nitride (h-BN) ceramics was carried out through microfluidization. The surface of BNNSs obtained was then functionalized with vinyl-trimethoxy silane (VTS) coupling agent through microfluidization once again in an effort to make them compatible with organic materials, especially those including polymers. The morphology of BNNSs with and without silane treatment was then systematically characterized by conducting various different analytical techniques, including Thermogravimetric analysis (TGA), X-ray diffraction (XRD), Scanning Electron Microscopy (SEM), Bright field Transmission Electron Microscopy (BF-TEM), Contact angle analyzer (CAA), Particle size analyzer (PSA)more » and Fourier Transmission Infrared (FTIR) spectroscopy attached with attenuated total reflectance (ATR) module. As a result, the silane treatment was determined to be properly and successfully carried out and to give rise to the irregularity of large flakes of the BNNSs by folding back their free edges upon themselves, which in turn assists in inducing further exfoliation of the few-layered nanosheets. To gain more insight into the effectiveness of the surface functionalization, thermal conductivity of polypropylene (PP) nanocomposites containing different amounts (1 wt% and 5 wt%) of BNNSs with and without silane treatment was experimentally investigated. Regardless of the weight content, PP nanocomposites containing silanized BNNSs were found to exhibit high thermal conductivity compared to PP nanocomposites containing BNNSs without silane treatment. It was concluded that microfluidization possesses the robustness to provide a reliable product quality, whether in small or large quantities, in a very time effective manner, when it comes to first exfoliating two-dimensional inorganic materials into few layered sheets, and functionalizing the surface of these sheets afterwards to make it possible to utilize them as promising filler constituent in manufacturing thermally conductive and electrically insulating polymer nanocomposites that could be considered as whole or a part of a heat-releasing device.« less

Silanization of boron nitride nanosheets (BNNSs) through microfluidization and their use for producing thermally conductive and electrically insulating polymer nanocomposites

NASA Astrophysics Data System (ADS)

Seyhan, A. Tuğrul; Göncü, Yapıncak; Durukan, Oya; Akay, Atakan; Ay, Nuran

2017-05-01

Chemical exfoliation of boron nitride nanosheets (BNNSs) from large flakes of specially synthesized micro-sized hexagonal boron nitride (h-BN) ceramics was carried out through microfluidization. The surface of BNNSs obtained was then functionalized with vinyl-trimethoxy silane (VTS) coupling agent through microfluidization once again in an effort to make them compatible with organic materials, especially those including polymers. The morphology of BNNSs with and without silane treatment was then systematically characterized by conducting various different analytical techniques, including Thermogravimetric analysis (TGA), X-ray diffraction (XRD), Scanning Electron Microscopy (SEM), Bright field Transmission Electron Microscopy (BF-TEM), Contact angle analyzer (CAA), Particle size analyzer (PSA) and Fourier Transmission Infrared (FTIR) spectroscopy attached with attenuated total reflectance (ATR) module. As a result, the silane treatment was determined to be properly and successfully carried out and to give rise to the irregularity of large flakes of the BNNSs by folding back their free edges upon themselves, which in turn assists in inducing further exfoliation of the few-layered nanosheets. To gain more insight into the effectiveness of the surface functionalization, thermal conductivity of polypropylene (PP) nanocomposites containing different amounts (1 wt% and 5 wt%) of BNNSs with and without silane treatment was experimentally investigated. Regardless of the weight content, PP nanocomposites containing silanized BNNSs were found to exhibit high thermal conductivity compared to PP nanocomposites containing BNNSs without silane treatment. It was concluded that microfluidization possesses the robustness to provide a reliable product quality, whether in small or large quantities, in a very time effective manner, when it comes to first exfoliating two-dimensional inorganic materials into few layered sheets, and functionalizing the surface of these sheets afterwards to make it possible to utilize them as promising filler constituent in manufacturing thermally conductive and electrically insulating polymer nanocomposites that could be considered as whole or a part of a heat-releasing device.

Development of a titanium dioxide-coated microfluidic-based photocatalyst-assisted reduction device to couple high-performance liquid chromatography with inductively coupled plasma-mass spectrometry for determination of inorganic selenium species.

PubMed

Shih, Tsung-Ting; Lin, Cheng-Hsing; Hsu, I-Hsiang; Chen, Jian-Yi; Sun, Yuh-Chang

2013-11-05

We developed a selective and sensitive hyphenated system employing a microfluidic-based vapor generation (VG) system in conjunction with high-performance liquid chromatography (HPLC) separation and inductively coupled plasma-mass spectrometry (ICPMS) detection for the determination of trace inorganic selenium (Se) species. The VG system exploited poly(methyl methacrylate) (PMMA) substrates of high optical quality to fabricate a microfluidic-based photocatalyst-assisted reduction device (microfluidic-based PCARD). Moreover, to reduce the consumption of photocatalysts during analytical procedures, a microfluidic-based PCARD coated with titanium dioxide nanoparticles (nano-TiO2) was employed to avoid consecutive loading. Notably, to simplify the coating procedure and improve the stability of the coating materials, a dynamic coating method was utilized. Under the optimized conditions for the selenicals of interest, the online HPLC/TiO2-coated microfluidic-based PCARD/ICPMS system enabled us to achieve detection limits (based on 3σ) of 0.043 and 0.042 μg L(-1) for Se(IV) and Se(VI), respectively. Both Se(IV) and Se(VI) could be efficiently vaporized within 15 s, while a series of validation experiments indicated that our proposed method could be satisfactorily applied to the determination of inorganic Se species in the environmental water samples.

3D-printed microfluidic chips with patterned, cell-laden hydrogel constructs.

PubMed

Knowlton, Stephanie; Yu, Chu Hsiang; Ersoy, Fulya; Emadi, Sharareh; Khademhosseini, Ali; Tasoglu, Savas

2016-06-20

Three-dimensional (3D) printing offers potential to fabricate high-throughput and low-cost fabrication of microfluidic devices as a promising alternative to traditional techniques which enables efficient design iterations in the development stage. In this study, we demonstrate a single-step fabrication of a 3D transparent microfluidic chip using two alternative techniques: a stereolithography-based desktop 3D printer and a two-step fabrication using an industrial 3D printer based on polyjet technology. This method, compared to conventional fabrication using relatively expensive materials and labor-intensive processes, presents a low-cost, rapid prototyping technique to print functional 3D microfluidic chips. We enhance the capabilities of 3D-printed microfluidic devices by coupling 3D cell encapsulation and spatial patterning within photocrosslinkable gelatin methacryloyl (GelMA). The platform presented here serves as a 3D culture environment for long-term cell culture and growth. Furthermore, we have demonstrated the ability to print complex 3D microfluidic channels to create predictable and controllable fluid flow regimes. Here, we demonstrate the novel use of 3D-printed microfluidic chips as controllable 3D cell culture environments, advancing the applicability of 3D printing to engineering physiological systems for future applications in bioengineering.

Digital hydraulic drive for microfluidics and miniaturized cell culture devices based on shape memory alloy actuators

NASA Astrophysics Data System (ADS)

Tsai, Cheng-Han; Wu, Xuanye; Kuan, Da-Han; Zimmermann, Stefan; Zengerle, Roland; Koltay, Peter

2018-08-01

In order to culture and analyze individual living cells, microfluidic cultivation and manipulation of cells become an increasingly important topic. Such microfluidic systems allow for exploring the phenotypic differences between thousands of genetically identical cells or pharmacological tests in parallel, which is impossible to achieve by traditional macroscopic cell culture methods. Therefore, plenty of microfluidic systems and devices have been developed for cell biological studies like cell culture, cell sorting, and cell lysis in the past. However, these microfluidic systems are still limited by the external pressure sources which most of the time are large in size and have to be connected by fluidic tubing leading to complex and delicate systems. In order to provide a miniaturized, more robust actuation system a novel, compact and low power consumption digital hydraulic drive (DHD) has been developed that is intended for use in portable and automated microfluidic systems for various applications. The DHD considered in this work consists of a shape memory alloy (SMA) actuator and a pneumatic cylinder. The switching time of the digital modes (pressure ON versus OFF) can be adjusted from 1 s to min. Thus, the DHDs might have many applications for driving microfluidic devices. In this work, different implementations of DHDs are presented and their performance is characterized by experiments. In particular, it will be shown that DHDs can be used for microfluidic large-scale integration (mLSI) valve control (256 valves in parallel) as well as potentially for droplet-based microfluidic systems. As further application example, high-throughput mixing of cell cultures (96 wells in parallel) is demonstrated employing the DHD to drive a so-called ‘functional lid’ (FL), to enable a miniaturized micro bioreactor in a regular 96-well micro well plate.

Split and flow: reconfigurable capillary connection for digital microfluidic devices.

PubMed

Lapierre, Florian; Harnois, Maxime; Coffinier, Yannick; Boukherroub, Rabah; Thomy, Vincent

2014-09-21

Supplying liquid to droplet-based microfluidic microsystems remains a delicate task facing the problems of coupling continuous to digital or macro- to microfluidic systems. Here, we take advantage of superhydrophobic microgrids to address this problem. Insertion of a capillary tube inside a microgrid aperture leads to a simple and reconfigurable droplet generation setup.

Open-source, community-driven microfluidics with Metafluidics.

PubMed

Kong, David S; Thorsen, Todd A; Babb, Jonathan; Wick, Scott T; Gam, Jeremy J; Weiss, Ron; Carr, Peter A

2017-06-07

Microfluidic devices have the potential to automate and miniaturize biological experiments, but open-source sharing of device designs has lagged behind sharing of other resources such as software. Synthetic biologists have used microfluidics for DNA assembly, cell-free expression, and cell culture, but a combination of expense, device complexity, and reliance on custom set-ups hampers their widespread adoption. We present Metafluidics, an open-source, community-driven repository that hosts digital design files, assembly specifications, and open-source software to enable users to build, configure, and operate a microfluidic device. We use Metafluidics to share designs and fabrication instructions for both a microfluidic ring-mixer device and a 32-channel tabletop microfluidic controller. This device and controller are applied to build genetic circuits using standard DNA assembly methods including ligation, Gateway, Gibson, and Golden Gate. Metafluidics is intended to enable a broad community of engineers, DIY enthusiasts, and other nontraditional participants with limited fabrication skills to contribute to microfluidic research.

Organ/body-on-a-chip based on microfluidic technology for drug discovery.

PubMed

Kimura, Hiroshi; Sakai, Yasuyuki; Fujii, Teruo

2018-02-01

Although animal experiments are indispensable for preclinical screening in the drug discovery process, various issues such as ethical considerations and species differences remain. To solve these issues, cell-based assays using human-derived cells have been actively pursued. However, it remains difficult to accurately predict drug efficacy, toxicity, and organs interactions, because cultivated cells often do not retain their original organ functions and morphologies in conventional in vitro cell culture systems. In the μTAS research field, which is a part of biochemical engineering, the technologies of organ-on-a-chip, based on microfluidic devices built using microfabrication, have been widely studied recently as a novel in vitro organ model. Since it is possible to physically and chemically mimic the in vitro environment by using microfluidic device technology, maintenance of cellular function and morphology, and replication of organ interactions can be realized using organ-on-a-chip devices. So far, functions of various organs and tissues, such as the lung, liver, kidney, and gut have been reproduced as in vitro models. Furthermore, a body-on-a-chip, integrating multi organ functions on a microfluidic device, has also been proposed for prediction of organ interactions. We herein provide a background of microfluidic systems, organ-on-a-chip, Body-on-a-chip technologies, and their challenges in the future. Copyright © 2017 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.

Isolation of breast cancer and gastric cancer circulating tumor cells by use of an anti HER2-based microfluidic device.

PubMed

Galletti, Giuseppe; Sung, Matthew S; Vahdat, Linda T; Shah, Manish A; Santana, Steven M; Altavilla, Giuseppe; Kirby, Brian J; Giannakakou, Paraskevi

2014-01-07

Circulating tumor cells (CTCs) have emerged as a reliable source of tumor cells, and their concentration has prognostic implications. CTC capture offers real-time access to cancer tissue without the need of an invasive biopsy, while their phenotypic and molecular interrogation can provide insight into the biological changes of the tumor that occur during treatment. The majority of the CTC capture methods are based on EpCAM expression as a surface marker of tumor-derived cells. However, EpCAM protein expression levels can be significantly down regulated during cancer progression as a consequence of the process of epithelial to mesenchymal transition. In this paper, we describe a novel HER2 (Human Epidermal Receptor 2)-based microfluidic device for the isolation of CTCs from peripheral blood of patients with HER2-expressing solid tumors. We selected HER2 as an alternative to EpCAM as the receptor is biologically and therapeutically relevant in several solid tumors, like breast cancer (BC), where it is overexpressed in 30% of the patients and expressed in 90%, and gastric cancer (GC), in which HER2 presence is identified in more than 60% of the cases. We tested the performance of various anti HER2 antibodies in a panel of nine different BC cell lines with varying HER2 protein expression levels, using immunoblotting, confocal microscopy, live cells imaging and flow cytometry analyses. The antibody associated with the highest capture efficiency and sensitivity for HER2 expressing cells on the microfluidic device was the one that performed best in live cells imaging and flow cytometry assays as opposed to the fixed cell analyses, suggesting that recognition of the native conformation of the HER2 extracellular epitope on living cells was essential for specificity and sensitivity of CTC capture. Next, we tested the performance of the HER2 microfluidic device using blood from metastatic breast and gastric cancer patients. The HER2 microfluidic device exhibited CTC capture in 9/9 blood samples. Thus, the described HER2-based microfluidic device can be considered as a valid clinically relevant method for CTC capture in HER2 expressing solid cancers.

Fused Deposition Modeling 3D Printing for (Bio)analytical Device Fabrication: Procedures, Materials, and Applications

PubMed Central

2017-01-01

In this work, the use of fused deposition modeling (FDM) in a (bio)analytical/lab-on-a-chip research laboratory is described. First, the specifications of this 3D printing method that are important for the fabrication of (micro)devices were characterized for a benchtop FDM 3D printer. These include resolution, surface roughness, leakage, transparency, material deformation, and the possibilities for integration of other materials. Next, the autofluorescence, solvent compatibility, and biocompatibility of 12 representative FDM materials were tested and evaluated. Finally, we demonstrate the feasibility of FDM in a number of important applications. In particular, we consider the fabrication of fluidic channels, masters for polymer replication, and tools for the production of paper microfluidic devices. This work thus provides a guideline for (i) the use of FDM technology by addressing its possibilities and current limitations, (ii) material selection for FDM, based on solvent compatibility and biocompatibility, and (iii) application of FDM technology to (bio)analytical research by demonstrating a broad range of illustrative examples. PMID:28628294

Note: On-chip multifunctional fluorescent-magnetic Janus helical microswimmers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hwang, G., E-mail: gilgueng.hwang@lpn.cnrs.fr; Decanini, D.; Leroy, L.

Microswimmers integrated into microfluidic devices that are capable of self-illumination through fluorescence could revolutionize many aspects of technology, especially for biological applications. Few illumination and propulsion techniques of helical microswimmers inside microfluidic channels have been demonstrated. This paper presents the fabrication, detachment, and magnetic propulsions of multifunctional fluorescent-magnetic helical microswimmers integrated inside microfluidics. The fabrication process is based on two-photon laser lithography to pattern 3-D nanostructures from fluorescent photoresist coupled with conventional microfabrication techniques for magnetic thin film deposition by shadowing. After direct integration inside a microfluidic device, injected gas bubble allows gentle detachment of the integrated helical microswimmers whosemore » magnetic propulsion can then be directly applied inside the microfluidic channel using external electromagnetic coil setup. With their small scale, fluorescence, excellent resistance to liquid/gas surface tension, and robust propulsion capability inside the microfluidic channel, the microswimmers can be used as high-resolution and large-range mobile micromanipulators inside microfluidic channels.« less

A rapid, straightforward, and print house compatible mass fabrication method for integrating 3D paper-based microfluidics.

PubMed

Xiao, Liangpin; Liu, Xianming; Zhong, Runtao; Zhang, Kaiqing; Zhang, Xiaodi; Zhou, Xiaomian; Lin, Bingcheng; Du, Yuguang

2013-11-01

Three-dimensional (3D) paper-based microfluidics, which is featured with high performance and speedy determination, promise to carry out multistep sample pretreatment and orderly chemical reaction, which have been used for medical diagnosis, cell culture, environment determination, and so on with broad market prospect. However, there are some drawbacks in the existing fabrication methods for 3D paper-based microfluidics, such as, cumbersome and time-consuming device assembly; expensive and difficult process for manufacture; contamination caused by organic reagents from their fabrication process. Here, we present a simple printing-bookbinding method for mass fabricating 3D paper-based microfluidics. This approach involves two main steps: (i) wax-printing, (ii) bookbinding. We tested the delivery capability, diffusion rate, homogeneity and demonstrated the applicability of the device to chemical analysis by nitrite colorimetric assays. The described method is rapid (<30 s), cheap, easy to manipulate, and compatible with the flat stitching method that is common in a print house, making itself an ideal scheme for large-scale production of 3D paper-based microfluidics. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Monolithic integration of microfluidic channels and semiconductor lasers.

PubMed

Cran-McGreehin, Simon J; Dholakia, Kishan; Krauss, Thomas F

2006-08-21

We present a fabrication method for the monolithic integration of microfluidic channels into semiconductor laser material. Lasers are designed to couple directly into the microfluidic channel, allowing submerged particles pass through the output beams of the lasers. The interaction between particles in the channel and the lasers, operated in either forward or reverse bias, allows for particle detection, and the optical forces can be used to trap and move particles. Both interrogation and manipulation are made more amenable for lab-on-a-chip applications through monolithic integration. The devices are very small, they require no external optical components, have perfect intrinsic alignment, and can be created with virtually any planar configuration of lasers in order to perform a variety of tasks. Their operation requires no optical expertise and only low electrical power, thus making them suitable for computer interfacing and automation. Insulating the pn junctions from the fluid is the key challenge, which is overcome by using photo-definable SU8-2000 polymer.

Monolithic integration of microfluidic channels and semiconductor lasers

NASA Astrophysics Data System (ADS)

Cran-McGreehin, Simon J.; Dholakia, Kishan; Krauss, Thomas F.

2006-08-01

We present a fabrication method for the monolithic integration of microfluidic channels into semiconductor laser material. Lasers are designed to couple directly into the microfluidic channel, allowing submerged particles pass through the output beams of the lasers. The interaction between particles in the channel and the lasers, operated in either forward or reverse bias, allows for particle detection, and the optical forces can be used to trap and move particles. Both interrogation and manipulation are made more amenable for lab-on-a-chip applications through monolithic integration. The devices are very small, they require no external optical components, have perfect intrinsic alignment, and can be created with virtually any planar configuration of lasers in order to perform a variety of tasks. Their operation requires no optical expertise and only low electrical power, thus making them suitable for computer interfacing and automation. Insulating the pn junctions from the fluid is the key challenge, which is overcome by using photo-definable SU8-2000 polymer.

Microfluidic magnetic fluidized bed for DNA analysis in continuous flow mode.

PubMed

Hernández-Neuta, Iván; Pereiro, Iago; Ahlford, Annika; Ferraro, Davide; Zhang, Qiongdi; Viovy, Jean-Louis; Descroix, Stéphanie; Nilsson, Mats

2018-04-15

Magnetic solid phase substrates for biomolecule manipulation have become a valuable tool for simplification and automation of molecular biology protocols. However, the handling of magnetic particles inside microfluidic chips for miniaturized assays is often challenging due to inefficient mixing, aggregation, and the advanced instrumentation required for effective actuation. Here, we describe the use of a microfluidic magnetic fluidized bed approach that enables dynamic, highly efficient and simplified magnetic bead actuation for DNA analysis in a continuous flow platform with minimal technical requirements. We evaluate the performance of this approach by testing the efficiency of individual steps of a DNA assay based on padlock probes and rolling circle amplification. This assay comprises common nucleic acid analysis principles, such as hybridization, ligation, amplification and restriction digestion. We obtained efficiencies of up to 90% for these reactions with high throughput processing up to 120μL of DNA dilution at flow rates ranging from 1 to 5μL/min without compromising performance. The fluidized bed was 20-50% more efficient than a commercially available solution for microfluidic manipulation of magnetic beads. Moreover, to demonstrate the potential of this approach for integration into micro-total analysis systems, we optimized the production of a low-cost polymer based microarray and tested its analytical performance for integrated single-molecule digital read-out. Finally, we provide the proof-of-concept for a single-chamber microfluidic chip that combines the fluidized bed with the polymer microarray for a highly simplified and integrated magnetic bead-based DNA analyzer, with potential applications in diagnostics. Copyright © 2017 Elsevier B.V. All rights reserved.

Manufacturing and application of a fully polymeric electrophoresis chip with integrated polyaniline electrodes.

PubMed

Henderson, Rowan D; Guijt, Rosanne M; Haddad, Paul R; Hilder, Emily F; Lewis, Trevor W; Breadmore, Michael C

2010-07-21

This work describes the development of a fully polymeric microchip with integrated polymeric electrodes suitable for performing microchip electrophoresis. The polymer electrodes were fabricated in a thin film of the conducting polymer, polyaniline (PANI), by flash lithography using a studio camera flash and a transparency mask. During flash welding, exposed regions welded into non-conducting regions forming a conducting polymer circuit in the non-exposed regions. Using a structured layer of dry film photoresist for sealing, a polydimethylsiloxane (PDMS) substrate containing channels and reservoirs was bound to the PANI film to form an integrated microfluidic device. The conducting regions of the PANI film were shown to be capable of carrying the high voltages of up to 2000 V required for chip electrophoresis, and were stable for up to 30 minutes under these conditions. The PANI electrodes were used for the electrophoretic separation of three sugars labelled with 8-amino-1,3,6-pyrenetrisulfonic acid (APTS) in the dry film resist-PDMS hybrid device. Highly efficient separations comparable to those achieved in similar microchips using platinum electrodes confirm the potential of polyaniline as a new material suitable for high voltage electrodes in Lab-on-a-chip devices.

Microfluidics for producing poly (lactic-co-glycolic acid)-based pharmaceutical nanoparticles.

PubMed

Li, Xuanyu; Jiang, Xingyu

2017-12-24

Microfluidic chips allow the rapid production of a library of nanoparticles (NPs) with distinct properties by changing the precursors and the flow rates, significantly decreasing the time for screening optimal formulation as carriers for drug delivery compared to conventional methods. The batch-to-batch reproducibility which is essential for clinical translation is achieved by precisely controlling the precursors and the flow rate, regardless of operators. Poly (lactic-co-glycolic acid) (PLGA) is the most widely used Food and Drug Administration (FDA)-approved biodegradable polymers. Researchers often combine PLGA with lipids or amphiphilic molecules to assemble into a core/shell structure to exploit the potential of PLGA-based NPs as powerful carriers for cancer-related drug delivery. In this review, we discuss the advantages associated with microfluidic chips for producing PLGA-based functional nanocomplexes for drug delivery. These laboratory-based methods can readily scale up to provide sufficient amount of PLGA-based NPs in microfluidic chips for clinical studies and industrial-scale production. Copyright © 2017. Published by Elsevier B.V.

Principles, Techniques, and Applications of Tissue Microfluidics

NASA Technical Reports Server (NTRS)

Wade, Lawrence A.; Kartalov, Emil P.; Shibata, Darryl; Taylor, Clive

2011-01-01

The principle of tissue microfluidics and its resultant techniques has been applied to cell analysis. Building microfluidics to suit a particular tissue sample would allow the rapid, reliable, inexpensive, highly parallelized, selective extraction of chosen regions of tissue for purposes of further biochemical analysis. Furthermore, the applicability of the techniques ranges beyond the described pathology application. For example, they would also allow the posing and successful answering of new sets of questions in many areas of fundamental research. The proposed integration of microfluidic techniques and tissue slice samples is called tissue microfluidics because it molds the microfluidic architectures in accordance with each particular structure of each specific tissue sample. Thus, microfluidics can be built around the tissues, following the tissue structure, or alternatively, the microfluidics can be adapted to the specific geometry of particular tissues. By contrast, the traditional approach is that microfluidic devices are structured in accordance with engineering considerations, while the biological components in applied devices are forced to comply with these engineering presets. The proposed principles represent a paradigm shift in microfluidic technology in three important ways: Microfluidic devices are to be directly integrated with, onto, or around tissue samples, in contrast to the conventional method of off-chip sample extraction followed by sample insertion in microfluidic devices. Architectural and operational principles of microfluidic devices are to be subordinated to suit specific tissue structure and needs, in contrast to the conventional method of building devices according to fluidic function alone and without regard to tissue structure. Sample acquisition from tissue is to be performed on-chip and is to be integrated with the diagnostic measurement within the same device, in contrast to the conventional method of off-chip sample prep and subsequent insertion into a diagnostic device. A more advanced form of tissue integration with microfluidics is tissue encapsulation, wherein the sample is completely encapsulated within a microfluidic device, to allow for full surface access. The immediate applications of these approaches lie with diagnostics of tissue slices and biopsy samples e.g. for cancer but the approaches would also be very useful in comparative genomics and other areas of fundamental research involving heterogeneous tissue samples.

Towards non- and minimally instrumented, microfluidics-based diagnostic devices†

PubMed Central

Weigl, Bernhard; Domingo, Gonzalo; LaBarre, Paul; Gerlach, Jay

2009-01-01

In many health care settings, it is uneconomical, impractical, or unaffordable to maintain and access a fully equipped diagnostics laboratory. Examples include home health care, developing-country health care, and emergency situations in which first responders are dealing with pandemics or biowarfare agent release. In those settings, fully disposable diagnostic devices that require no instrument support, reagent, or significant training are well suited. Although the only such technology to have found widespread adoption so far is the immunochromatographic rapid assay strip test, microfluidics holds promise to expand the range of assay technologies that can be performed in formats similar to that of a strip test. In this paper, we review progress toward development of disposable, low-cost, easy-to-use microfluidics-based diagnostics that require no instrument at all. We also present examples of microfluidic functional elements—including mixers, separators, and detectors—as well as complete microfluidic devices that function entirely without any moving parts and external power sources. PMID:19023463

Three-Dimensionally Printed Microfluidic Cross-flow System for Ultrafiltration/Nanofiltration Membrane Performance Testing.

PubMed

Wardrip, Nathaniel C; Arnusch, Christopher J

2016-02-13

Minimization and management of membrane fouling is a formidable challenge in diverse industrial processes and other practices that utilize membrane technology. Understanding the fouling process could lead to optimization and higher efficiency of membrane based filtration. Here we show the design and fabrication of an automated three-dimensionally (3-D) printed microfluidic cross-flow filtration system that can test up to 4 membranes in parallel. The microfluidic cells were printed using multi-material photopolymer 3-D printing technology, which used a transparent hard polymer for the microfluidic cell body and incorporated a thin rubber-like polymer layer, which prevents leakages during operation. The performance of ultrafiltration (UF), and nanofiltration (NF) membranes were tested and membrane fouling could be observed with a model foulant bovine serum albumin (BSA). Feed solutions containing BSA showed flux decline of the membrane. This protocol may be extended to measure fouling or biofouling with many other organic, inorganic or microbial containing solutions. The microfluidic design is especially advantageous for testing materials that are costly or only available in small quantities, for example polysaccharides, proteins, or lipids due to the small surface area of the membrane being tested. This modular system may also be easily expanded for high throughput testing of membranes.

Three-Dimensionally Printed Microfluidic Cross-flow System for Ultrafiltration/Nanofiltration Membrane Performance Testing

PubMed Central

Wardrip, Nathaniel C.; Arnusch, Christopher J.

2016-01-01

Minimization and management of membrane fouling is a formidable challenge in diverse industrial processes and other practices that utilize membrane technology. Understanding the fouling process could lead to optimization and higher efficiency of membrane based filtration. Here we show the design and fabrication of an automated three-dimensionally (3-D) printed microfluidic cross-flow filtration system that can test up to 4 membranes in parallel. The microfluidic cells were printed using multi-material photopolymer 3-D printing technology, which used a transparent hard polymer for the microfluidic cell body and incorporated a thin rubber-like polymer layer, which prevents leakages during operation. The performance of ultrafiltration (UF), and nanofiltration (NF) membranes were tested and membrane fouling could be observed with a model foulant bovine serum albumin (BSA). Feed solutions containing BSA showed flux decline of the membrane. This protocol may be extended to measure fouling or biofouling with many other organic, inorganic or microbial containing solutions. The microfluidic design is especially advantageous for testing materials that are costly or only available in small quantities, for example polysaccharides, proteins, or lipids due to the small surface area of the membrane being tested. This modular system may also be easily expanded for high throughput testing of membranes.  PMID:26968008

Plastic Polymers for Efficient DNA Microarray Hybridization: Application to Microbiological Diagnostics▿

PubMed Central

Zhao, Zhengshan; Peytavi, Régis; Diaz-Quijada, Gerardo A.; Picard, Francois J.; Huletsky, Ann; Leblanc, Éric; Frenette, Johanne; Boivin, Guy; Veres, Teodor; Dumoulin, Michel M.; Bergeron, Michel G.

2008-01-01

Fabrication of microarray devices using traditional glass slides is not easily adaptable to integration into microfluidic systems. There is thus a need for the development of polymeric materials showing a high hybridization signal-to-background ratio, enabling sensitive detection of microbial pathogens. We have developed such plastic supports suitable for highly sensitive DNA microarray hybridizations. The proof of concept of this microarray technology was done through the detection of four human respiratory viruses that were amplified and labeled with a fluorescent dye via a sensitive reverse transcriptase PCR (RT-PCR) assay. The performance of the microarray hybridization with plastic supports made of PMMA [poly(methylmethacrylate)]-VSUVT or Zeonor 1060R was compared to that with high-quality glass slide microarrays by using both passive and microfluidic hybridization systems. Specific hybridization signal-to-background ratios comparable to that obtained with high-quality commercial glass slides were achieved with both polymeric substrates. Microarray hybridizations demonstrated an analytical sensitivity equivalent to approximately 100 viral genome copies per RT-PCR, which is at least 100-fold higher than the sensitivities of previously reported DNA hybridizations on plastic supports. Testing of these plastic polymers using a microfluidic microarray hybridization platform also showed results that were comparable to those with glass supports. In conclusion, PMMA-VSUVT and Zeonor 1060R are both suitable for highly sensitive microarray hybridizations. PMID:18784318

Fabrication of microscale materials with programmable composition gradients.

PubMed

Laval, Cédric; Bouchaudy, Anne; Salmon, Jean-Baptiste

2016-04-07

We present an original microfluidic technique coupling pervaporation and the use of Quake valves to fabricate microscale materials (∼10 × 100 μm(2) × 1 cm) with composition gradients along their longest dimension. Our device exploits pervaporation of water through a thin poly(dimethylsiloxane) (PDMS) membrane to continuously pump solutions (or dispersions) contained in different reservoirs connected to a microfluidic channel. This pervaporation-induced flow concentrates solutes (or particles) at the tip of the channel up to the formation of a dense material. The latter invades the channel as it is constantly enriched by an incoming flux of solutes/particles. Upstream Quake valves are used to select which reservoir is connected to the pervaporation channel and thus which solution (or dispersion) enriches the material during its growth. The microfluidic configuration of the pervaporation process is used to impose controlled growth along the channel thus enabling one to program spatial composition gradients using appropriate actuations of the valves. We demonstrate the possibilities offered by our technique through the fabrication of dense assemblies of nanoparticles and polymer composites with programmed gradients of fluorescent dyes. We also address the key issue of the spatial resolution of our gradients and we show that well-defined spatial modulations down to ≈50 μm can be obtained within colloidal materials, whereas gradients within polymer materials are resolved on length scales down to ≈1 mm due to molecular diffusion.

Combined SERS biotags (SBTs) and microfluidic platform for the quantitative ratiometric discrimination between noncancerous and cancerous cells in flow

NASA Astrophysics Data System (ADS)

Pallaoro, Alessia; Hoonejani, Mehran R.; Braun, Gary B.; Meinhart, Carl; Moskovits, Martin

2012-10-01

SERS biotags are made from polymer-encapsulated silver nanoparticle dimers infused with unique Raman reporter molecules, and carry peptides as cell recognition moieties. We demonstrate their potential use for early and rapid identification of malignant cells, a central goal in cancer research. SERS biotags (SBTs) can be routinely synthesized and simultaneously excited with a single, low intensity laser source, making the determination of the relative contribution of the individual SBTs to the overall spectrum tractable. Importantly for biomedical applications, SERS employs tissuepenetrating lasers in the red to near-infrared range resulting in low autofluorescence. We have previously described a multiplexed, ratiometric method that can confidently distinguish between cancerous and noncancerous epithelial prostate cells in vitro based on receptor overexpression. Here we present the progress towards the application of this quantitative methodology for the identification of cancer cells in a microfluidic flow-focusing device. Beads are used as cell mimics to characterize the devices. Cells (and beads) are simultaneously incubated with two sets of SBTs while in suspension (simulating cells' capture from blood), then injected into the device for laser interrogation under flow. Each cell event is characterized by a composite Raman spectrum, deconvoluted into its single components to ultimately determine their relative contribution. We show that using SBTs ratiometrically can provide cell identification insensitive to normal causes of uncertainty in optical measurements such as variations in focal plane, cell concentration, autofluorescence, and turbidity.

Micro-scale extensional rheometry using hyperbolic converging/diverging channels and jet breakup

PubMed Central

Keshavarz, Bavand

2016-01-01

Understanding the elongational rheology of dilute polymer solutions plays an important role in many biological and industrial applications ranging from microfluidic lab-on-a-chip diagnostics to phenomena such as fuel atomization and combustion. Making quantitative measurements of the extensional viscosity for dilute viscoelastic fluids is a long-standing challenge and it motivates developments in microfluidic fabrication techniques and high speed/strobe imaging of millifluidic capillary phenomena in order to develop new classes of instruments. In this paper, we study the elongational rheology of a family of dilute polymeric solutions in two devices: first, steady pressure-driven flow through a hyperbolic microfluidic contraction/expansion and, second, the capillary driven breakup of a thin filament formed from a small diameter jet (Dj∼O(100 μm)). The small length scale of the device allows very large deformation rates to be achieved. Our results show that in certain limits of low viscosity and elasticity, jet breakup studies offer significant advantages over the hyperbolic channel measurements despite the more complex implementation. Using our results, together with scaling estimates of the competing viscous, elastic, inertial and capillary timescales that control the dynamics, we construct a dimensionless map or nomogram summarizing the operating space for each instrument. PMID:27375824

Benchtop fabrication of microfluidic systems based on curable polymers with improved solvent compatibility.

PubMed

Hashimoto, Michinao; Langer, Robert; Kohane, Daniel S

2013-01-21

This paper describes a general scheme to fabricate microchannels from curable polymers on a laboratory benchtop. Using the scheme described here, benchtop fabrication of SU-8 microfluidic systems was demonstrated for the first time, and their compatibility with organic solvents was demonstrated. The fabrication process has three major stages: 1) transferring patterns of microchannels to polymer films by molding, 2) releasing the patterned film and creating inlets and outlets for fluids, and 3) sealing two films together to create a closed channel system. Addition of a PDMS slab supporting the polymer film provided structural integrity during and after fabrication, allowing manipulation of the polymer films without fracturing or deformation. SU-8 channels fabricated according to this scheme exhibited solvent compatibility against continuous exposure to acetone and ethylacetate, which are incompatible with native PDMS. Using the SU-8 channels, continuous generation of droplets of ethylacetate, and templated synthesis of poly (lactic-co-glycolic acid) (PLGA) microparticles, both with stable size, were demonstrated continuously over 24 h, and at intervals over 75 days.

Characterization and optimization of low cost microfluidic thread based electroanalytical device for micro flow injection analysis.

PubMed

Agustini, Deonir; Bergamini, Márcio F; Marcolino-Junior, Luiz Humberto

2017-01-25

The micro flow injection analysis (μFIA) is a powerful technique that uses the principles of traditional flow analysis in a microfluidic device and brings a number of improvements related to the consumption of reagents and samples, speed of analysis and portability. However, the complexity and cost of manufacturing processes, difficulty in integrating micropumps and the limited performance of systems employing passive pumps are challenges that must be overcome. Here, we present the characterization and optimization of a low cost device based on cotton threads as microfluidic channel to perform μFIA based on passive pumps with good analytical performance in a simple, easy and inexpensive way. The transport of solutions is made through cotton threads by capillary force facilitated by gravity. After studying and optimizing several features related to the device, were obtained a flow rate of 2.2 ± 0.1 μL s -1 , an analytical frequency of 208 injections per hour, a sample injection volume of 2.0 μL and a waste volume of approximately 40 μL per analysis. For chronoamperometric determination of naproxen, a detection limit of 0.29 μmol L -1 was reached, with a relative standard deviation (RSD) of 1.69% between injections and a RSD of 3.79% with five different devices. Thus, based on the performance presented by proposed microfluidic device, it is possible to overcome some limitations of the μFIA systems based on passive pumps and allow expansion in the use of this technique. Copyright © 2016 Elsevier B.V. All rights reserved.

Rapid Real-time Electrical Detection of Proteins Using Single Conducting Polymer Nanowire-Based Microfluidic Aptasensor

PubMed Central

Huang, Jiyong; Luo, Xiliang; Lee, Innam; Hu, Yushi; Cui, Xinyan Tracy; Yun, Minhee

2011-01-01

Single polypyrrole (PPy) nanowire-based microfluidic aptasensors were fabricated using a one-step electrochemical deposition method. The successful incorporation of the aptamers into the PPy nanowire was confirmed by fluorescence microscopy image. The microfluidic aptasensor showed responses to IgE protein solutions in the range from 0.01 nM to 100 nM, and demonstrated excellent specificity and sensitivity with faster response and rapid stabilization times (~20 s). At the lowest examined IgE concentration of 0.01nM, the microfluidic aptasensor still exhibited ~0.32% change in the conductance. The functionality of this aptasensor was able to be regenerated using an acid treatment with no major change in sensitivity. In addition, the detection of cancer biomarker MUC1 was performed using another microfluidic aptasensor, which showed a very low detection limit of 2.66 nM MUC1 compared to commercially available MUC1 diagnosis assay (800 nM). PMID:21937215

Multiplexed electrokinetic sample fractionation, preconcentration and elution for proteomics.

PubMed

Hua, Yujuan; Jemere, Abebaw B; Dragoljic, Jelena; Harrison, D Jed

2013-07-07

Both 6 and 8-channel integrated microfluidic sample pretreatment devices capable of performing "in space" sample fractionation, collection, preconcentration and elution of captured analytes via sheath flow assisted electrokinetic pumping are described. Coatings and monolithic polymer beds were developed for the glass devices to provide cationic surface charge and anodal electroosmotic flow for delivery to an electrospray emitter tip. A mixed cationic ([2-(methacryloyloxy)ethyl] trimethylammonium chloride) (META) and hydrophobic butyl methacrylate-based monolithic porous polymer, photopolymerized in the 6- or 8-fractionation channels, was used to capture and preconcentrate samples. A 0.45 wt% META loaded bed generated comparable anodic electroosmotic flow to the cationic polymer PolyE-323 coated channel segments in the device. The balanced electroosmotic flow allowed stable electrokinetic sheath flow to prevent cross contamination of separated protein fractions, while reducing protein/peptide adsorption on the channel walls. Sequential elution of analytes trapped in the SPE beds revealed that the monolithic columns could be efficiently used to provide sheath flow during elution of analytes, as demonstrated for neutral carboxy SNARF (residual signal, 0.08% RSD, n = 40) and charged fluorescein (residual signal, 2.5% n = 40). Elution from monolithic columns showed reproducible performance with peak area reproducibility of ~8% (n = 6 columns) in a single sequential elution and the run-to-run reproducibility was 2.4-6.7% RSD (n = 4) for elution from the same bed. The demonstrated ability of this device design and operation to elute from multiple fractionation beds into a single exit channel for sample analysis by fluorescence or electrospray mass spectrometry is a crucial component of an integrated fractionation and assay system for proteomics.

Microfluidic Pneumatic Logic Circuits and Digital Pneumatic Microprocessors for Integrated Microfluidic Systems

PubMed Central

Rhee, Minsoung

2010-01-01

We have developed pneumatic logic circuits and microprocessors built with microfluidic channels and valves in polydimethylsiloxane (PDMS). The pneumatic logic circuits perform various combinational and sequential logic calculations with binary pneumatic signals (atmosphere and vacuum), producing cascadable outputs based on Boolean operations. A complex microprocessor is constructed from combinations of various logic circuits and receives pneumatically encoded serial commands at a single input line. The device then decodes the temporal command sequence by spatial parallelization, computes necessary logic calculations between parallelized command bits, stores command information for signal transportation and maintenance, and finally executes the command for the target devices. Thus, such pneumatic microprocessors will function as a universal on-chip control platform to perform complex parallel operations for large-scale integrated microfluidic devices. To demonstrate the working principles, we have built 2-bit, 3-bit, 4-bit, and 8-bit microprecessors to control various target devices for applications such as four color dye mixing, and multiplexed channel fluidic control. By significantly reducing the need for external controllers, the digital pneumatic microprocessor can be used as a universal on-chip platform to autonomously manipulate microfluids in a high throughput manner. PMID:19823730

Design and integration of a generic disposable array-compatible sensor housing into an integrated disposable indirect microfluidic flow injection analysis system.

PubMed

Rapp, Bastian E; Schickling, Benjamin; Prokop, Jürgen; Piotter, Volker; Rapp, Michael; Länge, Kerstin

2011-10-01

We describe an integration strategy for arbitrary sensors intended to be used as biosensors in biomedical or bioanalytical applications. For such devices ease of handling (by a potential end user) as well as strict disposable usage are of importance. Firstly we describe a generic array compatible polymer sensor housing with an effective sample volume of 1.55 μl. This housing leaves the sensitive surface of the sensor accessible for the application of biosensing layers even after the embedding. In a second step we show how this sensor housing can be used in combination with a passive disposable microfluidic chip to set up arbitrary 8-fold sensor arrays and how such a system can be complemented with an indirect microfluidic flow injection analysis (FIA) system. This system is designed in a way that it strictly separates between disposable and reusable components- by introducing tetradecane as an intermediate liquid. This results in a sensor system compatible with the demands of most biomedical applications. Comparative measurements between a classical macroscopic FIA system and this integrated indirect microfluidic system are presented. We use a surface acoustic wave (SAW) sensor as an exemplary detector in this work.

Electrowetting (EW)-based valve combined with hydrophilic teflon microfluidic guidance in controlling continuous fluid flow.

PubMed

Cheng, Ji-Yen; Hsiung, Lo-Chang

2004-12-01

Electrowetting (EW)-based techniques have been widely used in manipulating discrete liquid. However, few articles discussed the controlling of continuous fluid flow by using EW-based techniques. In this paper, an EW-based valve combined with plasma-modified Teflon surface, which serves as a microfluidic guidance, in controlling continuous fluid flow has been demonstrated. The plasma-modified Teflon surface is firstly demonstrated for confining continuous fluid flow. The EW-based microfluidic device possesses the functions of a valve and a microchannel without complex moving parts and grooved microchannels. The quantitative characteristics of the EW-based valve are also studied. Propylene carbonate (PC) is firstly demonstrated as the working liquid in the EW-based device because of its applications in parallel oligonucleotide synthesis. It is found that lower valve actuation voltage reduces the deterioration of the valve and improves the valve stability.

Simple and Versatile 3D Printed Microfluidics Using Fused Filament Fabrication.

PubMed

Morgan, Alex J L; Hidalgo San Jose, Lorena; Jamieson, William D; Wymant, Jennifer M; Song, Bing; Stephens, Phil; Barrow, David A; Castell, Oliver K

2016-01-01

The uptake of microfluidics by the wider scientific community has been limited by the fabrication barrier created by the skills and equipment required for the production of traditional microfluidic devices. Here we present simple 3D printed microfluidic devices using an inexpensive and readily accessible printer with commercially available printer materials. We demonstrate that previously reported limitations of transparency and fidelity have been overcome, whilst devices capable of operating at pressures in excess of 2000 kPa illustrate that leakage issues have also been resolved. The utility of the 3D printed microfluidic devices is illustrated by encapsulating dental pulp stem cells within alginate droplets; cell viability assays show the vast majority of cells remain live, and device transparency is sufficient for single cell imaging. The accessibility of these devices is further enhanced through fabrication of integrated ports and by the introduction of a Lego®-like modular system facilitating rapid prototyping whilst offering the potential for novices to build microfluidic systems from a database of microfluidic components.

Simple and Versatile 3D Printed Microfluidics Using Fused Filament Fabrication

PubMed Central

Morgan, Alex J. L.; Hidalgo San Jose, Lorena; Jamieson, William D.; Wymant, Jennifer M.; Song, Bing; Stephens, Phil

2016-01-01

The uptake of microfluidics by the wider scientific community has been limited by the fabrication barrier created by the skills and equipment required for the production of traditional microfluidic devices. Here we present simple 3D printed microfluidic devices using an inexpensive and readily accessible printer with commercially available printer materials. We demonstrate that previously reported limitations of transparency and fidelity have been overcome, whilst devices capable of operating at pressures in excess of 2000 kPa illustrate that leakage issues have also been resolved. The utility of the 3D printed microfluidic devices is illustrated by encapsulating dental pulp stem cells within alginate droplets; cell viability assays show the vast majority of cells remain live, and device transparency is sufficient for single cell imaging. The accessibility of these devices is further enhanced through fabrication of integrated ports and by the introduction of a Lego®-like modular system facilitating rapid prototyping whilst offering the potential for novices to build microfluidic systems from a database of microfluidic components. PMID:27050661

Microfluidic devices for modeling cell-cell and particle-cell interactions in the microvasculature

PubMed Central

Prabhakarpandian, Balabhaskar; Shen, Ming-Che; Pant, Kapil; Kiani, Mohammad F.

2011-01-01

Cell-fluid and cell-cell interactions are critical components of many physiological and pathological conditions in the microvasculature. Similarly, particle-cell interactions play an important role in targeted delivery of therapeutics to tissue. Development of in vitro fluidic devices to mimic these microcirculatory processes has been a critical step forward in our understanding of the inflammatory process, development of nano-particulate drug carriers, and developing realistic in vitro models of the microvasculature and its surrounding tissue. However, widely used parallel plate flow based devices and assays have a number of important limitations for studying the physiological conditions in vivo. In addition, these devices are resource hungry and time consuming for performing various assays. Recently developed, more realistic, microfluidic based devices have been able to overcome many of these limitations. In this review, an overview of the fluidic devices and their use in studying the effects of shear forces on cell-cell and cell-particle interactions is presented. In addition, use of mathematical models and Computational Fluid Dynamics (CFD) based models for interpreting the complex flow patterns in the microvasculature are highlighted. Finally, the potential of 3D microfluidic devices and imaging for better representing in vivo conditions under which cell-cell and cell-particle interactions take place are discussed. PMID:21763328

Predicting the behavior of microfluidic circuits made from discrete elements

PubMed Central

Bhargava, Krisna C.; Thompson, Bryant; Iqbal, Danish; Malmstadt, Noah

2015-01-01

Microfluidic devices can be used to execute a variety of continuous flow analytical and synthetic chemistry protocols with a great degree of precision. The growing availability of additive manufacturing has enabled the design of microfluidic devices with new functionality and complexity. However, these devices are prone to larger manufacturing variation than is typical of those made with micromachining or soft lithography. In this report, we demonstrate a design-for-manufacturing workflow that addresses performance variation at the microfluidic element and circuit level, in context of mass-manufacturing and additive manufacturing. Our approach relies on discrete microfluidic elements that are characterized by their terminal hydraulic resistance and associated tolerance. Network analysis is employed to construct simple analytical design rules for model microfluidic circuits. Monte Carlo analysis is employed at both the individual element and circuit level to establish expected performance metrics for several specific circuit configurations. A protocol based on osmometry is used to experimentally probe mixing behavior in circuits in order to validate these approaches. The overall workflow is applied to two application circuits with immediate use at on the bench-top: series and parallel mixing circuits that are modularly programmable, virtually predictable, highly precise, and operable by hand. PMID:26516059

A review of digital microfluidics as portable platforms for lab-on a-chip applications.

PubMed

Samiei, Ehsan; Tabrizian, Maryam; Hoorfar, Mina

2016-07-07

Following the development of microfluidic systems, there has been a high tendency towards developing lab-on-a-chip devices for biochemical applications. A great deal of effort has been devoted to improve and advance these devices with the goal of performing complete sets of biochemical assays on the device and possibly developing portable platforms for point of care applications. Among the different microfluidic systems used for such a purpose, digital microfluidics (DMF) shows high flexibility and capability of performing multiplex and parallel biochemical operations, and hence, has been considered as a suitable candidate for lab-on-a-chip applications. In this review, we discuss the most recent advances in the DMF platforms, and evaluate the feasibility of developing multifunctional packages for performing complete sets of processes of biochemical assays, particularly for point-of-care applications. The progress in the development of DMF systems is reviewed from eight different aspects, including device fabrication, basic fluidic operations, automation, manipulation of biological samples, advanced operations, detection, biological applications, and finally, packaging and portability of the DMF devices. Success in developing the lab-on-a-chip DMF devices will be concluded based on the advances achieved in each of these aspects.

Integrated microdroplet-based system for enzyme synthesis and sampling

NASA Astrophysics Data System (ADS)

Lapierre, Florian; Best, Michel; Stewart, Robert; Oakeshott, John; Peat, Thomas; Zhu, Yonggang

2013-12-01

Microdroplet-based microfluidic devices are emerging as powerful tools for a wide range of biochemical screenings and analyses. Monodispersed aqueous microdroplets from picoliters to nanoliters in volume are generated inside microfluidic channels within an immiscible oil phase. This results in the formation of emulsions which can contain various reagents for chemical reactions and can be considered as discrete bioreactors. In this paper an integrated microfluidic platform for the synthesis, screening and sorting of libraries of an organophosphate degrading enzyme is presented. The variants of the selected enzyme are synthesized from a DNA source using in-vitro transcription and translation method. The synthesis occurs inside water-in-oil emulsion droplets, acting as bioreactors. Through a fluorescence based detection system, only the most efficient enzymes are selected. All the necessary steps from the enzyme synthesis to selection of the best genes (producing the highest enzyme activity) are thus integrated inside a single and unique device. In the second part of the paper, an innovative design of the microfluidic platform is presented, integrating an electronic prototyping board for ensuring the communication between the various components of the platform (camera, syringe pumps and high voltage power supply), resulting in a future handheld, user-friendly, fully automated device for enzyme synthesis, screening and selection. An overview on the capabilities as well as future perspectives of this new microfluidic platform is provided.

A microsensor for the detection of a single pathogenic bacterium using magnetotactic bacteria-based bio-carriers: simulations and preliminary experiments.

PubMed

Denomme, Ryan C; Lu, Zhao; Martel, Sylvain

2007-01-01

The proposed Magnetotactic Bacteria (MTB) based bio-carrier has the potential to greatly improve pathogenic bacteria detection time, specificity, and sensitivity. Microbeads are attached to the MTB and are modified with a coating of an antibody or phage that is specific to the target pathogenic bacteria. Using magnetic fields, the modified MTB are swept through a solution and the target bacteria present become attached to the microbeads (due to the coating). Then, the MTB are brought to the detection region and the number of pathogenic bacteria is determined. The high swimming speed and controllability of the MTB make this method ideal for the fast detection of small concentrations of specific bacteria. This paper focuses on an impedimetric detection system that will be used to identify if a target bacterium is attached to the microbead. The proposed detection system measures changes in electrical impedance as objects (MTB, microbeads, and pathogenic bacteria) pass through a set of microelectrodes embedded in a microfluidic device. FEM simulation is used to acquire the optimized parameters for the design of such a system. Specifically, factors such as electrode/detection channel geometry, object size and position, which have direct effects on the detection sensitivity for a single bacterium or microparticle, are investigated. Polymer microbeads and the MTB system with an E. coli bacterium are considered to investigate their impedance variations. Furthermore, preliminary experimental data using a microfabricated microfluidic device connected to an impedance analyzer are presented.

Microfluidics-based, time-resolved mechanical phenotyping of cells using high-speed imaging

NASA Astrophysics Data System (ADS)

Belotti, Yuri; Conneely, Michael; Huang, Tianjun; McKenna, Stephen; Nabi, Ghulam; McGloin, David

2017-07-01

We demonstrate a single channel hydrodynamic stretching microfluidic device that relies on high-speed imaging to allow repeated dynamic cell deformation measurements. Experiments on prostate cancer cells suggest richer data than current approaches.

A Comprehensive Microfluidics Device Construction and Characterization Module for the Advanced Undergraduate Analytical Chemistry Laboratory

ERIC Educational Resources Information Center

Piunno, Paul A. E.; Zetina, Adrian; Chu, Norman; Tavares, Anthony J.; Noor, M. Omair; Petryayeva, Eleonora; Uddayasankar, Uvaraj; Veglio, Andrew

2014-01-01

An advanced analytical chemistry undergraduate laboratory module on microfluidics that spans 4 weeks (4 h per week) is presented. The laboratory module focuses on comprehensive experiential learning of microfluidic device fabrication and the core characteristics of microfluidic devices as they pertain to fluid flow and the manipulation of samples.…

Fabrication of raised and inverted SU8 polymer waveguides

NASA Astrophysics Data System (ADS)

Holland, Anthony S.; Mitchell, Arnan; Balkunje, Vishal S.; Austin, Mike W.; Raghunathan, Mukund K.

2005-01-01

Polymer films with high optical transmission have been investigated for making optical devices for several years. SU8 photoresist and optical adhesives have been investigated for use as thin films for optical devices, not what they were originally designed for. Optical adhesives are typically a one component thermoset polymer and are convenient to use for making thin film optical devices such as waveguides. They are prepared in minutes as thin films unlike SU8, which has to be carefully thermally cured over several hours for optimum results. However SU8 can be accurately patterned to form the geometry of structures required for single mode optical waveguides. SU8 in combination with the lower refractive index optical adhesive films such as UV15 from Master Bond are used to form single and multi mode waveguides. SU8 is photopatternable but we have also used dry etching of the SU8 layer or the other polymer layers e.g. UV15 to form the ribs, ridges or trenches required to guide single modes of light. Optical waveguides were also fabricated using only optical adhesives of different refractive indices. The resolution obtainable is poorer than with SU8 and hence multi mode waveguides are obtained. Loss measurements have been obtained for waveguides of different geometries and material combinations. The process for making polymer waveguides is demonstrated for making large multi mode waveguides and microfluidic channels by scaling the process up in size.

High-aspect ratio magnetic nanocomposite polymer cilium

NASA Astrophysics Data System (ADS)

Rahbar, M.; Tseng, H. Y.; Gray, B. L.

2014-03-01

This paper presents a new fabrication technique to achieve ultra high-aspect ratio artificial cilia micro-patterned from flexible highly magnetic rare earth nanoparticle-doped polymers. We have developed a simple, inexpensive and scalable fabrication method to create cilia structures that can be actuated by miniature electromagnets, that are suitable to be used for lab-on-a chip (LOC) and micro-total-analysis-system (μ-TAS) applications such as mixers and flow-control elements. The magnetic cilia are fabricated and magnetically polarized directly in microfluidic channels or reaction chambers, allowing for easy integration with complex microfluidic systems. These cilia structures can be combined on a single chip with other microfluidic components employing the same permanently magnetic nano-composite polymer (MNCP), such as valves or pumps. Rare earth permanent magnetic powder, (Nd0.7Ce0.3)10.5Fe83.9B5.6, is used to dope polydimethylsiloxane (PDMS), resulting in a highly flexible M-NCP of much higher magnetization and remanence [1] than ferromagnetic polymers typically employed in magnetic microfluidics. Sacrificial poly(ethylene-glycol) (PEG) is used to mold the highly magnetic polymer into ultra high-aspect ratio artificial cilia. Cilia structures with aspect ratio exceeding 8:0.13 can be easily fabricated using this technique and are actuated using miniature electromagnets to achieve a high range of motion/vibration.

Recent advancements in chemical luminescence-based lab-on-chip and microfluidic platforms for bioanalysis.

PubMed

Mirasoli, Mara; Guardigli, Massimo; Michelini, Elisa; Roda, Aldo

2014-01-01

Miniaturization of analytical procedures through microchips, lab-on-a-chip or micro total analysis systems is one of the most recent trends in chemical and biological analysis. These systems are designed to perform all the steps in an analytical procedure, with the advantages of low sample and reagent consumption, fast analysis, reduced costs, possibility of extra-laboratory application. A range of detection technologies have been employed in miniaturized analytical systems, but most applications relied on fluorescence and electrochemical detection. Chemical luminescence (which includes chemiluminescence, bioluminescence, and electrogenerated chemiluminescence) represents an alternative detection principle that offered comparable (or better) analytical performance and easier implementation in miniaturized analytical devices. Nevertheless, chemical luminescence-based ones represents only a small fraction of the microfluidic devices reported in the literature, and until now no review has been focused on these devices. Here we review the most relevant applications (since 2009) of miniaturized analytical devices based on chemical luminescence detection. After a brief overview of the main chemical luminescence systems and of the recent technological advancements regarding their implementation in miniaturized analytical devices, analytical applications are reviewed according to the nature of the device (microfluidic chips, microchip electrophoresis, lateral flow- and paper-based devices) and the type of application (micro-flow injection assays, enzyme assays, immunoassays, gene probe hybridization assays, cell assays, whole-cell biosensors). Copyright © 2013 Elsevier B.V. All rights reserved.

Introducing biomimetic shear and ion gradients to microfluidic spinning improves silk fiber strength.

PubMed

Li, David; Jacobsen, Matthew M; Gyune Rim, Nae; Backman, Daniel; Kaplan, David L; Wong, Joyce Y

2017-05-31

Silkworm silk is an attractive biopolymer for biomedical applications due to its high mechanical strength and biocompatibility; as a result, there is increasing interest in scalable devices to spin silk and recombinant silk so as to improve and customize their properties for diverse biomedical purposes (Vepari and Kaplan 2007 Prog. Polym. Sci. 32 ). While artificial spinning of regenerated silk fibroins adds tunability to properties such as degradation rate and surface functionalization, the resulting fibers do not yet approach the mechanical strength of native silkworm silk. These drawbacks reduce the applicability and attractiveness of artificial silk (Kinahan et al 2011 Biomacromolecules 12 ). Here, we used computational fluid dynamic simulations to incorporate shear in tandem with biomimetic ion gradients by coupling a modular novel glass microfluidic device to our previous co-axial flow device. Fibers spun with this combined apparatus demonstrated a significant increase in mechanical strength compared to fibers spun with the basic apparatus alone, with a three-fold increase in Young's modulus and extensibility and a twelve-fold increase in toughness. These results thus demonstrate the critical importance of ionic milieu and shear stress in spinning strong fibers from solubilized silk fibroin.

Product qualification: a barrier to point-of-care microfluidic-based diagnostics?

PubMed

Tantra, Ratna; van Heeren, Henne

2013-06-21

One of the most exciting applications of microfluidics-based diagnostics is its potential use in next generation point-of-care (POC) devices. Many prototypes are already in existence, but, as of yet, few have achieved commercialisation. In this article, we consider the issue surrounding product qualification as a potential barrier to market success. The study discusses, in the context of POC microfluidics-based diagnostics, what the generic issues are and potential solutions. Our findings underline the need for a community-based effort that is necessary to speed up the product qualification process.

Automated electrotransformation of Escherichia coli on a digital microfluidic platform using bioactivated magnetic beads.

PubMed

Moore, J A; Nemat-Gorgani, M; Madison, A C; Sandahl, M A; Punnamaraju, S; Eckhardt, A E; Pollack, M G; Vigneault, F; Church, G M; Fair, R B; Horowitz, M A; Griffin, P B

2017-01-01

This paper reports on the use of a digital microfluidic platform to perform multiplex automated genetic engineering (MAGE) cycles on droplets containing Escherichia coli cells. Bioactivated magnetic beads were employed for cell binding, washing, and media exchange in the preparation of electrocompetent cells in the electrowetting-on-dieletric (EWoD) platform. On-cartridge electroporation was used to deliver oligonucleotides into the cells. In addition to the optimization of a magnetic bead-based benchtop protocol for generating and transforming electrocompetent E. coli cells, we report on the implementation of this protocol in a fully automated digital microfluidic platform. Bead-based media exchange and electroporation pulse conditions were optimized on benchtop for transformation frequency to provide initial parameters for microfluidic device trials. Benchtop experiments comparing electrotransformation of free and bead-bound cells are presented. Our results suggest that dielectric shielding intrinsic to bead-bound cells significantly reduces electroporation field exposure efficiency. However, high transformation frequency can be maintained in the presence of magnetic beads through the application of more intense electroporation pulses. As a proof of concept, MAGE cycles were successfully performed on a commercial EWoD cartridge using variations of the optimal magnetic bead-based preparation procedure and pulse conditions determined by the benchtop results. Transformation frequencies up to 22% were achieved on benchtop; this frequency was matched within 1% (21%) by MAGE cycles on the microfluidic device. However, typical frequencies on the device remain lower, averaging 9% with a standard deviation of 9%. The presented results demonstrate the potential of digital microfluidics to perform complex and automated genetic engineering protocols.

Automated electrotransformation of Escherichia coli on a digital microfluidic platform using bioactivated magnetic beads

PubMed Central

Moore, J. A.; Nemat-Gorgani, M.; Madison, A. C.; Punnamaraju, S.; Eckhardt, A. E.; Pollack, M. G.; Church, G. M.; Fair, R. B.; Horowitz, M. A.; Griffin, P. B.

2017-01-01

This paper reports on the use of a digital microfluidic platform to perform multiplex automated genetic engineering (MAGE) cycles on droplets containing Escherichia coli cells. Bioactivated magnetic beads were employed for cell binding, washing, and media exchange in the preparation of electrocompetent cells in the electrowetting-on-dieletric (EWoD) platform. On-cartridge electroporation was used to deliver oligonucleotides into the cells. In addition to the optimization of a magnetic bead-based benchtop protocol for generating and transforming electrocompetent E. coli cells, we report on the implementation of this protocol in a fully automated digital microfluidic platform. Bead-based media exchange and electroporation pulse conditions were optimized on benchtop for transformation frequency to provide initial parameters for microfluidic device trials. Benchtop experiments comparing electrotransformation of free and bead-bound cells are presented. Our results suggest that dielectric shielding intrinsic to bead-bound cells significantly reduces electroporation field exposure efficiency. However, high transformation frequency can be maintained in the presence of magnetic beads through the application of more intense electroporation pulses. As a proof of concept, MAGE cycles were successfully performed on a commercial EWoD cartridge using variations of the optimal magnetic bead-based preparation procedure and pulse conditions determined by the benchtop results. Transformation frequencies up to 22% were achieved on benchtop; this frequency was matched within 1% (21%) by MAGE cycles on the microfluidic device. However, typical frequencies on the device remain lower, averaging 9% with a standard deviation of 9%. The presented results demonstrate the potential of digital microfluidics to perform complex and automated genetic engineering protocols. PMID:28191268

Micro-fluidic interconnect

DOEpatents

Okandan, Murat [Albuquerque, NM; Galambos, Paul C [Albuquerque, NM; Benavides, Gilbert L [Los Ranchos, NM; Hetherington, Dale L [Albuquerque, NM

2006-02-28

An apparatus for simultaneously aligning and interconnecting microfluidic ports is presented. Such interconnections are required to utilize microfluidic devices fabricated in Micro-Electromechanical-Systems (MEMS) technologies, that have multiple fluidic access ports (e.g. 100 micron diameter) within a small footprint, (e.g. 3 mm.times.6 mm). Fanout of the small ports of a microfluidic device to a larger diameter (e.g. 500 microns) facilitates packaging and interconnection of the microfluidic device to printed wiring boards, electronics packages, fluidic manifolds etc.

Optofluidic encapsulation and manipulation of silicon microchips using image processing based optofluidic maskless lithography and railed microfluidics.

PubMed

Chung, Su Eun; Lee, Seung Ah; Kim, Jiyun; Kwon, Sunghoon

2009-10-07

We demonstrate optofluidic encapsulation of silicon microchips using image processing based optofluidic maskless lithography and manipulation using railed microfluidics. Optofluidic maskless lithography is a dynamic photopolymerization technique of free-floating microstructures within a fluidic channel using spatial light modulator. Using optofluidic maskless lithography via computer-vision aided image processing, polymer encapsulants are fabricated for chip protection and guiding-fins for efficient chip conveying within a fluidic channel. Encapsulated silicon chips with guiding-fins are assembled using railed microfluidics, which is an efficient guiding and heterogeneous self-assembly system of microcomponents. With our technology, externally fabricated silicon microchips are encapsulated, fluidically guided and self-assembled potentially enabling low cost fluidic manipulation and assembly of integrated circuits.

Integrated Microfluidic Variable Optical Attenuator

DTIC Science & Technology

2005-11-28

Quantum Electron. 5, pp. 1289–1297 (1999). 5. G. Z. Xiao, Z. Zhang, and C. P. Grover, “A variable optical attenuator based on a straight polymer –silica...1998). 18. Y. Huang, G.T. Paloczi, J. K. S. Poon, and A. Yariv, “Bottom-up soft-lithographic fabrication of three- dimensional multilayer polymer ...quality without damaging polymer materials under high temperatures, resulting in a core index of 1.561 and cladding index of 1.546. The refractive

Fabrication of a microfluidic device for the compartmentalization of neuron soma and axons.

PubMed

Harris, Joseph; Lee, Hyuna; Vahidi, Behrad; Tu, Christina; Cribbs, David; Jeon, Noo Li; Cotman, Carl

2007-01-01

In this video, we demonstrate the technique of soft lithography with polydimethyl siloxane (PDMS) which we use to fabricate a microfluidic device for culturing neurons. Previously, a silicon wafer was patterned with the design for the neuron microfluidic device using SU-8 and photolithography to create a master mold, or what we simply refer to as a "master". Next, we pour the silicon polymer PDMS on top of the master which is then cured by heating the PDMS to 80 degrees C for 1 hour. The PDMS forms a negative mold of the device. The PDMS is then carefully cut and lifted away from the master. Holes are punched where the reservoirs will be and the excess PDMS trimmed away from the device. Nitrogen is used to blow away any excess debris from the device. At this point the devices are now ready for use and can either bonded to corning No. 1 cover glass with a plasma sterilizer/cleaner or can be reversibly bound to the cover glass by simply placing the device on top of the cover glass. The reversible bonding of the device to glass is covered in a separate video and requires first that the device be sterilized either with 70% ethanol or by autoclaving. Plasma treating sterilizes the devices so no further treatment is necessary. It is, however, important, when plasma-treating the devices, to add liquid to the devices within 10 minutes of the plasma treatment while the surfaces are still hydrophilic. Waiting longer than 10 minutes to add liquid to the device makes it difficult for the liquid to enter the device. The neuron devices are typically plasma-bound to cover glass and 0.5 mg/ml poly-L-lysine (PLL) in pH 8.5 borate buffer is immediately added to the device. After a minimum of 3 hours incubating with PLL, the devices are washed with dH2O water a minimum of 3 times with at least 15 minutes between each wash. Next, the water is removed and fresh media is added to the device. At this point the device is ready for use. It is important to remember at this point to never remove all the media from the device. Always leave media in the main channel.

Volumetric measurement of human red blood cells by MOSFET-based microfluidic gate.

PubMed

Guo, Jinhong; Ai, Ye; Cheng, Yuanbing; Li, Chang Ming; Kang, Yuejun; Wang, Zhiming

2015-08-01

In this paper, we present a MOSFET-based (metal oxide semiconductor field-effect transistor) microfluidic gate to characterize the translocation of red blood cells (RBCs) through a gate. In the microfluidic system, the bias voltage modulated by the particles or biological cells is connected to the gate of MOSFET. The particles or cells can be detected by monitoring the MOSFET drain current instead of DC/AC-gating method across the electronic gate. Polystyrene particles with various standard sizes are utilized to calibrate the proposed device. Furthermore, RBCs from both adults and newborn blood sample are used to characterize the performance of the device in distinguishing the two types of RBCs. As compared to conventional DC/AC current modulation method, the proposed device demonstrates a higher sensitivity and is capable of being a promising platform for bioassay analysis. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Continuous separation of multiple size microparticles using alternating current dielectrophoresis in microfluidic device with acupuncture needle electrodes

NASA Astrophysics Data System (ADS)

Tao, Ye; Ren, Yukun; Yan, Hui; Jiang, Hongyuan

2016-03-01

The need to continuously separate multiple microparticles is required for the recent development of lab-on-chip technology. Dielectrophoresis(DEP)-based separation device is extensively used in kinds of microfluidic applications. However, such conventional DEP-based device is relatively complicated and difficult for fabrication. A concise microfluidic device is presented for effective continuous separation of multiple size particle mixtures. A pair of acupuncture needle electrodes are creatively employed and embedded in a PDMS(poly-dimethylsiloxane) hurdle for generating non-uniform electric field thereby achieving a continuous DEP separation. The separation mechanism is that the incoming particle samples with different sizes experience different negative DEP(nDEP) forces and then they can be transported into different downstream outlets. The DEP characterizations of particles are calculated, and their trajectories are numerically predicted by considering the combined action of the incoming laminar flow and the nDEP force field for guiding the separation experiments. The device performance is verified by successfully separating a three-sized particle mixture, including polystyrene microspheres with diameters of 3 μm, 10 μm and 25 μm. The separation purity is below 70% when the flow rate ratio is less than 3.5 or more than 5.1, while the separation purity can be up to more than 90% when the flow rate ratio is between 3.5 and 5.1 and meanwhile ensure the voltage output falls in between 120 V and 150 V. Such simple DEP-based separation device has extensive applications in future microfluidic systems.

Material- and feature-dependent effects on cell adhesion to micro injection moulded medical polymers.

PubMed

Choi, Seong Ying; Habimana, Olivier; Flood, Peter; Reynaud, Emmanuel G; Rodriguez, Brian J; Zhang, Nan; Casey, Eoin; Gilchrist, Michael D

2016-09-01

Two polymers, polymethylmethacrylate (PMMA) and cyclic olefin copolymer (COC), containing a range of nano- to micron- roughness surfaces (Ra 0.01, 0.1, 0.4, 1.0, 2.0, 3.2 and 5.0μm) were fabricated using electrical discharge machining (EDM) and replicated using micro injection moulding (μIM). Polymer samples were characterized using optical profilometry, atomic force microscopy (AFM) and water surface contact angle. Cell adhesion tests were carried out using bacterial Pseudomonas fluorescens and mammalian Madin-Darby Canine Kidney (MDCK) cells to determine the effect of surface hydrophobicity, surface roughness and stiffness. It is found that there are features which gave insignificant differences (feature-dependent effect) in cell adhesion, albeit a significant difference in the physicochemical properties (material-dependent effect) of substrata. In bacterial cell adhesion, the strongest feature-dependence is found at Ra 0.4μm surfaces, with material-dependent effects strongest at Ra 0.01μm. Ra 0.1μm surfaces exhibited strongest feature-dependent effects and Ra 5.0μm has strongest material-dependent effects on mammalian cell adhesion. Bacterial cell adhesion is found to be favourable to hydrophobic surfaces (COC), with the lowest adhesion at Ra 0.4μm for both materials. Mammalian cell adhesion is lowest in Ra 0.1μm and highest in Ra 1.0μm, and generally favours hydrophilic surfaces (PMMA). These findings can be used as a basis for developing medical implants or microfluidic devices using micro injection moulding for diagnostic purposes, by tuning the cell adhesion on different areas containing different surface roughnesses on the diagnostic microfluidic devices or medical implants. Copyright © 2016 Elsevier B.V. All rights reserved.

Label-free in-flow detection of single DNA molecules using glass nanopipettes.

PubMed

Gong, Xiuqing; Patil, Amol V; Ivanov, Aleksandar P; Kong, Qingyuan; Gibb, Thomas; Dogan, Fatma; deMello, Andrew J; Edel, Joshua B

2014-01-07

With the view of enhancing the functionality of label-free single molecule nanopore-based detection, we have designed and developed a highly robust, mechanically stable, integrated nanopipette-microfluidic device which combines the recognized advantages of microfluidic systems and the unique properties/advantages of nanopipettes. Unlike more typical planar solid-state nanopores, which have inherent geometrical constraints, nanopipettes can be easily positioned at any point within a microfluidic channel. This is highly advantageous, especially when taking into account fluid flow properties. We show that we are able to detect and discriminate between DNA molecules of varying lengths when motivated through a microfluidic channel, upon the application of appropriate voltage bias across the nanopipette. The effects of applied voltage and volumetric flow rates have been studied to ascertain translocation event frequency and capture rate. Additionally, by exploiting the advantages associated with microfluidic systems (such as flow control and concomitant control over analyte concentration/presence), we show that the technology offers a new opportunity for single molecule detection and recognition in microfluidic devices.

Accurately tracking single-cell movement trajectories in microfluidic cell sorting devices.

PubMed

Jeong, Jenny; Frohberg, Nicholas J; Zhou, Enlu; Sulchek, Todd; Qiu, Peng

2018-01-01

Microfluidics are routinely used to study cellular properties, including the efficient quantification of single-cell biomechanics and label-free cell sorting based on the biomechanical properties, such as elasticity, viscosity, stiffness, and adhesion. Both quantification and sorting applications require optimal design of the microfluidic devices and mathematical modeling of the interactions between cells, fluid, and the channel of the device. As a first step toward building such a mathematical model, we collected video recordings of cells moving through a ridged microfluidic channel designed to compress and redirect cells according to cell biomechanics. We developed an efficient algorithm that automatically and accurately tracked the cell trajectories in the recordings. We tested the algorithm on recordings of cells with different stiffness, and showed the correlation between cell stiffness and the tracked trajectories. Moreover, the tracking algorithm successfully picked up subtle differences of cell motion when passing through consecutive ridges. The algorithm for accurately tracking cell trajectories paves the way for future efforts of modeling the flow, forces, and dynamics of cell properties in microfluidics applications.

Development and Applications of Portable Biosensors.

PubMed

Srinivasan, Balaji; Tung, Steve

2015-08-01

The significance of microfluidics-based and microelectromechanical systems-based biosensors has been widely acknowledged, and many reviews have explored their potential applications in clinical diagnostics, personalized medicine, global health, drug discovery, food safety, and forensics. Because health care costs are increasing, there is an increasing need to remotely monitor the health condition of patients by point-of-care-testing. The demand for biosensors for detection of biological warfare agents has increased, and research is focused on ways of producing small portable devices that would allow fast, accurate, and on-site detection. In the past decade, the demand for rapid and accurate on-site detection of plant disease diagnosis has increased due to emerging pathogens with resistance to pesticides, increased human mobility, and regulations limiting the application of toxic chemicals to prevent spread of diseases. The portability of biosensors for on-site diagnosis is limited due to various issues, including sample preparation techniques, fluid-handling techniques, the limited lifetime of biological reagents, device packaging, integrating electronics for data collection/analysis, and the requirement of external accessories and power. Many microfluidic, electronic, and biological design strategies, such as handling liquids in biosensors without pumps/valves, the application of droplet-based microfluidics, paper-based microfluidic devices, and wireless networking capabilities for data transmission, are being explored. © 2015 Society for Laboratory Automation and Screening.

Flow control for a paper-based microfluidic device by adjusting permeability of paper

NASA Astrophysics Data System (ADS)

Jang, Ilhoon; Kim, Gangjune; Song, Simon

2014-11-01

The paper-based microfluidics has attracted intensive attention as a prospective substitute for conventional microfluidic substrates used for a point-of-care diagnostics due to its superior advantages such as the cost effectiveness and production simplicity. Generally, a paper-based microfluidic device utilizes capillary force to drive a flow. Recent studies on flow control in such a device aimed at obtaining accurate and quantitative results by varying a channel geometry like width and length. According to the Darcy's law describing a flow in a porous media like paper, a flow rate can be adjusted the permeability of paper. In this study, we investigate a flow control method by adjusting the permeability of paper. We utilize the wax printing for the adjustment and the fabrication of paper channels. A rectangular wax pattern was printed on one inlet channel of a Y-channel geometry. By varying the brightness of the wax pattern, a relationship between the flow rate and permeability changes due to the wax was investigated. As a result, we obtained an effective permeability contour with respect to the wax pattern length and brightness. In addition, we developed a paper-based micromixer of which the mixing ratio was controlled precisely by adjusting the permeability.

Plasma treatments of wool fiber surface for microfluidic applications

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jeon, So-Hyoun; Hwang, Ki-Hwan; Lee, Jin Su

Highlights: • We used atmospheric plasma for tuning the wettability of wool fibers. • The wicking rates of the wool fibers increased with increasing treatment time. • The increasing of wettability results in removement of fatty acid on the wool surface. - Abstract: Recent progress in health diagnostics has led to the development of simple and inexpensive systems. Thread-based microfluidic devices allow for portable and inexpensive field-based technologies enabling medical diagnostics, environmental monitoring, and food safety analysis. However, controlling the flow rate of wool thread, which is a very important part of thread-based microfluidic devices, is quite difficult. For thismore » reason, we focused on thread-based microfluidics in the study. We developed a method of changing the wettability of hydrophobic thread, including wool thread. Thus, using natural wool thread as a channel, we demonstrate herein that the manipulation of the liquid flow, such as micro selecting and micro mixing, can be achieved by applying plasma treatment to wool thread. In addition to enabling the flow control of the treated wool channels consisting of all natural substances, this procedure will also be beneficial for biological sensing devices. We found that wools treated with various gases have different flow rates. We used an atmospheric plasma with O{sub 2}, N{sub 2} and Ar gases.« less

A versatile valving toolkit for automating fluidic operations in paper microfluidic devices.

PubMed

Toley, Bhushan J; Wang, Jessica A; Gupta, Mayuri; Buser, Joshua R; Lafleur, Lisa K; Lutz, Barry R; Fu, Elain; Yager, Paul

2015-03-21

Failure to utilize valving and automation techniques has restricted the complexity of fluidic operations that can be performed in paper microfluidic devices. We developed a toolkit of paper microfluidic valves and methods for automatic valve actuation using movable paper strips and fluid-triggered expanding elements. To the best of our knowledge, this is the first functional demonstration of this valving strategy in paper microfluidics. After introduction of fluids on devices, valves can actuate automatically after a) a certain period of time, or b) the passage of a certain volume of fluid. Timing of valve actuation can be tuned with greater than 8.5% accuracy by changing lengths of timing wicks, and we present timed on-valves, off-valves, and diversion (channel-switching) valves. The actuators require ~30 μl fluid to actuate and the time required to switch from one state to another ranges from ~5 s for short to ~50 s for longer wicks. For volume-metered actuation, the size of a metering pad can be adjusted to tune actuation volume, and we present two methods - both methods can achieve greater than 9% accuracy. Finally, we demonstrate the use of these valves in a device that conducts a multi-step assay for the detection of the malaria protein PfHRP2. Although slightly more complex than devices that do not have moving parts, this valving and automation toolkit considerably expands the capabilities of paper microfluidic devices. Components of this toolkit can be used to conduct arbitrarily complex, multi-step fluidic operations on paper-based devices, as demonstrated in the malaria assay device.

A versatile valving toolkit for automating fluidic operations in paper microfluidic devices

PubMed Central

Toley, Bhushan J.; Wang, Jessica A.; Gupta, Mayuri; Buser, Joshua R.; Lafleur, Lisa K.; Lutz, Barry R.; Fu, Elain; Yager, Paul

2015-01-01

Failure to utilize valving and automation techniques has restricted the complexity of fluidic operations that can be performed in paper microfluidic devices. We developed a toolkit of paper microfluidic valves and methods for automatic valve actuation using movable paper strips and fluid-triggered expanding elements. To the best of our knowledge, this is the first functional demonstration of this valving strategy in paper microfluidics. After introduction of fluids on devices, valves can actuate automatically a) after a certain period of time, or b) after the passage of a certain volume of fluid. Timing of valve actuation can be tuned with greater than 8.5% accuracy by changing lengths of timing wicks, and we present timed on-valves, off-valves, and diversion (channel-switching) valves. The actuators require ~30 μl fluid to actuate and the time required to switch from one state to another ranges from ~5 s for short to ~50s for longer wicks. For volume-metered actuation, the size of a metering pad can be adjusted to tune actuation volume, and we present two methods – both methods can achieve greater than 9% accuracy. Finally, we demonstrate the use of these valves in a device that conducts a multi-step assay for the detection of the malaria protein PfHRP2. Although slightly more complex than devices that do not have moving parts, this valving and automation toolkit considerably expands the capabilities of paper microfluidic devices. Components of this toolkit can be used to conduct arbitrarily complex, multi-step fluidic operations on paper-based devices, as demonstrated in the malaria assay device. PMID:25606810

Mass and Momentum Transport in Microcavities for Diffusion-Dominant Cell Culture Applications

NASA Technical Reports Server (NTRS)

Yew, Alvin G.; Pinero, Daniel; Hsieh, Adam H.; Atencia, Javier

2012-01-01

For the informed design of microfluidic devices, it is important to understand transport phenomena at the microscale. This letter outlines an analytically-driven approach to the design of rectangular microcavities extending perpendicular to a perfusion microchannel for microfluidic cell culture devices. We present equations to estimate the spatial transition from advection- to diffusion-dominant transport inside cavities as a function of the geometry and flow conditions. We also estimate the time required for molecules, such as nutrients or drugs to travel from the microchannel to a given depth into the cavity. These analytical predictions can facilitate the rational design of microfluidic devices to optimize and maintain long-term, physiologically-based culture conditions with low fluid shear stress.

Fabrication of a multifunctional nano-in-micro drug delivery platform by microfluidic templated encapsulation of porous silicon in polymer matrix.

PubMed

Zhang, Hongbo; Liu, Dongfei; Shahbazi, Mohammad-Ali; Mäkilä, Ermei; Herranz-Blanco, Bárbara; Salonen, Jarno; Hirvonen, Jouni; Santos, Hélder A

2014-07-09

A multifunctional nano-in-micro drug delivery platform is developed by conjugating the porous silicon nanoparticles with mucoadhesive polymers and subsequent encapsulation into a pH-responsive polymer using microfluidics. The multistage platform shows monodisperse size distribution and pH-responsive payload release, and the released nanoparticles are mucoadhesive. Moreover, this platform is capable of simultaneously loading and releasing multidrugs with distinct properties. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

3D-PRINTING OF TRANSPARENT BIO-MICROFLUIDIC DEVICES IN PEG-DA

PubMed Central

Urrios, Arturo; Parra-Cabrera, Cesar; Bhattacharjee, Nirveek; Gonzalez-Suarez, Alan M.; Rigat-Brugarolas, Luis G.; Nallapatti, Umashree; Samitier, Josep; DeForest, Cole A.; Posas, Francesc; Garcia-Cordero, José L.; Folch, Albert

2016-01-01

The vast majority of microfluidic systems are molded in poly(dimethylsiloxane) (PDMS) by soft lithography due to the favorable properties of PDMS: biocompatible, elastomeric, transparent, gas-permeable, inexpensive, and copyright-free. However, PDMS molding involves tedious manual labor, which makes PDMS devices prone to assembly failures and difficult to disseminate to research and clinical settings. Furthermore, the fabrication procedures limit the 3D complexity of the devices to layered designs. Stereolithography (SL), a form of 3D-printing, has recently attracted attention as a way to customize the fabrication of biomedical devices due to its automated, assembly-free 3D fabrication, rapidly decreasing costs, and fast-improving resolution and throughput. However, existing SL resins are not biocompatible and patterning transparent resins at high resolution remains difficult. Here we report procedures for the preparation and patterning of a transparent resin based on low-MW poly(ethylene glycol) diacrylate (MW 250) (PEG-DA-250). The 3D-printed devices are highly transparent and cells can be cultured on PEG-DA-250 prints for several days. This biocompatible SL resin and printing process solves some of the main drawbacks of 3D-printed microfluidic devices: biocompatibility and transparency. In addition, it should also enable the production of non-microfluidic biomedical devices. PMID:27217203

Benzocyclobutene-based electric micromachines supported on microball bearings: Design, fabrication, and characterization

NASA Astrophysics Data System (ADS)

Modafe, Alireza

This dissertation summarizes the research activities that led to the development of the first microball-bearing-supported linear electrostatic micromotor with benzocyclobutene (BCB) low-k polymer insulating layers. The primary application of this device is long-range, high-speed linear micropositioning. The future generations of this device include rotary electrostatic micromotors and microgenerators. The development of the first generation of microball-bearing-supported micromachines, including device theory, design, and modeling, material characterization, process development, device fabrication, and device test and characterization is presented. The first generation of these devices is based on a 6-phase, bottom-drive, linear, variable-capacitance micromotor (B-LVCM). The design of the electrical and mechanical components of the micromotor, lumped-circuit modeling of the device and electromechanical characteristics, including variable capacitance, force, power, and speed are presented. Electrical characterization of BCB polymers, characterization of BCB chemical mechanical planarization (CMP), development of embedded BCB in silicon (EBiS) process, and integration of device components using microfabrication techniques are also presented. The micromotor consists of a silicon stator, a silicon slider, and four stainless-steel microballs. The aligning force profile of the micromotor was extracted from simulated and measured capacitances of all phases. An average total aligning force of 0.27 mN with a maximum of 0.41 mN, assuming a 100 V peak-to-peak square-wave voltage, was measured. The operation of the micromotor was verified by applying square-wave voltages and characterizing the slider motion. An average slider speed of 7.32 mm/s when excited by a 40 Hz, 120 V square-wave voltage was reached without losing the synchronization. This research has a pivotal impact in the field of power microelectromechanical systems (MEMS). It establishes the foundation for the development of more reliable, efficient electrostatic micromachines with variety of applications such as micropropulsion, high-speed micropumping, microfluid delivery, and microsystem power generation.

Multimodal Microchannel and Nanowell-Based Microfluidic Platforms for Bioimaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Geng, Tao; Smallwood, Chuck R.; Zhu, Ying

2017-03-30

Modern live-cell imaging approaches permit real-time visualization of biological processes. However, limitations for unicellular organism trapping, culturing and long-term imaging can preclude complete understanding of how such microorganisms respond to perturbations in their local environment or linking single-cell variability to whole population dynamics. We have developed microfluidic platforms to overcome prior technical bottlenecks to allow both chemostat and compartmentalized cellular growth conditions using the same device. Additionally, a nanowell-based platform enables a high throughput approach to scale up compartmentalized imaging optimized within the microfluidic device. These channel and nanowell platforms are complementary, and both provide fine control over the localmore » environment as well as the ability to add/replace media components at any experimental time point.« less

Prediction and validation of concentration gradient generation in a paper-based microfluidic channel

NASA Astrophysics Data System (ADS)

Jang, Ilhoon; Kim, Gang-June; Song, Simon

2016-11-01

A paper-based microfluidic channel has obtained attention as a diagnosis device that can implement various chemical or biological reactions. With benefits of thin, flexible, and strong features of paper devices, for example, it is often utilized for cell culture where controlling oxygen, nutrients, metabolism, and signaling molecules gradient affects the growth and movement of the cells. Among various features of paper-based microfluidic devices, we focus on establishment of concentration gradient in a paper channel. The flow is subject to dispersion and capillary effects because a paper is a porous media. In this presentation, we describe facile, fast and accurate method of generating a concentration gradient by using flow mixing of different concentrations. Both theoretical prediction and experimental validation are discussed along with inter-diffusion characteristics of porous flows. This work was supported by the National Research Foundation of Korea(NRF) Grant funded by the Korea government(MSIP) (No. 2016R1A2B3009541).

Development of paper-based microfluidic analytical device for iron assay using photomask printed with 3D printer for fabrication of hydrophilic and hydrophobic zones on paper by photolithography.

PubMed

Asano, Hitoshi; Shiraishi, Yukihide

2015-07-09

This paper describes a paper-based microfluidic analytical device for iron assay using a photomask printed with a 3D printer for fabrication of hydrophilic and hydrophobic zones on the paper by photolithography. Several designed photomasks for patterning paper-based microfluidic analytical devices can be printed with a 3D printer easily, rapidly and inexpensively. A chromatography paper was impregnated with the octadecyltrichlorosilane n-hexane solution and hydrophobized. After the hydrophobic zone of the paper was exposed to the UV light through the photomask, the hydrophilic zone was generated. The smallest functional hydrophilic channel and hydrophobic barrier were ca. 500 μm and ca. 100 μm in width, respectively. The fabrication method has high stability, resolution and precision for hydrophilic channel and hydrophobic barrier. This test paper was applied to the analysis of iron in water samples using a colorimetry with phenanthroline. Copyright © 2015 Elsevier B.V. All rights reserved.

A research factory for polymer microdevices: muFac

NASA Astrophysics Data System (ADS)

Anthony, Brian W.; Hardt, David E.; Hale, Melinda; Zarrouati, Nadege

2010-02-01

As part of our research on the manufacturing science of micron scale polymer-based devices, an automated production cell has been developed to explore its use in a volume manufacturing environment. This "micro-factory" allows the testing of models and hardware that have resulted from research on material characterization and simulation, tooling and equipment design and control, and process control and metrology. More importantly it has allowed us to identify the problems that exist between and within unit-processes. This paper details our efforts to produce basic micro-fluidic products in high volume at acceptable production rates and quality levels. The device chosen for our first product is a simple binary micromixer with 40×50 micron channel cross section manufactured by embossing of PMMA. The processes in the cell include laser cutting and drilling, hot embossing, thermal bonding and high-speed inspection of the components. Our goal is to create a "lights-out" factory that can make long production runs (e.g. an 8 hour shift) at high rates (Takt time of less than 3 minutes) with consistent quality. This contrasts with device foundries where prototypes in limited quantities but with high variety are the goal. Accordingly, rate and yield are dominant factors in this work, along with the need for precise material handling strategies. Production data will be presented to include process run charts, sampled functional testing of the products and measures of the overall system throughput.

Multiwell capillarity-based microfluidic device for the study of 3D tumour tissue-2D endothelium interactions and drug screening in co-culture models.

PubMed

Virumbrales-Muñoz, María; Ayuso, José María; Olave, Marta; Monge, Rosa; de Miguel, Diego; Martínez-Lostao, Luis; Le Gac, Séverine; Doblare, Manuel; Ochoa, Ignacio; Fernandez, Luis J

2017-09-20

The tumour microenvironment is very complex, and essential in tumour development and drug resistance. The endothelium is critical in the tumour microenvironment: it provides nutrients and oxygen to the tumour and is essential for systemic drug delivery. Therefore, we report a simple, user-friendly microfluidic device for co-culture of a 3D breast tumour model and a 2D endothelium model for cross-talk and drug delivery studies. First, we demonstrated the endothelium was functional, whereas the tumour model exhibited in vivo features, e.g., oxygen gradients and preferential proliferation of cells with better access to nutrients and oxygen. Next, we observed the endothelium structure lost its integrity in the co-culture. Following this, we evaluated two drug formulations of TRAIL (TNF-related apoptosis inducing ligand): soluble and anchored to a LUV (large unilamellar vesicle). Both diffused through the endothelium, LUV-TRAIL being more efficient in killing tumour cells, showing no effect on the integrity of endothelium. Overall, we have developed a simple capillary force-based microfluidic device for 2D and 3D cell co-cultures. Our device allows high-throughput approaches, patterning different cell types and generating gradients without specialised equipment. We anticipate this microfluidic device will facilitate drug screening in a relevant microenvironment thanks to its simple, effective and user-friendly operation.

Linking Findings in Microfluidics to Membrane Emulsification Process Design: The Importance of Wettability and Component Interactions with Interfaces

PubMed Central

Schroën, Karin; Ferrando, Montse; de Lamo-Castellví, Silvia; Sahin, Sami; Güell, Carme

2016-01-01

In microfluidics and other microstructured devices, wettability changes, as a result of component interactions with the solid wall, can have dramatic effects. In emulsion separation and emulsification applications, the desired behavior can even be completely lost. Wettability changes also occur in one phase systems, but the effect is much more far-reaching when using two-phase systems. For microfluidic emulsification devices, this can be elegantly demonstrated and quantified for EDGE (Edge-base Droplet GEneration) devices that have a specific behavior that allows us to distinguish between surfactant and liquid interactions with the solid surface. Based on these findings, design rules can be defined for emulsification with any micro-structured emulsification device, such as direct and premix membrane emulsification. In general, it can be concluded that mostly surface interactions increase the contact angle toward 90°, either through the surfactant, or the oil that is used. This leads to poor process stability, and very limited pressure ranges at which small droplets can be made in microfluidic systems, and cross-flow membrane emulsification. In a limited number of cases, surface interactions can also lead to lower contact angles, thereby increasing the operational stability. This paper concludes with a guideline that can be used to come to the appropriate combination of membrane construction material (or any micro-structured device), surfactants and liquids, in combination with process conditions. PMID:27187484

A vertically-stacked, polymer, microfluidic point mutation analyzer: Rapid, high accuracy detection of low-abundance K-ras mutations

PubMed Central

Han, Kyudong; Lee, Tae Yoon; Nikitopoulos, Dimitris E.; Soper, Steven A.; Murphy, Michael C.

2011-01-01

Recognition of point mutations in the K-ras gene can be used for the clinical management of several types of cancers. Unfortunately, several assay and hardware concerns must be addressed to allow users not well-trained in performing molecular analyses the opportunity to undertake these measurements. To provide for a larger user-base for these types of molecular assays, a vertically-stacked microfluidic analyzer with a modular architecture and process automation was developed. The analyzer employed a primary PCR coupled to an allele-specific ligase detection reaction (LDR). Each functional device, including continuous flow thermal reactors for the PCR and LDR, passive micromixers and ExoSAP-IT® purification, was designed and tested. Individual devices were fabricated in polycarbonate using hot embossing and assembled using adhesive bonding for system assembly. The system produced LDR products from a DNA sample in ~1 h, an 80% reduction in time compared to conventional bench-top instrumentation. Purifying the post-PCR products with the ExoSAP-IT® enzyme led to optimized LDR performance minimizing false positive signals and producing reliable results. Mutant alleles in genomic DNA were quantified to the level of 0.25 ng of mutant DNA in 50 ng of wild-type DNA for a 25 μL sample, equivalent to DNA from 42 mutant cells. PMID:21771577

Nano-islands integrated evanescence-based lab-on-a-chip on silica-on-silicon and polydimethylsiloxane hybrid platform for detection of recombinant growth hormone

PubMed Central

Ozhikandathil, J.; Packirisamy, M.

2012-01-01

Integration of nano-materials in optical microfluidic devices facilitates the realization of miniaturized analytical systems with enhanced sensing abilities for biological and chemical substances. In this work, a novel method of integration of gold nano-islands in a silica-on-silicon-polydimethylsiloxane microfluidic device is reported. The device works based on the nano-enhanced evanescence technique achieved by interacting the evanescent tail of propagating wave with the gold nano-islands integrated on the core of the waveguide resulting in the modification of the propagating UV-visible spectrum. The biosensing ability of the device is investigated by finite-difference time-domain simulation with a simplified model of the device. The performance of the proposed device is demonstrated for the detection of recombinant growth hormone based on antibody-antigen interaction. PMID:24106526

Paper-based microfluidics with an erodible polymeric bridge giving controlled release and timed flow shutoff.

PubMed

Jahanshahi-Anbuhi, Sana; Henry, Aleah; Leung, Vincent; Sicard, Clémence; Pennings, Kevin; Pelton, Robert; Brennan, John D; Filipe, Carlos D M

2014-01-07

Water soluble pullulan films were formatted into paper-based microfluidic devices, serving as a controlled time shutoff valve. The utility of the valve was demonstrated by a one-step, fully automatic implementation of a complex pesticide assay requiring timed, sequential exposure of an immobilized enzyme layer to separate liquid streams. Pullulan film dissolution and the capillary wicking of aqueous solutions through the device were measured and modeled providing valve design criteria. The films dissolve mainly by surface erosion, meaning the film thickness mainly controls the shutoff time. This method can also provide time-dependent sequential release of reagents without compromising the simplicity and low cost of paper-based devices.

Surface-Micromachined Microfluidic Devices

DOEpatents

Galambos, Paul C.; Okandan, Murat; Montague, Stephen; Smith, James H.; Paul, Phillip H.; Krygowski, Thomas W.; Allen, James J.; Nichols, Christopher A.; Jakubczak, II, Jerome F.

2004-09-28

Microfluidic devices are disclosed which can be manufactured using surface-micromachining. These devices utilize an electroosmotic force or an electromagnetic field to generate a flow of a fluid in a microchannel that is lined, at least in part, with silicon nitride. Additional electrodes can be provided within or about the microchannel for separating particular constituents in the fluid during the flow based on charge state or magnetic moment. The fluid can also be pressurized in the channel. The present invention has many different applications including electrokinetic pumping, chemical and biochemical analysis (e.g. based on electrophoresis or chromatography), conducting chemical reactions on a microscopic scale, and forming hydraulic actuators. Microfluidic devices are disclosed which can be manufactured using surface-micromachining. These devices utilize an electroosmotic force or an electromagnetic field to generate a flow of a fluid in a microchannel that is lined, at least in part, with silicon nitride. Additional electrodes can be provided within or about the microchannel for separating particular constituents in the fluid during the flow based on charge state or magnetic moment. The fluid can also be pressurized in the channel. The present invention has many different applications including electrokinetic pumping, chemical and biochemical analysis (e.g. based on electrophoresis or chromatography), conducting chemical reactions on a microscopic scale, and forming hydraulic actuators.

Laser-induced fluorescence detection platform for point-of-care testing

NASA Astrophysics Data System (ADS)

Berner, Marcel; Hilbig, Urs; Schubert, Markus B.; Gauglitz, Günter

2017-08-01

Point-of-care testing (POCT) devices for continuous low-cost monitoring of critical patient parameters require miniaturized and integrated setups for performing quick high-sensitivity analyses, away from central clinical laboratories. This work presents a novel and promising laser-induced fluorescence platform for measurements in direct optical test formats that leads towards such powerful POCT devices based on fluorescence-labeled immunoassays. Ultimate sensitivity of thin film photodetectors, integrated with microfluidics, and a comprehensive optimization of all system components aim at low-level signal detection in the targeted biosensor application. The setup acquires fluorescence signals from the volume of a microfluidic channel. An innovative sandwiching process forms a flow channel in the microfluidic chips by embedding laser-cut double-sided adhesive tapes. The custom fit of amorphous silicon based photodiode arrays to the geometry of the flow channel enables miniaturization, fully adequate for POCT devices. A free-beam laser excitation with line focus provides excellent alignment stability, allows for easy and reliable swapping of the disposable microfluidic chips, and therewith greatly improves the ease of use of the resulting integrated device. As a proof-of-concept of this novel in-volume measurement approach, the limit of detection for the dye DY636-COOH in pure water as a model fluorophore is examined and found to be 26 nmol l-1 .

Multivariate analysis for the optimization of microfluidics-assisted nanoprecipitation method intended for the loading of small hydrophilic drugs into PLGA nanoparticles.

PubMed

Chiesa, E; Dorati, R; Modena, T; Conti, B; Genta, I

2018-01-30

Design of Experiment-assisted evaluation of critical process (total flow rate, TFR, flow rate ratio, FRR) and formulation (polymer concentration and structure, drug:polymer ratio) variables in a novel microfluidics-based device, a staggered herringbone micromixer (SHM), for poly(lactic-co-glycolic acid) copolymer (PLGA) nanoparticles (NPs) manufacturing was performed in order to systematically evaluate and mathematically describe their effects on NPs sizes and drug encapsulation; a small hydrophilic moiety, N-acetylcysteine, was chosen as challenging model drug. SHM-assisted nanoprecipitation method consistently yielded NPs with tailor made sizes (in the range of 100-900 nm) and polydispersity index range from 0.061 to 0.286. Significant effects on NPs sizes were highlighted for TFR and FRR: increasing TFR (from 5 to 15 mL/min) and decreasing FRR (from 1:1 to 1:5 v/v, acetonitrile: buffer) NPs with mean diameter <200 nm were obtained. SHM technique allowed for flexible, application-specific tuning of PLGA NPs size using organic solvents with relatively low toxicity (acetone, acetonitrile), varying aqueous phase composition (Tris buffer vs PVA aqueous solution) and PLGA characteristics (Mw ranging from 25-90 kDa, capped or un-capped PLGA, different lactide:glycolide molar ratio). A very satisfactory N-Ac encapsulation efficiency (more than 67%) and a prolonged release (by 168 h) were achieved. Copyright © 2017 Elsevier B.V. All rights reserved.

Surface-micromachined microfluidic devices

DOEpatents

Galambos, Paul C.; Okandan, Murat; Montague, Stephen; Smith, James H.; Paul, Phillip H.; Krygowski, Thomas W.; Allen, James J.; Nichols, Christopher A.; Jakubczak, II, Jerome F.

2003-01-01

Microfluidic devices are disclosed which can be manufactured using surface-micromachining. These devices utilize an electroosmotic force or an electromagnetic field to generate a flow of a fluid in a microchannel that is lined, at least in part, with silicon nitride. Additional electrodes can be provided within or about the microchannel for separating particular constituents in the fluid during the flow based on charge state or magnetic moment. The fluid can also be pressurized in the channel. The present invention has many different applications including electrokinetic pumping, chemical and biochemical analysis (e.g. based on electrophoresis or chromatography), conducting chemical reactions on a microscopic scale, and forming hydraulic actuators.

Synthesis and characterization of polymer layers for control of fluid transport

NASA Astrophysics Data System (ADS)

Vatansever, Fehime

The level of wetting of fiber surface with liquids is an important characteristic of fibrous materials. It is related to fiber surface energy and the structure of the material. Surface energy can be changed by surface modification via the grafting methodologies that have been reported for introducing new and stable functionality to fibrous substrates without changing bulk properties. Present work is dedicated to synthesis and characterization of macromolecular layers grafted to fiber surface in order to achieve directional liquid transport for the modified fabric. Modification technique used here is based on formation of stable polymer layer on fabric surface using "grafting to" technique. Specifically, modification of fabric with wettability gradient for facilitated one way-liquid transport, and pointed modification of yarn-based channels on textile microfluidic device for directional liquid transport are reported here. First, fabric was activated with alkali (NaOH) solution. Second, poly (glycidyl methacrylate) (PGMA) was deposited on fabric as an anchoring layer. Finally, polymers of interest were grafted to surface through the epoxy functionality of PGMA. Effect of polymer grafting on the wicking property of the fabric has been evaluated by vertical wicking technique at the each step of surface modification. The results shows that wicking performance of fabric can be altered by grafting of a thin nanoscale polymeric film. For the facilitated liquid transport, the gradient polymer coating was created using "grafting to" technique and its dependence on the grafting temperature. Wettability gradient from hydrophilic to hydrophobic (change in water contact angle from 0 to 140 degrees on fabric) was achieved by grafting of polystyrene (PS) and polyacrylic acid (PAA) sequentially with concentration gradient. This study proposes that fabric with wettability gradient property can be used to transfer sweat from skin and support moisture management when it is used in a laminated garment structure. For cooling performance evaluation, modified fabrics were tested with surface differential scanning calorimeter, and improved cooling effect was found with the fabric that has wettability gradient. Directional liquid transport can be achieved on amphiphilic fabric. To this end, fabric consisting of PET and PP yarn is fabricated. Activation and PGMA deposition yields an array of highly reactive PET channels that are constrained by hydrophobic PP boundaries. Aqueous solutions are transported in the channels by capillary forces where the direction of the liquid transport is defined by pH-response of the grafted polymers. The system of pH-selective channels in the developed textile based microfluidic chip could find analytical applications and can be used for smart cloth.

Thermoplastic microfluidic devices and their applications in protein and DNA analysis

PubMed Central

Liu, Ke; Fan, Z. Hugh

2013-01-01

Microfluidics is a platform technology that has been used for genomics, proteomics, chemical synthesis, environment monitoring, cellular studies, and other applications. The fabrication materials of microfluidic devices have traditionally included silicon and glass, but plastics have gained increasing attention in the past few years. We focus this review on thermoplastic microfluidic devices and their applications in protein and DNA analysis. We outline the device design and fabrication methods, followed by discussion on the strategies of surface treatment. We then concentrate on several significant advancements in applying thermoplastic microfluidic devices to protein separation, immunoassays, and DNA analysis. Comparison among numerous efforts, as well as the discussion on the challenges and innovation associated with detection, is presented. PMID:21274478

Hot embossed polyethylene through-hole chips for bead-based microfluidic devices.

PubMed

Chou, Jie; Du, Nan; Ou, Tina; Floriano, Pierre N; Christodoulides, Nicolaos; McDevitt, John T

2013-04-15

Over the past decade, there has been a growth of interest in the translation of microfluidic systems into real-world clinical practice, especially for use in point-of-care or near patient settings. While initial fabrication advances in microfluidics involved mainly the etching of silicon and glass, the economics of scaling of these materials is not amendable for point-of-care usage where single-test applications force cost considerations to be kept low and throughput high. As such, materials base more consistent with point-of-care needs is required. In this manuscript, the fabrication of a hot embossed, through-hole low-density polyethylene ensembles derived from an anisotropically etched silicon wafer is discussed. This semi-opaque polymer that can be easily sterilized and recycled provides low background noise for fluorescence measurements and yields more affordable cost than other thermoplastics commonly used for microfluidic applications such as cyclic olefin copolymer (COC). To fabrication through-hole microchips from this alternative material for microfluidics, a fabrication technique that uses a high-temperature, high-pressure resistant mold is described. This aluminum-based epoxy mold, serving as the positive master mold for embossing, is casted over etched arrays of pyramidal pits in a silicon wafer. Methods of surface treatment of the wafer prior to casting and PDMS casting of the epoxy are discussed to preserve the silicon wafer for future use. Changes in the thickness of polyethylene are observed for varying embossing temperatures. The methodology described herein can quickly fabricate 20 disposable, single use chips in less than 30 min with the ability to scale up 4 times by using multiple molds simultaneously. When coupled as a platform supporting porous bead sensors, as in the recently developed Programmable Bio-Nano-Chip, this bead chip system can achieve limits of detection, for the cardiac biomarker C-reactive protein, of 0.3 ng/mL, thereby demonstrating that the approach is compatible with high performance, real-world clinical measurements in the context of point-of-care testing. Copyright © 2012 Elsevier B.V. All rights reserved.

An electric stimulation system for electrokinetic particle manipulation in microfluidic devices.

PubMed

Lopez-de la Fuente, M S; Moncada-Hernandez, H; Perez-Gonzalez, V H; Lapizco-Encinas, B H; Martinez-Chapa, S O

2013-03-01

Microfluidic devices have grown significantly in the number of applications. Microfabrication techniques have evolved considerably; however, electric stimulation systems for microdevices have not advanced at the same pace. Electric stimulation of micro-fluidic devices is an important element in particle manipulation research. A flexible stimulation instrument is desired to perform configurable, repeatable, automated, and reliable experiments by allowing users to select the stimulation parameters. The instrument presented here is a configurable and programmable stimulation system for electrokinetic-driven microfluidic devices; it consists of a processor, a memory system, and a user interface to deliver several types of waveforms and stimulation patterns. It has been designed to be a flexible, highly configurable, low power instrument capable of delivering sine, triangle, and sawtooth waveforms with one single frequency or two superimposed frequencies ranging from 0.01 Hz to 40 kHz, and an output voltage of up to 30 Vpp. A specific stimulation pattern can be delivered over a single time period or as a sequence of different signals for different time periods. This stimulation system can be applied as a research tool where manipulation of particles suspended in liquid media is involved, such as biology, medicine, environment, embryology, and genetics. This system has the potential to lead to new schemes for laboratory procedures by allowing application specific and user defined electric stimulation. The development of this device is a step towards portable and programmable instrumentation for electric stimulation on electrokinetic-based microfluidic devices, which are meant to be integrated with lab-on-a-chip devices.

An electric stimulation system for electrokinetic particle manipulation in microfluidic devices

NASA Astrophysics Data System (ADS)

Lopez-de la Fuente, M. S.; Moncada-Hernandez, H.; Perez-Gonzalez, V. H.; Lapizco-Encinas, B. H.; Martinez-Chapa, S. O.

2013-03-01

Microfluidic devices have grown significantly in the number of applications. Microfabrication techniques have evolved considerably; however, electric stimulation systems for microdevices have not advanced at the same pace. Electric stimulation of micro-fluidic devices is an important element in particle manipulation research. A flexible stimulation instrument is desired to perform configurable, repeatable, automated, and reliable experiments by allowing users to select the stimulation parameters. The instrument presented here is a configurable and programmable stimulation system for electrokinetic-driven microfluidic devices; it consists of a processor, a memory system, and a user interface to deliver several types of waveforms and stimulation patterns. It has been designed to be a flexible, highly configurable, low power instrument capable of delivering sine, triangle, and sawtooth waveforms with one single frequency or two superimposed frequencies ranging from 0.01 Hz to 40 kHz, and an output voltage of up to 30 Vpp. A specific stimulation pattern can be delivered over a single time period or as a sequence of different signals for different time periods. This stimulation system can be applied as a research tool where manipulation of particles suspended in liquid media is involved, such as biology, medicine, environment, embryology, and genetics. This system has the potential to lead to new schemes for laboratory procedures by allowing application specific and user defined electric stimulation. The development of this device is a step towards portable and programmable instrumentation for electric stimulation on electrokinetic-based microfluidic devices, which are meant to be integrated with lab-on-a-chip devices.

A flexible future for paper-based electronics

NASA Astrophysics Data System (ADS)

Liang, Tongfen; Zou, Xiyue; Mazzeo, Aaron D.

2016-05-01

This paper will review the origins and state of the art in paper-based electronics, suggesting the stage is set for future promising applications. Current interest in paper-based electronics can trace its roots to recent developments in paper-based microfluidics. With a need to improve the reliability and sensitivity of paperbased microfluidics for certain tasks, there were natural efforts to begin embedding sensing electrodes into microfluidic devices. Recognizing the general benefits of paper as an advanced material (e.g., its environmental friendliness, bendable nature, and low cost), efforts in paper-based electronics also began to take a life of their own with demonstrations of transistors, batteries and devices for energy storage, energy harvesting, sensors to improve situational awareness, acoustics, and displays. The state-of-the-art paper-based electronic devices have benefited and will continue to profit from technologies for printing and transferring electronic functionality onto the surfaces of paper-based substrates. Nonetheless, the authors suggest that many future promising applications will go beyond using paper as a carrier/substrate for electronic components to explore tuning of the electrical, mechanical, and chemical properties of the paper itself. With these technical advances, paper-based electronics will move closer to economically viable killer applications.

Programmable diagnostic devices made from paper and tape.

PubMed

Martinez, Andres W; Phillips, Scott T; Nie, Zhihong; Cheng, Chao-Min; Carrilho, Emanuel; Wiley, Benjamin J; Whitesides, George M

2010-10-07

This paper describes three-dimensional microfluidic paper-based analytical devices (3-D microPADs) that can be programmed (postfabrication) by the user to generate multiple patterns of flow through them. These devices are programmed by pressing single-use 'on' buttons, using a stylus or a ballpoint pen. Pressing a button closes a small space (gap) between two vertically aligned microfluidic channels, and allows fluids to wick from one channel to the other. These devices are simple to fabricate, and are made entirely out of paper and double-sided adhesive tape. Programmable devices expand the capabilities of microPADs and provide a simple method for controlling the movement of fluids in paper-based channels. They are the conceptual equivalent of field-programmable gate arrays (FPGAs) widely used in electronics.

Fabrication of composite poly(d,l-lactide)/montmorillonite nanoparticles for controlled delivery of acetaminophen by solvent-displacement method using glass capillary microfluidics.

PubMed

Othman, Rahimah; Vladisavljević, Goran T; Thomas, Noreen L; Nagy, Zoltan K

2016-05-01

Paracetamol (PCM)-loaded composite nanoparticles (NPs) composed of a biodegradable poly(d,l-lactide) (PLA) polymer matrix filled with organically modified montmorillonite (MMT) nanoparticles were fabricated by antisolvent nanoprecipitation in a microfluidic co-flow glass capillary device. The incorporation of MMT in the polymer improved both the drug encapsulation efficiency and the drug loading, and extended the rate of drug release in simulated intestinal fluid (pH 7.4). The particle size increased on increasing both the drug loading and the concentration of MMT in the polymer matrix, and decreased on increasing the aqueous to organic flow rate ratio. The drug encapsulation efficiency in the NPs was higher at higher aqueous to organic flow rate ratio due to faster formation of the NPs. The PCM-loaded PLA NPs containing 2 wt% MMT in PLA prepared at an aqueous to organic flow rate ratio of 10 with an orifice size of 200 μm exhibited a spherical shape with a mean size of 296 nm, a drug encapsulation efficiency of 38.5% and a drug loading of 5.4%. The encapsulation of MMT and PCM in the NPs was confirmed by transmission electron microscopy, energy dispersive X-ray spectroscopy, X-ray diffraction, differential scanning calorimetry, thermogravimetric analysis and attenuated total reflection-Fourier transform infrared spectroscopy. Copyright © 2016 Elsevier B.V. All rights reserved.

Fabrication and characterization of a micromachined swirl-shaped ionic polymer metal composite actuator with electrodes exhibiting asymmetric resistance.

PubMed

Feng, Guo-Hua; Liu, Kim-Min

2014-05-12

This paper presents a swirl-shaped microfeatured ionic polymer-metal composite (IPMC) actuator. A novel micromachining process was developed to fabricate an array of IPMC actuators on a glass substrate and to ensure that no shortcircuits occur between the electrodes of the actuator. We demonstrated a microfluidic scheme in which surface tension was used to construct swirl-shaped planar IPMC devices of microfeature size and investigated the flow velocity of Nafion solutions, which formed the backbone polymer of the actuator, within the microchannel. The unique fabrication process yielded top and bottom electrodes that exhibited asymmetric surface resistance. A tool for measuring surface resistance was developed and used to characterize the resistances of the electrodes for the fabricated IPMC device. The actuator, which featured asymmetric electrode resistance, caused a nonzero-bias current when the device was driven using a zero-bias square wave, and we propose a circuit model to describe this phenomenon. Moreover, we discovered and characterized a bending and rotating motion when the IPMC actuator was driven using a square wave. We observed a strain rate of 14.6% and a displacement of 700 μm in the direction perpendicular to the electrode surfaces during 4.5-V actuation.

Fabrication and Characterization of a Micromachined Swirl-Shaped Ionic Polymer Metal Composite Actuator with Electrodes Exhibiting Asymmetric Resistance

PubMed Central

Feng, Guo-Hua; Liu, Kim-Min

2014-01-01

This paper presents a swirl-shaped microfeatured ionic polymer-metal composite (IPMC) actuator. A novel micromachining process was developed to fabricate an array of IPMC actuators on a glass substrate and to ensure that no shortcircuits occur between the electrodes of the actuator. We demonstrated a microfluidic scheme in which surface tension was used to construct swirl-shaped planar IPMC devices of microfeature size and investigated the flow velocity of Nafion solutions, which formed the backbone polymer of the actuator, within the microchannel. The unique fabrication process yielded top and bottom electrodes that exhibited asymmetric surface resistance. A tool for measuring surface resistance was developed and used to characterize the resistances of the electrodes for the fabricated IPMC device. The actuator, which featured asymmetric electrode resistance, caused a nonzero-bias current when the device was driven using a zero-bias square wave, and we propose a circuit model to describe this phenomenon. Moreover, we discovered and characterized a bending and rotating motion when the IPMC actuator was driven using a square wave. We observed a strain rate of 14.6% and a displacement of 700 μm in the direction perpendicular to the electrode surfaces during 4.5-V actuation. PMID:24824370

Ion channel recordings on an injection-molded polymer chip.

PubMed

Tanzi, Simone; Matteucci, Marco; Christiansen, Thomas Lehrmann; Friis, Søren; Christensen, Mette Thylstrup; Garnaes, Joergen; Wilson, Sandra; Kutchinsky, Jonatan; Taboryski, Rafael

2013-12-21

In this paper, we demonstrate recordings of the ion channel activity across the cell membrane in a biological cell by employing the so-called patch clamping technique on an injection-molded polymer microfluidic device. The findings will allow direct recordings of ion channel activity to be made using the cheapest materials and production platform to date and with the potential for very high throughput. The employment of cornered apertures for cell capture allowed the fabrication of devices without through holes and via a scheme comprising master origination by dry etching in a silicon substrate, electroplating in nickel and injection molding of the final part. The most critical device parameters were identified as the length of the patching capillary and the very low surface roughness on the inside of the capillary. The cross-sectional shape of the orifice was found to be less critical, as both rectangular and semicircular profiles seemed to have almost the same ability to form tight seals with cells with negligible leak currents. The devices were functionally tested using human embryonic kidney cells expressing voltage-gated sodium channels (Nav1.7) and benchmarked against a commercial state-of-the-art system for automated ion channel recordings. These experiments considered current-voltage (IV) relationships for activation and inactivation of the Nav1.7 channels and their sensitivity to a local anesthetic, lidocaine. Both IVs and lidocaine dose-response curves obtained from the injection-molded polymer device were in good agreement with data obtained from the commercial system.

Finite Element Model of Oxygen Transport for the Design of Geometrically Complex Microfluidic Devices Used in Biological Studies

PubMed Central

Fraser, Graham M.; Goldman, Daniel; Ellis, Christopher G.

2016-01-01

Red blood cells play a crucial role in the local regulation of oxygen supply in the microcirculation through the oxygen dependent release of ATP. Since red blood cells serve as an oxygen sensor for the circulatory system, the dynamics of ATP release determine the effectiveness of red blood cells to relate the oxygen levels to the vessels. Previous work has focused on the feasibility of developing a microfluidic system to measure the dynamics of ATP release. The objective was to determine if a steep oxygen gradient could be developed in the channel to cause a rapid decrease in hemoglobin oxygen saturation in order to measure the corresponding levels of ATP released from the red blood cells. In the present study, oxygen transport simulations were used to optimize the geometric design parameters for a similar system which is easier to fabricate. The system is composed of a microfluidic device stacked on top of a large, gas impermeable flow channel with a hole to allow gas exchange. The microfluidic device is fabricated using soft lithography in polydimethyl-siloxane, an oxygen permeable material. Our objective is twofold: (1) optimize the parameters of our system and (2) develop a method to assess the oxygen distribution in complex 3D microfluidic device geometries. 3D simulations of oxygen transport were performed to simulate oxygen distribution throughout the device. The simulations demonstrate that microfluidic device geometry plays a critical role in molecule exchange, for instance, changing the orientation of the short wide microfluidic channel results in a 97.17% increase in oxygen exchange. Since microfluidic devices have become a more prominent tool in biological studies, understanding the transport of oxygen and other biological molecules in microfluidic devices is critical for maintaining a physiologically relevant environment. We have also demonstrated a method to assess oxygen levels in geometrically complex microfluidic devices. PMID:27829071

Finite Element Model of Oxygen Transport for the Design of Geometrically Complex Microfluidic Devices Used in Biological Studies.

PubMed

Sové, Richard J; Fraser, Graham M; Goldman, Daniel; Ellis, Christopher G

2016-01-01

Red blood cells play a crucial role in the local regulation of oxygen supply in the microcirculation through the oxygen dependent release of ATP. Since red blood cells serve as an oxygen sensor for the circulatory system, the dynamics of ATP release determine the effectiveness of red blood cells to relate the oxygen levels to the vessels. Previous work has focused on the feasibility of developing a microfluidic system to measure the dynamics of ATP release. The objective was to determine if a steep oxygen gradient could be developed in the channel to cause a rapid decrease in hemoglobin oxygen saturation in order to measure the corresponding levels of ATP released from the red blood cells. In the present study, oxygen transport simulations were used to optimize the geometric design parameters for a similar system which is easier to fabricate. The system is composed of a microfluidic device stacked on top of a large, gas impermeable flow channel with a hole to allow gas exchange. The microfluidic device is fabricated using soft lithography in polydimethyl-siloxane, an oxygen permeable material. Our objective is twofold: (1) optimize the parameters of our system and (2) develop a method to assess the oxygen distribution in complex 3D microfluidic device geometries. 3D simulations of oxygen transport were performed to simulate oxygen distribution throughout the device. The simulations demonstrate that microfluidic device geometry plays a critical role in molecule exchange, for instance, changing the orientation of the short wide microfluidic channel results in a 97.17% increase in oxygen exchange. Since microfluidic devices have become a more prominent tool in biological studies, understanding the transport of oxygen and other biological molecules in microfluidic devices is critical for maintaining a physiologically relevant environment. We have also demonstrated a method to assess oxygen levels in geometrically complex microfluidic devices.

Development & Characterization of Multifunctional Microfluidic Materials

NASA Astrophysics Data System (ADS)

Ucar, Ahmet Burak

The field of microfluidics has been mostly investigated for miniaturized lab on a chip devices for analytical and clinical applications. However, there is an emerging class of "smart" microfluidic materials, combining microfluidics with soft polymers to yield new functionalities. The best inspiration for such materials found in nature is skin, whose functions are maintained and controlled by a vascular "microfluidic" network. We report here the development and characterization of a few new classes of microfluidic materials. First, we introduced microfluidic materials that can change their stiffness on demand. These materials were based on an engineered microchannel network embedded into a matrix of polydimethylsiloxane (PDMS), whose channels were filled with a liquid photoresist (SU- 8). The elastomer filled with the photoresist was initially soft. The materials were shaped into a desired geometry and then exposed to UV-light. Once photocured, the material preserved the defined shape and it could be bent, twisted or stretched with a very high recoverable strain. As soon as the external force was removed the material returned back to its predefined shape. Thus, the polymerized SU-8 acted as the 'endoskeleton' of the microfluidic network, which drastically increased the composite's elastic and bending moduli. Second, we demonstrated a class of simple and versatile soft microfluidic materials that can be turned optically transparent or colored on demand. These materials were made in the form of flexible sheets containing a microchannel network embedded in PDMS, similar to the photocurable materials. However, this time the channels were filled with a glycerolwater mixture, whose refractive index was matched with that of the PDMS matrix. By pumping such dye solutions into the channel network and consecutively replacing the medium, we showed that we can control the material's color and light transmittance in the visible and near-infrared regions, which can be used for developing 'smart' windows and heat management. To better design new color changing elastomers, we investigated the role of the network geometry on liquid replacement efficiency with the aid of a multiphysics modeling and simulation software package, COMSOL. We simulated the liquid flow in various network geometries. Serpentine, parallel channel and lattice networks, as well as their tapered versions were compared. The comparison criteria were based on rapid and uniform liquid replacement with the least amount of dye/liquid required, for which we set multiple constraints such as constant inlet pressure or total channel area. We demonstrated that the tapered lattice type network provided the most rapid and uniform replacement with minimal liquid waste. Next, we designed a simple and inexpensive liquid dispensing microfluidic material which does not require complex micromachining techniques or automated actuators. It consisted of only a PDMS matrix with embedded chambers and channels. 'Pores/slits' were made on the surface and the liquid was released by contact on the dispensing surface of the material. We varied the network design, geometry, dimension, slit shape and length, and tested the material's liquid release performance. Promising preliminary results were obtained but for an end product with repeatable and reproducible performance, both material fabrication and characterization need to be improved further. Finally, we describe an alternative material/method for the fabrication of microfluidic materials. We aimed to replace the conventional fabrication material PDMS with Polyethylene (PE) sheets. The sheets were as transparent and flexible as PDMS, and also thinner. Channel patterns were drawn with a polymer solution of PolyVinylAlcohol (PVA), which is immiscible with PE, and captured in between the two PE sheets. After fusing the PE sheets on a hot press, PVA was washed off with water, so that the 'microfluidic channels' were successfully created. The produced channel widths were ˜0.7-0.8 mm. This novel method eliminates the need for soft lithography and master fabrication, thus decreases the cost and time of the material fabrication.

Microfluidic mixing triggered by an external LED illumination.

PubMed

Venancio-Marques, Anna; Barbaud, Fanny; Baigl, Damien

2013-02-27

The mixing of confined liquids is a central yet challenging operation in miniaturized devices. Microfluidic mixing is usually achieved with passive mixers that are robust but poorly flexible, or active mixers that offer dynamic control but mainly rely on electrical or mechanical transducers, which increase the fragility, cost, and complexity of the device. Here, we describe the first remote and reversible control of microfluidic mixing triggered by a light illumination simply provided by an external LED illumination device. The approach is based on the light-induced generation of water microdroplets acting as reversible stirrers of two continuous oil phase flows containing samples to be mixed. We demonstrate many cycles of reversible photoinduced transitions between a nonmixing behavior and full homogenization of the two oil phases. The method is cheap, portable, and adaptable to many device configurations, thus constituting an essential brick for the generation of future all-optofluidic chip.

Microbioreactors with microfluidic control and a user-friendly connection to the actuator hardware

NASA Astrophysics Data System (ADS)

Buchenauer, A.; Funke, M.; Büchs, J.; Mokwa, W.; Schnakenberg, U.

2009-07-01

In this study, an array of microbioreactors based on the format of 48-well microtiter plates (MTPs) is presented. The process parameters pH and biomass are monitored online using commercially available optical sensor technology. A microfluidic device dispenses acid or base individually into each well for controlling the pH of fermentations. Fluid volumes from 72 nL to 940 nL can be supplied with valve opening times between 10 ms and 200 ms. One microfluidic device is capable of supplying four wells from two reservoirs. Up to four microfluidic devices can be integrated on the area of a prototype MTP. The devices are fabricated in polydimethylsiloxane (PDMS) using soft lithographic techniques and utilize pneumatically actuated microvalves. During fermentations, the microbioreactor is clamped to an orbital shaker and a temporary pneumatic connection guides the externally controlled pressurized air to the microfluidic device. Finally, fermentations of Escherichia coli in the presence and absence of pH control are carried out in the microbioreactor system over 18 h. During the fermentation the pH of the cultures is continuously monitored by means of optodes. An ammonia solution or phosphoric acid is dispensed to adjust the pH if it differs from the set point of 7.2. In a controlled culture, the pH can be sustained within 7.0 to 7.3 while the pH in an uncontrolled culture ranges between 6.5 and 9.0. This microbioreactor demonstrates the possibility of pH-controlled fermentations in micro-scale. The process control and the user friendly connection to the actuation hardware provide an easy handling comparable to standard MTPs.

Validation of long-term primary neuronal cultures and network activity through the integration of reversibly bonded microbioreactors and MEA substrates.

PubMed

Biffi, Emilia; Menegon, Andrea; Piraino, Francesco; Pedrocchi, Alessandra; Fiore, Gianfranco B; Rasponi, Marco

2012-01-01

In vitro recording of neuronal electrical activity is a widely used technique to understand brain functions and to study the effect of drugs on the central nervous system. The integration of microfluidic devices with microelectrode arrays (MEAs) enables the recording of networks activity in a controlled microenvironment. In this work, an integrated microfluidic system for neuronal cultures was developed, reversibly coupling a PDMS microfluidic device with a commercial flat MEA through magnetic forces. Neurons from mouse embryos were cultured in a 100 µm channel and their activity was followed up to 18 days in vitro. The maturation of the networks and their morphological and functional characteristics were comparable with those of networks cultured in macro-environments and described in literature. In this work, we successfully demonstrated the ability of long-term culturing of primary neuronal cells in a reversible bonded microfluidic device (based on magnetism) that will be fundamental for neuropharmacological studies. Copyright © 2011 Wiley Periodicals, Inc.

Magnetically-guided assembly of microfluidic fibers for ordered construction of diverse netlike modules

NASA Astrophysics Data System (ADS)

Li, Xingfu; Shi, Qing; Wang, Huaping; Sun, Tao; Huang, Qiang; Fukuda, Toshio

2017-12-01

In this paper, a magnetically-guided assembly method is proposed to methodically construct diverse modules with a microfiber-based network for promoting nutrient circulation and waste excretion of cell culture. The microfiber is smoothly spun from the microfluidic device via precise control of the volumetric flow rate, and superparamagnetic nanoparticles within the alginate solution of the microfluidic fiber enable its magnetic response. The magnetized device is used to effectively capture the microfiber using its powerful magnetic flux density and high magnetic field gradient. Subsequently, the dot-matrix magnetic flux density is used to distribute the microfibers in an orderly fashion that depends on the array structure of the magnetized device. Furthermore, the magnetic microfluidic fibers are spatially organized into desired locations and are cross-aligned to form highly interconnected netlike modules in a liquid environment. Therefore, the experimental results herein demonstrate the structural controllability and stability of various modules and establish the effectiveness of the proposed method.

Dissolved oxygen sensing using organometallic dyes deposited within a microfluidic environment

NASA Astrophysics Data System (ADS)

Chen, Q. L.; Ho, H. P.; Jin, L.; Chu, B. W.-K.; Li, M. J.; Yam, V. W.-W.

2008-02-01

This work primarily aims to integrate dissolved oxygen sensing capability with a microfluidic platform containing arrays of micro bio-reactors or bio-activity indicators. The measurement of oxygen concentration is of significance for a variety of bio-related applications such as cell culture and gene expression. Optical oxygen sensors based on luminescence quenching are gaining much interest in light of their low power consumption, quick response and high analyte sensitivity in comparison to similar oxygen sensing devices. In our microfluidic oxygen sensor device, a thin layer of oxygen-sensitive luminescent organometallic dye is covalently bonded to a glass slide. Micro flow channels are formed on the glass slide using patterned PDMS (Polydimethylsiloxane). Dissolved oxygen sensing is then performed by directing an optical excitation probe beam to the area of interest within the microfluidic channel. The covalent bonding approach for sensor layer formation offers many distinct advantages over the physical entrapment method including minimizing dye leaching, ensuring good stability and fabrication simplicity. Experimental results confirm the feasibility of the device.

Microfluidic Separation of Circulating Tumor Cells Based on Size and Deformability.

PubMed

Park, Emily S; Duffy, Simon P; Ma, Hongshen

2017-01-01

Circulating tumor cells (CTCs) have been implicated as the seeds of cancer metastasis and therefore have the potential to provide significant prognostic and diagnostic values. Here, we describe a procedure for separating CTCs from whole blood based on size and deformability using the microfluidic ratchet device. This device leverages the ratcheting motion of single cells created as they are deformed through funnel-shaped constrictions using oscillatory flow in order to divert cells based on differences in size and deformability. Subsequent methods for CTC identification and enumeration using immunofluorescence after separation are also described.

Paper-based analytical devices for environmental analysis.

PubMed

Meredith, Nathan A; Quinn, Casey; Cate, David M; Reilly, Thomas H; Volckens, John; Henry, Charles S

2016-03-21

The field of paper-based microfluidics has experienced rapid growth over the past decade. Microfluidic paper-based analytical devices (μPADs), originally developed for point-of-care medical diagnostics in resource-limited settings, are now being applied in new areas, such as environmental analyses. Low-cost paper sensors show great promise for on-site environmental analysis; the theme of ongoing research complements existing instrumental techniques by providing high spatial and temporal resolution for environmental monitoring. This review highlights recent applications of μPADs for environmental analysis along with technical advances that may enable μPADs to be more widely implemented in field testing.

Reactions in Droplets in Microfluidic Channels

PubMed Central

Song, Helen; Chen, Delai L.; Ismagilov, Rustem F.

2006-01-01

Fundamental and applied research in chemistry and biology benefits from opportunities provided by droplet-based microfluidic systems. These systems enable the miniaturization of reactions by compartmentalizing reactions in droplets of femoliter to microliter volumes. Compartmentalization in droplets provides rapid mixing of reagents, control of the timing of reactions on timescales from milliseconds to months, control of interfacial properties, and the ability to synthesize and transport solid reagents and products. Droplet-based microfluidics can help to enhance and accelerate chemical and biochemical screening, protein crystallization, enzymatic kinetics, and assays. Moreover, the control provided by droplets in microfluidic devices can lead to new scientific methods and insights. PMID:17086584

Droplet Microfluidics for Chip-Based Diagnostics

PubMed Central

Kaler, Karan V. I. S.; Prakash, Ravi

2014-01-01

Droplet microfluidics (DMF) is a fluidic handling technology that enables precision control over dispensing and subsequent manipulation of droplets in the volume range of microliters to picoliters, on a micro-fabricated device. There are several different droplet actuation methods, all of which can generate external stimuli, to either actively or passively control the shape and positioning of fluidic droplets over patterned substrates. In this review article, we focus on the operation and utility of electro-actuation-based DMF devices, which utilize one or more micro-/nano-patterned substrates to facilitate electric field-based handling of chemical and/or biological samples. The underlying theory of DMF actuations, device fabrication methods and integration of optical and opto-electronic detectors is discussed in this review. Example applications of such electro-actuation-based DMF devices have also been included, illustrating the various actuation methods and their utility in conducting chip-based laboratory and clinical diagnostic assays. PMID:25490590

Approaching near real-time biosensing: microfluidic microsphere based biosensor for real-time analyte detection.

PubMed

Cohen, Noa; Sabhachandani, Pooja; Golberg, Alexander; Konry, Tania

2015-04-15

In this study we describe a simple lab-on-a-chip (LOC) biosensor approach utilizing well mixed microfluidic device and a microsphere-based assay capable of performing near real-time diagnostics of clinically relevant analytes such cytokines and antibodies. We were able to overcome the adsorption kinetics reaction rate-limiting mechanism, which is diffusion-controlled in standard immunoassays, by introducing the microsphere-based assay into well-mixed yet simple microfluidic device with turbulent flow profiles in the reaction regions. The integrated microsphere-based LOC device performs dynamic detection of the analyte in minimal amount of biological specimen by continuously sampling micro-liter volumes of sample per minute to detect dynamic changes in target analyte concentration. Furthermore we developed a mathematical model for the well-mixed reaction to describe the near real time detection mechanism observed in the developed LOC method. To demonstrate the specificity and sensitivity of the developed real time monitoring LOC approach, we applied the device for clinically relevant analytes: Tumor Necrosis Factor (TNF)-α cytokine and its clinically used inhibitor, anti-TNF-α antibody. Based on the reported results herein, the developed LOC device provides continuous sensitive and specific near real-time monitoring method for analytes such as cytokines and antibodies, reduces reagent volumes by nearly three orders of magnitude as well as eliminates the washing steps required by standard immunoassays. Copyright © 2014 Elsevier B.V. All rights reserved.

A Microfluidics-based Pulpal Arteriole Blood Flow Phantom for Validation of Doppler Ultrasound Devices in Pulpal Blood Flow Velocity Measurement.

PubMed

Kim, Dohyun; Park, Sung-Ho

2016-11-01

Recently, Doppler ultrasound has been used for the measurement of pulpal blood flow in human teeth. However, the reliability of this method has not been verified. In this study, we developed a model to simulate arteriole blood flow within the dental pulp by using microfluidics. This arteriole simulator, or flow phantom, was used to determine the reliability of measurements obtained by using a Doppler ultrasound device. A microfluidic chip was fabricated by using the soft lithography technique, and blood-mimicking fluid was pumped through the channel by a microfluidic system. A Doppler ultrasound device was used for the measurement of flow velocity. The peak, mean, and minimal flow velocities obtained from the phantom and the Doppler ultrasound device were compared by using linear regression analysis and Pearson correlation coefficient. Bland-Altman analyses were performed to evaluate the velocity differences between the flow generated by the phantom and the flow measurements made with the Doppler ultrasound device. The microfluidic system was able to generate the flow profiles as intended, and the fluid flow could be monitored and controlled by the software program. There were excellent linear correlations between the peak, mean, and minimal flow velocities of the phantom and those of the Doppler ultrasound device (r = 0.94-0.996, P < .001). However, the velocities were overestimated by the Doppler ultrasound device. This phantom provides opportunities for research and education involving the Doppler ultrasound technique in dentistry. Although Doppler ultrasound can be an effective tool for the measurement of pulpal blood flow velocity, it is essential to validate and calibrate the device before clinical use. Copyright © 2016 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

3D printed Lego®-like modular microfluidic devices based on capillary driving.

PubMed

Nie, Jing; Gao, Qing; Qiu, Jing-Jiang; Sun, Miao; Liu, An; Shao, Lei; Fu, Jian-Zhong; Zhao, Peng; He, Yong

2018-03-12

The field of how to rapidly assemble microfluidics with modular components continuously attracts researchers' attention, however, extra efforts must be devoted to solving the problems of leaking and aligning between individual modules. This paper presents a novel type of modular microfluidic device, driven by capillary force. There is no necessity for a strict seal or special alignment, and its open structures make it easy to integrate various stents and reactants. The key rationale for this method is to print different functional modules with a low-cost three-dimensional (3D) printer, then fill the channels with capillary materials and assemble them with plugs like Lego ® bricks. This rapidly reconstructed modular microfluidic device consists of a variety of common functional modules and other personalized modules, each module having a unified standard interface for easy assembly. As it can be printed by a desktop 3D printer, the manufacturing process is simple and efficient, with controllable regulation of the flow channel scale. Through diverse combinations of different modules, a variety of different functions can be achieved, without duplicating the manufacturing process. A single module can also be taken out for testing and analysis. What's more, combined with basic circuit components, it can serve as a low-cost Lego ® -like modular microfluidic circuits. As a proof of concept, the modular microfluidic device has been successfully demonstrated and used for stent degradation and cell cultures, revealing the potential use of this method in both chemical and biological research.

Microfluidic optoelectronic sensor for salivary diagnostics of stomach cancer.

PubMed

Zilberman, Yael; Sonkusale, Sameer R

2015-05-15

We present a microfluidic optoelectronic sensor for saliva diagnostics with a potential application for non-invasive early diagnosis of stomach cancer. Stomach cancer is the second most common cause of cancer-related deaths in the world. The primary identified cause is infection by a gram-negative bacterium Helicobacter pylori. These bacteria secrete the enzyme urease that converts urea into carbon dioxide (CO2) and ammonia (NH3), leading to their elevated levels in breath and body fluids. The proposed optoelectronic sensor will detect clinically relevant levels of CO2 and NH3 in saliva that can potentially be used for early diagnosis of stomach cancer. The sensor is composed of the embedded in a microfluidic device array of microwells filled with ion-exchange polymer microbeads doped with various organic dyes. The optical response of this unique highly diverse sensor is monitored over a broad spectrum, which provides a platform for cross-reactive sensitivity and allows detection of CO2 and NH3 in saliva at ppm levels. Copyright © 2014 Elsevier B.V. All rights reserved.

Microfluidic paper-based device for colorimetric determination of glucose based on a metal-organic framework acting as peroxidase mimetic.

PubMed

Ortiz-Gómez, Inmaculada; Salinas-Castillo, Alfonso; García, Amalia García; Álvarez-Bermejo, José Antonio; de Orbe-Payá, Ignacio; Rodríguez-Diéguez, Antonio; Capitán-Vallvey, Luis Fermín

2017-12-13

This work presents a microfluidic paper-based analytical device (μPAD) for glucose determination using a supported metal-organic framework (MOF) acting as a peroxidase mimic. The catalytic action of glucose oxidase (GOx) on glucose causes the formation of H 2 O 2 , and the MOF causes the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) by H 2 O 2 to form a blue-green product with an absorption peak at 650 nm in the detection zone. A digital camera and the iOS feature of a smartphone are used for the quantitation of glucose with the S coordinate of the HSV color space as the analytical parameter. Different factors such as the concentration of TMB, GOx and MOF, pH and buffer, sample volume, reaction time and reagent position in the μPAD were optimized. Under optimal conditions, the value for the S coordinate increases linearly up to 150 μmol·L -1 glucose concentrations, with a 2.5 μmol·L -1 detection limit. The μPAD remains stable for 21 days under conventional storage conditions. Such an enzyme mimetic-based assay to glucose determination using Fe-MIL-101 MOF implemented in a microfluidic paper-based device possesses advantages over enzyme-based assays in terms of costs, durability and stability compared to other existing glucose determination methods. The procedure was applied to the determination of glucose in (spiked) serum and urine. Graphical abstract Schematic representation of microfluidic paper-based analytical device using metal-organic framework as a peroxidase mimic for colorimetric glucose detection with digital camera or smartphone and iOS app readout.

Microfabrication and Test of a Three-Dimensional Polymer Hydro-focusing Unit for Flow Cytometry Applications

NASA Technical Reports Server (NTRS)

Yang, Ren; Feeback, Daniel L.; Wang, Wan-Jun

2005-01-01

This paper details a novel three-dimensional (3D) hydro-focusing micro cell sorter for micro flow cytometry applications. The unit was microfabricated by means of SU-8 3D lithography. The 3D microstructure for coaxial sheathing was designed, microfabricated, and tested. Three-dimensional hydrofocusing capability was demonstrated with an experiment to sort labeled tanned sheep erythrocytes (red blood cells). This polymer hydro-focusing microstructure is easily microfabricated and integrated with other polymer microfluidic structures. Keywords: SU-8, three-dimensional hydro-focusing, microfluidic, microchannel, cytometer

Acoustic force measurements on polymer-coated microbubbles in a microfluidic device

PubMed Central

Memoli, Gianluca; Fury, Christopher R.; Baxter, Kate O.; Gélat, Pierre N.; Jones, Philip H.

2017-01-01

This work presents an acoustofluidic device for manipulating coated microbubbles, designed for the simultaneous use of optical and acoustical tweezers. A comprehensive characterization of the acoustic pressure in the device is presented, obtained by the synergic use of different techniques in the range of acoustic frequencies where visual observations showed aggregation of polymer-coated microbubbles. In absence of bubbles, the combined use of laser vibrometry and finite element modelling supported a non-invasive measurement of the acoustic pressure and an enhanced understanding of the system resonances. Calibrated holographic optical tweezers were used for direct measurements of the acoustic forces acting on an isolated microbubble, at low driving pressures, and to confirm the spatial distribution of the acoustic field. This allowed quantitative acoustic pressure measurements by particle tracking, using polystyrene beads, and an evaluation of the related uncertainties. This process facilitated the extension of tracking to microbubbles, which have a negative acoustophoretic contrast factor, allowing acoustic force measurements on bubbles at higher pressures than optical tweezers, highlighting four peaks in the acoustic response of the device. Results and methodologies are relevant to acoustofluidic applications requiring a precise characterization of the acoustic field and, in general, to biomedical applications with microbubbles or deformable particles. PMID:28599556

Microfluidic bead-based diodes with targeted circular microchannels for low Reynolds number applications.

PubMed

Sochol, Ryan D; Lu, Albert; Lei, Jonathan; Iwai, Kosuke; Lee, Luke P; Lin, Liwei

2014-05-07

Self-regulating fluidic components are critical to the advancement of microfluidic processors for chemical and biological applications, such as sample preparation on chip, point-of-care molecular diagnostics, and implantable drug delivery devices. Although researchers have developed a wide range of components to enable flow rectification in fluidic systems, engineering microfluidic diodes that function at the low Reynolds number (Re) flows and smaller scales of emerging micro/nanofluidic platforms has remained a considerable challenge. Recently, researchers have demonstrated microfluidic diodes that utilize high numbers of suspended microbeads as dynamic resistive elements; however, using spherical particles to block fluid flow through rectangular microchannels is inherently limited. To overcome this issue, here we present a single-layer microfluidic bead-based diode (18 μm in height) that uses a targeted circular-shaped microchannel for the docking of a single microbead (15 μm in diameter) to rectify fluid flow under low Re conditions. Three-dimensional simulations and experimental results revealed that adjusting the docking channel geometry and size to better match the suspended microbead greatly increased the diodicity (Di) performance. Arraying multiple bead-based diodes in parallel was found to adversely affect system efficacy, while arraying multiple diodes in series was observed to enhance device performance. In particular, systems consisting of four microfluidic bead-based diodes with targeted circular-shaped docking channels in series revealed average Di's ranging from 2.72 ± 0.41 to 10.21 ± 1.53 corresponding to Re varying from 0.1 to 0.6.

One-Step Optogenetics with Multifunctional Flexible Polymer Fibers

PubMed Central

Park, Seongjun; Guo, Yuanyuan; Jia, Xiaoting; Choe, Han Kyoung; Grena, Benjamin; Kang, Jeewoo; Park, Jiyeon; Lu, Chi; Canales, Andres; Chen, Ritchie; Yim, Yeong Shin; Choi, Gloria B.; Fink, Yoel; Anikeeva, Polina

2017-01-01

Optogenetic interrogation of neural pathways relies on delivery of light-sensitive opsins into tissue and subsequent optical illumination and electrical recording from the regions of interest. Despite the recent development of multifunctional neural probes, integration of these modalities within a single biocompatible platform remains a challenge. Here, we introduce a device composed of an optical waveguide, six electrodes, and two microfluidic channels produced via fiber drawing. Our probes facilitated injections of viral vectors carrying opsin genes, while providing collocated neural recording and optical stimulation. The miniature (< 200 μm) footprint and modest weight (<0.5 g) of these probes allowed for multiple implantations into the mouse brain, which enabled opto-electrophysiological investigation of projections from the basolateral amygdala to the medial prefrontal cortex and ventral hippocampus during behavioral experiments. Fabricated solely from polymers and polymer composites, these flexible probes minimized tissue response to achieve chronic multimodal interrogation of brain circuits with high fidelity. PMID:28218915

Elastic instability in stratified core annular flow.

PubMed

Bonhomme, Oriane; Morozov, Alexander; Leng, Jacques; Colin, Annie

2011-06-01

We study experimentally the interfacial instability between a layer of dilute polymer solution and water flowing in a thin capillary. The use of microfluidic devices allows us to observe and quantify in great detail the features of the flow. At low velocities, the flow takes the form of a straight jet, while at high velocities, steady or advected wavy jets are produced. We demonstrate that the transition between these flow regimes is purely elastic--it is caused by the viscoelasticity of the polymer solution only. The linear stability analysis of the flow in the short-wave approximation supplemented with a kinematic criterion captures quantitatively the flow diagram. Surprisingly, unstable flows are observed for strong velocities, whereas convected flows are observed for low velocities. We demonstrate that this instability can be used to measure the rheological properties of dilute polymer solutions that are difficult to assess otherwise.

Effects of Hofmeister Anions on the LCST of PNIPAM as a Function of Molecular Weight

PubMed Central

Zhang, Yanjie; Furyk, Steven; Sagle, Laura B.; Cho, Younhee; Bergbreiter, David E.; Cremer, Paul S.

2008-01-01

The effect of a series of sodium salts on the lower critical solution temperature (LCST) of poly(N-isopropylacrylamide), PNIPAM, was investigated as a function of molecular weight and polymer concentration with a temperature gradient microfluidic device under a dark-field microscope. In solutions containing sufficient concentrations of kosmotropic anions, the phase transition of PNIPAM was resolved into two separate steps for higher molecular weight samples. The first step of this two step transition was found to be sensitive to the polymer’s molecular weight and solution concentration, while the second step was not. Moreover, the binding of chaotropic anions to the polymer was also influenced by molecular weight. Both sets of results could be explained by the formation of intramolecular and intermolecular hydrogen-bonding between polymer chains. By contrast, the hydrophobic hydration of the isopropyl moieties and polymer backbone was found to be unaffected by either the polymer’s molecular weight or solution concentration. PMID:18820735

Microfluidics meets metabolomics to reveal the impact of Campylobacter jejuni infection on biochemical pathways.

PubMed

Mortensen, Ninell P; Mercier, Kelly A; McRitchie, Susan; Cavallo, Tammy B; Pathmasiri, Wimal; Stewart, Delisha; Sumner, Susan J

2016-06-01

Microfluidic devices that are currently being used in pharmaceutical research also have a significant potential for utilization in investigating exposure to infectious agents. We have established a microfluidic device cultured with Caco-2 cells, and utilized metabolomics to investigate the biochemical responses to the bacterial pathogen Campylobacter jejuni. In the microfluidic devices, Caco-2 cells polarize at day 5, are uniform, have defined brush borders and tight junctions, and form a mucus layer. Metabolomics analysis of cell culture media collected from both Caco-2 cell culture systems demonstrated a more metabolic homogenous biochemical profile in the media collected from microfluidic devices, compared with media collected from transwells. GeneGo pathway mapping indicated that aminoacyl-tRNA biosynthesis was perturbed by fluid flow, suggesting that fluid dynamics and shear stress impacts the cells translational quality control. Both microfluidic device and transwell culturing systems were used to investigate the impact of Campylobacter jejuni infection on biochemical processes. Caco-2 cells cultured in either system were infected at day 5 with C. jejuni 81-176 for 48 h. Metabolomics analysis clearly differentiated C. jejuni 81-176 infected and non-infected medias collected from the microfluidic devices, and demonstrated that C. jejuni 81-176 infection in microfluidic devices impacts branched-chain amino acid metabolism, glycolysis, and gluconeogenesis. In contrast, no distinction was seen in the biochemical profiles of infected versus non-infected media collected from cells cultured in transwells. Microfluidic culturing conditions demonstrated a more metabolically homogenous cell population, and present the opportunity for studying host-pathogen interactions for extended periods of time.

Microfluidics Meets Metabolomics to Reveal the Impact of Campylobacter jejuni Infection on Biochemical Pathways

PubMed Central

Mortensen, Ninell P.; Mercier, Kelly A.; McRitchie, Susan; Cavallo, Tammy B.; Pathmasiri, Wimal; Stewart, Delisha; Sumner, Susan J.

2016-01-01

Microfluidic devices that are currently being used in pharmaceutical research also have a significant potential for utilization in investigating exposure to infectious agents. We have established a microfluidic device cultured with Caco-2 cells, and utilized metabolomics to investigate the biochemical responses to the bacterial pathogen Campylobacter jejuni. In the microfluidic devices, Caco-2 cells polarize at day 5, are uniform, have defined brush borders and tight junctions, and form a mucus layer. Metabolomics analysis of cell culture media collected from both Caco-2 cell culture systems demonstrated a more metabolic homogenous biochemical profile in the media collected from microfluidic devices, compared with media collected from transwells. GeneGo pathway mapping indicated that aminoacyl-tRNA biosynthesis was perturbed by fluid flow, suggesting that fluid dynamics and shear stress impacts the cells translational quality control. Both microfluidic device and transwell culturing systems were used to investigate the impact of Campylobacter jejuni infection on biochemical processes. Caco-2 cells cultured in either system were infected at day 5 with C. jejuni 81-176 for 48 hours. Metabolomics analysis clearly differentiated C. jejuni 81-176 infected and non-infected medias collected from the microfluidic devices, and demonstrated that C. jejuni 81-176 infection in microfluidic devices impacts branched-chain amino acid metabolism, glycolysis, and gluconeogenesis. In contrast, no distinction was seen in the biochemical profiles of infected versus non-infected media collected from cells cultured in transwells. Microfluidic culturing conditions demonstrated a more metabolically homogenous cell population, and present the opportunity for studying host-pathogen interactions for extended periods of time. PMID:27231016

Microfluidic Devices in Advanced Caenorhabditis elegans Research.

PubMed

Muthaiyan Shanmugam, Muniesh; Subhra Santra, Tuhin

2016-08-02

The study of model organisms is very important in view of their potential for application to human therapeutic uses. One such model organism is the nematode worm, Caenorhabditis elegans. As a nematode, C. elegans have ~65% similarity with human disease genes and, therefore, studies on C. elegans can be translated to human, as well as, C. elegans can be used in the study of different types of parasitic worms that infect other living organisms. In the past decade, many efforts have been undertaken to establish interdisciplinary research collaborations between biologists, physicists and engineers in order to develop microfluidic devices to study the biology of C. elegans. Microfluidic devices with the power to manipulate and detect bio-samples, regents or biomolecules in micro-scale environments can well fulfill the requirement to handle worms under proper laboratory conditions, thereby significantly increasing research productivity and knowledge. The recent development of different kinds of microfluidic devices with ultra-high throughput platforms has enabled researchers to carry out worm population studies. Microfluidic devices primarily comprises of chambers, channels and valves, wherein worms can be cultured, immobilized, imaged, etc. Microfluidic devices have been adapted to study various worm behaviors, including that deepen our understanding of neuromuscular connectivity and functions. This review will provide a clear account of the vital involvement of microfluidic devices in worm biology.

Microfluidic cell culture systems for drug research.

PubMed

Wu, Min-Hsien; Huang, Song-Bin; Lee, Gwo-Bin

2010-04-21

In pharmaceutical research, an adequate cell-based assay scheme to efficiently screen and to validate potential drug candidates in the initial stage of drug discovery is crucial. In order to better predict the clinical response to drug compounds, a cell culture model that is faithful to in vivo behavior is required. With the recent advances in microfluidic technology, the utilization of a microfluidic-based cell culture has several advantages, making it a promising alternative to the conventional cell culture methods. This review starts with a comprehensive discussion on the general process for drug discovery and development, the role of cell culture in drug research, and the characteristics of the cell culture formats commonly used in current microfluidic-based, cell-culture practices. Due to the significant differences in several physical phenomena between microscale and macroscale devices, microfluidic technology provides unique functionality, which is not previously possible by using traditional techniques. In a subsequent section, the niches for using microfluidic-based cell culture systems for drug research are discussed. Moreover, some critical issues such as cell immobilization, medium pumping or gradient generation in microfluidic-based, cell-culture systems are also reviewed. Finally, some practical applications of microfluidic-based, cell-culture systems in drug research particularly those pertaining to drug toxicity testing and those with a high-throughput capability are highlighted.

Improving Sample Distribution Homogeneity in Three-Dimensional Microfluidic Paper-Based Analytical Devices by Rational Device Design.

PubMed

Morbioli, Giorgio Gianini; Mazzu-Nascimento, Thiago; Milan, Luis Aparecido; Stockton, Amanda M; Carrilho, Emanuel

2017-05-02

Paper-based devices are a portable, user-friendly, and affordable technology that is one of the best analytical tools for inexpensive diagnostic devices. Three-dimensional microfluidic paper-based analytical devices (3D-μPADs) are an evolution of single layer devices and they permit effective sample dispersion, individual layer treatment, and multiplex analytical assays. Here, we present the rational design of a wax-printed 3D-μPAD that enables more homogeneous permeation of fluids along the cellulose matrix than other existing designs in the literature. Moreover, we show the importance of the rational design of channels on these devices using glucose oxidase, peroxidase, and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) reactions. We present an alternative method for layer stacking using a magnetic apparatus, which facilitates fluidic dispersion and improves the reproducibility of tests performed on 3D-μPADs. We also provide the optimized designs for printing, facilitating further studies using 3D-μPADs.

Carbon nanoparticle doped micro-patternable nano-composites for wearable sensing applications (Conference Presentation)

NASA Astrophysics Data System (ADS)

Khosla, Ajit

2017-04-01

This talk focuses on preparation, characterization and micropatterning of electrically conducting KETJENBLACK carbon black nanoparticle (80 nm-diameter) doped Polydimethylsiloxane (PDMS) by employing extrusion mixing. Previously, we had reported fabrication of various micropatternable nanocomposites for wearable sensing applications vis solvent assisted ultrasonic mixing technique[1-16] . Extrusion mixing has an advantage as no organic solvents are used and homogenous dispersion of carbon nanoparticles is observed, which is confirmed by SEM analysis. The developed nanocomposite can be micropatterened using standard microfabrication techniques. It is also observed that percolation threshold occurs at 0.51 wt% of carbon nanoparticles in polymer matrix. Examples of developed nano-composites for wearable sensing applications for precision medicine will also be discussed. References: 1.http://summit.sfu.ca/item/12017 A. Khosla. Micropatternable multifunctional nanocomposite polymers for flexible soft MEMS applications. Diss. Applied Science: School of Engineering Science, 2011. 2. A. Khosla ; B. L. Gray; Fabrication of multiwalled carbon nanotube polydimethylsiloxne nanocomposite polymer flexible microelectrodes for microfluidics and MEMS. Proc. SPIE 7642, Electroactive Polymer Actuators and Devices (EAPAD) 2010, 76421V (April 09, 2010); doi:10.1117/12.847292. 3. Ang Li ; Ajit Khosla ; Connie Drewbrook ; Bonnie L. Gray; Fabrication and testing of thermally responsive hydrogel-based actuators using polymer heater elements for flexible microvalves. Proc. SPIE 7929, Microfluidics, BioMEMS, and Medical Microsystems IX, 79290G (February 14, 2011); doi:10.1117/12.873197. 4. Khosla, A. and Gray, B. L. (2010), Preparation, Micro-Patterning and Electrical Characterization of Functionalized Carbon-Nanotube Polydimethylsiloxane Nanocomposite Polymer. Macromol. Symp., 297: 210-218. doi:10.1002/masy.200900165 5. A. Khosla ; D. Hilbich ; C. Drewbrook ; D. Chung ; B. L. Gray; Large scale micropatterning of multi-walled carbon nanotube/polydimethylsiloxane nanocomposite polymer on highly flexible 12×24 inch substrates. Proc. SPIE 7926, Micromachining and Microfabrication Process Technology XVI, 79260L (February 15, 2011); doi:10.1117/12.876738. 6. A. Khosla, and Bonnie L. Gray. "(Invited) Micropatternable Multifunctional Nanocomposite Polymers for Flexible Soft NEMS and MEMS Applications." ECS Transactions 45.3 (2012): 477-494. doi: 10.1149/1.3700913 7. Khosla, Ajit. "Nanoparticle-doped electrically-conducting polymers for flexible nano-micro Systems." Electrochemical Society Interface 21.3-4 (2012): 67-70. 8. Ajit Khosla; Smart garments in chronic disease management: progress and challenges. Proc. SPIE 8548, Nanosystems in Engineering and Medicine, 85482O (October 24, 2012); doi:10.1117/12.979667. 9. D. Chung ; A. Khosla ; B. L. Gray; Screen printable flexible conductive nanocomposite polymer with applications to wearable sensors. Proc. SPIE 9060, Nanosensors, Biosensors, and Info-Tech Sensors and Systems 2014, 90600U (April 16, 2014); doi:10.1117/12.2046548. 10. Daehan Chung ; Sam Seyfollahi ; Ajit Khosla ; Bonnie Gray ; Ash Parameswaran ; Ramani Ramaseshan ; Kirpal Kohli; Initial experiments with flexible conductive electrodes for potential applications in cancer tissue screening. Proc. SPIE 7929, Microfluidics, BioMEMS, and Medical Microsystems IX, 79290Z (February 14, 2011); doi:10.1117/12.875563. 11. A. Khosla ; B. L. Gray; New technologies for large-scale micropatterning of functional nanocomposite polymers. Proc. SPIE 8344, Nanosensors, Biosensors, and Info-Tech Sensors and Systems 2012, 83440W (April 26, 2012); doi:10.1117/12.915178. 12. A. Khosla, B.L. Gray, Preparation, characterization and micromolding of multi-walled carbon nanotube polydimethylsiloxane conducting nanocomposite polymer, Materials Letters, Volume 63, Issues 13-14, 31 May 2009, Pages 1203-1206, ISSN 0167-577X, http://dx.doi.org/10.1016/j.matlet.2009.02.043. 13. Giassa, M., Khosla, A., Gray, B. et al. J Electron Test (2010) 26: 139. doi:10.1007/s10836-009-5125-3 14.Ozhikandathil, Jayan, Ajit Khosla, and Muthukumaran Packirisamy. "Electrically Conducting PDMS Nanocomposite Using In Situ Reduction of Gold Nanostructures and Mechanical Stimulation of Carbon Nanotubes and Silver Nanoparticles." ECS Journal of Solid State Science and Technology 4.10 (2015): S3048-S3052. doi:10.1149/2.0091510jss 15. Kassegne, Sam, Maria Vomero, Roberto Gavuglio, Mieko Hirabayashi, Emre Özyilmaz, Sebastien Nguyen, Jesus Rodriguez, Eda Özyilmaz, Pieter van Niekerk, and Ajit Khosla. "Electrical impedance, electrochemistry, mechanical stiffness, and hardness tunability in glassy carbon MEMS μECoG electrodes." Microelectronic Engineering 133 (2015): 36-44. 16. A. Khosla ; B. L. Gray; Fabrication and properties of conductive micromoldable thermosetting polymer for electronic routing in highly flexible microfluidic systems. Proc. SPIE 7593, Microfluidics, BioMEMS, and Medical Microsystems VIII, 759314 (February 17, 2010); doi:10.1117/12.840911.

3D Printed Microfluidic Devices with Integrated Versatile and Reusable Electrodes

PubMed Central

Erkal, Jayda L.; Selimovic, Asmira; Gross, Bethany C.; Lockwood, Sarah Y.; Walton, Eric L.; McNamara, Stephen; Martin, R. Scott; Spence, Dana M.

2014-01-01

We report two 3D printed devices that can be used for electrochemical detection. In both cases, the electrode is housed in commercially available, polymer-based fittings so that the various electrode materials (platinum, platinum black, carbon, gold, silver) can be easily added to a threaded receiving port printed on the device; this enables a module-like approach to the experimental design, where the electrodes are removable and can be easily repolished for reuse after exposure to biological samples. The first printed device represents a microfluidic platform with a 500 × 500 μm channel and a threaded receiving port to allow integration of either polyetheretherketone (PEEK) nut-encased glassy carbon or platinum black (Pt-black) electrodes for dopamine and nitric oxide (NO) detection, respectively. The embedded 1 mm glassy carbon electrode had a limit of detection (LOD) of 500 nM for dopamine and a linear response (R2= 0.99) for concentrations between 25-500 μM. When the glassy carbon electrode was coated with 0.05% Nafion, significant exclusion of nitrite was observed when compared to signal obtained from equimolar injections of dopamine. When using flow injection analysis with a Pt/Pt-black electrode and standards derived from NO gas, a linear correlation (R2 = 0.99) over a wide range of concentrations (7.6 - 190 μM) was obtained, with the LOD for NO being 1 μM. The second application showcases a 3D printed fluidic device that allows collection of the biologically relevant analyte adenosine triphosphate (ATP) while simultaneously measuring the release stimulus (reduced oxygen concentration). The hypoxic sample (4.76 ± 0.53 ppm oxygen) released 2.37 ± 0.37 times more ATP than the normoxic sample (8.22 ± 0.60 ppm oxygen). Importantly, the results reported here verify the reproducible and transferable nature of using 3D printing as a fabrication technique, as devices and electrodes were moved between labs multiple times during completion of the study. PMID:24763966

[Fabrications of a poly (methyl methacrylate) (PMMA) microfluidic chip-based DNA analysis device].

PubMed

Du, Xiao-Guang

2009-12-01

A DNA analysis device based on poly(methyl methacrylate) (PMMA) microfluidic chips was developed. A PMMA chip with cross microchannels was fabricated by a simple hot embossing. Microchannels were modified with a static adsorptive coating method using 2% hydroxyethyl cellulose. A high-voltage power unit, variable in the range 0-1 800 V, was used for on-chip DNA sample injection and gel electrophoretic separation. High speed, high resolution DNA analysis was obtained with the home-built PMMA chip in a sieving matrix containing 2% hydroxyethyl cellulose with a blue intercalating dye, TO-PRO-3 (TP3), by using diode laser induced fluorescence detection based on optical fibers with a 670 nm long-pass filter. The DNA analysis device was applied for the separation of phiX-174/HaeIII DNA digest sample with 11 fragments ranging from 72 to 1 353 bp. A separation efficiency of 1.14 x 10(6) plates/m was obtained for the 603 bp fragments, while the R of 271/281 bp fragments was 1.2. The device was characterized by simple design, low cost for fabrication and operation, reusable PMMA chips, and good reproducibility. A portable microfluidic device for DNA analysis can be developed for clinical diagnosis and disease screening.

Development of droplet microfluidic platforms for the synthesis of monodisperse lipid vesicles and polymer particles

NASA Astrophysics Data System (ADS)

Teh, Shia-Yen

This body of work presents my approaches to the design and development of microfluidic platforms for synthesizing monodisperse polymer particles and phospholipid vesicles. There is interest in both of these particles for use in a variety of biomedical applications. Poly(D,L-lactide-co-glycolic acid) (PLGA) particles in particular have been sought out as vehicles for drug delivery due to their biocompatibility and because the rate of degradation -- hence cargo release - can be controlled. On the other hand, liposomes possess membrane structures resembling that of cells, an ability to adopt both hydrophilic and hydrophobic molecules, and are easily functionalized, which make lipid vesicles the ideal candidate for applications ranging from targeted therapeutic delivery to formation of artificial cells. However, current methods of production for both of these particles result in a wide range of sizes and poor cargo uptake efficiency. We address these challenges by utilizing a flow focusing droplet generation design, which allows for fine control over droplet size and improves encapsulation efficiencies. The size of these droplets can be determined by channel geometry and the ratio of fluid flow rates. I will discuss the work I have done to improve upon current technologies to form nano- to micrometer sized PLGA particles and cell-sized lipid vesicles. Solvent evaporation and solvent extraction methods were implemented and tested in several device designs to optimize the formation process. The particles produced were characterized for their stability, size variation, and ability to encapsulate a model drug. The release profiles of PLGA particles were also measured to determine the length of delivery. In addition, I worked on the generation of monodisperse lipid vesicles to investigate the application of liposomes as an artificial cell. As a proof of principle, expression of green fluorescent protein (GFP) was successfully carried out in the lipid vesicles. This demonstrates the versatility of the microfluidic device for generating a range of particles of controlled size for therapeutic agent delivery and artificial cell applications.

3D printed polymers toxicity profiling: a caution for biodevice applications

NASA Astrophysics Data System (ADS)

Zhu, Feng; Skommer, Joanna; Friedrich, Timo; Kaslin, Jan; Wlodkowic, Donald

2015-12-01

A recent revolution in additive manufacturing technologies and access to 3D Computer Assisted Design (CAD) software has spurred an explosive growth of new technologies in biomedical engineering. This includes biomodels for diagnosis, surgical training, hard and soft tissue replacement, biodevices and tissue engineering. Moreover, recent developments in high-definition additive manufacturing systems such as Multi-Jet Modelling (MJM) and Stereolithography (SLA), capable of reproducing feature sizes close to 100 μm, promise brand new capabilities in fabrication of optical-grade biomicrofluidic Lab-on-a-Chip and MEMS devices. Compared with other rapid prototyping technologies such as soft lithography and infrared laser micromachining in PMMA, SLA and MJM systems can enable user-friendly production of prototypes, superior feature reproduction quality and comparable levels of optical transparency. Prospectively they can revolutionize fabrication of microfluidic devices with complex geometric features and eliminate the need to use clean room environment and conventional microfabrication techniques. In this work we demonstrate preliminary data on toxicity profiling of a panel of common polymers used in 3D printing applications. The main motivation of our work was to evaluate toxicity profiles of most commonly used polymers using standardized biotests according to OECD guidelines for testing of chemic risk assessment. Our work for the first time provides a multispecies view of potential dangers and limitation for building biocompatible devices using FDM, SLA and MJM additive manufacturing systems. Our work shows that additive manufacturing holds significant promise for fabricating LOC and MEMS but requires caution when selecting systems and polymers due to toxicity exhibited by some 3D printing polymers.

Optimized Mixing in Microchannels with Integrated Microactuators

NASA Astrophysics Data System (ADS)

Folk, Christopher Richard

Microscale valves and pumps have been designed and fabricated for integration into a microfluidic circuit. Furthermore, a micromixer for this circuit has been designed and optimized. N-isopropylacrylamide (NIPA) gels have been fabricated and actuated directly with heat and indirectly by laser. A new method for photopatterning these gels based on photoinitiation has been used to fabricate hydrogel valves down to 50 mum in diameter. Hydrogel valves have been fabricated in situ in a microfluidic network. The valves open in 27 seconds and close via diffusion of water into the gel in 128 seconds, which is faster than other optically-driven polymers used for large displacements. In this research, azobis-isobutyronitrile (AIBN) is incorporated into a variety of polydimethylsiloxane (PDMS) pump chambers. The AIBN is heated via integrated resistive heaters and decomposes to release nitrogen gas. The nitrogen gas provides impulse power to a PDMS diaphragm to displace the fluid. The pump devices have been built and characterized. Lastly, in this work, we describe the use of combined fluid dynamic and diffusion modeling to simulate a micromixer based on the elements above. The micromixer is optimized via Design of Experiments to produce an optimized geometry for mixing. The optimization is validated via comparison to previous work through the Strouhal number.

A microfluidic platform for precision small-volume sample processing and its use to size separate biological particles with an acoustic microdevice [Precision size separation of biological particles in small-volume samples by an acoustic microfluidic system

DOE PAGES

Fong, Erika J.; Huang, Chao; Hamilton, Julie; ...

2015-11-23

Here, a major advantage of microfluidic devices is the ability to manipulate small sample volumes, thus reducing reagent waste and preserving precious sample. However, to achieve robust sample manipulation it is necessary to address device integration with the macroscale environment. To realize repeatable, sensitive particle separation with microfluidic devices, this protocol presents a complete automated and integrated microfluidic platform that enables precise processing of 0.15–1.5 ml samples using microfluidic devices. Important aspects of this system include modular device layout and robust fixtures resulting in reliable and flexible world to chip connections, and fully-automated fluid handling which accomplishes closed-loop sample collection,more » system cleaning and priming steps to ensure repeatable operation. Different microfluidic devices can be used interchangeably with this architecture. Here we incorporate an acoustofluidic device, detail its characterization, performance optimization, and demonstrate its use for size-separation of biological samples. By using real-time feedback during separation experiments, sample collection is optimized to conserve and concentrate sample. Although requiring the integration of multiple pieces of equipment, advantages of this architecture include the ability to process unknown samples with no additional system optimization, ease of device replacement, and precise, robust sample processing.« less

Geometric effects in microfluidics on heterogeneous cell stress using an Eulerian-Lagrangian approach.

PubMed

Warren, K M; Mpagazehe, J N; LeDuc, P R; Higgs, C F

2016-02-07

The response of individual cells at the micro-scale in cell mechanics is important in understanding how they are affected by changing environments. To control cell stresses, microfluidics can be implemented since there is tremendous control over the geometry of the devices. Designing microfluidic devices to induce and manipulate stress levels on biological cells can be aided by computational modeling approaches. Such approaches serve as an efficient precursor to fabricating various microfluidic geometries that induce predictable levels of stress on biological cells, based on their mechanical properties. Here, a three-dimensional, multiphase computational fluid dynamics (CFD) modeling approach was implemented for soft biological materials. The computational model incorporates the physics of the particle dynamics, fluid dynamics and solid mechanics, which allows us to study how stresses affect the cells. By using an Eulerian-Lagrangian approach to treat the fluid domain as a continuum in the microfluidics, we are conducting studies of the cells' movement and the stresses applied to the cell. As a result of our studies, we were able to determine that a channel with periodically alternating columns of obstacles was capable of stressing cells at the highest rate, and that microfluidic systems can be engineered to impose heterogenous cell stresses through geometric configuring. We found that when using controlled geometries of the microfluidics channels with staggered obstructions, we could increase the maximum cell stress by nearly 200 times over cells flowing through microfluidic channels with no obstructions. Incorporating computational modeling in the design of microfluidic configurations for controllable cell stressing could help in the design of microfludic devices for stressing cells such as cell homogenizers.

Portable microfluidic and smartphone-based devices for monitoring of cardiovascular diseases at the point of care.

PubMed

Hu, Jie; Cui, Xingye; Gong, Yan; Xu, Xiayu; Gao, Bin; Wen, Ting; Lu, Tian Jian; Xu, Feng

2016-01-01

Cardiovascular diseases (CVDs) are the main causes of morbidity and mortality in the world where about 4 in every 5 CVD deaths happen in low- and middle-income countries (LMICs). Most CVDs are preventable and curable, which is largely dependent on timely and effective interventions, including diagnosis, prognosis and therapeutic monitoring. However, these interventions are high-cost in high income countries and are usually lacking in LMICs. Thanks to the rapid development of microfluidics and nanotechnology, lots of portable analytical devices are developed for detection of CVDs at the point-of-care (POC). In the meantime, smartphone, as a versatile and powerful handheld tool, has been employed not only as a reader for microfluidic assays, but also as an analyzer for physiological indexes. In this review, we present a comprehensive introduction of the current status and potential development direction on POC diagnostics for CVDs. First of all, we introduce some main facts about CVDs and their standard diagnostic procedures and methods. Second, we discuss about both commercially available POC devices and developed prototypes for detection of CVDs via immunoassays. Subsequently, we report the advances in smartphone-based readout for microfluidic assays. Finally, we present some examples using smartphone, individually or combined with other components or devices, for CVD monitoring. We envision an integrated smartphone-based system capable of functioning blood tests, disease examination, and imaging will come in the future. Copyright © 2016 Elsevier Inc. All rights reserved.

Tapered Microfluidic for Continuous Micro-Object Separation Based on Hydrodynamic Principle.

PubMed

Ahmad, Ida Laila; Ahmad, Mohd Ridzuan; Takeuchi, Masaru; Nakajima, Masahiro; Hasegawa, Yasuhisa

2017-12-01

Recent advances in microfluidic technologies have created a demand for a simple and efficient separation intended for various applications such as food industries, biological preparation, and medical diagnostic. In this paper, we report a tapered microfluidic device for passive continuous separation of microparticles by using hydrodynamic separation. By exploiting the hydrodynamic properties of the fluid flow and physical characteristics of micro particles, effective size based separation is demonstrated. The tapered microfluidic device has widening geometries with respect to specific taper angle which amplify the sedimentation effect experienced by particles of different sizes. A mixture of 3-μm and 10-μm polystyrene microbeads are successfully separated using 20° and 25° taper angles. The results obtained are in agreement with three-dimensional finite element simulation conducted using Abaqus 6.12. Moreover, the feasibility of this mechanism for biological separation is demonstrated by using polydisperse samples consists of 3-μm polystyrene microbeads and human epithelial cervical carcinoma (HeLa) cells. 98% of samples purity is recovered at outlet 1 and outlet 3 with flow rate of 0.5-3.0 μl/min. Our device is interesting despite adopting passive separation approach. This method enables straightforward, label-free, and continuous separation of multiparticles in a stand-alone device without the need for bulky apparatus. Therefore, this device may become an enabling technology for point of care diagnosis tools and may hold potential for micrototal analysis system applications.

Fundamentals of microfluidics for high school students with no prior knowledge of fluid mechanics.

PubMed

Tandon, Vishal; Peck, Walter

2013-01-01

Three microfluidics-based laboratory exercises were developed and implemented in a high school science classroom setting. The first exercise demonstrated ways in which flows are characterized, including viscosity, turbulence, shear stress, reversibility, compressibility, and hydrodynamic resistance. Students characterized flows in poly(dimethylsiloxane) microfluidic devices in the other two exercises, where they observed the mixing characteristics of laminar flows, and conservation of volumetric flow rate for incompressible flows. In surveys, the students self-reported increased knowledge of microfluidics, and an improved attitude toward science and nanotechnology.

Behaviour and design considerations for continuous flow closed-open-closed liquid microchannels.

PubMed

Melin, Jessica; van der Wijngaart, Wouter; Stemme, Göran

2005-06-01

This paper introduces a method of combining open and closed microchannels in a single component in a novel way which couples the benefits of both open and closed microfluidic systems and introduces interesting on-chip microfluidic behaviour. Fluid behaviour in such a component, based on continuous pressure driven flow and surface tension, is discussed in terms of cross sectional flow behaviour, robustness, flow-pressure performance, and its application to microfluidic interfacing. The closed-open-closed microchannel possesses the versatility of upstream and downstream closed microfluidics along with open fluidic direct access. The device has the advantage of eliminating gas bubbles present upstream when these enter the open channel section. The unique behaviour of this device opens the door to applications including direct liquid sample interfacing without the need for additional and bulky sample tubing.

3D-printed Microfluidic Devices: Fabrication, Advantages and Limitations—a Mini Review

PubMed Central

Chen, Chengpeng; Mehl, Benjamin T.; Munshi, Akash S.; Townsend, Alexandra D.; Spence, Dana M.; Martin, R. Scott

2016-01-01

A mini-review with 79 references. In this review, the most recent trends in 3D-printed microfluidic devices are discussed. In addition, a focus is given to the fabrication aspects of these devices, with the supplemental information containing detailed instructions for designing a variety of structures including: a microfluidic channel, threads to accommodate commercial fluidic fittings, a flow splitter; a well plate, a mold for PDMS channel casting; and how to combine multiple designs into a single device. The advantages and limitations of 3D-printed microfluidic devices are thoroughly discussed, as are some future directions for the field. PMID:27617038

3D-printed Microfluidic Devices: Fabrication, Advantages and Limitations-a Mini Review.

PubMed

Chen, Chengpeng; Mehl, Benjamin T; Munshi, Akash S; Townsend, Alexandra D; Spence, Dana M; Martin, R Scott

2016-08-21

A mini-review with 79 references. In this review, the most recent trends in 3D-printed microfluidic devices are discussed. In addition, a focus is given to the fabrication aspects of these devices, with the supplemental information containing detailed instructions for designing a variety of structures including: a microfluidic channel, threads to accommodate commercial fluidic fittings, a flow splitter; a well plate, a mold for PDMS channel casting; and how to combine multiple designs into a single device. The advantages and limitations of 3D-printed microfluidic devices are thoroughly discussed, as are some future directions for the field.

Resolution improvement of 3D stereo-lithography through the direct laser trajectory programming: Application to microfluidic deterministic lateral displacement device.

PubMed

Juskova, Petra; Ollitrault, Alexis; Serra, Marco; Viovy, Jean-Louis; Malaquin, Laurent

2018-02-13

The vast majority of current microfluidic devices are produced using soft lithography, a technique with strong limitations regarding the fabrication of three-dimensional architectures. Additive manufacturing holds great promises to overcome these limitations, but conventional machines still lack the resolution required by most microfluidic applications. 3D printing machines based on two-photon lasers, in contrast, have the needed resolution but are too limited in speed and size of the global device. Here we demonstrate how the resolution of conventional stereolithographic machines can be improved by a direct programming of the laser path and can contribute to bridge the gap between the two above technologies, allowing the direct printing of features between 10 and 100 μm, corresponding to a large fraction of microfluidic applications. This strategy allows to achieve resolutions limited only by the physical size of the laser beam, decreasing by a factor at least 2× the size of the smallest features printable, and increasing their reproducibility by a factor 5. The approach was applied to produce an open microfluidic device with the reversible seal, integrating periodical patterns using the simple motifs, and validated by the fabrication of a deterministic lateral displacement particles sorting device. The sorting of polystyrene beads (diameter: 20 μm and 45 μm) was achieved with a specificity >95%, comparable with that achieved with arrays prepared by microlithography. Copyright © 2017 Elsevier B.V. All rights reserved.

Microfluidics-to-Mass Spectrometry: A review of coupling methods and applications

PubMed Central

Wang, Xue; Yi, Lian; Mukhitov, Nikita; Schrell, Adrian M.; Dhumpa, Raghuram; Roper, Michael G.

2014-01-01

Microfluidic devices offer great advantages in integrating sample processes, minimizing sample and reagent volumes, and increasing analysis speed, while mass spectrometry detection provides high information content, is sensitive, and can be used in quantitative analyses. The coupling of microfluidic devices to mass spectrometers is becoming more common with the strengths of both systems being combined to analyze precious and complex samples. This review summarizes select achievements published between 2010 – July 2014 in novel coupling between microfluidic devices and mass spectrometers. The review is subdivided by the types of ionization sources employed, and the different microfluidic systems used. PMID:25458901

Fabrication, Metrology, and Transport Characteristics of Single Polymeric Nanopores in Three-Dimensional Hybrid Microfluidic/Nanofluidic Devices

ERIC Educational Resources Information Center

King, Travis L.

2009-01-01

The incorporation of nanofluidic elements between microfluidic channels to form hybrid microfluidic/nanofluidic architectures allows the extension of microfluidic systems into the third dimension, thus removing the constraints imposed by planarity. Measuring and understanding the behavior of these devices creates new analytical challenges due to…

In vitro development of donated frozen-thawed human embryos in a prototype static microfluidic device: a randomized controlled trial.

PubMed

Kieslinger, Dorit C; Hao, Zhenxia; Vergouw, Carlijn G; Kostelijk, Elisabeth H; Lambalk, Cornelis B; Le Gac, Séverine

2015-03-01

To compare the development of human embryos in microfluidic devices with culture in standard microdrop dishes, both under static conditions. Prospective randomized controlled trial. In vitro fertilization laboratory. One hundred eighteen donated frozen-thawed human day-4 embryos. Random allocation of embryos that fulfilled the inclusion criteria to single-embryo culture in a microfluidics device (n = 58) or standard microdrop dish (n = 60). Blastocyst formation rate and quality after 24, 28, 48, and 72 hours of culture. The percentage of frozen-thawed day-4 embryos that developed to the blastocyst stage did not differ significantly in the standard microdrop dishes and microfluidic devices after 28 hours of culture (53.3% vs. 58.6%) or at any of the other time points. The proportion of embryos that would have been suitable for embryo transfer was comparable after 28 hours of culture in the control dishes and microfluidic devices (90.0% vs. 93.1%). Furthermore, blastocyst quality was similar in the two study groups. This study shows that a microfluidic device can successfully support human blastocyst development in vitro under static culture conditions. Future studies need to clarify whether earlier stage embryos will benefit from the culture in microfluidic devices more than the tested day-4 embryos because many important steps in the development of human embryos already take place before day 4. Further improvements of the microfluidic device will include parallel culture of single embryos, application of medium refreshment, and built-in sensors. NTR3867. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Photoresponsive Passive Micromixers Based on Spiropyran Size-Tunable Hydrogels.

PubMed

Ter Schiphorst, Jeroen; Melpignano, Giuseppe G; Amirabadi, Hossein Eslami; Houben, Menno H J M; Bakker, Sterre; den Toonder, Jaap M J; Schenning, Albertus P H J

2018-01-01

Microfluidic devices allow the manipulation of fluids down to the micrometer scale and are receiving a lot of attention for applications where low volumes and high throughputs are required. In these micro channels, laminar flow usually dominates, which requires long residence times of the fluids, limiting the flow speed and throughput. Here a switchable passive mixer has been developed to control mixing and to easily clean microchannels. The mixer is based on a photoresponsive spiropyran based hydrogel of which the dimensions can be tuned by changing the intensity of the light. The size-tunable gels have been used to fabricate a passive slanted groove mixer that can be switched off by light allowing to change mixing of microfluidics to non-mixed flows. These findings open new possibilities for multi-purpose microfluidic devices where mixers and valves can be tuned by light. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Field Effect Flow Control in a Polymer T-Intersection Microfluidic Network

NASA Technical Reports Server (NTRS)

Sniadecki, Nathan J.; Chang, Richard; Beamesderfer, Mike; Lee, Cheng S.; DeVoe, Don L.

2003-01-01

We present a study of induced pressure pumping in a polymer microchannel due to differential electroosmotic flow @OF) rates via field-effect flow control (FEFC). The experimental results demonstrate that the induced pressure pumping is dependent on the distance of the FEFC gate from the cathodic gate. A proposed flow model based on a linearly-decaying zeta potential profile is found to successfully predict experimental trends.

Monolithic microfabricated valves and pumps by multilayer soft lithography.

PubMed

Unger, M A; Chou, H P; Thorsen, T; Scherer, A; Quake, S R

2000-04-07

Soft lithography is an alternative to silicon-based micromachining that uses replica molding of nontraditional elastomeric materials to fabricate stamps and microfluidic channels. We describe here an extension to the soft lithography paradigm, multilayer soft lithography, with which devices consisting of multiple layers may be fabricated from soft materials. We used this technique to build active microfluidic systems containing on-off valves, switching valves, and pumps entirely out of elastomer. The softness of these materials allows the device areas to be reduced by more than two orders of magnitude compared with silicon-based devices. The other advantages of soft lithography, such as rapid prototyping, ease of fabrication, and biocompatibility, are retained.

Integrated electrofluidic circuits: pressure sensing with analog and digital operation functionalities for microfluidics.

PubMed

Wu, Chueh-Yu; Lu, Jau-Ching; Liu, Man-Chi; Tung, Yi-Chung

2012-10-21

Microfluidic technology plays an essential role in various lab on a chip devices due to its desired advantages. An automated microfluidic system integrated with actuators and sensors can further achieve better controllability. A number of microfluidic actuation schemes have been well developed. In contrast, most of the existing sensing methods still heavily rely on optical observations and external transducers, which have drawbacks including: costly instrumentation, professional operation, tedious interfacing, and difficulties of scaling up and further signal processing. This paper reports the concept of electrofluidic circuits - electrical circuits which are constructed using ionic liquid (IL)-filled fluidic channels. The developed electrofluidic circuits can be fabricated using a well-developed multi-layer soft lithography (MSL) process with polydimethylsiloxane (PDMS) microfluidic channels. Electrofluidic circuits allow seamless integration of pressure sensors with analog and digital operation functions into microfluidic systems and provide electrical readouts for further signal processing. In the experiments, the analog operation device is constructed based on electrofluidic Wheatstone bridge circuits with electrical outputs of the addition and subtraction results of the applied pressures. The digital operation (AND, OR, and XOR) devices are constructed using the electrofluidic pressure controlled switches, and output electrical signals of digital operations of the applied pressures. The experimental results demonstrate the designed functions for analog and digital operations of applied pressures are successfully achieved using the developed electrofluidic circuits, making them promising to develop integrated microfluidic systems with capabilities of precise pressure monitoring and further feedback control for advanced lab on a chip applications.

Commercialization of microfluidic devices.

PubMed

Volpatti, Lisa R; Yetisen, Ali K

2014-07-01

Microfluidic devices offer automation and high-throughput screening, and operate at low volumes of consumables. Although microfluidics has the potential to reduce turnaround times and costs for analytical devices, particularly in medical, veterinary, and environmental sciences, this enabling technology has had limited diffusion into consumer products. This article analyzes the microfluidics market, identifies issues, and highlights successful commercialization strategies. Addressing niche markets and establishing compatibility with existing workflows will accelerate market penetration. Copyright © 2014 Elsevier Ltd. All rights reserved.

Microchip-based electrochemical detection using a 3-D printed wall-jet electrode device.

PubMed

Munshi, Akash S; Martin, R Scott

2016-02-07

Three dimensional (3-D) printing technology has evolved dramatically in the last few years, offering the capability of printing objects with a variety of materials. Printing microfluidic devices using this technology offers various advantages such as ease and uniformity of fabrication, file sharing between laboratories, and increased device-to-device reproducibility. One unique aspect of this technology, when used with electrochemical detection, is the ability to produce a microfluidic device as one unit while also allowing the reuse of the device and electrode for multiple analyses. Here we present an alternate electrode configuration for microfluidic devices, a wall-jet electrode (WJE) approach, created by 3-D printing. Using microchip-based flow injection analysis, we compared the WJE design with the conventionally used thin-layer electrode (TLE) design. It was found that the optimized WJE system enhances analytical performance (as compared to the TLE design), with improvements in sensitivity and the limit of detection. Experiments were conducted using two working electrodes - 500 μm platinum and 1 mm glassy carbon. Using the 500 μm platinum electrode the calibration sensitivity was 16 times higher for the WJE device (as compared to the TLE design). In addition, use of the 1 mm glassy carbon electrode led to limit of detection of 500 nM for catechol, as compared to 6 μM for the TLE device. Finally, to demonstrate the versatility and applicability of the 3-D printed WJE approach, the device was used as an inexpensive electrochemical detector for HPLC. The number of theoretical plates was comparable to the use of commercially available UV and MS detectors, with the WJE device being inexpensive to utilize. These results show that 3-D-printing can be a powerful tool to fabricate reusable and integrated microfluidic detectors in configurations that are not easily achieved with more traditional lithographic methods.

Integration of minisolenoids in microfluidic device for magnetic bead-based immunoassays

NASA Astrophysics Data System (ADS)

Liu, Yan-Jun; Guo, Shi-Shang; Zhang, Zhi-Ling; Huang, Wei-Hua; Baigl, Damien; Chen, Yong; Pang, Dai-Wen

2007-10-01

Microfluidic devices with integrated minisolenoids, microvalves, and channels have been fabricated for fast and low-volume immunoassay using superparamagnetic beads and well-known surface bioengineering protocols. A magnetic reaction area can be formed in the microchannel, featuring a high surface-to-volume ratio and low diffusion distances for the reagents to the bead surface. Such a method has the obvious advantage of easy implementation at low cost. Moreover, the minisolenoids can be switched on or off and the magnetic field intensity can be tuned on demand. Fluids can be manipulated by controlling the integrated air-pressure-actuated microvalves. Accordingly, magnetic bead-based immunoassay, as a typical example of biochemical detection and analysis, has been successfully performed on the integrated microfluidic device automatically in longitudinal mode. With a sample consumption of 0.5μl and a total assay time of less than 15min, goat immunoglobulin G was detected and the method exhibited a detection limit of 4.7ng/ml.

A Student-Made Microfluidic Device for Electrophoretic Separation of Food Dyes

ERIC Educational Resources Information Center

Teerasong, Saowapak; McClain, Robert L.

2011-01-01

We have developed an undergraduate laboratory activity to introduce students to microfluidics. In the activity, each student constructs their own microfluidic device using simple photolithographic techniques and then uses the device to separate a food dye mixture by electrophoresis. Dyes are used so that students are able to visually observe the…

Precise pooling and dispensing of microfluidic droplets towards micro- to macro-world interfacing

PubMed Central

Brouzes, Eric; Carniol, April; Bakowski, Tomasz; Strey, Helmut H.

2014-01-01

Droplet microfluidics possesses unique properties such as the ability to carry out multiple independent reactions without dispersion of samples in microchannels. We seek to extend the use of droplet microfluidics to a new range of applications by enabling its integration into workflows based on traditional technologies, such as microtiter plates. Our strategy consists in developing a novel method to manipulate, pool and deliver a precise number of microfluidic droplets. To this aim, we present a basic module that combines droplet trapping with an on-chip valve. We quantitatively analyzed the trapping efficiency of the basic module in order to optimize its design. We also demonstrate the integration of the basic module into a multiplex device that can deliver 8 droplets at every cycle. This device will have a great impact in low throughput droplet applications that necessitate interfacing with macroscale technologies. The micro- to macro- interface is particularly critical in microfluidic applications that aim at sample preparation and has not been rigorously addressed in this context. PMID:25485102

Instability in extensional microflow of aqueous gel

NASA Astrophysics Data System (ADS)

Bryce, Robert; Freeman, Mark

2007-03-01

Microfluidic devices are typically characterized by laminar flows, often leading to diffusion limited mixing. Recently it has been demonstrated that the addition of polymer to fluids can lead to elastic instabilities and, under some conditions, turbulence at arbitrarily low Reynolds numbers in mechanically driven flows [1]. We investigated electroosmotic driven extensional flow of an aqueous polymer gel. Microchannels with 100 micron width and 20 micron depth with the characteristic ``D'' chemical etch cross section were formed in glass. A Y-channel geometry with two input channels and a single output created extensional flow at the channel intersection. Instabilities where observed in the extensional region by fluorescently tagging one input stream. Instabilities were characterized by 1/f spectra in laser induced fluorescent brightness profiles. Due to the simple geometry of extensional flow and the importance of electroosmotic flows for integrated applications and in scaling, this is of interest for device applications. [1] A. Groisman and V. Steinberg, Nature 405, 53-55, 2000.

Fabrication of robust hydrogel coatings on polydimethylsiloxane substrates using micropillar anchor structures with chemical surface modification.

PubMed

Zhang, Hongbin; Bian, Chao; Jackson, John K; Khademolhosseini, Farzad; Burt, Helen M; Chiao, Mu

2014-06-25

A durable hydrophilic and protein-resistant surface of polydimethylsiloxane (PDMS) based devices is desirable in many biomedical applications such as implantable and microfluidic devices. This paper describes a stable antifouling hydrogel coating on PDMS surfaces. The coating method combines chemical modification and surface microstructure fabrication of PDMS substrates. Three-(trimethoxysilyl)propyl methacrylates containing C═C groups were used to modify PDMS surfaces with micropillar array structures fabricated by a replica molding method. The micropillar structures increase the surface area of PDMS surfaces, which facilitates secure bonding with a hydrogel coating compared to flat PMDS surfaces. The adhesion properties of the hydrogel coating on PDMS substrates were characterized using bending, stretching and water immersion tests. Long-term hydrophilic stability (maintaining a contact angle of 55° for a month) and a low protein adsorption property (35 ng/cm(2) of adsorbed BSA-FITC) of the hydrogel coated PDMS were demonstrated. This coating method is suitable for PDMS modification with most crosslinkable polymers containing C═C groups, which can be useful for improving the anti-biofouling performance of PDMS-based biomedical microdevices.

Design keys for paper-based concentration gradient generators.

PubMed

Schaumburg, Federico; Urteaga, Raúl; Kler, Pablo A; Berli, Claudio L A

2018-08-03

The generation of concentration gradients is an essential operation for several analytical processes implemented on microfluidic paper-based analytical devices. The dynamic gradient formation is based on the transverse dispersion of chemical species across co-flowing streams. In paper channels, this transverse flux of molecules is dominated by mechanical dispersion, which is substantially different than molecular diffusion, which is the mechanism acting in conventional microchannels. Therefore, the design of gradient generators on paper requires strategies different from those used in traditional microfluidics. This work considers the foundations of transverse dispersion in porous substrates to investigate the optimal design of microfluidic paper-based concentration gradient generators (μPGGs) by computer simulations. A set of novel and versatile μPGGs were designed in the format of numerical prototypes, and virtual experiments were run to explore the ranges of operation and the overall performance of such devices. Then physical prototypes were fabricated and experimentally tested in our lab. Finally, some basic rules for the design of optimized μPGGs are proposed. Apart from improving the efficiency of mixers, diluters and μPGGs, the results of this investigation are relevant to attain highly controlled concentration fields on paper-based devices. Copyright © 2018 Elsevier B.V. All rights reserved.

Novel and facile viscometer using a paper-based microfluidic device

NASA Astrophysics Data System (ADS)

Kang, Hyunwoong; Jang, Ilhoon; Song, Simon

2017-11-01

In clinical applications, it is important to rapidly estimate the blood viscosity of a patient with a high accuracy and a small sample consumption. Unfortunately, ordinary mechanical viscometers require long analysis time, large volume of sample and skilled person. To address this issue, silicon-based viscometers have been developed, but they are still far from prevail usage in clinical environments due to complexity in process and analysis. Recently, a paper-based microfluidic device is emerged as a new platform for a facile point-of-care diagnostic device due to low cost, disposability and ease of use. Thus, we propose a novel and facile method of measuring a viscosity with a paper-based microfluidic devices and a smartphone. This viscometer utilizes mixing characteristics of two fluid flows in a T-shape channel: one for reference and the other for test fluid. The mixing strongly depends on viscosity difference between the two fluids. Also, the fluids are dyed for colorimetric analysis with a smartphone. We found that the accuracy of viscometer is about 3 percent when it was tested for various glycerin aqueous solutions. More detailed information will be discussed in the presentation. This work was supported by the National Research Foundation of Korea(NRF) Grant funded by the Korea government(MSIP) (No. 2016R1A2B3009541).

Magnetic-adhesive based valves for microfluidic devices used in low-resource settings.

PubMed

Harper, Jason C; Andrews, Jenna M; Ben, Candice; Hunt, Andrew C; Murton, Jaclyn K; Carson, Bryan D; Bachand, George D; Lovchik, Julie A; Arndt, William D; Finley, Melissa R; Edwards, Thayne L

2016-10-18

Since the introduction of micro total analytical systems (μTASs), significant advances have been made toward development of lab-on-a-chip platforms capable of performing complex biological assays that can revolutionize public health, among other applications. However, use of these platforms in low-resource environments (e.g. developing countries) has yet to be realized as the majority of technologies used to control microfluidic flow rely on off-device hardware with non-negligible size, cost, power requirements and skill/training to operate. In this paper we describe a magnetic-adhesive based valve that is simple to construct and operate, and can be used to control fluid flow and store reagents within a microfluidic device. The design consists of a port connecting two chambers on different planes in the device that is closed by a neodymium disk magnet seated on a thin ring of adhesive. Bringing an external magnet into contact with the outer surface of the device unseats and displaces the valve magnet from the adhesive ring, exposing the port. Using this configuration, we demonstrate on-device reagent storage and on-demand transport and reaction of contents between chambers. This design requires no power or external instrumentation to operate, is extremely low cost ($0.20 materials cost per valve), can be used by individuals with no technical training, and requires only a hand-held magnet to actuate. Additionally, valve actuation does not compromise the integrity of the completely sealed microfluidic device, increasing safety for the operator when toxic or harmful substances are contained within. This valve concept has the potential to simplify design of μTASs, facilitating development of lab-on-a-chip systems that may be practical for use in point-of-care and low-resource settings.

The effects of polymers' visco-elastoplastic properties on the micro cavities filling step of hot embossing process

NASA Astrophysics Data System (ADS)

Cheng, Gang; Barrière, Thierry

2018-05-01

The hot embossing process has been widely used in the manufacturing of polymer components, especially for the fabrication of micro or nano components. The significant advantage of the hot embossing process compared to the traditional injection moulding process is the excellent effective filling ratio for the high aspect ratio components and large surface structural components. The lack of material behavior modeling and numerical simulation limits the further development the hot embossing process, especially at the micro and nano scales. In this paper, a visco-elastoplastic behavior law has been proposed to describe the amorphous thermoplastic polymer mechanical properties in the hot embossing processing temperature range, which is lightly above their glass transition temperature. Uniaxial compression tests have been carried out in order to investigate the amorphous thermoplastic polymers properties. The material parameters in the visco-elastoplastic model have been identified according to the experimental results. A 3D numerical model has been created in the simulation software, which is based on the finite element method. The numerical simulation of the filling step of the hot embossing process has been effectuated by taking into account the viscous, elastic and plastic behaviors of thermoplastic polymers. The micro hot embossing process has been carried out using horizontal injection compression moulding equipment. A complete compression mould tool, equipped with the heating system, the cooling system, the ejection system and the vacuum system, has been designed and elaborated for this research work. The microfluidic devices based on the amorphous thermoplastic polymers have been successfully elaborated by hot embossing process. Proper agreement between the numerical simulation and the experimental elaboration has been obtained.

Different in vitro cellular responses to tamoxifen treatment in polydimethylsiloxane-based devices compared to normal cell culture.

PubMed

Wang, Lingyu; Yu, Linfen; Grist, Samantha; Cheung, Karen C; Chen, David D Y

2017-11-15

Cell culture systems based on polydimethylsiloxane (PDMS) microfluidic devices offer great flexibility because of their simple fabrication and adaptability. PDMS devices also make it straightforward to set up parallel experiments and can facilitate process automation, potentially speeding up the drug discovery process. However, cells grown in PDMS-based systems can develop in different ways to those grown with conventional culturing systems because of the differences in the containers' surfaces. Despite the growing number of studies on microfluidic cell culture devices, the differences in cellular behavior in PDMS-based devices and normal cell culture systems are poorly characterized. In this work, we investigated the proliferation and autophagy of MCF7 cells cultured in uncoated and Parylene-C coated PDMS wells. Using a quantitative method combining solid phase extraction and liquid chromatography mass spectrometry we developed, we showed that Tamoxifen uptake into the surfaces of uncoated PDMS wells can change the drug's effective concentration in the culture medium, affecting the results of Tamoxifen-induced autophagy and cytotoxicity assays. Such changes must be carefully analyzed before transferring in vitro experiments from a traditional culture environment to a PDMS-based microfluidic system. We also found that cells cultured in Parylene-C coated PDMS wells showed similar proliferation and drug response characteristics to cells cultured in standard polystyrene (PS) plates, indicating that Parylene-C deposition offers an easy way of limiting the uptake of small molecules into porous PDMS materials and significantly improves the performance of PDMS-based device for cell related research. Copyright © 2017 Elsevier B.V. All rights reserved.

Microfluidic Organ/Body-on-a-Chip Devices at the Convergence of Biology and Microengineering.

PubMed

Perestrelo, Ana Rubina; Águas, Ana C P; Rainer, Alberto; Forte, Giancarlo

2015-12-10

Recent advances in biomedical technologies are mostly related to the convergence of biology with microengineering. For instance, microfluidic devices are now commonly found in most research centers, clinics and hospitals, contributing to more accurate studies and therapies as powerful tools for drug delivery, monitoring of specific analytes, and medical diagnostics. Most remarkably, integration of cellularized constructs within microengineered platforms has enabled the recapitulation of the physiological and pathological conditions of complex tissues and organs. The so-called "organ-on-a-chip" technology, which represents a new avenue in the field of advanced in vitro models, with the potential to revolutionize current approaches to drug screening and toxicology studies. This review aims to highlight recent advances of microfluidic-based devices towards a body-on-a-chip concept, exploring their technology and broad applications in the biomedical field.

Isolation and detection of circulating tumour cells from metastatic melanoma patients using a slanted spiral microfluidic device.

PubMed

Aya-Bonilla, Carlos A; Marsavela, Gabriela; Freeman, James B; Lomma, Chris; Frank, Markus H; Khattak, Muhammad A; Meniawy, Tarek M; Millward, Michael; Warkiani, Majid E; Gray, Elin S; Ziman, Mel

2017-09-15

Circulating Tumour Cells (CTCs) are promising cancer biomarkers. Several methods have been developed to isolate CTCs from blood samples. However, the isolation of melanoma CTCs is very challenging as a result of their extraordinary heterogeneity, which has hindered their biological and clinical study. Thus, methods that isolate CTCs based on their physical properties, rather than surface marker expression, such as microfluidic devices, are greatly needed in melanoma. Here, we assessed the ability of the slanted spiral microfluidic device to isolate melanoma CTCs via label-free enrichment. We demonstrated that this device yields recovery rates of spiked melanoma cells of over 80% and 55%, after one or two rounds of enrichment, respectively. Concurrently, a two to three log reduction of white blood cells was achieved with one or two rounds of enrichment, respectively. We characterised the isolated CTCs using multimarker flow cytometry, immunocytochemistry and gene expression. The results demonstrated that CTCs from metastatic melanoma patients were highly heterogeneous and commonly expressed stem-like markers such as PAX3 and ABCB5. The implementation of the slanted microfluidic device for melanoma CTC isolation enables further understanding of the biology of melanoma metastasis for biomarker development and to inform future treatment approaches.

Microfluidic assembly of a nano-in-micro dual drug delivery platform composed of halloysite nanotubes and a pH-responsive polymer for colon cancer therapy.

PubMed

Li, Wei; Liu, Dongfei; Zhang, Hongbo; Correia, Alexandra; Mäkilä, Ermei; Salonen, Jarno; Hirvonen, Jouni; Santos, Hélder A

2017-01-15

Harsh conditions of the gastrointestinal tract hinder the oral delivery of many drugs. Developing oral drug delivery systems based on commercially available materials is becoming more challenging due to the demand for simultaneously delivering physicochemically different drugs for treating complex diseases. A novel architecture, namely nanotube-in-microsphere, was developed as a drug delivery platform by encapsulating halloysite nanotubes (HNTs) in a pH-responsive hydroxypropyl methylcellulose acetate succinate polymer using microfluidics. HNTs were selected as orally acceptable clay mineral and their lumen was enlarged by selective acid etching. Model drugs (atorvastatin and celecoxib) with different physicochemical properties and synergistic effect on colon cancer prevention and inhibition were simultaneously incorporated into the microspheres at a precise ratio, with atorvastatin and celecoxib being loaded in the HNTs and polymer matrix, respectively. The microspheres showed spherical shape, narrow particle size distribution and pH-responsive dissolution behavior. This nanotube/pH-responsive polymer composite protected the loaded drugs from premature release at pH⩽6.5, but allowed their fast release and enhanced the drug permeability, and the inhibition of colon cancer cell proliferation at pH 7.4. Overall, the nano-in-micro drug delivery composite fabricated by microfluidics is a promising and flexible platform for the delivery of multiple drugs for combination therapy. Halloysite nanotubes (HNTs) are attracting increasing attention for drug delivery applications. However, conventional HNTs-based oral drug delivery systems are lack of the capability to precisely control the drug release at a desired site in the gastrointestinal tract. In this study, a nanotube-in-microsphere drug delivery platform is developed by encapsulating HNTs in a pH-responsive polymer using microfluidics. Drugs with different physicochemical properties and synergistic effect on colon cancer therapy were simultaneously incorporated in the microspheres. The prepared microspheres prevented the premature release of the loaded drugs after exposure to the harsh conditions of the gastrointestinal tract, but allowed their simultaneously fast release, and enhanced the drug permeability and the inhibition of colon cancer cell proliferation in response to the colon pH. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Recent advancements in ion concentration polarization.

PubMed

Li, Min; Anand, Robbyn K

2016-06-21

In this minireview, we discuss advancements in ion concentration polarization (ICP)-based preconcentration, separation, desalination, and dielectrophoresis that have been made over the past three years. ICP as a means of controlling the distribution of the ions and electric field in a microfluidic device has rapidly expanded its areas of application. Recent advancements have focused on the development of ion-permselective materials with tunable dimensions and surface chemistry, adaptation to paper microfluidics, higher-throughput device geometries, and coupling ICP with other separation (isotachophoresis and dielectrophoresis) and fluidic (valve and droplet microfluidic) strategies. These studies have made great strides toward solving real-world problems such as low-cost and rapid analysis, accessible desalination technology, and single-cell research tools.

Three-dimensional femtosecond laser processing for lab-on-a-chip applications

NASA Astrophysics Data System (ADS)

Sima, Felix; Sugioka, Koji; Vázquez, Rebeca Martínez; Osellame, Roberto; Kelemen, Lóránd; Ormos, Pal

2018-02-01

The extremely high peak intensity associated with ultrashort pulse width of femtosecond laser allows us to induce nonlinear interaction such as multiphoton absorption and tunneling ionization with materials that are transparent to the laser wavelength. More importantly, focusing the femtosecond laser beam inside the transparent materials confines the nonlinear interaction only within the focal volume, enabling three-dimensional (3D) micro- and nanofabrication. This 3D capability offers three different schemes, which involve undeformative, subtractive, and additive processing. The undeformative processing preforms internal refractive index modification to construct optical microcomponents including optical waveguides. Subtractive processing can realize the direct fabrication of 3D microfluidics, micromechanics, microelectronics, and photonic microcomponents in glass. Additive processing represented by two-photon polymerization enables the fabrication of 3D polymer micro- and nanostructures for photonic and microfluidic devices. These different schemes can be integrated to realize more functional microdevices including lab-on-a-chip devices, which are miniaturized laboratories that can perform reaction, detection, analysis, separation, and synthesis of biochemical materials with high efficiency, high speed, high sensitivity, low reagent consumption, and low waste production. This review paper describes the principles and applications of femtosecond laser 3D micro- and nanofabrication for lab-on-a-chip applications. A hybrid technique that promises to enhance functionality of lab-on-a-chip devices is also introduced.

Microfluidic White Organic Light-Emitting Diode Based on Integrated Patterns of Greenish-Blue and Yellow Solvent-Free Liquid Emitters

NASA Astrophysics Data System (ADS)

Kobayashi, Naofumi; Kasahara, Takashi; Edura, Tomohiko; Oshima, Juro; Ishimatsu, Ryoichi; Tsuwaki, Miho; Imato, Toshihiko; Shoji, Shuichi; Mizuno, Jun

2015-10-01

We demonstrated a novel microfluidic white organic light-emitting diode (microfluidic WOLED) based on integrated sub-100-μm-wide microchannels. Single-μm-thick SU-8-based microchannels, which were sandwiched between indium tin oxide (ITO) anode and cathode pairs, were fabricated by photolithography and heterogeneous bonding technologies. 1-Pyrenebutyric acid 2-ethylhexyl ester (PLQ) was used as a solvent-free greenish-blue liquid emitter, while 2,8-di-tert-butyl-5,11-bis(4-tert-butylphenyl)-6,12-diphenyltetracene (TBRb)-doped PLQ was applied as a yellow liquid emitter. In order to form the liquid white light-emitting layer, the greenish-blue and yellow liquid emitters were alternately injected into the integrated microchannels. The fabricated electro-microfluidic device successfully exhibited white electroluminescence (EL) emission via simultaneous greenish-blue and yellow emissions under an applied voltage of 100 V. A white emission with Commission Internationale de l’Declairage (CIE) color coordinates of (0.40, 0.42) was also obtained; the emission corresponds to warm-white light. The proposed device has potential applications in subpixels of liquid-based microdisplays and for lighting.

Direct 3D-printing of cell-laden constructs in microfluidic architectures.

PubMed

Liu, Justin; Hwang, Henry H; Wang, Pengrui; Whang, Grace; Chen, Shaochen

2016-04-21

Microfluidic platforms have greatly benefited the biological and medical fields, however standard practices require a high cost of entry in terms of time and energy. The utilization of three-dimensional (3D) printing technologies has greatly enhanced the ability to iterate and build functional devices with unique functions. However, their inability to fabricate within microfluidic devices greatly increases the cost of producing several different devices to examine different scientific questions. In this work, a variable height micromixer (VHM) is fabricated using projection 3D-printing combined with soft lithography. Theoretical and flow experiments demonstrate that altering the local z-heights of VHM improved mixing at lower flow rates than simple geometries. Mixing of two fluids occurs as low as 320 μL min(-1) in VHM whereas the planar zigzag region requires a flow rate of 2.4 mL min(-1) before full mixing occurred. Following device printing, to further demonstrate the ability of this projection-based method, complex, user-defined cell-laden scaffolds are directly printed inside the VHM. The utilization of this unique ability to produce 3D tissue models within a microfluidic system could offer a unique platform for medical diagnostics and disease modeling.

Recent advances in low-cost microfluidic platforms for diagnostic applications.

PubMed

Tomazelli Coltro, Wendell Karlos; Cheng, Chao-Min; Carrilho, Emanuel; de Jesus, Dosil Pereira

2014-08-01

The use of inexpensive materials and cost-effective manufacturing processes for mass production of microfluidic devices is very attractive and has spurred a variety of approaches. Such devices are particularly suited for diagnostic applications in limited resource settings. This review describes the recent and remarkable advances in the use of low-cost substrates for the development of microfluidic devices for diagnostics and clinical assays. Thus, a plethora of new and improved fabrication methods, designs, capabilities, detections, and applications of microfluidic devices fabricated with paper, plastic, and threads are covered. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Optimized holographic femtosecond laser patterning method towards rapid integration of high-quality functional devices in microchannels.

PubMed

Zhang, Chenchu; Hu, Yanlei; Du, Wenqiang; Wu, Peichao; Rao, Shenglong; Cai, Ze; Lao, Zhaoxin; Xu, Bing; Ni, Jincheng; Li, Jiawen; Zhao, Gang; Wu, Dong; Chu, Jiaru; Sugioka, Koji

2016-09-13

Rapid integration of high-quality functional devices in microchannels is in highly demand for miniature lab-on-a-chip applications. This paper demonstrates the embellishment of existing microfluidic devices with integrated micropatterns via femtosecond laser MRAF-based holographic patterning (MHP) microfabrication, which proves two-photon polymerization (TPP) based on spatial light modulator (SLM) to be a rapid and powerful technology for chip functionalization. Optimized mixed region amplitude freedom (MRAF) algorithm has been used to generate high-quality shaped focus field. Base on the optimized parameters, a single-exposure approach is developed to fabricate 200 × 200 μm microstructure arrays in less than 240 ms. Moreover, microtraps, QR code and letters are integrated into a microdevice by the advanced method for particles capture and device identification. These results indicate that such a holographic laser embellishment of microfluidic devices is simple, flexible and easy to access, which has great potential in lab-on-a-chip applications of biological culture, chemical analyses and optofluidic devices.

Optimized holographic femtosecond laser patterning method towards rapid integration of high-quality functional devices in microchannels

NASA Astrophysics Data System (ADS)

Zhang, Chenchu; Hu, Yanlei; Du, Wenqiang; Wu, Peichao; Rao, Shenglong; Cai, Ze; Lao, Zhaoxin; Xu, Bing; Ni, Jincheng; Li, Jiawen; Zhao, Gang; Wu, Dong; Chu, Jiaru; Sugioka, Koji

2016-09-01

Rapid integration of high-quality functional devices in microchannels is in highly demand for miniature lab-on-a-chip applications. This paper demonstrates the embellishment of existing microfluidic devices with integrated micropatterns via femtosecond laser MRAF-based holographic patterning (MHP) microfabrication, which proves two-photon polymerization (TPP) based on spatial light modulator (SLM) to be a rapid and powerful technology for chip functionalization. Optimized mixed region amplitude freedom (MRAF) algorithm has been used to generate high-quality shaped focus field. Base on the optimized parameters, a single-exposure approach is developed to fabricate 200 × 200 μm microstructure arrays in less than 240 ms. Moreover, microtraps, QR code and letters are integrated into a microdevice by the advanced method for particles capture and device identification. These results indicate that such a holographic laser embellishment of microfluidic devices is simple, flexible and easy to access, which has great potential in lab-on-a-chip applications of biological culture, chemical analyses and optofluidic devices.

Development of a Plastic-Based Microfluidic Immunosensor Chip for Detection of H1N1 Influenza

PubMed Central

Lee, Kyoung G.; Lee, Tae Jae; Jeong, Soon Woo; Choi, Ho Woon; Heo, Nam Su; Park, Jung Youn; Park, Tae Jung; Lee, Seok Jae

2012-01-01

Lab-on-a-chip can provide convenient and accurate diagnosis tools. In this paper, a plastic-based microfluidic immunosensor chip for the diagnosis of swine flu (H1N1) was developed by immobilizing hemagglutinin antigen on a gold surface using a genetically engineered polypeptide. A fluorescent dye-labeled antibody (Ab) was used for quantifying the concentration of Ab in the immunosensor chip using a fluorescent technique. For increasing the detection efficiency and reducing the errors, three chambers and three microchannels were designed in one microfluidic chip. This protocol could be applied to the diagnosis of other infectious diseases in a microfluidic device. PMID:23112630

Bubble production using a Non-Newtonian fluid in microfluidic flow focusing device

NASA Astrophysics Data System (ADS)

Wang, Yi-Lin; Ward, Thomas; Grant, Christine

2012-02-01

We experimentally study the production of micrometer-sized bubbles using microfluidic technology and a flow-focusing geometry. Bubbles are produced by using a mixture containing aqueous polyacrylamide of concentrations ranging from 0.01-0.10% by weight and several solution also containing a sodium-lauryl-sulfate (SLS) surfactant at concentrations ranging 0.01-0.1% by weight. The fluids are driven by controlling the static pressure above a hydrostatic head of the liquid while the disperse phase fluid static pressure is held constant (air). In the absence of surfactant the bubble production is discontinuous. The addition of surfactant stabilizes the bubble production. In each type of experiment, the bubble length l, velocity U and production frequency φ are measured and compared as a function of the inlet pressure ratio. The bubbles exhibit a contraction in their downstream length as a function of the polymer concentration which is investigated.

Measuring the equation of state for a 2D colloidal membrane: A microfluidic approach to buffer exchange

NASA Astrophysics Data System (ADS)

Balchunas, Andrew; Cabanas, Rafael; Fraden, Seth; Dogic, Zvonimir

Previous work has shown that monodisperse rod-like colloidal particles, such as a filamentous bacteriophage, self assemble into a 2D monolayer smectic in the presence of a non-adsorbing depleting polymer. These structures have the same functional form of bending rigidity and lateral compressibility as conventional lipid bi-layers, so we name the monolayer smectic a colloidal membrane. We have developed a microfluidic device such that the osmotic pressure acting on a colloidal membrane may be controlled via a full in situ buffer exchange. Rod density within individual colloidal membranes was measured as a function of osmotic pressure and a first order phase transition, from 2D fluid to 2D solid, was observed. kon and koff rates of rod to membrane binding were measured by lowering the osmotic pressure until membrane evaporation occurred.

A fluidic diode, valves, and a sequential-loading circuit fabricated on layered paper.

PubMed

Chen, Hong; Cogswell, Jeremy; Anagnostopoulos, Constantine; Faghri, Mohammad

2012-08-21

Current microfluidic paper-based devices lack crucial components for fluid manipulation. We created a fluidic diode fabricated entirely on a single layer of paper to control the wicking of fluids. The fluidic diode is a two-terminal component that promotes or stops wicking along a paper channel. We further constructed a trigger and a delay valve based on the fluidic diode. Furthermore, we demonstrated a high-level functional circuit, consisting of a diode and a delay valve, to manipulate two fluids in a sequential manner. Our study provides new, transformative tools to manipulate fluid in microfluidic paper-based devices.

Control of microparticles packing density in a microfluidic channel for bead based immunoassays applications

NASA Astrophysics Data System (ADS)

Caballero-Robledo, Gabriel; Guevara-Pantoja, Pablo

2014-11-01

Bead based immunoassays in microfluidic devices have shown to greatly outperform conventional methods. But if functional point-of-care devices are to be developed, precise and reproducible control over the granulate packings inside microchannels is needed. In this work we study the efficiency of a nanoparticles magnetic trap previously developed by B. Teste et al. [Lab Chip 11, 4207 (2011)] when we vary the compaction of micrometric iron beads packed against a restriction inside a microfluidic channel. The packing density of the beads is finely and reproducibly changed by applying a vibrational protocol originally developed for macroscopic, dry granular systems. We find, counterintuitively, that the most compact and stable packings are up to four times less efficient in trapping nano particles than the loosest packings. This work has been supported by Conacyt, Mexico, under Grant No. 180873.

UV activation of polymeric high aspect ratio microstructures: ramifications in antibody surface loading for circulating tumor cell selection.

PubMed

Jackson, Joshua M; Witek, Małgorzata A; Hupert, Mateusz L; Brady, Charles; Pullagurla, Swathi; Kamande, Joyce; Aufforth, Rachel D; Tignanelli, Christopher J; Torphy, Robert J; Yeh, Jen Jen; Soper, Steven A

2014-01-07

The need to activate thermoplastic surfaces using robust and efficient methods has been driven by the fact that replication techniques can be used to produce microfluidic devices in a high production mode and at low cost, making polymer microfluidics invaluable for in vitro diagnostics, such as circulating tumor cell (CTC) analysis, where device disposability is critical to mitigate artifacts associated with sample carryover. Modifying the surface chemistry of thermoplastic devices through activation techniques can be used to increase the wettability of the surface or to produce functional scaffolds to allow for the covalent attachment of biologics, such as antibodies for CTC recognition. Extensive surface characterization tools were used to investigate UV activation of various surfaces to produce uniform and high surface coverage of functional groups, such as carboxylic acids in microchannels of different aspect ratios. We found that the efficiency of the UV activation process is highly dependent on the microchannel aspect ratio and the identity of the thermoplastic substrate. Colorimetric assays and fluorescence imaging of UV-activated microchannels following EDC/NHS coupling of Cy3-labeled oligonucleotides indicated that UV-activation of a PMMA microchannel with an aspect ratio of ~3 was significantly less efficient toward the bottom of the channel compared to the upper sections. This effect was a consequence of the bulk polymer's damping of the modifying UV radiation due to absorption artifacts. In contrast, this effect was less pronounced for COC. Moreover, we observed that after thermal fusion bonding of the device's cover plate to the substrate, many of the generated functional groups buried into the bulk rendering them inaccessible. The propensity of this surface reorganization was found to be higher for PMMA compared to COC. As an example of the effects of material and microchannel aspect ratios on device functionality, thermoplastic devices for the selection of CTCs from whole blood were evaluated, which required the immobilization of monoclonal antibodies to channel walls. From our results, we concluded the CTC yield and purity of isolated CTCs were dependent on the substrate material with COC producing the highest clinical yields for CTCs as well as better purities compared to PMMA.

Characterization of three-dimensional cancer cell migration in mixed collagen-Matrigel scaffolds using microfluidics and image analysis.

PubMed

Anguiano, María; Castilla, Carlos; Maška, Martin; Ederra, Cristina; Peláez, Rafael; Morales, Xabier; Muñoz-Arrieta, Gorka; Mujika, Maite; Kozubek, Michal; Muñoz-Barrutia, Arrate; Rouzaut, Ana; Arana, Sergio; Garcia-Aznar, José Manuel; Ortiz-de-Solorzano, Carlos

2017-01-01

Microfluidic devices are becoming mainstream tools to recapitulate in vitro the behavior of cells and tissues. In this study, we use microfluidic devices filled with hydrogels of mixed collagen-Matrigel composition to study the migration of lung cancer cells under different cancer invasion microenvironments. We present the design of the microfluidic device, characterize the hydrogels morphologically and mechanically and use quantitative image analysis to measure the migration of H1299 lung adenocarcinoma cancer cells in different experimental conditions. Our results show the plasticity of lung cancer cell migration, which turns from mesenchymal in collagen only matrices, to lobopodial in collagen-Matrigel matrices that approximate the interface between a disrupted basement membrane and the underlying connective tissue. Our quantification of migration speed confirms a biphasic role of Matrigel. At low concentration, Matrigel facilitates migration, most probably by providing a supportive and growth factor retaining environment. At high concentration, Matrigel slows down migration, possibly due excessive attachment. Finally, we show that antibody-based integrin blockade promotes a change in migration phenotype from mesenchymal or lobopodial to amoeboid and analyze the effect of this change in migration dynamics, in regards to the structure of the matrix. In summary, we describe and characterize a robust microfluidic platform and a set of software tools that can be used to study lung cancer cell migration under different microenvironments and experimental conditions. This platform could be used in future studies, thus benefitting from the advantages introduced by microfluidic devices: precise control of the environment, excellent optical properties, parallelization for high throughput studies and efficient use of therapeutic drugs.

Magneto-Hydrodynamics Based Microfluidics

PubMed Central

Qian, Shizhi; Bau, Haim H.

2009-01-01

In microfluidic devices, it is necessary to propel samples and reagents from one part of the device to another, stir fluids, and detect the presence of chemical and biological targets. Given the small size of these devices, the above tasks are far from trivial. Magnetohydrodynamics (MHD) offers an elegant means to control fluid flow in microdevices without a need for mechanical components. In this paper, we review the theory of MHD for low conductivity fluids and describe various applications of MHD such as fluid pumping, flow control in fluidic networks, fluid stirring and mixing, circular liquid chromatography, thermal reactors, and microcoolers. PMID:20046890

Review of microfluidic cell culture devices for the control of gaseous microenvironments in vitro

NASA Astrophysics Data System (ADS)

Wu, H.-M.; Lee, T.-A.; Ko, P.-L.; Chiang, H.-J.; Peng, C.-C.; Tung, Y.-C.

2018-04-01

Gaseous microenvironments play important roles in various biological activities in vivo. However, it is challenging to precisely control gaseous microenvironments in vitro for cell culture due to the high diffusivity nature of gases. In recent years, microfluidics has paved the way for the development of new types of cell culture devices capable of manipulating cellular microenvironments, and provides a powerful tool for in vitro cell studies. This paper reviews recent developments of microfluidic cell culture devices for the control of gaseous microenvironments, and discusses the advantages and limitations of current devices. We conclude with suggestions for the future development of microfluidic cell culture devices for the control of gaseous microenvironments.

Microfluidics: an enabling screening technology for enhanced oil recovery (EOR).

PubMed

Lifton, Victor A

2016-05-21

Oil production is a critical industrial process that affects the entire world population and any improvements in its efficiency while reducing its environmental impact are of utmost societal importance. The paper reviews recent applications of microfluidics and microtechnology to study processes of oil extraction and recovery. It shows that microfluidic devices can be useful tools in investigation and visualization of such processes used in the oil & gas industry as fluid propagation, flooding, fracturing, emulsification and many others. Critical macro-scale processes that define oil extraction and recovery are controlled by the micro-scale processes based on wetting, adhesion, surface tension, colloids and other concepts of microfluidics. A growing number of research efforts demonstrates that microfluidics is becoming, albeit slowly, an accepted methodology in this area. We propose several areas of development where implementation of microfluidics may bring about deeper understanding and hence better control over the processes of oil recovery based on fluid propagation, droplet generation, wettability control. Studies of processes such as hydraulic fracturing, sand particle propagation in porous networks, high throughput screening of chemicals (for example, emulsifiers and surfactants) in microfluidic devices that simulate oil reservoirs are proposed to improve our understanding of these complicated physico-chemical systems. We also discuss why methods of additive manufacturing (3D printing) should be evaluated for quick prototyping and modification of the three-dimensional structures replicating natural oil-bearing rock formations for studies accessible to a wider audience of researchers.

Translational Application of Microfluidics and Bioprinting for Stem Cell-Based Cartilage Repair

PubMed Central

Mondadori, Carlotta; Mainardi, Valerio Luca; Talò, Giuseppe; Candrian, Christian; Święszkowski, Wojciech

2018-01-01

Cartilage defects can impair the most elementary daily activities and, if not properly treated, can lead to the complete loss of articular function. The limitations of standard treatments for cartilage repair have triggered the development of stem cell-based therapies. In this scenario, the development of efficient cell differentiation protocols and the design of proper biomaterial-based supports to deliver cells to the injury site need to be addressed through basic and applied research to fully exploit the potential of stem cells. Here, we discuss the use of microfluidics and bioprinting approaches for the translation of stem cell-based therapy for cartilage repair in clinics. In particular, we will focus on the optimization of hydrogel-based materials to mimic the articular cartilage triggered by their use as bioinks in 3D bioprinting applications, on the screening of biochemical and biophysical factors through microfluidic devices to enhance stem cell chondrogenesis, and on the use of microfluidic technology to generate implantable constructs with a complex geometry. Finally, we will describe some new bioprinting applications that pave the way to the clinical use of stem cell-based therapies, such as scaffold-free bioprinting and the development of a 3D handheld device for the in situ repair of cartilage defects. PMID:29535776

A microfluidic chip containing a molecularly imprinted polymer and a DNA aptamer for voltammetric determination of carbofuran.

PubMed

Li, Shuhuai; Li, Jianping; Luo, Jinhui; Xu, Zhi; Ma, Xionghui

2018-05-11

An electrochemical microfluidic chip is described for the determination of the insecticide carbofuran. It is making use of a molecularly imprinted film (MIP) and a DNA aptamer as dual recognition units. The analyte (carbofuran) is transported to the MIP and captured at the identification site in the channel. Then, carbofuran is eluted with carbinol-acetic acid and transported to the DNA aptamer on the testing position of the chip. It is captured again, this time by the aptamer, and detected by differential pulse voltammetry (DPV). The dual recognition (by aptamer and MIP) results in outstanding selectivity. Additionally, graphene oxide-supported gold nanoparticles (GO-AuNPs) were used to improve the sensitivity of electrochemical detector. DPV response is linear in the 0.2 to 50 nM carbofuran concentration range at a potential of -1.2 V, with a 67 pM detection limit. The method has attractive features such as its potential for high throughput, high degree of automation, and high integration. Conceivably, the method may be extended to other analytes for which appropriate MIPs and aptamers are available. Graphical abstract Schematic of an electrochemical microfluidic chip for carbofuran detection based on a molecularly imprinted film (MIP) and a DNA aptamer as dual recognition units. In the chip, targets were recognized by MIP and aptamer, respectively. It shows promising potential for the design of electrochemical devices with high throughput, high automation, and high integration.

Paper-based analytical devices for clinical diagnosis: recent advances in the fabrication techniques and sensing mechanisms

PubMed Central

Sher, Mazhar; Zhuang, Rachel; Demirci, Utkan; Asghar, Waseem

2017-01-01

Introduction There is a significant interest in developing inexpensive portable biosensing platforms for various applications including disease diagnostics, environmental monitoring, food safety, and water testing at the point-of-care (POC) settings. Current diagnostic assays available in the developed world require sophisticated laboratory infrastructure and expensive reagents. Hence, they are not suitable for resource-constrained settings with limited financial resources, basic health infrastructure, and few trained technicians. Cellulose and flexible transparency paper-based analytical devices have demonstrated enormous potential for developing robust, inexpensive and portable devices for disease diagnostics. These devices offer promising solutions to disease management in resource-constrained settings where the vast majority of the population cannot afford expensive and highly sophisticated treatment options. Areas covered In this review, the authors describe currently developed cellulose and flexible transparency paper-based microfluidic devices, device fabrication techniques, and sensing technologies that are integrated with these devices. The authors also discuss the limitations and challenges associated with these devices and their potential in clinical settings. Expert commentary In recent years, cellulose and flexible transparency paper-based microfluidic devices have demonstrated the potential to become future healthcare options despite a few limitations such as low sensitivity and reproducibility. PMID:28103450

Paper-based analytical devices for clinical diagnosis: recent advances in the fabrication techniques and sensing mechanisms.

PubMed

Sher, Mazhar; Zhuang, Rachel; Demirci, Utkan; Asghar, Waseem

2017-04-01

There is a significant interest in developing inexpensive portable biosensing platforms for various applications including disease diagnostics, environmental monitoring, food safety, and water testing at the point-of-care (POC) settings. Current diagnostic assays available in the developed world require sophisticated laboratory infrastructure and expensive reagents. Hence, they are not suitable for resource-constrained settings with limited financial resources, basic health infrastructure, and few trained technicians. Cellulose and flexible transparency paper-based analytical devices have demonstrated enormous potential for developing robust, inexpensive and portable devices for disease diagnostics. These devices offer promising solutions to disease management in resource-constrained settings where the vast majority of the population cannot afford expensive and highly sophisticated treatment options. Areas covered: In this review, the authors describe currently developed cellulose and flexible transparency paper-based microfluidic devices, device fabrication techniques, and sensing technologies that are integrated with these devices. The authors also discuss the limitations and challenges associated with these devices and their potential in clinical settings. Expert commentary: In recent years, cellulose and flexible transparency paper-based microfluidic devices have demonstrated the potential to become future healthcare options despite a few limitations such as low sensitivity and reproducibility.

Efficient generation of hepatic cells from mesenchymal stromal cells by an innovative bio-microfluidic cell culture device.

PubMed

Yen, Meng-Hua; Wu, Yuan-Yi; Liu, Yi-Shiuan; Rimando, Marilyn; Ho, Jennifer Hui-Chun; Lee, Oscar Kuang-Sheng

2016-08-19

Mesenchymal stromal cells (MSCs) are multipotent and have great potential in cell therapy. Previously we reported the differentiation potential of human MSCs into hepatocytes in vitro and that these cells can rescue fulminant hepatic failure. However, the conventional static culture method neither maintains growth factors at an optimal level constantly nor removes cellular waste efficiently. In addition, not only is the duration of differentiating hepatocyte lineage cells from MSCs required to improve, but also the need for a large number of hepatocytes for cell therapy has not to date been addressed fully. The purpose of this study is to design and develop an innovative microfluidic device to overcome these shortcomings. We designed and fabricated a microfluidic device and a culture system for hepatic differentiation of MSCs using our protocol reported previously. The microfluidic device contains a large culture chamber with a stable uniform flow to allow homogeneous distribution and expansion as well as efficient induction of hepatic differentiation for MSCs. The device enables real-time observation under light microscopy and exhibits a better differentiation efficiency for MSCs compared with conventional static culture. MSCs grown in the microfluidic device showed a higher level of hepatocyte marker gene expression under hepatic induction. Functional analysis of hepatic differentiation demonstrated significantly higher urea production in the microfluidic device after 21 days of hepatic differentiation. The microfluidic device allows the generation of a large number of MSCs and induces hepatic differentiation of MSCs efficiently. The device can be adapted for scale-up production of hepatic cells from MSCs for cellular therapy.

Rapid mask prototyping for microfluidics.

PubMed

Maisonneuve, B G C; Honegger, T; Cordeiro, J; Lecarme, O; Thiry, T; Fuard, D; Berton, K; Picard, E; Zelsmann, M; Peyrade, D

2016-03-01

With the rise of microfluidics for the past decade, there has come an ever more pressing need for a low-cost and rapid prototyping technology, especially for research and education purposes. In this article, we report a rapid prototyping process of chromed masks for various microfluidic applications. The process takes place out of a clean room, uses a commercially available video-projector, and can be completed in less than half an hour. We quantify the ranges of fields of view and of resolutions accessible through this video-projection system and report the fabrication of critical microfluidic components (junctions, straight channels, and curved channels). To exemplify the process, three common devices are produced using this method: a droplet generation device, a gradient generation device, and a neuro-engineering oriented device. The neuro-engineering oriented device is a compartmentalized microfluidic chip, and therefore, required the production and the precise alignment of two different masks.

Rapid mask prototyping for microfluidics

PubMed Central

Maisonneuve, B. G. C.; Honegger, T.; Cordeiro, J.; Lecarme, O.; Thiry, T.; Fuard, D.; Berton, K.; Picard, E.; Zelsmann, M.; Peyrade, D.

2016-01-01

With the rise of microfluidics for the past decade, there has come an ever more pressing need for a low-cost and rapid prototyping technology, especially for research and education purposes. In this article, we report a rapid prototyping process of chromed masks for various microfluidic applications. The process takes place out of a clean room, uses a commercially available video-projector, and can be completed in less than half an hour. We quantify the ranges of fields of view and of resolutions accessible through this video-projection system and report the fabrication of critical microfluidic components (junctions, straight channels, and curved channels). To exemplify the process, three common devices are produced using this method: a droplet generation device, a gradient generation device, and a neuro-engineering oriented device. The neuro-engineering oriented device is a compartmentalized microfluidic chip, and therefore, required the production and the precise alignment of two different masks. PMID:27014396

Continuous nucleus extraction by optically-induced cell lysis on a batch-type microfluidic platform.

PubMed

Huang, Shih-Hsuan; Hung, Lien-Yu; Lee, Gwo-Bin

2016-04-21

The extraction of a cell's nucleus is an essential technique required for a number of procedures, such as disease diagnosis, genetic replication, and animal cloning. However, existing nucleus extraction techniques are relatively inefficient and labor-intensive. Therefore, this study presents an innovative, microfluidics-based approach featuring optically-induced cell lysis (OICL) for nucleus extraction and collection in an automatic format. In comparison to previous micro-devices designed for nucleus extraction, the new OICL device designed herein is superior in terms of flexibility, selectivity, and efficiency. To facilitate this OICL module for continuous nucleus extraction, we further integrated an optically-induced dielectrophoresis (ODEP) module with the OICL device within the microfluidic chip. This on-chip integration circumvents the need for highly trained personnel and expensive, cumbersome equipment. Specifically, this microfluidic system automates four steps by 1) automatically focusing and transporting cells, 2) releasing the nuclei on the OICL module, 3) isolating the nuclei on the ODEP module, and 4) collecting the nuclei in the outlet chamber. The efficiency of cell membrane lysis and the ODEP nucleus separation was measured to be 78.04 ± 5.70% and 80.90 ± 5.98%, respectively, leading to an overall nucleus extraction efficiency of 58.21 ± 2.21%. These results demonstrate that this microfluidics-based system can successfully perform nucleus extraction, and the integrated platform is therefore promising in cell fusion technology with the goal of achieving genetic replication, or even animal cloning, in the near future.

Integrated Microfluidic System for Size-Based Selection and Trapping of Giant Vesicles.

PubMed

Kazayama, Yuki; Teshima, Tetsuhiko; Osaki, Toshihisa; Takeuchi, Shoji; Toyota, Taro

2016-01-19

Vesicles composed of phospholipids (liposomes) have attracted interest as artificial cell models and have been widely studied to explore lipid-lipid and lipid-protein interactions. However, the size dispersity of liposomes prepared by conventional methods was a major problem that inhibited their use in high-throughput analyses based on monodisperse liposomes. In this study, we developed an integrative microfluidic device that enables both the size-based selection and trapping of liposomes. This device consists of hydrodynamic selection and trapping channels in series, which made it possible to successfully produce an array of more than 60 monodisperse liposomes from a polydisperse liposome suspension with a narrow size distribution (the coefficient of variation was less than 12%). We successfully observed a size-dependent response of the liposomes to sequential osmotic stimuli, which had not clarified so far, by using this device. Our device will be a powerful tool to facilitate the statistical analysis of liposome dynamics.

Low power integrated pumping and valving arrays for microfluidic systems

DOEpatents

Krulevitch, Peter A [Pleasanton, CA; Benett, William J [Livermore, CA; Rose, Klint A [Livermore, CA; Hamilton, Julie [Tracy, CA; Maghribi, Mariam [Davis, CA

2006-04-11

Low power integrated pumping and valving arrays which provide a revolutionary approach for performing pumping and valving approach for performing pumping and valving operations in microfabricated fluidic systems for applications such as medical diagnostic microchips. Traditional methods rely on external, large pressure sources that defeat the advantages of miniaturization. Previously demonstrated microfabrication devices are power and voltage intensive, only function at sufficient pressure to be broadly applicable. This approach integrates a lower power, high-pressure source with a polymer, ceramic, or metal plug enclosed within a microchannel, analogous to a microsyringe. When the pressure source is activated, the polymer plug slides within the microchannel, pumping the fluid on the opposite side of the plug without allowing fluid to leak around the plug. The plugs also can serve as microvalves.

Batch-reactor microfluidic device: first human use of a microfluidically produced PET radiotracer†

PubMed Central

Miraghaie, Reza; Kotta, Kishore; Ball, Carroll E.; Zhang, Jianzhong; Buchsbaum, Monte S.; Kolb, Hartmuth C.; Elizarov, Arkadij

2013-01-01

The very first microfluidic device used for the production of 18F-labeled tracers for clinical research is reported along with the first human Positron Emission Tomography scan obtained with a microfluidically produced radiotracer. The system integrates all operations necessary for the transformation of [18F]fluoride in irradiated cyclotron target water to a dose of radiopharmaceutical suitable for use in clinical research. The key microfluidic technologies developed for the device are a fluoride concentration system and a microfluidic batch reactor assembly. Concentration of fluoride was achieved by means of absorption of the fluoride anion on a micro ion-exchange column (5 μL of resin) followed by release of the radioactivity with 45 μL of the release solution (95 ± 3% overall efficiency). The reactor assembly includes an injection-molded reactor chip and a transparent machined lid press-fitted together. The resulting 50 μL cavity has a unique shape designed to minimize losses of liquid during reactor filling and liquid evaporation. The cavity has 8 ports for gases and liquids, each equipped with a 2-way on-chip mechanical valve rated for pressure up to 20.68 bar (300 psi). The temperature is controlled by a thermoelectric heater capable of heating the reactor up to 180 °C from RT in 150 s. A camera captures live video of the processes in the reactor. HPLC-based purification and reformulation units are also integrated in the device. The system is based on “split-box architecture”, with reagents loaded from outside of the radiation shielding. It can be installed either in a standard hot cell, or as a self-shielded unit. Along with a high level of integration and automation, split-box architecture allowed for multiple production runs without the user being exposed to radiation fields. The system was used to support clinical trials of [18F]fallypride, a neuroimaging radiopharmaceutical under IND Application #109,880. PMID:23135409

Soft tubular microfluidics for 2D and 3D applications

PubMed Central

Xi, Wang; Kong, Fang; Yeo, Joo Chuan; Yu, Longteng; Sonam, Surabhi; Dao, Ming; Gong, Xiaobo; Lim, Chwee Teck

2017-01-01

Microfluidics has been the key component for many applications, including biomedical devices, chemical processors, microactuators, and even wearable devices. This technology relies on soft lithography fabrication which requires cleanroom facilities. Although popular, this method is expensive and labor-intensive. Furthermore, current conventional microfluidic chips precludes reconfiguration, making reiterations in design very time-consuming and costly. To address these intrinsic drawbacks of microfabrication, we present an alternative solution for the rapid prototyping of microfluidic elements such as microtubes, valves, and pumps. In addition, we demonstrate how microtubes with channels of various lengths and cross-sections can be attached modularly into 2D and 3D microfluidic systems for functional applications. We introduce a facile method of fabricating elastomeric microtubes as the basic building blocks for microfluidic devices. These microtubes are transparent, biocompatible, highly deformable, and customizable to various sizes and cross-sectional geometries. By configuring the microtubes into deterministic geometry, we enable rapid, low-cost formation of microfluidic assemblies without compromising their precision and functionality. We demonstrate configurable 2D and 3D microfluidic systems for applications in different domains. These include microparticle sorting, microdroplet generation, biocatalytic micromotor, triboelectric sensor, and even wearable sensing. Our approach, termed soft tubular microfluidics, provides a simple, cheaper, and faster solution for users lacking proficiency and access to cleanroom facilities to design and rapidly construct microfluidic devices for their various applications and needs. PMID:28923968

Soft tubular microfluidics for 2D and 3D applications

NASA Astrophysics Data System (ADS)

Xi, Wang; Kong, Fang; Yeo, Joo Chuan; Yu, Longteng; Sonam, Surabhi; Dao, Ming; Gong, Xiaobo; Teck Lim, Chwee

2017-10-01

Microfluidics has been the key component for many applications, including biomedical devices, chemical processors, microactuators, and even wearable devices. This technology relies on soft lithography fabrication which requires cleanroom facilities. Although popular, this method is expensive and labor-intensive. Furthermore, current conventional microfluidic chips precludes reconfiguration, making reiterations in design very time-consuming and costly. To address these intrinsic drawbacks of microfabrication, we present an alternative solution for the rapid prototyping of microfluidic elements such as microtubes, valves, and pumps. In addition, we demonstrate how microtubes with channels of various lengths and cross-sections can be attached modularly into 2D and 3D microfluidic systems for functional applications. We introduce a facile method of fabricating elastomeric microtubes as the basic building blocks for microfluidic devices. These microtubes are transparent, biocompatible, highly deformable, and customizable to various sizes and cross-sectional geometries. By configuring the microtubes into deterministic geometry, we enable rapid, low-cost formation of microfluidic assemblies without compromising their precision and functionality. We demonstrate configurable 2D and 3D microfluidic systems for applications in different domains. These include microparticle sorting, microdroplet generation, biocatalytic micromotor, triboelectric sensor, and even wearable sensing. Our approach, termed soft tubular microfluidics, provides a simple, cheaper, and faster solution for users lacking proficiency and access to cleanroom facilities to design and rapidly construct microfluidic devices for their various applications and needs.

Fabrication of rectangular cross-sectional microchannels on PMMA with a CO2 laser and underwater fabricated copper mask

NASA Astrophysics Data System (ADS)

Prakash, Shashi; Kumar, Subrata

2017-09-01

CO2 lasers are commonly used for fabricating polymer based microfluidic devices. Despite several key advantages like low cost, time effectiveness, easy to operate and no requirement of clean room facility, CO2 lasers suffer from few disadvantages like thermal bulging, improper dimensional control, difficulty to produce microchannels of other than Gaussian cross sectional shapes and inclined surface walls. Many microfluidic devices require square or rectangular cross-sections which are difficult to produce using normal CO2 laser procedures. In this work, a thin copper sheet of 40 μm was used as a mask above the PMMA (Polymethyl-methacrylate) substrate while fabricating the microchannels utilizing the raster scanning feature of the CO2 lasers. Microchannels with different width dimensions were fabricated utilizing a CO2 laser in with mask and without-mask conditions. A comparison of both the fabricating process has been made. It was found that microchannels with U shape cross section and rectangular cross-section can efficiently be produced using the with mask technique. In addition to this, this technique can provide perfect dimensional control and better surface quality of the microchannel walls. Such a microchannel fabrication process do not require any post-processing. The fabrication of mask using a nanosecond fiber laser has been discussed in details. An underwater laser fabrication method was adopted to overcome heat related defects in mask preparation. Overall, the technique was found to be easy to adopt and significant improvements were observed in microchannel fabrication.

Microfluidic Arrayed Lab-On-A-Chip for Electrochemical Capacitive Detection of DNA Hybridization Events.

PubMed

Ben-Yoav, Hadar; Dykstra, Peter H; Bentley, William E; Ghodssi, Reza

2017-01-01

A microfluidic electrochemical lab-on-a-chip (LOC) device for DNA hybridization detection has been developed. The device comprises a 3 × 3 array of microelectrodes integrated with a dual layer microfluidic valved manipulation system that provides controlled and automated capabilities for high throughput analysis of microliter volume samples. The surface of the microelectrodes is functionalized with single-stranded DNA (ssDNA) probes which enable specific detection of complementary ssDNA targets. These targets are detected by a capacitive technique which measures dielectric variation at the microelectrode-electrolyte interface due to DNA hybridization events. A quantitative analysis of the hybridization events is carried out based on a sensing modeling that includes detailed analysis of energy storage and dissipation components. By calculating these components during hybridization events the device is able to demonstrate specific and dose response sensing characteristics. The developed microfluidic LOC for DNA hybridization detection offers a technology for real-time and label-free assessment of genetic markers outside of laboratory settings, such as at the point-of-care or in-field environmental monitoring.

Radiation dominated acoustophoresis driven by surface acoustic waves.

PubMed

Guo, Jinhong; Kang, Yuejun; Ai, Ye

2015-10-01

Acoustophoresis-based particle manipulation in microfluidics has gained increasing attention in recent years. Despite the fact that experimental studies have been extensively performed to demonstrate this technique for various microfluidic applications, numerical simulation of acoustophoresis driven by surface acoustic waves (SAWs) has still been largely unexplored. In this work, a numerical model taking into account the acoustic-piezoelectric interaction was developed to simulate the generation of a standing surface acoustic wave (SSAW) field and predict the acoustic pressure field in the liquid. Acoustic radiation dominated particle tracing was performed to simulate acoustophoresis of particles with different sizes undergoing a SSAW field. A microfluidic device composed of two interdigital transducers (IDTs) for SAW generation and a microfluidic channel was fabricated for experimental validation. Numerical simulations could well capture the focusing phenomenon of particles to the pressure nodes in the experimental observation. Further comparison of particle trajectories demonstrated considerably quantitative agreement between numerical simulations and experimental results with fitting in the applied voltage. Particle switching was also demonstrated using the fabricated device that could be further developed as an active particle sorting device. Copyright © 2015 Elsevier Inc. All rights reserved.

Droplet Velocity Measurement Based on Dielectric Layer Thickness Variation Using Digital Microfluidic Devices.

PubMed

Zulkepli, Siti Noor Idora Syafinaz; Hamid, Nor Hisham; Shukla, Vineeta

2018-05-08

In recent years, the number of interdisciplinary research works related to the development of miniaturized systems with integrated chemical and biological analyses is increasing. Digital microfluidic biochips (DMFBs) are one kind of miniaturized systems designed for conducting inexpensive, fast, convenient and reliable biochemical assay procedures focusing on basic scientific research and medical diagnostics. The role of a dielectric layer in the digital microfluidic biochips is prominent as it helps in actuating microliter droplets based on the electrowetting-on-dielectric (EWOD) technique. The advantages of using three different material layers of dielectric such as parafilm, polytetrafluoroethylene (PTFE) and ethylene tetrafluoroethylene (ETFE) were reported in the current work. A simple fabrication process of a digital microfluidic device was performed and good results were obtained. The threshold of the actuation voltage was determined for all dielectric materials of varying thicknesses. Additionally, the OpenDrop device was tested by utilizing a single-plate system to transport microliter droplets for a bioassay operation. With the newly proposed fabrication methods, these dielectric materials showed changes in contact angle and droplet velocity when the actuation voltage was applied. The threshold actuation voltage for the dielectric layers of 10⁻13 μm was 190 V for the open plate DMFBs.

3D-printed microfluidic automation.

PubMed

Au, Anthony K; Bhattacharjee, Nirveek; Horowitz, Lisa F; Chang, Tim C; Folch, Albert

2015-04-21

Microfluidic automation - the automated routing, dispensing, mixing, and/or separation of fluids through microchannels - generally remains a slowly-spreading technology because device fabrication requires sophisticated facilities and the technology's use demands expert operators. Integrating microfluidic automation in devices has involved specialized multi-layering and bonding approaches. Stereolithography is an assembly-free, 3D-printing technique that is emerging as an efficient alternative for rapid prototyping of biomedical devices. Here we describe fluidic valves and pumps that can be stereolithographically printed in optically-clear, biocompatible plastic and integrated within microfluidic devices at low cost. User-friendly fluid automation devices can be printed and used by non-engineers as replacement for costly robotic pipettors or tedious manual pipetting. Engineers can manipulate the designs as digital modules into new devices of expanded functionality. Printing these devices only requires the digital file and electronic access to a printer.

Microfluidic production of polymeric functional microparticles

NASA Astrophysics Data System (ADS)

Jiang, Kunqiang

This dissertation focuses on applying droplet-based microfluidics to fabricate new classes of polymeric microparticles with customized properties for various applications. The integration of microfluidic techniques with microparticle engineering allows for unprecedented control over particle size, shape, and functional properties. Specifically, three types of microparticles are discussed here: (1) Magnetic and fluorescent chitosan hydrogel microparticles and their in-situ assembly into higher-order microstructures; (2) Polydimethylsiloxane (PDMS) microbeads with phosphorescent properties for oxygen sensing; (3) Macroporous microparticles as biological immunosensors. First, we describe a microfluidic approach to generate monodisperse chitosan hydrogel microparticles that can be further connected in-situ into higher-order microstructures. Microparticles of the biopolymer chitosan are created continuously by contacting an aqueous solution of chitosan at a microfluidic T-junction with a stream of hexadecane containing a nonionic detergent, followed by downstream crosslinking of the generated droplets by a ternary flow of glutaraldehyde. Functional properties of the microparticles can be easily varied by introducing payloads such as magnetic nanoparticles and/or fluorescent dyes into the chitosan solution. We then use these prepared microparticles as "building blocks" and assemble them into high ordered microstructures, i.e. microchains with controlled geometry and flexibility. Next, we describe a new approach to produce monodisperse microbeads of PDMS using microfluidics. Using a flow-focusing configuration, a PDMS precursor solution is dispersed into microdroplets within an aqueous continuous phase. These droplets are collected and thermally cured off-chip into soft, solid microbeads. In addition, our technique allows for direct integration of payloads, such as an oxygen-sensitive porphyrin dye, into the PDMS microbeads. We then show that the resulting dye-bearing beads can function as non-invasive and real-time oxygen micro-sensors. Finally, we report a co-flow microfluidic method to prepare uniform polymer microparticles with macroporous texture, and investigate their application as discrete immunological biosensors for the detection of biological species. The matrix of such microparticles is based on macroporous polymethacrylate polymers configured with tailored pores ranging from hundreds of nanometers to a few microns. Subsequently, we immobilize bioactive antibodies on the particle surface, and demonstrate the immunological performance of these functionalized porous microbeads over a range of antigen concentrations.

Optical diagnostics of osteoblast cells and osteogenic drug screening

NASA Astrophysics Data System (ADS)

Kolanti, Elayaraja; Veerla, Sarath C.; Khajuria, Deepak K.; Roy Mahapatra, D.

2016-02-01

Microfluidic device based diagnostics involving optical fibre path, in situ imaging and spectroscopy are gaining importance due to recent advances in diagnostics instrumentation and methods, besides other factors such as low amount of reagent required for analysis, short investigation times, and potential possibilities to replace animal model based study in near future. It is possible to grow and monitor tissues in vitro in microfluidic lab-on-chip. It may become a transformative way of studying how cells interact with drugs, pathogens and biomaterials in physiologically relevant microenvironments. To a large extent, progress in developing clinically viable solutions has been constrained because of (i) contradiction between in vitro and in vivo results and (ii) animal model based and clinical studies which is very expensive. Our study here aims to evaluate the usefulness of microfluidic device based 3D tissue growth and monitoring approach to better emulate physiologically and clinically relevant microenvironments in comparison to conventional in vitro 2D culture. Moreover, the microfluidic methodology permits precise high-throughput investigations through real-time imaging while using very small amounts of reagents and cells. In the present study, we report on the details of an osteoblast cell based 3D microfluidic platform which we employ for osteogenic drug screening. The drug formulation is functionalized with fluorescence and other biomarkers for imaging and spectroscopy, respectively. Optical fibre coupled paths are used to obtain insight regarding the role of stress/flow pressure fluctuation and nanoparticle-drug concentration on the osteoblast growth and osteogenic properties of bone.

Robust and Elastic Polymer Membranes with Tunable Properties for Gas Separation

DOE PAGES

Cao, Peng -Fei; Li, Bingrui; Hong, Tao; ...

2017-07-17

Here, polymer membranes with the capability to process a massive volume of gas are especially attractive for practical applications of gas separation. Although much effort has been devoted to develop novel polymer membranes with increased selectivity, the overall gas-separation performance and lifetime of membrane are still negatively affected by the weak mechanical performance, low plasticization resistance and poor physical aging tolerance. Recently, elastic polymer membranes with tunable mechanical properties have been attracting significant attentions due to their tremendous potential applications. Herein, we report a series of urethanerich PDMS-based polymer networks (U-PDMS-NW) with improved mechanical performance for gas separation. The cross-linkmore » density of U-PDMS-NWs is tailored by varying the molecular weight ( M n) of PDMS. The U-PDMS-NWs show up to 400% elongation and tunable Young’s modulus (1.3–122.2 MPa), ultimate tensile strength (1.1–14.3 MPa), and toughness (0.7–24.9 MJ/m 3). All of the U-PDMS-NWs exhibit salient gas-separation performance with excellent thermal resistance and aging tolerance, high gas permeability (>100 Barrer), and tunable gas selectivity (up to α[ P CO2/ P N2] ≈ 41 and α[ P CO2/ P CH4] ≈ 16). With well-controlled mechanical properties and gas-separation performance, these U-PDMS-NW can be used as a polymermembrane platform not only for gas separation but also for other applications such as microfluidic channels and stretchable electronic devices.« less

Modular microfluidic valve structures based on reversible thermoresponsive ionogel actuators.

PubMed

Benito-Lopez, Fernando; Antoñana-Díez, Marta; Curto, Vincenzo F; Diamond, Dermot; Castro-López, Vanessa

2014-09-21

This paper reports for the first time the use of a cross-linked poly(N-isopropylacrylamide) ionogel encapsulating the ionic liquid 1-ethyl-3-methylimidazolium ethyl sulphate as a thermoresponsive and modular microfluidic valve. The ionogel presents superior actuation behaviour to its equivalent hydrogel. Ionogel swelling and shrinking mechanisms and kinetics are investigated as well as the performance of the ionogel when integrated as a valve in a microfluidic device. The modular microfluidic valve demonstrates fully a reversible on-off behaviour without failure for up to eight actuation cycles and a pressure resistance of 1100 mbar.

Hydrogel-coated microfluidic channels for cardiomyocyte culture

PubMed Central

Annabi, Nasim; Selimović, Šeila; Cox, Juan Pablo Acevedo; Ribas, João; Bakooshli, Mohsen Afshar; Heintze, Déborah; Weiss, Anthony S.; Cropek, Donald; Khademhosseini, Ali

2013-01-01

The research areas of tissue engineering and drug development have displayed increased interest in organ-on-a-chip studies, in which physiologically or pathologically relevant tissues can be engineered to test pharmaceutical candidates. Microfluidic technologies enable the control of the cellular microenvironment for these applications through the topography, size, and elastic properties of the microscale cell culture environment, while delivering nutrients and chemical cues to the cells through continuous media perfusion. Traditional materials used in the fabrication of microfluidic devices, such as poly(dimethylsiloxane) (PDMS), offer high fidelity and high feature resolution, but do not facilitate cell attachment. To overcome this challenge, we have developed a method for coating microfluidic channels inside a closed PDMS device with a cell-compatible hydrogel layer. We have synthesized photocrosslinkable gelatin and tropoelastin-based hydrogel solutions that were used to coat the surfaces under continuous flow inside 50 μm wide, straight microfluidic channels to generate a hydrogel layer on the channel walls. Our observation of primary cardiomyocytes seeded on these hydrogel layers showed preferred attachment as well as higher spontaneous beating rates on tropoelastin coatings compared to gelatin. In addition, cellular attachment, alignment and beating were stronger on 5 % (w/v) hydrogel-coated devices than on 10 % (w/v) gel-coated channels. Our results demonstrate that cardiomyocytes respond favorably to the elastic, soft tropoelastin culture substrates, indicating that tropoelastin-based hydrogels may be a suitable coating choice for some organ-on-a-chip applications. We anticipate that the proposed hydrogel coating method and tropoelastin as a cell culture substrate may be useful for the generation of elastic tissues, e.g. blood vessels, using microfluidic approaches. PMID:23728018

A novel microfluidics-based method for probing weak protein-protein interactions.

PubMed

Tan, Darren Cherng-wen; Wijaya, I Putu Mahendra; Andreasson-Ochsner, Mirjam; Vasina, Elena Nikolaevna; Nallani, Madhavan; Hunziker, Walter; Sinner, Eva-Kathrin

2012-08-07

We report the use of a novel microfluidics-based method to detect weak protein-protein interactions between membrane proteins. The tight junction protein, claudin-2, synthesised in vitro using a cell-free expression system in the presence of polymer vesicles as membrane scaffolds, was used as a model membrane protein. Individual claudin-2 molecules interact weakly, although the cumulative effect of these interactions is significant. This effect results in a transient decrease of average vesicle dispersivity and reduction in transport speed of claudin-2-functionalised vesicles. Polymer vesicles functionalised with claudin-2 were perfused through a microfluidic channel and the time taken to traverse a defined distance within the channel was measured. Functionalised vesicles took 1.19 to 1.69 times longer to traverse this distance than unfunctionalised ones. Coating the channel walls with protein A and incubating the vesicles with anti-claudin-2 antibodies prior to perfusion resulted in the functionalised vesicles taking 1.75 to 2.5 times longer to traverse this distance compared to the controls. The data show that our system is able to detect weak as well as strong protein-protein interactions. This system offers researchers a portable, easily operated and customizable platform for the study of weak protein-protein interactions, particularly between membrane proteins.

Waste-to-energy conversion from a microfluidic device

NASA Astrophysics Data System (ADS)

López-González, B.; Jiménez-Valdés, R. J.; Moreno-Zuria, A.; Cuevas-Muñiz, F. M.; Ledesma-García, J.; García-Cordero, J. L.; Arriaga, L. G.

2017-08-01

This work reports the successful harvesting of energy from waste produced in a microfluidic device using a fuel cell. A miniaturized glucose air-breathing microfluidic fuel cell (ABμFFC) was designed, fabricated and tested with three different configurations according to their electrode nature: inorganic, hybrid and biofuel cell. Each ABμFFC was characterized using an ideal medium, with sterile cell culture medium, and with waste produced on a microfluidic device. The inorganic-ABμFFC exhibited the highest performance compared to the rest of the configurations. As a proof-of-concept, cancer cells were cultured on a microfluidic device and the consumed cell culture media (glucose concentration <11 mM) was used as an energy source without further treatment, into the inorganic-ABμFFC. The fuel cell generated a maximum total power of 5.2 μW, which is enough energy to power low-consumption microelectronic chips. This application demonstrates that the waste produced by microfluidic applications could be potentially scavenged to produce electrical energy. It also opens the possibility to develop truly energy self-sufficient portable devices.

Integration of Stable Droplet Formation on a CD Microfluidic Device for Extreme Point of Care Applications

NASA Astrophysics Data System (ADS)

Ganesh, Shruthi Vatsyayani

With the advent of microfluidic technologies for molecular diagnostics, a lot of emphasis has been placed on developing diagnostic tools for resource poor regions in the form of Extreme Point of Care devices. To ensure commercial viability of such a device there is a need to develop an accurate sample to answer system, which is robust, portable, isolated yet highly sensitive and cost effective. This need has been a driving force for research involving integration of different microsystems like droplet microfluidics, Compact-disc (CD)microfluidics along with sample preparation and detection modules on a single platform. This work attempts to develop a proof of concept prototype of one such device using existing CD microfluidics tools to generate stable droplets used in point of care diagnostics (POC diagnostics). Apart from using a fairly newer technique for droplet generation and stabilization, the work aims to develop this method focused towards diagnostics for rural healthcare. The motivation for this work is first described with an emphasis on the current need for diagnostic testing in rural health-care and the general guidelines prescribed by WHO for such a sample to answer system. Furthermore, a background on CD and droplet microfluidics is presented to understand the merits and de-merits of each system and the need for integrating the two. This phase of the thesis also includes different methods employed/demonstrated to generate droplets on a spinning platform. An overview on the detection platforms is also presented to understand the challenges involved in building an extreme point of care device. In the third phase of the thesis, general manufacturing techniques and materials used to accomplish this work is presented. Lastly, design trials for droplet generation is presented. The shortcomings of these trials are solved by investigating mechanisms pertaining to design modification and use of agarose based droplet generation to ensure a more robust sample processing method. This method is further characterized and compared with non-agarose based system and the results are analyzed. In conclusion, future prospects of this work are discussed in relation to extreme POC applications.

Use of Ice-Nucleating Proteins To Improve the Performance of Freeze-Thaw Valves in Microfluidic Devices.

PubMed

Gaiteri, Joseph C; Henley, W Hampton; Siegfried, Nathan A; Linz, Thomas H; Ramsey, J Michael

2017-06-06

Currently, reliable valving on integrated microfluidic devices fabricated from rigid materials is confined to expensive and complex methods. Freeze-thaw valves (FTVs) can provide a low cost, low complexity valving mechanism, but reliable implementation of them has been greatly hindered by the lack of ice nucleation sites within the valve body's small volume. Work to date has required very low temperatures (on the order of -40 °C or colder) to induce freezing without nucleation sites, making FTVs impractical due to instrument engineering challenges. Here, we report the use of ice-nucleating proteins (INPs) to induce ice formation at relatively warm temperatures in microfluidic devices. Microfluidic channels were filled with buffers containing femtomolar INP concentrations from Pseudomonas syringae. The channels were cooled externally with simple, small-footprint Peltier thermoelectric coolers (TECs), and the times required for channel freezing (valve closure) and thawing (valve opening) were measured. Under optimized conditions in plastic chips, INPs made sub-10 s actuations possible at TEC temperatures as warm as -13 °C. Additionally, INPs were found to have no discernible inhibitory effects in model enzyme-linked immunosorbent assays or polymerase chain reactions, indicating their compatibility with microfluidic systems that incorporate these widely used bioassays. FTVs with INPs provide a much needed reliable valving scheme for rigid plastic devices with low complexity, low cost, and no moving parts on the device or instrument. The reduction in freeze time, accessible actuation temperatures, chemical compatibility, and low complexity make the implementation of compact INP-based FTV arrays practical and attractive for the control of integrated biochemical assays.

A microfluidic device for studying cell signaling with multiple inputs and adjustable amplitudes and frequencies

NASA Astrophysics Data System (ADS)

Ningsih, Zubaidah; Chon, James W. M.; Clayton, Andrew H. A.

2013-12-01

Cell function is largely controlled by an intricate web of macromolecular interactions called signaling networks. It is known that the type and the intensity (concentration) of stimulus affect cell behavior. However, the temporal aspect of the stimulus is not yet fully understood. Moreover, the process of distinguishing between two stimuli by a cell is still not clear. A microfluidic device enables the delivery of a precise and exact stimulus to the cell due to the laminar flow established inside its micro-channel. The slow stream delivers a constant stimulus which is adjustable according to the experiment set up. Moreover, with controllable inputs, microfluidic facilitates the stimuli delivery according to a certain pattern with adjustable amplitude, frequency and phase. Several designs of PDMS microfluidic device has been produced in this project via photolithography and soft lithography processes. To characterize the microfluidic performance, two experiments has been conducted. First, by comparing the fluorescence intensity and the lifetime of fluorescein in the present of KI, mixing extent between two inputs was observed using Frequency Lifetime Imaging Microscopy (FLIM). Furthermore, the input-output relationship of fluorescein concentration delivered was also drawn to characterize the amplitude, frequency and phase of the inputs. Second experiment involved the cell culturing inside microfluidic. Using NG108-15 cells, proliferation and differentiation were observed based on the cell number and cell physiological changes. Our results demonstrate that hurdle design gives 86% mixing of fluorescein and buffer. Relationship between inputoutput fluorescein concentrations delivered has also been demonstrated and cells were successfully cultured inside the microfluidic.