Simple and cost-effective fabrication of microvalve arrays in PDMS using laser cut molds with application to C. elegans manipulation in microfluidics

NASA Astrophysics Data System (ADS)

Samuel, R.; Thacker, C. M.; Maricq, A. V.; Gale, B. K.

2014-09-01

We present a new fabrication protocol for fabricating pneumatically controlled microvalve arrays (consisting of 100 s of microvalves) in PDMS substrates. The protocol utilizes rapid and cost-effective fabrication of molds using laser cutting of adhesive vinyl tapes and replica molding of PDMS. Hence the protocol is fast, simple and avoids cleanroom use. The results show that effective doormat-style microvalves can be easily fabricated in arrays by manipulating the stiffness of the actuating membrane through varying the valve-chamber area/shape. Three frequently used valve-chamber shapes (circle, square and capsule) were tested and all showed advantages in different situations. Circular valve chambers were best for small valves, square valves were best for medium-sized valves, and the capsule valves were best for larger valves. An application of this protocol has been demonstrated in the fabrication of a microfluidic 32-well plate for high-throughput manipulation of C. elegans for biomedical research.

Hybrid optofluidic biosensors

NASA Astrophysics Data System (ADS)

Parks, Joshua W.

Optofluidics, born of the desire to create a system containing microfluidic environments with integrated optical elements, has seen dramatic increases in popularity over the last 10 years. In particular, the application of this technology towards chip based molecular sensors has undergone significant development. The most sensitive of these biosensors interface liquid- and solid-core antiresonant reflecting optical waveguides (ARROWs). These sensor chips are created using conventional silicon microfabrication. As such, ARROW technology has previously been unable to utilize state-of-the-art microfluidic developments because the technology used--soft polydimethyl siloxane (PDMS) micromolded chips--is unamenable to the silicon microfabrication workflows implemented in the creation of ARROW detection chips. The original goal of this thesis was to employ hybrid integration, or the connection of independently designed and fabricated optofluidic and microfluidic chips, to create enhanced biosensors with the capability of processing and detecting biological samples on a single hybrid system. After successful demonstration of this paradigm, this work expanded into a new direction--direct integration of sensing and detection technologies on a new platform with dynamic, multi-dimensional photonic re-configurability. This thesis reports a number of firsts, including: • 1,000 fold optical transmission enhancement of ARROW optofluidic detection chips through thermal annealing, • Detection of single nucleic acids on a silicon-based ARROW chip, • Hybrid optofluidic integration of ARROW detection chips and passive PDMS microfluidic chips, • Hybrid optofluidic integration of ARROW detection chips and actively controllable PDMS microfluidic chips with integrated microvalves, • On-chip concentration and detection of clinical Ebola nucleic acids, • Multimode interference (MMI) waveguide based wavelength division multiplexing for detection of single influenza virions, • All PDMS platform created from monolithically integrated solid- and liquid-core waveguides with single particle detection efficiency and directly integrated microvalves, featuring: ∘ Tunable/tailorable PDMS MMI waveguides, ∘ Lightvalves (optical switch/fluidic microvalve) with the ability to dynamically control light and fluid flow simultaneously, ∘ Lightvalve trap architecture with the ability to physically trap, detect, and analyze single biomolecules.

A programmable droplet-based microfluidic device applied to multiparameter analysis of single microbes and microbial communities

PubMed Central

Leung, Kaston; Zahn, Hans; Leaver, Timothy; Konwar, Kishori M.; Hanson, Niels W.; Pagé, Antoine P.; Lo, Chien-Chi; Chain, Patrick S.; Hallam, Steven J.; Hansen, Carl L.

2012-01-01

We present a programmable droplet-based microfluidic device that combines the reconfigurable flow-routing capabilities of integrated microvalve technology with the sample compartmentalization and dispersion-free transport that is inherent to droplets. The device allows for the execution of user-defined multistep reaction protocols in 95 individually addressable nanoliter-volume storage chambers by consecutively merging programmable sequences of picoliter-volume droplets containing reagents or cells. This functionality is enabled by “flow-controlled wetting,” a droplet docking and merging mechanism that exploits the physics of droplet flow through a channel to control the precise location of droplet wetting. The device also allows for automated cross-contamination-free recovery of reaction products from individual chambers into standard microfuge tubes for downstream analysis. The combined features of programmability, addressability, and selective recovery provide a general hardware platform that can be reprogrammed for multiple applications. We demonstrate this versatility by implementing multiple single-cell experiment types with this device: bacterial cell sorting and cultivation, taxonomic gene identification, and high-throughput single-cell whole genome amplification and sequencing using common laboratory strains. Finally, we apply the device to genome analysis of single cells and microbial consortia from diverse environmental samples including a marine enrichment culture, deep-sea sediments, and the human oral cavity. The resulting datasets capture genotypic properties of individual cells and illuminate known and potentially unique partnerships between microbial community members. PMID:22547789

Micro-valve using induced-charge electrokinetic motion of Janus particle.

PubMed

Daghighi, Yasaman; Li, Dongqing

2011-09-07

A new micro-valve using the electrokinetic motion of a Janus particle is introduced in this paper. A Janus particle with a conducting hemisphere and a non-conducting hemisphere is placed in a junction of several microchannels. Under an applied electric field, the induced-charge electrokinetic flow around the conducting side of the Janus particle forms vortices. The vortices push the particle moving forwards to block the entrance of a microchannel. By switching the direction of the applied electric field, the motion of the Janus particle can be changed to block different microchannels. This paper develops a theoretical model and conducts numerical simulations of the three-dimensional transient motion of the Janus particle. The results show that this Janus particle-based micro-valve is feasible for switching and controlling the flow rate in a microfluidic chip. This method is simple in comparison with other types of micro-valve methods. It is easy for fabrication, for operation control, and has a fast response time. To better understand the micro-valve functions, comparisons with a non-conducting particle and a fully conducting particle were made. Results proved that only a Janus particle can fulfill the requirements of such a micro-valve.

A highly addressable static droplet array enabling digital control of a single droplet at pico-volume resolution.

PubMed

Jeong, Heon-Ho; Lee, Byungjin; Jin, Si Hyung; Jeong, Seong-Geun; Lee, Chang-Soo

2016-04-26

Droplet-based microfluidics enabling exquisite liquid-handling has been developed for diagnosis, drug discovery and quantitative biology. Compartmentalization of samples into a large number of tiny droplets is a great approach to perform multiplex assays and to improve reliability and accuracy using a limited volume of samples. Despite significant advances in microfluidic technology, individual droplet handling in pico-volume resolution is still a challenge in obtaining more efficient and varying multiplex assays. We present a highly addressable static droplet array (SDA) enabling individual digital manipulation of a single droplet using a microvalve system. In a conventional single-layer microvalve system, the number of microvalves required is dictated by the number of operation objects; thus, individual trap-and-release on a large-scale 2D array format is highly challenging. By integrating double-layer microvalves, we achieve a "balloon" valve that preserves the pressure-on state under released pressure; this valve can allow the selective releasing and trapping of 7200 multiplexed pico-droplets using only 1 μL of sample without volume loss. This selectivity and addressability completely arranged only single-cell encapsulated droplets from a mixture of droplet compositions via repetitive selective trapping and releasing. Thus, it will be useful for efficient handling of miniscule volumes of rare or clinical samples in multiplex or combinatory assays, and the selective collection of samples.

Microvalve-based microfluidic device for C. elegans manipulation

NASA Astrophysics Data System (ADS)

Johari, S.; Nock, V.; Alkaisi, M. M.; Wang, W.

2017-09-01

In this paper, we report on the integration of a force measurement application capable of continuously measuring the forces generated by C. elegans in motion with a series of controllable microvalves which have an additional ability to increase control over worm selection and manipulation. The three-layer device consists of a pneumatic layer at the top, and a fluidic layer at the bottom with a thin PDMS membrane which functions as a microvalve sandwiched in between. The pneumatic layer functions as valves, whose operation is controlled pneumatically. The fluidic layer contains of PDMS micropillars for resolving the worm force from the deflection of the cantilever-like pillars. The measured force is horizontal and equivalent to a point force acting at half of the pillar height. By carefully controlling the incorporated microvalves, the proposed device is able to select and direct worm movement and at the same time increase the number of force measurement results collected. The integration of the microvalve with the PDMS micropillar-based on chip system can be easily combined with existing screening and imaging systems and also has the capability to facilitate high-throughput screening of force patterns in C. elegans locomotion behaviour.

Analysis of Poiseuille Flow Property in Two-Dimensional Mi-cro Channels of Microfluidic Pneumatic Micro-Valve

NASA Astrophysics Data System (ADS)

Yang, Shaohua; Long, Wei; Chen, Yajun

2018-03-01

In this paper, the control mechanism and mathematical description of the microfluidic flow in the microfluidic process of the PDMS membrane type pneumatic micro-valve were studied. The velocity and pressure variation law of the velocity field inside micro valve was analyzed by numerical simulation method. The influence of the two kinds of inlet drive modes on the working effect and the pressure flow characteristics of the pneumatic micro-valve was studied. The structure of the elastic solid valve diaphragm under the dual action of the airway and the liquid channel was analyzed. Deformation and stress distribution. The results show that the gas flow in the gas flow channel under the diaphragm by the vacuum part of the role of the formation of a suction gas vortex, pressure-driven mode was easier under the diaphragm to produce a strong gas vortex, resulting in internal and external pressure to promote diaphragm cut-off liquid channel; In the pressure pneumatic mode, the stress at both ends of the diaphragm was smaller, the membrane was not easy to tear failure.

Microfluidic valve array control system integrating a fluid demultiplexer circuit

NASA Astrophysics Data System (ADS)

Kawai, Kentaro; Arima, Kenta; Morita, Mizuho; Shoji, Shuichi

2015-06-01

This paper proposes an efficient control method for the large-scale integration of microvalves in microfluidic systems. The proposed method can control 2n individual microvalves with 2n + 2 control lines (where n is an integer). The on-chip valves are closed by applying pressure to a control line, similar to conventional pneumatic microvalves. Another control line closes gate valves between the control line to the on-chip valves and the on-chip valves themselves, to preserve the state of the on-chip valves. The remaining control lines select an activated gate valve. While the addressed gate valve is selected by the other control lines, the corresponding on-chip valve is actuated by applying input pressure to the control line to the on-chip valves. Using this method would substantially reduce the number of world-to-chip connectors and off-chip valve controllers. Experiments conducted using a fabricated 28 microvalve array device, comprising 256 individual on-chip valves controlled with 18 (2   ×   8 + 2) control lines, yielded switching speeds for the selected on-chip valve under 90 ms.

A PDMS membrane microvalve with one-dimensional line valve seat for robust microfluidics

NASA Astrophysics Data System (ADS)

Park, Chin-Sung; Hwang, Kyu-Youn; Jung, Wonjong; Namkoong, Kak; Chung, Wonseok; Kim, Joon-Ho; Huh, Nam

2014-02-01

We have developed a monolithic polydimethylsiloxane (PDMS) membrane microvalve with an isotropically etched valve seat for robust microfluidics. In order to avoid bonding or sticking of the PDMS membrane to the valve seat during the bonding process, the valve seat was wet-etched to be a one-dimensional line instead of a plane. The simple wet-etching technique allowed for the fabrication of an anti-bonding architecture in a scalable manner, and it intrinsically prevented contact between the PDMS membrane and valve seat when no external force was applied (i.e., normally open). This approach enables the permanent device assembly so that the microfluidic chip can be operable in a wide range of fluid pressures (e.g., over 200 kPa) without any leakage and sticking problems.

Electrostatic actuators for portable microfluidic systems

NASA Astrophysics Data System (ADS)

Tice, Joshua

Both developed and developing nations have an urgent need to diagnose disease cheaply, reliably, and independently of centralized facilities. Microfulidic platforms are well-positioned to address the need for portable diagnostics, mainly due to their obvious advantage in size. However, most microfluidic methods rely on equipment outside of the chip either for driving fluid flow (e.g., syringe pumps) or for taking measurements (e.g., lasers or microscopes). The energy and space requirements of the whole system inhibit portability and contribute to costs. To capitalize on the strengths of microfluidic platforms and address the serious needs of society, system components need to be miniaturized. Also, miniaturization should be accomplished as simply as possible, considering that simplicity is usually requisite for achieving truly transformative technology. Herein, I attempt to address the issue of controlling fluid flow in portable microfluidic systems. I focus on systems that are driven by elastomer-based membrane valves, since these valves are inherently simple, yet they are capable of sophisticated fluid manipulation. Others have attempted to modify pneumatic microvalves for portable applications, e.g., by transitioning to electromagnetic, thermopneumatic, or piezoelectric actuation principles. However, none of these strategies maintain the proper balance of simplicity, functionality, and ease of integration. My research centers on electrostatic actuators, due to their conceptual simplicity and the efficacy of electrostatic forces on the microscale. To ensure easy integration with polymer-based systems, and to maintain simplicity in the fabrication procedure, the actuators were constructed solely from poly(dimethylsiloxane) and multi-walled carbon nanotubes. In addition, the actuators were fabricated exclusively with soft-lithographic techniques. A mathematical model was developed to identify actuator parameters compatible with soft-lithography, and also to minimize actuation potentials while eliminating stiction. Two strategies were developed to overcome challenges with electrode screening in the presence of aqueous fluids. First, instead of using the electrostatic actuators to interact directly with aqueous solutions, the actuators were used to regulate pressurized control lines for pneumatic microvalves. Secondly, by adopting a normally-closed architecture, the actuators were converted into microvalves capable of directly interacting with aqueous solutions. The two strategies are complementary, and together should enable sophisticated microfluidic systems for applications ranging from point-of-care diagnostics to portable chemical detection. To conclude the dissertation, I demonstrate a proof-of-principle microfluidic system that contained sixteen independently-operated electrostatic valves, operated with battery-operated electrical ancillaries in a hand-held format.

Microfluidic valve with cored glass microneedle for microinjection.

PubMed

Lee, Sanghoon; Jeong, Wonje; Beebe, David J

2003-08-01

In this paper, a new microinjection device was constructed by fusing a glass microneedle and a PDMS-based microvalve. The microneedle was fabricated via traditional micropipette pulling. The PDMS-based microvalve regulates the fluid flow in the microchannel and microneedle. The 'ON/OFF' operation of the valve was controlled by manually supplied pneumatic pressure. The valve membrane utilized a two level geometry to improve control at low flow rates. The relation between pressure and flow was measured and the results showed that very small volumes of fluid (>1 nl) could be controlled. The valve operation was investigated by monitoring the tip of the needle and pneumatic pressure simultaneously and it demonstrated very stable 'ON/OFF' operation to the pressure change.

UV-driven microvalve based on a micro-nano TiO₂/SiO₂ composite surface for microscale flow control.

PubMed

Guo, Ting; Meng, Tao; Li, Wei; Qin, Jilong; Tong, Zhiping; Zhang, Qing; Li, Xueru

2014-03-28

This paper presents a novel ultraviolet (UV)-driven microvalve based on the concept of inserting a trimethyl chlorosilane (CTMS) modified TiO₂/SiO₂ composite patch of switchable wettability in a microfluidic system. A unique micro-nano hierarchical structure was designed and used to enhance the overall wetting contrast with the aim of improving the wetting-based valve performances. Field-emission scanning electron microscopy (FE-SEM) and x-ray photoelectron spectroscopy (XPS) were used to characterize the morphology and chemical composition of the surface. UV-driven wettability conversion on the patched microchannel was investigated using water column relative height tests, and the results confirmed the significant improvement of the hierarchical structure with the surface hydrophobic/hydrophilic conversion, which produced enhancements of 276% and 95% of the water-repellent and water-sucking pressures, respectively, compared with those of the single-scale TiO₂ nanopatterned structure. Accordingly, a good reversible and repeated on-off performance was identified by the valve tests, highlighting the potential application of the novel microvalve in the efficient control of microscale flow.

UV-driven microvalve based on a micro-nano TiO2/SiO2 composite surface for microscale flow control

NASA Astrophysics Data System (ADS)

Guo, Ting; Meng, Tao; Li, Wei; Qin, Jilong; Tong, Zhiping; Zhang, Qing; Li, Xueru

2014-03-01

This paper presents a novel ultraviolet (UV)-driven microvalve based on the concept of inserting a trimethyl chlorosilane (CTMS) modified TiO2/SiO2 composite patch of switchable wettability in a microfluidic system. A unique micro-nano hierarchical structure was designed and used to enhance the overall wetting contrast with the aim of improving the wetting-based valve performances. Field-emission scanning electron microscopy (FE-SEM) and x-ray photoelectron spectroscopy (XPS) were used to characterize the morphology and chemical composition of the surface. UV-driven wettability conversion on the patched microchannel was investigated using water column relative height tests, and the results confirmed the significant improvement of the hierarchical structure with the surface hydrophobic/hydrophilic conversion, which produced enhancements of 276% and 95% of the water-repellent and water-sucking pressures, respectively, compared with those of the single-scale TiO2 nanopatterned structure. Accordingly, a good reversible and repeated on-off performance was identified by the valve tests, highlighting the potential application of the novel microvalve in the efficient control of microscale flow.

Electrokinetic sample preconcentration and hydrodynamic sample injection for microchip electrophoresis using a pneumatic microvalve.

PubMed

Cong, Yongzheng; Katipamula, Shanta; Geng, Tao; Prost, Spencer A; Tang, Keqi; Kelly, Ryan T

2016-02-01

A microfluidic platform was developed to perform online electrokinetic sample preconcentration and rapid hydrodynamic sample injection for zone electrophoresis using a single microvalve. The polydimethylsiloxane microchip comprises a separation channel, a side channel for sample introduction, and a control channel which is used as a pneumatic microvalve aligned at the intersection of the two flow channels. The closed microvalve, created by multilayer soft lithography, serves as a nanochannel preconcentrator under an applied electric potential, enabling current to pass through while preventing bulk flow. Once analytes are concentrated, the valve is briefly opened and the stacked sample is pressure injected into the separation channel for electrophoretic separation. Fluorescently labeled peptides were enriched by a factor of ∼450 in 230 s. This method enables both rapid analyte concentration and controlled injection volume for high sensitivity, high-resolution CE. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Inkjet 3D printed check microvalve

NASA Astrophysics Data System (ADS)

Walczak, Rafał; Adamski, Krzysztof; Lizanets, Danylo

2017-04-01

3D printing enables fast and relatively easy fabrication of various microfluidic structures including microvalves. A check microvalve is the simplest valve enabling control of the fluid flow in microchannels. Proper operation of the check valve is ensured by a movable element that tightens the valve seat during backward flow and enables free flow for forward pressure. Thus, knowledge of the mechanical properties of the movable element is crucial for optimal design and operation of the valve. In this paper, we present for the first time the results of investigations on basic mechanical properties of the building material used in multijet 3D printing. Specified mechanical properties were used in the design and fabrication of two types of check microvalve—with deflecting or hinge-fixed microflap—with 200 µm and 300 µm thickness. Results of numerical simulation and experimental data of the microflap deflection were obtained and compared. The valves were successfully 3D printed and characterised. Opening/closing characteristics of the microvalve for forward and backward pressures were determined. Thus, proper operation of the check microvalve so developed was confirmed.

An electrochemical albumin-sensing system utilizing microfluidic technology

NASA Astrophysics Data System (ADS)

Huang, Chao-June; Lu, Chiu-Chun; Lin, Thong-Yueh; Chou, Tse-Chuan; Lee, Gwo-Bin

2007-04-01

This paper reports an integrated microfluidic chip capable of detecting the concentration of albumin in urine by using an electrochemical method in an automatic format. The integrated microfluidic chip was fabricated by using microelectromechanical system techniques. The albumin detection was conducted by using the electrochemical sensing method, in which the albumin in urine was detected by measuring the difference of peak currents between a bare reference electrode and an albumin-adsorption electrode. To perform the detection of the albumin in an automatic format, pneumatic microvalves and micropumps were integrated onto the microfluidic chip. The albumin sample and interference mixture solutions such as homovanillic acid, dopamine, norepinephrine and epinephrine were first stored in one of the three reservoirs. Then the solution comprising the albumin sample and interference solutions was transported to pass through the detection zone utilizing the pneumatic micropump. Experimental data showed that the developed system can successfully detect the concentration of the albumin in the existence of interference materials. When compared with the traditional albumin-sensing method, smaller amounts of samples were required to perform faster detection by using the integrated microfluidic chip. Additionally, the microfluidic chip integrated with pneumatic micropumps and microvalves facilitates the transportation of the samples in an automatic mode with lesser human intervention. The development of the integrated microfluidic albumin-sensing system may be promising for biomedical applications. Preliminary results of the current paper were presented at the 2nd International Meeting on Microsensors and Microsystems 2006 (National Cheng Kung University, Tainan, Taiwan, 15-18 January).

Characterization of electrokinetic gating valve in microfluidic channels.

PubMed

Zhang, Guiseng; Du, Wei; Liu, Bi-Feng; Hisamoto, Hideaki; Terabe, Shigeru

2007-02-12

Electrokinetic gating, functioning as a micro-valve, has been widely employed in microfluidic chips for sample injection and flow switch. Investigating its valving performance is fundamentally vital for microfluidics and microfluidics-based chemical analysis. In this paper, electrokinetic gating valve in microchannels was evaluated using optical imaging technique. Microflow profiles at channels junction were examined, revealing that molecular diffusion played a significant role in the valving disable; which could cause analyte leakage in sample injection. Due to diffusion, the analyte crossed the interface of the analyte flow and gating flow, and then formed a cometic tail-like diffusion area at channels junction. From theoretical calculation and some experimental evidences, the size of the area was related to the diffusion coefficient and the velocity of analytes. Additionally, molecular diffusion was also believed to be another reason of sampling bias in gated injection.

Electrokinetic Sample Preconcentration and Hydrodynamic Sample Injection for Microchip Electrophoresis Using a Pneumatic Microvalve

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

Cong, Yongzheng; Katipamula, Shanta; Geng, Tao

2016-02-01

A microfluidic platform was developed to perform online electrokinetic sample preconcentration and rapid hydrodynamic sample injection for electrophoresis using a single microvalve. The PDMS microchip consists of a separation channel, a side channel for sample introduction, and a control channel which is used as a pneumatic microvalve aligned at the intersection of the two flow channels. The closed microvalve, created by multilayer soft lithography, can serve as a preconcentrator under an applied electric potential, enabling current to pass through while blocking bulk flow. Once analytes are concentrated, the valve is briefly opened and the stacked sample is pressure injected intomore » the separation channel for electrophoretic separation. Fluorescently labeled peptides were enriched by a factor of ~450 in 230 s. The performance of the platform was validated by the online preconcentration, injection and electrophoretic separation of fluorescently labeled peptides. This method enables both rapid analyte concentration and controlled injection volume for high sensitivity, high resolution capillary electrophoresis.« less

A microfluidic system with integrated molecular imprinting polymer films for surface plasmon resonance detection

NASA Astrophysics Data System (ADS)

Huang, Shih-Chiang; Lee, Gwo-Bin; Chien, Fan-Ching; Chen, Shean-Jen; Chen, Wen-Janq; Yang, Ming-Chang

2006-07-01

This paper presents a novel microfluidic system with integrated molecular imprinting polymer (MIP) films designed for surface plasmon resonance (SPR) biosensing of multiple nanoscale biomolecules. The innovative microfluidic chip uses pneumatic microvalves and micropumps to transport a precise amount of the biosample through multiple microchannels to sensing regions containing the locally spin-coated MIP films. The signals of SPR biosensing are basically proportional to the number of molecules adsorbed on the MIP films. Hence, a precise control of flow rates inside microchannels is important to determine the adsorption amount of the molecules in the SPR/MIP chips. The integration of micropumps and microvalves can automate the sample introduction process and precisely control the amount of the sample injection to the microfluidic system. The proposed biochip enables the label-free biosensing of biomolecules in an automatic format, and provides a highly sensitive, highly specific and high-throughput detection performance. Three samples, i.e. progesterone, cholesterol and testosterone, are successfully detected using the developed system. The experimental results show that the proposed SPR/MIP microfluidic chip provides a comparable sensitivity to that of large-scale SPR techniques, but with reduced sample consumption and an automatic format. As such, the developed biochip has significant potential for a wide variety of nanoscale biosensing applications. The preliminary results of the current paper were presented at Transducers 2005, Seoul, Korea, 5-9 June 2005.

Flow restrictor silicon membrane microvalve actuated by optically controlled paraffin phase transition

NASA Astrophysics Data System (ADS)

Kolari, K.; Havia, T.; Stuns, I.; Hjort, K.

2014-08-01

Restrictor valves allow proportional control of fluid flow but are rarely integrated in microfluidic systems. In this study, an optically actuated silicon membrane restrictor microvalve is demonstrated. Its actuation is based on the phase transition of paraffin, using a paraffin wax mixed with a suitable concentration of optically absorbing nanographite particles. Backing up the membrane with oil (the melted paraffin) allows for a compliant yet strong contact to the valve seat, which enables handling of high pressures. At flow rates up to 30 µL min-1 and at a pressure of 2 bars, the valve can successfully be closed and control the flow level by restriction. The use of this paraffin composite as an adhesive layer sandwiched between the silicon valve and glass eases fabrication. This type of restrictor valve is best suited for high pressure, low volume flow silicon-based nanofluidic systems.

Use of Buckling Instabilities in Micro Pumps, Valves, and Mixers

NASA Astrophysics Data System (ADS)

Tavakol, Behrouz; Chawan, Aschvin; Holmes, Douglas

2014-03-01

We use the buckling of thin, flexible plates for pumping fluids, controlling the flow rate, and mixing different media within a microfluidic channel. A dielectric elastomeric film with a confined geometry buckles out of the plane when exposed to an electric field. Solid or grease electrodes have traditionally been used as conductive materials to aid in voltage application to both sides of the film. In this work, we use an electrolytic fluid solution as the electrode to enable buckling at relatively low voltages, and to enhance the rate of deformation. We show that this mechanism can be implemented as a microvalve that controls flow rate, or as a micropump that operates over a range of frequencies. A similar mechanism can be used to aid diffusion between two adjacent laminar streams and improve mixing. These low-cost micropumps, microvalves, and micromixers rely on the reversible buckling of thin plates, are easily embeddable in a microfluidic chip, and can potentially be used in variety of applications to accurately control and manipulate fluid flow in a microchannel.

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.

Development of an Extraterrestrial Organic Analyzer (EOA) for Highly Sensitive Organic Detection on an Ice Shell Impact Penetrator (IceShIP)

NASA Astrophysics Data System (ADS)

Stockton, A. M.; Duca, Z. A.; Cato, M.; Cantrell, T.; Kim, J.; Putman, P.; Schmidt, B. E.

2016-12-01

Kinetic penetrators have the potential to enable low cost in situ measurements of the ice of worlds including Europa and Enceladus [1]. Their small size and mass, critical to limiting their kinetic energy, makes them ideal small landers riding on primarily orbiter missions, while enabling sampling at several m depth due to burial and excavation. In situ microfluidic-based organic analysis systems are a powerful, miniaturized approach for detecting markers of habitability and recent biological activity. Development of microfluidic technology, like that of the Mars Organic Analyzer (MOA) [2,3] and Enceladus Organic Analyzer (EOA), has led to an instrument capable of in situ organic chemical analysis compatible with a kinetic penetrator platform. This technology uses an integrated microfluidic processor to prepare samples for analysis via fluorescent derivatization prior to highly sensitive laser-induced fluorescence (LIF) detection. Selective derivatization in the presence of a chiral selector enables distinction between amino acid enantiomers. Finite element analysis of the core microfluidic processing and analytical device indicated that the device itself is more than capable of surviving the stresses associated with an impact acceleration of >50,000g. However, a number of developments were still required to enable a flight-ready system. Preliminary experiments indicated that moving from a pneumatically-actuated to a hydraulically-actuated microvalve system may provide better impact resistance. A hydraulically-actuated microvalve system was developed and tested. A modification of an established microfabricated LIF detection system would use indium bump bonding to permanently weld optical components using standard microfabrication techniques with perfect alignment. Recent work has also focused on developing and characterizing impact-resistant electronics. This work shows the low-TRL development of EOA's LIF and microfluidic subsystems for future planetary impact penetrator missions. With correct structural decisions and optimizations, EOA can survive a 50,000g impact, making it the only current optical instrument with this capability. References: [1] Gowen et al., Adv. Space Res., 2011, 725. [2] Skelley et al, PNAS USA, 2005, 102, 1041. [3] Kim J., et al, Anal. Chem., 2013, 85, 7682.

Force measurements of a magnetic micro actuator proposed for a microvalve array

NASA Astrophysics Data System (ADS)

Chang, Pauline J.; Chang, Frank W.; Yuen, Michelle C.; Otillar, Robert; Horsley, David A.

2014-03-01

Low-cost, easily-fabricated and power-efficient microvalves are necessary for many microfluidic lab-on-a-chip applications. In this study, we present a simple, low-power, scalable, CMOS-compatible magnetic actuator for microvalve applications composed of a paramagnetic bead as the ball valve over a picoliter reaction well etched into a silicon substrate. The paramagnetic bead, composed of either pure FeSi or magnetite in a SiO2 matrix, is actuated by the local magnetic field gradient generated by a microcoil in an aqueous environment, and the reaction well is situated at the microcoil center. A permanent magnet beneath the microvalve device provides an external magnetic biasing field that magnetizes the bead, enabling bidirectional actuation and reducing the current required to actuate the bead to a level below 10 mA. The vertical and radial magnetic forces exerted on the bead by the microcoil were measured for both pure FeSi and composite beads and agree well with the predictions of 2D axisymmetric finite element method models. Vertical forces were within a range of 13-80 nN, and radial forces were 11-60 nN depending on the bead type. The threshold current required to initiate bead actuation was measured as a function of bead diameter and is found to scale inversely with volume for small beads, as expected based on the magnetic force model. To provide an estimate of the stiction force acting between the bead and the passivation layer on the substrate, repeated actuation trials were used to study the bead throw distance for substrates coated with silicon dioxide, Parylene-C, and photoresist. The stiction observed was lowest for a photoresist-coated substrate, while silicon dioxide and Parylene-C coated substrates exhibited similar levels of stiction.

Photothermal generation of microbubbles on plasmonic nanostructures inside microfluidic channels

NASA Astrophysics Data System (ADS)

Li, Jingting; Li, Ming; Santos, Greggy M.; Zhao, Fusheng; Shih, Wei-Chuan

2016-03-01

Microbubbles have been utilized as micro-pumps, micro-mixers, micro-valves, micro-robots and surface cleaners. Various generation techniques can be found in the literature, including resistive heating, hydrodynamic methods, illuminating patterned metal films and noble metal nanoparticles of Au or Ag. We present photothermal microbubble generation by irradiating nanoporous gold disk covered microfluidic channels. The size of the microbubble can be controlled by adjusting the laser power. The dynamics of both bubble growth and shrinkage are studied. The advantages of this technique are flexible bubble generation locations, long bubble lifetimes, no need for light-adsorbing dyes, high controllability over bubble size, low power consumption, etc. This technique has the potential to provide new flow control functions 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.

A valveless rotary microfluidic device for multiplex point mutation identification based on ligation-rolling circle amplification.

PubMed

Heo, Hyun Young; Chung, Soyi; Kim, Yong Tae; Kim, Do Hyun; Seo, Tae Seok

2016-04-15

Genetic variations such as single nucleotide polymorphism (SNP) and point mutations are important biomarkers to monitor disease prognosis and diagnosis. In this study, we developed a novel rotary microfluidic device which can perform multiplex SNP typing on the mutation sites of TP53 genes. The microdevice consists of three glass layers: a channel wafer, a Ti/Pt electrode-patterned resistance temperature detector (RTD) wafer, and a rotary plate in which twelve reaction chambers were fabricated. A series of sample injection, ligation-rolling circle amplification (L-RCA) reaction, and fluorescence detection of the resultant amplicons could be executed by rotating the top rotary plate, identifying five mutation points related with cancer prognosis. The use of the rotary plate eliminates the necessity of microvalves and micropumps to control the microfluidic flow in the channel, simplifying the chip design and chip operation for multiplex SNP detection. The proposed microdevice provides an advanced genetic analysis platform in terms of multiplexity, simplicity, and portability in the fields of biomedical diagnostics. Copyright © 2015 Elsevier B.V. All rights reserved.

A light writable microfluidic "flash memory": optically addressed actuator array with latched operation for microfluidic applications.

PubMed

Hua, Zhishan; Pal, Rohit; Srivannavit, Onnop; Burns, Mark A; Gulari, Erdogan

2008-03-01

This paper presents a novel optically addressed microactuator array (microfluidic "flash memory") with latched operation. Analogous to the address-data bus mediated memory address protocol in electronics, the microactuator array consists of individual phase-change based actuators addressed by localized heating through focused light patterns (address bus), which can be provided by a modified projector or high power laser pointer. A common pressure manifold (data bus) for the entire array is used to generate large deflections of the phase change actuators in the molten phase. The use of phase change material as the working media enables latched operation of the actuator array. After the initial light "writing" during which the phase is temporarily changed to molten, the actuated status is self-maintained by the solid phase of the actuator without power and pressure inputs. The microfluidic flash memory can be re-configured by a new light illumination pattern and common pressure signal. The proposed approach can achieve actuation of arbitrary units in a large-scale array without the need for complex external equipment such as solenoid valves and electrical modules, which leads to significantly simplified system implementation and compact system size. The proposed work therefore provides a flexible, energy-efficient, and low cost multiplexing solution for microfluidic applications based on physical displacements. As an example, the use of the latched microactuator array as "normally closed" or "normally open" microvalves is demonstrated. The phase-change wax is fully encapsulated and thus immune from contamination issues in fluidic environments.

Microprocessor-based integration of microfluidic control for the implementation of automated sensor monitoring and multithreaded optimization algorithms.

PubMed

Ezra, Elishai; Maor, Idan; Bavli, Danny; Shalom, Itai; Levy, Gahl; Prill, Sebastian; Jaeger, Magnus S; Nahmias, Yaakov

2015-08-01

Microfluidic applications range from combinatorial synthesis to high throughput screening, with platforms integrating analog perfusion components, digitally controlled micro-valves and a range of sensors that demand a variety of communication protocols. Currently, discrete control units are used to regulate and monitor each component, resulting in scattered control interfaces that limit data integration and synchronization. Here, we present a microprocessor-based control unit, utilizing the MS Gadgeteer open framework that integrates all aspects of microfluidics through a high-current electronic circuit that supports and synchronizes digital and analog signals for perfusion components, pressure elements, and arbitrary sensor communication protocols using a plug-and-play interface. The control unit supports an integrated touch screen and TCP/IP interface that provides local and remote control of flow and data acquisition. To establish the ability of our control unit to integrate and synchronize complex microfluidic circuits we developed an equi-pressure combinatorial mixer. We demonstrate the generation of complex perfusion sequences, allowing the automated sampling, washing, and calibrating of an electrochemical lactate sensor continuously monitoring hepatocyte viability following exposure to the pesticide rotenone. Importantly, integration of an optical sensor allowed us to implement automated optimization protocols that require different computational challenges including: prioritized data structures in a genetic algorithm, distributed computational efforts in multiple-hill climbing searches and real-time realization of probabilistic models in simulated annealing. Our system offers a comprehensive solution for establishing optimization protocols and perfusion sequences in complex microfluidic circuits.

A novel microfluidic valve controlledby induced charge electro-osmotic flow

NASA Astrophysics Data System (ADS)

Wang, Chengfa; Song, Yongxin; Pan, Xinxiang; Li, Dongqing

2016-07-01

In this paper, a novel microfluidic valve by utilizing induced charge electro-osmotic flow (ICEOF) is proposed and analyzed. The key part of the microfluidic valve is a Y-shaped microchannel. A small metal plate is placed at each corner of the junction of the Y-shaped microchannel. When a DC electrical field is applied through the channels, electro-osmotic flows occur in the channels, and two vortices will be formed near each of the metal plates due to the ICEOF. The two vortices behave like virtual ‘blocking columns’ to restrain and direct the flow in the Y-channel. In this paper, effects of the length of the metal plates, the applied voltages, the width of the microchannel, the zeta potential of the non-metal microchannel wall, and the orientation of the branch channels on the flow switching between two outlet channels are numerically investigated. The results show that the flow switching between the two outlet channels can be flexibly achieved by adjusting the applied DC voltages. The critical switching voltage (CSV), under which one outlet channel is closed, decreases with the increase in the metal plate length and the orientation angle of the outlet channels. The CSV, however, increases with the increase in the inlet voltage, the width of the microchannel, and the absolute value of the zeta potential of the non-metal microchannel wall. Compared with other types of micro-valves, the proposed micro-valve is simple in structure without any moving parts. Only a DC power source is needed for its actuation, thus it can operate automatically by controlling the applied voltages.

On-demand generation and mixing of liquid-in-gas slugs with digitally-programmable composition and size

PubMed Central

Chen, Yi-Chun; Liu, Kan; Shen, Clifton Kwang-Fu; van Dam, R. Michael

2017-01-01

Microscopic droplets or slugs of mixed reagents provide a convenient platform for performing large numbers of isolated biochemical or chemical reactions for many screening and optimization applications. Myriad microfluidic approaches have emerged for creating droplets or slugs with controllable size and composition, generally using an immiscible carrier fluid to assist with the formation or merging processes. We report a novel device for generation of liquid slugs in air when the use of a carrier liquid is not compatible with the application. The slug generator contains two adjacent chambers, each of which has a volume that can be digitally adjusted by closing selected microvalves. Reagents are filled into the two chambers, merged together into a contiguous liquid slug, ejected at the desired time from the device using gas pressure, and mixed by flowing in a downstream channel. Programmable size and composition of slugs is achieved by dynamically adjusting the volume of each chamber prior to filling. Slug formation in this fashion is independent of fluid properties and can easily be scaled to mix larger numbers of reagents. This device has already been used to screen monomer ratios in supramolecular nanoparticle assembly and radiolabeling conditions of engineered antibodies, and here we provide a detailed description of the underlying device. PMID:29167603

Punch card programmable microfluidics.

PubMed

Korir, George; Prakash, Manu

2015-01-01

Small volume fluid handling in single and multiphase microfluidics provides a promising strategy for efficient bio-chemical assays, low-cost point-of-care diagnostics and new approaches to scientific discoveries. However multiple barriers exist towards low-cost field deployment of programmable microfluidics. Incorporating multiple pumps, mixers and discrete valve based control of nanoliter fluids and droplets in an integrated, programmable manner without additional required external components has remained elusive. Combining the idea of punch card programming with arbitrary fluid control, here we describe a self-contained, hand-crank powered, multiplex and robust programmable microfluidic platform. A paper tape encodes information as a series of punched holes. A mechanical reader/actuator reads these paper tapes and correspondingly executes operations onto a microfluidic chip coupled to the platform in a plug-and-play fashion. Enabled by the complexity of codes that can be represented by a series of holes in punched paper tapes, we demonstrate independent control of 15 on-chip pumps with enhanced mixing, normally-closed valves and a novel on-demand impact-based droplet generator. We demonstrate robustness of operation by encoding a string of characters representing the word "PUNCHCARD MICROFLUIDICS" using the droplet generator. Multiplexing is demonstrated by implementing an example colorimetric water quality assays for pH, ammonia, nitrite and nitrate content in different water samples. With its portable and robust design, low cost and ease-of-use, we envision punch card programmable microfluidics will bring complex control of microfluidic chips into field-based applications in low-resource settings and in the hands of children around the world.

Mobile monolithic polymer elements for flow control in microfluidic devices

DOEpatents

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

2004-08-31

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 either fluid or gas pressure 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.

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.

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.

Digital microfluidics: A promising technique for biochemical applications

NASA Astrophysics Data System (ADS)

Wang, He; Chen, Liguo; Sun, Lining

2017-12-01

Digital microfluidics (DMF) is a versatile microfluidics technology that has significant application potential in the areas of automation and miniaturization. In DMF, discrete droplets containing samples and reagents are controlled to implement a series of operations via electrowetting-on-dielectric. This process works by applying electrical potentials to an array of electrodes coated with a hydrophobic dielectric layer. Unlike microchannels, DMF facilitates precise control over multiple reaction processes without using complex pump, microvalve, and tubing networks. DMF also presents other distinct features, such as portability, less sample consumption, shorter chemical reaction time, flexibility, and easier combination with other technology types. Due to its unique advantages, DMF has been applied to a broad range of fields (e.g., chemistry, biology, medicine, and environment). This study reviews the basic principles of droplet actuation, configuration design, and fabrication of the DMF device, as well as discusses the latest progress in DMF from the biochemistry perspective.

Morphology-Patterned Anisotropic Wetting Surface for Fluid Control and Gas-Liquid Separation in Microfluidics.

PubMed

Wang, Shuli; Yu, Nianzuo; Wang, Tieqiang; Ge, Peng; Ye, Shunsheng; Xue, Peihong; Liu, Wendong; Shen, Huaizhong; Zhang, Junhu; Yang, Bai

2016-05-25

This article shows morphology-patterned stripes as a new platform for directing flow guidance of the fluid in microfluidic devices. Anisotropic (even unidirectional) spreading behavior due to anisotropic wetting of the underlying surface is observed after integrating morphology-patterned stripes with a Y-shaped microchannel. The anisotropic wetting flow of the fluid is influenced by the applied pressure, dimensions of the patterns, including the period and depth of the structure, and size of the channels. Fluids with different surface tensions show different flowing anisotropy in our microdevice. Moreover, the morphology-patterned surfaces could be used as a microvalve, and gas-water separation in the microchannel was realized using the unidirectional flow of water. Therefore, benefiting from their good performance and simple fabrication process, morphology-patterned surfaces are good candidates to be applied in controlling the fluid behavior in microfluidics.

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.

A negative-pressure-driven microfluidic chip for the rapid detection of a bladder cancer biomarker in urine using bead-based enzyme-linked immunosorbent assay.

PubMed

Lin, Yen-Heng; Chen, Ying-Ju; Lai, Chao-Sung; Chen, Yi-Ting; Chen, Chien-Lun; Yu, Jau-Song; Chang, Yu-Sun

2013-01-01

This paper describes an integrated microfluidic chip that is capable of rapidly and quantitatively measuring the concentration of a bladder cancer biomarker, apolipoprotein A1, in urine samples. All of the microfluidic components, including the fluid transport system, the micro-valve, and the micro-mixer, were driven by negative pressure, which simplifies the use of the chip and facilitates commercialization. Magnetic beads were used as a solid support for the primary antibody, which captured apolipoprotein A1 in patients' urine. Because of the three-dimensional structure of the magnetic beads, the concentration range of the target that could be detected was as high as 2000 ng ml(-1). Because this concentration is 100 times higher than that quantifiable using a 96-well plate with the same enzyme-linked immunosorbent assay (ELISA) kit, the dilution of the patient's urine can be avoided or greatly reduced. The limit of detection was determined to be approximately 10 ng ml(-1), which is lower than the cutoff value for diagnosing bladder cancer (11.16 ng ml(-1)). When the values measured using the microfluidic chip were compared with those measured using conventional ELISA using a 96-well plate for five patients, the deviations were 0.9%, 6.8%, 9.4%, 1.8%, and 5.8%. The entire measurement time is 6-fold faster than that of conventional ELISA. This microfluidic device shows significant potential for point-of-care applications.

Punch Card Programmable Microfluidics

PubMed Central

Korir, George; Prakash, Manu

2015-01-01

Small volume fluid handling in single and multiphase microfluidics provides a promising strategy for efficient bio-chemical assays, low-cost point-of-care diagnostics and new approaches to scientific discoveries. However multiple barriers exist towards low-cost field deployment of programmable microfluidics. Incorporating multiple pumps, mixers and discrete valve based control of nanoliter fluids and droplets in an integrated, programmable manner without additional required external components has remained elusive. Combining the idea of punch card programming with arbitrary fluid control, here we describe a self-contained, hand-crank powered, multiplex and robust programmable microfluidic platform. A paper tape encodes information as a series of punched holes. A mechanical reader/actuator reads these paper tapes and correspondingly executes operations onto a microfluidic chip coupled to the platform in a plug-and-play fashion. Enabled by the complexity of codes that can be represented by a series of holes in punched paper tapes, we demonstrate independent control of 15 on-chip pumps with enhanced mixing, normally-closed valves and a novel on-demand impact-based droplet generator. We demonstrate robustness of operation by encoding a string of characters representing the word “PUNCHCARD MICROFLUIDICS” using the droplet generator. Multiplexing is demonstrated by implementing an example colorimetric water quality assays for pH, ammonia, nitrite and nitrate content in different water samples. With its portable and robust design, low cost and ease-of-use, we envision punch card programmable microfluidics will bring complex control of microfluidic chips into field-based applications in low-resource settings and in the hands of children around the world. PMID:25738834

Manually Operatable On-Chip Bistable Pneumatic Microstructures for Microfluidic Manipulations

PubMed Central

Chen, A.; Pan, T.

2014-01-01

Bistable microvalves are of particular interest because of their distinct nature requiring energy consumption only during the transition between the open and closed states. This characteristic can be highly advantageous in reducing the number of external inputs and the complexity of control circuitries for microfluidic devices as contemporary lab-on-a-chip platforms are transferring from research settings to low-resource environments with high integratability and small form factor. In this paper, we first present manually operatable, on-chip bistable pneumatic microstructures (BPM) for microfluidic manipulation. The structural design and operation of the BPM devices can be readily integrated into any pneumatically powered microfluidic network consisting of pneumatic and fluidic channels. It is mainly comprised of a vacuum activation chamber (VAC) and a pressure release chamber (PRC), which users have direct control through finger pressing to switch between bistable vacuum state (VS) or atmospheric state (AS). We have integrated multiple BPM devices into a 4-to-1 microfluidic multiplexor to demonstrate on-chip digital flow switching from different sources. Furthermore, we have shown its clinical relevance in a point-of-care diagnostic chip that process blood samples to identify the distinct blood types (A/B/O) on chip. PMID:25007840

Manually operatable on-chip bistable pneumatic microstructures for microfluidic manipulations.

PubMed

Chen, Arnold; Pan, Tingrui

2014-09-07

Bistable microvalves are of particular interest because of their distinct nature of requiring energy consumption only during the transition between the open and closed states. This characteristic can be highly advantageous in reducing the number of external inputs and the complexity of control circuitries since microfluidic devices as contemporary lab-on-a-chip platforms are transferring from research settings to low-resource environments with high integrability and a small form factor. In this paper, we first present manually operatable, on-chip bistable pneumatic microstructures (BPMs) for microfluidic manipulation. The structural design and operation of the BPM devices can be readily integrated into any pneumatically powered microfluidic network consisting of pneumatic and fluidic channels. It is mainly composed of a vacuum activation chamber (VAC) and a pressure release chamber (PRC), of which users have direct control through finger pressing to switch either to the bistable vacuum state (VS) or the atmospheric state (AS). We have integrated multiple BPM devices into a 4-to-1 microfluidic multiplexor to demonstrate on-chip digital flow switching from different sources. Furthermore, we have shown its clinical relevance in a point-of-care diagnostic chip that processes blood samples to identify the distinct blood types (A/B/O) on-chip.

MEMS Micro-Valve for Space Applications

NASA Technical Reports Server (NTRS)

Chakraborty, I.; Tang, W. C.; Bame, D. P.; Tang, T. K.

1998-01-01

We report on the development of a Micro-ElectroMechanical Systems (MEMS) valve that is designed to meet the rigorous performance requirements for a variety of space applications, such as micropropulsion, in-situ chemical analysis of other planets, or micro-fluidics experiments in micro-gravity. These systems often require very small yet reliable silicon valves with extremely low leak rates and long shelf lives. Also, they must survive the perils of space travel, which include unstoppable radiation, monumental shock and vibration forces, as well as extreme variations in temperature. Currently, no commercial MEMS valve meets these requirements. We at JPL are developing a piezoelectric MEMS valve that attempts to address the unique problem of space. We begin with proven configurations that may seem familiar. However, we have implemented some major design innovations that should produce a superior valve. The JPL micro-valve is expected to have an extremely low leak rate, limited susceptibility to particulates, vibration or radiation, as well as a wide operational temperature range.

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.

Field-programmable lab-on-a-chip based on microelectrode dot array architecture.

PubMed

Wang, Gary; Teng, Daniel; Lai, Yi-Tse; Lu, Yi-Wen; Ho, Yingchieh; Lee, Chen-Yi

2014-09-01

The fundamentals of electrowetting-on-dielectric (EWOD) digital microfluidics are very strong: advantageous capability in the manipulation of fluids, small test volumes, precise dynamic control and detection, and microscale systems. These advantages are very important for future biochip developments, but the development of EWOD microfluidics has been hindered by the absence of: integrated detector technology, standard commercial components, on-chip sample preparation, standard manufacturing technology and end-to-end system integration. A field-programmable lab-on-a-chip (FPLOC) system based on microelectrode dot array (MEDA) architecture is presented in this research. The MEDA architecture proposes a standard EWOD microfluidic component called 'microelectrode cell', which can be dynamically configured into microfluidic components to perform microfluidic operations of the biochip. A proof-of-concept prototype FPLOC, containing a 30 × 30 MEDA, was developed by using generic integrated circuits computer aided design tools, and it was manufactured with standard low-voltage complementary metal-oxide-semiconductor technology, which allows smooth on-chip integration of microfluidics and microelectronics. By integrating 900 droplet detection circuits into microelectrode cells, the FPLOC has achieved large-scale integration of microfluidics and microelectronics. Compared to the full-custom and bottom-up design methods, the FPLOC provides hierarchical top-down design approach, field-programmability and dynamic manipulations of droplets for advanced microfluidic operations.

Design and Fabrication of a PDMS Microchip Based Immunoassay

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

Shao, Guocheng; Wang, Wanjun; Wang, Jun

2010-07-01

In this paper, we describe the design and fabrication process of a polydimethylsiloxane (PDMS) microchip for on-chip multiplex immunoassay application. The microchip consists of a PDMS microfluidic channel layer and a micro pneumatic valve control layer. By selectively pressurizing the pneumatic microvalves, immuno reagents were controlled to flow and react in certain fluidic channel sites. Cross contamination was prevented by tightly closed valves. Our design was proposed to utilize PDMS micro channel surface as the solid phase immunoassay substrate and simultaneously detect four targets antigens on chip. Experiment result shows that 20psi valve pressure is sufficient to tightly close amore » 200µm wide micro channel with flow rate up to 20µl/min.« less

Microfabricated valveless devices for thermal bioreactions based on diffusion-limited evaporation.

PubMed

Wang, Fang; Yang, Ming; Burns, Mark A

2008-01-01

Microfluidic devices that reduce evaporative loss during thermal bioreactions such as PCR without microvalves have been developed by relying on the principle of diffusion-limited evaporation. Both theoretical and experimental results demonstrate that the sample evaporative loss can be reduced by more than 20 times using long narrow diffusion channels on both sides of the reaction region. In order to further suppress the evaporation, the driving force for liquid evaporation is reduced by two additional techniques: decreasing the interfacial temperature using thermal isolation and reducing the vapor concentration gradient by replenishing water vapor in the diffusion channels. Both thermal isolation and vapor replenishment techniques can limit the sample evaporative loss to approximately 1% of the reaction content.

Characterization of Bonding Between Poly(dimethylsiloxane) and Cyclic Olefin Coplymer Using Corona Discharge Induced Grafting Polymerization

PubMed Central

Liu, Ke; Gu, Pan; Hamaker, Kiri; Fan, Z. Hugh

2011-01-01

Thermoplastics have been increasingly used for fabricating microfluidic devices because of their low cost, mechanical/biocompatible attributes, and well-established manufacturing processes. However, there is sometimes a need to integrate such a device with components made from other materials such as polydimethylsiloxane (PDMS). Bonding thermoplastics with PDMS to produce hybrid devices is not straightforward. We have reported our method to modify the surface property of a cyclic olefin copolymer (COC) substrate by using corona discharge and grafting polymerization of 3-(trimethoxysilyl)propyl methacrylate; the modified surface enabled strong bonding of COC with PDMS. In this paper, we report our studies on the surface modification mechanism using attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR), X-ray photoelectron spectroscopy (XPS), atomic force microscopy (AFM) and contact angle measurement. Using this bonding method, we fabricated a three-layer (COC/PDMS/COC) hybrid device consisting of elastomer-based valve arrays. The microvalve operation was confirmed through the displacement of a dye solution in a fluidic channel when the elastomer membrane was pneumatically actuated. Valve-enabled microfluidic handling was demonstrated. PMID:21962541

Anisotropic Janus Si nanopillar arrays as a microfluidic one-way valve for gas-liquid separation.

PubMed

Wang, Tieqiang; Chen, Hongxu; Liu, Kun; Li, Yang; Xue, Peihong; Yu, Ye; Wang, Shuli; Zhang, Junhu; Kumacheva, Eugenia; Yang, Bai

2014-04-07

In this paper, we demonstrate a facile strategy for the fabrication of a one-way valve for microfluidic (MF) systems. The micro-valve was fabricated by embedding arrays of Janus Si elliptical pillars (Si-EPAs) with anisotropic wettability into a MF channel fabricated in poly(dimethylsiloxane) (PDMS). Two sides of the Janus pillar are functionalized with molecules with distinct surface energies. The ability of the Janus pillar array to act as a valve was proved by investigating the flow behaviour of water in a T-shaped microchannel at different flow rates and pressures. In addition, the one-way valve was used to achieve gas-liquid separation. We believe that the Janus Si-EPAs modified by specific surface functionalization provide a new strategy to control the flow and motion of fluids in MF channels.

Getting started with Open-Hardware: Development and Control of Microfluidic Devices

PubMed Central

da Costa, Eric Tavares; Mora, Maria F.; Willis, Peter A.; do Lago, Claudimir L.; Jiao, Hong; Garcia, Carlos D.

2014-01-01

Understanding basic concepts of electronics and computer programming allows researchers to get the most out of the equipment found in their laboratories. Although a number of platforms have been specifically designed for the general public and are supported by a vast array of on-line tutorials, this subject is not normally included in university chemistry curricula. Aiming to provide the basic concepts of hardware and software, this article is focused on the design and use of a simple module to control a series of PDMS-based valves. The module is based on a low-cost microprocessor (Teensy) and open-source software (Arduino). The microvalves were fabricated using thin sheets of PDMS and patterned using CO2 laser engraving, providing a simple and efficient way to fabricate devices without the traditional photolithographic process or facilities. Synchronization of valve control enabled the development of two simple devices to perform injection (1.6 ± 0.4 μL/stroke) and mixing of different solutions. Furthermore, a practical demonstration of the utility of this system for microscale chemical sample handling and analysis was achieved performing an on-chip acid-base titration, followed by conductivity detection with an open-source low-cost detection system. Overall, the system provided a very reproducible (98%) platform to perform fluid delivery at the microfluidic scale. PMID:24823494

PMMA/PDMS valves and pumps for disposable microfluidics.

PubMed

Zhang, Wenhua; Lin, Shuichao; Wang, Chunming; Hu, Jia; Li, Cong; Zhuang, Zhixia; Zhou, Yongliang; Mathies, Richard A; Yang, Chaoyong James

2009-11-07

Poly(methyl methacrylate) (PMMA) is gaining in popularity in microfluidic devices because of its low cost, excellent optical transparency, attractive mechanical/chemical properties, and simple fabrication procedures. It has been used to fabricate micromixers, PCR reactors, CE and many other microdevices. Here we present the design, fabrication, characterization and application of pneumatic microvalves and micropumps based on PMMA. Valves and pumps are fabricated by sandwiching a PDMS membrane between PMMA fluidic channel and manifold wafers. Valve closing or opening can be controlled by adjusting the pressure in a displacement chamber on the pneumatic layer via a computer regulated solenoid. The valve provides up to 15.4 microL s(-1) at 60 kPa fluid pressure and seals reliably against forward fluid pressure as high as 60 kPa. A PMMA diaphragm pump can be assembled by simply connecting three valves in series. By varying valve volume or opening time, pumping rates ranging from nL to microL per second can be accurately achieved. The PMMA based valves and pumps were further tested in a disposable automatic nucleic acid extraction microchip to extract DNA from human whole blood. The DNA extraction efficiency was about 25% and the 260 nm/280 nm UV absorption ratio for extracted DNA was 1.72. Because of its advantages of inexpensive, facile fabrication, robust and easy integration, the PMMA valve and pump will find their wide application for fluidic manipulation in portable and disposable microfluidic devices.

Design and analysis of a low actuation voltage electrowetting-on-dielectric microvalve for drug delivery applications.

PubMed

Samad, Mst Fateha; Kouzani, Abbas Z

2014-01-01

This paper presents a low actuation voltage microvalve with optimized insulating layers that manipulates a conducting ferro-fluid droplet by the principle of electrowetting-on-dielectric (EWOD). The proposed EWOD microvalve contains an array of chromium (Cr) electrodes on the soda-lime glass substrate, covered by both dielectric and hydrophobic layers. Various dielectric layers including Su-8 2002, Polyvinylidenefluoride (PVDF) and Cyanoethyl pullulan (CEP), and thin (50 nm) hydrophobic Teflon and Cytonix are used to analyze the EWOD microvalves at different voltages. The Finite Element Method (FEM) based software, Coventorware is used to carry out the simulation analysis. It is observed that the EWOD microvalve having a CEP dielectric layer with dielectric constant of about 20 and thickness of 1 μm, and a Cytonix hydrophobic layer with thickness of 50 nm operated the conducting ferro-fluid droplet at the actuation voltage as low as 7.8 V.

A normally-closed piezoelectric micro-valve with flexible stopper

NASA Astrophysics Data System (ADS)

Chen, Song; Lu, Song; Liu, Yong; Wang, Jiantao; Tian, Xiaochao; Liu, Guojun; Yang, Zhigang

2016-04-01

In the field of controlled drug delivery system, there are still many problems on those reported micro-valves, such as the small opening height, unsatisfactory particle tolerance and high cost. To solve the above problems, a novel normally-closed piezoelectric micro-valve is presented in this paper. The micro-valve was driven by circular unimorph piezoelectric vibrator and natural rubber membrane with high elasticity was used as the valve stopper. The small axial displacement of piezoelectric vibrator can be converted into a large stroke of valve stopper based on hydraulic amplification mechanism. The experiment indicates that maximum hydraulic amplification ratio is up to 14, and the cut-off pressure of the micro-valve is 39kPa in the case of no working voltage. The presented micro valve has a large flow control range (ranging from 0 to 8.75mL/min).

Microvalve-based bioprinting - process, bio-inks and applications.

PubMed

Ng, Wei Long; Lee, Jia Min; Yeong, Wai Yee; Win Naing, May

2017-03-28

Bioprinting is an emerging research field that has attracted tremendous attention for various applications; it offers a highly automated, advanced manufacturing platform for the fabrication of complex bioengineered constructs. Different bio-inks comprising multiple types of printable biomaterials and cells are utilized during the bioprinting process to improve the homology to native tissues and/or organs in a highly reproducible manner. This paper, presenting a first-time comprehensive yet succinct review of microvalve-based bioprinting, provides an in-depth analysis and comparison of different drop-on-demand bioprinting systems and highlights the important considerations for microvalve-based bioprinting systems. This review paper reports a detailed analysis of its printing process, bio-ink properties and cellular components on the printing outcomes. Lastly, this review highlights the significance of drop-on-demand bioprinting for various applications such as high-throughput screening, fundamental cell biology research, in situ bioprinting and fabrication of in vitro tissue constructs and also presents future directions to transform the microvalve-based bioprinting technology into imperative tools for tissue engineering and regenerative medicine.

Characterization of bonding between poly(dimethylsiloxane) and cyclic olefin copolymer using corona discharge induced grafting polymerization.

PubMed

Liu, Ke; Gu, Pan; Hamaker, Kiri; Fan, Z Hugh

2012-01-01

Thermoplastics have been increasingly used for fabricating microfluidic devices because of their low cost, mechanical/biocompatible attributes, and well-established manufacturing processes. However, there is sometimes a need to integrate such a device with components made from other materials such as polydimethylsiloxane (PDMS). Bonding thermoplastics with PDMS to produce hybrid devices is not straightforward. We have reported our method to modify the surface property of a cyclic olefin copolymer (COC) substrate by using corona discharge and grafting polymerization of 3-(trimethoxysilyl)propyl methacrylate; the modified surface enabled strong bonding of COC with PDMS. In this paper, we report our studies on the surface modification mechanism using attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR), X-ray photoelectron spectroscopy (XPS), atomic force microscopy (AFM) and contact angle measurement. Using this bonding method, we fabricated a three-layer (COC/PDMS/COC) hybrid device consisting of elastomer-based valve arrays. The microvalve operation was confirmed through the displacement of a dye solution in a fluidic channel when the elastomer membrane was pneumatically actuated. Valve-enabled microfluidic handling was demonstrated. Copyright © 2011 Elsevier Inc. All rights reserved.

Getting started with open-hardware: development and control of microfluidic devices.

PubMed

da Costa, Eric Tavares; Mora, Maria F; Willis, Peter A; do Lago, Claudimir L; Jiao, Hong; Garcia, Carlos D

2014-08-01

Understanding basic concepts of electronics and computer programming allows researchers to get the most out of the equipment found in their laboratories. Although a number of platforms have been specifically designed for the general public and are supported by a vast array of on-line tutorials, this subject is not normally included in university chemistry curricula. Aiming to provide the basic concepts of hardware and software, this article is focused on the design and use of a simple module to control a series of PDMS-based valves. The module is based on a low-cost microprocessor (Teensy) and open-source software (Arduino). The microvalves were fabricated using thin sheets of PDMS and patterned using CO2 laser engraving, providing a simple and efficient way to fabricate devices without the traditional photolithographic process or facilities. Synchronization of valve control enabled the development of two simple devices to perform injection (1.6 ± 0.4 μL/stroke) and mixing of different solutions. Furthermore, a practical demonstration of the utility of this system for microscale chemical sample handling and analysis was achieved performing an on-chip acid-base titration, followed by conductivity detection with an open-source low-cost detection system. Overall, the system provided a very reproducible (98%) platform to perform fluid delivery at the microfluidic scale. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Larger-Stroke Piezoelectrically Actuated Microvalve

NASA Technical Reports Server (NTRS)

Yang, Eui-Hyeok

2003-01-01

A proposed normally-closed microvalve would contain a piezoelectric bending actuator instead of a piezoelectric linear actuator like that of the microvalve described in the preceding article. Whereas the stroke of the linear actuator of the preceding article would be limited to approximately equal to 6 micrometers, the stroke of the proposed bending actuator would lie in the approximate range of 10 to 15 micrometers-large enough to enable the microvalve to handle a variety of liquids containing suspended particles having sizes up to 10 m. Such particulate-laden liquids occur in a variety of microfluidic systems, one example being a system that sorts cells or large biomolecules for analysis. In comparison with the linear actuator of the preceding article, the bending actuator would be smaller and less massive. The combination of increased stroke, smaller mass, and smaller volume would be obtained at the cost of decreased actuation force: The proposed actuator would generate a force in the approximate range of 1 to 4 N, the exact amount depending on operating conditions and details of design. This level of actuation force would be too low to enable the valve to handle a fluid at the high pressure level mentioned in the preceding article. The proposal encompasses two alternative designs one featuring a miniature piezoelectric bimorph actuator and one featuring a thick-film unimorph piezoelectric actuator (see figure). In either version, the valve would consume a power of only 0.01 W when actuated at a frequency of 100 Hz. Also, in either version, it would be necessary to attach a soft elastomeric sealing ring to the valve seat so that any particles that settle on the seat would be pushed deep into the elastomeric material to prevent or reduce leakage. The overall dimensions of the bimorph version would be 7 by 7 by 1 mm. The actuator in this version would generate a force of 1 N and a stroke of 10 m at an applied potential of 150 V. The actuation force would be sufficient to enable the valve to handle a fluid pressurized up to about 50 psi (approximately equal to 0.35 MPa). The overall dimensions of the unimorph version would be 2 by 2 by 0.5 mm. In this version, an electric field across the piezoelectric film on a diaphragm would cause the film to pull on, and thereby bend, the diaphragm. At an applied potential of 20 V, the actuator in this version would generate a stroke of 10 micrometers and a force of 0.01 N. This force level would be too low to enable handling of fluids at pressures comparable to those of the bimorph version. This version would be useful primarily in microfluidic and nanofluidic applications that involve extremely low differential pressures and in which there are requirements for extreme miniaturization of valves. Examples of such applications include liquid chromatography and sequencing of deoxyribonucleic acid.

Design of protein-responsive micro-sized hydrogels for self-regulating microfluidic systems

NASA Astrophysics Data System (ADS)

Hirayama, Mayu; Tsuruta, Kazuhiro; Kawamura, Akifumi; Ohara, Masayuki; Shoji, Kan; Kawano, Ryuji; Miyata, Takashi

2018-03-01

Diagnosis sensors using micro-total analysis systems (µ-TAS) have been developed for detecting target biomolecules such as proteins and saccharides because they are signal biomolecules for monitoring body conditions and diseases. In this study, biomolecularly stimuli-responsive micro-sized hydrogels that exhibited quick shrinkage in response to lectin concanavalinA (ConA) were prepared in a microchannel by photopolymerization using a fluorescence microscope. In preparing the micro-size hydrogels, glycosyloxyethyl methacrylate (GEMA) as a ligand monomer was copolymerized with a crosslinker in the presence of template ConA in molecular imprinting. The ConA-imprinted micro-hydrogel showed greater shrinkage in response to target ConA than nonimprinted micro-hydrogel. When a buffer solution was switched to an aqueous ConA solution in the Y-shaped microchannel, the flow rates changed quickly because of the responsive shrinkage of the micro-hydrogel prepared in the microchannel. These results suggest that the ConA-imprinted micro-hydrogel acted as a self-regulated microvalve in microfluidic systems.

Deformability and size-based cancer cell separation using an integrated microfluidic device.

PubMed

Pang, Long; Shen, Shaofei; Ma, Chao; Ma, Tongtong; Zhang, Rui; Tian, Chang; Zhao, Lei; Liu, Wenming; Wang, Jinyi

2015-11-07

Cell sorting by filtration techniques offers a label-free approach for cell separation on the basis of size and deformability. However, filtration is always limited by the unpredictable variation of the filter hydrodynamic resistance due to cell accumulation and clogging in the microstructures. In this study, we present a new integrated microfluidic device for cell separation based on the cell size and deformability by combining the microstructure-constricted filtration and pneumatic microvalves. Using this device, the cell populations sorted by the microstructures can be easily released in real time for subsequent analysis. Moreover, the periodical sort and release of cells greatly avoided cell accumulation and clogging and improved the selectivity. Separation of cancer cells (MCF-7, MDA-MB-231 and MDA231-LM2) with different deformability showed that the mixture of the less flexible cells (MCF-7) and the flexible cells (MDA-MB-231 and MDA231-LM2) can be well separated with more than 75% purity. Moreover, the device can be used to separate cancer cells from the blood samples with more than 90% cell recovery and more than 80% purity. Compared with the current filtration methods, the device provides a new approach for cancer cell separation with high collection recovery and purity, and also, possesses practical potential to be applied as a sample preparation platform for fundamental studies and clinical applications.

Reconfigurable virtual electrowetting channels.

PubMed

Banerjee, Ananda; Kreit, Eric; Liu, Yuguang; Heikenfeld, Jason; Papautsky, Ian

2012-02-21

Lab-on-a-chip systems rely on several microfluidic paradigms. The first uses a fixed layout of continuous microfluidic channels. Such lab-on-a-chip systems are almost always application specific and far from a true "laboratory." The second involves electrowetting droplet movement (digital microfluidics), and allows two-dimensional computer control of fluidic transport and mixing. The merging of the two paradigms in the form of programmable electrowetting channels takes advantage of both the "continuous" functionality of rigid channels based on which a large number of applications have been developed to date and the "programmable" functionality of digital microfluidics that permits electrical control of on-chip functions. In this work, we demonstrate for the first time programmable formation of virtual microfluidic channels and their continuous operation with pressure driven flows using an electrowetting platform. Experimental, theoretical, and numerical analyses of virtual channel formation with biologically relevant electrolyte solutions and electrically-programmable reconfiguration are presented. We demonstrate that the "wall-less" virtual channels can be formed reliably and rapidly, with propagation rates of 3.5-3.8 mm s(-1). Pressure driven transport in these virtual channels at flow rates up to 100 μL min(-1) is achievable without distortion of the channel shape. We further demonstrate that these virtual channels can be switched on-demand between multiple inputs and outputs. Ultimately, we envision a platform that would provide rapid prototyping of microfluidic concepts and would be capable of a vast library of functions and benefitting applications from clinical diagnostics in resource-limited environments to rapid system prototyping to high throughput pharmaceutical applications.

Electrically controlled microvalves to integrate microchip polymerase chain reaction and capillary electrophoresis.

PubMed

Kaigala, Govind V; Hoang, Viet N; Backhouse, Christopher J

2008-07-01

Microvalves are key in realizing portable miniaturized diagnostic platforms. We present a scalable microvalve that integrates well with standard lab on a chip (LOC) implementations, yet which requires essentially no external infrastructure for its operation. This electrically controlled, phase-change microvalve is used to integrate genetic amplification and analysis via capillary electrophoresis--the basis of many diagnostics. The microvalve is actuated using a polymer (polyethylene glycol, PEG) that exhibits a large volumetric change between its solid and liquid phases. Both the phase change of the PEG and the genetic amplification via polymerase chain reaction (PCR) are thermally controlled using thin film resistive elements that are patterned using standard microfabrication methods. By contrast with many other valve technologies, these microvalves and their control interface scale down in size readily. The novelty here lies in the use of fully integrated microvalves that require only electrical connections to realize a portable and inexpensive genetic analysis platform.

Paper pump for passive and programmable transport

PubMed Central

Wang, Xiao; Hagen, Joshua A.; Papautsky, Ian

2013-01-01

In microfluidic systems, a pump for fluid-driving is often necessary. To keep the size of microfluidic systems small, a pump that is small in size, light-weight and needs no external power source is advantageous. In this work, we present a passive, simple, ultra-low-cost, and easily controlled pumping method based on capillary action of paper that pumps fluid through conventional polymer-based microfluidic channels with steady flow rate. By using inexpensive cutting tools, paper can be shaped and placed at the outlet port of a conventional microfluidic channel, providing a wide range of pumping rates. A theoretical model was developed to describe the pumping mechanism and aid in the design of paper pumps. As we show, paper pumps can provide steady flow rates from 0.3 μl/s to 1.7 μl/s and can be cascaded to achieve programmable flow-rate tuning during the pumping process. We also successfully demonstrate transport of the most common biofluids (urine, serum, and blood). With these capabilities, the paper pump has the potential to become a powerful fluid-driving approach that will benefit the fielding of microfluidic systems for point-of-care applications. PMID:24403999

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.

Synthesis and cell-free cloning of DNA libraries using programmable microfluidics

PubMed Central

Yehezkel, Tuval Ben; Rival, Arnaud; Raz, Ofir; Cohen, Rafael; Marx, Zipora; Camara, Miguel; Dubern, Jean-Frédéric; Koch, Birgit; Heeb, Stephan; Krasnogor, Natalio; Delattre, Cyril; Shapiro, Ehud

2016-01-01

Microfluidics may revolutionize our ability to write synthetic DNA by addressing several fundamental limitations associated with generating novel genetic constructs. Here we report the first de novo synthesis and cell-free cloning of custom DNA libraries in sub-microliter reaction droplets using programmable digital microfluidics. Specifically, we developed Programmable Order Polymerization (POP), Microfluidic Combinatorial Assembly of DNA (M-CAD) and Microfluidic In-vitro Cloning (MIC) and applied them to de novo synthesis, combinatorial assembly and cell-free cloning of genes, respectively. Proof-of-concept for these methods was demonstrated by programming an autonomous microfluidic system to construct and clone libraries of yeast ribosome binding sites and bacterial Azurine, which were then retrieved in individual droplets and validated. The ability to rapidly and robustly generate designer DNA molecules in an autonomous manner should have wide application in biological research and development. PMID:26481354

Digital quantification of DNA via isothermal amplification on a self-driven microfluidic chip featuring hydrophilic film-coated polydimethylsiloxane.

PubMed

Ma, Yu-Dong; Chang, Wen-Hsin; Luo, Kang; Wang, Chih-Hung; Liu, Shih-Yuan; Yen, Wen-Hsiang; Lee, Gwo-Bin

2018-01-15

Loop-mediated isothermal amplification (LAMP) is a DNA amplification approach characterized by high sensitivity and specificity. In "digital LAMP", small quantities of both template DNA and reagents are encapsulated within a droplet or microwell, allowing for analysis of precious nucleic acid samples in shorter amounts of time relative to traditional DNA amplification protocols (e.g., PCR) with an improved limit of detection. In this study, an integrated, self-driven microfluidic chip was designed to carry out digital LAMP. The entire quantification process could be automatically performed on this chip via capillary forces enabled through microwells comprised of polydimethylsiloxane (PDMS) surfaces coated with a hydrophilic film; no external pumps were required. Moreover, digitized droplets could be separated from each other by normally-closed microvalves. The contact angle of the hydrophilic film-coated PDMS surface was only 14.3°. This is the first time that a rapid (30min) and simple method has been used to create hydrophilic PDMS surfaces that allow for digital LAMP to be performed in a self-driven microfluidic device. As a proof of concept, amplification of a gene specific to a vancomycin-resistant Enterococcus strain was performed on the developed microfluidic chip within 30min, and the limit of detection was only 11 copies with a volume of 30μL. This device may therefore become a promising tool for clinical diagnosis and point-of-care applications. Copyright © 2017 Elsevier B.V. All rights reserved.

Directions for rf-controlled intelligent microvalve

NASA Astrophysics Data System (ADS)

Enderling, Stefan; Varadan, Vijay K.; Abbott, Derek

2001-03-01

In this paper, we consider the novel concept of a Radio Frequency (RF) controllable microvalve for different medical applications. Wireless communication via a Surface Acoustic Wave Identification-mark (SAW ID-tag) is used to control, drive and locate the microvalve inside the human body. The energy required for these functions is provided by RF pulses, which are transmitted to the valve and back by a reader/transmitter system outside of the body. These RF bursts are converted into Surface Acoustic Waves (SAWs), which propagate along the piezoelectric actuator material of the microvalve. These waves cause deflections, which are employed to open and close the microvalve. We identified five important areas of application of the microvalve in biomedicine: 1) fertility control; 2) artificial venous valves; 3) flow cytometry; 4) drug delivery and 5) DNA mapping.

A simple strategy for in situ fabrication of a smart hydrogel microvalve within microchannels for thermostatic control.

PubMed

Lin, Shuo; Wang, Wei; Ju, Xiao-Jie; Xie, Rui; Chu, Liang-Yin

2014-08-07

Self-regulation of temperature in microchip systems is crucial for their applications in biomedical fields such as cell culture and biomolecule synthesis as well as those cases that require constant temperature conditions. Here we report on a simple and versatile approach for in situ fabrication of a smart hydrogel microvalve within a microchip for thermostatic control. The thermo-responsive hydrogel microvalve enables the "on-off" switch by sensing temperature fluctuations to control the fluid flux as well as the fluid heat exchange for self-regulation of the temperature at a constant range. Such temperature self-regulation is demonstrated by integrating the microvalve-incorporated microchip into the flow circulation loop of a micro-heat-exchanging system for thermostatic control. Moreover, the microvalve-incorporated microchip is employed for culturing cells under temperature self-regulation. The smart microvalve shows great potential as a temperature controller for applications that require thermostatic conditions. This approach offers a facile and flexible strategy for in situ fabricating hydrogel microvalves within microchips as chemostats and microreactors for biomedical applications.

A microfluidic chip with a staircase pH gradient generator, a packed column and a fraction collector for chromatofocusing of proteins.

PubMed

Rho, Hoon Suk; Hanke, Alexander Thomas; Ottens, Marcel; Gardeniers, Han J G E

2018-04-01

A microfluidic device for pH gradient chromatofocusing is presented, which performs creation of a micro-column, pH gradient generation, and fraction collection in a single device. Using a sieve micro-valve, anion exchange particles were packed into a microchannel in order to realize a solid-phase absorption column. To fractionate proteins according to their isoelectric points, elution buffer solutions with a stepwise pH gradient were prepared in 16 parallel mixing reactors and flowed through the micro-column, wherein a protein mixture was previously loaded. The volume of the column is only 20 nL, hence it allows extremely low sample consumption and fast analysis compared with a conventional system. We demonstrated separation of two proteins, albumin-fluorescein isothiocyanate conjugate (FITC-BSA) and R-Phycoerythrin (R-PE), by using a microcolumn of commercial charged polymeric particles (Source 15Q). The microfluidic device can be used as a rapid diagnostic tool to analyse crude mixtures of proteins or nucleic acids and determine adsorption/desorption characteristics of various biochemical products, which can be helpful for scientific fundamental understanding as well as instrumental in various industrial applications, especially in early stage screening and process development. © 2018 The Authors Electrophoresis Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Bistable Microvalve For Use With Microcatheter System

DOEpatents

Seward, Kirk Patrick

2003-12-16

A bistable microvalve of shape memory material is operatively connected to a microcatheter. The bistable microvalve includes a tip that can be closed off until it is in the desired position. Once it is in position it can be opened and closed. The system uses heat and pressure to open and close the microvalve. The shape memory material will change stiffness and shape when heated above a transition temperature. The shape memory material is adapted to move from a first shape to a second shape, either open or closed, where it can perform a desired function.

Bistable microvalve and microcatheter system

DOEpatents

Seward, Kirk Patrick

2003-05-20

A bistable microvalve of shape memory material is operatively connected to a microcatheter. The bistable microvalve includes a tip that can be closed off until it is in the desired position. Once it is in position it can opened and closed. The system uses heat and pressure to open and close the microvalve. The shape memory material will change stiffness and shape when heated above a transition temperature. The shape memory material is adapted to move from a first shape to a second shape, either open or closed, where it can perform a desired function.

Fabricating microfluidic valve master molds in SU-8 photoresist

NASA Astrophysics Data System (ADS)

Dy, Aaron J.; Cosmanescu, Alin; Sluka, James; Glazier, James A.; Stupack, Dwayne; Amarie, Dragos

2014-05-01

Multilayer soft lithography has become a powerful tool in analytical chemistry, biochemistry, material and life sciences, and medical research. Complex fluidic micro-circuits require reliable components that integrate easily into microchips. We introduce two novel approaches to master mold fabrication for constructing in-line micro-valves using SU-8. Our fabrication techniques enable robust and versatile integration of many lab-on-a-chip functions including filters, mixers, pumps, stream focusing and cell-culture chambers, with in-line valves. SU-8 created more robust valve master molds than the conventional positive photoresists used in multilayer soft lithography, but maintained the advantages of biocompatibility and rapid prototyping. As an example, we used valve master molds made of SU-8 to fabricate PDMS chips capable of precisely controlling beads or cells in solution.

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.

Anisotropic Janus Si nanopillar arrays as a microfluidic one-way valve for gas-liquid separation

NASA Astrophysics Data System (ADS)

Wang, Tieqiang; Chen, Hongxu; Liu, Kun; Li, Yang; Xue, Peihong; Yu, Ye; Wang, Shuli; Zhang, Junhu; Kumacheva, Eugenia; Yang, Bai

2014-03-01

In this paper, we demonstrate a facile strategy for the fabrication of a one-way valve for microfluidic (MF) systems. The micro-valve was fabricated by embedding arrays of Janus Si elliptical pillars (Si-EPAs) with anisotropic wettability into a MF channel fabricated in poly(dimethylsiloxane) (PDMS). Two sides of the Janus pillar are functionalized with molecules with distinct surface energies. The ability of the Janus pillar array to act as a valve was proved by investigating the flow behaviour of water in a T-shaped microchannel at different flow rates and pressures. In addition, the one-way valve was used to achieve gas-liquid separation. We believe that the Janus Si-EPAs modified by specific surface functionalization provide a new strategy to control the flow and motion of fluids in MF channels.In this paper, we demonstrate a facile strategy for the fabrication of a one-way valve for microfluidic (MF) systems. The micro-valve was fabricated by embedding arrays of Janus Si elliptical pillars (Si-EPAs) with anisotropic wettability into a MF channel fabricated in poly(dimethylsiloxane) (PDMS). Two sides of the Janus pillar are functionalized with molecules with distinct surface energies. The ability of the Janus pillar array to act as a valve was proved by investigating the flow behaviour of water in a T-shaped microchannel at different flow rates and pressures. In addition, the one-way valve was used to achieve gas-liquid separation. We believe that the Janus Si-EPAs modified by specific surface functionalization provide a new strategy to control the flow and motion of fluids in MF channels. Electronic supplementary information (ESI) available: The XPS spectrum of the as-prepared Janus arrays after the MHA modification; the SEM images of the PFS-MHA Janus Si pillar arrays fabricated through oblique evaporation of gold along the short axis of the elliptical pillars; images of the cross-shaped MF channel and Rhodamine aqueous solution injecting in a cross-shaped MF channel taken at different times; the plot data of DPFS/DMHA against the flow rate of the aqueous solution; the plot data of failure pressure against the bottom size of the channel; optical microscopy images of the Janus pillar array with less density of pillars; optical microscopy images of the T junction with higher magnification; the video of Rhodamine solution running in the T-shaped microchannel integrated with the Janus Si-EPAs; the video of the entire gas-liquid separation process. See DOI: 10.1039/c3nr05865d

Actuator operated microvalves

NASA Technical Reports Server (NTRS)

Okojie, Robert S. (Inventor)

2008-01-01

An actuator operated microvalve and the method of making same is disclosed and claimed. The microvalve comprises a SiC housing which includes a first lower portion and a second upper portion. The lower portion of the SiC housing includes a passageway therethrough, a microvalve seat, and a moveable SiC diaphragm. The SiC diaphragm includes a centrally located boss and radially extending corrugations which may be sinusoidally shaped. The boss of the SiC diaphragm moves and modulates in a range of positions between a closed position wherein the boss interengages said microvalve seat prohibiting communication of fluid through the passageway and a fully open position when the boss is spaced apart from the seat at its maximum permitting communication of fluid through said passageway. The actuator includes a SiC top plate affixed to the boss of the diaphragm and a first electrode and the second upper portion of the SiC housing further includes a second electrode.

Fabrication of heterogeneous nanomaterial array by programmable heating and chemical supply within microfluidic platform towards multiplexed gas sensing application

PubMed Central

Yang, Daejong; Kang, Kyungnam; Kim, Donghwan; Li, Zhiyong; Park, Inkyu

2015-01-01

A facile top-down/bottom-up hybrid nanofabrication process based on programmable temperature control and parallel chemical supply within microfluidic platform has been developed for the all liquid-phase synthesis of heterogeneous nanomaterial arrays. The synthesized materials and locations can be controlled by local heating with integrated microheaters and guided liquid chemical flow within microfluidic platform. As proofs-of-concept, we have demonstrated the synthesis of two types of nanomaterial arrays: (i) parallel array of TiO2 nanotubes, CuO nanospikes and ZnO nanowires, and (ii) parallel array of ZnO nanowire/CuO nanospike hybrid nanostructures, CuO nanospikes and ZnO nanowires. The laminar flow with negligible ionic diffusion between different precursor solutions as well as localized heating was verified by numerical calculation and experimental result of nanomaterial array synthesis. The devices made of heterogeneous nanomaterial array were utilized as a multiplexed sensor for toxic gases such as NO2 and CO. This method would be very useful for the facile fabrication of functional nanodevices based on highly integrated arrays of heterogeneous nanomaterials. PMID:25634814

A High-Voltage Integrated Circuit Engine for a Dielectrophoresis-based Programmable Micro-Fluidic Processor

PubMed Central

Current, K. Wayne; Yuk, Kelvin; McConaghy, Charles; Gascoyne, Peter R. C.; Schwartz, Jon A.; Vykoukal, Jody V.; Andrews, Craig

2010-01-01

A high-voltage (HV) integrated circuit has been demonstrated to transport droplets on programmable paths across its coated surface. This chip is the engine for a dielectrophoresis (DEP)-based micro-fluidic lab-on-a-chip system. This chip creates DEP forces that move and help inject droplets. Electrode excitation voltage and frequency are variable. With the electrodes driven with a 100V peak-to-peak periodic waveform, the maximum high-voltage electrode waveform frequency is about 200Hz. Data communication rate is variable up to 250kHz. This demonstration chip has a 32×32 array of nominally 100V electrode drivers. It is fabricated in a 130V SOI CMOS fabrication technology, dissipates a maximum of 1.87W, and is about 10.4 mm × 8.2 mm. PMID:23989241

A microfluidic approach to parallelized transcriptional profiling of single cells.

PubMed

Sun, Hao; Olsen, Timothy; Zhu, Jing; Tao, Jianguo; Ponnaiya, Brian; Amundson, Sally A; Brenner, David J; Lin, Qiao

2015-12-01

The ability to correlate single-cell genetic information with cellular phenotypes is of great importance to biology and medicine, as it holds the potential to gain insight into disease pathways that is unavailable from ensemble measurements. We present a microfluidic approach to parallelized, rapid, quantitative analysis of messenger RNA from single cells via RT-qPCR. The approach leverages an array of single-cell RT-qPCR analysis units formed by a set of parallel microchannels concurrently controlled by elastomeric pneumatic valves, thereby enabling parallelized handling and processing of single cells in a drastically simplified operation procedure using a relatively small number of microvalves. All steps for single-cell RT-qPCR, including cell isolation and immobilization, cell lysis, mRNA purification, reverse transcription and qPCR, are integrated on a single chip, eliminating the need for off-chip manual cell and reagent transfer and qPCR amplification as commonly used in existing approaches. Additionally, the approach incorporates optically transparent microfluidic components to allow monitoring of single-cell trapping without the need for molecular labeling that can potentially alter the targeted gene expression and utilizes a polycarbonate film as a barrier against evaporation to minimize the loss of reagents at elevated temperatures during the analysis. We demonstrate the utility of the approach by the transcriptional profiling for the induction of the cyclin-dependent kinase inhibitor 1a and the glyceraldehyde 3-phosphate dehydrogenase in single cells from the MCF-7 breast cancer cell line. Furthermore, the methyl methanesulfonate is employed to allow measurement of the expression of the genes in individual cells responding to a genotoxic stress.

Self-priming compartmentalization digital LAMP for point-of-care.

PubMed

Zhu, Qiangyuan; Gao, Yibo; Yu, Bingwen; Ren, Hao; Qiu, Lin; Han, Sihai; Jin, Wei; Jin, Qinhan; Mu, Ying

2012-11-21

Digital nucleic acid amplification provides unprecedented opportunities for absolute nucleic acid quantification by counting of single molecules. This technique is useful for molecular genetic analysis in cancer, stem cell, bacterial, non-invasive prenatal diagnosis in which many biologists are interested. This paper describes a self-priming compartmentalization (SPC) microfluidic chip platform for performing digital loop-mediated amplification (LAMP). The energy for the pumping is pre-stored in the degassed bulk PDMS by exploiting the high gas solubility of PDMS; therefore, no additional structures other than channels and reservoirs are required. The sample and oil are sequentially sucked into the channels, and the pressure difference of gas dissolved in PDMS allows sample self-compartmentalization without the need for further chip manipulation such as with pneumatic microvalves and control systems, and so on. The SPC digital LAMP chip can be used like a 384-well plate, so, the world-to-chip fluidic interconnections are avoided. The microfluidic chip contains 4 separate panels, each panel contains 1200 independent 6 nL chambers and can be used to detect 4 samples simultaneously. Digital LAMP on the microfluidic chip was tested quantitatively by using β-actin DNA from humans. The self-priming compartmentalization behavior is roughly predictable using a two-dimensional model. The uniformity of compartmentalization was analyzed by fluorescent intensity and fraction of volume. The results showed that the feasibility and flexibility of the microfluidic chip platform for amplifying single nucleic acid molecules in different chambers made by diluting and distributing sample solutions. The SPC chip has the potential to meet the requirements of a general laboratory: power-free, valve-free, operating at isothermal temperature, inexpensive, sensitive, economizing labour time and reagents. The disposable analytical devices with appropriate air-tight packaging should be useful for point-of-care, and enabling it to become one of the common tools for biology research, especially, in point-of-care testing.

Ultrasensitive microfluidic solid-phase ELISA using an actuatable microwell-patterned PDMS chip.

PubMed

Wang, Tanyu; Zhang, Mohan; Dreher, Dakota D; Zeng, Yong

2013-11-07

Quantitative detection of low abundance proteins is of significant interest for biological and clinical applications. Here we report an integrated microfluidic solid-phase ELISA platform for rapid and ultrasensitive detection of proteins with a wide dynamic range. Compared to the existing microfluidic devices that perform affinity capture and enzyme-based optical detection in a constant channel volume, the key novelty of our design is two-fold. First, our system integrates a microwell-patterned assay chamber that can be pneumatically actuated to significantly reduce the volume of chemifluorescent reaction, markedly improving the sensitivity and speed of ELISA. Second, monolithic integration of on-chip pumps and the actuatable assay chamber allow programmable fluid delivery and effective mixing for rapid and sensitive immunoassays. Ultrasensitive microfluidic ELISA was demonstrated for insulin-like growth factor 1 receptor (IGF-1R) across at least five orders of magnitude with an extremely low detection limit of 21.8 aM. The microwell-based solid-phase ELISA strategy provides an expandable platform for developing the next-generation microfluidic immunoassay systems that integrate and automate digital and analog measurements to further improve the sensitivity, dynamic ranges, and reproducibility of proteomic analysis.

Development of a facile droplet-based single-cell isolation platform for cultivation and genomic analysis in microorganisms.

PubMed

Zhang, Qiang; Wang, Tingting; Zhou, Qian; Zhang, Peng; Gong, Yanhai; Gou, Honglei; Xu, Jian; Ma, Bo

2017-01-23

Wider application of single-cell analysis has been limited by the lack of an easy-to-use and low-cost strategy for single-cell isolation that can be directly coupled to single-cell sequencing and single-cell cultivation, especially for small-size microbes. Herein, a facile droplet microfluidic platform was developed to dispense individual microbial cells into conventional standard containers for downstream analysis. Functional parts for cell encapsulation, droplet inspection and sorting, as well as a chip-to-tube capillary interface were integrated on one single chip with simple architecture, and control of the droplet sorting was achieved by a low-cost solenoid microvalve. Using microalgal and yeast cells as models, single-cell isolation success rate of over 90% and single-cell cultivation success rate of 80% were demonstrated. We further showed that the individual cells isolated can be used in high-quality DNA and RNA analyses at both gene-specific and whole-genome levels (i.e. real-time quantitative PCR and genome sequencing). The simplicity and reliability of the method should improve accessibility of single-cell analysis and facilitate its wider application in microbiology researches.

Development of a facile droplet-based single-cell isolation platform for cultivation and genomic analysis in microorganisms

PubMed Central

Zhang, Qiang; Wang, Tingting; Zhou, Qian; Zhang, Peng; Gong, Yanhai; Gou, Honglei; Xu, Jian; Ma, Bo

2017-01-01

Wider application of single-cell analysis has been limited by the lack of an easy-to-use and low-cost strategy for single-cell isolation that can be directly coupled to single-cell sequencing and single-cell cultivation, especially for small-size microbes. Herein, a facile droplet microfluidic platform was developed to dispense individual microbial cells into conventional standard containers for downstream analysis. Functional parts for cell encapsulation, droplet inspection and sorting, as well as a chip-to-tube capillary interface were integrated on one single chip with simple architecture, and control of the droplet sorting was achieved by a low-cost solenoid microvalve. Using microalgal and yeast cells as models, single-cell isolation success rate of over 90% and single-cell cultivation success rate of 80% were demonstrated. We further showed that the individual cells isolated can be used in high-quality DNA and RNA analyses at both gene-specific and whole-genome levels (i.e. real-time quantitative PCR and genome sequencing). The simplicity and reliability of the method should improve accessibility of single-cell analysis and facilitate its wider application in microbiology researches. PMID:28112223

Semiconductor sensor embedded microfluidic chip for protein biomarker detection using a bead-based immunoassay combined with deoxyribonucleic acid strand labeling.

PubMed

Lin, Yen-Heng; Peng, Po-Yu

2015-04-15

Two major issues need to be addressed in applying semiconductor biosensors to detecting proteins in immunoassays. First, the length of the antibody on the sensor surface surpasses the Debye lengths (approximately 1 nm, in normal ionic strength solution), preventing certain specifically bound proteins from being tightly attached to the sensor surface. Therefore, these proteins do not contribute to the sensor's surface potential change. Second, these proteins carry a small charge and can be easily affected by the pH of the surrounding solution. This study proposes a magnetic bead-based immunoassay using a secondary antibody to label negatively charged DNA fragments for signal amplification. An externally imposed magnetic force attaches the analyte tightly to the sensor surface, thereby effectively solving the problem of the analyte protein's distance to the sensor surface surpassing the Debye lengths. In addition, a normal ion intensity buffer can be used without dilution for the proposed method. Experiments revealed that the sensitivity can be improved by using a longer DNA fragment for labeling and smaller magnetic beads as solid support for the antibody. By using a 90 base pair DNA label, the signal was 15 times greater than that without labeling. In addition, by using a 120 nm magnetic bead, a minimum detection limit of 12.5 ng mL(-1) apolipoprotein A1 can be measured. Furthermore, this study integrates a semiconductor sensor with a microfluidic chip. With the help of microvalves and micromixers in the chip, the length of the mixing step for each immunoassay has been reduced from 1h to 20 min, and the sample volume has been reduced from 80 μL to 10 μL. In practice, a protein biomarker in a urinary bladder cancer patient's urine was successfully measured using this technique. This study provides a convenient and effective method to measure protein using a semiconductor sensor. Copyright © 2015 Elsevier B.V. All rights reserved.

Programmable Bio-Nano-Chip Systems for Serum CA125 Quantification: Towards Ovarian Cancer Diagnostics at the Point-of-Care

PubMed Central

Raamanathan, Archana; Simmons, Glennon W.; Christodoulides, Nicolaos; Floriano, Pierre N.; Furmaga, Wieslaw B.; Redding, Spencer W.; Lu, Karen H.; Bast, Robert C.; McDevitt, John T.

2013-01-01

Point-of-care (POC) implementation of early detection and screening methodologies for ovarian cancer may enable improved survival rates through early intervention. Current laboratory-confined immunoanalyzers have long turnaround times and are often incompatible with multiplexing and POC implementation. Rapid, sensitive and multiplexable POC diagnostic platforms compatible with promising early detection approaches for ovarian cancer are needed. To this end, we report the adaptation of the programmable bio-nano-chip (p-BNC), an integrated, microfluidic, modular (Programmable) platform for CA125 serum quantitation, a biomarker prominently implicated in multi-modal and multi-marker screening approaches. In the p-BNC, CA125 from diseased sera (Bio) is sequestered and assessed with a fluorescence-based sandwich immunoassay, completed in the nano-nets (Nano) of sensitized agarose microbeads localized in individually addressable wells (Chip), housed in a microfluidic module, capable of integrating multiple sample, reagent and biowaste processing and handling steps. Antibody pairs that bind to distinct epitopes on CA125 were screened. To permit efficient biomarker sequestration in a 3-D microfluidic environment, the p-BNC operating variables (incubation times, flow rates and reagent concentrations) were tuned to deliver optimal analytical performance under 45 minutes. With short analysis times, competitive analytical performance (Inter- and intra-assay precision of 1.2% and 1.9% and LODs of 1.0 U/mL) was achieved on this mini-sensor ensemble. Further validation with sera of ovarian cancer patients (n=20) demonstrated excellent correlation (R2 = 0.97) with gold-standard ELISA. Building on the integration capabilities of novel microfluidic systems programmed for ovarian cancer, the rapid, precise and sensitive miniaturized p-BNC system shows strong promise for ovarian cancer diagnostics. PMID:22490510

Programmable bio-nano-chip systems for serum CA125 quantification: toward ovarian cancer diagnostics at the point-of-care.

PubMed

Raamanathan, Archana; Simmons, Glennon W; Christodoulides, Nicolaos; Floriano, Pierre N; Furmaga, Wieslaw B; Redding, Spencer W; Lu, Karen H; Bast, Robert C; McDevitt, John T

2012-05-01

Point-of-care (POC) implementation of early detection and screening methodologies for ovarian cancer may enable improved survival rates through early intervention. Current laboratory-confined immunoanalyzers have long turnaround times and are often incompatible with multiplexing and POC implementation. Rapid, sensitive, and multiplexable POC diagnostic platforms compatible with promising early detection approaches for ovarian cancer are needed. To this end, we report the adaptation of the programmable bio-nano-chip (p-BNC), an integrated, microfluidic, and modular (programmable) platform for CA125 serum quantitation, a biomarker prominently implicated in multimodal and multimarker screening approaches. In the p-BNCs, CA125 from diseased sera (Bio) is sequestered and assessed with a fluorescence-based sandwich immunoassay, completed in the nano-nets (Nano) of sensitized agarose microbeads localized in individually addressable wells (Chip), housed in a microfluidic module, capable of integrating multiple sample, reagent and biowaste processing, and handling steps. Antibody pairs that bind to distinct epitopes on CA125 were screened. To permit efficient biomarker sequestration in a three-dimensional microfluidic environment, the p-BNC operating variables (incubation times, flow rates, and reagent concentrations) were tuned to deliver optimal analytical performance under 45 minutes. With short analysis times, competitive analytical performance (inter- and intra-assay precision of 1.2% and 1.9% and limit of detection of 1.0 U/mL) was achieved on this minisensor ensemble. Furthermore, validation with sera of patients with ovarian cancer (n = 20) showed excellent correlation (R(2) = 0.97) with gold-standard ELISA. Building on the integration capabilities of novel microfluidic systems programmed for ovarian cancer, the rapid, precise, and sensitive miniaturized p-BNC system shows strong promise for ovarian cancer diagnostics.

PNEUMATIC MICROVALVE FOR ELECTROKINETIC SAMPLE PRECONCENTRATION AND CAPILLARY ELECTROPHORESIS INJECTION

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

Cong, Yongzheng; Rausch, Sarah J.; Geng, Tao

2014-10-27

Here we show that a closed pneumatic microvalve on a PDMS chip can serve as a semipermeable membrane under an applied potential, enabling current to pass through while blocking the passage of charged analytes. Enrichment of both anionic and cationic species has been demonstrated, and concentration factors of ~70 have been achieved in just 8 s. Once analytes are concentrated, the valve is briefly opened and the sample is hydrodynamically injected onto an integrated microchip or capillary electrophoresis (CE) column. In contrast to existing preconcentration approaches, the membrane-based method described here enables both rapid analyte concentration as well as highmore » resolution separations.« less

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.

Graphene doped ZnO films for photoelectrowetting on microchannels

NASA Astrophysics Data System (ADS)

Al-Aribe, Khaled; Knopf, George K.

2017-02-01

Photoelectrowetting on dielectric surfaces can be used to drive droplets of liquid along reconfigurable paths on a microfluidic chip using controlled optical signals. These electrostatically activated surfaces along the desired path eliminate the need for precision molded channels and discrete functional components such as microvalves and micropumps. The photoelectrowetting effect exploits the surface tension of the droplet to maintain its volume during the transportation pathway and the photoelectric properties of the substrate surface are used to induce reversible fluidic flow. The active light-driven substrate is structured from graphene doped zinc-oxide (ZnO-G) films deposited on ITO coated glass. This substrate is coated from the ZnO-G side with Ruthenium-based dye (N719) to maximize its absorbability. The light triggers two forces that enable the droplet to be transported along the substrate. The first arises from the induced hydrophobicity gradient formed across the droplet contact area with the substrate surface. Exposing the ZnO-G film to a broad spectrum white light source alters the surface's electric potential which induces a change in the droplet's contact angle and the associated hydrophobicity. Once the hydrophobicity gradient is generated the droplet will start to move in the direction of the wetting zone. The second force is also created by the optical input when the absorbed light generates a photoelectric potential that produces a piezo-electrical effect on the ZnO-G film. The light triggered piezo-electrical behavior of the ZnO-G film can be used to generate the erasable microchannels that can guide droplet movement through a microfluidic chip. Preliminary experiments are performed to investigate the photoelectric potential of light activated ZnO-G films.

Design and operation of a portable scanner for high performance microchip capillary array electrophoresis.

PubMed

Scherer, James R; Liu, Peng; Mathies, Richard A

2010-11-01

We have developed a compact, laser-induced fluorescence detection scanner, the multichannel capillary array electrophoresis portable scanner (McCAEPs) as a platform for electrophoretic detection and control of high-throughput, integrated microfluidic devices for genetic and other analyses. The instrument contains a confocal optical system with a rotary objective for detecting four different fluorescence signals, a pneumatic system consisting of two pressure/vacuum pumps and 28 individual addressable solenoid valves for control of on-chip microvalves and micropumps, four Polymerase Chain Reaction (PCR) temperature control systems, and four high voltage power supplies for electrophoresis. The detection limit of the instrument is ~20 pM for on-chip capillary electrophoresis of fluorescein dyes. To demonstrate the system performance for forensic short tandem repeat (STR) analysis, two experiments were conducted: (i) electrophoretic separation and detection of STR samples on a 96-lane microfabricated capillary array electrophoresis microchip. Fully resolved PowerPlex(®) 16 STR profiles amplified from 1 ng of 9947A female standard DNA were successfully obtained; (ii) nine-plex STR amplification, sample injection, separation, and fluorescence detection of 100-copy 9948 male standard DNA in a single integrated PCR- capillary electrophoresis microchip. These results demonstrate that the McCAEPs can be used as a versatile control and detection instrument that operates integrated microfluidic devices for high-performance forensic human identification.

Design and operation of a portable scanner for high performance microchip capillary array electrophoresis

NASA Astrophysics Data System (ADS)

Scherer, James R.; Liu, Peng; Mathies, Richard A.

2010-11-01

We have developed a compact, laser-induced fluorescence detection scanner, the multichannel capillary array electrophoresis portable scanner (McCAEPs) as a platform for electrophoretic detection and control of high-throughput, integrated microfluidic devices for genetic and other analyses. The instrument contains a confocal optical system with a rotary objective for detecting four different fluorescence signals, a pneumatic system consisting of two pressure/vacuum pumps and 28 individual addressable solenoid valves for control of on-chip microvalves and micropumps, four Polymerase Chain Reaction (PCR) temperature control systems, and four high voltage power supplies for electrophoresis. The detection limit of the instrument is ˜20 pM for on-chip capillary electrophoresis of fluorescein dyes. To demonstrate the system performance for forensic short tandem repeat (STR) analysis, two experiments were conducted: (i) electrophoretic separation and detection of STR samples on a 96-lane microfabricated capillary array electrophoresis microchip. Fully resolved PowerPlex® 16 STR profiles amplified from 1 ng of 9947A female standard DNA were successfully obtained; (ii) nine-plex STR amplification, sample injection, separation, and fluorescence detection of 100-copy 9948 male standard DNA in a single integrated PCR- capillary electrophoresis microchip. These results demonstrate that the McCAEPs can be used as a versatile control and detection instrument that operates integrated microfluidic devices for high-performance forensic human identification.

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

Field programmable chemistry: integrated chemical and electronic processing of informational molecules towards electronic chemical cells.

PubMed

Wagler, Patrick F; Tangen, Uwe; Maeke, Thomas; McCaskill, John S

2012-07-01

The topic addressed is that of combining self-constructing chemical systems with electronic computation to form unconventional embedded computation systems performing complex nano-scale chemical tasks autonomously. The hybrid route to complex programmable chemistry, and ultimately to artificial cells based on novel chemistry, requires a solution of the two-way massively parallel coupling problem between digital electronics and chemical systems. We present a chemical microprocessor technology and show how it can provide a generic programmable platform for complex molecular processing tasks in Field Programmable Chemistry, including steps towards the grand challenge of constructing the first electronic chemical cells. Field programmable chemistry employs a massively parallel field of electrodes, under the control of latched voltages, which are used to modulate chemical activity. We implement such a field programmable chemistry which links to chemistry in rather generic, two-phase microfluidic channel networks that are separated into weakly coupled domains. Electric fields, produced by the high-density array of electrodes embedded in the channel floors, are used to control the transport of chemicals across the hydrodynamic barriers separating domains. In the absence of electric fields, separate microfluidic domains are essentially independent with only slow diffusional interchange of chemicals. Electronic chemical cells, based on chemical microprocessors, exploit a spatially resolved sandwich structure in which the electronic and chemical systems are locally coupled through homogeneous fine-grained actuation and sensor networks and play symmetric and complementary roles. We describe how these systems are fabricated, experimentally test their basic functionality, simulate their potential (e.g. for feed forward digital electrophoretic (FFDE) separation) and outline the application to building electronic chemical cells. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

3D Printed Multimaterial Microfluidic Valve.

PubMed

Keating, Steven J; Gariboldi, Maria Isabella; Patrick, William G; Sharma, Sunanda; Kong, David S; Oxman, Neri

2016-01-01

We present a novel 3D printed multimaterial microfluidic proportional valve. The microfluidic valve is a fundamental primitive that enables the development of programmable, automated devices for controlling fluids in a precise manner. We discuss valve characterization results, as well as exploratory design variations in channel width, membrane thickness, and membrane stiffness. Compared to previous single material 3D printed valves that are stiff, these printed valves constrain fluidic deformation spatially, through combinations of stiff and flexible materials, to enable intricate geometries in an actuated, functionally graded device. Research presented marks a shift towards 3D printing multi-property programmable fluidic devices in a single step, in which integrated multimaterial valves can be used to control complex fluidic reactions for a variety of applications, including DNA assembly and analysis, continuous sampling and sensing, and soft robotics.

A reconfigurable tactile display based on polymer MEMS technology

NASA Astrophysics Data System (ADS)

Wu, Xiaosong

A tactile display provides information such as shape, texture, temperature, and hardness to a user. Ultimately, a tactile display could be used to recreate a virtual object that may be stored in a computer. However, such advanced displays are not yet widely available, primarily due to the lack of low cost, large area, compact actuator arrays that can stimulate the large numbers of receptors of the user and that can also meet the high requirements for user safety and comfort. This research focuses on the development of polymer microfabrication technologies for the realization of two major components of a pneumatic tactile display: a microactuator array and a complementary microvalve (control) array. In this work, the concept, fabrication, and characterization of a kinematically-stabilized polymeric microbubble actuator ("endoskeletal microbubble actuator") is presented. A systematic design and modeling procedure was carried out to generate an optimized geometry of the corrugated diaphragm to satisfy membrane deflection, force, and stability requirements set forth by the tactile display goals. A mass-manufacturable actuator has been fabricated using the approaches of lithography and micromolding. A prototype of a single endoskeletal bubble actuator with a diameter of 2.6mm has been fabricated and characterized. In addition, in order to further reduce the size and cost of the tactile display, a microvalve array can be integrated into the tactile display system to control the pneumatic fluid that actuates the microbubble actuator. A piezoelectrically-driven and hydraulically-amplified polymer microvalve has been designed, fabricated, and tested. An incompressible elastomer was used as a solid hydraulic medium to convert the small axial displacement of a piezoelectric actuator into a large valve head stroke while maintaining a large blocking force. The function of the microvalve as an on-off switch for a pneumatic microbubble tactile actuator has been demonstrated. Compared to present technologies, the microvalve developed can achieve large flow rate control due to its amplification mechanism, can avoid complex sealing problem because solid rather than liquid medium is used, and can form a dense valve array due to the small lateral dimension of the actuator used. To further reduce the cost of the microvalve, a laterally-laminated multilayer PZT actuator has been fabricated using diced PZT multilayer, high aspect ratio SU-8 photolithography, and molding of electrically conductive polymer composite electrodes. This fabrication process is simple and straightforward compared to previous lateral lamination approaches. An 8-layer device has shown a displacement of 0.63 micron at 100V driving voltage, which agrees well with simulation results. The lateral lamination fabrication process provides a valuable alternative for making compact, low-voltage, multilayer piezoelectric micro-actuators as microvalve driving element. A refreshable Braille cell as a tactile display prototype has been developed based on a 2x3 endoskeletal microbubble array and an array of commercial valves. The prototype can provide both a static display (which meets the displacement and force requirement of a Braille display) and vibratory tactile sensations. Along with the above capabilities, the device was designed to meet the criteria of lightness and compactness to permit portable operation. The design is scalable with respect to the number of tactile actuators while still being simple to fabricate.

Design and simulation of MEMS microvalves for silicon photonic biosensor chip

NASA Astrophysics Data System (ADS)

Amemiya, Yoshiteru; Nakashima, Yuuto; Maeda, Jun; Yokoyama, Shin

2018-04-01

For the early and easy diagnosis of diseases, we have proposed a silicon photonic biosensor chip with two kinds of MEMS microvalves for a multiple-item detection system. The driving voltage of the vertical type with the circular-plate capacitor structure and that of the lateral type with the comb-shaped electrode are investigated. From mechanical calculations, the driving voltage of the vertical type is estimated to be 30 V and that of the lateral type to be 15 V. The propagation loss at the intersecting waveguides of arrayed ring-resonator biosensors is also estimated. In the case of optimized intersecting waveguides, more than 67% transmittance of TE-mode light is simulated for the series connection of 20 intersecting waveguides. It is confirmed that it is possible to fabricate an 8 × 12 arrayed biosensor chip in an area of 1 × 1.5 mm2 taking the device size of the microvalves into consideration. We have, for the first time, designed a whole system, including sensors and a fluid channel with MEMS microvalves.

Piezoelectric axial flow microvalve

DOEpatents

Gemmen, Randall; Thornton, Jimmy; Vipperman, Jeffrey S.; Clark, William W.

2007-01-09

This invention is directed to a fuel cell operable with a quantity of fuel and a quantity of an oxidizer to produce electrical power, the fuel cell including a fuel cell body including a labyrinth system structured to permit the fuel and the oxidizer to flow therethrough; at least a first catalyst in fluid communication with the labyrinth; and at least a first microvalve operably disposed within at least a portion of the labyrinth. The microvalve utilizes a deflectable member operable upon the application of a voltage from a voltage source. The microvalve includes an elongated flow channel formed therein and extending substantially longitudinally between the first and second ends to permit substantially longitudinal flow of the fluid therethrough and between the first and second ends; and the deflectable member disposed on the valve body, the deflectable member including at least a first piezoelectric portion that is piezoelectrically operable to deflect the deflectable member between an open position and a closed position upon the application of a voltage, the deflectable member in the closed position being operable to resist the flow of the fluid through the flow channel.

Pre-stressed piezoelectric bimorph micro-actuators based on machined 40 µm PZT thick films: batch scale fabrication and integration with MEMS

NASA Astrophysics Data System (ADS)

Wilson, S. A.; Jourdain, R. P.; Owens, S.

2010-09-01

The projected force-displacement capability of piezoelectric ceramic films in the 20-50 µm thickness range suggests that they are well suited to many micro-fluidic and micro-pneumatic applications. Furthermore when they are configured as bending actuators and operated at ~ 1 V µm - 1 they do not necessarily conform to the high-voltage, very low-displacement piezoelectric stereotype. Even so they are rarely found today in commercial micro-electromechanical devices, such as micro-pumps and micro-valves, and the main barriers to making them much more widely available would appear to be processing incompatibilities rather than commercial desirability. In particular, the issues associated with integration of these devices into MEMS at the production level are highly significant and they have perhaps received less attention in the mainstream than they deserve. This paper describes a fabrication route based on ultra-precision ceramic machining and full-wafer bonding for cost-effective batch scale production of thick film PZT bimorph micro-actuators and their integration with MEMS. The resulting actuators are pre-stressed (ceramic in compression) which gives them added performance, they are true bimorphs with bi-directional capability and they exhibit full bulk piezoelectric ceramic properties. The devices are designed to integrate with ancillary systems components using transfer-bonding techniques. The work forms part of the European Framework 6 Project 'Q2M—Quality to Micro'.

Experimental evaluation of an adaptive Joule–Thomson cooling system including silicon-microfabricated heat exchanger and microvalve components

PubMed Central

Zhu, Weibin; Park, Jong M.; White, Michael J.; Nellis, Gregory F.; Gianchandani, Yogesh B.

2011-01-01

This article reports the evaluation of a Joule–Thomson (JT) cooling system that combines two custom micromachined components—a Si/glass-stack recuperative heat exchanger and a piezoelectrically actuated expansion microvalve. With the microvalve controlling the flow rate, this system can modulate cooling to accommodate varying refrigeration loads. The perforated plate Si/glass heat exchanger is fabricated with a stack of alternating silicon plates and Pyrex glass spacers. The microvalve utilizes a lead zirconate titanate actuator to push a Si micromachined valve seat against a glass plate, thus modulating the flow passing through the gap between the valve seat and the glass plate. The fabricated heat exchanger has a footprint of 1×1 cm2 and a length of 35 mm. The size of the micromachined piezoelectrically actuated valve is about 1×1×1 cm3. In JT cooling tests, the temperature of the system was successfully controlled by adjusting the input voltage of the microvalve. When the valve was fully opened (at an input voltage of −30 V), the system cooled down to a temperature as low as 254.5 K at 430 kPa pressure difference between inlet and outlet at steady state and 234 K at 710 kPa in a transient state. The system provided cooling powers of 75 mW at 255 K and 150 mW at 258 K. Parasitic heat loads at 255 K are estimated at approximately 700 mW. PMID:21552354

A new electrowetting lab-on-a-chip platform based on programmable and virtual wall-less channels

NASA Astrophysics Data System (ADS)

Banerjee, Ananda; Kreit, Eric; Dhindsa, Manjeet; Heikenfeld, Jason; Papautsky, Ian

2011-02-01

Microscale liquid handling based on electrowetting has been previously demonstrated by several groups. Such liquid manipulation however is limited to control of individual droplets, aptly termed digital microfluidics. The inability to form continuous channels thus prevents conventional microfluidic sample manipulation and analysis approaches, such as electroosmosis and electrophoresis. In this paper, we discuss our recent progress on the development of electrowettingbased virtual channels. These channels can be created and reconfigured on-demand and preserve their shape without external stimulus. We also discuss recent progress towards demonstrating electroosmotic flows in such microchannels for fluid transport. This would permit a variety of basic functionalities in this new platform including sample transport and mixing between various functional areas of the chip.

3D Printed Multimaterial Microfluidic Valve

PubMed Central

Patrick, William G.; Sharma, Sunanda; Kong, David S.; Oxman, Neri

2016-01-01

We present a novel 3D printed multimaterial microfluidic proportional valve. The microfluidic valve is a fundamental primitive that enables the development of programmable, automated devices for controlling fluids in a precise manner. We discuss valve characterization results, as well as exploratory design variations in channel width, membrane thickness, and membrane stiffness. Compared to previous single material 3D printed valves that are stiff, these printed valves constrain fluidic deformation spatially, through combinations of stiff and flexible materials, to enable intricate geometries in an actuated, functionally graded device. Research presented marks a shift towards 3D printing multi-property programmable fluidic devices in a single step, in which integrated multimaterial valves can be used to control complex fluidic reactions for a variety of applications, including DNA assembly and analysis, continuous sampling and sensing, and soft robotics. PMID:27525809

Pharmacokinetics-on-a-Chip Using Label-Free SERS Technique for Programmable Dual-Drug Analysis.

PubMed

Fei, Jiayuan; Wu, Lei; Zhang, Yizhi; Zong, Shenfei; Wang, Zhuyuan; Cui, Yiping

2017-06-23

Synergistic effects of dual or multiple drugs have attracted great attention in medical fields, especially in cancer therapies. We provide a programmable microfluidic platform for pharmacokinetic detection of multiple drugs in multiple cells. The well-designed microfluidic platform includes two 2 × 3 microarrays of cell chambers, two gradient generators, and several pneumatic valves. Through the combined use of valves and gradient generators, each chamber can be controlled to infuse different kinds of living cells and drugs with specific concentrations as needed. In our experiments, 6-mercaptopurine (6MP) and methimazole (MMI) were chosen as two drug models and their pharmacokinetic parameters in different living cells were monitored through intracellular SERS spectra, which reflected the molecular structure of these drugs. The dynamic change of SERS fingerprints from 6MP and MMI molecules were recorded during drug metabolism in living cells. The results indicated that both 6MP and MMI molecules were diffused into the cells within 4 min and excreted out after 36 h. Moreover, the intracellular distribution of these drugs was monitored through SERS mapping. Thus, our microfluidic platform simultaneously accomplishes the functions to monitor pharmacokinetic action, distribution, and fingerprint of multiple drugs in multiple cells. Owing to its real-time, rapid-speed, high-precision, and programmable capability of multiple-drug and multicell analysis, such a microfluidic platform has great potential in drug design and development.

Path-programmable water droplet manipulations on an adhesion controlled superhydrophobic surface

PubMed Central

Seo, Jungmok; Lee, Seoung-Ki; Lee, Jaehong; Seung Lee, Jung; Kwon, Hyukho; Cho, Seung-Woo; Ahn, Jong-Hyun; Lee, Taeyoon

2015-01-01

Here, we developed a novel and facile method to control the local water adhesion force of a thin and stretchable superhydrophobic polydimethylsiloxane (PDMS) substrate with micro-pillar arrays that allows the individual manipulation of droplet motions including moving, merging and mixing. When a vacuum pressure was applied below the PDMS substrate, a local dimple structure was formed and the water adhesion force of structure was significantly changed owing to the dynamically varied pillar density. With the help of the lowered water adhesion force and the slope angle of the formed dimple structure, the motion of individual water droplets could be precisely controlled, which facilitated the creation of a droplet-based microfluidic platform capable of a programmable manipulation of droplets. We showed that the platform could be used in newer and emerging microfluidic operations such as surface-enhanced Raman spectroscopy with extremely high sensing capability (10−15 M) and in vitro small interfering RNA transfection with enhanced transfection efficiency of ~80%. PMID:26202206

Assessment of thermal effects in a model of the human head implanted with a wireless active microvalve for the treatment of glaucoma creating a filtering bleb

NASA Astrophysics Data System (ADS)

Schaumburg, F.; Guarnieri, F. A.

2017-05-01

A 3D anatomical computational model is developed to assess thermal effects due to exposure to the electromagnetic field required to power a new investigational active implantable microvalve for the treatment of glaucoma. Such a device, located in the temporal superior eye quadrant, produces a filtering bleb, which is included in the geometry of the model, together with the relevant ocular structures. The electromagnetic field source—a planar coil—as well as the microvalve antenna and casing are also included. Exposure to the electromagnetic field source of an implanted and a non-implanted subject are simulated by solving a magnetic potential formulation, using the finite element method. The maximum SAR10 is reached in the eyebrow and remains within the limits suggested by the IEEE and ICNIRP standards. The anterior chamber, filtering bleb, iris and ciliary body are the ocular structures where more absorption occurs. The temperature rise distribution is also obtained by solving the bioheat equation with the finite element method. The numerical results are compared with the in vivo measurements obtained from four rabbits implanted with the microvalve and exposed to the electromagnetic field source.

Assessment of thermal effects in a model of the human head implanted with a wireless active microvalve for the treatment of glaucoma creating a filtering bleb.

PubMed

Schaumburg, F; Guarnieri, F A

2017-05-07

A 3D anatomical computational model is developed to assess thermal effects due to exposure to the electromagnetic field required to power a new investigational active implantable microvalve for the treatment of glaucoma. Such a device, located in the temporal superior eye quadrant, produces a filtering bleb, which is included in the geometry of the model, together with the relevant ocular structures. The electromagnetic field source-a planar coil-as well as the microvalve antenna and casing are also included. Exposure to the electromagnetic field source of an implanted and a non-implanted subject are simulated by solving a magnetic potential formulation, using the finite element method. The maximum SAR 10 is reached in the eyebrow and remains within the limits suggested by the IEEE and ICNIRP standards. The anterior chamber, filtering bleb, iris and ciliary body are the ocular structures where more absorption occurs. The temperature rise distribution is also obtained by solving the bioheat equation with the finite element method. The numerical results are compared with the in vivo measurements obtained from four rabbits implanted with the microvalve and exposed to the electromagnetic field source.

Microfabricated Renewable Beads-Trapping/Releasing Flow Cell for Rapid Antigen-Antibody Reaction in Chemiluminescent Immunoassay

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

Fu, Zhifeng; Shao, Guocheng; Wang, Jun

2011-04-01

A filter pillar-array microstructure was coupled with a pneumatic micro-valve to fabricate a reusable miniaturized beads-trapping/releasing flow cell, in which trapping and releasing beads can be conveniently realized by switching the micro-valve. This miniaturized device was suitable to construct automatic fluidic system for “renewable surface analysis”. The renewable surface strategy based on pneumatic micro-valve enabled capture of beads in beads chamber prior to each assay, and release of the used beads after the assay. Chemiluminescent competitive immunoassay of 3,5,6-trichloropyridinol (TCP) was performed as a model to demonstrate the application potential of this reusable miniaturized flow cell. The whole fluidic assaymore » process including beads trapping, immuno-binding, beads washing, beads releasing and signal collection could be completed in 10 min. Immunoassay of TCP using this miniaturized device showed a linear range of 0.20-70 ng/mL with a limit of detection of 0.080 ng/mL. The device had been successfully used for detection of TCP spiked in rat serum with average recovery of 97%. This investigation provides a rapid, sensitive, reusable, low-cost and automatic miniaturized device for solid-phase biochemical analysis for various purposes.« less

High energy microelectromechanical oscillator based on the electrostatic microactuator

NASA Astrophysics Data System (ADS)

Baginsky, I.; Kostsov, Edvard; Sobolev, Victor

2008-03-01

Electrostatic high energy micromotor based on the ferroelectric films is studied as applied to microelectromechanical devices operating in vibrational mode. It is shown that the micromotor can be efficiently used in high frequency micromechanical vibrators that are used in high energy MEMS devices, such as micropumps, microvalves, microinjectors, adaptive microoptic devices etc.

On demand nanoliter-scale microfluidic droplet generation, injection, and mixing using a passive microfluidic device

PubMed Central

Tangen, Uwe; Sharma, Abhishek

2015-01-01

We here present and characterize a programmable nanoliter scale droplet-on-demand device that can be used separately or readily integrated into low cost single layer rapid prototyping microfluidic systems for a wide range of user applications. The passive microfluidic device allows external (off-the-shelf) electronically controlled pinch valves to program the delivery of nanoliter scale aqueous droplets from up to 9 different inputs to a central outlet channel. The inputs can be either continuous aqueous fluid streams or microliter scale aqueous plugs embedded in a carrier fluid, in which case the number of effective input solutions that can be employed in an experiment is no longer strongly constrained (100 s–1000 s). Both nanoliter droplet sequencing output and nanoliter-scale droplet mixing are reported with this device. Optimization of the geometry and pressure relationships in the device was achieved in several hardware iterations with the support of open source microfluidic simulation software and equivalent circuit models. The requisite modular control of pressure relationships within the device is accomplished using hydrodynamic barriers and matched resistance channels with three different channel heights, custom parallel reversible microfluidic I/O connections, low dead-volume pinch valves, and a simply adjustable array of external screw valves. Programmable sequences of droplet mixes or chains of droplets can be achieved with the device at low Hz frequencies, limited by device elasticity, and could be further enhanced by valve integration. The chip has already found use in the characterization of droplet bunching during export and the synthesis of a DNA library. PMID:25759752

On demand nanoliter-scale microfluidic droplet generation, injection, and mixing using a passive microfluidic device.

PubMed

Tangen, Uwe; Sharma, Abhishek; Wagler, Patrick; McCaskill, John S

2015-01-01

We here present and characterize a programmable nanoliter scale droplet-on-demand device that can be used separately or readily integrated into low cost single layer rapid prototyping microfluidic systems for a wide range of user applications. The passive microfluidic device allows external (off-the-shelf) electronically controlled pinch valves to program the delivery of nanoliter scale aqueous droplets from up to 9 different inputs to a central outlet channel. The inputs can be either continuous aqueous fluid streams or microliter scale aqueous plugs embedded in a carrier fluid, in which case the number of effective input solutions that can be employed in an experiment is no longer strongly constrained (100 s-1000 s). Both nanoliter droplet sequencing output and nanoliter-scale droplet mixing are reported with this device. Optimization of the geometry and pressure relationships in the device was achieved in several hardware iterations with the support of open source microfluidic simulation software and equivalent circuit models. The requisite modular control of pressure relationships within the device is accomplished using hydrodynamic barriers and matched resistance channels with three different channel heights, custom parallel reversible microfluidic I/O connections, low dead-volume pinch valves, and a simply adjustable array of external screw valves. Programmable sequences of droplet mixes or chains of droplets can be achieved with the device at low Hz frequencies, limited by device elasticity, and could be further enhanced by valve integration. The chip has already found use in the characterization of droplet bunching during export and the synthesis of a DNA library.

Optical coherence tomography characterization of femtosecond laser manufactured microfluidic circuits

NASA Astrophysics Data System (ADS)

De Pretto, Lucas Ramos; Samad, Ricardo Elgul; de Rossi, Wagner; de Freitas, Anderson Zanardi

2018-02-01

Dimensional characterization of microfluidic circuits were performed using three-dimensional models constructed from OCT images of such circuits. Were fabricated microchannels on the same BK7 glass plate, under different laser ablation conditions and substrate displacement velocity in relation to laser beam. Were used the following combination of energy, from 30 μJ to 60 μJ and velocity from 588 mm/min to 1176 mm/min, at 1 kHz laser repetition rate and 40 fs of pulse duration (FWHM). For OCT imaging we used an OCP930SR (Thorlabs System Inc) with 930 nm central wavelength, 6 μm of lateral and axial resolution, and image of 500 x 512 pixel corresponding to 2.0 mm x 1.6 mm of lateral and axial scans respectively at 8 frames per second. We also characterized devices like, micropumps, microvalves and microreactors. It was possible register the micropumps and valves in action in real time. Using the OCT images analyses was possible to select the best combination of laser pulse energy and substrate velocity. All the devices were made in raster protocol, where laser beam pass through the same path in a controlled number of times, and with each iteration more material is removed and deeper the channels remain. We found a deformation at the edge of fabricated structures, due to velocity reduction of substrate in relation to laser beam, which causes more laser pulses superposition in these regions, and more material is ablated. The technique was thus evaluated as a potential tool to aid in the inspection of microchannels.

A Novel Microfluidic Cell Co-culture Platform for the Study of the Molecular Mechanisms of Parkinson's Disease and Other Synucleinopathies.

PubMed

Fernandes, João T S; Chutna, Oldriska; Chu, Virginia; Conde, João P; Outeiro, Tiago F

2016-01-01

Although, the precise molecular mechanisms underlying Parkinson's disease (PD) are still elusive, it is now known that spreading of alpha-synuclein (aSyn) pathology and neuroinflammation are important players in disease progression. Here, we developed a novel microfluidic cell-culture platform for studying the communication between two different cell populations, a process of critical importance not only in PD but also in many biological processes. The integration of micro-valves in the device enabled us to control fluid routing, cellular microenvironments, and to simulate paracrine signaling. As proof of concept, two sets of experiments were designed to show how this platform can be used to investigate specific molecular mechanisms associated with PD. In one experiment, naïve H4 neuroglioma cells were co-cultured with cells expressing aSyn tagged with GFP (aSyn-GFP), to study the release and spreading of the protein. In our experimental set up, we induced the release of the contents of aSyn-GFP producing cells to the medium and monitored the protein's diffusion. In another experiment, H4 cells were co-cultured with N9 microglial cells to assess the interplay between two cell lines in response to environmental stimuli. Here, we observed an increase in the levels of reactive oxygen species in H4 cells cultured in the presence of activated N9 cells, confirming the cross talk between different cell populations. In summary, the platform developed in this study affords novel opportunities for the study of the molecular mechanisms involved in PD and other neurodegenerative diseases.

Plastic-Based Structurally Programmable Microfluidic Biochips for Clinical Diagnostics

DTIC Science & Technology

2005-05-01

BIOCOMPATIBILITY CRITERIA OF SELECTED UV ADHESIVE LOCTITE 3211™......... 63 1 I. Executive Summary The objective of this project is to develop a smart...added into biochip design for improving the biocompatibility of entire biochip. Detailed problems include: • Design and development of structure... biocompatible biosensor array. 6 • Design and development of the sensor-to-circuit interface. Electronic Control System and Analyzer Design of the

Microfluidic integration of parallel solid-phase liquid chromatography.

PubMed

Huft, Jens; Haynes, Charles A; Hansen, Carl L

2013-03-05

We report the development of a fully integrated microfluidic chromatography system based on a recently developed column geometry that allows for robust packing of high-performance separation columns in poly(dimethylsiloxane) microfluidic devices having integrated valves made by multilayer soft lithography (MSL). The combination of parallel high-performance separation columns and on-chip plumbing was used to achieve a fully integrated system for on-chip chromatography, including all steps of automated sample loading, programmable gradient generation, separation, fluorescent detection, and sample recovery. We demonstrate this system in the separation of fluorescently labeled DNA and parallel purification of reverse transcription polymerase chain reaction (RT-PCR) amplified variable regions of mouse immunoglobulin genes using a strong anion exchange (AEX) resin. Parallel sample recovery in an immiscible oil stream offers the advantage of low sample dilution and high recovery rates. The ability to perform nucleic acid size selection and recovery on subnanogram samples of DNA holds promise for on-chip genomics applications including sequencing library preparation, cloning, and sample fractionation for diagnostics.

Design and Development of a Miniaturized Double Latching Solenoid Valve for the Sample Analysis at Mars Instrument Suite

NASA Technical Reports Server (NTRS)

Smith, James T.

2008-01-01

The development of the in-house Miniaturized Double Latching Solenoid Valve, or Microvalve, for the Gas Processing System (GPS) of the Sample Analysis at Mars (SAM) instrument suite is described. The Microvalve is a double latching solenoid valve that actuates a pintle shaft axially to hermetically seal an orifice. The key requirements and the design innovations implemented to meet them are described.

Separation and counting of single molecules through nanofluidics, programmable electrophoresis, and nanoelectrode-gated tunneling and dielectric detection

DOEpatents

Lee, James W.; Thundat, Thomas G.

2006-04-25

An apparatus for carrying out the separation, detection, and/or counting of single molecules at nanometer scale. Molecular separation is achieved by driving single molecules through a microfluidic or nanofluidic medium using programmable and coordinated electric fields. In various embodiments, the fluidic medium is a strip of hydrophilic material on nonconductive hydrophobic surface, a trough produced by parallel strips of hydrophobic nonconductive material on a hydrophilic base, or a covered passageway produced by parallel strips of hydrophobic nonconductive material on a hydrophilic base together with a nonconductive cover on the parallel strips of hydrophobic nonconductive material. The molecules are detected and counted using nanoelectrode-gated electron tunneling methods, dielectric monitoring, and other methods.

Multicellular Vascularized Engineered Tissues through User-Programmable Biomaterial Photodegradation.

PubMed

Arakawa, Christopher K; Badeau, Barry A; Zheng, Ying; DeForest, Cole A

2017-10-01

A photodegradable material-based approach to generate endothelialized 3D vascular networks within cell-laden hydrogel biomaterials is introduced. Exploiting multiphoton lithography, microchannel networks spanning nearly all size scales of native human vasculature are readily generated with unprecedented user-defined 4D control. Intraluminal channel architectures of synthetic vessels are fully customizable, providing new opportunities for next-generation microfluidics and directed cell function. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Computerized microfluidic cell culture using elastomeric channels and Braille displays.

PubMed

Gu, Wei; Zhu, Xiaoyue; Futai, Nobuyuki; Cho, Brenda S; Takayama, Shuichi

2004-11-09

Computer-controlled microfluidics would advance many types of cellular assays and microscale tissue engineering studies wherever spatiotemporal changes in fluidics need to be defined. However, this goal has been elusive because of the limited availability of integrated, programmable pumps and valves. This paper demonstrates how a refreshable Braille display, with its grid of 320 vertically moving pins, can power integrated pumps and valves through localized deformations of channel networks within elastic silicone rubber. The resulting computerized fluidic control is able to switch among: (i) rapid and efficient mixing between streams, (ii) multiple laminar flows with minimal mixing between streams, and (iii) segmented plug-flow of immiscible fluids within the same channel architecture. The same control method is used to precisely seed cells, compartmentalize them into distinct subpopulations through channel reconfiguration, and culture each cell subpopulation for up to 3 weeks under perfusion. These reliable microscale cell cultures showed gradients of cellular behavior from C2C12 myoblasts along channel lengths, as well as differences in cell density of undifferentiated myoblasts and differentiation patterns, both programmable through different flow rates of serum-containing media. This technology will allow future microscale tissue or cell studies to be more accessible, especially for high-throughput, complex, and long-term experiments. The microfluidic actuation method described is versatile and computer programmable, yet simple, well packaged, and portable enough for personal use.

Computerized microfluidic cell culture using elastomeric channels and Braille displays

PubMed Central

Gu, Wei; Zhu, Xiaoyue; Futai, Nobuyuki; Cho, Brenda S.; Takayama, Shuichi

2004-01-01

Computer-controlled microfluidics would advance many types of cellular assays and microscale tissue engineering studies wherever spatiotemporal changes in fluidics need to be defined. However, this goal has been elusive because of the limited availability of integrated, programmable pumps and valves. This paper demonstrates how a refreshable Braille display, with its grid of 320 vertically moving pins, can power integrated pumps and valves through localized deformations of channel networks within elastic silicone rubber. The resulting computerized fluidic control is able to switch among: (i) rapid and efficient mixing between streams, (ii) multiple laminar flows with minimal mixing between streams, and (iii) segmented plug-flow of immiscible fluids within the same channel architecture. The same control method is used to precisely seed cells, compartmentalize them into distinct subpopulations through channel reconfiguration, and culture each cell subpopulation for up to 3 weeks under perfusion. These reliable microscale cell cultures showed gradients of cellular behavior from C2C12 myoblasts along channel lengths, as well as differences in cell density of undifferentiated myoblasts and differentiation patterns, both programmable through different flow rates of serum-containing media. This technology will allow future microscale tissue or cell studies to be more accessible, especially for high-throughput, complex, and long-term experiments. The microfluidic actuation method described is versatile and computer programmable, yet simple, well packaged, and portable enough for personal use. PMID:15514025

Microfluidic device for robust generation of two-component liquid-in-air slugs with individually controlled composition

PubMed Central

Liu, Kan; Chen, Yi-Chun; Tseng, Hsian-Rong

2010-01-01

Using liquid slugs as microreactors and microvessels enable precise control over the conditions of their contents on short-time scales for a wide variety of applications. Particularly for screening applications, there is a need for control of slug parameters such as size and composition. We describe a new microfluidic approach for creating slugs in air, each comprising a size and composition that can be selected individually for each slug. Two-component slugs are formed by first metering the desired volume of each reagent, merging the two volumes into an end-to-end slug, and propelling the slug to induce mixing. Volume control is achieved by a novel mechanism: two closed chambers on the chip are initially filled with air, and a valve in each is briefly opened to admit one of the reagents. The pressure of each reagent can be individually selected and determines the amount of air compression, and thus the amount of liquid that is admitted into each chamber. We describe the theory of operation, characterize the slug generation chip, and demonstrate the creation of slugs of different compositions. The use of microvalves in this approach enables robust operation with different liquids, and also enables one to work with extremely small samples, even down to a few slug volumes. The latter is important for applications involving precious reagents such as optimizing the reaction conditions for radiolabeling biological molecules as tracers for positron emission tomography. Electronic supplementary material The online version of this article (doi:10.1007/s10404-010-0617-0) contains supplementary material, which is available to authorized users. PMID:20930933

Voltage-programmable liquid optical interface

NASA Astrophysics Data System (ADS)

Brown, C. V.; Wells, G. G.; Newton, M. I.; McHale, G.

2009-07-01

Recently, there has been intense interest in photonic devices based on microfluidics, including displays and refractive tunable microlenses and optical beamsteerers that work using the principle of electrowetting. Here, we report a novel approach to optical devices in which static wrinkles are produced at the surface of a thin film of oil as a result of dielectrophoretic forces. We have demonstrated this voltage-programmable surface wrinkling effect in periodic devices with pitch lengths of between 20 and 240 µm and with response times of less than 40 µs. By a careful choice of oils, it is possible to optimize either for high-amplitude sinusoidal wrinkles at micrometre-scale pitches or more complex non-sinusoidal profiles with higher Fourier components at longer pitches. This opens up the possibility of developing rapidly responsive voltage-programmable, polarization-insensitive transmission and reflection diffraction devices and arbitrary surface profile optical devices.

A reconfigurable continuous-flow fluidic routing fabric using a modular, scalable primitive.

PubMed

Silva, Ryan; Bhatia, Swapnil; Densmore, Douglas

2016-07-05

Microfluidic devices, by definition, are required to move liquids from one physical location to another. Given a finite and frequently fixed set of physical channels to route fluids, a primitive design element that allows reconfigurable routing of that fluid from any of n input ports to any n output ports will dramatically change the paradigms by which these chips are designed and applied. Furthermore, if these elements are "regular" regarding their design, the programming and fabrication of these elements becomes scalable. This paper presents such a design element called a transposer. We illustrate the design, fabrication and operation of a single transposer. We then scale this design to create a programmable fabric towards a general-purpose, reconfigurable microfluidic platform analogous to the Field Programmable Gate Array (FPGA) found in digital electronics.

M3: Microscope-based maskless micropatterning with dry film photoresist

PubMed Central

Leigh, Steven Y.; Tattu, Aashay; Mitchell, Joseph S. B.

2011-01-01

We present a maskless micropatterning system that utilizes a fluorescence microscope with programmable X-Y stage and dry film photoresist to realize feature sizes in the sub-millimeter range (40–700 μm). The method allows for flexible in-house maskless photolithography without a dedicated microfabrication facility and is well-suited for rapid prototyping of microfluidic channels, scaffold templates for protein/cell patterning or optically-guided cell encapsulation for biomedical applications. PMID:21190086

Silicone-Rubber Microvalves Actuated by Paraffin

NASA Technical Reports Server (NTRS)

Svelha, Danielle; Feldman, Sabrina; Barsic, David

2004-01-01

Microvalves containing silicone-rubber seals actuated by heating and cooling of paraffin have been proposed for development as integral components of microfluidic systems. In comparison with other microvalves actuated by various means (electrostatic, electromagnetic, piezoelectric, pneumatic, and others), the proposed valves (1) would contain simpler structures that could be fabricated at lower cost and (2) could be actuated by simpler (and thus less expensive) control systems. Each valve according to the proposal would include a flow channel bounded on one side by a flat surface and on the other side by a curved surface defined by an arched-cross-section, elastic seal made of silicone rubber [polydimethylsilane (PDMS)]. The seal would be sized and shaped so that the elasticity of the PDMS would hold the channel open except when the seal was pressed down onto the flat surface to close the channel. The principle of actuation would exploit the fact that upon melting or freezing, the volume of a typical paraffin increases or decreases, respectively, by about 15 percent. In a valve according to the proposal, the seal face opposite that of the channel would be in contact with a piston-like plug of paraffin. In the case of a valve designed to be normally open at ambient temperature, one would use a paraffin having a melting temperature above ambient. The seal would be pushed against the flat surface to close the channel by heating the paraffin above its melting temperature. In the case of a valve designed to be normally closed at ambient temperature, one would use a paraffin having a melting temperature below ambient. The seal would be allowed to spring away from the flat surface to open the channel by cooling the paraffin below its melting temperature. The availability of paraffins that have melting temperatures from 70 to +80 C should make it possible to develop a variety of normally closed and normally open valves. The figure depicts examples of prototype normally open and normally closed valves according to the proposal. In each valve, an arch cross section defining a channel having dimensions of the order of tens of micrometers would be formed in a silicone-rubber sheet about 40 m thick. The silicone rubber sheet would be hermetically sealed to a lower glass plate that would define the sealing surface and to an upper glass plate containing a well. The well would be filled with paraffin and capped with a rigid restraining layer of epoxy. In the normally open valve, the paraffin would have a melting temperature above ambient (e.g., 40 C) and the wall of the well would be coated with a layer of titanium that would serve as an electric heater. In the normally closed valve, the paraffin would have a melting temperature below ambient (e.g.-5 C). Instead of a heater in the well, the normally closed valve would include a thermoelectric cooler on top of the epoxy cap.

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

Colloid Microthruster Feed System Development for Fine Pointing and Drag-Free Control of Multi-Year Astronomical Observatories

NASA Astrophysics Data System (ADS)

Ziemer, John; Mueller, J.; Spence, D.; Hruby, V.

2014-01-01

A new Colloid Microthruster feed system, including a propellant tank and redundant Microvalves, is being developed for fine pointing and drag-free operations of multi-year astronomical observatories under the PCOS SAT program. Almost all Gravitational Wave Observatory (GWO) concepts require microthrusters to maintain a drag-free environment for the inertial sensor instrument to meet the mission science objectives. The current state-of-the-art microthruster in the US is the Busek Colloid Micro-Newton Thruster (CMNT) originally developed under the New Millennium Program for the Space Technology 7 (ST7) and ESA's LISA Pathfinder (LPF) technology demonstration mission. The ST7 CMNT design includes a bellows propellant storage tank that is sized to provide up to 90 days of maximum thrust (30 µN). The new propellant tank is based on a blow-down, metal-diaphragm spherical tank design with enough capacity for a 5-year GWO mission. The new feed system will also include the third generation of Busek’s Microvalve, currently being developed under a NASA Phase II SBIR. The Microvalve is responsible for the picoliter per second control of the propellant from the tank to the thruster head, demanding parts with micron-level tolerances, critical alignments, and challenging acceptance test protocols. This microthruster system could also be considered for replacement of reaction wheels for slewing and fine pointing of other astronomical observatories, including Exo-Planet Observatory concepts. The goal of the PCOS SAT effort is to raise the new system to TRL 5 with performance and environmental testing within the next two years.

Pneumatic Microvalve-Based Hydrodynamic Sample Injection for High-Throughput, Quantitative Zone Electrophoresis in Capillaries

PubMed Central

2015-01-01

A hybrid microchip/capillary electrophoresis (CE) system was developed to allow unbiased and lossless sample loading and high-throughput repeated injections. This new hybrid CE system consists of a poly(dimethylsiloxane) (PDMS) microchip sample injector featuring a pneumatic microvalve that separates a sample introduction channel from a short sample loading channel, and a fused-silica capillary separation column that connects seamlessly to the sample loading channel. The sample introduction channel is pressurized such that when the pneumatic microvalve opens briefly, a variable-volume sample plug is introduced into the loading channel. A high voltage for CE separation is continuously applied across the loading channel and the fused-silica capillary separation column. Analytes are rapidly separated in the fused-silica capillary, and following separation, high-sensitivity MS detection is accomplished via a sheathless CE/ESI-MS interface. The performance evaluation of the complete CE/ESI-MS platform demonstrated that reproducible sample injection with well controlled sample plug volumes could be achieved by using the PDMS microchip injector. The absence of band broadening from microchip to capillary indicated a minimum dead volume at the junction. The capabilities of the new CE/ESI-MS platform in performing high-throughput and quantitative sample analyses were demonstrated by the repeated sample injection without interrupting an ongoing separation and a linear dependence of the total analyte ion abundance on the sample plug volume using a mixture of peptide standards. The separation efficiency of the new platform was also evaluated systematically at different sample injection times, flow rates, and CE separation voltages. PMID:24865952

Pneumatic Microvalve-Based Hydrodynamic Sample Injection for High-Throughput, Quantitative Zone Electrophoresis in Capillaries

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

Kelly, Ryan T.; Wang, Chenchen; Rausch, Sarah J.

2014-07-01

A hybrid microchip/capillary CE system was developed to allow unbiased and lossless sample loading and high throughput repeated injections. This new hybrid CE system consists of a polydimethylsiloxane (PDMS) microchip sample injector featuring a pneumatic microvalve that separates a sample introduction channel from a short sample loading channel and a fused silica capillary separation column that connects seamlessly to the sample loading channel. The sample introduction channel is pressurized such that when the pneumatic microvalve opens briefly, a variable-volume sample plug is introduced into the loading channel. A high voltage for CE separation is continuously applied across the loading channelmore » and the fused silica capillary separation column. Analytes are rapidly separated in the fused silica capillary with high resolution. High sensitivity MS detection after CE separation is accomplished via a sheathless CE/ESI-MS interface. The performance evaluation of the complete CE/ESI-MS platform demonstrated that reproducible sample injection with well controlled sample plug volumes could be achieved by using the PDMS microchip injector. The absence of band broadening from microchip to capillary indicated a minimum dead volume at the junction. The capabilities of the new CE/ESI-MS platform in performing high throughput and quantitative sample analyses were demonstrated by the repeated sample injection without interrupting an ongoing separation and a good linear dependence of the total analyte ion abundance on the sample plug volume using a mixture of peptide standards. The separation efficiency of the new platform was also evaluated systematically at different sample injection times, flow rates and CE separation voltages.« less

DNA and RNA sequencing by nanoscale reading through programmable electrophoresis and nanoelectrode-gated tunneling and dielectric detection

DOEpatents

Lee, James W.; Thundat, Thomas G.

2005-06-14

An apparatus and method for performing nucleic acid (DNA and/or RNA) sequencing on a single molecule. The genetic sequence information is obtained by probing through a DNA or RNA molecule base by base at nanometer scale as though looking through a strip of movie film. This DNA sequencing nanotechnology has the theoretical capability of performing DNA sequencing at a maximal rate of about 1,000,000 bases per second. This enhanced performance is made possible by a series of innovations including: novel applications of a fine-tuned nanometer gap for passage of a single DNA or RNA molecule; thin layer microfluidics for sample loading and delivery; and programmable electric fields for precise control of DNA or RNA movement. Detection methods include nanoelectrode-gated tunneling current measurements, dielectric molecular characterization, and atomic force microscopy/electrostatic force microscopy (AFM/EFM) probing for nanoscale reading of the nucleic acid sequences.

Optofluidic microvalve-on-a-chip with a surface plasmon-enhanced fiber optic microheater

PubMed Central

Zhang, Zhijian; Kusimo, Abisola; Yu, Miao

2014-01-01

We present an optofluidic microvalve utilizing an embedded, surface plasmon-enhanced fiber optic microheater. The fiber optic microheater is formed by depositing a titanium thin film on the roughened end-face of a silica optical fiber that serves as a waveguide to deliver laser light to the titanium film. The nanoscale roughness at the titanium-silica interface enables strong light absorption enhancement in the titanium film through excitation of localized surface plasmons as well as facilitates bubble nucleation. Our experimental results show that due to the unique design of the fiber optic heater, the threshold laser power required to generate a bubble is greatly reduced and the bubble growth rate is significantly increased. By using the microvalve, stable vapor bubble generation in the microchannel is demonstrated, which does not require complex optical focusing and alignment. The generated vapor bubble is shown to successfully block a liquid flow channel with a size of 125 μm × 125 μm and a flow rate of ∼10 μl/min at ∼120 mW laser power. PMID:25538813

Low-cost feedback-controlled syringe pressure pumps for microfluidics applications.

PubMed

Lake, John R; Heyde, Keith C; Ruder, Warren C

2017-01-01

Microfluidics are widely used in research ranging from bioengineering and biomedical disciplines to chemistry and nanotechnology. As such, there are a large number of options for the devices used to drive and control flow through microfluidic channels. Commercially available syringe pumps are probably the most commonly used instruments for this purpose, but are relatively high-cost and have inherent limitations due to their flow profiles when they are run open-loop. Here, we present a low-cost ($110) syringe pressure pump that uses feedback control to regulate the pressure into microfluidic chips. Using an open-source microcontroller board (Arduino), we demonstrate an easily operated and programmable syringe pump that can be run using either a PID or bang-bang control method. Through feedback control of the pressure at the inlets of two microfluidic geometries, we have shown stability of our device to within ±1% of the set point using a PID control method and within ±5% of the set point using a bang-bang control method with response times of less than 1 second. This device offers a low-cost option to drive and control well-regulated pressure-driven flow through microfluidic chips.

Low-cost feedback-controlled syringe pressure pumps for microfluidics applications

PubMed Central

Lake, John R.; Heyde, Keith C.

2017-01-01

Microfluidics are widely used in research ranging from bioengineering and biomedical disciplines to chemistry and nanotechnology. As such, there are a large number of options for the devices used to drive and control flow through microfluidic channels. Commercially available syringe pumps are probably the most commonly used instruments for this purpose, but are relatively high-cost and have inherent limitations due to their flow profiles when they are run open-loop. Here, we present a low-cost ($110) syringe pressure pump that uses feedback control to regulate the pressure into microfluidic chips. Using an open-source microcontroller board (Arduino), we demonstrate an easily operated and programmable syringe pump that can be run using either a PID or bang-bang control method. Through feedback control of the pressure at the inlets of two microfluidic geometries, we have shown stability of our device to within ±1% of the set point using a PID control method and within ±5% of the set point using a bang-bang control method with response times of less than 1 second. This device offers a low-cost option to drive and control well-regulated pressure-driven flow through microfluidic chips. PMID:28369134

Nanoliter-Scale Protein Crystallization and Screening with a Microfluidic Droplet Robot

PubMed Central

Zhu, Ying; Zhu, Li-Na; Guo, Rui; Cui, Heng-Jun; Ye, Sheng; Fang, Qun

2014-01-01

Large-scale screening of hundreds or even thousands of crystallization conditions while with low sample consumption is in urgent need, in current structural biology research. Here we describe a fully-automated droplet robot for nanoliter-scale crystallization screening that combines the advantages of both automated robotics technique for protein crystallization screening and the droplet-based microfluidic technique. A semi-contact dispensing method was developed to achieve flexible, programmable and reliable liquid-handling operations for nanoliter-scale protein crystallization experiments. We applied the droplet robot in large-scale screening of crystallization conditions of five soluble proteins and one membrane protein with 35–96 different crystallization conditions, study of volume effects on protein crystallization, and determination of phase diagrams of two proteins. The volume for each droplet reactor is only ca. 4–8 nL. The protein consumption significantly reduces 50–500 fold compared with current crystallization stations. PMID:24854085

Nanoliter-scale protein crystallization and screening with a microfluidic droplet robot.

PubMed

Zhu, Ying; Zhu, Li-Na; Guo, Rui; Cui, Heng-Jun; Ye, Sheng; Fang, Qun

2014-05-23

Large-scale screening of hundreds or even thousands of crystallization conditions while with low sample consumption is in urgent need, in current structural biology research. Here we describe a fully-automated droplet robot for nanoliter-scale crystallization screening that combines the advantages of both automated robotics technique for protein crystallization screening and the droplet-based microfluidic technique. A semi-contact dispensing method was developed to achieve flexible, programmable and reliable liquid-handling operations for nanoliter-scale protein crystallization experiments. We applied the droplet robot in large-scale screening of crystallization conditions of five soluble proteins and one membrane protein with 35-96 different crystallization conditions, study of volume effects on protein crystallization, and determination of phase diagrams of two proteins. The volume for each droplet reactor is only ca. 4-8 nL. The protein consumption significantly reduces 50-500 fold compared with current crystallization stations.

Reversible thermo-pneumatic valves on centrifugal microfluidic platforms.

PubMed

Aeinehvand, Mohammad Mahdi; Ibrahim, Fatimah; Harun, Sulaiman Wadi; Kazemzadeh, Amin; Rothan, Hussin A; Yusof, Rohana; Madou, Marc

2015-08-21

Centrifugal microfluidic systems utilize a conventional spindle motor to automate parallel biochemical assays on a single microfluidic disk. The integration of complex, sequential microfluidic procedures on these platforms relies on robust valving techniques that allow for the precise control and manipulation of fluid flow. The ability of valves to consistently return to their former conditions after each actuation plays a significant role in the real-time manipulation of fluidic operations. In this paper, we introduce an active valving technique that operates based on the deflection of a latex film with the potential for real-time flow manipulation in a wide range of operational spinning speeds. The reversible thermo-pneumatic valve (RTPV) seals or reopens an inlet when a trapped air volume is heated or cooled, respectively. The RTPV is a gas-impermeable valve composed of an air chamber enclosed by a latex membrane and a specially designed liquid transition chamber that enables the efficient usage of the applied thermal energy. Inputting thermo-pneumatic (TP) energy into the air chamber deflects the membrane into the liquid transition chamber against an inlet, sealing it and thus preventing fluid flow. From this point, a centrifugal pressure higher than the induced TP pressure in the air chamber reopens the fluid pathway. The behaviour of this newly introduced reversible valving system on a microfluidic disk is studied experimentally and theoretically over a range of rotational frequencies from 700 RPM to 2500 RPM. Furthermore, adding a physical component (e.g., a hemispherical rubber element) to induce initial flow resistance shifts the operational range of rotational frequencies of the RTPV to more than 6000 RPM. An analytical solution for the cooling of a heated RTPV on a spinning disk is also presented, which highlights the need for the future development of time-programmable RTPVs. Moreover, the reversibility and gas impermeability of the RTPV in the microfluidic networks are validated on a microfluidic disk designed for performing liquid circulation. Finally, an array of RTPVs is integrated into a microfluidic cartridge to enable sequential aliquoting for the conversion of dengue virus RNA to cDNA and the preparation of PCR reaction mixtures.

Printed droplet microfluidics for on demand dispensing of picoliter droplets and cells

PubMed Central

Cole, Russell H.; Tang, Shi-Yang; Siltanen, Christian A.; Shahi, Payam; Zhang, Jesse Q.; Poust, Sean; Gartner, Zev J.; Abate, Adam R.

2017-01-01

Although the elementary unit of biology is the cell, high-throughput methods for the microscale manipulation of cells and reagents are limited. The existing options either are slow, lack single-cell specificity, or use fluid volumes out of scale with those of cells. Here we present printed droplet microfluidics, a technology to dispense picoliter droplets and cells with deterministic control. The core technology is a fluorescence-activated droplet sorter coupled to a specialized substrate that together act as a picoliter droplet and single-cell printer, enabling high-throughput generation of intricate arrays of droplets, cells, and microparticles. Printed droplet microfluidics provides a programmable and robust technology to construct arrays of defined cell and reagent combinations and to integrate multiple measurement modalities together in a single assay. PMID:28760972

Printed droplet microfluidics for on demand dispensing of picoliter droplets and cells.

PubMed

Cole, Russell H; Tang, Shi-Yang; Siltanen, Christian A; Shahi, Payam; Zhang, Jesse Q; Poust, Sean; Gartner, Zev J; Abate, Adam R

2017-08-15

Although the elementary unit of biology is the cell, high-throughput methods for the microscale manipulation of cells and reagents are limited. The existing options either are slow, lack single-cell specificity, or use fluid volumes out of scale with those of cells. Here we present printed droplet microfluidics, a technology to dispense picoliter droplets and cells with deterministic control. The core technology is a fluorescence-activated droplet sorter coupled to a specialized substrate that together act as a picoliter droplet and single-cell printer, enabling high-throughput generation of intricate arrays of droplets, cells, and microparticles. Printed droplet microfluidics provides a programmable and robust technology to construct arrays of defined cell and reagent combinations and to integrate multiple measurement modalities together in a single assay.

Printed droplet microfluidics for on demand dispensing of picoliter droplets and cells

NASA Astrophysics Data System (ADS)

Cole, Russell H.; Tang, Shi-Yang; Siltanen, Christian A.; Shahi, Payam; Zhang, Jesse Q.; Poust, Sean; Gartner, Zev J.; Abate, Adam R.

2017-08-01

Although the elementary unit of biology is the cell, high-throughput methods for the microscale manipulation of cells and reagents are limited. The existing options either are slow, lack single-cell specificity, or use fluid volumes out of scale with those of cells. Here we present printed droplet microfluidics, a technology to dispense picoliter droplets and cells with deterministic control. The core technology is a fluorescence-activated droplet sorter coupled to a specialized substrate that together act as a picoliter droplet and single-cell printer, enabling high-throughput generation of intricate arrays of droplets, cells, and microparticles. Printed droplet microfluidics provides a programmable and robust technology to construct arrays of defined cell and reagent combinations and to integrate multiple measurement modalities together in a single assay.

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.

End-to-end automated microfluidic platform for synthetic biology: from design to functional analysis

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

Linshiz, Gregory; Jensen, Erik; Stawski, Nina

Synthetic biology aims to engineer biological systems for desired behaviors. The construction of these systems can be complex, often requiring genetic reprogramming, extensive de novo DNA synthesis, and functional screening. Here, we present a programmable, multipurpose microfluidic platform and associated software and apply the platform to major steps of the synthetic biology research cycle: design, construction, testing, and analysis. We show the platform’s capabilities for multiple automated DNA assembly methods, including a new method for Isothermal Hierarchical DNA Construction, and for Escherichia coli and Saccharomyces cerevisiae transformation. The platform enables the automated control of cellular growth, gene expression induction, andmore » proteogenic and metabolic output analysis. Finally, taken together, we demonstrate the microfluidic platform’s potential to provide end-to-end solutions for synthetic biology research, from design to functional analysis.« less

End-to-end automated microfluidic platform for synthetic biology: from design to functional analysis

DOE PAGES

Linshiz, Gregory; Jensen, Erik; Stawski, Nina; ...

2016-02-02

Synthetic biology aims to engineer biological systems for desired behaviors. The construction of these systems can be complex, often requiring genetic reprogramming, extensive de novo DNA synthesis, and functional screening. Here, we present a programmable, multipurpose microfluidic platform and associated software and apply the platform to major steps of the synthetic biology research cycle: design, construction, testing, and analysis. We show the platform’s capabilities for multiple automated DNA assembly methods, including a new method for Isothermal Hierarchical DNA Construction, and for Escherichia coli and Saccharomyces cerevisiae transformation. The platform enables the automated control of cellular growth, gene expression induction, andmore » proteogenic and metabolic output analysis. Finally, taken together, we demonstrate the microfluidic platform’s potential to provide end-to-end solutions for synthetic biology research, from design to functional analysis.« less

Pressure driven digital logic in PDMS based microfluidic devices fabricated by multilayer soft lithography.

PubMed

Devaraju, Naga Sai Gopi K; Unger, Marc A

2012-11-21

Advances in microfluidics now allow an unprecedented level of parallelization and integration of biochemical reactions. However, one challenge still faced by the field has been the complexity and cost of the control hardware: one external pressure signal has been required for each independently actuated set of valves on chip. Using a simple post-modification to the multilayer soft lithography fabrication process, we present a new implementation of digital fluidic logic fully analogous to electronic logic with significant performance advances over the previous implementations. We demonstrate a novel normally closed static gain valve capable of modulating pressure signals in a fashion analogous to an electronic transistor. We utilize these valves to build complex fluidic logic circuits capable of arbitrary control of flows by processing binary input signals (pressure (1) and atmosphere (0)). We demonstrate logic gates and devices including NOT, NAND and NOR gates, bi-stable flip-flops, gated flip-flops (latches), oscillators, self-driven peristaltic pumps, delay flip-flops, and a 12-bit shift register built using static gain valves. This fluidic logic shows cascade-ability, feedback, programmability, bi-stability, and autonomous control capability. This implementation of fluidic logic yields significantly smaller devices, higher clock rates, simple designs, easy fabrication, and integration into MSL microfluidics.

Electrically Controllable Microparticle Synthesis and Digital Microfluidic Manipulation by Electric-Field-Induced Droplet Dispensing into Immiscible Fluids

PubMed Central

Um, Taewoong; Hong, Jiwoo; Im, Do Jin; Lee, Sang Joon; Kang, In Seok

2016-01-01

The dispensing of tiny droplets is a basic and crucial process in a myriad of applications, such as DNA/protein microarray, cell cultures, chemical synthesis of microparticles, and digital microfluidics. This work systematically demonstrates droplet dispensing into immiscible fluids through electric charge concentration (ECC) method. It exhibits three main modes (i.e., attaching, uniform, and bursting modes) as a function of flow rates, applied voltages, and gap distances between the nozzle and the oil surface. Through a conventional nozzle with diameter of a few millimeters, charged droplets with volumes ranging from a few μL to a few tens of nL can be uniformly dispensed into the oil chamber without reduction in nozzle size. Based on the features of the proposed method (e.g., formation of droplets with controllable polarity and amount of electric charge in water and oil system), a simple and straightforward method is developed for microparticle synthesis, including preparation of colloidosomes and fabrication of Janus microparticles with anisotropic internal structures. Finally, a combined system consisting of ECC-induced droplet dispensing and electrophoresis of charged droplet (ECD)-driven manipulation systems is constructed. This integrated platform will provide increased utility and flexibility in microfluidic applications because a charged droplet can be delivered toward the intended position by programmable electric control. PMID:27534580

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.

Microfluidic device for novel breast cancer screening by blood test using miRNA beacon probe.

PubMed

Salim, Bindu; Athira, M V; Kandaswamy, A; Vijayakumar, Madhulika; Saravanan, T; Sairam, Thiagarajan

2017-09-30

Breast cancer is identified as the highest cause of death in women suffering from cancer. Early diagnosis is the key to increase the survival of breast cancer victims. Molecular diagnosis using biomarkers have advanced much in the recent years. The cost involved in such diagnosis is not affordable for most of the population. The concept being investigated here is to realize a simple diagnosis system for screening cancer by way of a blood test utilizing a miRNA based biomarker with a complementary molecular beacon probe. A microfluidic platform was designed and attached with a fluorescence reader, which is portable and cost effective. Experiments were performed with 51 blood samples of which 30 were healthy and 21 were positive for breast cancer, collected against institutional human ethical clearance, IHEC 16/180-7-9-2016. miRNA 21 was chosen as the biomarker because it is overexpressed 4-fold in the serum of breast cancer patients. This work involved design of an experiment to prove the concept of miRNA over expression followed by detection of miRNA 21 using the microfluidic platform attached with a fluorescence reader and validation of the results using quantitative Real Time Polymerase Chain Reaction (qRT-PCR). The results obtained from the microfluidic device concurred with qRT-PCR results. The device is suitable for point-of-care application in a mass-screening programme. The study also has revealed that the stage of the cancer could be indicated by this test, which will be further useful for deciding a therapeutic regime.

Screw-actuated displacement micropumps for thermoplastic microfluidics.

PubMed

Han, J Y; Rahmanian, O D; Kendall, E L; Fleming, N; DeVoe, D L

2016-10-05

The fabrication of on-chip displacement pumps integrated into thermoplastic chips is explored as a simple and low cost method for achieving precise and programmable flow control for disposable microfluidic systems. The displacement pumps consist of stainless steel screws inserted into threaded ports machined into a thermoplastic substrate which also serve as on-chip reagent storage reservoirs. Three different methods for pump sealing are investigated to enable high pressure flows without leakage, and software-defined control of multiple pumps is demonstrated in a self-contained platform using a compact and self-contained microcontroller for operation. Using this system, flow rates ranging from 0.5-40 μl min -1 are demonstrated. The pumps are combined with on-chip burst valves to fully seal multiple reagents into fabricated chips while providing on-demand fluid distribution in a downstream microfluidic network, and demonstrated for the generation of size-tunable water-in-oil emulsions.

Active mixing of complex fluids at the microscale

DOE PAGES

Ober, Thomas J.; Foresti, Daniele; Lewis, Jennifer A.

2015-09-22

Mixing of complex fluids at low Reynolds number is fundamental for a broad range of applications, including materials assembly, microfluidics, and biomedical devices. Of these materials, yield stress fluids (and gels) pose the most significant challenges, especially when they must be mixed in low volumes over short timescales. New scaling relationships between mixer dimensions and operating conditions are derived and experimentally verified to create a framework for designing active microfluidic mixers that can efficiently homogenize a wide range of complex fluids. As a result, active mixing printheads are then designed and implemented for multimaterial 3D printing of viscoelastic inks withmore » programmable control of local composition.« less

Active mixing of complex fluids at the microscale

PubMed Central

Ober, Thomas J.; Foresti, Daniele; Lewis, Jennifer A.

2015-01-01

Mixing of complex fluids at low Reynolds number is fundamental for a broad range of applications, including materials assembly, microfluidics, and biomedical devices. Of these materials, yield stress fluids (and gels) pose the most significant challenges, especially when they must be mixed in low volumes over short timescales. New scaling relationships between mixer dimensions and operating conditions are derived and experimentally verified to create a framework for designing active microfluidic mixers that can efficiently homogenize a wide range of complex fluids. Active mixing printheads are then designed and implemented for multimaterial 3D printing of viscoelastic inks with programmable control of local composition. PMID:26396254

[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.

3D packaging of a microfluidic system with sensory applications

NASA Astrophysics Data System (ADS)

Morrissey, Anthony; Kelly, Gerard; Alderman, John C.

1997-09-01

Among the main benefits of microsystem technology are its contributions to cost reductio, reliability and improved performance. however, the packaging of microsystems, and particularly microsensor, has proven to be one of the biggest limitations to their commercialization and the packaging of silicon sensor devices can be the most costly part of their fabrication. This paper describes the integration of 3D packaging of a microsystem. Central to the operation of the 3D demonstrator is a micromachined silicon membrane pump to supply fluids to a sensing chamber constructed about the active area of a sensor chip. This chip carries ISFET based chemical sensors, pressure sensors and thermal sensors. The electronics required for controlling and regulating the activity of the various sensors ar also available on this chip and as other chips in the 3D assembly. The demonstrator also contains a power supply module with optical fiber interconnections. All of these modules are integrated into a single plastic- encapsulated 3D vertical multichip module. The reliability of such a structure, initially proposed by Val was demonstrated by Barrett et al. An additional module available for inclusion in some of our assemblies is a test chip capable of measuring the packaging-induced stress experienced during and after assembly. The packaging process described produces a module with very high density and utilizes standard off-the-shelf components to minimize costs. As the sensor chip and micropump include micromachined silicon membranes and microvalves, the packaging of such structures has to allow consideration for the minimization of the packaging-induced stresses. With this in mind, low stress techniques, including the use of soft glob-top materials, were employed.

A lab-in-a-droplet bioassay strategy for centrifugal microfluidics with density difference pumping, power to disc and bidirectional flow control.

PubMed

Wang, Guanghui; Ho, Ho-Pui; Chen, Qiulan; Yang, Alice Kar-Lai; Kwok, Ho-Chin; Wu, Shu-Yuen; Kong, Siu-Kai; Kwan, Yiu-Wa; Zhang, Xuping

2013-09-21

In this paper, we present a lab-in-a-droplet bioassay strategy for a centrifugal microfluidics or lab-on-a-disc (LOAD) platform with three important advancements including density difference pumping, power to disc and bidirectional flow control. First, with the water based bioassay droplets trapped in a micro-channel filled with mineral oil, centrifugal force due to the density difference between the water and oil phases actuates droplet movement while the oil based medium remains stationary. Second, electricity is coupled to the rotating disc through a split-core transformer, thus enabling on-chip real-time heating in selected areas as desired and wireless programmable functionality. Third, an inertial mechanical structure is proposed to achieve bidirectional flow control within the spinning disc. The droplets can move back and forth between two heaters upon changing the rotational speed. Our platform is an essential and versatile solution for bioassays such as those involving DNA amplification, where localized temperature cycling is required. Finally, without the loss of generality, we demonstrate the functionality of our platform by performing real-time polymerase chain reaction (RT-PCR) in a linear microchannel made with PTFE (Teflon) micro-tubing.

Preparation of molecule-responsive microsized hydrogels via photopolymerization for smart microchannel microvalves.

PubMed

Shiraki, Yusuke; Tsuruta, Kazuhiro; Morimoto, Junpei; Ohba, Chihiro; Kawamura, Akifumi; Yoshida, Ryo; Kawano, Ryuji; Uragami, Tadashi; Miyata, Takashi

2015-03-01

Microdevices designed for practical environmental pollution monitoring need to detect specific pollutants such as dioxins. Bisphenol A (BPA) has been widely used as a monomer for the synthesis of polycarbonate and epoxy resins. However, the recent discovery of its high potential ability to disrupt human endocrine systems has made the development of smart systems and microdevices for its detection and removal necessary. Molecule-responsive microsized hydrogels with β-cycrodextrin (β-CD) as ligands are prepared by photopolymerization using a fluorescence microscope. The molecule-responsive micro-hydrogels show ultra-quick shrinkage in response to target BPA. Furthermore, the flow rate of a microchannel is autonomously regulated by the molecule-responsive shrinking of their hydrogels as smart microvalves. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Dotette: Programmable, high-precision, plug-and-play droplet pipetting.

PubMed

Fan, Jinzhen; Men, Yongfan; Hao Tseng, Kuo; Ding, Yi; Ding, Yunfeng; Villarreal, Fernando; Tan, Cheemeng; Li, Baoqing; Pan, Tingrui

2018-05-01

Manual micropipettes are the most heavily used liquid handling devices in biological and chemical laboratories; however, they suffer from low precision for volumes under 1  μ l and inevitable human errors. For a manual device, the human errors introduced pose potential risks of failed experiments, inaccurate results, and financial costs. Meanwhile, low precision under 1  μ l can cause severe quantification errors and high heterogeneity of outcomes, becoming a bottleneck of reaction miniaturization for quantitative research in biochemical labs. Here, we report Dotette, a programmable, plug-and-play microfluidic pipetting device based on nanoliter liquid printing. With automated control, protocols designed on computers can be directly downloaded into Dotette, enabling programmable operation processes. Utilizing continuous nanoliter droplet dispensing, the precision of the volume control has been successfully improved from traditional 20%-50% to less than 5% in the range of 100 nl to 1000 nl. Such a highly automated, plug-and-play add-on to existing pipetting devices not only improves precise quantification in low-volume liquid handling and reduces chemical consumptions but also facilitates and automates a variety of biochemical and biological operations.

Rapid prototyping of 2D glass microfluidic devices based on femtosecond laser assisted selective etching process

NASA Astrophysics Data System (ADS)

Kim, Sung-Il; Kim, Jeongtae; Koo, Chiwan; Joung, Yeun-Ho; Choi, Jiyeon

2018-02-01

Microfluidics technology which deals with small liquid samples and reagents within micro-scale channels has been widely applied in various aspects of biological, chemical, and life-scientific research. For fabricating microfluidic devices, a silicon-based polymer, PDMS (Polydimethylsiloxane), is widely used in soft lithography, but it has several drawbacks for microfluidic applications. Glass has many advantages over PDMS due to its excellent optical, chemical, and mechanical properties. However, difficulties in fabrication of glass microfluidic devices that requires multiple skilled steps such as MEMS technology taking several hours to days, impedes broad application of glass based devices. Here, we demonstrate a rapid and optical prototyping of a glass microfluidic device by using femtosecond laser assisted selective etching (LASE) and femtosecond laser welding. A microfluidic droplet generator was fabricated as a demonstration of a microfluidic device using our proposed prototyping. The fabrication time of a single glass chip containing few centimeter long and complex-shaped microfluidic channels was drastically reduced in an hour with the proposed laser based rapid and simple glass micromachining and hermetic packaging technique.

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.

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.

Biodriven microsystem for treatment of hydrocephalus

NASA Astrophysics Data System (ADS)

Joswig, Jurgen; Oswald, Jens; Seifert, Steffen

1995-09-01

A microvalve system made of silicon for use in hydrocephalus therapy is presented, which will provide an excellent intracranial pressure stabilization. Design and processing are described. Testing results (in vitro) are presented.

Analysis system for characterisation of simple, low-cost microfluidic components

NASA Astrophysics Data System (ADS)

Smith, Suzanne; Naidoo, Thegaran; Nxumalo, Zandile; Land, Kevin; Davies, Emlyn; Fourie, Louis; Marais, Philip; Roux, Pieter

2014-06-01

There is an inherent trade-off between cost and operational integrity of microfluidic components, especially when intended for use in point-of-care devices. We present an analysis system developed to characterise microfluidic components for performing blood cell counting, enabling the balance between function and cost to be established quantitatively. Microfluidic components for sample and reagent introduction, mixing and dispensing of fluids were investigated. A simple inlet port plugging mechanism is used to introduce and dispense a sample of blood, while a reagent is released into the microfluidic system through compression and bursting of a blister pack. Mixing and dispensing of the sample and reagent are facilitated via air actuation. For these microfluidic components to be implemented successfully, a number of aspects need to be characterised for development of an integrated point-of-care device design. The functional components were measured using a microfluidic component analysis system established in-house. Experiments were carried out to determine: 1. the force and speed requirements for sample inlet port plugging and blister pack compression and release using two linear actuators and load cells for plugging the inlet port, compressing the blister pack, and subsequently measuring the resulting forces exerted, 2. the accuracy and repeatability of total volumes of sample and reagent dispensed, and 3. the degree of mixing and dispensing uniformity of the sample and reagent for cell counting analysis. A programmable syringe pump was used for air actuation to facilitate mixing and dispensing of the sample and reagent. Two high speed cameras formed part of the analysis system and allowed for visualisation of the fluidic operations within the microfluidic device. Additional quantitative measures such as microscopy were also used to assess mixing and dilution accuracy, as well as uniformity of fluid dispensing - all of which are important requirements towards the successful implementation of a blood cell counting system.

High-throughput microfluidics to control and measure signaling dynamics in single yeast cells

PubMed Central

Hansen, Anders S.; Hao, Nan; O'Shea, Erin K.

2015-01-01

Microfluidics coupled to quantitative time-lapse fluorescence microscopy is transforming our ability to control, measure, and understand signaling dynamics in single living cells. Here we describe a pipeline that incorporates multiplexed microfluidic cell culture, automated programmable fluid handling for cell perturbation, quantitative time-lapse microscopy, and computational analysis of time-lapse movies. We illustrate how this setup can be used to control the nuclear localization of the budding yeast transcription factor Msn2. Using this protocol, we generate oscillations of Msn2 localization and measure the dynamic gene expression response of individual genes in single cells. The protocol allows a single researcher to perform up to 20 different experiments in a single day, whilst collecting data for thousands of single cells. Compared to other protocols, the present protocol is relatively easy to adopt and higher-throughput. The protocol can be widely used to control and monitor single-cell signaling dynamics in other signal transduction systems in microorganisms. PMID:26158443

Integrated bioassays in microfluidic devices: botulinum toxin assays.

PubMed

Mangru, Shakuntala; Bentz, Bryan L; Davis, Timothy J; Desai, Nitin; Stabile, Paul J; Schmidt, James J; Millard, Charles B; Bavari, Sina; Kodukula, Krishna

2005-12-01

A microfluidic assay was developed for screening botulinum neurotoxin serotype A (BoNT-A) by using a fluorescent resonance energy transfer (FRET) assay. Molded silicone microdevices with integral valves, pumps, and reagent reservoirs were designed and fabricated. Electrical and pneumatic control hardware were constructed, and software was written to automate the assay protocol and data acquisition. Detection was accomplished by fluorescence microscopy. The system was validated with a peptide inhibitor, running 2 parallel assays, as a feasibility demonstration. The small footprint of each bioreactor cell (0.5 cm2) and scalable fluidic architecture enabled many parallel assays on a single chip. The chip is programmable to run a dilution series in each lane, generating concentration-response data for multiple inhibitors. The assay results showed good agreement with the corresponding experiments done at a macroscale level. Although the system has been developed for BoNT-A screening, a wide variety of assays can be performed on the microfluidic chip with little or no modification.

Multi-parametric polymer-based potentiometric analytical microsystem for future manned space missions.

PubMed

Calvo-López, Antonio; Puyol, Mar; Casalta, Joan Manel; Alonso-Chamarro, Julián

2017-12-01

The construction and evaluation of a Cyclic Olefin Copolymer (COC)-based continuous flow potentiometric microanalyzer to simultaneously monitor potassium, chloride and nitrate ions in samples from an on-board water recycling process expected to be installed in future manned space missions is presented. The main goals accomplished in this work address the specific required characteristics for a miniaturized on-line monitoring system to control water quality in such missions. To begin with, the integration of three ion-selective electrodes (ISEs) and a reference electrode in a compact microfluidic platform that incorporates a simple automatic autocalibration process allows obtaining information about the concentration of the three ions with optimal analytical response characteristics, but moreover with low reagents consumption and therefore with few waste generation, which is critical for this specific application. By a simple signal processing (signal removal) the chloride ion interference on the nitrate electrode response can be eliminated. Furthermore, all fluidics management is performed by computer-controlled microvalves and micropumps, so no manual intervention of the crew is necessary. The analytical features provided by the microsystem after the optimization process were a linear range from 6.3 to 630 mg L -1 and a detection limit of 0.51 mg L -1 for the potassium electrode, a linear range from 10 to 1000 mg L -1 and a detection limit of 1.58 mg L -1 for the chloride electrode and a linear range from 10 to 1000 mg L -1 and a detection limit of 3.37 mg L -1 for the nitrate electrode with a reproducibility (RSD) of 4%, 2% and 3% respectively. Sample throughput was 12 h -1 with a reagent consumptions lower than 2 mL per analysis. Copyright © 2017 Elsevier B.V. All rights reserved.

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.

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.

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.

Printing-based fabrication method using sacrificial paper substrates for flexible and wearable microfluidic devices

NASA Astrophysics Data System (ADS)

Chung, Daehan; Gray, Bonnie L.

2017-11-01

We present a simple, fast, and inexpensive new printing-based fabrication process for flexible and wearable microfluidic channels and devices. Microfluidic devices are fabricated on textiles (fabric) for applications in clothing-based wearable microfluidic sensors and systems. The wearable and flexible microfluidic devices are comprised of water-insoluable screen-printable plastisol polymer. Sheets of paper are used as sacrificial substrates for multiple layers of polymer on the fabric’s surface. Microfluidic devices can be made within a short time using simple processes and inexpensive equipment that includes a laser cutter and a thermal laminator. The fabrication process is characterized to demonstrate control of microfluidic channel thickness and width. Film thickness smaller than 100 micrometers and lateral dimensions smaller than 150 micrometers are demonstrated. A flexible microfluidic mixer is also developed on fabric and successfully tested on both flat and curved surfaces at volumetric flow rates ranging from 5.5-46 ml min-1.

Precise and programmable manipulation of microbubbles by two-dimensional standing surface acoustic waves

NASA Astrophysics Data System (ADS)

Meng, Long; Cai, Feiyan; Chen, Juanjuan; Niu, Lili; Li, Yanming; Wu, Junru; Zheng, Hairong

2012-04-01

A microfluidic device is developed to transport microbubbles (MBs) along a desired trajectory in fluid by introducing the phase-shift to a planar standing surface acoustic wave (SSAW). The radiation force of SSAW due to the acoustic pressure gradient modulated by a phase-shift can move MBs to anticipated potential wells in a programmable manner. The resolution of the transportation is approximately 2.2 µm and the estimated radiation force on the MBs is on the order of 10-9 N. This device can be used for manipulation of bioparticles, cell sorting, tissue engineering, and other biomedical applications.

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.

Applications of Microfluidics in Quantitative Biology.

PubMed

Bai, Yang; Gao, Meng; Wen, Lingling; He, Caiyun; Chen, Yuan; Liu, Chenli; Fu, Xiongfei; Huang, Shuqiang

2018-05-01

Quantitative biology is dedicated to taking advantage of quantitative reasoning and advanced engineering technologies to make biology more predictable. Microfluidics, as an emerging technique, provides new approaches to precisely control fluidic conditions on small scales and collect data in high-throughput and quantitative manners. In this review, the authors present the relevant applications of microfluidics to quantitative biology based on two major categories (channel-based microfluidics and droplet-based microfluidics), and their typical features. We also envision some other microfluidic techniques that may not be employed in quantitative biology right now, but have great potential in the near future. © 2017 Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences. Biotechnology Journal Published by Wiley-VCH Verlag GmbH & Co. KGaA.

The pumping lid: investigating multi-material 3D printing for equipment-free, programmable generation of positive and negative pressures for microfluidic applications.

PubMed

Begolo, Stefano; Zhukov, Dmitriy V; Selck, David A; Li, Liang; Ismagilov, Rustem F

2014-12-21

Equipment-free pumping is a challenging problem and an active area of research in microfluidics, with applications for both laboratory and limited-resource settings. This paper describes the pumping lid method, a strategy to achieve equipment-free pumping by controlled generation of pressure. Pressure was generated using portable, lightweight, and disposable parts that can be integrated with existing microfluidic devices to simplify workflow and eliminate the need for pumping equipment. The development of this method was enabled by multi-material 3D printing, which allows fast prototyping, including composite parts that combine materials with different mechanical properties (e.g. both rigid and elastic materials in the same part). The first type of pumping lid we describe was used to produce predictable positive or negative pressures via controlled compression or expansion of gases. A model was developed to describe the pressures and flow rates generated with this approach and it was validated experimentally. Pressures were pre-programmed by the geometry of the parts and could be tuned further even while the experiment was in progress. Using multiple lids or a composite lid with different inlets enabled several solutions to be pumped independently in a single device. The second type of pumping lid, which relied on vapor-liquid equilibrium to generate pressure, was designed, modeled, and experimentally characterized. The pumping lid method was validated by controlling flow in different types of microfluidic applications, including the production of droplets, control of laminar flow profiles, and loading of SlipChip devices. We believe that applying the pumping lid methodology to existing microfluidic devices will enhance their use as portable diagnostic tools in limited resource settings as well as accelerate adoption of microfluidics in laboratories.

A multi-scale PDMS fabrication strategy to bridge the size mismatch between integrated circuits and microfluidics.

PubMed

Muluneh, Melaku; Issadore, David

2014-12-07

In recent years there has been great progress harnessing the small-feature size and programmability of integrated circuits (ICs) for biological applications, by building microfluidics directly on top of ICs. However, a major hurdle to the further development of this technology is the inherent size-mismatch between ICs (~mm) and microfluidic chips (~cm). Increasing the area of the ICs to match the size of the microfluidic chip, as has often been done in previous studies, leads to a waste of valuable space on the IC and an increase in fabrication cost (>100×). To address this challenge, we have developed a three dimensional PDMS chip that can straddle multiple length scales of hybrid IC/microfluidic chips. This approach allows millimeter-scale ICs, with no post-processing, to be integrated into a centimeter-sized PDMS chip. To fabricate this PDMS chip we use a combination of soft-lithography and laser micromachining. Soft lithography was used to define micrometer-scale fluid channels directly on the surface of the IC, allowing fluid to be controlled with high accuracy and brought into close proximity to sensors for highly sensitive measurements. Laser micromachining was used to create ~50 μm vias to connect these molded PDMS channels to a larger PDMS chip, which can connect multiple ICs and house fluid connections to the outside world. To demonstrate the utility of this approach, we built and demonstrated an in-flow magnetic cytometer that consisted of a 5 × 5 cm(2) microfluidic chip that incorporated a commercial 565 × 1145 μm(2) IC with a GMR sensing circuit. We additionally demonstrated the modularity of this approach by building a chip that incorporated two of these GMR chips connected in series.

Shannon Meets Fick on the Microfluidic Channel: Diffusion Limit to Sum Broadcast Capacity for Molecular Communication.

PubMed

Bicen, A Ozan; Lehtomaki, Janne J; Akyildiz, Ian F

2018-03-01

Molecular communication (MC) over a microfluidic channel with flow is investigated based on Shannon's channel capacity theorem and Fick's laws of diffusion. Specifically, the sum capacity for MC between a single transmitter and multiple receivers (broadcast MC) is studied. The transmitter communicates by using different types of signaling molecules with each receiver over the microfluidic channel. The transmitted molecules propagate through microfluidic channel until reaching the corresponding receiver. Although the use of different types of molecules provides orthogonal signaling, the sum broadcast capacity may not scale with the number of the receivers due to physics of the propagation (interplay between convection and diffusion based on distance). In this paper, the performance of broadcast MC on a microfluidic chip is characterized by studying the physical geometry of the microfluidic channel and leveraging the information theory. The convergence of the sum capacity for microfluidic broadcast channel is analytically investigated based on the physical system parameters with respect to the increasing number of molecular receivers. The analysis presented here can be useful to predict the achievable information rate in microfluidic interconnects for the biochemical computation and microfluidic multi-sample assays.

A perspective on paper-based microfluidics: Current status and future trends

PubMed Central

Li, Xu; Ballerini, David R.; Shen, Wei

2012-01-01

“Paper-based microfluidics” or “lab on paper,” as a burgeoning research field with its beginning in 2007, provides a novel system for fluid handling and fluid analysis for a variety of applications including health diagnostics, environmental monitoring as well as food quality testing. The reasons why paper becomes an attractive substrate for making microfluidic systems include: (1) it is a ubiquitous and extremely cheap cellulosic material; (2) it is compatible with many chemical/biochemical/medical applications; and (3) it transports liquids using capillary forces without the assistance of external forces. By building microfluidic channels on paper, liquid flow is confined within the channels, and therefore, liquid flow can be guided in a controlled manner. A variety of 2D and even 3D microfluidic channels have been created on paper, which are able to transport liquids in the predesigned pathways on paper. At the current stage of its development, paper-based microfluidic system is claimed to be low-cost, easy-to-use, disposable, and equipment-free, and therefore, is a rising technology particularly relevant to improving the healthcare and disease screening in the developing world, especially for those areas with no- or low-infrastructure and limited trained medical and health professionals. The research in paper-based microfluidics is experiencing a period of explosion; most published works have focused on: (1) inventing low-cost and simple fabrication techniques for paper-based microfluidic devices; and (2) exploring new applications of paper-based microfluidics by incorporating efficient detection methods. This paper aims to review both the fabrication techniques and applications of paper-based microfluidics reported to date. This paper also attempts to convey to the readers, from the authors’ point of view the current limitations of paper-based microfluidics which require further research, and a few perspective directions this new analytical system may take in its development. PMID:22662067

Microfluidic networks embedded in a printed circuit board

NASA Astrophysics Data System (ADS)

Dong, Liangwei; Hu, Yueli

2017-07-01

In order to improve the robustness of microfluidic networks in printed circuit board (PCB)-based microfluidic platforms, a new method was presented. A pattern in a PCB was formed using hollowed-out technology. Polydimethylsiloxane was partly filled in the hollowed-out fields after mounting an adhesive tape on the bottom of the PCB, and solidified in an oven. Then, microfluidic networks were built using soft lithography technology. Microfluidic transportation and dilution operations were demonstrated using the fabricated microfluidic platform. Results show that this method can embed microfluidic networks into a PCB, and microfluidic operations can be implemented in the microfluidic networks embedded into the PCB.

On-chip wavelength multiplexed detection of cancer DNA biomarkers in blood

PubMed Central

Cai, H.; Stott, M. A.; Ozcelik, D.; Parks, J. W.; Hawkins, A. R.; Schmidt, H.

2016-01-01

We have developed an optofluidic analysis system that processes biomolecular samples starting from whole blood and then analyzes and identifies multiple targets on a silicon-based molecular detection platform. We demonstrate blood filtration, sample extraction, target enrichment, and fluorescent labeling using programmable microfluidic circuits. We detect and identify multiple targets using a spectral multiplexing technique based on wavelength-dependent multi-spot excitation on an antiresonant reflecting optical waveguide chip. Specifically, we extract two types of melanoma biomarkers, mutated cell-free nucleic acids —BRAFV600E and NRAS, from whole blood. We detect and identify these two targets simultaneously using the spectral multiplexing approach with up to a 96% success rate. These results point the way toward a full front-to-back chip-based optofluidic compact system for high-performance analysis of complex biological samples. PMID:28058082

Microfluidic-Based Robotic Sampling System for Radioactive Solutions

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

Jack D. Law; Julia L. Tripp; Tara E. Smith

A novel microfluidic based robotic sampling system has been developed for sampling and analysis of liquid solutions in nuclear processes. This system couples the use of a microfluidic sample chip with a robotic system designed to allow remote, automated sampling of process solutions in-cell and facilitates direct coupling of the microfluidic sample chip with analytical instrumentation. This system provides the capability for near real time analysis, reduces analytical waste, and minimizes the potential for personnel exposure associated with traditional sampling methods. A prototype sampling system was designed, built and tested. System testing demonstrated operability of the microfluidic based sample systemmore » and identified system modifications to optimize performance.« less

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.

Fast and accurate enzyme activity measurements using a chip-based microfluidic calorimeter.

PubMed

van Schie, Morten M C H; Ebrahimi, Kourosh Honarmand; Hagen, Wilfred R; Hagedoorn, Peter-Leon

2018-03-01

Recent developments in microfluidic and nanofluidic technologies have resulted in development of new chip-based microfluidic calorimeters with potential use in different fields. One application would be the accurate high-throughput measurement of enzyme activity. Calorimetry is a generic way to measure activity of enzymes, but unlike conventional calorimeters, chip-based calorimeters can be easily automated and implemented in high-throughput screening platforms. However, application of chip-based microfluidic calorimeters to measure enzyme activity has been limited due to problems associated with miniaturization such as incomplete mixing and a decrease in volumetric heat generated. To address these problems we introduced a calibration method and devised a convenient protocol for using a chip-based microfluidic calorimeter. Using the new calibration method, the progress curve of alkaline phosphatase, which has product inhibition for phosphate, measured by the calorimeter was the same as that recorded by UV-visible spectroscopy. Our results may enable use of current chip-based microfluidic calorimeters in a simple manner as a tool for high-throughput screening of enzyme activity with potential applications in drug discovery and enzyme engineering. Copyright © 2017. Published by Elsevier Inc.

Microvalve

DOEpatents

Lee, A.P.; Krulevitch, P.A.; Northrup, M.A.; Trevino, J.C.

1998-10-13

Micromachined thin film cantilever actuators having means for individually controlling the deflection of the cantilevers, valve members, and rudders for steering same through blood vessels, or positioning same within a blood vessel, for example. Such cantilever actuators include tactile sensor arrays mounted on a catheter or guide wire tip for navigation and tissues identification, shape-memory alloy film based catheter/guide wire steering mechanisms, and rudder-based steering devices that allow the selective actuation of rudders that use the flowing blood itself to help direct the catheter direction through the blood vessel. While particularly adapted for medical applications, these cantilever actuators can be used for steering through piping and tubing systems. 14 figs.

Microvalve

DOEpatents

Lee, Abraham P.; Krulevitch, Peter A.; Northrup, M. Allen; Trevino, Jimmy C.

1998-01-01

Micromachined thin film cantilever actuators having means for individually controlling the deflection of the cantilevers, valve members, and rudders for steering same through blood vessels, or positioning same within a blood vessel, for example. Such cantilever actuators include tactile sensor arrays mounted on a catheter or guide wire tip for navigation and tissues identification, shape-memory alloy film based catheter/guide wire steering mechanisms, and rudder-based steering devices that allow the selective actuation of rudders that use the flowing blood itself to help direct the catheter direction through the blood vessel. While particularly adapted for medical applications, these cantilever actuators can be used for steering through piping and tubing systems.

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

Hyperuniform materials made with microfluidics

NASA Astrophysics Data System (ADS)

Yazhgur, Pavel; Ricouvier, Joshua; Pierrat, Romain; Carminati, RéMi; Tabeling, Patrick

Hyperuniform materials, being disordered systems with suppressed long-scale fluctuations, now attract a significant scientific interest, especially due to their potential applications for disordered photonic materials production. In our project we study a jammed packing of oil droplets in water. The droplets are produced in a PDMS microfluidic chip and directly assembled in a microfluidic channel. By varying the fluid pressures we manage to sharply control the droplet production and thereby govern the structural properties of the obtained material. The pseudo-2D (a monolayer of droplets) and 3D systems are investigated. Our results show that at appropriate experimental conditions droplets self-organize in hyperuniform patterns. Our electromagnetic simulations also show that the obtained material can be transparent while staying optically dense. As far as we know, the proposed material is one of the first examples of experimentally made hyperuniform materials. We hope that our studies will help to establish a new way of disordered photonic materials production. The Microflusa project receives funding from the European Union's Horizon 2020 research and innovation programme under Grant Agreement No. 664823.

Applications of antibodies in microfluidics-based analytical systems: challenges and strategies for success

NASA Astrophysics Data System (ADS)

O’Kennedy, Richard; Fitzgerald, Jenny; Cassedy, Arabelle; Crawley, Aoife; Zhang, Xin; Carrera, Sandro

2018-06-01

This review is designed to focus on antibodies and the attributes that make them ideal for applications in microfluidics-based diagnostic/separation platforms. The structures of different antibody formats and how they can be engineered to be highly effective in microfluidics-based environments will be highlighted. Suggested novel stratagems on the ideal way in which they can be employed in microfluidics systems, based on an informed knowledge of their structures and properties rather than random choice selection, as is often currently employed, will be provided. Finally, a critical assessment of current shortcomings in the approaches used along with possible ways for their resolution will be given.

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

Microfluidics for cell-based high throughput screening platforms - A review.

PubMed

Du, Guansheng; Fang, Qun; den Toonder, Jaap M J

2016-01-15

In the last decades, the basic techniques of microfluidics for the study of cells such as cell culture, cell separation, and cell lysis, have been well developed. Based on cell handling techniques, microfluidics has been widely applied in the field of PCR (Polymerase Chain Reaction), immunoassays, organ-on-chip, stem cell research, and analysis and identification of circulating tumor cells. As a major step in drug discovery, high-throughput screening allows rapid analysis of thousands of chemical, biochemical, genetic or pharmacological tests in parallel. In this review, we summarize the application of microfluidics in cell-based high throughput screening. The screening methods mentioned in this paper include approaches using the perfusion flow mode, the droplet mode, and the microarray mode. We also discuss the future development of microfluidic based high throughput screening platform for drug discovery. Copyright © 2015 Elsevier B.V. All rights reserved.

Paper-based microfluidic approach for surface-enhanced raman spectroscopy and highly reproducible detection of proteins beyond picomolar concentration.

PubMed

Saha, Arindam; Jana, Nikhil R

2015-01-14

Although microfluidic approach is widely used in various point of care diagnostics, its implementation in surface enhanced Raman spectroscopy (SERS)-based detection is challenging. This is because SERS signal depends on plasmonic nanoparticle aggregation induced generation of stable electromagnetic hot spots and in currently available microfluidic platform this condition is difficult to adapt. Here we show that SERS can be adapted using simple paper based microfluidic system where both the plasmonic nanomaterials and analyte are used in mobile phase. This approach allows analyte induced controlled particle aggregation and electromagnetic hot spot generation inside the microfluidic channel with the resultant SERS signal, which is highly reproducible and sensitive. This approach has been used for reproducible detection of protein in the pico to femtomolar concentration. Presented approach is simple, rapid, and cost-effective, and requires low sample volume. Method can be extended for SERS-based detection of other biomolecules.

Integrated microfluidic technology for sub-lethal and behavioral marine ecotoxicity biotests

NASA Astrophysics Data System (ADS)

Huang, Yushi; Reyes Aldasoro, Constantino Carlos; Persoone, Guido; Wlodkowic, Donald

2015-06-01

Changes in behavioral traits exhibited by small aquatic invertebrates are increasingly postulated as ethically acceptable and more sensitive endpoints for detection of water-born ecotoxicity than conventional mortality assays. Despite importance of such behavioral biotests, their implementation is profoundly limited by the lack of appropriate biocompatible automation, integrated optoelectronic sensors, and the associated electronics and analysis algorithms. This work outlines development of a proof-of-concept miniaturized Lab-on-a-Chip (LOC) platform for rapid water toxicity tests based on changes in swimming patterns exhibited by Artemia franciscana (Artoxkit M™) nauplii. In contrast to conventionally performed end-point analysis based on counting numbers of dead/immobile specimens we performed a time-resolved video data analysis to dynamically assess impact of a reference toxicant on swimming pattern of A. franciscana. Our system design combined: (i) innovative microfluidic device keeping free swimming Artemia sp. nauplii under continuous microperfusion as a mean of toxin delivery; (ii) mechatronic interface for user-friendly fluidic actuation of the chip; and (iii) miniaturized video acquisition for movement analysis of test specimens. The system was capable of performing fully programmable time-lapse and video-microscopy of multiple samples for rapid ecotoxicity analysis. It enabled development of a user-friendly and inexpensive test protocol to dynamically detect sub-lethal behavioral end-points such as changes in speed of movement or distance traveled by each animal.

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.

Microfluidic Dynamic Interfacial Tensiometry (μDIT).

PubMed

Brosseau, Quentin; Vrignon, Jérémy; Baret, Jean-Christophe

2014-05-07

We designed, developed and characterized a microfluidic method for the measurement of surfactant adsorption kinetics via interfacial tensiometry on a microfluidic chip. The principle of the measurement is based on the deformability of droplets as a response to hydrodynamic forcing through a series of microfluidic expansions. We focus our analysis on one perfluoro surfactant molecule of practical interest for droplet-based microfluidic applications. We show that although the adsorption kinetics is much faster than the kinetics of the corresponding pendant drop experiment, our droplet-based microfluidic system has a sufficient time resolution to obtain quantitative measurement at the sub-second time-scale on nanoliter droplet volumes, leading to both a gain by a factor of ∼10 in time resolution and a downscaling of the measurement volumes by a factor of ∼1000 compared to standard techniques. Our approach provides new insight into the adsorption of surfactant molecules at liquid-liquid interfaces in a confined environment, relevant to emulsification, encapsulation and foaming, and the ability to measure adsorption and desorption rate constants.

Microfluidic integrated acoustic waving for manipulation of cells and molecules.

PubMed

Barani, Alireza; Paktinat, Hossein; Janmaleki, Mohsen; Mohammadi, Aminollah; Mosaddegh, Peiman; Fadaei-Tehrani, Alireza; Sanati-Nezhad, Amir

2016-11-15

Acoustophoresis with its simple and low-cost fabrication, rapid and localized fluid actuation, compatibility with microfluidic components, and biocompatibility for cellular studies, has been extensively integrated into microfluidics to provide on-chip microdevices for a variety of applications in biology, bioengineering and chemistry. Among different applications, noninvasive manipulation of cells and biomolecules are significantly important, which are addressed by acoustic-based microfluidics. Here in this paper, we briefly explain the principles and different configurations of acoustic wave and acoustic streaming for the manipulation of cells and molecules and overview its applications for single cell isolation, cell focusing and sorting, cell washing and patterning, cell-cell fusion and communication, and tissue engineering. We further discuss the application of acoustic-based microfluidic systems for the mixing and transport of liquids, manipulation of deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) molecules, followed by explanation on the present challenges of acoustic-based microfluidics for the handling of cells and molecules, and highlighting the future directions. Crown Copyright © 2016. Published by Elsevier B.V. All rights reserved.

Aptamer-based microfluidic beads array sensor for simultaneous detection of multiple analytes employing multienzyme-linked nanoparticle amplification and quantum dots labels.

PubMed

Zhang, He; Hu, Xinjiang; Fu, Xin

2014-07-15

This study reports the development of an aptamer-mediated microfluidic beads-based sensor for multiple analytes detection and quantification using multienzyme-linked nanoparticle amplification and quantum dots labels. Adenosine and cocaine were selected as the model analytes to validate the assay design based on strand displacement induced by target-aptamer complex. Microbeads functionalized with the aptamers and modified electron rich proteins were arrayed within a microfluidic channel and were connected with the horseradish peroxidases (HRP) and capture DNA probe derivative gold nanoparticles (AuNPs) via hybridization. The conformational transition of aptamer induced by target-aptamer complex contributes to the displacement of functionalized AuNPs and decreases the fluorescence signal of microbeads. In this approach, increased binding events of HRP on each nanosphere and enhanced mass transport capability inherent from microfluidics are integrated for enhancing the detection sensitivity of analytes. Based on the dual signal amplification strategy, the developed aptamer-based microfluidic bead array sensor could discriminate as low as 0.1 pM of adenosine and 0.5 pM cocaine, and showed a 500-fold increase in detection limit of adenosine compared to the off-chip test. The results proved the microfluidic-based method was a rapid and efficient system for aptamer-based targets assays (adenosine (0.1 pM) and cocaine (0.5 pM)), requiring only minimal (microliter) reagent use. This work demonstrated the successful application of aptamer-based microfluidic beads array sensor for detection of important molecules in biomedical fields. Copyright © 2014 Elsevier B.V. All rights reserved.

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.

Microfluidic technology for molecular diagnostics.

PubMed

Robinson, Tom; Dittrich, Petra S

2013-01-01

Molecular diagnostics have helped to improve the lives of millions of patients worldwide by allowing clinicians to diagnose patients earlier as well as providing better ongoing therapies. Point-of-care (POC) testing can bring these laboratory-based techniques to the patient in a home setting or to remote settings in the developing world. However, despite substantial progress in the field, there still remain many challenges. Progress in molecular diagnostics has benefitted greatly from microfluidic technology. This chapter aims to summarise the more recent advances in microfluidic-based molecular diagnostics. Sections include an introduction to microfluidic technology, the challenges of molecular diagnostics, how microfluidic advances are working to solve these issues, some alternative design approaches, and detection within these systems.

The current status of alternatives to animal testing and predictive toxicology methods using liver microfluidic biochips.

PubMed

Prot, Jean Matthieu; Leclerc, Eric

2012-06-01

In this paper, we will consider new in vitro cell culture platforms and the progress made, based on the microfluidic liver biochips dedicated to pharmacological and toxicological studies. Particular emphasis will be given to recent developments in the microfluidic tools dedicated to cell culture (more particularly liver cell culture), in silico opportunities for Physiologically Based PharmacoKinetic (PBPK) modelling, the challenge of the mechanistic interpretations offered by the approaches resulting from "multi-omics" data (transcriptomics, proteomics, metabolomics, cytomics) and imaging microfluidic platforms. Finally, we will discuss the critical features regarding microfabrication, design and materials, and cell functionality as the key points for the future development of new microfluidic liver biochips.

Recent Progress of Microfluidics in Translational Applications

PubMed Central

Liu, Zongbin; Han, Xin

2016-01-01

Microfluidics, featuring microfabricated structures, is a technology for manipulating fluids at the micrometer scale. The small dimension and flexibility of microfluidic systems are ideal for mimicking molecular and cellular microenvironment, and show great potential in translational research and development. Here, the recent progress of microfluidics in biological and biomedical applications, including molecular analysis, cellular analysis, and chip-based material delivery and biomimetic design is presented. The potential future developments in the translational microfluidics field are also discussed. PMID:27091777

Microfluidic Impedance Flow Cytometry Enabling High-Throughput Single-Cell Electrical Property Characterization

PubMed Central

Chen, Jian; Xue, Chengcheng; Zhao, Yang; Chen, Deyong; Wu, Min-Hsien; Wang, Junbo

2015-01-01

This article reviews recent developments in microfluidic impedance flow cytometry for high-throughput electrical property characterization of single cells. Four major perspectives of microfluidic impedance flow cytometry for single-cell characterization are included in this review: (1) early developments of microfluidic impedance flow cytometry for single-cell electrical property characterization; (2) microfluidic impedance flow cytometry with enhanced sensitivity; (3) microfluidic impedance and optical flow cytometry for single-cell analysis and (4) integrated point of care system based on microfluidic impedance flow cytometry. We examine the advantages and limitations of each technique and discuss future research opportunities from the perspectives of both technical innovation and clinical applications. PMID:25938973

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.

A multi-scale PDMS fabrication strategy to bridge the size mismatch between integrated circuits and microfluidics†

PubMed Central

Muluneh, Melaku

2015-01-01

In recent years there has been great progress harnessing the small-feature size and programmability of integrated circuits (ICs) for biological applications, by building microfluidics directly on top of ICs. However, a major hurdle to the further development of this technology is the inherent size-mismatch between ICs (~mm) and microfluidic chips (~cm). Increasing the area of the ICs to match the size of the microfluidic chip, as has often been done in previous studies, leads to a waste of valuable space on the IC and an increase in fabrication cost (>100×). To address this challenge, we have developed a three dimensional PDMS chip that can straddle multiple length scales of hybrid IC/microfluidic chips. This approach allows millimeter-scale ICs, with no post-processing, to be integrated into a centimeter-sized PDMS chip. To fabricate this PDMS chip we use a combination of soft-lithography and laser micromachining. Soft lithography was used to define micrometer-scale fluid channels directly on the surface of the IC, allowing fluid to be controlled with high accuracy and brought into close proximity to sensors for highly sensitive measurements. Laser micromachining was used to create ~50 μm vias to connect these molded PDMS channels to a larger PDMS chip, which can connect multiple ICs and house fluid connections to the outside world. To demonstrate the utility of this approach, we built and demonstrated an in-flow magnetic cytometer that consisted of a 5 × 5 cm2 microfluidic chip that incorporated a commercial 565 × 1145 μm2 IC with a GMR sensing circuit. We additionally demonstrated the modularity of this approach by building a chip that incorporated two of these GMR chips connected in series. PMID:25284502

Towards microfluidic technology-based MALDI-MS platforms for drug discovery: a review.

PubMed

Winkle, Richard F; Nagy, Judit M; Cass, Anthony Eg; Sharma, Sanjiv

2008-11-01

Microfluidic methods have found applications in various disciplines. It has been predicted that the microfluidic technology would be useful in performing routine steps in drug discovery ranging from target identification to lead optimisation in which the number of compounds evaluated in this regard determines the success of combinatorial screening. The sheer size of the parameter space that can be explored often poses an enormous challenge. We set out to find how close we are towards the use of integrated matrix-assisted laser desorption/ionisation mass spectrometry (MALDI-MS) microfluidic systems for drug discovery. In this article we review the latest applications of microfluidic technology in the area of MALDI-MS and drug discovery. Our literature survey revealed microfluidic technologies-based approaches for various stages of drug discovery; however, they are in still in developmental stages. Furthermore, we speculate on how these technologies could be used in the future.

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.

Recent Progress of Microfluidics in Translational Applications.

PubMed

Liu, Zongbin; Han, Xin; Qin, Lidong

2016-04-20

Microfluidics, featuring microfabricated structures, is a technology for manipulating fluids at the micrometer scale. The small dimension and flexibility of microfluidic systems are ideal for mimicking molecular and cellular microenvironment, and show great potential in translational research and development. Here, the recent progress of microfluidics in biological and biomedical applications, including molecular analysis, cellular analysis, and chip-based material delivery and biomimetic design is presented. The potential future developments in the translational microfluidics field are also discussed. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

In-air microfluidics enables rapid fabrication of emulsions, suspensions, and 3D modular (bio)materials

PubMed Central

Visser, Claas Willem; Kamperman, Tom; Karbaat, Lisanne P.; Lohse, Detlef; Karperien, Marcel

2018-01-01

Microfluidic chips provide unparalleled control over droplets and jets, which have advanced all natural sciences. However, microfluidic applications could be vastly expanded by increasing the per-channel throughput and directly exploiting the output of chips for rapid additive manufacturing. We unlock these features with in-air microfluidics, a new chip-free platform to manipulate microscale liquid streams in the air. By controlling the composition and in-air impact of liquid microjets by surface tension–driven encapsulation, we fabricate monodisperse emulsions, particles, and fibers with diameters of 20 to 300 μm at rates that are 10 to 100 times higher than chip-based droplet microfluidics. Furthermore, in-air microfluidics uniquely enables module-based production of three-dimensional (3D) multiscale (bio)materials in one step because droplets are partially solidified in-flight and can immediately be printed onto a substrate. In-air microfluidics is cytocompatible, as demonstrated by additive manufacturing of 3D modular constructs with tailored microenvironments for multiple cell types. Its in-line control, high throughput and resolution, and cytocompatibility make in-air microfluidics a versatile platform technology for science, industry, and health care. PMID:29399628

Multifunctional System-on-Glass for Lab-on-Chip applications.

PubMed

Petrucci, G; Caputo, D; Lovecchio, N; Costantini, F; Legnini, I; Bozzoni, I; Nascetti, A; de Cesare, G

2017-07-15

Lab-on-Chip are miniaturized systems able to perform biomolecular analysis in shorter time and with lower reagent consumption than a standard laboratory. Their miniaturization interferes with the multiple functions that the biochemical procedures require. In order to address this issue, our paper presents, for the first time, the integration on a single glass substrate of different thin film technologies in order to develop a multifunctional platform suitable for on-chip thermal treatments and on-chip detection of biomolecules. The proposed System on-Glass hosts thin metal films acting as heating sources; hydrogenated amorphous silicon diodes acting both as temperature sensors to monitor the temperature distribution and photosensors for the on-chip detection and a ground plane ensuring that the heater operation does not affect the photodiode currents. The sequence of the technological steps, the deposition temperatures of the thin films and the parameters of the photolithographic processes have been optimized in order to overcome all the issues of the technological integration. The device has been designed, fabricated and tested for the implementation of DNA amplification through the Polymerase Chain Reaction (PCR) with thermal cycling among three different temperatures on a single site. The glass has been connected to an electronic system that drives the heaters and controls the temperature and light sensors. It has been optically and thermally coupled with another glass hosting a microfluidic network made in polydimethylsiloxane that includes thermally actuated microvalves and a PCR process chamber. The successful DNA amplification has been verified off-chip by using a standard fluorometer. Copyright © 2016 Elsevier B.V. All rights reserved.

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.

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.

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…

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.

Pen-on-paper strategy for point-of-care testing: Rapid prototyping of fully written microfluidic biosensor.

PubMed

Li, Zedong; Li, Fei; Xing, Yue; Liu, Zhi; You, Minli; Li, Yingchun; Wen, Ting; Qu, Zhiguo; Ling Li, Xiao; Xu, Feng

2017-12-15

Paper-based microfluidic biosensors have recently attracted increasing attentions in point-of-care testing (POCT) territories benefiting from their affordable, accessible and eco-friendly features, where technologies for fabricating such biosensors are preferred to be equipment free, easy-to-operate and capable of rapid prototyping. In this work, we developed a pen-on-paper (PoP) strategy based on two custom-made pens, i.e., a wax pen and a conductive-ink pen, to fully write paper-based microfluidic biosensors through directly writing both microfluidic channels and electrodes. Particularly, the proposed wax pen is competent to realize one-step fabrication of wax channels on paper, as the melted wax penetrates into paper during writing process without any post-treatments. The practical applications of the fabricated paper-based microfluidic biosensors are demonstrated by both colorimetric detection of Salmonella typhimurium DNA with detection limit of 1nM and electrochemical measurement of glucose with detection limit of 1mM. The developed PoP strategy for making microfluidic biosensors on paper characterized by true simplicity, prominent portability and excellent capability for rapid prototyping shows promising prospect in POCT applications. Copyright © 2017 Elsevier B.V. All rights reserved.

Microfluidic Lab-on-a-Chip Platforms: Requirements, Characteristics and Applications

NASA Astrophysics Data System (ADS)

Mark, D.; Haeberle, S.; Roth, G.; Von Stetten, F.; Zengerle, R.

This review summarizes recent developments in microfluidic platform approaches. In contrast to isolated application-specific solutions, a microfluidic platform provides a set of fluidic unit operations, which are designed for easy combination within a well-defined fabrication technology. This allows the implementation of different application-specific (bio-) chemical processes, automated by microfluidic process integration [1]. A brief introduction into technical advances, major market segments and promising applications is followed by a detailed characterization of different microfluidic platforms, comprising a short definition, the functional principle, microfluidic unit operations, application examples as well as strengths and limitations. The microfluidic platforms in focus are lateral flow tests, linear actuated devices, pressure driven laminar flow, microfluidic large scale integration, segmented flow microfluidics, centrifugal microfluidics, electro-kinetics, electrowetting, surface acoustic waves, and systems for massively parallel analysis. The review concludes with the attempt to provide a selection scheme for microfluidic platforms which is based on their characteristics according to key requirements of different applications and market segments. Applied selection criteria comprise portability, costs of instrument and disposable, sample throughput, number of parameters per sample, reagent consumption, precision, diversity of microfluidic unit operations and the flexibility in programming different liquid handling protocols.

A Microfluidics-HPLC/Differential Mobility Spectrometer Macromolecular Detection System for Human and Robotic Missions

NASA Technical Reports Server (NTRS)

Coy, S. L.; Killeen, K.; Han, J.; Eiceman, G. A.; Kanik, I.; Kidd, R. D.

2011-01-01

Our goal is to develop a unique, miniaturized, solute analyzer based on microfluidics technology. The analyzer consists of an integrated microfluidics High Performance Liquid Chromatographic chip / Differential Mobility Spectrometer (?HPLCchip/ DMS) detection system

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.

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.

A multi-functional bubble-based microfluidic system

PubMed Central

Khoshmanesh, Khashayar; Almansouri, Abdullah; Albloushi, Hamad; Yi, Pyshar; Soffe, Rebecca; Kalantar-zadeh, Kourosh

2015-01-01

Recently, the bubble-based systems have offered a new paradigm in microfluidics. Gas bubbles are highly flexible, controllable and barely mix with liquids, and thus can be used for the creation of reconfigurable microfluidic systems. In this work, a hydrodynamically actuated bubble-based microfluidic system is introduced. This system enables the precise movement of air bubbles via axillary feeder channels to alter the geometry of the main channel and consequently the flow characteristics of the system. Mixing of neighbouring streams is demonstrated by oscillating the bubble at desired displacements and frequencies. Flow control is achieved by pushing the bubble to partially or fully close the main channel. Patterning of suspended particles is also demonstrated by creating a large bubble along the sidewalls. Rigorous analytical and numerical calculations are presented to describe the operation of the system. The examples presented in this paper highlight the versatility of the developed bubble-based actuator for a variety of applications; thus providing a vision that can be expanded for future highly reconfigurable microfluidics. PMID:25906043

Manufacturing and characterization of a ceramic single-use microvalve

NASA Astrophysics Data System (ADS)

Khaji, Z.; Klintberg, L.; Thornell, G.

2016-09-01

We present the manufacturing and characterization of a ceramic single-use microvalve with the potential to be integrated in lab-on-a-chip devices, and forsee its utilization in space and other demanding applications. A 3 mm diameter membrane was used as the flow barrier, and the opening mechanism was based on cracking the membrane by inducing thermal stresses on it with fast and localized resistive heating. Four manufacturing schemes based on high-temperature co-fired ceramic technology were studied. Three designs for the integrated heaters and two thicknesses of 40 and 120 μm for the membranes were considered, and the heat distribution over their membranes, the required heating energies, their opening mode, and the flows admitted through were compared. Furthermore, the effect of applying  +1 and  -1 bar pressure difference on the membrane during cracking was investigated. Thick membranes demonstrated unpromising results for low-pressure applications since the heating either resulted in microcracks or cracking of the whole chip. Because of the higher pressure tolerance of the thick membranes, the design with microcracks can be considered for high-pressure applications where flow is facilitated anyway. Thin membranes, on the other hand, showed different opening sizes depending on heater design and, consequently, heat distribution over the membranes, from microcracks to holes with sizes of 3-100% of the membrane area. For all the designs, applying  +1 bar over pressure contributed to bigger openings, whereas  -1 bar pressure difference only did so for one of the designs, resulting in smaller openings for the other two. The energy required for breaking these membranes was a few hundred mJ with no significant dependence on design and applied pressure. The maximum sustainable pressure of the valve for the current design and thin membranes was 7 bar.

Microfluidic chip-based technologies: emerging platforms for cancer diagnosis

PubMed Central

2013-01-01

The development of early and personalized diagnostic protocols is considered the most promising avenue to decrease mortality from cancer and improve outcome. The emerging microfluidic-based analyzing platforms hold high promises to fulfill high-throughput and high-precision screening with reduced equipment cost and low analysis time, as compared to traditional bulky counterparts in bench-top laboratories. This article overviewed the potential applications of microfluidic technologies for detection and monitoring of cancer through nucleic acid and protein biomarker analysis. The implications of the technologies in cancer cytology that can provide functional personalized diagnosis were highlighted. Finally, the future niches for using microfluidic-based systems in tumor screening were briefly discussed. PMID:24070124

A self-triggered picoinjector in microfluidics

NASA Astrophysics Data System (ADS)

Yang, Yiming; Liu, Songsheng; Jia, Chunping; Mao, Hongju; Jin, Qinghui; Zhao, Jianlong; Zhou, Hongbo

2016-12-01

Droplet-based microfluidics has recently emerged as a potential platform for studies of single-cell, directed evolution, and genetic sequencing. In droplet-based microfluidics, adding reagents into drops is one of the most important functions. In this paper, we develop a new self-triggered picoinjector to add controlled volumes of reagent into droplets at kilohertz rates. In the picoinjector, the reagent injecting is triggered by the coming droplet itself, without needing a droplet detection module. Meanwhile, the dosing volume can be precisely controlled. These features make the system more practical and reliable. We expect the new picoinjector will find important applications of droplet-based microfluidics in automated biological assay, directed evolution, enzyme assay, and so on.

Vacuum-driven power-free microfluidics utilizing the gas solubility or permeability of polydimethylsiloxane (PDMS).

PubMed

Xu, Linfeng; Lee, Hun; Jetta, Deekshitha; Oh, Kwang W

2015-10-21

Suitable pumping methods for flow control remain a major technical hurdle in the path of biomedical microfluidic systems for point-of-care (POC) diagnostics. A vacuum-driven power-free micropumping method provides a promising solution to such a challenge. In this review, we focus on vacuum-driven power-free microfluidics based on the gas solubility or permeability of polydimethylsiloxane (PDMS); degassed PDMS can restore air inside itself due to its high gas solubility or gas permeable nature. PDMS allows the transfer of air into a vacuum through it due to its high gas permeability. Therefore, it is possible to store or transfer air into or through the gas soluble or permeable PDMS in order to withdraw liquids into the embedded dead-end microfluidic channels. This article provides a comprehensive look at the physics of the gas solubility and permeability of PDMS, a systematic review of different types of vacuum-driven power-free microfluidics, and guidelines for designing solubility-based or permeability-based PDMS devices, alongside existing applications. Advanced topics and the outlook in using micropumping that utilizes the gas solubility or permeability of PDMS will be also discussed. We strongly recommend that microfluidics and lab-on-chip (LOC) communities harness vacuum energy to develop smart vacuum-driven microfluidic systems.

Modular integration of electronics and microfluidic systems using flexible printed circuit boards.

PubMed

Wu, Amy; Wang, Lisen; Jensen, Erik; Mathies, Richard; Boser, Bernhard

2010-02-21

Microfluidic systems offer an attractive alternative to conventional wet chemical methods with benefits including reduced sample and reagent volumes, shorter reaction times, high-throughput, automation, and low cost. However, most present microfluidic systems rely on external means to analyze reaction products. This substantially adds to the size, complexity, and cost of the overall system. Electronic detection based on sub-millimetre size integrated circuits (ICs) has been demonstrated for a wide range of targets including nucleic and amino acids, but deployment of this technology to date has been limited due to the lack of a flexible process to integrate these chips within microfluidic devices. This paper presents a modular and inexpensive process to integrate ICs with microfluidic systems based on standard printed circuit board (PCB) technology to assemble the independently designed microfluidic and electronic components. The integrated system can accommodate multiple chips of different sizes bonded to glass or PDMS microfluidic systems. Since IC chips and flex PCB manufacturing and assembly are industry standards with low cost, the integrated system is economical for both laboratory and point-of-care settings.

Polymer-based microfluidic chips for isothermal amplification of nucleic acids

NASA Astrophysics Data System (ADS)

Posmitnaya, Y. S.; Rudnitskaya, G. E.; Tupik, A. N.; Lukashenko, T. A.; Bukatin, A. C.; Evstrapov, A. A.

2017-11-01

Creation of low-cost compact devices based on microfluidic platforms for biological and medical research depends on the degree of development and enhancement of prototyping technologies. Two designs of polymer and hybrid microfluidic devices fabricated by soft lithography and intended for isothermal amplification and polymerase chain reaction are presented in this paper. The digital helicase-dependent isothermal amplification was tested in the device containing a droplet generator. Polymerase chain reaction was carried out in the hybrid microfluidic device having ten reaction chambers. A synthesized cDNA fragment of GAPDH housekeeping gene was used as a target.

Inhibition of Breast Cancer Progression by Blocking Heterocellular Contact Between Epithelial Cells and Fibroblasts

DTIC Science & Technology

2013-04-01

by employing a microfluidic -based compartmentalized 3D co-culture platform enabling both contact-free and contact-associated co-cultures. 15...SUBJECT TERMS Heterocellular contact between cancer cells and stromal fibroblasts, Microfluidics , 3D 16. SECURITY CLASSIFICATION OF: 17. LIMITATION...and human mammary fibroblasts (HMFs) in breast cancer progression by employing a microfluidic - based compartmentalized 3D co-culture platform

New generation of amino coumarin methyl sulfonate-based fluorogenic substrates for amidase assays in droplet-based microfluidic applications.

PubMed

Woronoff, Gabrielle; El Harrak, Abdeslam; Mayot, Estelle; Schicke, Olivier; Miller, Oliver J; Soumillion, Patrice; Griffiths, Andrew D; Ryckelynck, Michael

2011-04-15

Droplet-based microfluidics is a powerful tool for biology and chemistry as it allows the production and the manipulation of picoliter-size droplets acting as individual reactors. In this format, high-sensitivity assays are typically based on fluorescence, so fluorophore exchange between droplets must be avoided. Fluorogenic substrates based on the coumarin leaving group are widely used to measure a variety of enzymatic activities, but their application in droplet-based microfluidic systems is severely impaired by the fast transport of the fluorescent product between compartments. Here we report the synthesis of new amidase fluorogenic substrates based on 7-aminocoumarin-4-methanesulfonic acid (ACMS), a highly water-soluble dye, and their suitability for droplet-based microfluidics applications. Both substrate and product had the required spectral characteristics and remained confined in droplets from hours to days. As a model experiment, a phenylacetylated ACMS was synthesized and used as a fluorogenic substrate of Escherichia coli penicillin G acylase. Kinetic parameters (k(cat) and K(M)) measured in bulk and in droplets on-chip were very similar, demonstrating the suitability of this synthesis strategy to produce a variety of ACMS-based substrates for assaying amidase activities both in microtiter plate and droplet-based microfluidic formats. © 2011 American Chemical Society

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

Microfluidic platform combining droplets and magnetic tweezers: application to HER2 expression in cancer diagnosis.

PubMed

Ferraro, Davide; Champ, Jérôme; Teste, Bruno; Serra, Marco; Malaquin, Laurent; Viovy, Jean-Louis; de Cremoux, Patricia; Descroix, Stephanie

2016-05-09

The development of precision medicine, together with the multiplication of targeted therapies and associated molecular biomarkers, call for major progress in genetic analysis methods, allowing increased multiplexing and the implementation of more complex decision trees, without cost increase or loss of robustness. We present a platform combining droplet microfluidics and magnetic tweezers, performing RNA purification, reverse transcription and amplification in a fully automated and programmable way, in droplets of 250nL directly sampled from a microtiter-plate. This platform decreases sample consumption about 100 fold as compared to current robotized platforms and it reduces human manipulations and contamination risk. The platform's performance was first evaluated on cell lines, showing robust operation on RNA quantities corresponding to less than one cell, and then clinically validated with a cohort of 21 breast cancer samples, for the determination of their HER2 expression status, in a blind comparison with an established routine clinical analysis.

Highly Stretchable and Transparent Microfluidic Strain Sensors for Monitoring Human Body Motions.

PubMed

Yoon, Sun Geun; Koo, Hyung-Jun; Chang, Suk Tai

2015-12-16

We report a new class of simple microfluidic strain sensors with high stretchability, transparency, sensitivity, and long-term stability with no considerable hysteresis and a fast response to various deformations by combining the merits of microfluidic techniques and ionic liquids. The high optical transparency of the strain sensors was achieved by introducing refractive-index matched ionic liquids into microfluidic networks or channels embedded in an elastomeric matrix. The microfluidic strain sensors offer the outstanding sensor performance under a variety of deformations induced by stretching, bending, pressing, and twisting of the microfluidic strain sensors. The principle of our microfluidic strain sensor is explained by a theoretical model based on the elastic channel deformation. In order to demonstrate its capability of practical usage, the simple-structured microfluidic strain sensors were performed onto a finger, wrist, and arm. The highly stretchable and transparent microfluidic strain sensors were successfully applied as potential platforms for distinctively monitoring a wide range of human body motions in real time. Our novel microfluidic strain sensors show great promise for making future stretchable electronic devices.

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.

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.

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.

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.

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.

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

Microfluidic strategies for design and assembly of microfibers and nanofibers with tissue engineering and regenerative medicine applications.

PubMed

Daniele, Michael A; Boyd, Darryl A; Adams, André A; Ligler, Frances S

2015-01-07

Fiber-based materials provide critical capabilities for biomedical applications. Microfluidic fiber fabrication has recently emerged as a very promising route to the synthesis of polymeric fibers at the micro and nanoscale, providing fine control over fiber shape, size, chemical anisotropy, and biological activity. This Progress Report summarizes advanced microfluidic methods for the fabrication of both microscale and nanoscale fibers and illustrates how different methods are enabling new biomedical applications. Microfluidic fabrication methods and resultant materials are explained from the perspective of their microfluidic device principles, including co-flow, cross-flow, and flow-shaping designs. It is then detailed how the microchannel design and flow parameters influence the variety of synthesis chemistries that can be utilized. Finally, the integration of biomaterials and microfluidic strategies is discussed to manufacture unique fiber-based systems, including cell scaffolds, cell encapsulation, and woven tissue matrices. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemical and Biological Dynamics Using Droplet-Based Microfluidics.

PubMed

Dressler, Oliver J; Casadevall I Solvas, Xavier; deMello, Andrew J

2017-06-12

Recent years have witnessed an increased use of droplet-based microfluidic techniques in a wide variety of chemical and biological assays. Nevertheless, obtaining dynamic data from these platforms has remained challenging, as this often requires reading the same droplets (possibly thousands of them) multiple times over a wide range of intervals (from milliseconds to hours). In this review, we introduce the elemental techniques for the formation and manipulation of microfluidic droplets, together with the most recent developments in these areas. We then discuss a wide range of analytical methods that have been successfully adapted for analyte detection in droplets. Finally, we highlight a diversity of studies where droplet-based microfluidic strategies have enabled the characterization of dynamic systems that would otherwise have remained unexplorable.

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

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.

Exosome separation using microfluidic systems: size-based, immunoaffinity-based and dynamic methodologies.

PubMed

Yang, Fang; Liao, Xiangzhi; Tian, Yuan; Li, Guiying

2017-04-01

Exosomes, nanovesicles secreted by most types of cells, exist in virtually all bodily fluids. Their rich nucleic acid and protein content make them potentially valuable biomarkers for noninvasive molecular diagnostics. They also show promise, after further development, to serve as a drug delivery system. Unfortunately, existing exosome separation technologies, such as ultracentrifugation and methods incorporating magnetic beads, are time-consuming, laborious and separate only exosomes of low purity. Thus, a more effective separation method is highly desirable. Microfluidic platforms are ideal tools for exosome separation, since they enable fast, cost-efficient, portable and precise processing of nanoparticles and small volumes of liquid samples. Recently, several microfluidic-based exosome separation technologies have been studied. In this article, the advantages of the most recent technologies, as well as their limitations, challenges and potential uses in novel microfluidic exosome separation and collection applications is reviewed. This review outlines the uses of new powerful microfluidic exosome detection tools for biologists and clinicians, as well as exosome separation tools for microfluidic engineers. Current challenges of exosome separation methodologies are also described, in order to highlight areas for future research and development. Copyright © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Machine vision for digital microfluidics

NASA Astrophysics Data System (ADS)

Shin, Yong-Jun; Lee, Jeong-Bong

2010-01-01

Machine vision is widely used in an industrial environment today. It can perform various tasks, such as inspecting and controlling production processes, that may require humanlike intelligence. The importance of imaging technology for biological research or medical diagnosis is greater than ever. For example, fluorescent reporter imaging enables scientists to study the dynamics of gene networks with high spatial and temporal resolution. Such high-throughput imaging is increasingly demanding the use of machine vision for real-time analysis and control. Digital microfluidics is a relatively new technology with expectations of becoming a true lab-on-a-chip platform. Utilizing digital microfluidics, only small amounts of biological samples are required and the experimental procedures can be automatically controlled. There is a strong need for the development of a digital microfluidics system integrated with machine vision for innovative biological research today. In this paper, we show how machine vision can be applied to digital microfluidics by demonstrating two applications: machine vision-based measurement of the kinetics of biomolecular interactions and machine vision-based droplet motion control. It is expected that digital microfluidics-based machine vision system will add intelligence and automation to high-throughput biological imaging in the future.

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.

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.

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.

Disposable luciferase-based microfluidic chip for rapid assay of water pollution.

PubMed

Denisov, Ivan; Lukyanenko, Kirill; Yakimov, Anton; Kukhtevich, Igor; Esimbekova, Elena; Belobrov, Peter

2018-06-21

In the present study, we demonstrate the use of a disposable luciferase-based microfluidic bioassay chip for environmental monitoring and methods for fabrication. The designed microfluidic system includes a chamber with immobilized enzymes of bioluminescent bacteria Photobacterium leiognathi and Vibrio fischeri and their substrates, which dissolve after the introduction of the water sample and thus activate bioluminescent reactions. Limits of detection for copper (II) sulfate, 1,3-dihydroxybenzene and 1,4-benzoquinone for the proposed microfluidic biosensor measured 3 μM, 15 mM, and 2 μM respectively, and these values are higher or close to the level of conventional environmental biosensors based on lyophilized bacteria. Approaches for entrapment of enzymes on poly(methyl methacrylate) (PMMA) plates using a gelatin scaffold and solvent bonding of PMMA chip plates under room temperature were suggested. The proposed microfluidic system may be used with some available luminometers and future portable luminescence readers. © 2018 John Wiley & Sons, Ltd.

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.

Introducing natural thermoplastic shellac to microfluidics: A green fabrication method for point-of-care devices

PubMed Central

Lausecker, R.; Badilita, V.; Wallrabe, U.

2016-01-01

We present a sustainable fabrication method for cheap point-of-care microfluidic systems, employing hot embossing of natural shellac as a key feature of an energy-efficient fabrication method that exclusively uses renewable materials as consumables. Shellac is a low-cost renewable biomaterial that features medium hydrophilicity (e.g., a water contact angle of ca. 73°) and a high chemical stability with respect to common solvents such as cyclohexane or toluene, rendering it an interesting candidate for low-cost microfluidics and a competitor to well-known systems such as paper-based or polydimethylsiloxane-based microfluidics. Moreover, its high replication accuracy for small features down to 30 μm lateral feature size and its ability to form smooth surfaces (surface roughness Ra = 29 nm) at low embossing temperatures (glass transition temperature Tg = 42.2 °C) enable energy-efficient hot embossing of microfluidic structures. Proof-of-concept for the implementation of shellac hot embossing as a green fabrication method for microfluidic systems is demonstrated through the successful fabrication of a microfluidic test setup and the assessment of its resource consumption. PMID:27478525

Microfluidics on compliant substrates: recent developments in foldable and bendable devices and system packaging

NASA Astrophysics Data System (ADS)

Gray, Bonnie L.

2012-04-01

Microfluidics is revolutionizing laboratory methods and biomedical devices, offering new capabilities and instrumentation in multiple areas such as DNA analysis, proteomics, enzymatic analysis, single cell analysis, immunology, point-of-care medicine, personalized medicine, drug delivery, and environmental toxin and pathogen detection. For many applications (e.g., wearable and implantable health monitors, drug delivery devices, and prosthetics) mechanically flexible polymer devices and systems that can conform to the body offer benefits that cannot be achieved using systems based on conventional rigid substrate materials. However, difficulties in implementing active devices and reliable packaging technologies have limited the success of flexible microfluidics. Employing highly compliant materials such as PDMS that are typically employed for prototyping, we review mechanically flexible polymer microfluidic technologies based on free-standing polymer substrates and novel electronic and microfluidic interconnection schemes. Central to these new technologies are hybrid microfabrication methods employing novel nanocomposite polymer materials and devices. We review microfabrication methods using these materials, along with demonstrations of example devices and packaging schemes that employ them. We review these recent developments and place them in the context of the fields of flexible microfluidics and conformable systems, and discuss cross-over applications to conventional rigid-substrate microfluidics.

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.

Gold nanoparticle-based optical microfluidic sensors for analysis of environmental pollutants.

PubMed

Lafleur, Josiane P; Senkbeil, Silja; Jensen, Thomas G; Kutter, Jörg P

2012-11-21

Conventional methods of environmental analysis can be significantly improved by the development of portable microscale technologies for direct in-field sensing at remote locations. This report demonstrates the vast potential of gold nanoparticle-based microfluidic sensors for the rapid, in-field, detection of two important classes of environmental contaminants - heavy metals and pesticides. Using gold nanoparticle-based microfluidic sensors linked to a simple digital camera as the detector, detection limits as low as 0.6 μg L(-1) and 16 μg L(-1) could be obtained for the heavy metal mercury and the dithiocarbamate pesticide ziram, respectively. These results demonstrate that the attractive optical properties of gold nanoparticle probes combine synergistically with the inherent qualities of microfluidic platforms to offer simple, portable and sensitive sensors for environmental contaminants.

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.

"Hot-wire" microfluidic flowmeter based on a microfiber coupler.

PubMed

Yan, Shao-Cheng; Liu, Zeng-Yong; Li, Cheng; Ge, Shi-Jun; Xu, Fei; Lu, Yan-Qing

2016-12-15

Using an optical microfiber coupler (MC), we present a microfluidic platform for strong direct or indirect light-liquid interaction by wrapping a MC around a functionalized capillary. The light propagating in the MC and the liquid flowing in the capillary can be combined and divorced smoothly, keeping a long-distance interaction without the conflict of input and output coupling. Using this approach, we experimentally demonstrate a "hot-wire" microfluidic flowmeter based on a gold-integrated helical MC device. The microfluid inside the glass channel takes away the heat, then cools the MC and shifts the resonant wavelength. Due to the long-distance interaction and high temperature sensitivity, the proposed microfluidic flowmeter shows an ultrahigh flow rate sensitivity of 2.183 nm/(μl/s) at a flow rate of 1 μl/s. The minimum detectable change of the flow rate is around 9 nl/s at 1 μl/s.

High-content screening in microfluidic devices.

PubMed

Cheong, Raymond; Paliwal, Saurabh; Levchenko, Andre

2010-08-01

Miniaturization is the key to advancing the state of the art in high-content screening (HCS) in order to enable dramatic cost savings through reduced usage of expensive biochemical reagents and to enable large-scale screening on primary cells. Microfluidic technology offers the potential to enable HCS to be performed with an unprecedented degree of miniaturization. This perspective highlights a real-world example from the authors’ work of HCS assays implemented in a highly miniaturized microfluidic format. The advantages of this technology are discussed, including cost savings, high-throughput screening on primary cells, improved accuracy, the ability to study complex time-varying stimuli, and ease of automation, integration and scaling. The reader will understand the capabilities of anew microfluidics-based platform for HCS and the advantages it provides over conventional plate-based HCS. Microfluidics technology will drive significant advancements and broader usage and applicability of HCS in drug discovery.

A novel approach to determine the efficacy of patterned surfaces for biofouling control in relation to its microfluidic environment.

PubMed

Halder, Partha; Nasabi, Mahyar; Lopez, Francisco Javier Tovar; Jayasuriya, Niranjali; Bhattacharya, Satinath; Deighton, Margaret; Mitchell, Arnan; Bhuiyan, Muhammed Ali

2013-01-01

Biofouling, the unwanted growth of sessile microorganisms on submerged surfaces, presents a serious problem for underwater structures. While biofouling can be controlled to various degrees with different microstructure-based patterned surfaces, understanding of the underlying mechanism is still imprecise. Researchers have long speculated that microtopographies might influence near-surface microfluidic conditions, thus microhydrodynamically preventing the settlement of microorganisms. It is therefore very important to identify the microfluidic environment developed on patterned surfaces and its relation with the antifouling behaviour of those surfaces. This study considered the wall shear stress distribution pattern as a significant aspect of this microfluidic environment. In this study, patterned surfaces with microwell arrays were assessed experimentally with a real-time biofilm development monitoring system using a novel microchannel-based flow cell reactor. Finally, computational fluid dynamics simulations were carried out to show how the microfluidic conditions were affecting the initial settlement of microorganisms.

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 systems for stem cell-based neural tissue engineering.

PubMed

Karimi, Mahdi; Bahrami, Sajad; Mirshekari, Hamed; Basri, Seyed Masoud Moosavi; Nik, Amirala Bakhshian; Aref, Amir R; Akbari, Mohsen; Hamblin, Michael R

2016-07-05

Neural tissue engineering aims at developing novel approaches for the treatment of diseases of the nervous system, by providing a permissive environment for the growth and differentiation of neural cells. Three-dimensional (3D) cell culture systems provide a closer biomimetic environment, and promote better cell differentiation and improved cell function, than could be achieved by conventional two-dimensional (2D) culture systems. With the recent advances in the discovery and introduction of different types of stem cells for tissue engineering, microfluidic platforms have provided an improved microenvironment for the 3D-culture of stem cells. Microfluidic systems can provide more precise control over the spatiotemporal distribution of chemical and physical cues at the cellular level compared to traditional systems. Various microsystems have been designed and fabricated for the purpose of neural tissue engineering. Enhanced neural migration and differentiation, and monitoring of these processes, as well as understanding the behavior of stem cells and their microenvironment have been obtained through application of different microfluidic-based stem cell culture and tissue engineering techniques. As the technology advances it may be possible to construct a "brain-on-a-chip". In this review, we describe the basics of stem cells and tissue engineering as well as microfluidics-based tissue engineering approaches. We review recent testing of various microfluidic approaches for stem cell-based neural tissue engineering.

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

Microfluidic and Label-Free Multi-Immunosensors Based on Carbon Nanotube Microelectrodes

NASA Astrophysics Data System (ADS)

Tsujita, Yuichi; Maehashi, Kenzo; Matsumoto, Kazuhiko; Chikae, Miyuki; Takamura, Yuzuru; Tamiya, Eiichi

2009-06-01

We fabricated microfluidic and label-free multi-immunosensors by the integration of carbon nanotube (CNT)-arrayed electrodes and microchannels with pneumatic micropumps made of poly(dimethylsiloxane). In the microfluidic systems, four kinds of sample solutions were transported from each liquid inlet to microchannels using six pneumatic micropumps. As a result, two kinds of antibodies were immobilized onto different CNT electrodes using the microfluidic systems. Next, two kinds of cancer markers, prostate specific antigen and human chorionic gonadotropin in phosphate buffer solution, were simultaneously detected by differential pulse voltammetry. Therefore, microfludic multi-immunosensors based on CNT electrodes and pneumatic micropumps are useful for the development of multiplex hand-held biosensors.

Microfluidic microscopy-assisted label-free approach for cancer screening: automated microfluidic cytology for cancer screening.

PubMed

Jagannadh, Veerendra Kalyan; Gopakumar, G; Subrahmanyam, Gorthi R K Sai; Gorthi, Sai Siva

2017-05-01

Each year, about 7-8 million deaths occur due to cancer around the world. More than half of the cancer-related deaths occur in the less-developed parts of the world. Cancer mortality rate can be reduced with early detection and subsequent treatment of the disease. In this paper, we introduce a microfluidic microscopy-based cost-effective and label-free approach for identification of cancerous cells. We outline a diagnostic framework for the same and detail an instrumentation layout. We have employed classical computer vision techniques such as 2D principal component analysis-based cell type representation followed by support vector machine-based classification. Analogous to criminal face recognition systems implemented with help of surveillance cameras, a signature-based approach for cancerous cell identification using microfluidic microscopy surveillance is demonstrated. Such a platform would facilitate affordable mass screening camps in the developing countries and therefore help decrease cancer mortality rate.

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.

An integrated direct loop-mediated isothermal amplification microdevice incorporated with an immunochromatographic strip for bacteria detection in human whole blood and milk without a sample preparation step.

PubMed

Lee, Dohwan; Kim, Yong Tae; Lee, Jee Won; Kim, Do Hyun; Seo, Tae Seok

2016-05-15

We have developed an integrated direct loop-mediated isothermal amplification (Direct LAMP) microdevice incorporated with an immunochromatographic strip (ICS) to identify bacteria contaminated in real samples. The Direct LAMP is a novel isothermal DNA amplification technique which does not require thermal cycling steps as well as any sample preparation steps such as cell lysis and DNA extraction for amplifying specific target genes. In addition, the resultant amplicons were colorimetrically detected on the ICS, thereby enabling the entire genetic analysis process to be simplified. The two functional units (Direct LAMP and ICS) were integrated on a single device without use of the tedious and complicated microvalve and tubing systems. The utilization of a slidable plate allows us to manipulate the fluidic control in the microchannels manually and the sequential operation of the Direct LAMP and ICS detection could be performed by switching the slidable plate to each functional unit. Thus, the combination of the direct isothermal amplification without any sample preparation and thermal cycling steps, the ICS based amplicon detection by naked eyes, and the slidable plate to eliminate the microvalves in the integrated microdevice would be an ideal platform for point-of-care DNA diaganotics. On the integrated Direct LAMP-ICS microdevice, we could analyze Staphylococcus aureus (S. aureus) and Escherichia coli O157:H7 (E. coli O157:H7) contaminated in human whole blood or milk at a single-cell level within 1h. Copyright © 2015 Elsevier B.V. All rights reserved.

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.

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.

Microfluidic magnetic switching valves based on aggregates of magnetic nanoparticles: Effects of aggregate length and nanoparticle sizes

NASA Astrophysics Data System (ADS)

Jiemsakul, Thanakorn; Manakasettharn, Supone; Kanharattanachai, Sivakorn; Wanna, Yongyuth; Wangsuya, Sujint; Pratontep, Sirapat

2017-01-01

We demonstrate microfluidic switching valves using magnetic nanoparticles blended within the working fluid as an alternative microfluidic flow control in microchannels. Y-shaped microchannels have been fabricated by using a CO2 laser cutter to pattern microchannels on transparent poly(methyl methacrylate) (PMMA) sheets covered with thermally bonded transparent polyvinyl chloride (PVC) sheets. To examine the performance of the microfluidic magnetic switching valves, an aqueous magnetic nanoparticle suspension was injected into the microchannels by a syringe pump. Neodymium magnets were then employed to attract magnetic nanoparticles and form an aggregate that blocked the microchannels at a required position. We have found that the maximum volumetric flow rate of the syringe pump that the magnetic nanoparticle aggregate can withstand scales with the square of the external magnetic flux density. The viscosity of the fluid exhibits dependent on the aggregate length and the size of the magnetic nanoparticles. This microfluidic switching valve based on aggregates of magnetic nanoparticles has strong potentials as an on-demand flow control, which may help simplifying microfluidic channel designs.

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.

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.

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.

Liposome production by microfluidics: potential and limiting factors

PubMed Central

Carugo, Dario; Bottaro, Elisabetta; Owen, Joshua; Stride, Eleanor; Nastruzzi, Claudio

2016-01-01

This paper provides an analysis of microfluidic techniques for the production of nanoscale lipid-based vesicular systems. In particular we focus on the key issues associated with the microfluidic production of liposomes. These include, but are not limited to, the role of lipid formulation, lipid concentration, residual amount of solvent, production method (including microchannel architecture), and drug loading in determining liposome characteristics. Furthermore, we propose microfluidic architectures for the mass production of liposomes with a view to potential industrial translation of this technology. PMID:27194474

Liposome production by microfluidics: potential and limiting factors.

PubMed

Carugo, Dario; Bottaro, Elisabetta; Owen, Joshua; Stride, Eleanor; Nastruzzi, Claudio

2016-05-19

This paper provides an analysis of microfluidic techniques for the production of nanoscale lipid-based vesicular systems. In particular we focus on the key issues associated with the microfluidic production of liposomes. These include, but are not limited to, the role of lipid formulation, lipid concentration, residual amount of solvent, production method (including microchannel architecture), and drug loading in determining liposome characteristics. Furthermore, we propose microfluidic architectures for the mass production of liposomes with a view to potential industrial translation of this technology.

Microfluidic desalination techniques and their potential applications.

PubMed

Roelofs, S H; van den Berg, A; Odijk, M

2015-09-07

In this review we discuss recent developments in the emerging research field of miniaturized desalination. Traditionally desalination is performed to convert salt water into potable water and research is focused on improving performance of large-scale desalination plants. Microfluidic desalination offers several new opportunities in comparison to macro-scale desalination, such as providing a platform to increase fundamental knowledge of ion transport on the nano- and microfluidic scale and new microfluidic sample preparation methods. This approach has also lead to the development of new desalination techniques, based on micro/nanofluidic ion-transport phenomena, which are potential candidates for up-scaling to (portable) drinking water devices. This review assesses microfluidic desalination techniques on their applications and is meant to contribute to further implementation of microfluidic desalination techniques in the lab-on-chip community.

Microfluidics for food, agriculture and biosystems industries.

PubMed

Neethirajan, Suresh; Kobayashi, Isao; Nakajima, Mitsutoshi; Wu, Dan; Nandagopal, Saravanan; Lin, Francis

2011-05-07

Microfluidics, a rapidly emerging enabling technology has the potential to revolutionize food, agriculture and biosystems industries. Examples of potential applications of microfluidics in food industry include nano-particle encapsulation of fish oil, monitoring pathogens and toxins in food and water supplies, micro-nano-filtration for improving food quality, detection of antibiotics in dairy food products, and generation of novel food structures. In addition, microfluidics enables applications in agriculture and animal sciences such as nutrients monitoring and plant cells sorting for improving crop quality and production, effective delivery of biopesticides, simplified in vitro fertilization for animal breeding, animal health monitoring, vaccination and therapeutics. Lastly, microfluidics provides new approaches for bioenergy research. This paper synthesizes information of selected microfluidics-based applications for food, agriculture and biosystems industries. © The Royal Society of Chemistry 2011

Study on Manipulations of Fluids in Micro-scale and Their Applications in Physical, Bio/chemistry

NASA Astrophysics Data System (ADS)

Zhou, Bingpu

Microfluidics is a highly interdisciplinary research field which manipulates, controls and analyzes fluids in micro-scale for physical and bio/chemical applications. In this thesis, several aspects of fluid manipulations in micro-scale were studied, discussed and employed for demonstrations of practical utilizations. To begin with, mixing in continuous flow microfluidic was raised and investigated. A simple method for mixing actuation based on magnetism was proposed and realized via integration of magnetically functionalized micropillar arrays inside the microfluidic channel.With such technique, microfluidic mixing could be swiftly switched on and off via simple application or retraction of the magnetic field. Thereafter, in Chapter 3 we mainly focused on how to establish stable while tunable concentration gradients inside microfluidic network using a simple design. The proposed scheme could also be modified with on-chip pneumatic actuated valve to realize pulsatile/temporal concentration gradients simultaneously in ten microfluidic branches. We further applied such methodology to obtain roughness gradients onPolydimethylsiloxane (PDMS) surface via combinations of the microfluidic network andphoto-polymerizations. The obtained materials were utilized in parallel cell culture to figure out the relationship between substrate morphologies and the cell behaviors. In the second part of this work, we emphasized on manipulations on microdroplets insidethe microfluidic channel and explored related applications in bio/chemical aspects. Firstly, microdroplet-based microfluidic universal logic gates were successfully demonstrated vialiquid-electronic hybrid divider. For application based on such novel scheme of control lable droplet generation, on-demand chemical reaction within paired microdroplets was presented using IF logic gate. Followed by this, another important operation of microdroplet - splitting -was investigated. Addition lateral continuous flow was applied at the bifurcation as a mediumto controllably divide microdroplets with highly tunable splitting ratios. Related physical mechanism was proposed and such approach was adopted further for rapid synthesis of multi-scale microspheres.

Suspended microfluidics.

PubMed

Casavant, Benjamin P; Berthier, Erwin; Theberge, Ashleigh B; Berthier, Jean; Montanez-Sauri, Sara I; Bischel, Lauren L; Brakke, Kenneth; Hedman, Curtis J; Bushman, Wade; Keller, Nancy P; Beebe, David J

2013-06-18

Although the field of microfluidics has made significant progress in bringing new tools to address biological questions, the accessibility and adoption of microfluidics within the life sciences are still limited. Open microfluidic systems have the potential to lower the barriers to adoption, but the absence of robust design rules has hindered their use. Here, we present an open microfluidic platform, suspended microfluidics, that uses surface tension to fill and maintain a fluid in microscale structures devoid of a ceiling and floor. We developed a simple and ubiquitous model predicting fluid flow in suspended microfluidic systems and show that it encompasses many known capillary phenomena. Suspended microfluidics was used to create arrays of collagen membranes, mico Dots (μDots), in a horizontal plane separating two fluidic chambers, demonstrating a transwell platform able to discern collective or individual cellular invasion. Further, we demonstrated that μDots can also be used as a simple multiplexed 3D cellular growth platform. Using the μDot array, we probed the combined effects of soluble factors and matrix components, finding that laminin mitigates the growth suppression properties of the matrix metalloproteinase inhibitor GM6001. Based on the same fluidic principles, we created a suspended microfluidic metabolite extraction platform using a multilayer biphasic system that leverages the accessibility of open microchannels to retrieve steroids and other metabolites readily from cell culture. Suspended microfluidics brings the high degree of fluidic control and unique functionality of closed microfluidics into the highly accessible and robust platform of open microfluidics.

Suspended microfluidics

PubMed Central

Casavant, Benjamin P.; Berthier, Erwin; Theberge, Ashleigh B.; Berthier, Jean; Montanez-Sauri, Sara I.; Bischel, Lauren L.; Brakke, Kenneth; Hedman, Curtis J.; Bushman, Wade; Keller, Nancy P.; Beebe, David J.

2013-01-01

Although the field of microfluidics has made significant progress in bringing new tools to address biological questions, the accessibility and adoption of microfluidics within the life sciences are still limited. Open microfluidic systems have the potential to lower the barriers to adoption, but the absence of robust design rules has hindered their use. Here, we present an open microfluidic platform, suspended microfluidics, that uses surface tension to fill and maintain a fluid in microscale structures devoid of a ceiling and floor. We developed a simple and ubiquitous model predicting fluid flow in suspended microfluidic systems and show that it encompasses many known capillary phenomena. Suspended microfluidics was used to create arrays of collagen membranes, mico Dots (μDots), in a horizontal plane separating two fluidic chambers, demonstrating a transwell platform able to discern collective or individual cellular invasion. Further, we demonstrated that μDots can also be used as a simple multiplexed 3D cellular growth platform. Using the μDot array, we probed the combined effects of soluble factors and matrix components, finding that laminin mitigates the growth suppression properties of the matrix metalloproteinase inhibitor GM6001. Based on the same fluidic principles, we created a suspended microfluidic metabolite extraction platform using a multilayer biphasic system that leverages the accessibility of open microchannels to retrieve steroids and other metabolites readily from cell culture. Suspended microfluidics brings the high degree of fluidic control and unique functionality of closed microfluidics into the highly accessible and robust platform of open microfluidics. PMID:23729815

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.

A dynamic bead-based microarray for parallel DNA detection

NASA Astrophysics Data System (ADS)

Sochol, R. D.; Casavant, B. P.; Dueck, M. E.; Lee, L. P.; Lin, L.

2011-05-01

A microfluidic system has been designed and constructed by means of micromachining processes to integrate both microfluidic mixing of mobile microbeads and hydrodynamic microbead arraying capabilities on a single chip to simultaneously detect multiple bio-molecules. The prototype system has four parallel reaction chambers, which include microchannels of 18 × 50 µm2 cross-sectional area and a microfluidic mixing section of 22 cm length. Parallel detection of multiple DNA oligonucleotide sequences was achieved via molecular beacon probes immobilized on polystyrene microbeads of 16 µm diameter. Experimental results show quantitative detection of three distinct DNA oligonucleotide sequences from the Hepatitis C viral (HCV) genome with single base-pair mismatch specificity. Our dynamic bead-based microarray offers an effective microfluidic platform to increase parallelization of reactions and improve microbead handling for various biological applications, including bio-molecule detection, medical diagnostics and drug screening.

High throughput single cell counting in droplet-based microfluidics.

PubMed

Lu, Heng; Caen, Ouriel; Vrignon, Jeremy; Zonta, Eleonora; El Harrak, Zakaria; Nizard, Philippe; Baret, Jean-Christophe; Taly, Valérie

2017-05-02

Droplet-based microfluidics is extensively and increasingly used for high-throughput single-cell studies. However, the accuracy of the cell counting method directly impacts the robustness of such studies. We describe here a simple and precise method to accurately count a large number of adherent and non-adherent human cells as well as bacteria. Our microfluidic hemocytometer provides statistically relevant data on large populations of cells at a high-throughput, used to characterize cell encapsulation and cell viability during incubation in droplets.

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.

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.

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

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.

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.

Droplet based microfluidics for highthroughput screening of antibody secreting cells

NASA Astrophysics Data System (ADS)

Cai, Liheng; Heyman, John; Mazutis, Linas; Ung, Lloyd; Guerra, Rodrigo; Aubrecht, Donald; Weitz, David

2014-03-01

We present a droplet based microfluidic platform that allows highthroughput screening of antibody secreting cells. We coencapsulate single cells, fluorescent probes, and detection beads into emulsion droplets with diameter of 40 micron. The beads capture antibodies secreted by cells, resulting in a pronounced fluorescent signal that activates dielectrophoresis sorting at rate about 500 droplets per second. Moreover, we demonstrate that Reverse Transcription Polymerase Chain Reaction (RT-PCR) can be successfully applied to the cell encapsulated in a single sorted droplet. Our work highlights the potential of droplet based microfluidics as a platform to generate recombinant antibodies.

Fabrication and Operation of Microfluidic Hanging-Drop Networks.

PubMed

Misun, Patrick M; Birchler, Axel K; Lang, Moritz; Hierlemann, Andreas; Frey, Olivier

2018-01-01

The hanging-drop network (HDN) is a technology platform based on a completely open microfluidic network at the bottom of an inverted, surface-patterned substrate. The platform is predominantly used for the formation, culturing, and interaction of self-assembled spherical microtissues (spheroids) under precisely controlled flow conditions. Here, we describe design, fabrication, and operation of microfluidic hanging-drop networks.

Self-contained microfluidic systems: a review.

PubMed

Boyd-Moss, Mitchell; Baratchi, Sara; Di Venere, Martina; Khoshmanesh, Khashayar

2016-08-16

Microfluidic systems enable rapid diagnosis, screening and monitoring of diseases and health conditions using small amounts of biological samples and reagents. Despite these remarkable features, conventional microfluidic systems rely on bulky expensive external equipment, which hinders their utility as powerful analysis tools outside of research laboratories. 'Self-contained' microfluidic systems, which contain all necessary components to facilitate a complete assay, have been developed to address this limitation. In this review, we provide an in-depth overview of self-contained microfluidic systems. We categorise these systems based on their operating mechanisms into three major groups: passive, hand-powered and active. Several examples are provided to discuss the structure, capabilities and shortcomings of each group. In particular, we discuss the self-contained microfluidic systems enabled by active mechanisms, due to their unique capability for running multi-step and highly controllable diagnostic assays. Integration of self-contained microfluidic systems with the image acquisition and processing capabilities of smartphones, especially those equipped with accessory optical components, enables highly sensitive and quantitative assays, which are discussed. Finally, the future trends and possible solutions to expand the versatility of self-contained, stand-alone microfluidic platforms are outlined.

Microfluidic 3D cell culture: potential application for tissue-based bioassays

PubMed Central

Li, XiuJun (James); Valadez, Alejandra V.; Zuo, Peng; Nie, Zhihong

2014-01-01

Current fundamental investigations of human biology and the development of therapeutic drugs, commonly rely on two-dimensional (2D) monolayer cell culture systems. However, 2D cell culture systems do not accurately recapitulate the structure, function, physiology of living tissues, as well as highly complex and dynamic three-dimensional (3D) environments in vivo. The microfluidic technology can provide micro-scale complex structures and well-controlled parameters to mimic the in vivo environment of cells. The combination of microfluidic technology with 3D cell culture offers great potential for in vivo-like tissue-based applications, such as the emerging organ-on-a-chip system. This article will review recent advances in microfluidic technology for 3D cell culture and their biological applications. PMID:22793034

A Microfluidic Cytometer for Complete Blood Count With a 3.2-Megapixel, 1.1- μm-Pitch Super-Resolution Image Sensor in 65-nm BSI CMOS.

PubMed

Liu, Xu; Huang, Xiwei; Jiang, Yu; Xu, Hang; Guo, Jing; Hou, Han Wei; Yan, Mei; Yu, Hao

2017-08-01

Based on a 3.2-Megapixel 1.1- μm-pitch super-resolution (SR) CMOS image sensor in a 65-nm backside-illumination process, a lens-free microfluidic cytometer for complete blood count (CBC) is demonstrated in this paper. Backside-illumination improves resolution and contrast at the device level with elimination of surface treatment when integrated with microfluidic channels. A single-frame machine-learning-based SR processing is further realized at system level for resolution correction with minimum hardware resources. The demonstrated microfluidic cytometer can detect the platelet cells (< 2 μm) required in CBC, hence is promising for point-of-care diagnostics.

High-throughput screening approaches and combinatorial development of biomaterials using microfluidics.

PubMed

Barata, David; van Blitterswijk, Clemens; Habibovic, Pamela

2016-04-01

From the first microfluidic devices used for analysis of single metabolic by-products to highly complex multicompartmental co-culture organ-on-chip platforms, efforts of many multidisciplinary teams around the world have been invested in overcoming the limitations of conventional research methods in the biomedical field. Close spatial and temporal control over fluids and physical parameters, integration of sensors for direct read-out as well as the possibility to increase throughput of screening through parallelization, multiplexing and automation are some of the advantages of microfluidic over conventional, 2D tissue culture in vitro systems. Moreover, small volumes and relatively small cell numbers used in experimental set-ups involving microfluidics, can potentially decrease research cost. On the other hand, these small volumes and numbers of cells also mean that many of the conventional molecular biology or biochemistry assays cannot be directly applied to experiments that are performed in microfluidic platforms. Development of different types of assays and evidence that such assays are indeed a suitable alternative to conventional ones is a step that needs to be taken in order to have microfluidics-based platforms fully adopted in biomedical research. In this review, rather than providing a comprehensive overview of the literature on microfluidics, we aim to discuss developments in the field of microfluidics that can aid advancement of biomedical research, with emphasis on the field of biomaterials. Three important topics will be discussed, being: screening, in particular high-throughput and combinatorial screening; mimicking of natural microenvironment ranging from 3D hydrogel-based cellular niches to organ-on-chip devices; and production of biomaterials with closely controlled properties. While important technical aspects of various platforms will be discussed, the focus is mainly on their applications, including the state-of-the-art, future perspectives and challenges. Microfluidics, being a technology characterized by the engineered manipulation of fluids at the submillimeter scale, offers some interesting tools that can advance biomedical research and development. Screening platforms based on microfluidic technologies that allow high-throughput and combinatorial screening may lead to breakthrough discoveries not only in basic research but also relevant to clinical application. This is further strengthened by the fact that reliability of such screens may improve, since microfluidic systems allow close mimicking of physiological conditions. Finally, microfluidic systems are also very promising as micro factories of a new generation of natural or synthetic biomaterials and constructs, with finely controlled properties. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Replaceable Microfluidic Cartridges for a PCR Biosensor

NASA Technical Reports Server (NTRS)

Francis, Kevin; Sullivan, Ron

2005-01-01

The figure depicts a replaceable microfluidic cartridge that is a component of a miniature biosensor that detects target deoxyribonucleic acid (DNA) sequences. The biosensor utilizes (1) polymerase chain reactions (PCRs) to multiply the amount of DNA to be detected, (2) fluorogenic polynucleotide probe chemicals for labeling the target DNA sequences, and (3) a high-sensitivity epifluorescence-detection optoelectronic subsystem. Microfluidics is a relatively new field of device development in which one applies techniques for fabricating microelectromechanical systems (MEMS) to miniature systems for containing and/or moving fluids. Typically, microfluidic devices are microfabricated, variously, from silicon or polymers. The development of microfluidic devices for applications that involve PCR and fluorescence-based detection of PCR products poses special challenges

"Print-n-Shrink" technology for the rapid production of microfluidic chips and protein microarrays.

PubMed

Sollier, Kevin; Mandon, Céline A; Heyries, Kevin A; Blum, Loïc J; Marquette, Christophe A

2009-12-21

An innovative method for the production of microfluidic chips integrating protein spots is described. The technology, called "Print-n-Shrink", is based on the screen-printing of a microfluidic design (using a dielectric ink) onto Polyshrink polystyrene sheets. The initial print which has a minimum size of 15 microm (height) x 230 microm (width) is thermally treated (30 seconds, 163 degrees C) to shrink and generate features of 85 microm (height) x 100 microm (width). Concomitantly, proteins such as monoclonal antibodies or cellular adhesion proteins are spotted onto the Polyshrink sheets and shrunk together with the microfluidic design, creating a complete biochip integrating both complex microfluidic designs and protein spots for bioanalytical applications.

Get to Understand More from Single-Cells: Current Studies of Microfluidic-Based Techniques for Single-Cell Analysis.

PubMed

Lo, Shih-Jie; Yao, Da-Jeng

2015-07-23

This review describes the microfluidic techniques developed for the analysis of a single cell. The characteristics of microfluidic (e.g., little sample amount required, high-throughput performance) make this tool suitable to answer and to solve biological questions of interest about a single cell. This review aims to introduce microfluidic related techniques for the isolation, trapping and manipulation of a single cell. The major approaches for detection in single-cell analysis are introduced; the applications of single-cell analysis are then summarized. The review concludes with discussions of the future directions and opportunities of microfluidic systems applied in analysis of a single cell.

Get to Understand More from Single-Cells: Current Studies of Microfluidic-Based Techniques for Single-Cell Analysis

PubMed Central

Lo, Shih-Jie; Yao, Da-Jeng

2015-01-01

This review describes the microfluidic techniques developed for the analysis of a single cell. The characteristics of microfluidic (e.g., little sample amount required, high-throughput performance) make this tool suitable to answer and to solve biological questions of interest about a single cell. This review aims to introduce microfluidic related techniques for the isolation, trapping and manipulation of a single cell. The major approaches for detection in single-cell analysis are introduced; the applications of single-cell analysis are then summarized. The review concludes with discussions of the future directions and opportunities of microfluidic systems applied in analysis of a single cell. PMID:26213918

Advances in Microfluidic Platforms for Analyzing and Regulating Human Pluripotent Stem Cells

PubMed Central

Qian, Tongcheng; Shusta, Eric V.; Palecek, Sean P.

2015-01-01

Microfluidic devices employ submillimeter length scale control of flow to achieve high-resolution spatial and temporal control over the microenvironment, providing powerful tools to elucidate mechanisms of human pluripotent stem cell (hPSC) regulation and to elicit desired hPSC fates. In addition, microfluidics allow control of paracrine and juxtracrine signaling, thereby enabling fabrication of microphysiological systems comprised of multiple cell types organized into organs-on-a-chip. Microfluidic cell culture systems can also be integrated with actuators and sensors, permitting construction of high-density arrays of cell-based biosensors for screening applications. This review describes recent advances in using microfluidics to understand mechanisms by which the microenvironment regulates hPSC fates and applications of microfluidics to realize the potential of hPSCs for in vitro modeling and screening applications. PMID:26313850

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.

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.

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.

Route to one-step microstructure mold fabrication for PDMS microfluidic chip

NASA Astrophysics Data System (ADS)

Lv, Xiaoqing; Geng, Zhaoxin; Fan, Zhiyuan; Wang, Shicai; Su, Yue; Fang, Weihao; Pei, Weihua; Chen, Hongda

2018-04-01

The microstructure mold fabrication for PDMS microfluidic chip remains complex and time-consuming process requiring special equipment and protocols: photolithography and etching. Thus, a rapid and cost-effective method is highly needed. Comparing with the traditional microfluidic chip fabricating process based on the micro-electromechanical system (MEMS), this method is simple and easy to implement, and the whole fabrication process only requires 1-2 h. Different size of microstructure from 100 to 1000 μm was fabricated, and used to culture four kinds of breast cancer cell lines. Cell viability and morphology was assessed when they were cultured in the micro straight channels, micro square holes and the bonding PDMS-glass microfluidic chip. The experimental results indicate that the microfluidic chip is good and meet the experimental requirements. This method can greatly reduce the process time and cost of the microfluidic chip, and provide a simple and effective way for the structure design and in the field of biological microfabrications and microfluidic chips.

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

Micro-optics for microfluidic analytical applications.

PubMed

Yang, Hui; Gijs, Martin A M

2018-02-19

This critical review summarizes the developments in the integration of micro-optical elements with microfluidic platforms for facilitating detection and automation of bio-analytical applications. Micro-optical elements, made by a variety of microfabrication techniques, advantageously contribute to the performance of an analytical system, especially when the latter has microfluidic features. Indeed the easy integration of optical control and detection modules with microfluidic technology helps to bridge the gap between the macroscopic world and chip-based analysis, paving the way for automated and high-throughput applications. In our review, we start the discussion with an introduction of microfluidic systems and micro-optical components, as well as aspects of their integration. We continue with a detailed description of different microfluidic and micro-optics technologies and their applications, with an emphasis on the realization of optical waveguides and microlenses. The review continues with specific sections highlighting the advantages of integrated micro-optical components in microfluidic systems for tackling a variety of analytical problems, like cytometry, nucleic acid and protein detection, cell biology, and chemical analysis 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.

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.

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.

Development of a digital microfluidic platform for point of care testing

PubMed Central

Sista, Ramakrishna; Hua, Zhishan; Thwar, Prasanna; Sudarsan, Arjun; Srinivasan, Vijay; Eckhardt, Allen; Pollack, Michael; Pamula, Vamsee

2009-01-01

Point of care testing is playing an increasingly important role in improving the clinical outcome in health care management. The salient features of a point of care device are quick results, integrated sample preparation and processing, small sample volumes, portability, multifunctionality and low cost. In this paper, we demonstrate some of these salient features utilizing an electrowetting-based Digital Microfluidic platform. We demonstrate the performance of magnetic bead-based immunoassays (cardiac troponin I) on a digital microfluidic cartridge in less than 8 minutes using whole blood samples. Using the same microfluidic cartridge, a 40-cycle real-time polymerase chain reaction was performed within 12 minutes by shuttling a droplet between two thermal zones. We further demonstrate, on the same cartridge, the capability to perform sample preparation for bacterial and fungal infectious disease pathogens (methicillin-resistance Staphylococcus aureus and Candida albicans) and for human genomic DNA using magnetic beads. In addition to rapid results and integrated sample preparation, electrowetting-based digital microfluidic instruments are highly portable because fluid pumping is performed electronically. All the digital microfluidic chips presented here were fabricated on printed circuit boards utilizing mass production techniques that keep the cost of the chip low. Due to the modularity and scalability afforded by digital microfluidics, multifunctional testing capability, such as combinations within and between immunoassays, DNA amplification, and enzymatic assays, can be brought to the point of care at a relatively low cost because a single chip can be configured in software for different assays required along the path of care. PMID:19023472

A hard-soft microfluidic-based biosensor flow cell for SPR imaging application.

PubMed

Liu, Changchun; Cui, Dafu; Li, Hui

2010-09-15

An ideal microfluidic-based biosensor flow cell should have not only a "soft" interface for high strength sealing with biosensing chips, but also "hard" macro-to-micro interface for tubing connection. Since these properties are exclusive of each other, no one material can provide the advantages of both. In this paper, we explore the application of a SiO(2) thin film, deposited by plasma-enhanced chemical vapor deposition (PECVD) technology, as an intermediate layer for irreversibly adhering polydimethylsiloxane (PDMS) to plastic substrate, and develop a hard-soft, compact, robust microfluidic-based biosensor flow cell for the multi-array immunoassay application of surface plasmon resonance (SPR) imaging. This hard-soft biosensor flow cell consists of one rigid, computer numerically controlled (CNC)-machined poly(methyl methacrylate) (PMMA) base coated with a 200 nm thick SiO(2) thin film, and one soft PDMS microfluidic layer. This novel microfluidic-based biosensor flow cell does not only keep the original advantage of conventional PDMS-based biosensor flow cell such as the intrinsically soft interface, easy-to-fabrication, and low cost, but also has a rigid, robust, easy-to-use interface to tubing connection and can be operated up to 185 kPa in aqueous environments without failure. Its application was successfully demonstrated with two types of experiments by coupling with SPR imaging biosensor: the real-time monitoring of the immunoglobulin G (IgG) interaction, as well as the detection of sulfamethoxazole (SMOZ) and sulfamethazine (SMZ) with the sensitivity of 3.5 and 0.6 ng/mL, respectively. This novel hard-soft microfluidic device is also useful for a variety of other biosensor flow cells. Copyright 2010 Elsevier B.V. All rights reserved.

Droplet-based microfluidic analysis and screening of single plant cells.

PubMed

Yu, Ziyi; Boehm, Christian R; Hibberd, Julian M; Abell, Chris; Haseloff, Jim; Burgess, Steven J; Reyna-Llorens, Ivan

2018-01-01

Droplet-based microfluidics has been used to facilitate high-throughput analysis of individual prokaryote and mammalian cells. However, there is a scarcity of similar workflows applicable to rapid phenotyping of plant systems where phenotyping analyses typically are time-consuming and low-throughput. We report on-chip encapsulation and analysis of protoplasts isolated from the emergent plant model Marchantia polymorpha at processing rates of >100,000 cells per hour. We use our microfluidic system to quantify the stochastic properties of a heat-inducible promoter across a population of transgenic protoplasts to demonstrate its potential for assessing gene expression activity in response to environmental conditions. We further demonstrate on-chip sorting of droplets containing YFP-expressing protoplasts from wild type cells using dielectrophoresis force. This work opens the door to droplet-based microfluidic analysis of plant cells for applications ranging from high-throughput characterisation of DNA parts to single-cell genomics to selection of rare plant phenotypes.

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

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.

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

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.

Modular microfluidic system for biological sample preparation

DOEpatents

Rose, Klint A.; Mariella, Jr., Raymond P.; Bailey, Christopher G.; Ness, Kevin Dean

2015-09-29

A reconfigurable modular microfluidic system for preparation of a biological sample including a series of reconfigurable modules for automated sample preparation adapted to selectively include a) a microfluidic acoustic focusing filter module, b) a dielectrophoresis bacteria filter module, c) a dielectrophoresis virus filter module, d) an isotachophoresis nucleic acid filter module, e) a lyses module, and f) an isotachophoresis-based nucleic acid filter.

DNA Assembly in 3D Printed Fluidics

PubMed Central

Patrick, William G.; Nielsen, Alec A. K.; Keating, Steven J.; Levy, Taylor J.; Wang, Che-Wei; Rivera, Jaime J.; Mondragón-Palomino, Octavio; Carr, Peter A.; Voigt, Christopher A.; Oxman, Neri; Kong, David S.

2015-01-01

The process of connecting genetic parts—DNA assembly—is a foundational technology for synthetic biology. Microfluidics present an attractive solution for minimizing use of costly reagents, enabling multiplexed reactions, and automating protocols by integrating multiple protocol steps. However, microfluidics fabrication and operation can be expensive and requires expertise, limiting access to the technology. With advances in commodity digital fabrication tools, it is now possible to directly print fluidic devices and supporting hardware. 3D printed micro- and millifluidic devices are inexpensive, easy to make and quick to produce. We demonstrate Golden Gate DNA assembly in 3D-printed fluidics with reaction volumes as small as 490 nL, channel widths as fine as 220 microns, and per unit part costs ranging from $0.61 to $5.71. A 3D-printed syringe pump with an accompanying programmable software interface was designed and fabricated to operate the devices. Quick turnaround and inexpensive materials allowed for rapid exploration of device parameters, demonstrating a manufacturing paradigm for designing and fabricating hardware for synthetic biology. PMID:26716448

Microfluidic platform combining droplets and magnetic tweezers: application to HER2 expression in cancer diagnosis

PubMed Central

Ferraro, Davide; Champ, Jérôme; Teste, Bruno; Serra, Marco; Malaquin, Laurent; Viovy, Jean-Louis; de Cremoux, Patricia; Descroix, Stephanie

2016-01-01

The development of precision medicine, together with the multiplication of targeted therapies and associated molecular biomarkers, call for major progress in genetic analysis methods, allowing increased multiplexing and the implementation of more complex decision trees, without cost increase or loss of robustness. We present a platform combining droplet microfluidics and magnetic tweezers, performing RNA purification, reverse transcription and amplification in a fully automated and programmable way, in droplets of 250nL directly sampled from a microtiter-plate. This platform decreases sample consumption about 100 fold as compared to current robotized platforms and it reduces human manipulations and contamination risk. The platform’s performance was first evaluated on cell lines, showing robust operation on RNA quantities corresponding to less than one cell, and then clinically validated with a cohort of 21 breast cancer samples, for the determination of their HER2 expression status, in a blind comparison with an established routine clinical analysis. PMID:27157697

Microfluidic platform combining droplets and magnetic tweezers: application to HER2 expression in cancer diagnosis

NASA Astrophysics Data System (ADS)

Ferraro, Davide; Champ, Jérôme; Teste, Bruno; Serra, Marco; Malaquin, Laurent; Viovy, Jean-Louis; de Cremoux, Patricia; Descroix, Stephanie

2016-05-01

The development of precision medicine, together with the multiplication of targeted therapies and associated molecular biomarkers, call for major progress in genetic analysis methods, allowing increased multiplexing and the implementation of more complex decision trees, without cost increase or loss of robustness. We present a platform combining droplet microfluidics and magnetic tweezers, performing RNA purification, reverse transcription and amplification in a fully automated and programmable way, in droplets of 250nL directly sampled from a microtiter-plate. This platform decreases sample consumption about 100 fold as compared to current robotized platforms and it reduces human manipulations and contamination risk. The platform’s performance was first evaluated on cell lines, showing robust operation on RNA quantities corresponding to less than one cell, and then clinically validated with a cohort of 21 breast cancer samples, for the determination of their HER2 expression status, in a blind comparison with an established routine clinical analysis.

Automated Microfluidic Platform for Serial Polymerase Chain Reaction and High-Resolution Melting Analysis.

PubMed

Cao, Weidong; Bean, Brian; Corey, Scott; Coursey, Johnathan S; Hasson, Kenton C; Inoue, Hiroshi; Isano, Taisuke; Kanderian, Sami; Lane, Ben; Liang, Hongye; Murphy, Brian; Owen, Greg; Shinoda, Nobuhiko; Zeng, Shulin; Knight, Ivor T

2016-06-01

We report the development of an automated genetic analyzer for human sample testing based on microfluidic rapid polymerase chain reaction (PCR) with high-resolution melting analysis (HRMA). The integrated DNA microfluidic cartridge was used on a platform designed with a robotic pipettor system that works by sequentially picking up different test solutions from a 384-well plate, mixing them in the tips, and delivering mixed fluids to the DNA cartridge. A novel image feedback flow control system based on a Canon 5D Mark II digital camera was developed for controlling fluid movement through a complex microfluidic branching network without the use of valves. The same camera was used for measuring the high-resolution melt curve of DNA amplicons that were generated in the microfluidic chip. Owing to fast heating and cooling as well as sensitive temperature measurement in the microfluidic channels, the time frame for PCR and HRMA was dramatically reduced from hours to minutes. Preliminary testing results demonstrated that rapid serial PCR and HRMA are possible while still achieving high data quality that is suitable for human sample testing. © 2015 Society for Laboratory Automation and Screening.

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

High content screening in microfluidic devices

PubMed Central

Cheong, Raymond; Paliwal, Saurabh; Levchenko, Andre

2011-01-01

Importance of the field Miniaturization is key to advancing the state-of-the-art in high content screening (HCS), in order to enable dramatic cost savings through reduced usage of expensive biochemical reagents and to enable large-scale screening on primary cells. Microfluidic technology offers the potential to enable HCS to be performed with an unprecedented degree of miniaturization. Areas covered in this review This perspective highlights a real-world example from the authors’ work of HCS assays implemented in a highly miniaturized microfluidic format. Advantages of this technology are discussed, including cost savings, high throughput screening on primary cells, improved accuracy, the ability to study complex time-varying stimuli, and ease of automation, integration, and scaling. What the reader will gain The reader will understand the capabilities of a new microfluidics-based platform for HCS, and the advantages it provides over conventional plate-based HCS. Take home message Microfluidics technology will drive significant advancements and broader usage and applicability of HCS in drug discovery. PMID:21852997

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

Characterization of a microfluidic microbial fuel cell as a power generator based on a nickel electrode.

PubMed

Mardanpour, Mohammad Mahdi; Yaghmaei, Soheila

2016-05-15

This study reports the fabrication of a microfluidic microbial fuel cell (MFC) using nickel as a novel alternative for conventional electrodes and a non-phatogenic strain of Escherichia coli as the biocatalyst. The feasibility of a microfluidic MFC as an efficient power generator for production of bioelectricity from glucose and urea as organic substrates in human blood and urine for implantable medical devices (IMDs) was investigated. A maximum open circuit potential of 459 mV was achieved for the batch-fed microfluidic MFC. During continuous mode operation, a maximum power density of 104 Wm(-3) was obtained with nutrient broth. For the glucose-fed microfluidic MFC, the maximum power density of 5.2 μW cm(-2) obtained in this study is significantly greater than the power densities reported previously for microsized MFCs and glucose fuel cells. The maximum power density of 14 Wm(-3) obtained using urea indicates the successful performance of a microfluidic MFC using human excreta. It features high power density, self-regeneration, waste management and a low production cost (<$1), which suggest it as a promising alternative to conventional power supplies for IMDs. The performance of the microfluidic MFC as a power supply was characterized based on polarization behavior and cell potential in different substrates, operational modes, and concentrations. Copyright © 2015 Elsevier B.V. All rights reserved.

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.

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.

Integrated Microfluidic Gas Sensors for Water Monitoring

NASA Technical Reports Server (NTRS)

Zhu, L.; Sniadecki, N.; DeVoe, D. L.; Beamesderfer, M.; Semancik, S.; DeVoe, D. L.

2003-01-01

A silicon-based microhotplate tin oxide (SnO2) gas sensor integrated into a polymer-based microfluidic system for monitoring of contaminants in water systems is presented. This device is designed to sample a water source, control the sample vapor pressure within a microchannel using integrated resistive heaters, and direct the vapor past the integrated gas sensor for analysis. The sensor platform takes advantage of novel technology allowing direct integration of discrete silicon chips into a larger polymer microfluidic substrate, including seamless fluidic and electrical interconnects between the substrate and silicon chip.

An automated microfluidic DNA microarray platform for genetic variant detection in inherited arrhythmic diseases.

PubMed

Huang, Shu-Hong; Chang, Yu-Shin; Juang, Jyh-Ming Jimmy; Chang, Kai-Wei; Tsai, Mong-Hsun; Lu, Tzu-Pin; Lai, Liang-Chuan; Chuang, Eric Y; Huang, Nien-Tsu

2018-03-12

In this study, we developed an automated microfluidic DNA microarray (AMDM) platform for point mutation detection of genetic variants in inherited arrhythmic diseases. The platform allows for automated and programmable reagent sequencing under precise conditions of hybridization flow and temperature control. It is composed of a commercial microfluidic control system, a microfluidic microarray device, and a temperature control unit. The automated and rapid hybridization process can be performed in the AMDM platform using Cy3 labeled oligonucleotide exons of SCN5A genetic DNA, which produces proteins associated with sodium channels abundant in the heart (cardiac) muscle cells. We then introduce a graphene oxide (GO)-assisted DNA microarray hybridization protocol to enable point mutation detection. In this protocol, a GO solution is added after the staining step to quench dyes bound to single-stranded DNA or non-perfectly matched DNA, which can improve point mutation specificity. As proof-of-concept we extracted the wild-type and mutant of exon 12 and exon 17 of SCN5A genetic DNA from patients with long QT syndrome or Brugada syndrome by touchdown PCR and performed a successful point mutation discrimination in the AMDM platform. Overall, the AMDM platform can greatly reduce laborious and time-consuming hybridization steps and prevent potential contamination. Furthermore, by introducing the reciprocating flow into the microchannel during the hybridization process, the total assay time can be reduced to 3 hours, which is 6 times faster than the conventional DNA microarray. Given the automatic assay operation, shorter assay time, and high point mutation discrimination, we believe that the AMDM platform has potential for low-cost, rapid and sensitive genetic testing in a simple and user-friendly manner, which may benefit gene screening in medical practice.

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.

High-throughput manufacturing of size-tuned liposomes by a new microfluidics method using enhanced statistical tools for characterization.

PubMed

Kastner, Elisabeth; Kaur, Randip; Lowry, Deborah; Moghaddam, Behfar; Wilkinson, Alexander; Perrie, Yvonne

2014-12-30

Microfluidics has recently emerged as a new method of manufacturing liposomes, which allows for reproducible mixing in miliseconds on the nanoliter scale. Here we investigate microfluidics-based manufacturing of liposomes. The aim of these studies was to assess the parameters in a microfluidic process by varying the total flow rate (TFR) and the flow rate ratio (FRR) of the solvent and aqueous phases. Design of experiment and multivariate data analysis were used for increased process understanding and development of predictive and correlative models. High FRR lead to the bottom-up synthesis of liposomes, with a strong correlation with vesicle size, demonstrating the ability to in-process control liposomes size; the resulting liposome size correlated with the FRR in the microfluidics process, with liposomes of 50 nm being reproducibly manufactured. Furthermore, we demonstrate the potential of a high throughput manufacturing of liposomes using microfluidics with a four-fold increase in the volumetric flow rate, maintaining liposome characteristics. The efficacy of these liposomes was demonstrated in transfection studies and was modelled using predictive modeling. Mathematical modelling identified FRR as the key variable in the microfluidic process, with the highest impact on liposome size, polydispersity and transfection efficiency. This study demonstrates microfluidics as a robust and high-throughput method for the scalable and highly reproducible manufacture of size-controlled liposomes. Furthermore, the application of statistically based process control increases understanding and allows for the generation of a design-space for controlled particle characteristics. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

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

One-Dimensional Nanostructures: Microfluidic-Based Synthesis, Alignment and Integration towards Functional Sensing Devices

PubMed Central

Xing, Yanlong; Dittrich, Petra S.

2018-01-01

Microfluidic-based synthesis of one-dimensional (1D) nanostructures offers tremendous advantages over bulk approaches e.g., the laminar flow, reduced sample consumption and control of self-assembly of nanostructures. In addition to the synthesis, the integration of 1D nanomaterials into microfluidic chips can enable the development of diverse functional microdevices. 1D nanomaterials have been used in applications such as catalysts, electronic instrumentation and sensors for physical parameters or chemical compounds and biomolecules and hence, can be considered as building blocks. Here, we outline and critically discuss promising strategies for microfluidic-assisted synthesis, alignment and various chemical and biochemical applications of 1D nanostructures. In particular, the use of 1D nanostructures for sensing chemical/biological compounds are reviewed. PMID:29303990

Dopamine-functionalized InP/ZnS quantum dots as fluorescence probes for the detection of adenosine in microfluidic chip.

PubMed

Ankireddy, Seshadri Reddy; Kim, Jongsung

2015-01-01

Microbeads are frequently used as solid supports for biomolecules such as proteins and nucleic acids in heterogeneous microfluidic assays. Chip-based, quantum dot (QD)-bead-biomolecule probes have been used for the detection of various types of DNA. In this study, we developed dopamine (DA)-functionalized InP/ZnS QDs (QDs-DA) as fluorescence probes for the detection of adenosine in microfluidic chips. The photoluminescence (PL) intensity of the QDs-DA is quenched by Zn(2+) because of the strong coordination interactions. In the presence of adenosine, Zn(2+) cations preferentially bind to adenosine, and the PL intensity of the QDs-DA is recovered. A polydimethylsiloxane-based microfluidic chip was fabricated, and adenosine detection was confirmed using QDs-DA probes.

Dopamine-functionalized InP/ZnS quantum dots as fluorescence probes for the detection of adenosine in microfluidic chip

PubMed Central

Ankireddy, Seshadri Reddy; Kim, Jongsung

2015-01-01

Microbeads are frequently used as solid supports for biomolecules such as proteins and nucleic acids in heterogeneous microfluidic assays. Chip-based, quantum dot (QD)-bead-biomolecule probes have been used for the detection of various types of DNA. In this study, we developed dopamine (DA)-functionalized InP/ZnS QDs (QDs-DA) as fluorescence probes for the detection of adenosine in microfluidic chips. The photoluminescence (PL) intensity of the QDs-DA is quenched by Zn2+ because of the strong coordination interactions. In the presence of adenosine, Zn2+ cations preferentially bind to adenosine, and the PL intensity of the QDs-DA is recovered. A polydimethylsiloxane-based microfluidic chip was fabricated, and adenosine detection was confirmed using QDs-DA probes. PMID:26347351

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.

Capillary-Driven Microfluidic Chips for Miniaturized Immunoassays: Efficient Fabrication and Sealing of Chips Using a "Chip-Olate" Process.

PubMed

Temiz, Yuksel; Delamarche, Emmanuel

2017-01-01

The fabrication of silicon-based microfluidic chips is invaluable in supporting the development of many microfluidic concepts for research in the life sciences and in vitro diagnostic applications such as the realization of miniaturized immunoassays using capillary-driven chips. While being extremely abundant, the literature covering microfluidic chip fabrication and assay development might not have addressed properly the challenge of fabricating microfluidic chips on a wafer level or the need for dicing wafers to release chips that need then to be further processed, cleaned, rinsed, and dried one by one. Here, we describe the "chip-olate" process wherein microfluidic structures are formed on a silicon wafer, followed by partial dicing, cleaning, and drying steps. Then, integration of reagents (if any) can be done, followed by lamination of a sealing cover. Breaking by hand the partially diced wafer yields individual chips ready for use.

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.

Remotely powered distributed microfluidic pumps and mixers based on miniature diodes.

PubMed

Chang, Suk Tai; Beaumont, Erin; Petsev, Dimiter N; Velev, Orlin D

2008-01-01

We demonstrate new principles of microfluidic pumping and mixing by electronic components integrated into a microfluidic chip. The miniature diodes embedded into the microchannel walls rectify the voltage induced between their electrodes from an external alternating electric field. The resulting electroosmotic flows, developed in the vicinity of the diode surfaces, were utilized for pumping or mixing of the fluid in the microfluidic channel. The flow velocity of liquid pumped by the diodes facing in the same direction linearly increased with the magnitude of the applied voltage and the pumping direction could be controlled by the pH of the solutions. The transverse flow driven by the localized electroosmotic flux between diodes oriented oppositely on the microchannel was used in microfluidic mixers. The experimental results were interpreted by numerical simulations of the electrohydrodynamic flows. The techniques may be used in novel actively controlled microfluidic-electronic chips.

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

Entropy-based separation of yeast cells using a microfluidic system of conjoined spheres

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

Huang, Kai-Jian; Qin, S.-J., E-mail: shuijie.qin@gmail.com; Bai, Zhong-Chen

2013-11-21

A physical model is derived to create a biological cell separator that is based on controlling the entropy in a microfluidic system having conjoined spherical structures. A one-dimensional simplified model of this three-dimensional problem in terms of the corresponding effects of entropy on the Brownian motion of particles is presented. This dynamic mechanism is based on the Langevin equation from statistical thermodynamics and takes advantage of the characteristics of the Fokker-Planck equation. This mechanism can be applied to manipulate biological particles inside a microfluidic system with identical, conjoined, spherical compartments. This theoretical analysis is verified by performing a rapid andmore » a simple technique for separating yeast cells in these conjoined, spherical microfluidic structures. The experimental results basically match with our theoretical model and we further analyze the parameters which can be used to control this separation mechanism. Both numerical simulations and experimental results show that the motion of the particles depends on the geometrical boundary conditions of the microfluidic system and the initial concentration of the diffusing material. This theoretical model can be implemented in future biophysics devices for the optimized design of passive cell sorters.« less

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.

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.

Engineering fluidic delays in paper-based devices using laser direct-writing.

PubMed

He, P J W; Katis, I N; Eason, R W; Sones, C L

2015-10-21

We report the use of a new laser-based direct-write technique that allows programmable and timed fluid delivery in channels within a paper substrate which enables implementation of multi-step analytical assays. The technique is based on laser-induced photo-polymerisation, and through adjustment of the laser writing parameters such as the laser power and scan speed we can control the depth and/or the porosity of hydrophobic barriers which, when fabricated in the fluid path, produce controllable fluid delay. We have patterned these flow delaying barriers at pre-defined locations in the fluidic channels using either a continuous wave laser at 405 nm, or a pulsed laser operating at 266 nm. Using this delay patterning protocol we generated flow delays spanning from a few minutes to over half an hour. Since the channels and flow delay barriers can be written via a common laser-writing process, this is a distinct improvement over other methods that require specialist operating environments, or custom-designed equipment. This technique can therefore be used for rapid fabrication of paper-based microfluidic devices that can perform single or multistep analytical assays.

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.

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

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.

Integrated microfluidic platforms for investigating neuronal networks

NASA Astrophysics Data System (ADS)

Kim, Hyung Joon

This dissertation describes the development and application of integrated microfluidics-based assay platforms to study neuronal activities in the nervous system in-vitro. The assay platforms were fabricated using soft lithography and micro/nano fabrication including microfluidics, surface patterning, and nanomaterial synthesis. The use of integrated microfluidics-based assay platform allows culturing and manipulating many types of neuronal tissues in precisely controlled microenvironment. Furthermore, they provide organized multi-cellular in-vitro model, long-term monitoring with live cell imaging, and compatibility with molecular biology techniques and electrophysiology experiment. In this dissertation, the integrated microfluidics-based assay platforms are developed for investigation of neuronal activities such as local protein synthesis, impairment of axonal transport by chemical/physical variants, growth cone path finding under chemical/physical cues, and synaptic transmission in neuronal circuit. Chapter 1 describes the motivation, objectives, and scope for developing in-vitro platform to study various neuronal activities. Chapter 2 introduces microfluidic culture platform for biochemical assay with large-scale neuronal tissues that are utilized as model system in neuroscience research. Chapter 3 focuses on the investigation of impaired axonal transport by beta-Amyloid and oxidative stress. The platform allows to control neuronal processes and to quantify mitochondrial movement in various regions of axons away from applied drugs. Chapter 4 demonstrates the development of microfluidics-based growth cone turning assay to elucidate the mechanism underlying axon guidance under soluble factors and shear flow. Using this platform, the behaviors of growth cone of mammalian neurons are verified under the gradient of inhibitory molecules and also shear flow in well-controlled manner. In Chapter 5, I combine in-vitro multicellular model with microfabricated MEA (multielectrode array) or nanowire electrode array to study electrophysiology in neuronal network. Also, "diode-like" microgrooves to control the number of neuronal processes is embedded in this platform. Chapter 6 concludes with a possible future direction of this work. Interfacing micro/nanotechnology with primary neuron culture would open many doors in fundamental neuroscience research and also biomedical innovation.

DNA Bipedal Motor Achieves a Large Number of Steps Due to Operation Using Microfluidics-Based Interface.

PubMed

Tomov, Toma E; Tsukanov, Roman; Glick, Yair; Berger, Yaron; Liber, Miran; Avrahami, Dorit; Gerber, Doron; Nir, Eyal

2017-04-25

Realization of bioinspired molecular machines that can perform many and diverse operations in response to external chemical commands is a major goal in nanotechnology, but current molecular machines respond to only a few sequential commands. Lack of effective methods for introduction and removal of command compounds and low efficiencies of the reactions involved are major reasons for the limited performance. We introduce here a user interface based on a microfluidics device and single-molecule fluorescence spectroscopy that allows efficient introduction and removal of chemical commands and enables detailed study of the reaction mechanisms involved in the operation of synthetic molecular machines. The microfluidics provided 64 consecutive DNA strand commands to a DNA-based motor system immobilized inside the microfluidics, driving a bipedal walker to perform 32 steps on a DNA origami track. The microfluidics enabled removal of redundant strands, resulting in a 6-fold increase in processivity relative to an identical motor operated without strand removal and significantly more operations than previously reported for user-controlled DNA nanomachines. In the motor operated without strand removal, redundant strands interfere with motor operation and reduce its performance. The microfluidics also enabled computer control of motor direction and speed. Furthermore, analysis of the reaction kinetics and motor performance in the absence of redundant strands, made possible by the microfluidics, enabled accurate modeling of the walker processivity. This enabled identification of dynamic boundaries and provided an explanation, based on the "trap state" mechanism, for why the motor did not perform an even larger number of steps. This understanding is very important for the development of future motors with significantly improved performance. Our universal interface enables two-way communication between user and molecular machine and, relying on concepts similar to that of solid-phase synthesis, removes limitations on the number of external stimuli. This interface, therefore, is an important step toward realization of reliable, processive, reproducible, and useful externally controlled DNA nanomachines.

Automated quantitative cytological analysis using portable microfluidic microscopy.

PubMed

Jagannadh, Veerendra Kalyan; Murthy, Rashmi Sreeramachandra; Srinivasan, Rajesh; Gorthi, Sai Siva

2016-06-01

In this article, a portable microfluidic microscopy based approach for automated cytological investigations is presented. Inexpensive optical and electronic components have been used to construct a simple microfluidic microscopy system. In contrast to the conventional slide-based methods, the presented method employs microfluidics to enable automated sample handling and image acquisition. The approach involves the use of simple in-suspension staining and automated image acquisition to enable quantitative cytological analysis of samples. The applicability of the presented approach to research in cellular biology is shown by performing an automated cell viability assessment on a given population of yeast cells. Further, the relevance of the presented approach to clinical diagnosis and prognosis has been demonstrated by performing detection and differential assessment of malaria infection in a given sample. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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.

Microfluidics Transport and Path Control via Programmable Electrowetting on Dielectric

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

Theodore W. Von Bitner, Ph.D.

2002-08-22

This research was conducted in collaboration with Professor Chang-Jin Kim of the University of California, Los Angeles. In phase I, the IOS-UCLA collaboration demonstrated the transport and manipulation of insulting liquid droplets using the principles of EWOD. A postage stamp sized array of electronically addressable Teflon pads, whose surface tension characteristics could be altered on command through computer algorithms, was developed and tested using deionized water as the liquid. Going beyond the tasks originally proposed for Phase I, droplet manipulation was achieved and droplet stability in the EWOD device was examined.

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.

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

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.

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.

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

Recent progress in the physics of microfluidics and related biotechnological applications.

PubMed

Tabeling, Patrick

2014-02-01

Since the mid-nineties, the physical understanding of microfluidic flows has reached a level sufficiently elaborate for envisaging applications in all sorts of domains. As the domain expanded, the existence of new situations where fluid dynamics at small or moderate Reynolds numbers combines with confinement, interfaces, transport, particles along with disordered substrates raised new challenges. The present review is restricted to three domains in which progress in the physical description has been made recently (droplet-based, inertial and paper-based microfluidics) and for which biotechnological applications are foreseeable. Copyright © 2013 Elsevier Ltd. All rights reserved.

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.

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.

A high efficiency microfluidic-based photocatalytic microreactor using electrospun nanofibrous TiO2 as a photocatalyst

NASA Astrophysics Data System (ADS)

Meng, Zhaoxu; Zhang, Xu; Qin, Jianhua

2013-05-01

We present a novel microfluidic-based photocatalytic microreactor by using electrospun nanofibrous TiO2 as a photocatalyst for the first time. The microreactor exhibits not only a simple fabrication process, but also much higher photocatalytic activity than that achieved by a TiO2 film microreactor.We present a novel microfluidic-based photocatalytic microreactor by using electrospun nanofibrous TiO2 as a photocatalyst for the first time. The microreactor exhibits not only a simple fabrication process, but also much higher photocatalytic activity than that achieved by a TiO2 film microreactor. Electronic supplementary information (ESI) available. See DOI: 10.1039/c3nr00775h

The use of carrier RNA to enhance DNA extraction from microfluidic-based silica monoliths.

PubMed

Shaw, Kirsty J; Thain, Lauren; Docker, Peter T; Dyer, Charlotte E; Greenman, John; Greenway, Gillian M; Haswell, Stephen J

2009-10-12

DNA extraction was carried out on silica-based monoliths within a microfluidic device. Solid-phase DNA extraction methodology was applied in which the DNA binds to silica in the presence of a chaotropic salt, such as guanidine hydrochloride, and is eluted in a low ionic strength solution, such as water. The addition of poly-A carrier RNA to the chaotropic salt solution resulted in a marked increase in the effective amount of DNA that could be recovered (25ng) compared to the absence of RNA (5ng) using the silica-based monolith. These findings confirm that techniques utilising nucleic acid carrier molecules can enhance DNA extraction methodologies in microfluidic applications.

Lab on a CD.

PubMed

Madou, Marc; Zoval, Jim; Jia, Guangyao; Kido, Horacio; Kim, Jitae; Kim, Nahui

2006-01-01

In this paper, centrifuge-based microfluidic platforms are reviewed and compared with other popular microfluidic propulsion methods. The underlying physical principles of centrifugal pumping in microfluidic systems are presented and the various centrifuge fluidic functions, such as valving, decanting, calibration, mixing, metering, heating, sample splitting, and separation, are introduced. Those fluidic functions have been combined with analytical measurement techniques, such as optical imaging, absorbance, and fluorescence spectroscopy and mass spectrometry, to make the centrifugal platform a powerful solution for medical and clinical diagnostics and high throughput screening (HTS) in drug discovery. Applications of a compact disc (CD)-based centrifuge platform analyzed in this review include two-point calibration of an optode-based ion sensor, an automated immunoassay platform, multiple parallel screening assays, and cellular-based assays. The use of modified commercial CD drives for high-resolution optical imaging is discussed as well. From a broader perspective, we compare technical barriers involved in applying microfluidics for sensing and diagnostic use and applying such techniques to HTS. The latter poses less challenges and explains why HTS products based on a CD fluidic platform are already commercially available, whereas we might have to wait longer to see commercial CD-based diagnostics.

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.

Droplet based microfluidics.

PubMed

Seemann, Ralf; Brinkmann, Martin; Pfohl, Thomas; Herminghaus, Stephan

2012-01-01

Droplet based microfluidics is a rapidly growing interdisciplinary field of research combining soft matter physics, biochemistry and microsystems engineering. Its applications range from fast analytical systems or the synthesis of advanced materials to protein crystallization and biological assays for living cells. Precise control of droplet volumes and reliable manipulation of individual droplets such as coalescence, mixing of their contents, and sorting in combination with fast analysis tools allow us to perform chemical reactions inside the droplets under defined conditions. In this paper, we will review available drop generation and manipulation techniques. The main focus of this review is not to be comprehensive and explain all techniques in great detail but to identify and shed light on similarities and underlying physical principles. Since geometry and wetting properties of the microfluidic channels are crucial factors for droplet generation, we also briefly describe typical device fabrication methods in droplet based microfluidics. Examples of applications and reaction schemes which rely on the discussed manipulation techniques are also presented, such as the fabrication of special materials and biophysical experiments.

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.

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.

A Microfluidic Chip Based on Localized Surface Plasmon Resonance for Real-Time Monitoring of Antigen-Antibody Reactions

NASA Astrophysics Data System (ADS)

Hiep, Ha Minh; Nakayama, Tsuyoshi; Saito, Masato; Yamamura, Shohei; Takamura, Yuzuru; Tamiya, Eiichi

2008-02-01

Localized surface plasmon resonance (LSPR) connecting to noble metal nanoparticles is an important issue for many analytical and biological applications. Therefore, the development of microfluidic LSPR chip that allows studying biomolecular interactions becomes an essential requirement for micro total analysis systems (µTAS) integration. However, miniaturized process of the conventional surface plasmon resonance system has been faced with some limitations, especially with the usage of Kretschmann configuration in total internal reflection mode. In this study, we have tried to solve this problem by proposing a novel microfluidic LSPR chip operated with a simple collinear optical system. The poly(dimethylsiloxane) (PDMS) based microfluidic chip was fabricated by soft-lithography technique and enables to interrogate specific insulin and anti-insulin antibody reaction in real-time after immobilizing antibody on its surface. Moreover, the sensing ability of microfluidic LSPR chip was also evaluated with various glucose concentrations. The kinetic constant of insulin and anti-insulin antibody was determined and the detection limit of 100 ng/mL insulin was archived.

Recent advances of controlled drug delivery using microfluidic platforms.

PubMed

Sanjay, Sharma T; Zhou, Wan; Dou, Maowei; Tavakoli, Hamed; Ma, Lei; Xu, Feng; Li, XiuJun

2018-03-15

Conventional systematically-administered drugs distribute evenly throughout the body, get degraded and excreted rapidly while crossing many biological barriers, leaving minimum amounts of the drugs at pathological sites. Controlled drug delivery aims to deliver drugs to the target sites at desired rates and time, thus enhancing the drug efficacy, pharmacokinetics, and bioavailability while maintaining minimal side effects. Due to a number of unique advantages of the recent microfluidic lab-on-a-chip technology, microfluidic lab-on-a-chip has provided unprecedented opportunities for controlled drug delivery. Drugs can be efficiently delivered to the target sites at desired rates in a well-controlled manner by microfluidic platforms via integration, implantation, localization, automation, and precise control of various microdevice parameters. These features accordingly make reproducible, on-demand, and tunable drug delivery become feasible. On-demand self-tuning dynamic drug delivery systems have shown great potential for personalized drug delivery. This review presents an overview of recent advances in controlled drug delivery using microfluidic platforms. The review first briefly introduces microfabrication techniques of microfluidic platforms, followed by detailed descriptions of numerous microfluidic drug delivery systems that have significantly advanced the field of controlled drug delivery. Those microfluidic systems can be separated into four major categories, namely drug carrier-free micro-reservoir-based drug delivery systems, highly integrated carrier-free microfluidic lab-on-a-chip systems, drug carrier-integrated microfluidic systems, and microneedles. Microneedles can be further categorized into five different types, i.e. solid, porous, hollow, coated, and biodegradable microneedles, for controlled transdermal drug delivery. At the end, we discuss current limitations and future prospects of microfluidic platforms for controlled drug delivery. Copyright © 2017 Elsevier B.V. All rights reserved.

A high efficiency microfluidic-based photocatalytic microreactor using electrospun nanofibrous TiO2 as a photocatalyst.

PubMed

Meng, Zhaoxu; Zhang, Xu; Qin, Jianhua

2013-06-07

We present a novel microfluidic-based photocatalytic microreactor by using electrospun nanofibrous TiO2 as a photocatalyst for the first time. The microreactor exhibits not only a simple fabrication process, but also much higher photocatalytic activity than that achieved by a TiO2 film microreactor.

Capillary-driven surface-enhanced Raman scattering (SERS)-based microfluidic chip for abrin detection

NASA Astrophysics Data System (ADS)

Yang, Hao; Deng, Min; Ga, Shan; Chen, Shouhui; Kang, Lin; Wang, Junhong; Xin, Wenwen; Zhang, Tao; You, Zherong; An, Yuan; Wang, Jinglin; Cui, Daxiang

2014-03-01

Herein, we firstly demonstrate the design and the proof-of-concept use of a capillary-driven surface-enhanced Raman scattering (SERS)-based microfluidic chip for abrin detection. The micropillar array substrate was etched and coated with a gold film by microelectromechanical systems (MEMS) process to integrate into a lateral flow test strip. The detection of abrin solutions of various concentrations was performed by the as-prepared microfluidic chip. It was shown that the correlation between the abrin concentration and SERS signal was found to be linear within the range of 0.1 ng/mL to 1 μg/mL with a limit of detection of 0.1 ng/mL. Our microfluidic chip design enhanced the operability of SERS-based immunodiagnostic techniques, significantly reducing the complication and cost of preparation as compared to previous SERS-based works. Meanwhile, this design proved the superiority to conventional lateral flow test strips in respect of both sensitivity and quantitation and showed great potential in the diagnosis and treatment for abrin poisoning as well as on-site screening of abrin-spiked materials.

Optical imaging of localized chemical events using programmable diamond quantum nanosensors

NASA Astrophysics Data System (ADS)

Rendler, Torsten; Neburkova, Jitka; Zemek, Ondrej; Kotek, Jan; Zappe, Andrea; Chu, Zhiqin; Cigler, Petr; Wrachtrup, Jörg

2017-03-01

Development of multifunctional nanoscale sensors working under physiological conditions enables monitoring of intracellular processes that are important for various biological and medical applications. By attaching paramagnetic gadolinium complexes to nanodiamonds (NDs) with nitrogen-vacancy (NV) centres through surface engineering, we developed a hybrid nanoscale sensor that can be adjusted to directly monitor physiological species through a proposed sensing scheme based on NV spin relaxometry. We adopt a single-step method to measure spin relaxation rates enabling time-dependent measurements on changes in pH or redox potential at a submicrometre-length scale in a microfluidic channel that mimics cellular environments. Our experimental data are reproduced by numerical simulations of the NV spin interaction with gadolinium complexes covering the NDs. Considering the versatile engineering options provided by polymer chemistry, the underlying mechanism can be expanded to detect a variety of physiologically relevant species and variables.

Counterflow Dielectrophoresis for Trypanosome Enrichment and Detection in Blood

NASA Astrophysics Data System (ADS)

Menachery, Anoop; Kremer, Clemens; Wong, Pui E.; Carlsson, Allan; Neale, Steven L.; Barrett, Michael P.; Cooper, Jonathan M.

2012-10-01

Human African trypanosomiasis or sleeping sickness is a deadly disease endemic in sub-Saharan Africa, caused by single-celled protozoan parasites. Although it has been targeted for elimination by 2020, this will only be realized if diagnosis can be improved to enable identification and treatment of afflicted patients. Existing techniques of detection are restricted by their limited field-applicability, sensitivity and capacity for automation. Microfluidic-based technologies offer the potential for highly sensitive automated devices that could achieve detection at the lowest levels of parasitemia and consequently help in the elimination programme. In this work we implement an electrokinetic technique for the separation of trypanosomes from both mouse and human blood. This technique utilises differences in polarisability between the blood cells and trypanosomes to achieve separation through opposed bi-directional movement (cell counterflow). We combine this enrichment technique with an automated image analysis detection algorithm, negating the need for a human operator.

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.

Easy route to superhydrophobic copper-based wire-guided droplet microfluidic systems.

PubMed

Mumm, Florian; van Helvoort, Antonius T J; Sikorski, Pawel

2009-09-22

Droplet-based microfluidic systems are an expansion of the lab on a chip concept toward flexible, reconfigurable setups based on the modification and analysis of individual droplets. Superhydrophobic surfaces are one suitable candidate for the realization of droplet-based microfluidic systems as the high mobility of aqueous liquids on such surfaces offers possibilities to use novel or more efficient approaches to droplet movement. Here, copper-based superhydrophobic surfaces were produced either by the etching of polycrystalline copper samples along the grain boundaries using etchants common in the microelectronics industry, by electrodeposition of copper films with subsequent nanowire decoration based on thermal oxidization, or by a combination of both. The surfaces could be easily hydrophobized with thiol-modified fluorocarbons, after which the produced surfaces showed a water contact angle as high as 171 degrees +/- 2 degrees . As copper was chosen as the base material, established patterning techniques adopted from printed circuit board fabrication could be used to fabricate macrostructures on the surfaces with the intention to confine the droplets and, thus, to reduce the system's sensitivity to tilting and vibrations. A simple droplet-based microfluidic chip with inlets, outlets, sample storage, and mixing areas was produced. Wire guidance, a relatively new actuation method applicable to aqueous liquids on superhydrophobic surfaces, was applied to move the droplets.

Controlling Shear Stress in 3D Bioprinting is a Key Factor to Balance Printing Resolution and Stem Cell Integrity.

PubMed

Blaeser, Andreas; Duarte Campos, Daniela Filipa; Puster, Uta; Richtering, Walter; Stevens, Molly M; Fischer, Horst

2016-02-04

A microvalve-based bioprinting system for the manufacturing of high-resolution, multimaterial 3D-structures is reported. Applying a straightforward fluid-dynamics model, the shear stress at the nozzle site can precisely be controlled. Using this system, a broad study on how cell viability and proliferation potential are affected by different levels of shear stress is conducted. Complex, multimaterial 3D structures are printed with high resolution. This work pioneers the investigation of shear stress-induced cell damage in 3D bioprinting and might help to comprehend and improve the outcome of cell-printing studies in the future. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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.

A compact disk-like centrifugal microfluidic system for high-throughput nanoliter-scale protein crystallization screening.

PubMed

Li, Gang; Chen, Qiang; Li, Junjun; Hu, Xiaojian; Zhao, Jianlong

2010-06-01

A centrifuge-based microfluidic system has been developed that enables automated high-throughput and low-volume protein crystallizations. In this system, protein solution was automatically and accurately metered and dispensed into nanoliter-sized multiple reaction chambers, and it was mixed with various types of precipitants using a combination of capillary effect and centrifugal force. It has the advantages of simple fabrication, easy operation, and extremely low waste. To demonstrate the feasibility of this system, we constructed a chip containing 24 units and used it to perform lysozyme and cyan fluorescent protein (CyPet) crystallization trials. The results demonstrate that high-quality crystals can be grown and harvested from such a nanoliter-volume microfluidic system. Compared to other microfluidic technologies for protein crystallization, this microfluidic system allows zero waste, simple structure and convenient operation, which suggests that our microfluidic disk can be applied not only to protein crystallization, but also to the miniaturization of various biochemical reactions requiring precise nanoscale control.

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.

Microfluidic Automation using elastomeric valves and droplets: reducing reliance on external controllers

PubMed Central

Kim, Sung-Jin; Lai, David; Park, Joong Yull; Yokokawa, Ryuji

2012-01-01

This paper gives an overview of elastomeric valve- and droplet-based microfluidic systems designed to minimize the need of external pressure to control fluid flow. This concept article introduces the working principle of representative components in these devices along with relevant biochemical applications. This is followed by providing a perspective on the roles of different microfluidic valves and systems through comparison of their similarities and differences with transistors (valves) and systems in microelectronics. Despite some physical limitation of drawing analogies from electronic circuits, automated microfluidic circuit design can gain insights from electronic circuits to minimize external control units, while implementing high complexity and throughput analysis. PMID:22761019

Highly stable liquid metal-based pressure sensor integrated with a microfluidic channel.

PubMed

Jung, Taekeon; Yang, Sung

2015-05-21

Pressure measurement is considered one of the key parameters in microfluidic systems. It has been widely used in various fields, such as in biology and biomedical fields. The electrical measurement method is the most widely investigated; however, it is unsuitable for microfluidic systems because of a complicated fabrication process and difficult integration. Moreover, it is generally damaged by large deflection. This paper proposes a thin-film-based pressure sensor that is free from these limitations, using a liquid metal called galinstan. The proposed pressure sensor is easily integrated into a microfluidic system using soft lithography because galinstan exists in a liquid phase at room temperature. We investigated the characteristics of the proposed pressure sensor by calibrating for a pressure range from 0 to 230 kPa (R2 > 0.98) using deionized water. Furthermore, the viscosity of various fluid samples was measured for a shear-rate range of 30-1000 s(-1). The results of Newtonian and non-Newtonian fluids were evaluated using a commercial viscometer and normalized difference was found to be less than 5.1% and 7.0%, respectively. The galinstan-based pressure sensor can be used in various microfluidic systems for long-term monitoring with high linearity, repeatability, and long-term stability.

Highly Stable Liquid Metal-Based Pressure Sensor Integrated with a Microfluidic Channel

PubMed Central

Jung, Taekeon; Yang, Sung

2015-01-01

Pressure measurement is considered one of the key parameters in microfluidic systems. It has been widely used in various fields, such as in biology and biomedical fields. The electrical measurement method is the most widely investigated; however, it is unsuitable for microfluidic systems because of a complicated fabrication process and difficult integration. Moreover, it is generally damaged by large deflection. This paper proposes a thin-film-based pressure sensor that is free from these limitations, using a liquid metal called galinstan. The proposed pressure sensor is easily integrated into a microfluidic system using soft lithography because galinstan exists in a liquid phase at room temperature. We investigated the characteristics of the proposed pressure sensor by calibrating for a pressure range from 0 to 230 kPa (R2 > 0.98) using deionized water. Furthermore, the viscosity of various fluid samples was measured for a shear-rate range of 30–1000 s−1. The results of Newtonian and non-Newtonian fluids were evaluated using a commercial viscometer and normalized difference was found to be less than 5.1% and 7.0%, respectively. The galinstan-based pressure sensor can be used in various microfluidic systems for long-term monitoring with high linearity, repeatability, and long-term stability. PMID:26007732

[Synthesis of hollow titania microspheres by using microfluidic droplet-template].

PubMed

Ma, Jingyun; Jiang, Lei; Qin, Jianhu

2011-09-01

Droplet-based microfluidics is of great interest due to its particular characteristics compared with the conventional methods, such as reduced reagent consumption, rapid mixing, high-throughput, shape controlled, etc. A novel method using microfluidic droplet as soft template for the synthesis of hollow titania microspheres was developed. A typical polydimethylsiloxane (PDMS) microfluidic device containing "flow-focusing" geometry was used to generate water/oil (W/O) droplet. The mechanism for the hollow structure formation was based on the interfacial hydrolysis reaction between the continuous phase containing titanium butoxide precursor and the dispersed containing water. The continuous phase mixed with butanol was added in the downstream of the channel after the hydrolysis reaction. This step was used for drawing the water out of the microgels for further hydrolysis. The microgels obtained through a glass pipe integrated were washed, dried under vacuum and calcined after aging for a certain time. The fluorescence and scanning electron microscope (SEM) image of the microspheres indicated the hollow structure and the thickness of the shell. In addition, these microspheres with thin shell (about 2 microm) were apt to rupture and collapse. Droplet-based microfluidic offered a gentle and size-controllable manner to moderate this problem. Moreover, it has potential applications in photocatalysis combined with some modification realized on the chip simultaneously.

Discrete microfluidics: Reorganizing droplet arrays at a bend

NASA Astrophysics Data System (ADS)

Surenjav, Enkhtuul; Herminghaus, Stephan; Priest, Craig; Seemann, Ralf

2009-10-01

Microfluidic manipulation of densely packed droplet arrangements (i.e., gel emulsions) using sharp microchannel bends was studied as a function of bend angle, droplet volume fraction, droplet size, and flow velocity. Emulsion reorganization was found to be specifically dependent on the pathlength that the droplets are forced to travel as they navigate the bend under spatial confinement. We describe how bend-induced droplet displacements might be exploited in complex, droplet-based microfluidics.

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.

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.

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.

Droplet microfluidics for single-cell analysis.

PubMed

Brouzes, Eric

2012-01-01

This book chapter aims at providing an overview of all the aspects and procedures needed to develop a droplet-based workflow for single-cell analysis (see Fig. 10.1). The surfactant system used to stabilize droplets is a critical component of droplet microfluidics; its properties define the type of droplet-based assays and workflows that can be developed. The scope of this book chapter is limited to fluorinated surfactant systems that have proved to generate extremely stable droplets and allow to easily retrieve the encapsulated material. The formulation section discusses how the experimental parameters influence the choice of the surfactant system to use. The circuit design section presents recipes to design and integrate different droplet modules into a whole assay. The fabrication section describes the manufacturing of microfluidic chip including the surface treatment which is pivotal in droplet microfluidics. Finally, the last section reviews the experimental setup for fluorescence detection with an emphasis on cell injection and incubation.

Microfluidic Pumps Containing Teflon [Trademark] AF Diaphragms

NASA Technical Reports Server (NTRS)

Willis, Peter; White, Victor; Grunthaner, Frank; Ikeda, Mike; Mathies, Richard A.

2009-01-01

Microfluidic pumps and valves based on pneumatically actuated diaphragms made of Teflon AF polymers are being developed for incorporation into laboratory-on-a-chip devices that must perform well over temperature ranges wider than those of prior diaphragm-based microfluidic pumps and valves. Other potential applications include implanted biomedical microfluidic devices, wherein the biocompatability of Teflon AF polymers would be highly advantageous. These pumps and valves have been demonstrated to function stably after cycling through temperatures from -125 to 120 C. These pumps and valves are intended to be successors to similar prior pumps and valves containing diaphragms made of polydimethylsiloxane (PDMS) [commonly known as silicone rubber]. The PDMS-containing valves ae designed to function stably only within the temperature range from 5 to 80 C. Undesirably, PDMS membranes are somwehat porous and retain water. PDMS is especially unsuitable for use at temperatures below 0 C because the formation of ice crystals increases porosity and introduces microshear.

Towards Biofilm Spectroscopy - A Novel Microfluidic Approach for Characterizing Biofilm Subpopulation by Microwave-Based Electrical Impedance Spectroscopy

NASA Astrophysics Data System (ADS)

Richter, Christiane; Schneider, Stefan; Rapp, Bastian E.; Schmidt, Sönke; Schüßler, Martin; Jakoby, Rolf; Bruchmann, Julia; Bischer, Moritz; Schwartz, Thomas

2018-03-01

In this work three disciplines - microfluidics, microbiology and microwave engineering - are utilized to develop a system for analyzing subpopulations of biofilms and their reaction to antibiotic treatment. We present handling strategies to destabilize a biofilm inside a microfluidic system down to aggregate sizes of<10 µm2 as well as microfluidic structures for the flow-through filtration of the resulting cell suspensions. For the analysis of the cell populations by microwave electrical impedance spectroscopy, two novel calibration schemes are demonstrated to cover both, reflection as well as transmission measurements of dielectric fluids. The broadband calibration strategies are solely based on liquid standards and allow a precise long-term monitoring with a resolution up to Δ ɛ = 6 Δ = 1.5 ‰ at H 5 GHz. Combining these three research topics therefore will open up new ways for analyzing biofilm effects.

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

Investigation on microfluidic particles manipulation by holographic 3D tracking strategies

NASA Astrophysics Data System (ADS)

Cacace, Teresa; Paturzo, Melania; Memmolo, Pasquale; Vassalli, Massimo; Fraldi, Massimiliano; Mensitieri, Giuseppe; Ferraro, Pietro

2017-06-01

We demonstrate a 3D holographic tracking method to investigate particles motion in a microfluidic channel while unperturbed while inducing their migration through microfluidic manipulation. Digital holography (DH) in microscopy is a full-field, label-free imaging technique able to provide quantitative phase-contrast. The employed 3D tracking method is articulated in steps. First, the displacements along the optical axis are assessed by numerical refocusing criteria. In particular, an automatic refocusing method to recover the particles axial position is implemented employing a contrast-based refocusing criterion. Then, the transverse position of the in-focus object is evaluated through quantitative phase map segmentation methods and centroid-based 2D tracking strategy. The introduction of DH is thus suggested as a powerful approach for control of particles and biological samples manipulation, as well as a possible aid to precise design and implementation of advanced lab-on-chip microfluidic devices.

Microfluidic on-chip biomimicry for 3D cell culture: a fit-for-purpose investigation from the end user standpoint

PubMed Central

Liu, Ye; Gill, Elisabeth; Shery Huang, Yan Yan

2017-01-01

A plethora of 3D and microfluidics-based culture models have been demonstrated in the recent years with the ultimate aim to facilitate predictive in vitro models for pharmaceutical development. This article summarizes to date the progress in the microfluidics-based tissue culture models, including organ-on-a-chip and vasculature-on-a-chip. Specific focus is placed on addressing the question of what kinds of 3D culture and system complexities are deemed desirable by the biological and biomedical community. This question is addressed through analysis of a research survey to evaluate the potential use of microfluidic cell culture models among the end users. Our results showed a willingness to adopt 3D culture technology among biomedical researchers, although a significant gap still exists between the desired systems and existing 3D culture options. With these results, key challenges and future directions are highlighted. PMID:28670465

Microfluidic on-chip biomimicry for 3D cell culture: a fit-for-purpose investigation from the end user standpoint.

PubMed

Liu, Ye; Gill, Elisabeth; Shery Huang, Yan Yan

2017-06-01

A plethora of 3D and microfluidics-based culture models have been demonstrated in the recent years with the ultimate aim to facilitate predictive in vitro models for pharmaceutical development. This article summarizes to date the progress in the microfluidics-based tissue culture models, including organ-on-a-chip and vasculature-on-a-chip. Specific focus is placed on addressing the question of what kinds of 3D culture and system complexities are deemed desirable by the biological and biomedical community. This question is addressed through analysis of a research survey to evaluate the potential use of microfluidic cell culture models among the end users. Our results showed a willingness to adopt 3D culture technology among biomedical researchers, although a significant gap still exists between the desired systems and existing 3D culture options. With these results, key challenges and future directions are highlighted.

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.

A hydrophilic polymer based microfluidic system with planar patch clamp electrode array for electrophysiological measurement from cells.

PubMed

Xu, Baojian; Ye, WeiWei; Zhang, Yu; Shi, JingYu; Chan, ChunYu; Yao, XiaoQiang; Yang, Mo

2014-03-15

This paper presents a microfluidic planar patch clamp system based on a hydrophilic polymer poly(ethylene glycol) diacrylate (PEGDA) for whole cell current recording. The whole chip is fabricated by UV-assisted molding method for both microfluidic channel structure and planar electrode partition. This hydrophilic patch clamp chip has demonstrated a relatively high gigaseal success rate of 44% without surface modification compared with PDMS based patch clamp devices. This chip also shows a capability of rapid intracellular and extracellular solution exchange with high stability of gigaseals. The capillary flow kinetic experiments demonstrate that the flow rates of PEGDA microfluidic channels are around two orders of magnitude greater than those for PDMS-glass channels with the same channel dimensions. This hydrophilic polymer based patch clamp chips have significant advantages over current PDMS elastomer based systems such as no need for surface modification, much higher success rate of cell gigaseals and rapid solution exchange with stable cell gigaseals. Our results indicate the potential of these devices to serve as useful tools for pharmaceutical screening and biosensing tasks. © 2013 Elsevier B.V. All rights reserved.

A highly efficient microfluidic nano biochip based on nanostructured nickel oxide.

PubMed

Ali, Md Azahar; Solanki, Pratima R; Patel, Manoj K; Dhayani, Hemant; Agrawal, Ved Varun; John, Renu; Malhotra, Bansi D

2013-04-07

We present results of the studies relating to fabrication of a microfluidic biosensor chip based on nickel oxide nanorods (NRs-NiO) that is capable of directly measuring the concentration of total cholesterol in human blood through electrochemical detection. Using this chip we demonstrate, with high reliability and in a time efficient manner, the detection of cholesterol present in buffer solutions at clinically relevant concentrations. The microfluidic channel has been fabricated onto a nickel oxide nanorod-based electrode co-immobilized with cholesterol esterase (ChEt) and cholesterol oxidase (ChOx) that serves as the working electrode. Bare indium tin oxide served as the counter electrode. A Ag/AgCl wire introduced to the outlet of the microchannel acts as a reference electrode. The fabricated NiO nanorod-based electrode has been characterized using X-ray diffraction, Raman spectroscopy, HR-TEM, FT-IR, UV-visible spectroscopy and electrochemical techniques. The presented NRs-NiO based microfluidic sensor exhibits linearity in the range of 1.5-10.3 mM, a high sensitivity of 0.12 mA mM(-1) cm(-2) and a low value of 0.16 mM of the Michaelis-Menten constant (Km).

Development of procedures for programmable proximity aperture lithography

NASA Astrophysics Data System (ADS)

Whitlow, H. J.; Gorelick, S.; Puttaraksa, N.; Napari, M.; Hokkanen, M. J.; Norarat, R.

2013-07-01

Programmable proximity aperture lithography (PPAL) with MeV ions has been used in Jyväskylä and Chiang Mai universities for a number of years. Here we describe a number of innovations and procedures that have been incorporated into the LabView-based software. The basic operation involves the coordination of the beam blanker and five motor-actuated translators with high accuracy, close to the minimum step size with proper anti-collision algorithms. By using special approaches, such writing calibration patterns, linearisation of position and careful backlash correction the absolute accuracy of the aperture size and position, can be improved beyond the standard afforded by the repeatability of the translator end-point switches. Another area of consideration has been the fluence control procedures. These involve control of the uniformity of the beam where different approaches for fluence measurement such as simultaneous aperture current and the ion current passing through the aperture using a Faraday cup are used. Microfluidic patterns may contain many elements that make-up mixing sections, reaction chambers, separation columns and fluid reservoirs. To facilitate conception and planning we have implemented a .svg file interpreter, that allows the use of scalable vector graphics files produced by standard drawing software for generation of patterns made up of rectangular elements.

A cell-laden microfluidic hydrogel.

PubMed

Ling, Yibo; Rubin, Jamie; Deng, Yuting; Huang, Catherine; Demirci, Utkan; Karp, Jeffrey M; Khademhosseini, Ali

2007-06-01

The encapsulation of mammalian cells within the bulk material of microfluidic channels may be beneficial for applications ranging from tissue engineering to cell-based diagnostic assays. In this work, we present a technique for fabricating microfluidic channels from cell-laden agarose hydrogels. Using standard soft lithographic techniques, molten agarose was molded against a SU-8 patterned silicon wafer. To generate sealed and water-tight microfluidic channels, the surface of the molded agarose was heated at 71 degrees C for 3 s and sealed to another surface-heated slab of agarose. Channels of different dimensions were generated and it was shown that agarose, though highly porous, is a suitable material for performing microfluidics. Cells embedded within the microfluidic molds were well distributed and media pumped through the channels allowed the exchange of nutrients and waste products. While most cells were found to be viable upon initial device fabrication, only those cells near the microfluidic channels remained viable after 3 days, demonstrating the importance of a perfused network of microchannels for delivering nutrients and oxygen to maintain cell viability in large hydrogels. Further development of this technique may lead to the generation of biomimetic synthetic vasculature for tissue engineering, diagnostics, and drug screening applications.

Materials for Microfluidic Immunoassays: A Review.

PubMed

Mou, Lei; Jiang, Xingyu

2017-08-01

Conventional immunoassays suffer from at least one of these following limitations: long processing time, high costs, poor user-friendliness, technical complexity, poor sensitivity and specificity. Microfluidics, a technology characterized by the engineered manipulation of fluids in channels with characteristic lengthscale of tens of micrometers, has shown considerable promise for improving immunoassays that could overcome these limitations in medical diagnostics and biology research. The combination of microfluidics and immunoassay can detect biomarkers with faster assay time, reduced volumes of reagents, lower power requirements, and higher levels of integration and automation compared to traditional approaches. This review focuses on the materials-related aspects of the recent advances in microfluidics-based immunoassays for point-of-care (POC) diagnostics of biomarkers. We compare the materials for microfluidic chips fabrication in five aspects: fabrication, integration, function, modification and cost, and describe their advantages and drawbacks. In addition, we review materials for modifying antibodies to improve the performance of the reaction of immunoassay. We also review the state of the art in microfluidic immunoassays POC platforms, from the laboratory to routine clinical practice, and also commercial products in the market. Finally, we discuss the current challenges and future developments in microfluidic immunoassays. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Detection of Micrococcus luteus biofilm formation in microfluidic environments by pH measurement using an ion-sensitive field-effect transistor.

PubMed

Matsuura, Koji; Asano, Yuka; Yamada, Akira; Naruse, Keiji

2013-02-18

Biofilm formation in microfluidic channels is difficult to detect because sampling volumes are too small for conventional turbidity measurements. To detect biofilm formation, we used an ion-sensitive field-effect transistor (ISFET) measurement system to measure pH changes in small volumes of bacterial suspension. Cells of Micrococcus luteus (M. luteus) were cultured in polystyrene (PS) microtubes and polymethylmethacrylate (PMMA)-based microfluidic channels laminated with polyvinylidene chloride. In microtubes, concentrations of bacteria and pH in the suspension were analyzed by measuring turbidity and using an ISFET sensor, respectively. In microfluidic channels containing 20 μL of bacterial suspension, we measured pH changes using the ISFET sensor and monitored biofilm formation using a microscope. We detected acidification and alkalinization phases of M. luteus from the ISFET sensor signals in both microtubes and microfluidic channels. In the alkalinization phase, after 2 day culture, dense biofilm formation was observed at the bottom of the microfluidic channels. In this study, we used an ISFET sensor to detect biofilm formation in clinical and industrial microfluidic environments by detecting alkalinization of the culture medium. 

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

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 Fast and Effective Microfluidic Spraying-Plunging Method for High-Resolution Single-Particle Cryo-EM.

PubMed

Feng, Xiangsong; Fu, Ziao; Kaledhonkar, Sandip; Jia, Yuan; Shah, Binita; Jin, Amy; Liu, Zheng; Sun, Ming; Chen, Bo; Grassucci, Robert A; Ren, Yukun; Jiang, Hongyuan; Frank, Joachim; Lin, Qiao

2017-04-04

We describe a spraying-plunging method for preparing cryoelectron microscopy (cryo-EM) grids with vitreous ice of controllable, highly consistent thickness using a microfluidic device. The new polydimethylsiloxane (PDMS)-based sprayer was tested with apoferritin. We demonstrate that the structure can be solved to high resolution with this method of sample preparation. Besides replacing the conventional pipetting-blotting-plunging method, one of many potential applications of the new sprayer is in time-resolved cryo-EM, as part of a PDMS-based microfluidic reaction channel to study short-lived intermediates on the timescale of 10-1,000 ms. Published by Elsevier Ltd.

Droplet-based Biosensing for Lab-on-a-Chip, Open Microfluidics Platforms

PubMed Central

Dak, Piyush; Ebrahimi, Aida; Swaminathan, Vikhram; Duarte-Guevara, Carlos; Bashir, Rashid; Alam, Muhammad A.

2016-01-01

Low cost, portable sensors can transform health care by bringing easily available diagnostic devices to low and middle income population, particularly in developing countries. Sample preparation, analyte handling and labeling are primary cost concerns for traditional lab-based diagnostic systems. Lab-on-a-chip (LoC) platforms based on droplet-based microfluidics promise to integrate and automate these complex and expensive laboratory procedures onto a single chip; the cost will be further reduced if label-free biosensors could be integrated onto the LoC platforms. Here, we review some recent developments of label-free, droplet-based biosensors, compatible with “open” digital microfluidic systems. These low-cost droplet-based biosensors overcome some of the fundamental limitations of the classical sensors, enabling timely diagnosis. We identify the key challenges that must be addressed to make these sensors commercially viable and summarize a number of promising research directions. PMID:27089377

Droplet-based Biosensing for Lab-on-a-Chip, Open Microfluidics Platforms.

PubMed

Dak, Piyush; Ebrahimi, Aida; Swaminathan, Vikhram; Duarte-Guevara, Carlos; Bashir, Rashid; Alam, Muhammad A

2016-04-14

Low cost, portable sensors can transform health care by bringing easily available diagnostic devices to low and middle income population, particularly in developing countries. Sample preparation, analyte handling and labeling are primary cost concerns for traditional lab-based diagnostic systems. Lab-on-a-chip (LoC) platforms based on droplet-based microfluidics promise to integrate and automate these complex and expensive laboratory procedures onto a single chip; the cost will be further reduced if label-free biosensors could be integrated onto the LoC platforms. Here, we review some recent developments of label-free, droplet-based biosensors, compatible with "open" digital microfluidic systems. These low-cost droplet-based biosensors overcome some of the fundamental limitations of the classical sensors, enabling timely diagnosis. We identify the key challenges that must be addressed to make these sensors commercially viable and summarize a number of promising research directions.

Electrofluidic Circuit-Based Microfluidic Viscometer for Analysis of Newtonian and Non-Newtonian Liquids under Different Temperatures.

PubMed

Lee, Tse-Ang; Liao, Wei-Hao; Wu, Yi-Fan; Chen, Yeng-Long; Tung, Yi-Chung

2018-02-06

This paper reports a microfluidic viscometer with an integrated pressure sensor based on electrofluidic circuits, which are electrical circuits constructed by ionic liquid-filled microfluidic channels. The electrofluidic circuit provides a pressure-sensing scheme with great long-term and thermal stability. The viscosity of the tested fluidic sample is estimated by its flow resistance, which is a function of pressure drop, flow rate, and the geometry of the microfluidic channel. The viscometer can be exploited to measure viscosity of either Newtonian or non-Newtonian power-law fluid under various shear rates (3-500 1/s) and temperatures (4-70 °C) with small sample volume (less than 400 μL). The developed sensor-integrated microfluidic viscometer is made of poly(dimethylsiloxane) (PDMS) with transparent electrofluidic circuit, which makes it feasible to simultaneously image samples under tests. In addition, the entire device is disposable to prevent cross-contamination between samples, which is desired for various chemical and biomedical applications. In the experiments, viscosities of Newtonian fluids, glycerol water solutions with different concentrations and a mixture of pyrogallol and sodium hydroxide (NaOH), and non-Newtonian fluids, xanthan gum solutions and human blood samples, have been characterized. The results demonstrate that the developed microfluidic viscometer provides a convenient and useful platform for practical viscosity characterization of fluidic samples for a wide variety of applications.

3D-glass molds for facile production of complex droplet microfluidic chips.

PubMed

Tovar, Miguel; Weber, Thomas; Hengoju, Sundar; Lovera, Andrea; Munser, Anne-Sophie; Shvydkiv, Oksana; Roth, Martin

2018-03-01

In order to leverage the immense potential of droplet microfluidics, it is necessary to simplify the process of chip design and fabrication. While polydimethylsiloxane (PDMS) replica molding has greatly revolutionized the chip-production process, its dependence on 2D-limited photolithography has restricted the design possibilities, as well as further dissemination of microfluidics to non-specialized labs. To break free from these restrictions while keeping fabrication straighforward, we introduce an approach to produce complex multi-height (3D) droplet microfluidic glass molds and subsequent chip production by PDMS replica molding. The glass molds are fabricated with sub-micrometric resolution using femtosecond laser machining technology, which allows directly realizing designs with multiple levels or even continuously changing heights. The presented technique significantly expands the experimental capabilities of the droplet microfluidic chip. It allows direct fabrication of multilevel structures such as droplet traps for prolonged observation and optical fiber integration for fluorescence detection. Furthermore, the fabrication of novel structures based on sloped channels (ramps) enables improved droplet reinjection and picoinjection or even a multi-parallelized drop generator based on gradients of confinement. The fabrication of these and other 3D-features is currently only available at such resolution by the presented strategy. Together with the simplicity of PDMS replica molding, this provides an accessible solution for both specialized and non-specialized labs to customize microfluidic experimentation and expand their possibilities.

Towards rapid prototyped convective microfluidic DNA amplification platform

NASA Astrophysics Data System (ADS)

Ajit, Smrithi; Praveen, Hemanth Mithun; Puneeth, S. B.; Dave, Abhishek; Sesham, Bharat; Mohan, K. N.; Goel, Sanket

2017-02-01

Today, Polymerase Chain Reaction (PCR) based DNA amplification plays an indispensable role in the field of biomedical research. Its inherent ability to exponentially amplify sample DNA has proven useful for the identification of virulent pathogens like those causing Multiple Drug-Resistant Tuberculosis (MDR-TB). The intervention of Microfluidics technology has revolutionized the concept of PCR from being a laborious and time consuming process into one that is faster, easily portable and capable of being multifunctional. The Microfluidics based PCR outweighs its traditional counterpart in terms of flexibility of varying reaction rate, operation simplicity, need of a fraction of volume and capability of being integrated with other functional elements. The scope of the present work involves the development of a real-time continuous flow microfluidic device, fabricated by 3D printing-governed rapid prototyping method, eventually leading to an automated and robust platform to process multiple DNA samples for detection of MDRTB-associated mutations. The thermal gradient characteristic to the PCR process is produced using peltier units appropriate to the microfluidic environment fully monitored and controlled by a low cost controller driven by a Data Acquisition System. The process efficiency achieved in the microfluidic environment in terms of output per cycle is expected to be on par with the traditional PCR and capable of earning the additional advantages of being faster and minimizing the handling.

NASA Tech Briefs, December 2003

NASA Technical Reports Server (NTRS)

2003-01-01

Topics covered include: Organic/Inorganic Hybrid Polymer/Clay Nanocomposites; Less-Toxic Coatings for Inhibiting Corrosion of Aluminum; Liquid Coatings for Reducing Corrosion of Steel in Concrete; Processable Polyimides Containing APB and Reactive End Caps; Rod/Coil Block Copolyimides for Ion-Conducting Membranes; Techniques for Characterizing Microwave Printed Antennas; Cylindrical Antenna With Partly Adaptive Phased-Array Feed; Command Interface ASIC - Analog Interface ASIC Chip Set; Predicting Accumulations of Ice on Aerodynamic Surfaces; Analyzing Aeroelasticity in Turbomachines; Software for Allocating Resources in the Deep Space Network; Expert Seeker; High-Speed Recording of Test Data on Hard Disks; Functionally Graded Nanophase Beryllium/Carbon Composites; Thin Thermal-Insulation Blankets for Very High Temperatures; Aerostructures Test Wing; Flight-Test Evaluation of Flutter-Prediction Methods; Piezoelectrically Actuated Microvalve for Liquid Effluents; Larger-Stroke Piezoelectrically Actuated Microvalve; Innovative, High-Pressure, Cryogenic Control Valve: Short Face-to-Face, Reduced Cost; Safer Roadside Crash Walls Would Limit Deceleration; Improved Interactive Medical-Imaging System; Scanning Microscopes Using X Rays and Microchannels; Slotting Fins of Heat Exchangers to Provide Thermal Breaks; Methane Clathrate Hydrate Prospecting; Automated Monitoring with a BSP Fault-Detection Test; Automated Monitoring with a BCP Fault-Decision Test; Vector-Ordering Filter Procedure for Data Reduction; Remote Sensing and Information Technology for Large Farms; Developments at the Advanced Design Technologies Testbed; Spore-Forming Bacteria that Resist Sterilization; and Acoustical Applications of the HHT Method.

Fluid injection microvalve

DOEpatents

Renzi, Ronald F.

2005-11-22

A microvalve for extracting small volume samples into analytical devices, e.g., high pressure liquid chromatography (HPLC) column, includes: a first body having a first interior surface and two or more outlet ports at the first interior surface that are in fluid communication with two or more first channels; a second body having a second interior surface and two or more inlet ports at the second interior surface that are in fluid communication with two or more second channels wherein the outlet ports of the first body are coaxial with the corresponding inlet ports of the second body such that there are at least two sets of coaxial port outlets and port inlets; a plate member, which has a substantially planar first mating surface and a substantially planar second mating surface, that is slidably positioned between the first interior surface and the second interior surface wherein the plate member has at least one aperture that traverses the height of the plate member, and wherein the aperture can be positioned to be coaxial with any of the at least two sets of coaxial port outlets and port inlets; and means for securing the first surface of the first body against the first mating surface and for securing the second surface of the second body against the second mating surface.

Activation of Actuating Hydrogels with WS2 Nanosheets for Biomimetic Cellular Structures and Steerable Prompt Deformation.

PubMed

Zong, Lu; Li, Xiankai; Han, Xiangsheng; Lv, Lili; Li, Mingjie; You, Jun; Wu, Xiaochen; Li, Chaoxu

2017-09-20

Macroscopic soft actuation is intrinsic to living organisms in nature, including slow deformation (e.g., contraction, bending, twisting, and curling) of plants motivated by microscopic swelling and shrinking of cells, and rapid motion of animals (e.g., deformation of jellyfish) motivated by cooperative nanoscale movement of motor proteins. These actuation behaviors, with an exceptional combination of tunable speed and programmable deformation direction, inspire us to design artificial soft actuators for broad applications in artificial muscles, nanofabrication, chemical valves, microlenses, soft robotics, etc. However, so far artificial soft actuators have been typically produced on the basis of poly(N-isopropylacrylamide) (PNiPAM), whose deformation is motived by volumetric shrinkage and swelling in analogue to plant cells, and exhibits sluggish actuation kinetics. In this study, alginate-exfoliated WS 2 nanosheets were incorporated into ice-template-polymerized PNiPAM hydrogels with the cellular microstructures which mimic plant cells, yet the prompt steerable actuation of animals. Because of the nanosheet-reinforced pore walls formed in situ in freezing polymerization and reasonable hierarchical water channels, this cellular hybrid hydrogel achieves super deformation speed (on the order of magnitude of 10° s), controllable deformation direction, and high near-infrared light responsiveness, offering an unprecedented platform of artificial muscles for various soft robotics and devices (e.g., rotator, microvalve, aquatic swimmer, and water-lifting filter).

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

Microfluidic viscometers for shear rheology of complex fluids and biofluids

PubMed Central

Wang, William S.; Vanapalli, Siva A.

2016-01-01

The rich diversity of man-made complex fluids and naturally occurring biofluids is opening up new opportunities for investigating their flow behavior and characterizing their rheological properties. Steady shear viscosity is undoubtedly the most widely characterized material property of these fluids. Although widely adopted, macroscale rheometers are limited by sample volumes, access to high shear rates, hydrodynamic instabilities, and interfacial artifacts. Currently, microfluidic devices are capable of handling low sample volumes, providing precision control of flow and channel geometry, enabling a high degree of multiplexing and automation, and integrating flow visualization and optical techniques. These intrinsic advantages of microfluidics have made it especially suitable for the steady shear rheology of complex fluids. In this paper, we review the use of microfluidics for conducting shear viscometry of complex fluids and biofluids with a focus on viscosity curves as a function of shear rate. We discuss the physical principles underlying different microfluidic viscometers, their unique features and limits of operation. This compilation of technological options will potentially serve in promoting the benefits of microfluidic viscometry along with evincing further interest and research in this area. We intend that this review will aid researchers handling and studying complex fluids in selecting and adopting microfluidic viscometers based on their needs. We conclude with challenges and future directions in microfluidic rheometry of complex fluids and biofluids. PMID:27478521

Electrogates for stop-and-go control of liquid flow in microfluidics

NASA Astrophysics Data System (ADS)

Arango, Y.; Temiz, Y.; Gökçe, O.; Delamarche, E.

2018-04-01

Diagnostics based on microfluidic devices necessitate specific reagents, flow conditions, and kinetics for optimal performance. Such an optimization is often achieved using assay-specific microfluidic chip designs or systems with external liquid pumps. Here, we present "electrogates" for stop-and-go control of flow of liquids in capillary-driven microfluidic chips by combining liquid pinning and electrowetting. Electrogates are simple to fabricate and efficient: a sample pipetted to a microfluidic chip flows autonomously in 15-μm-deep hydrophilic channels until the liquid meniscus is pinned at the edge of a 1.5-μm-deep trench patterned at the bottom of a rectangular microchannel. The flow can then be resumed by applying a DC voltage between the liquid and the trench via integrated electrodes. Using a trench geometry with a semicircular shape, we show that retention times longer than 30 min are achieved for various aqueous solutions such as biological buffers, artificial urine, and human serum. We studied the activation voltage and activation delay of electrogates using a chip architecture having 6 independent flow paths and experimentally showed that the flow can be resumed in less than 1 s for voltages smaller than 10 V, making this technique compatible with low-power and portable microfluidic systems. Electrogates therefore can make capillary-driven microfluidic chips very versatile by adding flow control in microfluidic channels in a flexible manner.

Rapid detection of hemagglutination using restrictive microfluidic channels equipped with waveguide-mode sensors

NASA Astrophysics Data System (ADS)

Ashiba, Hiroki; Fujimaki, Makoto; Awazu, Koichi; Fu, Mengying; Ohki, Yoshimichi; Tanaka, Torahiko; Makishima, Makoto

2016-02-01

Hemagglutination is utilized for various immunological assays, including blood typing and virus detection. Herein, we describe a method of rapid hemagglutination detection based on a microfluidic channel installed on an optical waveguide-mode sensor. Human blood samples mixed with hemagglutinating antibodies associated with different blood groups were injected into the microfluidic channel, and reflectance spectra of the samples were measured after stopping the flow. The agglutinated and nonagglutinated samples were distinguishable by the alterations in their reflectance spectra with time; the microfluidic channels worked as spatial restraints for agglutinated red blood cells. The demonstrated system allowed rapid hemagglutination detection within 1 min. The suitable height of the channels was also discussed.

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.

Note: A portable Raman analyzer for microfluidic chips based on a dichroic beam splitter for integration of imaging and signal collection light paths

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

Geng, Yijia; Xu, Shuping; Xu, Weiqing, E-mail: xuwq@jlu.edu.cn

An integrated and portable Raman analyzer featuring an inverted probe fixed on a motor-driving adjustable optical module was designed for the combination of a microfluidic system. It possesses a micro-imaging function. The inverted configuration is advantageous to locate and focus microfluidic channels. Different from commercial micro-imaging Raman spectrometers using manual switchable light path, this analyzer adopts a dichroic beam splitter for both imaging and signal collection light paths, which avoids movable parts and improves the integration and stability of optics. Combined with surface-enhanced Raman scattering technique, this portable Raman micro-analyzer is promising as a powerful tool for microfluidic analytics.

Exploiting an automated microfluidic hydrodynamic sequential injection system for determination of phosphate.

PubMed

Khongpet, Wanpen; Pencharee, Somkid; Puangpila, Chanida; Kradtap Hartwell, Supaporn; Lapanantnoppakhun, Somchai; Jakmunee, Jaroon

2018-01-15

A microfluidic hydrodynamic sequential injection (μHSI) spectrophotometric system was designed and fabricated. The system was built by laser engraving a manifold pattern on an acrylic block and sealing with another flat acrylic plate to form a microfluidic channel platform. The platform was incorporated with small solenoid valves to obtain a portable setup for programmable control of the liquid flow into the channel according to the HSI principle. The system was demonstrated for the determination of phosphate using a molybdenum blue method. An ascorbic acid, standard or sample, and acidic molybdate solutions were sequentially aspirated to fill the channel forming a stack zone before flowing to the detector. Under the optimum condition, a linear calibration graph in the range of 0.1-6mg P L -1 was obtained. The detection limit was 0.1mgL -1 . The system is compact (5.0mm thick, 80mm wide × 140mm long), durable, portable, cost-effective, and consumes little amount of chemicals (83μL each of molybdate and ascorbic acid, 133μL of the sample solution and 1.7mL of water carrier/run). It was applied for the determination of phosphate content in extracted soil samples. The percent recoveries of the analysis were obtained in the range of 91.2-107.3. The results obtained agreed well with those of the batch spectrophotometric method. Copyright © 2017 Elsevier B.V. All rights reserved.

Microfluidic device capable of medium recirculation for non-adherent cell culture

PubMed Central

Dixon, Angela R.; Rajan, Shrinidhi; Kuo, Chuan-Hsien; Bersano, Tom; Wold, Rachel; Futai, Nobuyuki; Takayama, Shuichi; Mehta, Geeta

2014-01-01

We present a microfluidic device designed for maintenance and culture of non-adherent mammalian cells, which enables both recirculation and refreshing of medium, as well as easy harvesting of cells from the device. We demonstrate fabrication of a novel microfluidic device utilizing Braille perfusion for peristaltic fluid flow to enable switching between recirculation and refresh flow modes. Utilizing fluid flow simulations and the human promyelocytic leukemia cell line, HL-60, non-adherent cells, we demonstrate the utility of this RECIR-REFRESH device. With computer simulations, we profiled fluid flow and concentration gradients of autocrine factors and found that the geometry of the cell culture well plays a key role in cell entrapping and retaining autocrine and soluble factors. We subjected HL-60 cells, in the device, to a treatment regimen of 1.25% dimethylsulfoxide, every other day, to provoke differentiation and measured subsequent expression of CD11b on day 2 and day 4 and tumor necrosis factor-alpha (TNF-α) on day 4. Our findings display perfusion sensitive CD11b expression, but not TNF-α build-up, by day 4 of culture, with a 1:1 ratio of recirculation to refresh flow yielding the greatest increase in CD11b levels. RECIR-REFRESH facilitates programmable levels of cell differentiation in a HL-60 non-adherent cell population and can be expanded to other types of non-adherent cells such as hematopoietic stem cells. PMID:24753733

Toward a solid-phase nucleic acid hybridization assay within microfluidic channels using immobilized quantum dots as donors in fluorescence resonance energy transfer.

PubMed

Chen, Lu; Algar, W Russ; Tavares, Anthony J; Krull, Ulrich J

2011-01-01

The optical properties and surface area of quantum dots (QDs) have made them an attractive platform for the development of nucleic acid biosensors based on fluorescence resonance energy transfer (FRET). Solid-phase assays based on FRET using mixtures of immobilized QD-oligonucleotide conjugates (QD biosensors) have been developed. The typical challenges associated with solid-phase detection strategies include non-specific adsorption, slow kinetics of hybridization, and sample manipulation. The new work herein has considered the immobilization of QD biosensors onto the surfaces of microfluidic channels in order to address these challenges. Microfluidic flow can be used to dynamically control stringency by adjustment of the potential in an electrokinetic-based microfluidics environment. The shearing force, Joule heating, and the competition between electroosmotic and electrophoretic mobilities allow the optimization of hybridization conditions, convective delivery of target to the channel surface to speed hybridization, amelioration of adsorption, and regeneration of the sensing surface. Microfluidic flow can also be used to deliver (for immobilization) and remove QD biosensors. QDs that were conjugated with two different oligonucleotide sequences were used to demonstrate feasibility. One oligonucleotide sequence on the QD was available as a linker for immobilization via hybridization with complementary oligonucleotides located on a glass surface within a microfluidic channel. A second oligonucleotide sequence on the QD served as a probe to transduce hybridization with target nucleic acid in a sample solution. A Cy3 label on the target was excited by FRET using green-emitting CdSe/ZnS QD donors and provided an analytical signal to explore this detection strategy. The immobilized QDs could be removed under denaturing conditions by disrupting the duplex that was used as the surface linker and thus allowed a new layer of QD biosensors to be re-coated within the channel for re-use of the microfluidic chip.

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.

Dielectrophoresis-based microfluidic platforms for cancer diagnostics.

PubMed

Chan, Jun Yuan; Ahmad Kayani, Aminuddin Bin; Md Ali, Mohd Anuar; Kok, Chee Kuang; Yeop Majlis, Burhanuddin; Hoe, Susan Ling Ling; Marzuki, Marini; Khoo, Alan Soo-Beng; Ostrikov, Kostya Ken; Ataur Rahman, Md; Sriram, Sharath

2018-01-01

The recent advancement of dielectrophoresis (DEP)-enabled microfluidic platforms is opening new opportunities for potential use in cancer disease diagnostics. DEP is advantageous because of its specificity, low cost, small sample volume requirement, and tuneable property for microfluidic platforms. These intrinsic advantages have made it especially suitable for developing microfluidic cancer diagnostic platforms. This review focuses on a comprehensive analysis of the recent developments of DEP enabled microfluidic platforms sorted according to the target cancer cell. Each study is critically analyzed, and the features of each platform, the performance, added functionality for clinical use, and the types of samples, used are discussed. We address the novelty of the techniques, strategies, and design configuration used in improving on existing technologies or previous studies. A summary of comparing the developmental extent of each study is made, and we conclude with a treatment of future trends and a brief summary.

Photo-actuation of liquids for light-driven microfluidics: state of the art and perspectives.

PubMed

Baigl, Damien

2012-10-07

Using light to control liquid motion is a new paradigm for the actuation of microfluidic systems. We review here the different principles and strategies to induce or control liquid motion using light, which includes the use of radiation pressure, optical tweezers, light-induced wettability gradients, the thermocapillary effect, photosensitive surfactants, the chromocapillary effect, optoelectrowetting, photocontrolled electroosmotic flows and optical dielectrophoresis. We analyze the performance of these approaches to control using light many kinds of microfluidic operations involving discrete pL- to μL-sized droplets (generation, driving, mixing, reaction, sorting) or fluid flows in microchannels (valve operation, injection, pumping, flow rate control). We show that a complete toolbox is now available to control microfluidic systems by light. We finally discuss the perspectives of digital optofluidics as well as microfluidics based on all optical fluidic chips and optically reconfigurable devices.

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.

CMOS Enabled Microfluidic Systems for Healthcare Based Applications.

PubMed

Khan, Sherjeel M; Gumus, Abdurrahman; Nassar, Joanna M; Hussain, Muhammad M

2018-04-01

With the increased global population, it is more important than ever to expand accessibility to affordable personalized healthcare. In this context, a seamless integration of microfluidic technology for bioanalysis and drug delivery and complementary metal oxide semiconductor (CMOS) technology enabled data-management circuitry is critical. Therefore, here, the fundamentals, integration aspects, and applications of CMOS-enabled microfluidic systems for affordable personalized healthcare systems are presented. Critical components, like sensors, actuators, and their fabrication and packaging, are discussed and reviewed in detail. With the emergence of the Internet-of-Things and the upcoming Internet-of-Everything for a people-process-data-device connected world, now is the time to take CMOS-enabled microfluidics technology to as many people as possible. There is enormous potential for microfluidic technologies in affordable healthcare for everyone, and CMOS technology will play a major role in making that happen. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

[Design and Optimization of Microfluidic Chips Used for Mixing Cryoprotectants].

PubMed

Zhou, Xinli; Yi, Xingyue; Zhou, Nanfeng; Yang, Yun

2016-06-01

Microfluidic chips can be used to realize continuous cryoprotectants(CPA)loading/unloading for oocytes,reducing osmotic damage and chemical toxicity of CPA.In this study,five different Y-shape microfluidic chips were fabricated to realize the continuous CPA loading/unloading.The effects of flow rate,entrance angle,aspect ratio and turning radius of microchannels on the mixing efficiency of microfluidic chips were analyzed quantitatively.The experimental results showed that with the decrease of flow rates,the increase of aspect ratios and the decrease of turning raradius of microchannel,the mixing length decreased and the mixing velocity was promoted,while the entrance angle had little effect on the mixing efficiency.However,the operating conditions and structural parameters of the chips in practical application should be determined based on an overall consideration of CPA loading/unloading time and machining accuracy.These results would provide a reference to the application of microfluidic chip in CPA mixing.

Single-cell analysis and sorting using droplet-based microfluidics.

PubMed

Mazutis, Linas; Gilbert, John; Ung, W Lloyd; Weitz, David A; Griffiths, Andrew D; Heyman, John A

2013-05-01

We present a droplet-based microfluidics protocol for high-throughput analysis and sorting of single cells. Compartmentalization of single cells in droplets enables the analysis of proteins released from or secreted by cells, thereby overcoming one of the major limitations of traditional flow cytometry and fluorescence-activated cell sorting. As an example of this approach, we detail a binding assay for detecting antibodies secreted from single mouse hybridoma cells. Secreted antibodies are detected after only 15 min by co-compartmentalizing single mouse hybridoma cells, a fluorescent probe and single beads coated with anti-mouse IgG antibodies in 50-pl droplets. The beads capture the secreted antibodies and, when the captured antibodies bind to the probe, the fluorescence becomes localized on the beads, generating a clearly distinguishable fluorescence signal that enables droplet sorting at ∼200 Hz as well as cell enrichment. The microfluidic system described is easily adapted for screening other intracellular, cell-surface or secreted proteins and for quantifying catalytic or regulatory activities. In order to screen ∼1 million cells, the microfluidic operations require 2-6 h; the entire process, including preparation of microfluidic devices and mammalian cells, requires 5-7 d.

A Multi-Phase Based Fluid-Structure-Microfluidic interaction sensor for Aerodynamic Shear Stress

NASA Astrophysics Data System (ADS)

Hughes, Christopher; Dutta, Diganta; Bashirzadeh, Yashar; Ahmed, Kareem; Qian, Shizhi

2014-11-01

A novel innovative microfluidic shear stress sensor is developed for measuring shear stress through multi-phase fluid-structure-microfluidic interaction. The device is composed of a microfluidic cavity filled with an electrolyte liquid. Inside the cavity, two electrodes make electrochemical velocimetry measurements of the induced convection. The cavity is sealed with a flexible superhydrophobic membrane. The membrane will dynamically stretch and flex as a result of direct shear cross-flow interaction with the seal structure, forming instability wave modes and inducing fluid motion within the microfluidic cavity. The shear stress on the membrane is measured by sensing the induced convection generated by membrane deflections. The advantages of the sensor over current MEMS based shear stress sensor technology are: a simplified design with no moving parts, optimum relationship between size and sensitivity, no gaps such as those created by micromachining sensors in MEMS processes. We present the findings of a feasibility study of the proposed sensor including wind-tunnel tests, microPIV measurements, electrochemical velocimetry, and simulation data results. The study investigates the sensor in the supersonic and subsonic flow regimes. Supported by a NASA SBIR phase 1 contract.

Single-cell analysis and sorting using droplet-based microfluidics

PubMed Central

Mazutis, Linas; Gilbert, John; Ung, W Lloyd; Weitz, David A; Griffiths, Andrew D; Heyman, John A

2014-01-01

We present a droplet-based microfluidics protocol for high-throughput analysis and sorting of single cells. compartmentalization of single cells in droplets enables the analysis of proteins released from or secreted by cells, thereby overcoming one of the major limitations of traditional flow cytometry and fluorescence-activated cell sorting. as an example of this approach, we detail a binding assay for detecting antibodies secreted from single mouse hybridoma cells. secreted antibodies are detected after only 15 min by co-compartmentalizing single mouse hybridoma cells, a fluorescent probe and single beads coated with anti-mouse IgG antibodies in 50-pl droplets. the beads capture the secreted antibodies and, when the captured antibodies bind to the probe, the fluorescence becomes localized on the beads, generating a clearly distinguishable fluorescence signal that enables droplet sorting at ~200 Hz as well as cell enrichment. the microfluidic system described is easily adapted for screening other intracellular, cell-surface or secreted proteins and for quantifying catalytic or regulatory activities. In order to screen ~1 million cells, the microfluidic operations require 2–6 h; the entire process, including preparation of microfluidic devices and mammalian cells, requires 5–7 d. PMID:23558786

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.

Advances in Testing Techniques for Digital Microfluidic Biochips

PubMed Central

Shukla, Vineeta; Hussin, Fawnizu Azmadi; Hamid, Nor Hisham; Zain Ali, Noohul Basheer

2017-01-01

With the advancement of digital microfluidics technology, applications such as on-chip DNA analysis, point of care diagnosis and automated drug discovery are common nowadays. The use of Digital Microfluidics Biochips (DMFBs) in disease assessment and recognition of target molecules had become popular during the past few years. The reliability of these DMFBs is crucial when they are used in various medical applications. Errors found in these biochips are mainly due to the defects developed during droplet manipulation, chip degradation and inaccuracies in the bio-assay experiments. The recently proposed Micro-electrode-dot Array (MEDA)-based DMFBs involve both fluidic and electronic domains in the micro-electrode cell. Thus, the testing techniques for these biochips should be revised in order to ensure proper functionality. This paper describes recent advances in the testing technologies for digital microfluidics biochips, which would serve as a useful platform for developing revised/new testing techniques for MEDA-based biochips. Therefore, the relevancy of these techniques with respect to testing of MEDA-based biochips is analyzed in order to exploit the full potential of these biochips. PMID:28749411

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

Nanomaterial-based Microfluidic Chips for the Capture and Detection of Circulating Tumor Cells.

PubMed

Sun, Duanping; Chen, Zuanguang; Wu, Minhao; Zhang, Yuanqing

2017-01-01

Circulating tumor cells (CTCs), a type of cancer cells that spreads from primary or metastatic tumors into the bloodstream, can lead to a new fatal metastasis. As a new type of liquid biopsy, CTCs have become a hot pursuit and detection of CTCs offers the possibility for early diagnosis of cancers, earlier evaluation of chemotherapeutic efficacy and cancer recurrence, and choice of individual sensitive anti-cancer drugs. The fundamental challenges of capturing and characterizing CTCs are the extremely low number of CTCs in the blood and the intrinsic heterogeneity of CTCs. A series of microfluidic devices have been proposed for the analysis of CTCs with automation capability, precise flow behaviors, and significant advantages over the conventional larger scale systems. This review aims to provide in-depth insights into CTCs analysis, including various nanomaterial-based microfluidic chips for the capture and detection of CTCs based on the specific biochemical and physical properties of CTCs. The current developmental trends and promising research directions in the establishment of microfluidic chips for the capture and detection of CTCs are also discussed.

Centrifugal Microfluidic System for Nucleic Acid Amplification and Detection

PubMed Central

Miao, Baogang; Peng, Niancai; Li, Lei; Li, Zheng; Hu, Fei; Zhang, Zengming; Wang, Chaohui

2015-01-01

We report here the development of a rapid PCR microfluidic system comprising a double-shaft turntable and centrifugal-based disc that rapidly drives the PCR mixture between chambers set at different temperatures, and the bidirectional flow improved the space utilization of the disc. Three heating resistors and thermistors maintained uniform, specific temperatures for the denaturation, annealing, and extension steps of the PCR. Infrared imaging showed that there was little thermal interference between reaction chambers; the system enabled the cycle number and reaction time of each step to be independently adjusted. To validate the function and efficiency of the centrifugal microfluidic system, a 350-base pair target gene from the hepatitis B virus was amplified and quantitated by fluorescence detection. By optimizing the cycling parameters, the reaction time was reduced to 32 min as compared to 120 min for a commercial PCR machine. DNA samples with concentrations ranging from 10 to 106 copies/mL could be quantitatively analyzed using this system. This centrifugal-based microfluidic platform is a useful system and possesses industrialization potential that can be used for portable diagnostics. PMID:26556354

Advances in Testing Techniques for Digital Microfluidic Biochips.

PubMed

Shukla, Vineeta; Hussin, Fawnizu Azmadi; Hamid, Nor Hisham; Zain Ali, Noohul Basheer

2017-07-27

With the advancement of digital microfluidics technology, applications such as on-chip DNA analysis, point of care diagnosis and automated drug discovery are common nowadays. The use of Digital Microfluidics Biochips (DMFBs) in disease assessment and recognition of target molecules had become popular during the past few years. The reliability of these DMFBs is crucial when they are used in various medical applications. Errors found in these biochips are mainly due to the defects developed during droplet manipulation, chip degradation and inaccuracies in the bio-assay experiments. The recently proposed Micro-electrode-dot Array (MEDA)-based DMFBs involve both fluidic and electronic domains in the micro-electrode cell. Thus, the testing techniques for these biochips should be revised in order to ensure proper functionality. This paper describes recent advances in the testing technologies for digital microfluidics biochips, which would serve as a useful platform for developing revised/new testing techniques for MEDA-based biochips. Therefore, the relevancy of these techniques with respect to testing of MEDA-based biochips is analyzed in order to exploit the full potential of these biochips.

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…

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.

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.

Absolute quantification of DNA methylation using microfluidic chip-based digital PCR.

PubMed

Wu, Zhenhua; Bai, Yanan; Cheng, Zule; Liu, Fangming; Wang, Ping; Yang, Dawei; Li, Gang; Jin, Qinghui; Mao, Hongju; Zhao, Jianlong

2017-10-15

Hypermethylation of CpG islands in the promoter region of many tumor suppressor genes downregulates their expression and in a result promotes tumorigenesis. Therefore, detection of DNA methylation status is a convenient diagnostic tool for cancer detection. Here, we reported a novel method for the integrative detection of methylation by the microfluidic chip-based digital PCR. This method relies on methylation-sensitive restriction enzyme HpaII, which cleaves the unmethylated DNA strands while keeping the methylated ones intact. After HpaII treatment, the DNA methylation level is determined quantitatively by the microfluidic chip-based digital PCR with the lower limit of detection equal to 0.52%. To validate the applicability of this method, promoter methylation of two tumor suppressor genes (PCDHGB6 and HOXA9) was tested in 10 samples of early stage lung adenocarcinoma and their adjacent non-tumorous tissues. The consistency was observed in the analysis of these samples using our method and a conventional bisulfite pyrosequencing. Combining high sensitivity and low cost, the microfluidic chip-based digital PCR method might provide a promising alternative for the detection of DNA methylation and early diagnosis of epigenetics-related diseases. Copyright © 2017 Elsevier B.V. All rights reserved.

Real-time detection and analysis of Whispering gallery mode resonance in high-throughput flowing monodisperse microdroplets

NASA Astrophysics Data System (ADS)

El Abed, Abdel I.; Taly, Valérie

2013-11-01

We investigate light coupling into highly monodisperse liquid microdroplets, which are produced and manipulated at kHz rates in a microfluidic device. We show that such coupling leads to Whispering gallery mode resonances (WGMs) which are detected and analyzed versus time during the fast displacement of microdroplets into the microfluidic channel. Our results show that droplet-based microfluidics may be applied advantageously in the promising field of high-throughput label-free biosensing.

Graphene-based inline pressure sensor integrated with microfluidic elastic tube

NASA Astrophysics Data System (ADS)

Inoue, Nagisa; Onoe, Hiroaki

2018-01-01

We propose an inline pressure sensor composed of a polydimethylsiloxane (PDMS) microfluidic tube integrated with graphene sheets. The PDMS tube was fabricated through molding, and a multilayered graphene sheet was transferred on the surface of the PDMS tube. The pressure inside the tube was monitored using the changes in the electrical resistance of the transferred graphene. The proposed pressure sensor could be suitable for precise pressure measurement for a small amount of fluid in microfluidic systems including organ-on-a-chip devices.

Microfluidic Transduction Harnesses Mass Transport Principles to Enhance Gene Transfer Efficiency.

PubMed

Tran, Reginald; Myers, David R; Denning, Gabriela; Shields, Jordan E; Lytle, Allison M; Alrowais, Hommood; Qiu, Yongzhi; Sakurai, Yumiko; Li, William C; Brand, Oliver; Le Doux, Joseph M; Spencer, H Trent; Doering, Christopher B; Lam, Wilbur A

2017-10-04

Ex vivo gene therapy using lentiviral vectors (LVs) is a proven approach to treat and potentially cure many hematologic disorders and malignancies but remains stymied by cumbersome, cost-prohibitive, and scale-limited production processes that cannot meet the demands of current clinical protocols for widespread clinical utilization. However, limitations in LV manufacture coupled with inefficient transduction protocols requiring significant excess amounts of vector currently limit widespread implementation. Herein, we describe a microfluidic, mass transport-based approach that overcomes the diffusion limitations of current transduction platforms to enhance LV gene transfer kinetics and efficiency. This novel ex vivo LV transduction platform is flexible in design, easy to use, scalable, and compatible with standard cell transduction reagents and LV preparations. Using hematopoietic cell lines, primary human T cells, primary hematopoietic stem and progenitor cells (HSPCs) of both murine (Sca-1 + ) and human (CD34 + ) origin, microfluidic transduction using clinically processed LVs occurs up to 5-fold faster and requires as little as one-twentieth of LV. As an in vivo validation of the microfluidic-based transduction technology, HSPC gene therapy was performed in hemophilia A mice using limiting amounts of LV. Compared to the standard static well-based transduction protocols, only animals transplanted with microfluidic-transduced cells displayed clotting levels restored to normal. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

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.

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.

Microfluidics and Cancer: Are we there yet?

PubMed Central

Zhang, Jennifer Zhuo; Nagrath, Sunitha

2013-01-01

More than two decades ago, microfluidics began to show its impact in biological research. Since then, the field of microfluidics has evolving rapidly. Cancer is one of the leading causes of death worldwide. Microfluidics holds great promise in cancer diagnosis and also serves as an emerging tool for understanding cancer biology. Microfluidics can be valuable for cancer investigation due to its high sensitivity, high throughput, less material-consumption, low cost, and enhanced spatio-temporal control. The physical laws on microscale offer an advantage enabling the control of physics, biology, chemistry and physiology at cellular level. Furthermore, microfluidic based platforms are portable and can be easily designed for point-of-care diagnostics. Developing and applying the state of the art microfluidic technologies to address the unmet challenges in cancer can expand the horizons of not only fundamental biology but also the management of disease and patient care. Despite the various microfluidic technologies available in the field, few have been tested clinically, which can be attributed to the various challenges existing in bridging the gap between the emerging technology and real world applications. We present a review of role of microlfuidcs in cancer research, including the history, recent advances and future directions to explore where the field stand currently in addressing complex clinical challenges and future of it. This review identifies four critical areas in cancer research, in which microfluidics can change the current paradigm. These include cancer cell isolation, molecular diagnostics, tumor biology and high-throughput screening for therapeutics. In addition, some of our lab’s current research is presented in the corresponding sections. PMID:23358873

Enabling Technologies for Microfluidic Flow Control and Detection

NASA Astrophysics Data System (ADS)

Leslie, Daniel Christopher

Advances in microfluidic technologies have expanded conventional chemical and biological techniques to the point where we can envision rapid, inexpensive and portable analysis. Among the numerous challenges in the development of portable, chip-based technologies are simple flow control and detection strategies, which will be essential to widespread acceptance and implementation at both the point-of-care and in locales with limited facilities/resources. The research presented in this dissertation is focused on the development of precise flow control techniques and new, simplified detection technologies aimed at addressing these challenges. An introduction to the concepts important to microfluidics and a brief history to the field are presented in Chapter 1. Chapter 2 will present the development of a technique for the precise control of small volumes of liquids, where well-studied electrical circuit concepts are employed to create frequency-dependent microfluidic circuits. In this system, elastomeric thin films act as fluidic capacitors and diodes, which, when combined with resistors (channels), make fluidic circuits that are described by analytical models. Metering of two separate chemical inputs with a single oscillatory pneumatic control line is demonstrated by combining simple fluidic circuits (i.e., band-pass filters) to significantly reduce the external hardware required for microfluidic flow control. In order to quantify multiple flow profiles in microfluidic circuits, a novel multiplexed flow measurement method using visible dyes is introduced in Chapter 3 and rapidly determines individual flow in connected channels, post-fabrication device quality and solution viscosity. Another thrust of this dissertation research has been to develop miniaturized bioanalytical systems. Chapter 4 describes the adaption of a nucleic-acid-tagged antibody protein detection reaction to a microfluidic platform for detection of down to 5 E. coli O157:H7 cells. Furthermore, a completely non-contact temperature control platform is developed in Chapter 5 for forensic human identification reactions, based on interferometric temperature sensing and infrared-mediated heating, which simplifies the microfluidic device and its operation. Finally, possible future directions are outlined in Chapter 6 including further simplification of microfluidic instrumentation.

Microfluidic-Based Platform for Universal Sample Preparation and Biological Assays Automation for Life-Sciences Research and Remote Medical Applications

NASA Astrophysics Data System (ADS)

Brassard, D.; Clime, L.; Daoud, J.; Geissler, M.; Malic, L.; Charlebois, D.; Buckley, N.; Veres, T.

2018-02-01

An innovative centrifugal microfluidic universal platform for remote bio-analytical assays automation required in life-sciences research and medical applications, including purification and analysis from body fluids of cellular and circulating markers.

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

Carbon nanotube sensors integrated inside a microfluidic channel for water quality monitoring

NASA Astrophysics Data System (ADS)

Liu, Yu; Li, Xinghui; Dokmeci, Mehmet R.; Wang, Ming L.

2011-04-01

Single-walled carbon nanotubes (SWNTs) with their unique electrical properties and large surface area are remarkable materials for detecting low concentration of toxic and hazardous chemicals (both from the gaseous and liquid phases). Ionic adsorbates in water will attach on to SWNTs and drastically alter their electrical properties. Several SWNTs based pH and chemical sensors have been demonstrated. However, most of them require external components to test and analyze the response of SWNTs to ions inside the liquid samples. Here, we report a water quality monitoring sensor composed of SWNTs integrated inside microfluidic channels and on-chip testing components with a wireless transmission board. To detect multiple analytes in water requires the functionalization of SWNTs with different chemistries. In addition, microfluidic channels are used to guide liquid samples to individual nanotube sensors in an efficient manner. Furthermore, the microfluidic system enables sample mixing and separation before testing. To realize the nanosensors, first microelectrodes were fabricated on an oxidized silicon substrate. Next, PDMS micro channels were fabricated and bonded on the substrate. These channels can be incorporated with a microfluidic system which can be designed to manipulate different analytes for specific molecule detection. Low temperature, solution based Dielectrophoretic (DEP) assembly was conducted inside this microfluidic system which successfully bridged SWNTs between the microelectrodes. The SWNTs sensors were next characterized with different pH buffer solutions. The resistance of SWNTs had a linearly increase as the pH values ranged from 5 to 8. The nanosensor incorporated within the microfluidic system is a versatile platform and can be utilized to detect numerous water pollutants, including toxic organics and microorganisms down to low concentrations. On-chip processing and wireless transmission enables the realization of a full autonomous system for real time monitoring of water quality.

Controlling nonspecific protein adsorption in a plug-based microfluidic system by controlling interfacial chemistry using fluorous-phase surfactants.

PubMed

Roach, L Spencer; Song, Helen; Ismagilov, Rustem F

2005-02-01

Control of surface chemistry and protein adsorption is important for using microfluidic devices for biochemical analysis and high-throughput screening assays. This paper describes the control of protein adsorption at the liquid-liquid interface in a plug-based microfluidic system. The microfluidic system uses multiphase flows of immiscible fluorous and aqueous fluids to form plugs, which are aqueous droplets that are completely surrounded by fluorocarbon oil and do not come into direct contact with the hydrophobic surface of the microchannel. Protein adsorption at the aqueous-fluorous interface was controlled by using surfactants that were soluble in fluorocarbon oil but insoluble in aqueous solutions. Three perfluorinated alkane surfactants capped with different functional groups were used: a carboxylic acid, an alcohol, and a triethylene glycol group that was synthesized from commercially available materials. Using complementary methods of analysis, adsorption was characterized for several proteins (bovine serum albumin (BSA) and fibrinogen), including enzymes (ribonuclease A (RNase A) and alkaline phosphatase). These complementary methods involved characterizing adsorption in microliter-sized droplets by drop tensiometry and in nanoliter plugs by fluorescence microscopy and kinetic measurements of enzyme catalysis. The oligoethylene glycol-capped surfactant prevented protein adsorption in all cases. Adsorption of proteins to the carboxylic acid-capped surfactant in nanoliter plugs could be described by using the Langmuir model and tensiometry results for microliter drops. The microfluidic system was fabricated using rapid prototyping in poly(dimethylsiloxane) (PDMS). Black PDMS microfluidic devices, fabricated by curing a suspension of charcoal in PDMS, were used to measure the changes in fluorescence intensity more sensitively. This system will be useful for microfluidic bioassays, enzymatic kinetics, and protein crystallization, because it does not require surface modification during fabrication to control surface chemistry and protein adsorption.

Digital microfluidics: Droplet based logic gates

NASA Astrophysics Data System (ADS)

Cheow, Lih Feng; Yobas, Levent; Kwong, Dim-Lee

2007-01-01

The authors present microfluidic logic gates based on two-phase flows at low Reynold's number. The presence and the absence of a dispersed phase liquid (slug) in a continuous phase liquid represent 1 and 0, respectively. The working principle of these devices is based on the change in hydrodynamic resistance for a channel containing droplets. Logical operations including AND, OR, and NOT are demonstrated, and may pave the way for microfludic system automation and computation.

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

Microfluidic acoustophoretic force based low-concentration oil separation and detection from the environment.

PubMed

Wang, Han; Liu, Zhongzheng; Kim, Sungman; Koo, Chiwan; Cho, Younghak; Jang, Dong-Young; Kim, Yong-Joe; Han, Arum

2014-03-07

Detecting and quantifying extremely low concentrations of oil from the environment have broad applications in oil spill monitoring in ocean and coastal areas as well as in oil leakage monitoring on land. Currently available methods for low-concentration oil detection are bulky or costly with limited sensitivities. Thus they are difficult to be used as portable and field-deployable detectors in the case of oil spills or for monitoring the long-term effects of dispersed oil on marine and coastal ecosystems. Here, we present a low-concentration oil droplet trapping and detection microfluidic system based on the acoustophoresis phenomenon where oil droplets in water having a negative acoustic contrast factor move towards acoustic pressure anti-nodes. By trapping oil droplets from water samples flowing through a microfluidic channel, even very low concentrations of oil droplets can be concentrated to a detectable level for further analyses, which is a significant improvement over currently available oil detection systems. Oil droplets in water were successfully trapped and accumulated in a circular acoustophoretic trapping chamber of the microfluidic device and detected using a custom-built compact fluorescent detector based on the natural fluorescence of the trapped crude oil droplets. After the on-line detection, crude oil droplets released from the trapping chamber were successfully separated into a collection outlet by acoustophoretic force for further off-chip analyses. The developed microfluidic system provides a new way of trapping, detecting, and separating low-concentration crude oil from environmental water samples and holds promise as a low-cost field-deployable oil detector with extremely high sensitivity. The microfluidic system and operation principle are expected to be utilized in a wide range of applications where separating, concentrating, and detecting small particles having a negative acoustic contrast factor are required.

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.

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.

Controlled growth of silica-titania hybrid functional nanoparticles through a multistep microfluidic approach.

PubMed

Shiba, K; Sugiyama, T; Takei, T; Yoshikawa, G

2015-11-11

Silica/titania-based functional nanoparticles were prepared through controlled nucleation of titania and subsequent encapsulation by silica through a multistep microfluidic approach, which was successfully applied to obtaining aminopropyl-functionalized silica/titania nanoparticles for a highly sensitive humidity sensor.

Flexible metal patterning in glass microfluidic structures using femtosecond laser direct-write ablation followed by electroless plating

NASA Astrophysics Data System (ADS)

Xu, Jian; Midorikawa, Katsumi; Sugioka, Koji

2014-03-01

A simple and flexible technique for integrating metal micropatterns into glass microfluidic structures based on threedimensional femtosecond laser microfabrication is presented. Femtosecond laser direct writing followed by thermal treatment and successive chemical etching allows us to fabricate three-dimensional microfluidic structures such as microchannels and microreservoirs inside photosensitive glass. Then, the femtosecond laser direct-write ablation followed by electroless metal plating enables space-selective deposition of patterned metal films on desired locations of internal walls of the fabricated microfluidic structures. The developed technique is applied to integrate a metal microheater into a glass microchannel to control the temperature of liquid samples in the channel, which can be used as a microreactor for enhancement of chemical reactions.

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.

Microfluidic automation using elastomeric valves and droplets: reducing reliance on external controllers.

PubMed

Kim, Sung-Jin; Lai, David; Park, Joong Yull; Yokokawa, Ryuji; Takayama, Shuichi

2012-10-08

This paper gives an overview of elastomeric valve- and droplet-based microfluidic systems designed to minimize the need of external pressure to control fluid flow. This Concept article introduces the working principle of representative components in these devices along with relevant biochemical applications. This is followed by providing a perspective on the roles of different microfluidic valves and systems through comparison of their similarities and differences with transistors (valves) and systems in microelectronics. Despite some physical limitation of drawing analogies from electronic circuits, automated microfluidic circuit design can gain insights from electronic circuits to minimize external control units, while implementing high-complexity and high-throughput analysis. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Evaluation of microfluidic channels with optical coherence tomography

NASA Astrophysics Data System (ADS)

Czajkowski, J.; Prykäri, T.; Alarousu, E.; Lauri, J.; Myllylä, R.

2010-11-01

Application of time domain, ultra high resolution optical coherence tomography (UHR-OCT) in evaluation of microfluidic channels is demonstrated. Presented study was done using experimental UHR-OCT device based on a Kerr-lens mode locked Ti:sapphire femtosecond laser, a photonic crystal fibre and modified, free-space Michelson interferometer. To show potential of the technique, microfluidic chip fabricated by VTT Center for Printed Intelligence (Oulu, Finland) was measured. Ability for full volumetric reconstruction in non-contact manner enabled complete characterization of closed entity of a microfluidic channel without contamination and harm for the sample. Measurement, occurring problems, and methods of postprocessing for raw data are described. Results present completely resolved physical structure of the channel, its spatial dimensions, draft angles and evaluation of lamination quality.

Recent Advancements towards Full-System Microfluidics

PubMed Central

Miled, Amine

2017-01-01

Microfluidics is quickly becoming a key technology in an expanding range of fields, such as medical sciences, biosensing, bioactuation, chemical synthesis, and more. This is helping its transformation from a promising R&D tool to commercially viable technology. Fuelling this expansion is the intensified focus on automation and enhanced functionality through integration of complex electrical control, mechanical properties, in situ sensing and flow control. Here we highlight recent contributions to the Sensors Special Issue series called “Microfluidics-Based Microsystem Integration Research” under the following categories: (i) Device fabrication to support complex functionality; (ii) New methods for flow control and mixing; (iii) Towards routine analysis and point of care applications; (iv) In situ characterization; and (v) Plug and play microfluidics. PMID:28757587

Microfluidic tools toward industrial biotechnology.

PubMed

Oliveira, Aline F; Pessoa, Amanda C S N; Bastos, Reinaldo G; de la Torre, Lucimara G

2016-11-01

Microfluidics is a technology that operates with small amounts of fluids and makes possible the investigation of cells, enzymes, and biomolecules and encapsulation of biocatalysts in a greater variety of conditions than permitted using conventional methods. This review discusses technological possibilities that can be applied in the field of industrial biotechnology, presenting the principal definitions and fundamental aspects of microfluidic parameters to better understand advanced approaches. Specifically, concentration gradient generators, droplet-based microfluidics, and microbioreactors are explored as useful tools that can contribute to industrial biotechnology. These tools present potential applications, inclusive as commercial platforms to optimizing in bioprocesses development as screening cells, encapsulating biocatalysts, and determining critical kinetic parameters. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:1372-1389, 2016. © 2016 American Institute of Chemical Engineers.

Dissecting enzyme function with microfluidic-based deep mutational scanning.

PubMed

Romero, Philip A; Tran, Tuan M; Abate, Adam R

2015-06-09

Natural enzymes are incredibly proficient catalysts, but engineering them to have new or improved functions is challenging due to the complexity of how an enzyme's sequence relates to its biochemical properties. Here, we present an ultrahigh-throughput method for mapping enzyme sequence-function relationships that combines droplet microfluidic screening with next-generation DNA sequencing. We apply our method to map the activity of millions of glycosidase sequence variants. Microfluidic-based deep mutational scanning provides a comprehensive and unbiased view of the enzyme function landscape. The mapping displays expected patterns of mutational tolerance and a strong correspondence to sequence variation within the enzyme family, but also reveals previously unreported sites that are crucial for glycosidase function. We modified the screening protocol to include a high-temperature incubation step, and the resulting thermotolerance landscape allowed the discovery of mutations that enhance enzyme thermostability. Droplet microfluidics provides a general platform for enzyme screening that, when combined with DNA-sequencing technologies, enables high-throughput mapping of enzyme sequence space.

Quantum dot-based microfluidic biosensor for cancer detection

NASA Astrophysics Data System (ADS)

Ghrera, Aditya Sharma; Pandey, Chandra Mouli; Ali, Md. Azahar; Malhotra, Bansi Dhar

2015-05-01

We report results of the studies relating to fabrication of an impedimetric microfluidic-based nucleic acid sensor for quantification of DNA sequences specific to chronic myelogenous leukemia (CML). The sensor chip is prepared by patterning an indium-tin-oxide (ITO) coated glass substrate via wet chemical etching method followed by sealing with polydimethylsiloxane (PDMS) microchannel for fluid control. The fabricated microfluidic chip comprising of a patterned ITO substrate is modified by depositing cadmium selenide quantum dots (QCdSe) via Langmuir-Blodgett technique. Further, the QCdSe surface has been functionalized with specific DNA probe for CML detection. The probe DNA functionalized QCdSe integrated miniaturized system has been used to monitor target complementary DNA concentration by measuring the interfacial charge transfer resistance via hybridization. The presence of complementary DNA in buffer solution significantly results in decreased electro-conductivity of the interface due to presence of a charge barrier for transport of the redox probe ions. The microfluidic DNA biosensor exhibits improved linearity in the concentration range of 10-15 M to 10-11 M.

A Laminar Flow-Based Microfluidic Tesla Pump via Lithography Enabled 3D Printing.

PubMed

Habhab, Mohammed-Baker; Ismail, Tania; Lo, Joe Fujiou

2016-11-23

Tesla turbine and its applications in power generation and fluid flow were demonstrated by Nicholas Tesla in 1913. However, its real-world implementations were limited by the difficulty to maintain laminar flow between rotor disks, transient efficiencies during rotor acceleration, and the lack of other applications that fully utilize the continuous flow outputs. All of the aforementioned limits of Tesla turbines can be addressed by scaling to the microfluidic flow regime. Demonstrated here is a microscale Tesla pump designed and fabricated using a Digital Light Processing (DLP) based 3D printer with 43 µm lateral and 30 µm thickness resolutions. The miniaturized pump is characterized by low Reynolds number of 1000 and a flow rate of up to 12.6 mL/min at 1200 rpm, unloaded. It is capable of driving a mixer network to generate microfluidic gradient. The continuous, laminar flow from Tesla turbines is well-suited to the needs of flow-sensitive microfluidics, where the integrated pump will enable numerous compact lab-on-a-chip applications.

Understanding thread properties for red blood cell antigen assays: weak ABO blood typing.

PubMed

Nilghaz, Azadeh; Zhang, Liyuan; Li, Miaosi; Ballerini, David R; Shen, Wei

2014-12-24

"Thread-based microfluidics" research has so far focused on utilizing and manipulating the wicking properties of threads to form controllable microfluidic channels. In this study we aim to understand the separation properties of threads, which are important to their microfluidic detection applications for blood analysis. Confocal microscopy was utilized to investigate the effect of the microscale surface morphologies of fibers on the thread's separation efficiency of red blood cells. We demonstrated the remarkably different separation properties of threads made using silk and cotton fibers. Thread separation properties dominate the clarity of blood typing assays of the ABO groups and some of their weak subgroups (Ax and A3). The microfluidic thread-based analytical devices (μTADs) designed in this work were used to accurately type different blood samples, including 89 normal ABO and 6 weak A subgroups. By selecting thread with the right surface morphology, we were able to build μTADs capable of providing rapid and accurate typing of the weak blood groups with high clarity.

Generation of microfluidic flow using an optically assembled and magnetically driven microrotor

NASA Astrophysics Data System (ADS)

Köhler, J.; Ghadiri, R.; Ksouri, S. I.; Guo, Q.; Gurevich, E. L.; Ostendorf, A.

2014-12-01

The key components in microfluidic systems are micropumps, valves and mixers. Depending on the chosen technology, the realization of these microsystems often requires rotational and translational control of subcomponents. The manufacturing of such active components as well as the driving principle are still challenging tasks. A promising all-optical approach could be the combination of laser direct writing and actuation based on optical forces. However, when higher actuation velocities are required, optical driving might be too slow. Hence, a novel approach based on optical assembling of microfluidic structures and subsequent magnetic actuation is proposed. By applying the optical assembly of microspherical building blocks as the manufacturing method and magnetic actuation, a microrotor was successfully fabricated and tested within a microfluidic channel. The resulting fluid flow was characterized by introducing an optically levitated measuring probe particle. Finally, a freely moving tracer particle visualizes the generated flow. The tracer particle analysis shows average velocities of 0.4-0.5 µm s-1 achieved with the presented technology.

Microfluidics‐based 3D cell culture models: Utility in novel drug discovery and delivery research

PubMed Central

Gupta, Nilesh; Liu, Jeffrey R.; Patel, Brijeshkumar; Solomon, Deepak E.; Vaidya, Bhuvaneshwar

2016-01-01

Abstract The implementation of microfluidic devices within life sciences has furthered the possibilities of both academic and industrial applications such as rapid genome sequencing, predictive drug studies, and single cell manipulation. In contrast to the preferred two‐dimensional cell‐based screening, three‐dimensional (3D) systems have more in vivo relevance as well as ability to perform as a predictive tool for the success or failure of a drug screening campaign. 3D cell culture has shown an adaptive response to the recent advancements in microfluidic technologies which has allowed better control over spheroid sizes and subsequent drug screening studies. In this review, we highlight the most significant developments in the field of microfluidic 3D culture over the past half‐decade with a special focus on their benefits and challenges down the lane. With the newer technologies emerging, implementation of microfluidic 3D culture systems into the drug discovery pipeline is right around the bend. PMID:29313007

Fluid delivery manifolds and microfluidic systems

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

Renzi, Ronald F.; Sommer, Gregory J.; Singh, Anup K.

2017-02-28

Embodiments of fluid distribution manifolds, cartridges, and microfluidic systems are described herein. Fluid distribution manifolds may include an insert member and a manifold base and may define a substantially closed channel within the manifold when the insert member is press-fit into the base. Cartridges described herein may allow for simultaneous electrical and fluidic interconnection with an electrical multiplex board and may be held in place using magnetic attraction.

Application of microfluidic technologies to human assisted reproduction

PubMed Central

Takayama, Shuichi

2017-01-01

Abstract Microfluidics can be considered both a science and a technology. It is defined as the study of fluid behavior at a sub-microliter level and the investigation into its application to cell biology, chemistry, genetics, molecular biology and medicine. There are at least two characteristics of microfluidics, mechanical and biochemical, which can be influential in the field of mammalian gamete and preimplantation embryo biology. These microfluidic characteristics can assist in basic biological studies on sperm, oocyte and preimplantation embryo structure, function and environment. The mechanical and biochemical characteristics of microfluidics may also have practical and/or technical application(s) to assisted reproductive technologies (ART) in rodents, domestic species, endangered species and humans. This review will consider data in mammals, and when available humans, addressing the potential application(s) of microfluidics to assisted reproduction. There are numerous sequential steps in the clinical assisted reproductive laboratory process that work, yet could be improved. Cause and effect relations of procedural inefficiencies can be difficult to identify and/or remedy. Data will be presented that consider microfluidic applications to sperm isolation, oocyte cumulus complex isolation, oocyte denuding, oocyte mechanical manipulation, conventional insemination, intracytoplasmic sperm injection, embryo culture, embryo analysis and oocyte and embryo cryopreservation. While these studies have progressed in animal models, data with human gametes and embryos are significantly lacking. These data from clinical trials are requisite for making future evidence-based decisions regarding the application of microfluidics in human ART. PMID:28130394

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.

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.

Biocompatible fluorinated polyglycerols for droplet microfluidics as an alternative to PEG-based copolymer surfactants.

PubMed

Wagner, Olaf; Thiele, Julian; Weinhart, Marie; Mazutis, Linas; Weitz, David A; Huck, Wilhelm T S; Haag, Rainer

2016-01-07

In droplet-based microfluidics, non-ionic, high-molecular weight surfactants are required to stabilize droplet interfaces. One of the most common structures that imparts stability as well as biocompatibility to water-in-oil droplets is a triblock copolymer surfactant composed of perfluoropolyether (PFPE) and polyethylene glycol (PEG) blocks. However, the fast growing applications of microdroplets in biology would benefit from a larger choice of specialized surfactants. PEG as a hydrophilic moiety, however, is a very limited tool in surfactant modification as one can only vary the molecular weight and chain-end functionalization. In contrast, linear polyglycerol offers further side-chain functionalization to create custom-tailored, biocompatible droplet interfaces. Herein, we describe the synthesis and characterization of polyglycerol-based triblock surfactants with tailored side-chain composition, and exemplify their application in cell encapsulation and in vitro gene expression studies in droplet-based microfluidics.

Droplet-based microfluidic washing module for magnetic particle-based assays

PubMed Central

Lee, Hun; Xu, Linfeng; Oh, Kwang W.

2014-01-01

In this paper, we propose a continuous flow droplet-based microfluidic platform for magnetic particle-based assays by employing in-droplet washing. The droplet-based washing was implemented by traversing functionalized magnetic particles across a laterally merged droplet from one side (containing sample and reagent) to the other (containing buffer) by an external magnetic field. Consequently, the magnetic particles were extracted to a parallel-synchronized train of washing buffer droplets, and unbound reagents were left in an original train of sample droplets. To realize the droplet-based washing function, the following four procedures were sequentially carried in a droplet-based microfluidic device: parallel synchronization of two trains of droplets by using a ladder-like channel network; lateral electrocoalescence by an electric field; magnetic particle manipulation by a magnetic field; and asymmetrical splitting of merged droplets. For the stable droplet synchronization and electrocoalescence, we optimized droplet generation conditions by varying the flow rate ratio (or droplet size). Image analysis was carried out to determine the fluorescent intensity of reagents before and after the washing step. As a result, the unbound reagents in sample droplets were significantly removed by more than a factor of 25 in the single washing step, while the magnetic particles were successfully extracted into washing buffer droplets. As a proof-of-principle, we demonstrate a magnetic particle-based immunoassay with streptavidin-coated magnetic particles and fluorescently labelled biotin in the proposed continuous flow droplet-based microfluidic platform. PMID:25379098

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.

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.

Chemistry in Microfluidic Channels

ERIC Educational Resources Information Center

Chia, Matthew C.; Sweeney, Christina M.; Odom, Teri W.

2011-01-01

General chemistry introduces principles such as acid-base chemistry, mixing, and precipitation that are usually demonstrated in bulk solutions. In this laboratory experiment, we describe how chemical reactions can be performed in a microfluidic channel to show advanced concepts such as laminar fluid flow and controlled precipitation. Three sets of…

Undergraduate Laboratory Module for Implementing ELISA on the High Performance Microfluidic Platform

ERIC Educational Resources Information Center

Giri, Basant; Peesara, Ravichander R.; Yanagisawa, Naoki; Dutta, Debashis

2015-01-01

Implementing enzyme-linked immunosorbent assays (ELISA) in microchannels offers several advantages over its traditional microtiter plate-based format, including a reduced sample volume requirement, shorter incubation period, and greater sensitivity. Moreover, microfluidic ELISA platforms are inexpensive to fabricate and allow integration of…

Bead-based microfluidic immunoassay for diagnosis of Johne's disease

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

Wadhwa, Ashutosh; Foote, Robert; Shaw, Robert W

2012-01-01

Microfluidics technology offers a platform for development of point-of-care diagnostic devices for various infectious diseases. In this study, we examined whether serodiagnosis of Johne s disease (JD) can be conducted in a bead-based microfluidic assay system. Magnetic micro-beads were coated with antigens of the causative agent of JD, Mycobacterium avium subsp. paratuberculosis. The antigen-coated beads were incubated with serum samples of JD-positive or negative serum samples and then with a fluorescently-labeled secondary antibody (SAB). To confirm binding of serum antibodies to the antigen, the beads were subjected to flow cytometric analysis. Different conditions (dilutions of serum and SAB, types ofmore » SAB, and types of magnetic beads) were optimized for a great degree of differentiation between the JD-negative and JD-positive samples. Using the optimized conditions, we tested a well-classified set of 155 serum samples from JD negative and JD-positive cattle by using the bead-based flow cytometric assay. Of 105 JD-positive samples, 63 samples (60%) showed higher antibody binding levels than a cut-off value determined by using antibody binding levels of JD-negative samples. In contrast, only 43-49 JD-positive samples showed higher antibody binding levels than the cut-off value when the samples were tested by commercially-available immunoassays. Microfluidic assays were performed by magnetically immobilizing a number of beads within a microchannel of a glass microchip and detecting antibody on the collected beads by laser-induced fluorescence. Antigen-coated magnetic beads treated with bovine serum sample and fluorescently-labeled SAB were loaded into a microchannel to measure the fluorescence (reflecting level of antibody binding) on the beads in the microfluidic system. When the results of five bovine serum samples obtained with the system were compared to those obtained with the flow cytometer, a high level of correlation (linear regression, r2 = 0.994) was observed. In a further experiment, we magnetically immobilized antigen-coated beads in a microchannel, reacted the beads with serum and SAB in the channel, and detected antibody binding to the beads in the microfluidic system. A strong antibody binding in JD-positive serum was detected, whereas there was only negligible binding in negative control experiments. Our data suggest that the bead-based microfluidic system may form a basis for development of an on-site serodiagnosis of JD. Key Words: Mycobacterium avium ssp. paratuberculosis, Johne s disease, microfluidics, lab-on-a-chip.« less

A microfluidic paper-based analytical device for the assay of albumin-corrected fructosamine values from whole blood samples.

PubMed

Boonyasit, Yuwadee; Laiwattanapaisal, Wanida

2015-01-01

A method for acquiring albumin-corrected fructosamine values from whole blood using a microfluidic paper-based analytical system that offers substantial improvement over previous methods is proposed. The time required to quantify both serum albumin and fructosamine is shortened to 10 min with detection limits of 0.50 g dl(-1) and 0.58 mM, respectively (S/N = 3). The proposed system also exhibited good within-run and run-to-run reproducibility. The results of the interference study revealed that the acceptable recoveries ranged from 95.1 to 106.2%. The system was compared with currently used large-scale methods (n = 15), and the results demonstrated good agreement among the techniques. The microfluidic paper-based system has the potential to continuously monitor glycemic levels in low resource settings.

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

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.

An oxidized liquid metal-based microfluidic platform for tunable electronic device applications.

PubMed

Li, Guangyong; Parmar, Mitesh; Lee, Dong-Weon

2015-02-07

Easy movement of oxidized Galinstan in microfluidic channels is a promising way for the wide application of the non-toxic liquid metal. In this paper, two different surface modification techniques (physical and chemical) are reported, which dramatically improve the non-wetting characteristics of oxidized Galinstan in the microfluidic channel. In the physical technique, normal paper textures are transferred to the inner wall of polydimethylsiloxane (PDMS) channels and four types of nanoparticles are then coated on the surface of the wall for further improvement of the non-wetting characteristics. Highest advancing angle of 167° and receding angle of 151° are achieved on the paper-textured PDMS with titanium oxide (TiO2) nanoparticles. In the chemical technique, three types of inorganic acids are employed to generate dual-scale structures on the PDMS surface. The inner wall surface treated with sulfuric acid (H2SO4) shows the highest contact angle of 167° and a low hysteresis of ~14° in the dynamic measurement. Creating, transporting, separating and merging of oxidized Galinstan droplets are successfully demonstrated in the fabricated PDMS microfluidic channels. After optimization of these modification techniques, the potential application of tunable capacitors and electronic filters is realized by using liquid metal-based microfluidic devices.

Manipulating freely diffusing single 20-nm particles in an Anti-Brownian Electrokinetic Trap (ABELtrap)

NASA Astrophysics Data System (ADS)

Zarrabi, Nawid; Clausen, Caterina; Düser, Monika G.; Börsch, Michael

2013-02-01

Conformational changes of individual fluorescently labeled proteins can be followed in solution using a confocal microscope. Two fluorophores attached to selected domains of the protein report fluctuating conformations. Based on Förster resonance energy transfer (FRET) between these fluorophores on a single protein, sequential distance changes between the dyes provide the real time trajectories of protein conformations. However, observation times are limited for freely diffusing biomolecules by Brownian motion through the confocal detection volume. A. E. Cohen and W. E. Moerner have invented and built microfluidic devices with 4 electrodes for an Anti-Brownian Electrokinetic Trap (ABELtrap). Here we present an ABELtrap based on a laser focus pattern generated by a pair of acousto-optical beam deflectors and controlled by a programmable FPGA chip. Fluorescent 20-nm beads in solution were used to mimic freely diffusing large proteins like solubilized FoF1-ATP synthase. The ABELtrap could hold these nanobeads for about 10 seconds at the given position. Thereby, observation times of a single particle were increased by a factor of 1000.

A novel polyimide based micro heater with high temperature uniformity

DOE PAGES

Yu, Shifeng; Wang, Shuyu; Lu, Ming; ...

2017-02-06

MEMS based micro heaters are a key component in micro bio-calorimetry, nondispersive infrared gas sensors, semiconductor gas sensors and microfluidic actuators. A micro heater with a uniform temperature distribution in the heating area and short response time is desirable in ultrasensitive temperature-dependent measurements. In this study, we propose a novel micro heater design to reach a uniform temperature in a large heating area by optimizing the heating power density distribution in the heating area. A polyimide membrane is utilized as the substrate to reduce the thermal mass and heat loss which allows for fast thermal response as well as amore » simplified fabrication process. A gold and titanium heating element is fabricated on the flexible polyimide substrate using the standard MEMS technique. The temperature distribution in the heating area for a certain power input is measured by an IR camera, and is consistent with FEA simulation results. Finally, this design can achieve fast response and uniform temperature distribution, which is quite suitable for the programmable heating such as impulse and step driving.« less

A novel polyimide based micro heater with high temperature uniformity

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

Yu, Shifeng; Wang, Shuyu; Lu, Ming

MEMS based micro heaters are a key component in micro bio-calorimetry, nondispersive infrared gas sensors, semiconductor gas sensors and microfluidic actuators. A micro heater with a uniform temperature distribution in the heating area and short response time is desirable in ultrasensitive temperature-dependent measurements. In this study, we propose a novel micro heater design to reach a uniform temperature in a large heating area by optimizing the heating power density distribution in the heating area. A polyimide membrane is utilized as the substrate to reduce the thermal mass and heat loss which allows for fast thermal response as well as amore » simplified fabrication process. A gold and titanium heating element is fabricated on the flexible polyimide substrate using the standard MEMS technique. The temperature distribution in the heating area for a certain power input is measured by an IR camera, and is consistent with FEA simulation results. Finally, this design can achieve fast response and uniform temperature distribution, which is quite suitable for the programmable heating such as impulse and step driving.« less

Differential white cell count by centrifugal microfluidics.

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

Sommer, Gregory Jon; Tentori, Augusto M.; Schaff, Ulrich Y.

We present a method for counting white blood cells that is uniquely compatible with centrifugation based microfluidics. Blood is deposited on top of one or more layers of density media within a microfluidic disk. Spinning the disk causes the cell populations within whole blood to settle through the media, reaching an equilibrium based on the density of each cell type. Separation and fluorescence measurement of cell types stained with a DNA dye is demonstrated using this technique. The integrated signal from bands of fluorescent microspheres is shown to be proportional to their initial concentration in suspension. Among the current generationmore » of medical diagnostics are devices based on the principle of centrifuging a CD sized disk functionalized with microfluidics. These portable 'lab on a disk' devices are capable of conducting multiple assays directly from a blood sample, embodied by platforms developed by Gyros, Samsung, and Abaxis. [1,2] However, no centrifugal platform to date includes a differential white blood cell count, which is an important metric complimentary to diagnostic assays. Measuring the differential white blood cell count (the relative fraction of granulocytes, lymphocytes, and monocytes) is a standard medical diagnostic technique useful for identifying sepsis, leukemia, AIDS, radiation exposure, and a host of other conditions that affect the immune system. Several methods exist for measuring the relative white blood cell count including flow cytometry, electrical impedance, and visual identification from a stained drop of blood under a microscope. However, none of these methods is easily incorporated into a centrifugal microfluidic diagnostic platform.« less

Construction of microscale structures in enclosed microfluidic networks by using a magnetic beads based method.

PubMed

Wang, Zhenyu; Zhang, Xiaojuan; Yang, Jun; Yang, Zhong; Wan, Xiaoping; Hu, Ning; Zheng, Xiaolin

2013-08-20

A large number of microscale structures have been used to elaborate flowing control or complex biological and chemical reaction on microfluidic chips. However, it is still inconvenient to fabricate microstructures with different heights (or depths) on the same substrate. These kinds of microstructures can be fabricated by using the photolithography and wet-etching method step by step, but involves time-consuming design and fabrication process, as well as complicated alignment of different masters. In addition, few existing methods can be used to perform fabrication within enclosed microfluidic networks. It is also difficult to change or remove existing microstructures within these networks. In this study, a magnetic-beads-based approach is presented to build microstructures in enclosed microfluidic networks. Electromagnetic field generated by microfabricated conducting wires (coils) is used to manipulate and trap magnetic beads on the bottom surface of a microchannel. These trapped beads are accumulated to form a microscale pile with desired shape, which can adjust liquid flow, dock cells, modify surface, and do some other things as those fabricated microstructures. Once the electromagnetic field is changed, trapped beads may form new shapes or be removed by a liquid flow. Besides being used in microfabrication, this magnetic-beads-based method can be used for novel microfluidic manipulation. It has been validated by forming microscale dam structure for cell docking and modified surface for cell patterning, as well as guiding the growth of neurons. Copyright © 2013 Elsevier B.V. All rights reserved.

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.

Fully inkjet-printed microfluidics: a solution to low-cost rapid three-dimensional microfluidics fabrication with numerous electrical and sensing applications

PubMed Central

Su, Wenjing; Cook, Benjamin S.; Fang, Yunnan; Tentzeris, Manos M.

2016-01-01

As the needs for low-cost rapidly-produced microfluidics are growing with the trend of Lab-on-a-Chip and distributed healthcare, the fully inkjet-printing of microfluidics can be a solution to it with numerous potential electrical and sensing applications. Inkjet-printing is an additive manufacturing technique featuring no material waste and a low equipment cost. Moreover, similar to other additive manufacturing techniques, inkjet-printing is easy to learn and has a high fabrication speed, while it offers generally a great planar resolution down to below 20 µm and enables flexible designs due to its inherent thin film deposition capabilities. Due to the thin film feature, the printed objects also usually obtain a high vertical resolution (such as 4.6 µm). This paper introduces a low-cost rapid three-dimensional fabrication process of microfluidics, that relies entirely on an inkjet-printer based single platform and can be implemented directly on top of virtually any substrates. PMID:27713545

Fully inkjet-printed microfluidics: a solution to low-cost rapid three-dimensional microfluidics fabrication with numerous electrical and sensing applications

NASA Astrophysics Data System (ADS)

Su, Wenjing; Cook, Benjamin S.; Fang, Yunnan; Tentzeris, Manos M.

2016-10-01

As the needs for low-cost rapidly-produced microfluidics are growing with the trend of Lab-on-a-Chip and distributed healthcare, the fully inkjet-printing of microfluidics can be a solution to it with numerous potential electrical and sensing applications. Inkjet-printing is an additive manufacturing technique featuring no material waste and a low equipment cost. Moreover, similar to other additive manufacturing techniques, inkjet-printing is easy to learn and has a high fabrication speed, while it offers generally a great planar resolution down to below 20 µm and enables flexible designs due to its inherent thin film deposition capabilities. Due to the thin film feature, the printed objects also usually obtain a high vertical resolution (such as 4.6 µm). This paper introduces a low-cost rapid three-dimensional fabrication process of microfluidics, that relies entirely on an inkjet-printer based single platform and can be implemented directly on top of virtually any substrates.