Design of a compact microfludic device for controllable cell distribution.

PubMed

Li, Jing-Liang; Day, Daniel; Gu, Min

2010-11-21

A compact microfluidic device with 96 microchambers allocated within four circular units was designed and examined for cell distribution. In each unit, cells were distributed to the surrounding chambers radially from the center. The circular arrangement of the chambers makes the design simple and compact. A controllable and quantitative cell distribution is achievable in this device. This design is significant to the microfluidic applications where controllable distribution of cells in multipule microchambers is demanded.

Efficient generation of hepatic cells from mesenchymal stromal cells by an innovative bio-microfluidic cell culture device.

PubMed

Yen, Meng-Hua; Wu, Yuan-Yi; Liu, Yi-Shiuan; Rimando, Marilyn; Ho, Jennifer Hui-Chun; Lee, Oscar Kuang-Sheng

2016-08-19

Mesenchymal stromal cells (MSCs) are multipotent and have great potential in cell therapy. Previously we reported the differentiation potential of human MSCs into hepatocytes in vitro and that these cells can rescue fulminant hepatic failure. However, the conventional static culture method neither maintains growth factors at an optimal level constantly nor removes cellular waste efficiently. In addition, not only is the duration of differentiating hepatocyte lineage cells from MSCs required to improve, but also the need for a large number of hepatocytes for cell therapy has not to date been addressed fully. The purpose of this study is to design and develop an innovative microfluidic device to overcome these shortcomings. We designed and fabricated a microfluidic device and a culture system for hepatic differentiation of MSCs using our protocol reported previously. The microfluidic device contains a large culture chamber with a stable uniform flow to allow homogeneous distribution and expansion as well as efficient induction of hepatic differentiation for MSCs. The device enables real-time observation under light microscopy and exhibits a better differentiation efficiency for MSCs compared with conventional static culture. MSCs grown in the microfluidic device showed a higher level of hepatocyte marker gene expression under hepatic induction. Functional analysis of hepatic differentiation demonstrated significantly higher urea production in the microfluidic device after 21 days of hepatic differentiation. The microfluidic device allows the generation of a large number of MSCs and induces hepatic differentiation of MSCs efficiently. The device can be adapted for scale-up production of hepatic cells from MSCs for cellular therapy.

Electrokinetic focusing injection methods on microfluidic devices.

PubMed

Fu, Lung-Ming; Yang, Ruey-Jen; Lee, Gwo-Bin

2003-04-15

This paper presents an experimental and numerical investigation into electrokinetic focusing injection on microfluidic chips. The valving characteristics on microfluidic devices are controlled through appropriate manipulations of the electric potential strengths during the sample loading and dispensing steps. The present study also addresses the design and testing of various injection systems used to deliver a sample plug. A novel double-cross injection microfluidic chip is fabricated, which employs electrokinetic focusing to deliver sample plugs of variable volume. The proposed design combines several functions of traditional sample plug injection systems on a single microfluidic chip. The injection technique uses an unique sequence of loading steps with different electric potential distributions and magnitudes within the various channels to effectuate a virtual valve.

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.

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.

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

PubMed

Matellan, Carlos; Del Río Hernández, Armando E

2018-05-03

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

Multi-step Variable Height Photolithography for Valved Multilayer Microfluidic Devices.

PubMed

Brower, Kara; White, Adam K; Fordyce, Polly M

2017-01-27

Microfluidic systems have enabled powerful new approaches to high-throughput biochemical and biological analysis. However, there remains a barrier to entry for non-specialists who would benefit greatly from the ability to develop their own microfluidic devices to address research questions. Particularly lacking has been the open dissemination of protocols related to photolithography, a key step in the development of a replica mold for the manufacture of polydimethylsiloxane (PDMS) devices. While the fabrication of single height silicon masters has been explored extensively in literature, fabrication steps for more complicated photolithography features necessary for many interesting device functionalities (such as feature rounding to make valve structures, multi-height single-mold patterning, or high aspect ratio definition) are often not explicitly outlined. Here, we provide a complete protocol for making multilayer microfluidic devices with valves and complex multi-height geometries, tunable for any application. These fabrication procedures are presented in the context of a microfluidic hydrogel bead synthesizer and demonstrate the production of droplets containing polyethylene glycol (PEG diacrylate) and a photoinitiator that can be polymerized into solid beads. This protocol and accompanying discussion provide a foundation of design principles and fabrication methods that enables development of a wide variety of microfluidic devices. The details included here should allow non-specialists to design and fabricate novel devices, thereby bringing a host of recently developed technologies to their most exciting applications in biological laboratories.

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.

Shrink film patterning by craft cutter: complete plastic chips with high resolution/high-aspect ratio channel.

PubMed

Taylor, Douglas; Dyer, David; Lew, Valerie; Khine, Michelle

2010-09-21

This paper presents a rapid, ultra-low-cost approach to fabricate microfluidic devices using a polyolefin shrink film and a digital craft cutter. The shrinking process (with a 95% reduction in area) results in relatively uniform and consistent microfluidic channels with smooth surfaces, vertical sidewalls, and high aspect ratio channels with lateral resolutions well beyond the tool used to cut them. The thermal bonding of the layers results in strongly bonded devices. Complex microfluidic designs are easily designed on the fly and protein assays are also readily integrated into the device. Full device characterization including channel consistency, optical properties, and bonding strength are assessed in this technical note.

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.

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

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

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

NASA Astrophysics Data System (ADS)

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

2017-12-01

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

3D-printed microfluidic automation.

PubMed

Au, Anthony K; Bhattacharjee, Nirveek; Horowitz, Lisa F; Chang, Tim C; Folch, Albert

2015-04-21

Microfluidic automation - the automated routing, dispensing, mixing, and/or separation of fluids through microchannels - generally remains a slowly-spreading technology because device fabrication requires sophisticated facilities and the technology's use demands expert operators. Integrating microfluidic automation in devices has involved specialized multi-layering and bonding approaches. Stereolithography is an assembly-free, 3D-printing technique that is emerging as an efficient alternative for rapid prototyping of biomedical devices. Here we describe fluidic valves and pumps that can be stereolithographically printed in optically-clear, biocompatible plastic and integrated within microfluidic devices at low cost. User-friendly fluid automation devices can be printed and used by non-engineers as replacement for costly robotic pipettors or tedious manual pipetting. Engineers can manipulate the designs as digital modules into new devices of expanded functionality. Printing these devices only requires the digital file and electronic access to a printer.

Recent microfluidic devices for studying gamete and embryo biomechanics.

PubMed

Lai, David; Takayama, Shuichi; Smith, Gary D

2015-06-25

The technical challenges of biomechanic research such as single cell analysis at a high monetary cost, labor, and time for just a small number of measurements is a good match to the strengths of microfluidic devices. New scientific discoveries in the fertilization and embryo development process, of which biomechanics is a major subset of interest, is crucial to fuel the continual improvement of clinical practice in assisted reproduction. The following review will highlight some recent microfluidic devices tailored for gamete and embryo biomechanics where biomimicry arises as a major theme of microfluidic device design and function, and the application of fundamental biomechanic principles are used to improve outcomes of cryopreservation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Mass and Momentum Transport in Microcavities for Diffusion-Dominant Cell Culture Applications

NASA Technical Reports Server (NTRS)

Yew, Alvin G.; Pinero, Daniel; Hsieh, Adam H.; Atencia, Javier

2012-01-01

For the informed design of microfluidic devices, it is important to understand transport phenomena at the microscale. This letter outlines an analytically-driven approach to the design of rectangular microcavities extending perpendicular to a perfusion microchannel for microfluidic cell culture devices. We present equations to estimate the spatial transition from advection- to diffusion-dominant transport inside cavities as a function of the geometry and flow conditions. We also estimate the time required for molecules, such as nutrients or drugs to travel from the microchannel to a given depth into the cavity. These analytical predictions can facilitate the rational design of microfluidic devices to optimize and maintain long-term, physiologically-based culture conditions with low fluid shear stress.

Integrated high pressure manifold for thermoplastic microfluidic devices

NASA Astrophysics Data System (ADS)

Aghvami, S. Ali; Fraden, Seth

2017-11-01

We introduce an integrated tubing manifold for thermoplastic microfluidic chips that tolerates high pressure. In contrast to easy tubing in PDMS microfluidic devices, tube connection has been challenging for plastic microfluidics. Our integrated manifold connection tolerates 360 psi while conventional PDMS connections fail at 50 psi. Important design considerations are incorporation of a quick-connect, leak-free and high-pressure manifold for the inlets and outlets on the lid and registration marks that allow the precise alignment of the inlets and outlets. In our method, devices are comprised of two molded pieces joined together to create a sealed device. The first piece contains the microfluidic features and the second contains the inlet and outlet manifold, a frame for rigidity and a viewing window. The mold for the lid with integrated manifold is CNC milled from aluminium. A cone shape PDMS component which acts as an O-ring, seals the connection between molded manifold and tubing. The lid piece with integrated inlet and outlets will be a standard piece and can be used for different chips and designs. Sealing the thermoplastic device is accomplished by timed immersion of the lid in a mixture of volatile and non-volatile solvents followed by application of heat and pressure.

Three-Dimensional Printing Based Hybrid Manufacturing of Microfluidic Devices.

PubMed

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

2015-05-01

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

Three-Dimensional Printing Based Hybrid Manufacturing of Microfluidic Devices

PubMed Central

Shen, Richang; Gurkan, Umut A.

2016-01-01

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

Multiphase flows with digital and traditional microfluidics

NASA Astrophysics Data System (ADS)

Nilsson, Michael A.

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

3D-Printed Microfluidic Automation

PubMed Central

Au, Anthony K.; Bhattacharjee, Nirveek; Horowitz, Lisa F.; Chang, Tim C.; Folch, Albert

2015-01-01

Microfluidic automation – the automated routing, dispensing, mixing, and/or separation of fluids through microchannels – generally remains a slowly-spreading technology because device fabrication requires sophisticated facilities and the technology’s use demands expert operators. Integrating microfluidic automation in devices has involved specialized multi-layering and bonding approaches. Stereolithography is an assembly-free, 3D-printing technique that is emerging as an efficient alternative for rapid prototyping of biomedical devices. Here we describe fluidic valves and pumps that can be stereolithographically printed in optically-clear, biocompatible plastic and integrated within microfluidic devices at low cost. User-friendly fluid automation devices can be printed and used by non-engineers as replacement for costly robotic pipettors or tedious manual pipetting. Engineers can manipulate the designs as digital modules into new devices of expanded functionality. Printing these devices only requires the digital file and electronic access to a printer. PMID:25738695

Droplet Microfluidic Device Fabrication and Use for Isothermal Amplification and Detection of MicroRNA.

PubMed

Giuffrida, Maria Chiara; D'Agata, Roberta; Spoto, Giuseppe

2017-01-01

Droplet microfluidics combined with the isothermal circular strand displacement polymerization (ICSDP) represents a powerful new technique to detect both single-stranded DNA and microRNA sequences. The method here described helps in overcoming some drawbacks of the lately introduced droplet polymerase chain reaction (PCR) amplification when implemented in microfluidic devices. The method also allows the detection of nanoliter droplets of nucleic acids sequences solutions, with a particular attention to microRNA sequences that are detected at the picomolar level. The integration of the ICSDP amplification protocol in droplet microfluidic devices reduces the time of analysis and the amount of sample required. In addition, there is also the possibility to design parallel analyses to be integrated in portable devices.

Waste-to-energy conversion from a microfluidic device

NASA Astrophysics Data System (ADS)

López-González, B.; Jiménez-Valdés, R. J.; Moreno-Zuria, A.; Cuevas-Muñiz, F. M.; Ledesma-García, J.; García-Cordero, J. L.; Arriaga, L. G.

2017-08-01

This work reports the successful harvesting of energy from waste produced in a microfluidic device using a fuel cell. A miniaturized glucose air-breathing microfluidic fuel cell (ABμFFC) was designed, fabricated and tested with three different configurations according to their electrode nature: inorganic, hybrid and biofuel cell. Each ABμFFC was characterized using an ideal medium, with sterile cell culture medium, and with waste produced on a microfluidic device. The inorganic-ABμFFC exhibited the highest performance compared to the rest of the configurations. As a proof-of-concept, cancer cells were cultured on a microfluidic device and the consumed cell culture media (glucose concentration <11 mM) was used as an energy source without further treatment, into the inorganic-ABμFFC. The fuel cell generated a maximum total power of 5.2 μW, which is enough energy to power low-consumption microelectronic chips. This application demonstrates that the waste produced by microfluidic applications could be potentially scavenged to produce electrical energy. It also opens the possibility to develop truly energy self-sufficient portable devices.

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.

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 tools for cell biological research

PubMed Central

Velve-Casquillas, Guilhem; Le Berre, Maël; Piel, Matthieu; Tran, Phong T.

2010-01-01

Summary Microfluidic technology is creating powerful tools for cell biologists to control the complete cellular microenvironment, leading to new questions and new discoveries. We review here the basic concepts and methodologies in designing microfluidic devices, and their diverse cell biological applications. PMID:21152269

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

PubMed

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

2012-03-01

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

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

PubMed Central

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

2012-01-01

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

Microfluidic 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

Diffusion phenomena of cells and biomolecules in microfluidic devices.

PubMed

Yildiz-Ozturk, Ece; Yesil-Celiktas, Ozlem

2015-09-01

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

Diffusion phenomena of cells and biomolecules in microfluidic devices

PubMed Central

Yildiz-Ozturk, Ece; Yesil-Celiktas, Ozlem

2015-01-01

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

Tilted pillar array fabrication by the combination of proton beam writing and soft lithography for microfluidic cell capture: Part 1 Design and feasibility.

PubMed

Rajta, Istvan; Huszánk, Robert; Szabó, Atilla T T; Nagy, Gyula U L; Szilasi, Szabolcs; Fürjes, Peter; Holczer, Eszter; Fekete, Zoltan; Járvás, Gabor; Szigeti, Marton; Hajba, Laszlo; Bodnár, Judit; Guttman, Andras

2016-02-01

Design, fabrication, integration, and feasibility test results of a novel microfluidic cell capture device is presented, exploiting the advantages of proton beam writing to make lithographic irradiations under multiple target tilting angles and UV lithography to easily reproduce large area structures. A cell capture device is demonstrated with a unique doubly tilted micropillar array design for cell manipulation in microfluidic applications. Tilting the pillars increased their functional surface, therefore, enhanced fluidic interaction when special bioaffinity coating was used, and improved fluid dynamic behavior regarding cell culture injection. The proposed microstructures were capable to support adequate distribution of body fluids, such as blood, spinal fluid, etc., between the inlet and outlet of the microfluidic sample reservoirs, offering advanced cell capture capability on the functionalized surfaces. The hydrodynamic characteristics of the microfluidic systems were tested with yeast cells (similar size as red blood cells) for efficient capture. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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.

Accurately tracking single-cell movement trajectories in microfluidic cell sorting devices.

PubMed

Jeong, Jenny; Frohberg, Nicholas J; Zhou, Enlu; Sulchek, Todd; Qiu, Peng

2018-01-01

Microfluidics are routinely used to study cellular properties, including the efficient quantification of single-cell biomechanics and label-free cell sorting based on the biomechanical properties, such as elasticity, viscosity, stiffness, and adhesion. Both quantification and sorting applications require optimal design of the microfluidic devices and mathematical modeling of the interactions between cells, fluid, and the channel of the device. As a first step toward building such a mathematical model, we collected video recordings of cells moving through a ridged microfluidic channel designed to compress and redirect cells according to cell biomechanics. We developed an efficient algorithm that automatically and accurately tracked the cell trajectories in the recordings. We tested the algorithm on recordings of cells with different stiffness, and showed the correlation between cell stiffness and the tracked trajectories. Moreover, the tracking algorithm successfully picked up subtle differences of cell motion when passing through consecutive ridges. The algorithm for accurately tracking cell trajectories paves the way for future efforts of modeling the flow, forces, and dynamics of cell properties in microfluidics applications.

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

PubMed

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

2017-04-13

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

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

NASA Astrophysics Data System (ADS)

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

2018-02-01

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

Development of a Pressure Switched Microfluidic Cell Sorter

NASA Astrophysics Data System (ADS)

Ozbay, Baris; Jones, Alex; Gibson, Emily

2009-10-01

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

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.

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.

Microfluidics @ the Beach: Introduction of Microfluidics Technology to the ChE Curriculum at Cal State Long Beach

ERIC Educational Resources Information Center

Lo, Roger C.; Bhatia, Hina; Venkatraman, Rahul; Jang, Larry K.

2015-01-01

Microfluidics involves the study of the behavior of fluids at microscale, fluid manipulations, and the design of the devices that can effectively perform such manipulations. We are developing two new elective courses to include microfluidics in our curriculum at CSULB. Herein, we present the results of the first course, Microfabrication and…

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

NASA Astrophysics Data System (ADS)

Alvankarian, Jafar; Yeop Majlis, Burhanuddin

2012-03-01

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

Microfluidic Mixing: A Review

PubMed Central

Lee, Chia-Yen; Chang, Chin-Lung; Wang, Yao-Nan; Fu, Lung-Ming

2011-01-01

The aim of microfluidic mixing is to achieve a thorough and rapid mixing of multiple samples in microscale devices. In such devices, sample mixing is essentially achieved by enhancing the diffusion effect between the different species flows. Broadly speaking, microfluidic mixing schemes can be categorized as either “active”, where an external energy force is applied to perturb the sample species, or “passive”, where the contact area and contact time of the species samples are increased through specially-designed microchannel configurations. Many mixers have been proposed to facilitate this task over the past 10 years. Accordingly, this paper commences by providing a high level overview of the field of microfluidic mixing devices before describing some of the more significant proposals for active and passive mixers. PMID:21686184

Microfluidic Device to Quantify the Behavior of Therapeutic Bacteria in Three-Dimensional Tumor Tissue.

PubMed

Brackett, Emily L; Swofford, Charles A; Forbes, Neil S

2016-01-01

Microfluidic devices enable precise quantification of the interactions between anti-cancer bacteria and tumor tissue. Direct observation of bacterial movement and gene expression in tissue is difficult with either monolayers of cells or tumor-bearing mice. Quantification of these interactions is necessary to understand the inherent mechanisms of bacterial targeting and to develop modified organisms with enhanced therapeutic properties. Here we describe the procedures for designing, printing, and assembling microfluidic tumor-on-a-chip devices. We also describe the procedures for inserting three-dimensional tumor-cell masses, exposure to bacteria, and analyzing the resultant images.

A small-scale, rolled-membrane microfluidic artificial lung designed towards future large area manufacturing.

PubMed

Thompson, A J; Marks, L H; Goudie, M J; Rojas-Pena, A; Handa, H; Potkay, J A

2017-03-01

Artificial lungs have been used in the clinic for multiple decades to supplement patient pulmonary function. Recently, small-scale microfluidic artificial lungs (μAL) have been demonstrated with large surface area to blood volume ratios, biomimetic blood flow paths, and pressure drops compatible with pumpless operation. Initial small-scale microfluidic devices with blood flow rates in the μ l/min to ml/min range have exhibited excellent gas transfer efficiencies; however, current manufacturing techniques may not be suitable for scaling up to human applications. Here, we present a new manufacturing technology for a microfluidic artificial lung in which the structure is assembled via a continuous "rolling" and bonding procedure from a single, patterned layer of polydimethyl siloxane (PDMS). This method is demonstrated in a small-scale four-layer device, but is expected to easily scale to larger area devices. The presented devices have a biomimetic branching blood flow network, 10  μ m tall artificial capillaries, and a 66  μ m thick gas transfer membrane. Gas transfer efficiency in blood was evaluated over a range of blood flow rates (0.1-1.25 ml/min) for two different sweep gases (pure O 2 , atmospheric air). The achieved gas transfer data closely follow predicted theoretical values for oxygenation and CO 2 removal, while pressure drop is marginally higher than predicted. This work is the first step in developing a scalable method for creating large area microfluidic artificial lungs. Although designed for microfluidic artificial lungs, the presented technique is expected to result in the first manufacturing method capable of simply and easily creating large area microfluidic devices from PDMS.

Student-Fabricated Microfluidic Devices as Flow Reactors for Organic and Inorganic Synthesis

ERIC Educational Resources Information Center

Feng, Z. Vivian; Edelman, Kate R.; Swanson, Benjamin P.

2015-01-01

Flow synthesis in microfluidic devices has been rapidly adapted in the pharmaceutical industry and in many research laboratories. Yet, the cost of commercial flow reactors is a major factor limiting the dissemination of this technology in the undergraduate curriculum. Here, we present a laboratory activity where students design and fabricate…

Microfluidic PMMA interfaces for rectangular glass capillaries

NASA Astrophysics Data System (ADS)

Evander, Mikael; Tenje, Maria

2014-02-01

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

A piezo-ring-on-chip microfluidic device for simple and low-cost mass spectrometry interfacing.

PubMed

Tsao, Chia-Wen; Lei, I-Chao; Chen, Pi-Yu; Yang, Yu-Liang

2018-02-12

Mass spectrometry (MS) interfacing technology provides the means for incorporating microfluidic processing with post MS analysis. In this study, we propose a simple piezo-ring-on-chip microfluidic device for the controlled spraying of MALDI-MS targets. This device uses a low-cost, commercially-available ring-shaped piezoelectric acoustic atomizer (piezo-ring) directly integrated into a polydimethylsiloxane microfluidic device to spray the sample onto the MS target substrate. The piezo-ring-on-chip microfluidic device's design, fabrication, and actuation, and its pulsatile pumping effects were evaluated. The spraying performance was examined by depositing organic matrix samples onto the MS target substrate by using both an automatic linear motion motor, and manual deposition. Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) was performed to analyze the peptide samples on the MALDI target substrates. Using our technique, model peptides with 10 -6 M concentration can be successfully detected. The results also indicate that the piezo-ring-on-chip approach forms finer matrix crystals and presents better MS signal uniformity with little sample consumption compared to the conventional pipetting method.

Recent developments in microfluidics for cell studies.

PubMed

Xiong, Bin; Ren, Kangning; Shu, Yiwei; Chen, Yin; Shen, Bo; Wu, Hongkai

2014-08-20

As a technique for precisely manipulating fluid at the micrometer scale, the field of microfluidics has experienced an explosive growth over the past two decades, particularly owing to the advances in device design and fabrication. With the inherent advantages associated with its scale of operation, and its flexibility in being incorporated with other microscale techniques for manipulation and detection, microfluidics has become a major enabling technology, which has introduced new paradigms in various fields involving biological cells. A microfluidic device is able to realize functions that are not easily imaginable in conventional biological analysis, such as highly parallel, sophisticated high-throughput analysis, single-cell analysis in a well-defined manner, and tissue engineering with the capability of manipulation at the single-cell level. Major advancements in microfluidic device fabrication and the growing trend of implementing microfluidics in cell studies are presented, with a focus on biological research and clinical diagnostics. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Finite element modeling simulation-assisted design of integrated microfluidic chips for heavy metal ion stripping analysis

NASA Astrophysics Data System (ADS)

Hong, Ying; Zou, Jianhua; Ge, Gang; Xiao, Wanyue; Gao, Ling; Shao, Jinjun; Dong, Xiaochen

2017-10-01

In this article, a transparent integrated microfluidic device composed of a 3D-printed thin-layer flow cell (3D-PTLFC) and an S-shaped screen-printed electrode (SPE) has been designed and fabricated for heavy metal ion stripping analysis. A finite element modeling (FEM) simulation is employed to optimize the shape of the electrode, the direction of the inlet pipeline, the thin-layer channel height and the sample flow rate to enhance the electron-enrichment efficiency for stripping analysis. The results demonstrate that the S-shaped SPE configuration matches the channel in 3D-PTLFC perfectly for the anodic stripping behavior of the heavy metal ions. Under optimized conditions, a wide linear range of 1-80 µg l-1 is achieved for Pb2+ detection with a limit of 0.3 µg l-1 for the microfluidic device. Thus, the obtained integrated microfluidic device proves to be a promising approach for heavy metal ions stripping analysis with low cost and high performance.

Culture and Sampling of Primary Adipose Tissue in Practical Microfluidic Systems.

PubMed

Brooks, Jessica C; Judd, Robert L; Easley, Christopher J

2017-01-01

Microfluidic culture of primary adipose tissue allows for reduced sample and reagent volumes as well as constant media perfusion of the cells. By continuously flowing media over the tissue, microfluidic sampling systems can more accurately mimic vascular flow in vivo. Quantitative measurements can be performed on or off chip to provide time-resolved secretion data, furthering insight into the dynamics of the function of adipose tissue. Buoyancy resulting from the large lipid storage capacity in this tissue presents a unique challenge for culture, and it is important to account for this buoyancy during microdevice design. Herein, we describe approaches for microfluidic device fabrication that utilize 3D-printed interface templating to help counteract cell buoyancy. We apply such methods to the culture of both isolated, dispersed primary adipocytes and epididymal adipose explants. To facilitate more widespread adoption of the methodology, the devices presented here are designed for user-friendly operation. Only handheld syringes are needed to control flow, and devices are inexpensive and disposable.

Single-cell cloning and expansion of human induced pluripotent stem cells by a microfluidic culture device.

PubMed

Matsumura, Taku; Tatsumi, Kazuya; Noda, Yuichiro; Nakanishi, Naoyuki; Okonogi, Atsuhito; Hirano, Kunio; Li, Liu; Osumi, Takashi; Tada, Takashi; Kotera, Hidetoshi

2014-10-10

The microenvironment of cells, which includes basement proteins, shear stress, and extracellular stimuli, should be taken into consideration when examining physiological cell behavior. Although microfluidic devices allow cellular responses to be analyzed with ease at the single-cell level, few have been designed to recover cells. We herein demonstrated that a newly developed microfluidic device helped to improve culture conditions and establish a clonality-validated human pluripotent stem cell line after tracing its growth at the single-cell level. The device will be a helpful tool for capturing various cell types in the human body that have not yet been established in vitro. Copyright © 2014 Elsevier Inc. All rights reserved.

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

PubMed

Silva, Bruno F B

2017-09-13

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

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

NASA Astrophysics Data System (ADS)

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

2017-09-01

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

Sperm quality assessment via separation and sedimentation in a microfluidic device.

PubMed

Chen, Chang-Yu; Chiang, Tsun-Chao; Lin, Cheng-Ming; Lin, Shu-Sheng; Jong, De-Shien; Tsai, Vincent F-S; Hsieh, Ju-Ton; Wo, Andrew M

2013-09-07

A major reason for infertility is due to male factors, including the quality of spermatozoa, which is a primary factor and often difficult to assess, particularly the total sperm concentration and its motile percentage. This work presents a simple microfluidic device to assess sperm quality by quantifying both total and motile sperm counts. The key design feature of the microfluidic device is two channels separated by a permeative phase-guide structure, where one channel is filled with raw semen and the other with pure buffer. The semen sample was allowed to reach equilibrium in both chambers, whereas non-motile sperms remained in the original channel, and roughly half of the motile sperms would swim across the phase-guide barrier into the buffer channel. Sperms in each channel agglomerated into pellets after centrifugation, with the corresponding area representing total and motile sperm concentrations. Total sperm concentration up to 10(8) sperms per ml and motile percentage in the range of 10-70% were tested, encompassing the cutoff value of 40% stated by World Health Organization standards. Results from patient samples show compact and robust pellets after centrifugation. Comparison of total sperm concentration between the microfluidic device and the Makler chamber reveal they agree within 5% and show strong correlation, with a coefficient of determination of R(2) = 0.97. Motile sperm count between the microfluidic device and the Makler chamber agrees within 5%, with a coefficient of determination of R(2) = 0.84. Comparison of results from the Makler Chamber, sperm quality analyzer, and the microfluidic device revealed that results from the microfluidic device agree well with the Makler chamber. The sperm microfluidic chip analyzes both total and motile sperm concentrations in one spin, is accurate and easy to use, and should enable sperm quality analysis with ease.

Accessing microfluidics through feature-based design software for 3D printing.

PubMed

Shankles, Peter G; Millet, Larry J; Aufrecht, Jayde A; Retterer, Scott T

2018-01-01

Additive manufacturing has been a cornerstone of the product development pipeline for decades, playing an essential role in the creation of both functional and cosmetic prototypes. In recent years, the prospects for distributed and open source manufacturing have grown tremendously. This growth has been enabled by an expanding library of printable materials, low-cost printers, and communities dedicated to platform development. The microfluidics community has embraced this opportunity to integrate 3D printing into the suite of manufacturing strategies used to create novel fluidic architectures. The rapid turnaround time and low cost to implement these strategies in the lab makes 3D printing an attractive alternative to conventional micro- and nanofabrication techniques. In this work, the production of multiple microfluidic architectures using a hybrid 3D printing-soft lithography approach is demonstrated and shown to enable rapid device fabrication with channel dimensions that take advantage of laminar flow characteristics. The fabrication process outlined here is underpinned by the implementation of custom design software with an integrated slicer program that replaces less intuitive computer aided design and slicer software tools. Devices are designed in the program by assembling parameterized microfluidic building blocks. The fabrication process and flow control within 3D printed devices were demonstrated with a gradient generator and two droplet generator designs. Precise control over the printing process allowed 3D microfluidics to be printed in a single step by extruding bridge structures to 'jump-over' channels in the same plane. This strategy was shown to integrate with conventional nanofabrication strategies to simplify the operation of a platform that incorporates both nanoscale features and 3D printed microfluidics.

Accessing microfluidics through feature-based design software for 3D printing

PubMed Central

Shankles, Peter G.; Millet, Larry J.; Aufrecht, Jayde A.

2018-01-01

Additive manufacturing has been a cornerstone of the product development pipeline for decades, playing an essential role in the creation of both functional and cosmetic prototypes. In recent years, the prospects for distributed and open source manufacturing have grown tremendously. This growth has been enabled by an expanding library of printable materials, low-cost printers, and communities dedicated to platform development. The microfluidics community has embraced this opportunity to integrate 3D printing into the suite of manufacturing strategies used to create novel fluidic architectures. The rapid turnaround time and low cost to implement these strategies in the lab makes 3D printing an attractive alternative to conventional micro- and nanofabrication techniques. In this work, the production of multiple microfluidic architectures using a hybrid 3D printing-soft lithography approach is demonstrated and shown to enable rapid device fabrication with channel dimensions that take advantage of laminar flow characteristics. The fabrication process outlined here is underpinned by the implementation of custom design software with an integrated slicer program that replaces less intuitive computer aided design and slicer software tools. Devices are designed in the program by assembling parameterized microfluidic building blocks. The fabrication process and flow control within 3D printed devices were demonstrated with a gradient generator and two droplet generator designs. Precise control over the printing process allowed 3D microfluidics to be printed in a single step by extruding bridge structures to ‘jump-over’ channels in the same plane. This strategy was shown to integrate with conventional nanofabrication strategies to simplify the operation of a platform that incorporates both nanoscale features and 3D printed microfluidics. PMID:29596418

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

PubMed Central

Alvankarian, Jafar; Majlis, Burhanuddin Yeop

2015-01-01

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

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

PubMed Central

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

2011-01-01

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

Analyzing threshold pressure limitations in microfluidic transistors for self-regulated microfluidic circuits.

PubMed

Kim, Sung-Jin; Yokokawa, Ryuji; Takayama, Shuichi

2012-12-03

This paper reveals a critical limitation in the electro-hydraulic analogy between a microfluidic membrane-valve (μMV) and an electronic transistor. Unlike typical transistors that have similar on and off threshold voltages, in hydraulic μMVs, the threshold pressures for opening and closing are significantly different and can change, even for the same μMVs depending on overall circuit design and operation conditions. We explain, in particular, how the negative values of the closing threshold pressures significantly constrain operation of even simple hydraulic μMV circuits such as autonomously switching two-valve microfluidic oscillators. These understandings have significant implications in designing self-regulated microfluidic devices.

Microchip-based electrochemical detection using a 3-D printed wall-jet electrode device.

PubMed

Munshi, Akash S; Martin, R Scott

2016-02-07

Three dimensional (3-D) printing technology has evolved dramatically in the last few years, offering the capability of printing objects with a variety of materials. Printing microfluidic devices using this technology offers various advantages such as ease and uniformity of fabrication, file sharing between laboratories, and increased device-to-device reproducibility. One unique aspect of this technology, when used with electrochemical detection, is the ability to produce a microfluidic device as one unit while also allowing the reuse of the device and electrode for multiple analyses. Here we present an alternate electrode configuration for microfluidic devices, a wall-jet electrode (WJE) approach, created by 3-D printing. Using microchip-based flow injection analysis, we compared the WJE design with the conventionally used thin-layer electrode (TLE) design. It was found that the optimized WJE system enhances analytical performance (as compared to the TLE design), with improvements in sensitivity and the limit of detection. Experiments were conducted using two working electrodes - 500 μm platinum and 1 mm glassy carbon. Using the 500 μm platinum electrode the calibration sensitivity was 16 times higher for the WJE device (as compared to the TLE design). In addition, use of the 1 mm glassy carbon electrode led to limit of detection of 500 nM for catechol, as compared to 6 μM for the TLE device. Finally, to demonstrate the versatility and applicability of the 3-D printed WJE approach, the device was used as an inexpensive electrochemical detector for HPLC. The number of theoretical plates was comparable to the use of commercially available UV and MS detectors, with the WJE device being inexpensive to utilize. These results show that 3-D-printing can be a powerful tool to fabricate reusable and integrated microfluidic detectors in configurations that are not easily achieved with more traditional lithographic methods.

Improving Sample Distribution Homogeneity in Three-Dimensional Microfluidic Paper-Based Analytical Devices by Rational Device Design.

PubMed

Morbioli, Giorgio Gianini; Mazzu-Nascimento, Thiago; Milan, Luis Aparecido; Stockton, Amanda M; Carrilho, Emanuel

2017-05-02

Paper-based devices are a portable, user-friendly, and affordable technology that is one of the best analytical tools for inexpensive diagnostic devices. Three-dimensional microfluidic paper-based analytical devices (3D-μPADs) are an evolution of single layer devices and they permit effective sample dispersion, individual layer treatment, and multiplex analytical assays. Here, we present the rational design of a wax-printed 3D-μPAD that enables more homogeneous permeation of fluids along the cellulose matrix than other existing designs in the literature. Moreover, we show the importance of the rational design of channels on these devices using glucose oxidase, peroxidase, and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) reactions. We present an alternative method for layer stacking using a magnetic apparatus, which facilitates fluidic dispersion and improves the reproducibility of tests performed on 3D-μPADs. We also provide the optimized designs for printing, facilitating further studies using 3D-μPADs.

Control and automation of multilayered integrated microfluidic device fabrication.

PubMed

Kipper, Sarit; Frolov, Ludmila; Guy, Ortal; Pellach, Michal; Glick, Yair; Malichi, Asaf; Knisbacher, Binyamin A; Barbiro-Michaely, Efrat; Avrahami, Dorit; Yavets-Chen, Yehuda; Levanon, Erez Y; Gerber, Doron

2017-01-31

Integrated microfluidics is a sophisticated three-dimensional (multi layer) solution for high complexity serial or parallel processes. Fabrication of integrated microfluidic devices requires soft lithography and the stacking of thin-patterned PDMS layers. Precise layer alignment and bonding is crucial. There are no previously reported standards for alignment of the layers, which is mostly performed using uncontrolled processes with very low alignment success. As a result, integrated microfluidics is mostly used in academia rather than in the many potential industrial applications. We have designed and manufactured a semiautomatic Microfluidic Device Assembly System (μDAS) for full device production. μDAS comprises an electrooptic mechanical system consisting of four main parts: optical system, smart media holder (for PDMS), a micropositioning xyzθ system and a macropositioning XY mechanism. The use of the μDAS yielded valuable information regarding PDMS as the material for device fabrication, revealed previously unidentified errors, and enabled optimization of a robust fabrication process. In addition, we have demonstrated the utilization of the μDAS technology for fabrication of a complex 3 layered device with over 12 000 micromechanical valves and an array of 64 × 64 DNA spots on a glass substrate with high yield and high accuracy. We increased fabrication yield from 25% to about 85% with an average layer alignment error of just ∼4 μm. It also increased our protein expression yields from 80% to over 90%, allowing us to investigate more proteins per experiment. The μDAS has great potential to become a valuable tool for both advancing integrated microfluidics in academia and producing and applying microfluidic devices in the industry.

Microfluidics for High School Chemistry Students.

PubMed

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

2014-01-14

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

Microfluidics for High School Chemistry Students

PubMed Central

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

2014-01-01

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

A hybrid microfluidic-vacuum device for direct interfacing with conventional cell culture methods

PubMed Central

Chung, Bong Geun; Park, Jeong Won; Hu, Jia Sheng; Huang, Carlos; Monuki, Edwin S; Jeon, Noo Li

2007-01-01

Background Microfluidics is an enabling technology with a number of advantages over traditional tissue culture methods when precise control of cellular microenvironment is required. However, there are a number of practical and technical limitations that impede wider implementation in routine biomedical research. Specialized equipment and protocols required for fabrication and setting up microfluidic experiments present hurdles for routine use by most biology laboratories. Results We have developed and validated a novel microfluidic device that can directly interface with conventional tissue culture methods to generate and maintain controlled soluble environments in a Petri dish. It incorporates separate sets of fluidic channels and vacuum networks on a single device that allows reversible application of microfluidic gradients onto wet cell culture surfaces. Stable, precise concentration gradients of soluble factors were generated using simple microfluidic channels that were attached to a perfusion system. We successfully demonstrated real-time optical live/dead cell imaging of neural stem cells exposed to a hydrogen peroxide gradient and chemotaxis of metastatic breast cancer cells in a growth factor gradient. Conclusion This paper describes the design and application of a versatile microfluidic device that can directly interface with conventional cell culture methods. This platform provides a simple yet versatile tool for incorporating the advantages of a microfluidic approach to biological assays without changing established tissue culture protocols. PMID:17883868

Investigation of micropump mechanism for medical application (blood transport application)

NASA Astrophysics Data System (ADS)

Piterah, N. S. M.; Ong, N. R.; Aziz, M. H. A.; Alcain, J. B.; Haimi, W. M. W. N.; Sauli, Z.

2017-09-01

A microfluidic device is a beneficial device in transporting and controling the flow of fluid in microfluidic system especially in biomedical research and application. This study proposed a valveless micropump design with reciprocating micropumping concept. This micropump mechanism model was specifically designed to overcome hydrodynamic reversibility effectively at low Reynolds number and work on finite pressure loads. The transportation of microfluidic especially biological material such as blood was presented clearly in this micropumping mechanism. The transportation of fluid throughout microchannel with low Reynolds number 16 produced 7.5 m3 maximum net volume of blood pumped from left to right and configured upstroke and downstroke situation during 0.74 seconds and 0.24 seconds respectively.

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

PubMed

Fu, Qiang; Liu, Jie

2005-07-21

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

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

PubMed

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

2017-08-01

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

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

NASA Astrophysics Data System (ADS)

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

2016-05-01

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

A metering rotary nanopump for microfluidic systems

PubMed Central

Darby, Scott G.; Moore, Matthew R.; Friedlander, Troy A.; Schaffer, David K.; Reiserer, Ron S.; Wikswo, John P.

2014-01-01

We describe the design, fabrication, and testing of a microfabricated metering rotary nanopump for the purpose of driving fluid flow in microfluidic devices. The miniature peristaltic pump is composed of a set of microfluidic channels wrapped in a helix around a central cam shaft in which a non-cylindrical cam rotates. The cam compresses the helical channels to induce peristaltic flow as it is rotated. The polydimethylsiloxane (PDMS) nanopump design is able to produce intermittent delivery or removal of several nanoliters of fluid per revolution as well as consistent continuous flow rates ranging from as low as 15 nL/min to above 1.0 µL/min. At back pressures encountered in typical microfluidic devices, the pump acts as a high impedance flow source. The durability, biocompatibility, ease of integration with soft-lithographic fabrication, the use of a simple rotary motor instead of multiple synchronized pneumatic or mechanical actuators, and the absence of power consumption or fluidic conductance in the resting state all contribute to a compact pump with a low cost of fabrication and versatile implementation. This suggests that the pump design may be useful for a wide variety of biological experiments and point of care devices. PMID:20959938

Efficient designs for powering microscale devices with nanoscale biomolecular motors.

PubMed

Lin, Chih-Ting; Kao, Ming-Tse; Kurabayashi, Katsuo; Meyhöfer, Edgar

2006-02-01

Current MEMS and microfluidic designs require external power sources and actuators, which principally limit such technology. To overcome these limitations, we have developed a number of microfluidic systems into which we can seamlessly integrate a biomolecular motor, kinesin, that transports microtubules by extracting chemical energy from its aqueous working environment. Here we establish that our microfabricated structures, the self-assembly of the bio-derived transducer, and guided, unidirectional transport of microtubules are ideally suited to create engineered arrays for efficiently powering nano- and microscale devices.

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.

Mechanically activated artificial cell by using microfluidics

NASA Astrophysics Data System (ADS)

Ho, Kenneth K. Y.; Lee, Lap Man; Liu, Allen P.

2016-09-01

All living organisms sense mechanical forces. Engineering mechanosensitive artificial cell through bottom-up in vitro reconstitution offers a way to understand how mixtures of macromolecules assemble and organize into a complex system that responds to forces. We use stable double emulsion droplets (aqueous/oil/aqueous) to prototype mechanosensitive artificial cells. In order to demonstrate mechanosensation in artificial cells, we develop a novel microfluidic device that is capable of trapping double emulsions into designated chambers, followed by compression and aspiration in a parallel manner. The microfluidic device is fabricated using multilayer soft lithography technology, and consists of a control layer and a deformable flow channel. Deflections of the PDMS membrane above the main microfluidic flow channels and trapping chamber array are independently regulated pneumatically by two sets of integrated microfluidic valves. We successfully compress and aspirate the double emulsions, which result in transient increase and permanent decrease in oil thickness, respectively. Finally, we demonstrate the influx of calcium ions as a response of our mechanically activated artificial cell through thinning of oil. The development of a microfluidic device to mechanically activate artificial cells creates new opportunities in force-activated synthetic biology.

Analysis of Electrically Induced Swirling Flow of Isotonic Saline in a Mixing Microchannel

NASA Astrophysics Data System (ADS)

Hirahara, Shuzo; Tsuruta, Tomoyuki; Matsumoto, Yoshinori; Minamitani, Haruyuki

We have designed a prototype microfluidic device to mix suspended particles with isotonic saline by use of electrically induced swirling flow in the microchannel. However, the principles underlying microfluidic rotation induced by AC electrodes are not well understood, and the characteristics of the rotation velocity are unpredictable. Furthermore, these properties have not been studied using a highly conductive liquid like isotonic saline, which is an important fluid in the medical and biological fields. The lack of such studies causes uncertainty in the design required for high-performance microfluidic devices. We have examined the electrical rotational properties of the microfluid at an isotonic concentration of saline using computer simulation, and here we show that buoyant flow, which has previously been largely ignored, has a significant effect in channels of 100-μm depth or deeper, and that AC electroosmotic flow is not induced at isotonic saline concentrations.

Microfluidics for rapid cytokeratin immunohistochemical staining in frozen sections.

PubMed

Brajkovic, Saska; Dupouy, Diego G; de Leval, Laurence; Gijs, Martin Am

2017-08-01

Frozen sections (FS) of tumor samples represent a cornerstone of pathological intraoperative consultation and have an important role in the microscopic analysis of specimens during surgery. So far, immunohistochemical (IHC) stainings on FS have been demonstrated for a few markers using manual methods. Microfluidic technologies have proven to bring substantial improvement in many fields of diagnostics, though only a few microfluidic devices have been designed to improve the performance of IHC assays. In this work, we show optimization of a complete pan-cytokeratin chromogenic immunostaining protocol on FS using a microfluidic tissue processor into a protocol taking <12 min. Our results showed specificity and low levels of background. The dimensions of the microfluidic prototype device are compatible with the space constraints of an intraoperative pathology laboratory. We therefore anticipate that the adoption of microfluidic technologies in the field of surgical pathology can significantly improve the way FSs influence surgical procedures.

Microfluidics for rapid cytokeratin immunohistochemical staining in frozen sections

PubMed Central

Brajkovic, Saska; Dupouy, Diego G.; de Leval, Laurence; Gijs, Martin A. M.

2017-01-01

Frozen sections (FS) of tumor samples represent a cornerstone of pathological intraoperative consultation and play an important role in the microscopic analysis of specimens during surgery. So far, immunohistochemical (IHC) stainings on FS have been demonstrated for a few markers using manual methods. Microfluidic technologies have proven to bring substantial improvement in many fields of diagnostics, though only a few microfluidic devices have been designed to improve the performance of IHC assays. In this work, we show optimization of a complete pan-cytokeratin chromogenic immunostaining protocol on FS using a microfluidic tissue processor, into a protocol taking less than 12 minutes. Our results showed specificity and low levels of background. The dimensions of the microfluidic prototype device are compatible with the space constraints of an intraoperative pathology laboratory. We therefore anticipate that the adoption of microfluidic technologies in the field of surgical pathology can significantly improve the way FSs influence surgical procedures. PMID:28553936

Analyzing threshold pressure limitations in microfluidic transistors for self-regulated microfluidic circuits

PubMed Central

Kim, Sung-Jin; Yokokawa, Ryuji; Takayama, Shuichi

2012-01-01

This paper reveals a critical limitation in the electro-hydraulic analogy between a microfluidic membrane-valve (μMV) and an electronic transistor. Unlike typical transistors that have similar on and off threshold voltages, in hydraulic μMVs, the threshold pressures for opening and closing are significantly different and can change, even for the same μMVs depending on overall circuit design and operation conditions. We explain, in particular, how the negative values of the closing threshold pressures significantly constrain operation of even simple hydraulic μMV circuits such as autonomously switching two-valve microfluidic oscillators. These understandings have significant implications in designing self-regulated microfluidic devices. PMID:23284181

Fundamentals of microfluidic cell culture in controlled microenvironments†

PubMed Central

Young, Edmond W. K.; Beebe, David J.

2010-01-01

Microfluidics has the potential to revolutionize the way we approach cell biology research. The dimensions of microfluidic channels are well suited to the physical scale of biological cells, and the many advantages of microfluidics make it an attractive platform for new techniques in biology. One of the key benefits of microfluidics for basic biology is the ability to control parameters of the cell microenvironment at relevant length and time scales. Considerable progress has been made in the design and use of novel microfluidic devices for culturing cells and for subsequent treatment and analysis. With the recent pace of scientific discovery, it is becoming increasingly important to evaluate existing tools and techniques, and to synthesize fundamental concepts that would further improve the efficiency of biological research at the microscale. This tutorial review integrates fundamental principles from cell biology and local microenvironments with cell culture techniques and concepts in microfluidics. Culturing cells in microscale environments requires knowledge of multiple disciplines including physics, biochemistry, and engineering. We discuss basic concepts related to the physical and biochemical microenvironments of the cell, physicochemical properties of that microenvironment, cell culture techniques, and practical knowledge of microfluidic device design and operation. We also discuss the most recent advances in microfluidic cell culture and their implications on the future of the field. The goal is to guide new and interested researchers to the important areas and challenges facing the scientific community as we strive toward full integration of microfluidics with biology. PMID:20179823

Inexpensive, rapid prototyping of microfluidic devices using overhead transparencies and a laser print, cut and laminate fabrication method.

PubMed

Thompson, Brandon L; Ouyang, Yiwen; Duarte, Gabriela R M; Carrilho, Emanuel; Krauss, Shannon T; Landers, James P

2015-06-01

We describe a technique for fabricating microfluidic devices with complex multilayer architectures using a laser printer, a CO2 laser cutter, an office laminator and common overhead transparencies as a printable substrate via a laser print, cut and laminate (PCL) methodology. The printer toner serves three functions: (i) it defines the microfluidic architecture, which is printed on the overhead transparencies; (ii) it acts as the adhesive agent for the bonding of multiple transparency layers; and (iii) it provides, in its unmodified state, printable, hydrophobic 'valves' for fluidic flow control. By using common graphics software, e.g., CorelDRAW or AutoCAD, the protocol produces microfluidic devices with a design-to-device time of ∼40 min. Devices of any shape can be generated for an array of multistep assays, with colorimetric detection of molecular species ranging from small molecules to proteins. Channels with varying depths can be formed using multiple transparency layers in which a CO2 laser is used to remove the polyester from the channel sections of the internal layers. The simplicity of the protocol, availability of the equipment and substrate and cost-effective nature of the process make microfluidic devices available to those who might benefit most from expedited, microscale chemistry.

Tape underlayment rotary-node (TURN) valves for simple on-chip microfluidic flow control

PubMed Central

Markov, Dmitry A.; Manuel, Steven; Shor, Leslie M.; Opalenik, Susan R.; Wikswo, John P.; Samson, Philip C.

2013-01-01

We describe a simple and reliable fabrication method for producing multiple, manually activated microfluidic control valves in polydimethylsiloxane (PDMS) devices. These screwdriver-actuated valves reside directly on the microfluidic chip and can provide both simple on/off operation as well as graded control of fluid flow. The fabrication procedure can be easily implemented in any soft lithography lab and requires only two specialized tools – a hot-glue gun and a machined brass mold. To facilitate use in multi-valve fluidic systems, the mold is designed to produce a linear tape that contains a series of plastic rotary nodes with small stainless steel machine screws that form individual valves which can be easily separated for applications when only single valves are required. The tape and its valves are placed on the surface of a partially cured thin PDMS microchannel device while the PDMS is still on the soft-lithographic master, with the master providing alignment marks for the tape. The tape is permanently affixed to the microchannel device by pouring an over-layer of PDMS, to form a full-thickness device with the tape as an enclosed underlayment. The advantages of these Tape Underlayment Rotary-Node (TURN) valves include parallel fabrication of multiple valves, low risk of damaging a microfluidic device during valve installation, high torque, elimination of stripped threads, the capabilities of TURN hydraulic actuators, and facile customization of TURN molds. We have utilized these valves to control microfluidic flow, to control the onset of molecular diffusion, and to manipulate channel connectivity. Practical applications of TURN valves include control of loading and chemokine release in chemotaxis assay devices, flow in microfluidic bioreactors, and channel connectivity in microfluidic devices intended to study competition and predator / prey relationships among microbes. PMID:19859812

Shrink-film microfluidic education modules: Complete devices within minutes

PubMed Central

Nguyen, Diep; McLane, Jolie; Lew, Valerie; Pegan, Jonathan; Khine, Michelle

2011-01-01

As advances in microfluidics continue to make contributions to diagnostics and life sciences, broader awareness of this expanding field becomes necessary. By leveraging low-cost microfabrication techniques that require no capital equipment or infrastructure, simple, accessible, and effective educational modules can be made available for a broad range of educational needs from middle school demonstrations to college laboratory classes. These modules demonstrate key microfluidic concepts such as diffusion and separation as well as “laboratory on-chip” applications including chemical reactions and biological assays. These modules are intended to provide an interdisciplinary hands-on experience, including chip design, fabrication of functional devices, and experiments at the microscale. Consequently, students will be able to conceptualize physics at small scales, gain experience in computer-aided design and microfabrication, and perform experiments—all in the context of addressing real-world challenges by making their own lab-on-chip devices. PMID:21799715

Shrink-film microfluidic education modules: Complete devices within minutes.

PubMed

Nguyen, Diep; McLane, Jolie; Lew, Valerie; Pegan, Jonathan; Khine, Michelle

2011-06-01

As advances in microfluidics continue to make contributions to diagnostics and life sciences, broader awareness of this expanding field becomes necessary. By leveraging low-cost microfabrication techniques that require no capital equipment or infrastructure, simple, accessible, and effective educational modules can be made available for a broad range of educational needs from middle school demonstrations to college laboratory classes. These modules demonstrate key microfluidic concepts such as diffusion and separation as well as "laboratory on-chip" applications including chemical reactions and biological assays. These modules are intended to provide an interdisciplinary hands-on experience, including chip design, fabrication of functional devices, and experiments at the microscale. Consequently, students will be able to conceptualize physics at small scales, gain experience in computer-aided design and microfabrication, and perform experiments-all in the context of addressing real-world challenges by making their own lab-on-chip devices.

Microfluidic perfusion culture.

PubMed

Hattori, Koji; Sugiura, Shinji; Kanamori, Toshiyuki

2014-01-01

Microfluidic perfusion culture is a novel technique to culture animal cells in a small-scale microchamber with medium perfusion. Polydimethylsiloxane (PDMS) is the most popular material to fabricate a microfluidic perfusion culture chip. Photolithography and replica molding techniques are generally used for fabrication of a microfluidic perfusion culture chip. Pressure-driven perfusion culture system is convenient technique to carry out the perfusion culture of animal cells in a microfluidic device. Here, we describe a general theory on microfluid network design, microfabrication technique, and experimental technique for pressure-driven perfusion culture in an 8 × 8 microchamber array on a glass slide-sized microchip made out of PDMS.

Magnetic-adhesive based valves for microfluidic devices used in low-resource settings.

PubMed

Harper, Jason C; Andrews, Jenna M; Ben, Candice; Hunt, Andrew C; Murton, Jaclyn K; Carson, Bryan D; Bachand, George D; Lovchik, Julie A; Arndt, William D; Finley, Melissa R; Edwards, Thayne L

2016-10-18

Since the introduction of micro total analytical systems (μTASs), significant advances have been made toward development of lab-on-a-chip platforms capable of performing complex biological assays that can revolutionize public health, among other applications. However, use of these platforms in low-resource environments (e.g. developing countries) has yet to be realized as the majority of technologies used to control microfluidic flow rely on off-device hardware with non-negligible size, cost, power requirements and skill/training to operate. In this paper we describe a magnetic-adhesive based valve that is simple to construct and operate, and can be used to control fluid flow and store reagents within a microfluidic device. The design consists of a port connecting two chambers on different planes in the device that is closed by a neodymium disk magnet seated on a thin ring of adhesive. Bringing an external magnet into contact with the outer surface of the device unseats and displaces the valve magnet from the adhesive ring, exposing the port. Using this configuration, we demonstrate on-device reagent storage and on-demand transport and reaction of contents between chambers. This design requires no power or external instrumentation to operate, is extremely low cost ($0.20 materials cost per valve), can be used by individuals with no technical training, and requires only a hand-held magnet to actuate. Additionally, valve actuation does not compromise the integrity of the completely sealed microfluidic device, increasing safety for the operator when toxic or harmful substances are contained within. This valve concept has the potential to simplify design of μTASs, facilitating development of lab-on-a-chip systems that may be practical for use in point-of-care and low-resource settings.

Fabrication and optimisation of a fused filament 3D-printed microfluidic platform

NASA Astrophysics Data System (ADS)

Tothill, A. M.; Partridge, M.; James, S. W.; Tatam, R. P.

2017-03-01

A 3D-printed microfluidic device was designed and manufactured using a low cost (2000) consumer grade fusion deposition modelling (FDM) 3D printer. FDM printers are not typically used, or are capable, of producing the fine detailed structures required for microfluidic fabrication. However, in this work, the optical transparency of the device was improved through manufacture optimisation to such a point that optical colorimetric assays can be performed in a 50 µl device. A colorimetric enzymatic cascade assay was optimised using glucose oxidase and horseradish peroxidase for the oxidative coupling of aminoantipyrine and chromotropic acid to produce a blue quinoneimine dye with a broad absorbance peaking at 590 nm for the quantification of glucose in solution. For comparison the assay was run in standard 96 well plates with a commercial plate reader. The results show the accurate and reproducible quantification of 0-10 mM glucose solution using a 3D-printed microfluidic optical device with performance comparable to that of a plate reader assay.

Single cell Enrichment with High Throughput Microfluidic Devices

NASA Astrophysics Data System (ADS)

Pakjesm Pourfard, Pedram

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

A microfluidic device for studying cell signaling with multiple inputs and adjustable amplitudes and frequencies

NASA Astrophysics Data System (ADS)

Ningsih, Zubaidah; Chon, James W. M.; Clayton, Andrew H. A.

2013-12-01

Cell function is largely controlled by an intricate web of macromolecular interactions called signaling networks. It is known that the type and the intensity (concentration) of stimulus affect cell behavior. However, the temporal aspect of the stimulus is not yet fully understood. Moreover, the process of distinguishing between two stimuli by a cell is still not clear. A microfluidic device enables the delivery of a precise and exact stimulus to the cell due to the laminar flow established inside its micro-channel. The slow stream delivers a constant stimulus which is adjustable according to the experiment set up. Moreover, with controllable inputs, microfluidic facilitates the stimuli delivery according to a certain pattern with adjustable amplitude, frequency and phase. Several designs of PDMS microfluidic device has been produced in this project via photolithography and soft lithography processes. To characterize the microfluidic performance, two experiments has been conducted. First, by comparing the fluorescence intensity and the lifetime of fluorescein in the present of KI, mixing extent between two inputs was observed using Frequency Lifetime Imaging Microscopy (FLIM). Furthermore, the input-output relationship of fluorescein concentration delivered was also drawn to characterize the amplitude, frequency and phase of the inputs. Second experiment involved the cell culturing inside microfluidic. Using NG108-15 cells, proliferation and differentiation were observed based on the cell number and cell physiological changes. Our results demonstrate that hurdle design gives 86% mixing of fluorescein and buffer. Relationship between inputoutput fluorescein concentrations delivered has also been demonstrated and cells were successfully cultured inside the microfluidic.

An integrated fiberoptic-microfluidic device for agglutination detection and blood typing.

PubMed

Ramasubramanian, Melur K; Alexander, Stewart P

2009-02-01

In this paper, an integrated fiberoptic-microfluidic device for the detection of agglutination for blood type cross-matching has been described. The device consists of a straight microfluidic channel through with a reacted RBC suspension is pumped with the help of a syringe pump. The flow intersects an optical path created by an emitter-received fiber optic pair integrated into the microfluidic device. A 650 nm laser diode is used as the light source and a silicon photodiode is used to detect the light intensity. The spacing between the tips of the two optic fibers can be adjusted. When fiber spacing is large and the concentration of the suspension is high, scattering phenomenon becomes the dominant mechanism for agglutination detection while at low concentrations and small spacing, optointerruption becomes the dominant mechanism. An agglutination strength factor (ASF) is calculated from the data. Studies with a variety of blood types indicate that the sensing method correctly identifies the agglutination reaction in all cases. A disposable integrated device can be designed for future implementation of the method for near-bedside pre-transfusion check.

Computational design optimization for microfluidic magnetophoresis

PubMed Central

Plouffe, Brian D.; Lewis, Laura H.; Murthy, Shashi K.

2011-01-01

Current macro- and microfluidic approaches for the isolation of mammalian cells are limited in both efficiency and purity. In order to design a robust platform for the enumeration of a target cell population, high collection efficiencies are required. Additionally, the ability to isolate pure populations with minimal biological perturbation and efficient off-chip recovery will enable subcellular analyses of these cells for applications in personalized medicine. Here, a rational design approach for a simple and efficient device that isolates target cell populations via magnetic tagging is presented. In this work, two magnetophoretic microfluidic device designs are described, with optimized dimensions and operating conditions determined from a force balance equation that considers two dominant and opposing driving forces exerted on a magnetic-particle-tagged cell, namely, magnetic and viscous drag. Quantitative design criteria for an electromagnetic field displacement-based approach are presented, wherein target cells labeled with commercial magnetic microparticles flowing in a central sample stream are shifted laterally into a collection stream. Furthermore, the final device design is constrained to fit on standard rectangular glass coverslip (60 (L)×24 (W)×0.15 (H) mm3) to accommodate small sample volume and point-of-care design considerations. The anticipated performance of the device is examined via a parametric analysis of several key variables within the model. It is observed that minimal currents (<500 mA) are required to generate magnetic fields sufficient to separate cells from the sample streams flowing at rate as high as 7 ml∕h, comparable to the performance of current state-of-the-art magnet-activated cell sorting systems currently used in clinical settings. Experimental validation of the presented model illustrates that a device designed according to the derived rational optimization can effectively isolate (∼100%) a magnetic-particle-tagged cell population from a homogeneous suspension even in a low abundance. Overall, this design analysis provides a rational basis to select the operating conditions, including chamber and wire geometry, flow rates, and applied currents, for a magnetic-microfluidic cell separation device. PMID:21526007

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

Microfluidics for Synthetic Biology: From Design to Execution

PubMed Central

Ferry, M. S.; Razinkov, I. A.; Hasty, J.

2016-01-01

With the expanding interest in cellular responses to dynamic environments, microfluidic devices have become important experimental platforms for biological research. Microfluidic “microchemostat” devices enable precise environmental control while capturing high quality, single-cell gene expression data. For studies of population heterogeneity and gene expression noise, these abilities are crucial. Here, we describe the necessary steps for experimental microfluidics using devices created in our lab as examples. First, we discuss the rational design of microchemostats and the tools available to predict their performance. We carefully analyze the critical parts of an example device, focusing on the most important part of any microchemostat: the cell trap. Next, we present a method for generating on-chip dynamic environments using an integrated fluidic junction coupled to linear actuators. Our system relies on the simple modulation of hydrostatic pressure to alter the mixing ratio between two source reservoirs and we detail the software and hardware behind it. To expand the throughput of microchemostat experiments, we describe how to build larger, parallel versions of simpler devices. To analyze the large amounts of data, we discuss methods for automated cell tracking, focusing on the special problems presented by Saccharomyces cerevisiae cells. The manufacturing of microchemostats is described in complete detail: from the photolithographic processing of the wafer to the final bonding of the PDMS chip to glass coverslip. Finally, the procedures for conducting Escherichia coli and S. cerevisiae microchemostat experiments are addressed. PMID:21601093

Linking Findings in Microfluidics to Membrane Emulsification Process Design: The Importance of Wettability and Component Interactions with Interfaces

PubMed Central

Schroën, Karin; Ferrando, Montse; de Lamo-Castellví, Silvia; Sahin, Sami; Güell, Carme

2016-01-01

In microfluidics and other microstructured devices, wettability changes, as a result of component interactions with the solid wall, can have dramatic effects. In emulsion separation and emulsification applications, the desired behavior can even be completely lost. Wettability changes also occur in one phase systems, but the effect is much more far-reaching when using two-phase systems. For microfluidic emulsification devices, this can be elegantly demonstrated and quantified for EDGE (Edge-base Droplet GEneration) devices that have a specific behavior that allows us to distinguish between surfactant and liquid interactions with the solid surface. Based on these findings, design rules can be defined for emulsification with any micro-structured emulsification device, such as direct and premix membrane emulsification. In general, it can be concluded that mostly surface interactions increase the contact angle toward 90°, either through the surfactant, or the oil that is used. This leads to poor process stability, and very limited pressure ranges at which small droplets can be made in microfluidic systems, and cross-flow membrane emulsification. In a limited number of cases, surface interactions can also lead to lower contact angles, thereby increasing the operational stability. This paper concludes with a guideline that can be used to come to the appropriate combination of membrane construction material (or any micro-structured device), surfactants and liquids, in combination with process conditions. PMID:27187484

Selecting and designing with the right thermoplastic polymer for your microfluidic chip: a close look into cyclo-olefin polymer

NASA Astrophysics Data System (ADS)

Nevitt, Mark

2013-03-01

Engineers who are developing microfluidic devices and bioMEMs for life science applications have many aspects to consider when selecting the proper base materials for constructing a device. While glass and polydimethylsiloxane (PDMS) are the staple materials for proof-of-concept and prototype chip fabrication, they are not a feasible solution for commercial production due to their slow, labor-intensive production rate. Alternatively, a molded or extruded thermoplastic solution can deliver the precision, consistency, and high volume capability required for commercial scale production. Traditional thermoplastics, such as polymethylmethacrylate (PMMA), polycarbonate (PC), and polystyrene (PS), are well known by development engineers in the bioscience community; however, cyclo-olefin polymer (COP), a relative newcomer in the world of plastics, is gaining increasing attention for use in microfluidic devices due to its unique balance of key properties compared to conventional thermoplastics. In this paper, we provide a comprehensive look at the properties which make COP an excellent candidate for providing the flow cell support and reagent storage functions in microfluidic assays. We also explore the processing attributes and capabilities of COP resin and film which are crucial for manufacturing high-performance microfluidic devices.

Design keys for paper-based concentration gradient generators.

PubMed

Schaumburg, Federico; Urteaga, Raúl; Kler, Pablo A; Berli, Claudio L A

2018-08-03

The generation of concentration gradients is an essential operation for several analytical processes implemented on microfluidic paper-based analytical devices. The dynamic gradient formation is based on the transverse dispersion of chemical species across co-flowing streams. In paper channels, this transverse flux of molecules is dominated by mechanical dispersion, which is substantially different than molecular diffusion, which is the mechanism acting in conventional microchannels. Therefore, the design of gradient generators on paper requires strategies different from those used in traditional microfluidics. This work considers the foundations of transverse dispersion in porous substrates to investigate the optimal design of microfluidic paper-based concentration gradient generators (μPGGs) by computer simulations. A set of novel and versatile μPGGs were designed in the format of numerical prototypes, and virtual experiments were run to explore the ranges of operation and the overall performance of such devices. Then physical prototypes were fabricated and experimentally tested in our lab. Finally, some basic rules for the design of optimized μPGGs are proposed. Apart from improving the efficiency of mixers, diluters and μPGGs, the results of this investigation are relevant to attain highly controlled concentration fields on paper-based devices. Copyright © 2018 Elsevier B.V. All rights reserved.

A practical guide to microfluidic perfusion culture of adherent mammalian cells.

PubMed

Kim, Lily; Toh, Yi-Chin; Voldman, Joel; Yu, Hanry

2007-06-01

Culturing cells at microscales allows control over microenvironmental cues, such as cell-cell and cell-matrix interactions; the potential to scale experiments; the use of small culture volumes; and the ability to integrate with microsystem technologies for on-chip experimentation. Microfluidic perfusion culture in particular allows controlled delivery and removal of soluble biochemical molecules in the extracellular microenvironment, and controlled application of mechanical forces exerted via fluid flow. There are many challenges to designing and operating a robust microfluidic perfusion culture system for routine culture of adherent mammalian cells. The current literature on microfluidic perfusion culture treats microfluidic design, device fabrication, cell culture, and micro-assays independently. Here we systematically present and discuss important design considerations in the context of the entire microfluidic perfusion culture system. These design considerations include the choice of materials, culture configurations, microfluidic network fabrication and micro-assays. We also present technical issues such as sterilization; seeding cells in both 2D and 3D configurations; and operating the system under optimized mass transport and shear stress conditions, free of air-bubbles. The integrative and systematic treatment of the microfluidic system design and fabrication, cell culture, and micro-assays provides novices with an effective starting point to build and operate a robust microfludic perfusion culture system for various applications.

Sensing Molecular Adsorption Through Interfacial Electron Scattering in Atom-Scale Junctions

DTIC Science & Technology

2005-10-15

Tulock, MA Shannon, JV Sweedler, PW Bohn: "Gateable nanofluidic interconnects for multilayered microfluidic separation systems" Anal. Chem. 75 (2003...1861-1867. (66) TC Kuo, DM Cannon, MA Shannon, PW Bohn, JV Sweedler: "Hybrid three- dimensional nanofluidic /microfluidic devices using molecular...boron doped ). The thin film electrodes were easily designed with lithographic techniques and allowed sealing of a PDMS microfluidic channel (Figure

Microfluidic device for trapping and monitoring three dimensional multicell spheroids using electrical impedance spectroscopy

PubMed Central

Luongo, Kevin; Holton, Angela; Kaushik, Ajeet; Spence, Paige; Ng, Beng; Deschenes, Robert; Sundaram, Shankar; Bhansali, Shekhar

2013-01-01

In this paper, we report the design, fabrication, and testing of a lab-on-a-chip based microfluidic device for application of trapping and measuring the dielectric properties of microtumors over time using electrical impedance spectroscopy (EIS). Microelectromechanical system (MEMS) techniques were used to embed opposing electrodes onto the top and bottom surfaces of a microfluidic channel fabricated using Pyrex substrate, chrome gold, SU-8, and polydimethylsiloxane. Differing concentrations of cell culture medium, differing sized polystyrene beads, and MCF-7 microtumor spheroids were used to validate the designs ability to detect background conductivity changes and dielectric particle diameter changes between electrodes. The observed changes in cell medium concentrations demonstrated a linear relation to extracted solution resistance (Rs), while polystyrene beads and multicell spheroids induced changes in magnitude consistent with diameter increase. This design permits optical correlation between electrical measurements and EIS spectra. PMID:24404028

Simple Check Valves for Microfluidic Devices

NASA Technical Reports Server (NTRS)

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

2010-01-01

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

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 Microfluidic Approach for Studying Piezo Channels.

PubMed

Maneshi, M M; Gottlieb, P A; Hua, S Z

2017-01-01

Microfluidics is an interdisciplinary field intersecting many areas in engineering. Utilizing a combination of physics, chemistry, biology, and biotechnology, along with practical applications for designing devices that use low volumes of fluids to achieve high-throughput screening, is a major goal in microfluidics. Microfluidic approaches allow the study of cells growth and differentiation using a variety of conditions including control of fluid flow that generates shear stress. Recently, Piezo1 channels were shown to respond to fluid shear stress and are crucial for vascular development. This channel is ideal for studying fluid shear stress applied to cells using microfluidic devices. We have developed an approach that allows us to analyze the role of Piezo channels on any given cell and serves as a high-throughput screen for drug discovery. We show that this approach can provide detailed information about the inhibitors of Piezo channels. Copyright © 2017 Elsevier Inc. All rights reserved.

Compact and controlled microfluidic mixing and biological particle capture

NASA Astrophysics Data System (ADS)

Ballard, Matthew; Owen, Drew; Mills, Zachary Grant; Hesketh, Peter J.; Alexeev, Alexander

2016-11-01

We use three-dimensional simulations and experiments to develop a multifunctional microfluidic device that performs rapid and controllable microfluidic mixing and specific particle capture. Our device uses a compact microfluidic channel decorated with magnetic features. A rotating magnetic field precisely controls individual magnetic microbeads orbiting around the features, enabling effective continuous-flow mixing of fluid streams over a compact mixing region. We use computer simulations to elucidate the underlying physical mechanisms that lead to effective mixing and compare them with experimental mixing results. We study the effect of various system parameters on microfluidic mixing to design an efficient micromixer. We also experimentally and numerically demonstrate that orbiting microbeads can effectively capture particles transported by the fluid, which has major implications in pre-concentration and detection of biological particles including various cells and bacteria, with applications in areas such as point-of-care diagnostics, biohazard detection, and food safety. Support from NSF and USDA is gratefully acknowledged.

Electron beam fabrication of a microfluidic device for studying submicron-scale bacteria

PubMed Central

2013-01-01

Background Controlled restriction of cellular movement using microfluidics allows one to study individual cells to gain insight into aspects of their physiology and behaviour. For example, the use of micron-sized growth channels that confine individual Escherichia coli has yielded novel insights into cell growth and death. To extend this approach to other species of bacteria, many of whom have dimensions in the sub-micron range, or to a larger range of growth conditions, a readily-fabricated device containing sub-micron features is required. Results Here we detail the fabrication of a versatile device with growth channels whose widths range from 0.3 μm to 0.8 μm. The device is fabricated using electron beam lithography, which provides excellent control over the shape and size of different growth channels and facilitates the rapid-prototyping of new designs. Features are successfully transferred first into silicon, and subsequently into the polydimethylsiloxane that forms the basis of the working microfluidic device. We demonstrate that the growth of sub-micron scale bacteria such as Lactococcus lactis or Escherichia coli cultured in minimal medium can be followed in such a device over several generations. Conclusions We have presented a detailed protocol based on electron beam fabrication together with specific dry etching procedures for the fabrication of a microfluidic device suited to study submicron-sized bacteria. We have demonstrated that both Gram-positive and Gram-negative bacteria can be successfully loaded and imaged over a number of generations in this device. Similar devices could potentially be used to study other submicron-sized organisms under conditions in which the height and shape of the growth channels are crucial to the experimental design. PMID:23575419

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.

Facile fabrication of microfluidic surface-enhanced Raman scattering devices via lift-up lithography

NASA Astrophysics Data System (ADS)

Wu, Yuanzi; Jiang, Ye; Zheng, Xiaoshan; Jia, Shasha; Zhu, Zhi; Ren, Bin; Ma, Hongwei

2018-04-01

We describe a facile and low-cost approach for a flexibly integrated surface-enhanced Raman scattering (SERS) substrate in microfluidic chips. Briefly, a SERS substrate was fabricated by the electrostatic assembling of gold nanoparticles, and shaped into designed patterns by subsequent lift-up soft lithography. The SERS micro-pattern could be further integrated within microfluidic channels conveniently. The resulting microfluidic SERS chip allowed ultrasensitive in situ SERS monitoring from the transparent glass window. With its advantages in simplicity, functionality and cost-effectiveness, this method could be readily expanded into optical microfluidic fabrication for biochemical applications.

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.

Water-assisted femtosecond laser machining of electrospray nozzles on glass microfluidic devices.

PubMed

An, Ran; Hoffman, Michelle D; Donoghue, Margaret A; Hunt, Alan J; Jacobson, Stephen C

2008-09-15

Using water-assisted femtosecond laser machining, we fabricated electrospray nozzles on glass coverslips and on assembled microfluidic devices. Machining the nozzles after device assembly facilitated alignment of the nozzles over the microchannels. The basic nozzle design is a through-hole in the coverslip to pass liquids and a trough machined around the through-hole to confine the electrospray and prevent liquid from wicking across the glass surface. Electrospray from the nozzles was stable with and without pressure-driven flow applied and was evaluated using mass spectra of the peptide bradykinin.

3D-PRINTING OF TRANSPARENT BIO-MICROFLUIDIC DEVICES IN PEG-DA

PubMed Central

Urrios, Arturo; Parra-Cabrera, Cesar; Bhattacharjee, Nirveek; Gonzalez-Suarez, Alan M.; Rigat-Brugarolas, Luis G.; Nallapatti, Umashree; Samitier, Josep; DeForest, Cole A.; Posas, Francesc; Garcia-Cordero, José L.; Folch, Albert

2016-01-01

The vast majority of microfluidic systems are molded in poly(dimethylsiloxane) (PDMS) by soft lithography due to the favorable properties of PDMS: biocompatible, elastomeric, transparent, gas-permeable, inexpensive, and copyright-free. However, PDMS molding involves tedious manual labor, which makes PDMS devices prone to assembly failures and difficult to disseminate to research and clinical settings. Furthermore, the fabrication procedures limit the 3D complexity of the devices to layered designs. Stereolithography (SL), a form of 3D-printing, has recently attracted attention as a way to customize the fabrication of biomedical devices due to its automated, assembly-free 3D fabrication, rapidly decreasing costs, and fast-improving resolution and throughput. However, existing SL resins are not biocompatible and patterning transparent resins at high resolution remains difficult. Here we report procedures for the preparation and patterning of a transparent resin based on low-MW poly(ethylene glycol) diacrylate (MW 250) (PEG-DA-250). The 3D-printed devices are highly transparent and cells can be cultured on PEG-DA-250 prints for several days. This biocompatible SL resin and printing process solves some of the main drawbacks of 3D-printed microfluidic devices: biocompatibility and transparency. In addition, it should also enable the production of non-microfluidic biomedical devices. PMID:27217203

Rapid and continuous analyte processing in droplet microfluidic devices

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

Strey, Helmut; Kimmerling, Robert; Bakowski, Tomasz

The compositions and methods described herein are designed to introduce functionalized microparticles into droplets that can be manipulated in microfluidic devices by fields, including electric (dielectrophoretic) or magnetic fields, and extracted by splitting a droplet to separate the portion of the droplet that contains the majority of the microparticles from the part that is largely devoid of the microparticles. Within the device, channels are variously configured at Y- or T junctions that facilitate continuous, serial isolation and dilution of analytes in solution. The devices can be limited in the sense that they can be designed to output purified analytes thatmore » are then further analyzed in separate machines or they can include additional channels through which purified analytes can be further processed and analyzed.« less

Mail-Order Microfluidics: Evaluation of Stereolithography for the Production of Microfluidic Devices

PubMed Central

Au, Anthony K.; Lee, Wonjae; Folch, Albert

2015-01-01

The vast majority of microfluidic devices are developed in PDMS by molding (“soft lithography”) because PDMS is an inexpensive material, has physicochemical properties that are well suited for biomedical and physical sciences applications, and design cycle lengths are generally adequate for prototype development. However, PDMS molding is tediously slow and thus cannot provide the high- or medium-volume production required for the commercialization of devices. While high-throughput plastic molding techniques (e.g. injection molding) exist, the exorbitant cost of the molds and/or the equipment can be a serious obstacle for device commercialization, especially for small startups. High-volume production is not required to reach niche markets such as clinical trials, biomedical research supplies, customized research equipment, and classroom projects. Crucially, both PDMS and plastic molding are layer-by-layer techniques where each layer is produced as a result of physicochemical processes not specified in the initial photomask(s) and where the final device requires assembly by bonding, all resulting in a cost that is very hard to predict at the start of the project. By contrast, stereolithography (SL) is an automated fabrication technique that allows for the production of quasi-arbitrary 3D shapes in a single polymeric material at medium-volume throughputs (ranging from a single part to hundreds of parts). Importantly, SL devices can be designed between several groups using CAD tools, conveniently ordered by mail, and their cost precisely predicted via a web interface. Here we evaluate the resolution of an SL mail-order service and the main causes of resolution loss; the optical clarity of the devices and how to address the lack of clarity for imaging in the channels; and the future role that SL could play in the commercialization of microfluidic devices. PMID:24510161

Mail-order microfluidics: evaluation of stereolithography for the production of microfluidic devices.

PubMed

Au, Anthony K; Lee, Wonjae; Folch, Albert

2014-04-07

The vast majority of microfluidic devices are developed in PDMS by molding ("soft lithography") because PDMS is an inexpensive material, has physicochemical properties that are well suited for biomedical and physical sciences applications, and design cycle lengths are generally adequate for prototype development. However, PDMS molding is tediously slow and thus cannot provide the high- or medium-volume production required for the commercialization of devices. While high-throughput plastic molding techniques (e.g. injection molding) exist, the exorbitant cost of the molds and/or the equipment can be a serious obstacle for device commercialization, especially for small startups. High-volume production is not required to reach niche markets such as clinical trials, biomedical research supplies, customized research equipment, and classroom projects. Crucially, both PDMS and plastic molding are layer-by-layer techniques where each layer is produced as a result of physicochemical processes not specified in the initial photomask(s) and where the final device requires assembly by bonding, all resulting in a cost that is very hard to predict at the start of the project. By contrast, stereolithography (SL) is an automated fabrication technique that allows for the production of quasi-arbitrary 3D shapes in a single polymeric material at medium-volume throughputs (ranging from a single part to hundreds of parts). Importantly, SL devices can be designed between several groups using CAD tools, conveniently ordered by mail, and their cost precisely predicted via a web interface. Here we evaluate the resolution of an SL mail-order service and the main causes of resolution loss; the optical clarity of the devices and how to address the lack of clarity for imaging in the channels; and the future role that SL could play in the commercialization of microfluidic devices.

Recent developments in microfluidics-based chemotaxis studies.

PubMed

Wu, Jiandong; Wu, Xun; Lin, Francis

2013-07-07

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

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.

Gas Transfer in Cellularized Collagen-Membrane Gas Exchange Devices.

PubMed

Lo, Justin H; Bassett, Erik K; Penson, Elliot J N; Hoganson, David M; Vacanti, Joseph P

2015-08-01

Chronic lower respiratory disease is highly prevalent in the United States, and there remains a need for alternatives to lung transplant for patients who progress to end-stage lung disease. Portable or implantable gas oxygenators based on microfluidic technologies can address this need, provided they operate both efficiently and biocompatibly. Incorporating biomimetic materials into such devices can help replicate native gas exchange function and additionally support cellular components. In this work, we have developed microfluidic devices that enable blood gas exchange across ultra-thin collagen membranes (as thin as 2 μm). Endothelial, stromal, and parenchymal cells readily adhere to these membranes, and long-term culture with cellular components results in remodeling, reflected by reduced membrane thickness. Functionally, acellular collagen-membrane lung devices can mediate effective gas exchange up to ∼288 mL/min/m(2) of oxygen and ∼685 mL/min/m(2) of carbon dioxide, approaching the gas exchange efficiency noted in the native lung. Testing several configurations of lung devices to explore various physical parameters of the device design, we concluded that thinner membranes and longer gas exchange distances result in improved hemoglobin saturation and increases in pO2. However, in the design space tested, these effects are relatively small compared to the improvement in overall oxygen and carbon dioxide transfer by increasing the blood flow rate. Finally, devices cultured with endothelial and parenchymal cells achieved similar gas exchange rates compared with acellular devices. Biomimetic blood oxygenator design opens the possibility of creating portable or implantable microfluidic devices that achieve efficient gas transfer while also maintaining physiologic conditions.

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

PubMed

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

2011-10-15

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

Microfluidic LC Device with Orthogonal Sample Extraction for On-Chip MALDI-MS Detection

PubMed Central

Lazar, Iulia M.; Kabulski, Jarod L.

2013-01-01

A microfluidic device that enables on-chip matrix assisted laser desorption ionization-mass spectrometry (MALDI-MS) detection for liquid chromatography (LC) separations is described. The device comprises an array of functional elements to carry out LC separations, integrates a novel microchip-MS interface to facilitate the orthogonal transposition of the microfluidic LC channel into an array of reservoirs, and enables sensitive MALDI-MS detection directly from the chip. Essentially, the device provides a snapshot MALDI-MS map of the content of the separation channel present on the chip. The detection of proteins with biomarker potential from MCF10A breast epithelial cell extracts, and detection limits in the low fmol range, are demonstrated. In addition, the design of the novel LC-MALDI-MS chip entices the promotion of a new concept for performing sample separations within the limited time-frame that accompanies the dead-volume of a separation channel. PMID:23592150

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.

Chemical vapor deposition of aminopropyl silanes in microfluidic channels for highly efficient microchip capillary electrophoresis-electrospray ionization-mass spectrometry.

PubMed

Batz, Nicholas G; Mellors, J Scott; Alarie, Jean Pierre; Ramsey, J Michael

2014-04-01

We describe a chemical vapor deposition (CVD) method for the surface modification of glass microfluidic devices designed to perform electrophoretic separations of cationic species. The microfluidic channel surfaces were modified using aminopropyl silane reagents. Coating homogeneity was inferred by precise measurement of the separation efficiency and electroosmotic mobility for multiple microfluidic devices. Devices coated with (3-aminopropyl)di-isopropylethoxysilane (APDIPES) yielded near diffusion-limited separations and exhibited little change in electroosmotic mobility between pH 2.8 and pH 7.5. We further evaluated the temporal stability of both APDIPES and (3-aminopropyl)triethoxysilane (APTES) coatings when stored for a total of 1 week under vacuum at 4 °C or filled with pH 2.8 background electrolyte at room temperature. Measurements of electroosmotic flow (EOF) and separation efficiency during this time confirmed that both coatings were stable under both conditions. Microfluidic devices with a 23 cm long, serpentine electrophoretic separation channel and integrated nanoelectrospray ionization emitter were CVD coated with APDIPES and used for capillary electrophoresis (CE)-electrospray ionization (ESI)-mass spectrometry (MS) of peptides and proteins. Peptide separations were fast and highly efficient, yielding theoretical plate counts over 600,000 and a peak capacity of 64 in less than 90 s. Intact protein separations using these devices yielded Gaussian peak profiles with separation efficiencies between 100,000 and 400,000 theoretical plates.

Microfluidics for synthetic biology: from design to execution.

PubMed

Ferry, M S; Razinkov, I A; Hasty, J

2011-01-01

With the expanding interest in cellular responses to dynamic environments, microfluidic devices have become important experimental platforms for biological research. Microfluidic "microchemostat" devices enable precise environmental control while capturing high quality, single-cell gene expression data. For studies of population heterogeneity and gene expression noise, these abilities are crucial. Here, we describe the necessary steps for experimental microfluidics using devices created in our lab as examples. First, we discuss the rational design of microchemostats and the tools available to predict their performance. We carefully analyze the critical parts of an example device, focusing on the most important part of any microchemostat: the cell trap. Next, we present a method for generating on-chip dynamic environments using an integrated fluidic junction coupled to linear actuators. Our system relies on the simple modulation of hydrostatic pressure to alter the mixing ratio between two source reservoirs and we detail the software and hardware behind it. To expand the throughput of microchemostat experiments, we describe how to build larger, parallel versions of simpler devices. To analyze the large amounts of data, we discuss methods for automated cell tracking, focusing on the special problems presented by Saccharomyces cerevisiae cells. The manufacturing of microchemostats is described in complete detail: from the photolithographic processing of the wafer to the final bonding of the PDMS chip to glass coverslip. Finally, the procedures for conducting Escherichia coli and S. cerevisiae microchemostat experiments are addressed. Copyright © 2011 Elsevier Inc. All rights reserved.

Microtechnology in Space: NASA's Lab-on-a-Chip Applications Development Program

NASA Technical Reports Server (NTRS)

Monaco, Lisa; Spearing, Scott; Jenkins, Andy; Symonds, Wes; Mayer, Derek; Gouldie, Edd; Wainwright, Norm; Fries, Marc; Maule, Jake; Toporski, Jan

2004-01-01

NASA's Marshall Space Flight Center (MSFC) Lab on a Chip Application Development LOCAD) team has worked with microfluidic technology for the past few years in an effort to support NASA's Mission. In that time, such microfluidic based Lab-on-a-Chip (LOC) systems have become common technology in clinical and diagnostic laboratories. The approach is most attractive due to its highly miniaturized platform and ability to perform reagent handling (i-e., dilution, mixing, separation) and diagnostics for multiple reactions in an integrated fashion. LOCAD, along with Caliper Life Sciences has successfully developed the first LOC device for macromolecular crystallization using a workstation acquired specifically for designing custom chips, the Caliper 42. LOCAD uses this, along with a novel MSFC-designed and built workstation for microfluidic development. The team has a cadre of LOC devices that can be used to perform initial feasibility testing to determine the efficacy of the LOC approach for a specific application. Once applicability has been established, the LOCAD team, along with the Army's Aviation and Missile Command microfabrication facility, can then begin to custom design and fabricate a device per the user's specifications. This presentation will highlight the LOCAD team's proven and unique expertise that has been utilized to provide end to end capabilities associated with applying microfluidics for applications that include robotic life detection instrumentation, crew health monitoring and microbial and environmental monitoring for human Exploration.

The design of a microfluidic biochip for the rapid, multiplexed detection of foodborne pathogens by surface plasmon resonance imaging

NASA Astrophysics Data System (ADS)

Zordan, Michael D.; Grafton, Meggie M. G.; Park, Kinam; Leary, James F.

2010-02-01

The rapid detection of foodborne pathogens is increasingly important due to the rising occurrence of contaminated food supplies. We have previously demonstrated the design of a hybrid optical device that has the capability to perform realtime surface plasmon resonance (SPR) and epi-fluorescence imaging. We now present the design of a microfluidic biochip consisting of a two-dimensional array of functionalized gold spots. The spots on the array have been functionalized with capture peptides that specifically bind E. coli O157:H7 or Salmonella enterica. This array is enclosed by a PDMS microfluidic flow cell. A magnetically pre-concentrated sample is injected into the biochip, and whole pathogens will bind to the capture array. The previously constructed optical device is being used to detect the presence and identity of captured pathogens using SPR imaging. This detection occurs in a label-free manner, and does not require the culture of bacterial samples. Molecular imaging can also be performed using the epi-fluorescence capabilities of the device to determine pathogen state, or to validate the identity of the captured pathogens using fluorescently labeled antibodies. We demonstrate the real-time screening of a sample for the presence of E. coli O157:H7 and Salmonella enterica. Additionally the mechanical properties of the microfluidic flow cell will be assessed. The effect of these properties on pathogen capture will be examined.

A Microfluidic Cell Concentrator

PubMed Central

Warrick, Jay; Casavant, Ben; Frisk, Megan; Beebe, David

2010-01-01

Cell concentration via centrifugation is a ubiquitous step in many cell culture procedures. At the macroscale, centrifugation suffers from a number of limitations particularly when dealing with small numbers of cells (e.g., less than 50,000). On the other hand, typical microscale methods for cell concentration can affect cell physiology and bias readouts of cell behavior and function. In this paper, we present a microfluidic concentrator device that utilizes the effects of gravity to allow cells to gently settle out of a suspension into a collection region without the use of specific adhesion ligands. Dimensional analysis was performed to compare different device designs and was verified with flow modeling to optimize operational parameters. We are able to concentrate low-density cell suspensions in a microfluidic chamber, achieving a cell loss of only 1.1 ± 0.6% (SD, n=7) with no observed loss during a subsequent cell staining protocol which incorporates ~36 complete device volume replacements. This method provides a much needed interface between rare cell samples and microfluidic culture assays. PMID:20843010

A microfluidic platform for chemical stimulation and real time analysis of catecholamine secretion from neuroendocrine cells.

PubMed

Ges, Igor A; Brindley, Rebecca L; Currie, Kevin P M; Baudenbacher, Franz J

2013-12-07

Release of neurotransmitters and hormones by calcium-regulated exocytosis is a fundamental cellular process that is disrupted in a variety of psychiatric, neurological, and endocrine disorders. As such, there is significant interest in targeting neurosecretion for drug and therapeutic development, efforts that will be aided by novel analytical tools and devices that provide mechanistic insight coupled with increased experimental throughput. Here, we report a simple, inexpensive, reusable, microfluidic device designed to analyze catecholamine secretion from small populations of adrenal chromaffin cells in real time, an important neuroendocrine component of the sympathetic nervous system and versatile neurosecretory model. The device is fabricated by replica molding of polydimethylsiloxane (PDMS) using patterned photoresist on silicon wafer as the master. Microfluidic inlet channels lead to an array of U-shaped "cell traps", each capable of immobilizing single or small groups of chromaffin cells. The bottom of the device is a glass slide with patterned thin film platinum electrodes used for electrochemical detection of catecholamines in real time. We demonstrate reliable loading of the device with small populations of chromaffin cells, and perfusion/repetitive stimulation with physiologically relevant secretagogues (carbachol, PACAP, KCl) using the microfluidic network. Evoked catecholamine secretion was reproducible over multiple rounds of stimulation, and graded as expected to different concentrations of secretagogue or removal of extracellular calcium. Overall, we show this microfluidic device can be used to implement complex stimulation paradigms and analyze the amount and kinetics of catecholamine secretion from small populations of neuroendocrine cells in real time.

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.

Centrifugal sedimentation for selectively packing channels with silica microbeads in three-dimensional micro/nanofluidic devices.

PubMed

Gong, Maojun; Bohn, Paul W; Sweedler, Jonathan V

2009-03-01

Incorporation of nanofluidic elements into microfluidic channels is one approach for adding filtration and partition functionality to planar microfluidic devices, as well as providing enhanced biomolecular separations. Here we introduce a strategy to pack microfluidic channels with silica nanoparticles and microbeads, thereby indirectly producing functional nanostructures; the method allows selected channels to be packed, here demonstrated so that a separation channel is packed while keeping an injection channel unpacked. A nanocapillary array membrane is integrated between two patterned microfluidic channels that cross each other in vertically separated layers. The membrane serves both as a frit for bead packing and as a fluid communication conduit between microfluidic channels. Centrifugal force-assisted sedimentation is then used to selectively pack the microfluidic channels using an aqueous silica bead suspension loaded into the appropriate inlet reservoirs. This packing approach may be used to simultaneously pack multiple channels with silica microbeads having different sizes and surface properties. The chip design and packing method introduced here are suitable for packing silica particles in sizes ranging from nanometers to micrometers and allow rapid (approximately 10 min) packing with high quality. The liquid/analyte transport characteristics of these packed micro/nanofluidic devices have potential utility in a wide range of applications, including electroosmotic pumping, liquid chromatographic separations, and electrochromatography.

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.

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

DOE PAGES

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

2015-08-14

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

Behaviour and design considerations for continuous flow closed-open-closed liquid microchannels.

PubMed

Melin, Jessica; van der Wijngaart, Wouter; Stemme, Göran

2005-06-01

This paper introduces a method of combining open and closed microchannels in a single component in a novel way which couples the benefits of both open and closed microfluidic systems and introduces interesting on-chip microfluidic behaviour. Fluid behaviour in such a component, based on continuous pressure driven flow and surface tension, is discussed in terms of cross sectional flow behaviour, robustness, flow-pressure performance, and its application to microfluidic interfacing. The closed-open-closed microchannel possesses the versatility of upstream and downstream closed microfluidics along with open fluidic direct access. The device has the advantage of eliminating gas bubbles present upstream when these enter the open channel section. The unique behaviour of this device opens the door to applications including direct liquid sample interfacing without the need for additional and bulky sample tubing.

Design of point-of-care (POC) microfluidic medical diagnostic devices

NASA Astrophysics Data System (ADS)

Leary, James F.

2018-02-01

Design of inexpensive and portable hand-held microfluidic flow/image cytometry devices for initial medical diagnostics at the point of initial patient contact by emergency medical personnel in the field requires careful design in terms of power/weight requirements to allow for realistic portability as a hand-held, point-of-care medical diagnostics device. True portability also requires small micro-pumps for high-throughput capability. Weight/power requirements dictate use of super-bright LEDs and very small silicon photodiodes or nanophotonic sensors that can be powered by batteries. Signal-to-noise characteristics can be greatly improved by appropriately pulsing the LED excitation sources and sampling and subtracting noise in between excitation pulses. The requirements for basic computing, imaging, GPS and basic telecommunications can be simultaneously met by use of smartphone technologies, which become part of the overall device. Software for a user-interface system, limited real-time computing, real-time imaging, and offline data analysis can be accomplished through multi-platform software development systems that are well-suited to a variety of currently available cellphone technologies which already contain all of these capabilities. Microfluidic cytometry requires judicious use of small sample volumes and appropriate statistical sampling by microfluidic cytometry or imaging for adequate statistical significance to permit real-time (typically < 15 minutes) medical decisions for patients at the physician's office or real-time decision making in the field. One or two drops of blood obtained by pin-prick should be able to provide statistically meaningful results for use in making real-time medical decisions without the need for blood fractionation, which is not realistic in the field.

Fabrication of a multiplexed microfluidic system for scaled up production of cross-linked biocatalytic microspheres

NASA Astrophysics Data System (ADS)

Mbanjwa, Mesuli B.; Chen, Hao; Fourie, Louis; Ngwenya, Sibusiso; Land, Kevin

2014-06-01

Multiplexed or parallelised droplet microfluidic systems allow for increased throughput in the production of emulsions and microparticles, while maintaining a small footprint and utilising minimal ancillary equipment. The current paper demonstrates the design and fabrication of a multiplexed microfluidic system for producing biocatalytic microspheres. The microfluidic system consists of an array of 10 parallel microfluidic circuits, for simultaneous operation to demonstrate increased production throughput. The flow distribution was achieved using a principle of reservoirs supplying individual microfluidic circuits. The microfluidic devices were fabricated in poly (dimethylsiloxane) (PDMS) using soft lithography techniques. The consistency of the flow distribution was determined by measuring the size variations of the microspheres produced. The coefficient of variation of the particles was determined to be 9%, an indication of consistent particle formation and good flow distribution between the 10 microfluidic circuits.

Design of a rapid magnetic microfluidic mixer

NASA Astrophysics Data System (ADS)

Ballard, Matthew; Owen, Drew; Mills, Zachary Grant; Hanasoge, Srinivas; Hesketh, Peter; Alexeev, Alexander

2015-11-01

Using three-dimensional simulations and experiments, we demonstrate rapid mixing of fluid streams in a microchannel using orbiting magnetic microbeads. We use a lattice Boltzmann model coupled to a Brownian dynamics model to perform numerical simulations that study in depth the effect of system parameters such as channel configuration and fluid and bead velocities. We use our findings to aid the design of an experimental micromixer. Using this experimental device, we demonstrate rapid microfluidic mixing over a compact channel length, and validate our numerical simulation results. Finally, we use numerical simulations to study the physical mechanisms leading to microfluidic mixing in our system. Our findings demonstrate a promising method of rapid microfluidic mixing over a short distance, with applications in lab-on-a-chip sample testing.

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.

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.

Microfluidic device for unidirectional axon growth

NASA Astrophysics Data System (ADS)

Malishev, E.; Pimashkin, A.; Gladkov, A.; Pigareva, Y.; Bukatin, A.; Kazantsev, V.; Mukhina, I.; Dubina, M.

2015-11-01

In order to better understand the communication and connectivity development of neuron networks, we designed microfluidic devices with several chambers for growing dissociated neuronal cultures from mice fetal hippocampus (E18). The chambers were connected with microchannels providing unidirectional axonal growth between “Source” and “Target” neural sub-networks. Experiments were performed in a hippocampal cultures plated in a poly-dimethylsiloxane (PDMS) microfluidic chip, aligned with a 60 microelectrode array (MEA). Axonal growth through microchannels was observed with brightfield, phase-contrast and fluorescence microscopy, and after 7 days in vitro electrical activity was recorded. Visual inspection and spike propagation analysis showed the predominant axonal growth in microchannels in a direction from “Source” to “Target”.

Rapid isolation of cancer cells using microfluidic deterministic lateral displacement structure.

PubMed

Liu, Zongbin; Huang, Fei; Du, Jinghui; Shu, Weiliang; Feng, Hongtao; Xu, Xiaoping; Chen, Yan

2013-01-01

This work reports a microfluidic device with deterministic lateral displacement (DLD) arrays allowing rapid and label-free cancer cell separation and enrichment from diluted peripheral whole blood, by exploiting the size-dependent hydrodynamic forces. Experiment data and theoretical simulation are presented to evaluate the isolation efficiency of various types of cancer cells in the microfluidic DLD structure. We also demonstrated the use of both circular and triangular post arrays for cancer cell separation in cell solution and blood samples. The device was able to achieve high cancer cell isolation efficiency and enrichment factor with our optimized design. Therefore, this platform with DLD structure shows great potential on fundamental and clinical studies of circulating tumor cells.

Investigation of Diffusion Characteristics through Microfluidic Channels for Passive Drug Delivery Applications

PubMed Central

Ghuman, Alyssa P.; Collins, Stephanie B.; Handa, Hitesh

2016-01-01

Microfluidics has many drug delivery applications due to the ability to easily create complex device designs with feature sizes reaching down to the 10s of microns. In this work, three different microchannel designs for an implantable device are investigated for treatment of ocular diseases such as glaucoma, age-related macular degeneration (AMD), and diabetic retinopathy. Devices were fabricated using polydimethylsiloxane (PDMS) and soft lithography techniques, where surface chemistry of the channels was altered using 2-[methoxy(polyethyleneoxy)propyl]trimethoxysilane (PEG-silane). An estimated delivery rate for a number of common drugs was approximated for each device through the ratio of the diffusion coefficients for the dye and the respective drug. The delivery rate of the model drugs was maintained at a physiological condition and the effects of channel design and surface chemistry on the delivery rate of the model drugs were recorded over a two-week period. Results showed that the surface chemistry of the device had no significant effect on the delivery rate of the model drugs. All designs were successful in delivering a constant daily dose for each model drug. PMID:27313895

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

Review of Recent Metamaterial Microfluidic Sensors

PubMed Central

Salim, Ahmed

2018-01-01

Metamaterial elements/arrays exhibit a sensitive response to fluids yet with a small footprint, therefore, they have been an attractive choice to realize various sensing devices when integrated with microfluidic technology. Micro-channels made from inexpensive biocompatible materials avoid any contamination from environment and require only microliter–nanoliter sample for sensing. Simple design, easy fabrication process, light weight prototype, and instant measurements are advantages as compared to conventional (optical, electrochemical and biological) sensing systems. Inkjet-printed flexible sensors find their utilization in rapidly growing wearable electronics and health-monitoring flexible devices. Adequate sensitivity and repeatability of these low profile microfluidic sensors make them a potential candidate for point-of-care testing which novice patients can use reliably. Aside from degraded sensitivity and lack of selectivity in all practical microwave chemical sensors, they require an instrument, such as vector network analyzer for measurements and not readily available as a self-sustained portable sensor. This review article presents state-of-the-art metamaterial inspired microfluidic bio/chemical sensors (passive devices ranging from gigahertz to terahertz range) with an emphasis on metamaterial sensing circuit and microfluidic detection. We also highlight challenges and strategies to cope these issues which set future directions. PMID:29342953

Review of Recent Metamaterial Microfluidic Sensors.

PubMed

Salim, Ahmed; Lim, Sungjoon

2018-01-15

Metamaterial elements/arrays exhibit a sensitive response to fluids yet with a small footprint, therefore, they have been an attractive choice to realize various sensing devices when integrated with microfluidic technology. Micro-channels made from inexpensive biocompatible materials avoid any contamination from environment and require only microliter-nanoliter sample for sensing. Simple design, easy fabrication process, light weight prototype, and instant measurements are advantages as compared to conventional (optical, electrochemical and biological) sensing systems. Inkjet-printed flexible sensors find their utilization in rapidly growing wearable electronics and health-monitoring flexible devices. Adequate sensitivity and repeatability of these low profile microfluidic sensors make them a potential candidate for point-of-care testing which novice patients can use reliably. Aside from degraded sensitivity and lack of selectivity in all practical microwave chemical sensors, they require an instrument, such as vector network analyzer for measurements and not readily available as a self-sustained portable sensor. This review article presents state-of-the-art metamaterial inspired microfluidic bio/chemical sensors (passive devices ranging from gigahertz to terahertz range) with an emphasis on metamaterial sensing circuit and microfluidic detection. We also highlight challenges and strategies to cope these issues which set future directions.

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.

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.

Hardware and circuit design of a vibrational cleaner

NASA Astrophysics Data System (ADS)

Fhong Soon, Chin; Thong, Kok Tung; Sek Tee, Kian; Nayan, Nafarizal; Khairul Ahmad, Mohd; Nurashikin Nordin, Anis

2016-11-01

Microtissue can be grown on soft substrates of hydrogel or liquid crystal gel. These gels are adherent to the microtissues and they may interfere fluorescence imaging as background noise due to their absorbance property. A microfluidic vibrational cleaner with polydimethylsiloxane (PDMS) microfluidic chip platform was proposed and developed to remove the residual gel of liquid crystal adhered to the microtissues. The microtissues were placed in a microfluidic chip attaching to a microfluidic vibrational platform. In the system design, two motorised vibrators vibrating attached to a microfluidic platform and generating vibration signals at 148 Hz and 0.89 Grms to clean the microtissues. The acceleration of the vibration increased gradually from 0 to 0.96 Grms when the duty cycle of PWM pulses increased from 50 - 90%. It dropped slightly to 0.89 Grms at 100% duty cycle. Irrigation water valve was designed to control the fluid flow from water pump during cleaning process. Water pumps were included to flush the channels of the microfluidic device. The signals in controlling the pump, motor and valve were linearly proportional to the duty cycles of the pulse width modulation signals generated from a microcontroller.

A self-loading microfluidic device for determining the minimum inhibitory concentration of antibiotics.

PubMed

Cira, Nate J; Ho, Jack Y; Dueck, Megan E; Weibel, Douglas B

2012-03-21

This article describes a portable microfluidic technology for determining the minimum inhibitory concentration (MIC) of antibiotics against bacteria. The microfluidic platform consists of a set of chambers molded in poly(dimethylsiloxane) (PDMS) that are preloaded with antibiotic, dried, and reversibly sealed to a second layer of PDMS containing channels that connect the chambers. The assembled device is degassed via vacuum prior to its use, and the absorption of gas by PDMS provides the mechanism for actuating and metering the flow of fluid in the microfluidic channels and chambers. During the operation of the device, degas driven flow introduces a suspension of bacterial cells, dissolves the antibiotic, and isolates cells in individual chambers without cross contamination. The growth of bacteria in the chambers in the presence of a pH indicator produces a colorimetric change that can be detected visually using ambient light. Using this device we measured the MIC of vancomycin, tetracycline, and kanamycin against Enterococcus faecalis 1131, Proteus mirabilis HI4320, Klebsiella pneumoniae, and Escherichia coli MG1655 and report values that are comparable to standard liquid broth dilution measurements. The device provides a simple method for MIC determination of individual antibiotics against human pathogens that will have applications for clinical and point-of-care medicine. Importantly, this device is designed around simplicity: it requires a single pipetting step to introduce the sample, no additional components or external equipment for its operation, and provides a straightforward visual measurement of cell growth. As the device introduces a novel approach for filling and isolating dead-end microfluidic chambers that does not require valves and actuators, this technology should find applications in other portable assays and devices.

A microfluidic device for 2D to 3D and 3D to 3D cell navigation

NASA Astrophysics Data System (ADS)

Shamloo, Amir; Amirifar, Leyla

2016-01-01

Microfluidic devices have received wide attention and shown great potential in the field of tissue engineering and regenerative medicine. Investigating cell response to various stimulations is much more accurate and comprehensive with the aid of microfluidic devices. In this study, we introduced a microfluidic device by which the matrix density as a mechanical property and the concentration profile of a biochemical factor as a chemical property could be altered. Our microfluidic device has a cell tank and a cell culture chamber to mimic both 2D to 3D and 3D to 3D migration of three types of cells. Fluid shear stress is negligible on the cells and a stable concentration gradient can be obtained by diffusion. The device was designed by a numerical simulation so that the uniformity of the concentration gradients throughout the cell culture chamber was obtained. Adult neural cells were cultured within this device and they showed different branching and axonal navigation phenotypes within varying nerve growth factor (NGF) concentration profiles. Neural stem cells were also cultured within varying collagen matrix densities while exposed to NGF concentrations and they experienced 3D to 3D collective migration. By generating vascular endothelial growth factor concentration gradients, adult human dermal microvascular endothelial cells also migrated in a 2D to 3D manner and formed a stable lumen within a specific collagen matrix density. It was observed that a minimum absolute concentration and concentration gradient were required to stimulate migration of all types of the cells. This device has the advantage of changing multiple parameters simultaneously and is expected to have wide applicability in cell studies.

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

Apparent Softening of Wet Graphene Membranes on a Microfluidic Platform.

PubMed

Ferrari, Gustavo A; de Oliveira, Alan B; Silvestre, Ive; Matos, Matheus J S; Batista, Ronaldo J C; Fernandes, Thales F D; Meireles, Leonel M; Eliel, Gomes S N; Chacham, Helio; Neves, Bernardo R A; Lacerda, Rodrigo G

2018-05-22

Graphene is regarded as the toughest two-dimensional material (highest in-plane elastic properties) and, as a consequence, it has been employed/proposed as an ultrathin membrane in a myriad of microfluidic devices. Yet, an experimental investigation of eventual variations on the apparent elastic properties of a suspended graphene membrane in contact with air or water is still missing. In this work, the mechanical response of suspended monolayer graphene membranes on a microfluidic platform is investigated via scanning probe microscopy experiments. A high elastic modulus is measured for the membrane when the platform is filled with air, as expected. However, a significant apparent softening of graphene is observed when water fills the microfluidic system. Through molecular dynamics simulations and a phenomenological model, we associate such softening to a water-induced uncrumpling process of the suspended graphene membrane. This result may bring substantial modifications on the design and operation of microfluidic devices which exploit pressure application on graphene membranes.

Precise pooling and dispensing of microfluidic droplets towards micro- to macro-world interfacing

PubMed Central

Brouzes, Eric; Carniol, April; Bakowski, Tomasz; Strey, Helmut H.

2014-01-01

Droplet microfluidics possesses unique properties such as the ability to carry out multiple independent reactions without dispersion of samples in microchannels. We seek to extend the use of droplet microfluidics to a new range of applications by enabling its integration into workflows based on traditional technologies, such as microtiter plates. Our strategy consists in developing a novel method to manipulate, pool and deliver a precise number of microfluidic droplets. To this aim, we present a basic module that combines droplet trapping with an on-chip valve. We quantitatively analyzed the trapping efficiency of the basic module in order to optimize its design. We also demonstrate the integration of the basic module into a multiplex device that can deliver 8 droplets at every cycle. This device will have a great impact in low throughput droplet applications that necessitate interfacing with macroscale technologies. The micro- to macro- interface is particularly critical in microfluidic applications that aim at sample preparation and has not been rigorously addressed in this context. PMID:25485102

Continuous nucleus extraction by optically-induced cell lysis on a batch-type microfluidic platform.

PubMed

Huang, Shih-Hsuan; Hung, Lien-Yu; Lee, Gwo-Bin

2016-04-21

The extraction of a cell's nucleus is an essential technique required for a number of procedures, such as disease diagnosis, genetic replication, and animal cloning. However, existing nucleus extraction techniques are relatively inefficient and labor-intensive. Therefore, this study presents an innovative, microfluidics-based approach featuring optically-induced cell lysis (OICL) for nucleus extraction and collection in an automatic format. In comparison to previous micro-devices designed for nucleus extraction, the new OICL device designed herein is superior in terms of flexibility, selectivity, and efficiency. To facilitate this OICL module for continuous nucleus extraction, we further integrated an optically-induced dielectrophoresis (ODEP) module with the OICL device within the microfluidic chip. This on-chip integration circumvents the need for highly trained personnel and expensive, cumbersome equipment. Specifically, this microfluidic system automates four steps by 1) automatically focusing and transporting cells, 2) releasing the nuclei on the OICL module, 3) isolating the nuclei on the ODEP module, and 4) collecting the nuclei in the outlet chamber. The efficiency of cell membrane lysis and the ODEP nucleus separation was measured to be 78.04 ± 5.70% and 80.90 ± 5.98%, respectively, leading to an overall nucleus extraction efficiency of 58.21 ± 2.21%. These results demonstrate that this microfluidics-based system can successfully perform nucleus extraction, and the integrated platform is therefore promising in cell fusion technology with the goal of achieving genetic replication, or even animal cloning, in the near future.

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.

Numerical design and optimization of hydraulic resistance and wall shear stress inside pressure-driven microfluidic networks.

PubMed

Damiri, Hazem Salim; Bardaweel, Hamzeh Khalid

2015-11-07

Microfluidic networks represent the milestone of microfluidic devices. Recent advancements in microfluidic technologies mandate complex designs where both hydraulic resistance and pressure drop across the microfluidic network are minimized, while wall shear stress is precisely mapped throughout the network. In this work, a combination of theoretical and modeling techniques is used to construct a microfluidic network that operates under minimum hydraulic resistance and minimum pressure drop while constraining wall shear stress throughout the network. The results show that in order to minimize the hydraulic resistance and pressure drop throughout the network while maintaining constant wall shear stress throughout the network, geometric and shape conditions related to the compactness and aspect ratio of the parent and daughter branches must be followed. Also, results suggest that while a "local" minimum hydraulic resistance can be achieved for a geometry with an arbitrary aspect ratio, a "global" minimum hydraulic resistance occurs only when the aspect ratio of that geometry is set to unity. Thus, it is concluded that square and equilateral triangular cross-sectional area microfluidic networks have the least resistance compared to all rectangular and isosceles triangular cross-sectional microfluidic networks, respectively. Precise control over wall shear stress through the bifurcations of the microfluidic network is demonstrated in this work. Three multi-generation microfluidic network designs are considered. In these three designs, wall shear stress in the microfluidic network is successfully kept constant, increased in the daughter-branch direction, or decreased in the daughter-branch direction, respectively. For the multi-generation microfluidic network with constant wall shear stress, the design guidelines presented in this work result in identical profiles of wall shear stresses not only within a single generation but also through all the generations of the microfluidic network under investigation. The results obtained in this work are consistent with previously reported data and suitable for a wide range of lab-on-chip applications.

Principles, Techniques, and Applications of Tissue Microfluidics

NASA Technical Reports Server (NTRS)

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

2011-01-01

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

Integrated electrofluidic circuits: pressure sensing with analog and digital operation functionalities for microfluidics.

PubMed

Wu, Chueh-Yu; Lu, Jau-Ching; Liu, Man-Chi; Tung, Yi-Chung

2012-10-21

Microfluidic technology plays an essential role in various lab on a chip devices due to its desired advantages. An automated microfluidic system integrated with actuators and sensors can further achieve better controllability. A number of microfluidic actuation schemes have been well developed. In contrast, most of the existing sensing methods still heavily rely on optical observations and external transducers, which have drawbacks including: costly instrumentation, professional operation, tedious interfacing, and difficulties of scaling up and further signal processing. This paper reports the concept of electrofluidic circuits - electrical circuits which are constructed using ionic liquid (IL)-filled fluidic channels. The developed electrofluidic circuits can be fabricated using a well-developed multi-layer soft lithography (MSL) process with polydimethylsiloxane (PDMS) microfluidic channels. Electrofluidic circuits allow seamless integration of pressure sensors with analog and digital operation functions into microfluidic systems and provide electrical readouts for further signal processing. In the experiments, the analog operation device is constructed based on electrofluidic Wheatstone bridge circuits with electrical outputs of the addition and subtraction results of the applied pressures. The digital operation (AND, OR, and XOR) devices are constructed using the electrofluidic pressure controlled switches, and output electrical signals of digital operations of the applied pressures. The experimental results demonstrate the designed functions for analog and digital operations of applied pressures are successfully achieved using the developed electrofluidic circuits, making them promising to develop integrated microfluidic systems with capabilities of precise pressure monitoring and further feedback control for advanced lab on a chip applications.

A microfluidic platform for chemical stimulation and real time analysis of catecholamine secretion from neuroendocrine cells

PubMed Central

Ges, Igor A.; Brindley, Rebecca L.; Currie, Kevin P.M.; Baudenbacher, Franz J.

2013-01-01

Release of neurotransmitters and hormones by calcium-regulated exocytosis is a fundamental cellular process that is disrupted in a variety of psychiatric, neurological, and endocrine disorders. As such, there is significant interest in targeting neurosecretion for drug and therapeutic development, efforts that will be aided by novel analytical tools and devices that provide mechanistic insight coupled with increased experimental throughput. Here, we report a simple, inexpensive, reusable, microfluidic device designed to analyze catecholamine secretion from small populations of adrenal chromaffin cells in real time, an important neuroendocrine component of the sympathetic nervous system and versatile neurosecretory model. The device is fabricated by replica molding of polydimethylsiloxane (PDMS) using patterned photoresist on silicon wafer as the master. Microfluidic inlet channels lead to an array of U-shaped “cell traps”, each capable of immobilizing single or small groups of chromaffin cells. The bottom of the device is a glass slide with patterned thin film platinum electrodes used for electrochemical detection of catecholamines in real time. We demonstrate reliable loading of the device with small populations of chromaffin cells, and perfusion / repetitive stimulation with physiologically relevant secretagogues (carbachol, PACAP, KCl) using the microfluidic network. Evoked catecholamine secretion was reproducible over multiple rounds of stimulation, and graded as expected to different concentrations of secretagogue or removal of extracellular calcium. Overall, we show this microfluidic device can be used to implement complex stimulation paradigms and analyze the amount and kinetics of catecholamine secretion from small populations of neuroendocrine cells in real time. PMID:24126415

Uniform, stable supply of medium for in vitro cell culture using a robust chamber

NASA Astrophysics Data System (ADS)

Wei, Juan; Liu, Chong; Jiang, Yang; Liu, Tao; Chen, Li; Liu, Bo; Li, Jingmin

2018-06-01

A uniform, stable supply of medium is important for in vitro cell culture. In this paper, a microfluidic device is presented for culturing cells inside a robust chamber with continuous perfusion of medium. The device consists of a main channel, two bifurcated channels and a culture chamber. The culture chamber connects to the bifurcated channels via multiple paths, and distributes symmetrically on the main channel, to improve the efficiency of medium exchange. Furthermore, regular polygonal chambers with various numbers of edges have been designed, to study the effects of chamber shape on flow fields. The finite element method has been employed to predict the effects of multiple paths on the uniformity and stability of flow fields in the culture chamber. Particle tracking technology has been used to evaluate the flow fields in the chambers, and PC-12 cells have been cultured using the microfluidic device, to test its validity. The results of simulation and experiment indicate that the microfluidic design could provide a continuous interstitial-like flow microenvironment, with a relatively stable and uniform supply of medium.

Three-dimensional parallelization of microfluidic droplet generators for a litre per hour volume production of single emulsions.

PubMed

Conchouso, D; Castro, D; Khan, S A; Foulds, I G

2014-08-21

This paper looks at the design, fabrication and characterization of stackable microfluidic emulsion generators, with coefficients of variation as low as ~6% and with production rates as high as ~1 L h(-1). This work reports the highest throughput reported in the literature for a microfluidic device with simultaneous operation of liquid-liquid droplet generators. The device was achieved by stacking several layers of 128 flow-focusing droplet generators, organized in a circular array. These layers are interconnected via through-holes and fed with designated fractal distribution networks. The proposed layers were milled on poly(methylmethacrylate) (PMMA) sheets and the stack was thermo-compression bonded to create a three-dimensional device with a high density of generators and an integrated hydraulic manifold. The effect of stacking multiple layers was studied and the results show that fabrication accuracy has a greater impact on the dispersity of the emulsion than the addition of more layers to the stack. Particle crystallization of drugs was also demonstrated as a possible application of this technology in industry.

Microfluidic PDMS on paper (POP) devices.

PubMed

Shangguan, Jin-Wen; Liu, Yu; Pan, Jian-Bin; Xu, Bi-Yi; Xu, Jing-Juan; Chen, Hong-Yuan

2016-12-20

In this paper, we propose a generalized concept of microfluidic polydimethylsiloxane (PDMS) on paper (POP) devices, which combines well the merits of paper chips and PDMS chips. First, we optimized the conditions for accurate PDMS spatial patterning on paper, based on screen printing and a high temperature enabled superfast curing technique, which enables PDMS patterning to an accuracy of tens of microns in less than ten seconds. This, in turn, makes it available for seamless, reversible and reliable integration of the resulting paper layer with other PDMS channel structures. The integrated POP devices allow for both porous paper and smooth channels to be spatially defined on the devices, greatly extending the flexibility for designers to be able to construct powerful functional structures. To demonstrate the versatility of this design, a prototype POP device for the colorimetric analysis of liver function markers, serum protein, alkaline phosphatase (ALP) and aspartate aminotransferase (AST), was constructed. On this POP device, quantitative sample loading, mixing and multiplex analysis have all been realized.

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.

Paper Capillary Enables Effective Sampling for Microfluidic Paper Analytical Devices.

PubMed

Shangguan, Jin-Wen; Liu, Yu; Wang, Sha; Hou, Yun-Xuan; Xu, Bi-Yi; Xu, Jing-Juan; Chen, Hong-Yuan

2018-06-06

Paper capillary is introduced to enable effective sampling on microfluidic paper analytical devices. By coupling mac-roscale capillary force of paper capillary and microscale capillary forces of native paper, fluid transport can be flexibly tailored with proper design. Subsequently, a hybrid-fluid-mode paper capillary device was proposed, which enables fast and reliable sampling in an arrayed form, with less surface adsorption and bias for different components. The resulting device thus well supports high throughput, quantitative, and repeatable assays all by hands operation. With all these merits, multiplex analysis of ions, proteins, and microbe have all been realized on this platform, which has paved the way to level-up analysis on μPADs.

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.

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.

Integration of Stable Droplet Formation on a CD Microfluidic Device for Extreme Point of Care Applications

NASA Astrophysics Data System (ADS)

Ganesh, Shruthi Vatsyayani

With the advent of microfluidic technologies for molecular diagnostics, a lot of emphasis has been placed on developing diagnostic tools for resource poor regions in the form of Extreme Point of Care devices. To ensure commercial viability of such a device there is a need to develop an accurate sample to answer system, which is robust, portable, isolated yet highly sensitive and cost effective. This need has been a driving force for research involving integration of different microsystems like droplet microfluidics, Compact-disc (CD)microfluidics along with sample preparation and detection modules on a single platform. This work attempts to develop a proof of concept prototype of one such device using existing CD microfluidics tools to generate stable droplets used in point of care diagnostics (POC diagnostics). Apart from using a fairly newer technique for droplet generation and stabilization, the work aims to develop this method focused towards diagnostics for rural healthcare. The motivation for this work is first described with an emphasis on the current need for diagnostic testing in rural health-care and the general guidelines prescribed by WHO for such a sample to answer system. Furthermore, a background on CD and droplet microfluidics is presented to understand the merits and de-merits of each system and the need for integrating the two. This phase of the thesis also includes different methods employed/demonstrated to generate droplets on a spinning platform. An overview on the detection platforms is also presented to understand the challenges involved in building an extreme point of care device. In the third phase of the thesis, general manufacturing techniques and materials used to accomplish this work is presented. Lastly, design trials for droplet generation is presented. The shortcomings of these trials are solved by investigating mechanisms pertaining to design modification and use of agarose based droplet generation to ensure a more robust sample processing method. This method is further characterized and compared with non-agarose based system and the results are analyzed. In conclusion, future prospects of this work are discussed in relation to extreme POC applications.

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.

Characterization of three-dimensional cancer cell migration in mixed collagen-Matrigel scaffolds using microfluidics and image analysis.

PubMed

Anguiano, María; Castilla, Carlos; Maška, Martin; Ederra, Cristina; Peláez, Rafael; Morales, Xabier; Muñoz-Arrieta, Gorka; Mujika, Maite; Kozubek, Michal; Muñoz-Barrutia, Arrate; Rouzaut, Ana; Arana, Sergio; Garcia-Aznar, José Manuel; Ortiz-de-Solorzano, Carlos

2017-01-01

Microfluidic devices are becoming mainstream tools to recapitulate in vitro the behavior of cells and tissues. In this study, we use microfluidic devices filled with hydrogels of mixed collagen-Matrigel composition to study the migration of lung cancer cells under different cancer invasion microenvironments. We present the design of the microfluidic device, characterize the hydrogels morphologically and mechanically and use quantitative image analysis to measure the migration of H1299 lung adenocarcinoma cancer cells in different experimental conditions. Our results show the plasticity of lung cancer cell migration, which turns from mesenchymal in collagen only matrices, to lobopodial in collagen-Matrigel matrices that approximate the interface between a disrupted basement membrane and the underlying connective tissue. Our quantification of migration speed confirms a biphasic role of Matrigel. At low concentration, Matrigel facilitates migration, most probably by providing a supportive and growth factor retaining environment. At high concentration, Matrigel slows down migration, possibly due excessive attachment. Finally, we show that antibody-based integrin blockade promotes a change in migration phenotype from mesenchymal or lobopodial to amoeboid and analyze the effect of this change in migration dynamics, in regards to the structure of the matrix. In summary, we describe and characterize a robust microfluidic platform and a set of software tools that can be used to study lung cancer cell migration under different microenvironments and experimental conditions. This platform could be used in future studies, thus benefitting from the advantages introduced by microfluidic devices: precise control of the environment, excellent optical properties, parallelization for high throughput studies and efficient use of therapeutic drugs.

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

PubMed

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

2016-01-01

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

Simple and Versatile 3D Printed Microfluidics Using Fused Filament Fabrication

PubMed Central

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

2016-01-01

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

Small volume low mechanical stress cytometry using computer-controlled Braille display microfluidics.

PubMed

Tung, Yi-Chung; Torisawa, Yu-suke; Futai, Nobuyuki; Takayama, Shuichi

2007-11-01

This paper describes a micro flow cytometer system designed for efficient and non-damaging analysis of samples with small numbers of precious cells. The system utilizes actuation of Braille-display pins for micro-scale fluid manipulation and a fluorescence microscope with a CCD camera for optical detection. The microfluidic chip is fully disposable and is composed of a polydimethylsiloxane (PDMS) slab with microchannel features sealed against a thin deformable PDMS membrane. The channels are designed with diffusers to alleviate pulsatile flow behaviors inherent in pin actuator-based peristaltic pumping schemes to maximize hydrodynamic focusing of samples with minimal disturbances in the laminar streams within the channel. A funnel connected to the microfluidic channel is designed for efficient loading of samples with small number of cells and is also positioned on the chip to prevent physical damages of the samples by the squeezing actions of Braille pins during actuation. The sample loading scheme was characterized by both computational fluidic dynamics (CFD) simulation and experimental observation. A fluorescein solution was first used for flow field investigation, followed by use of fluorescence beads with known relative intensities for optical detection performance calibration. Murine myoblast cells (C2C12) were exploited to investigate cell viability for the sample loading scheme of the device. Furthermore, human promyelocytic leukemia (HL60) cells stained by hypotonic DNA staining buffer were also tested in the system for cell cycle analysis. The ability to efficiently analyze cellular samples where the number of cells is small was demonstrated by analyzing cells from a single embryoid body derived from mouse embryonic stem cells. Consequently, the designed microfluidic device reported in this paper is promising for easy-to-use, small sample size flow cytometric analysis, and has potential to be further integrated with other Braille display-based microfluidic devices to facilitate a multi-functional lab-on-a-chip for mammalian cell manipulations.

[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.

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

ERIC Educational Resources Information Center

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

2014-01-01

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

Soft Lithographic Procedure for Producing Plastic Microfluidic Devices with View-ports Transparent to Visible and Infrared Light.

PubMed

Suryana, Mona; Shanmugarajah, Jegan V; Maniam, Sivakumar M; Grenci, Gianluca

2017-08-17

Infrared (IR) spectro-microscopy of living biological samples is hampered by the absorption of water in the mid-IR range and by the lack of suitable microfluidic devices. Here, a protocol for the fabrication of plastic microfluidic devices is demonstrated, where soft lithographic techniques are used to embed transparent Calcium Fluoride (CaF2) view-ports in connection with observation chamber(s). The method is based on a replica casting approach, where a polydimethylsiloxane (PDMS) mold is produced through standard lithographic procedures and then used as the template to produce a plastic device. The plastic device features ultraviolet/visible/infrared (UV/Vis/IR) -transparent windows made of CaF2 to allow for direct observation with visible and IR light. The advantages of the proposed method include: a reduced need for accessing a clean room micro-fabrication facility, multiple view-ports, an easy and versatile connection to an external pumping system through the plastic body, flexibility of the design, e.g., open/closed channels configuration, and the possibility to add sophisticated features such as nanoporous membranes.

Fluidic optics

NASA Astrophysics Data System (ADS)

Whitesides, George M.; Tang, Sindy K. Y.

2006-09-01

Fluidic optics is a new class of optical system with real-time tunability and reconfigurability enabled by the introduction of fluidic components into the optical path. We describe the design, fabrication, operation of a number of fluidic optical systems, and focus on three devices, liquid-core/liquid-cladding (L2) waveguides, microfluidic dye lasers, and diffraction gratings based on flowing, crystalline lattices of bubbles, to demonstrate the integration of microfluidics and optics. We fabricate these devices in poly(dimethylsiloxane) (PDMS) with soft-lithographic techniques. They are simple to construct, and readily integrable with microanalytical or lab-on-a-chip systems.

Micro-fluidic interconnect

DOEpatents

Okandan, Murat [Albuquerque, NM; Galambos, Paul C [Albuquerque, NM; Benavides, Gilbert L [Los Ranchos, NM; Hetherington, Dale L [Albuquerque, NM

2006-02-28

An apparatus for simultaneously aligning and interconnecting microfluidic ports is presented. Such interconnections are required to utilize microfluidic devices fabricated in Micro-Electromechanical-Systems (MEMS) technologies, that have multiple fluidic access ports (e.g. 100 micron diameter) within a small footprint, (e.g. 3 mm.times.6 mm). Fanout of the small ports of a microfluidic device to a larger diameter (e.g. 500 microns) facilitates packaging and interconnection of the microfluidic device to printed wiring boards, electronics packages, fluidic manifolds etc.

Development of an evaporation-based microfluidic sample concentrator

NASA Astrophysics Data System (ADS)

Sharma, Nigel R.; Lukyanov, Anatoly; Bardell, Ron L.; Seifried, Lynn; Shen, Mingchao

2008-02-01

MicroPlumbers Microsciences LLC, has developed a relatively simple concentrator device based on isothermal evaporation. The device allows for rapid concentration of dissolved or dispersed substances or microorganisms (e.g. bacteria, viruses, proteins, toxins, enzymes, antibodies, etc.) under conditions gentle enough to preserve their specific activity or viability. It is capable of removing of 0.8 ml of water per minute at 37°C, and has dimensions compatible with typical microfluidic devices. The concentrator can be used as a stand-alone device or integrated into various processes and analytical instruments, substantially increasing their sensitivity while decreasing processing time. The evaporative concentrator can find applications in many areas such as biothreat detection, environmental monitoring, forensic medicine, pathogen analysis, and agricultural industrial monitoring. In our presentation, we describe the design, fabrication, and testing of the concentrator. We discuss multiphysics simulations of the heat and mass transport in the device that we used to select the design of the concentrator and the protocol of performance testing. We present the results of experiments evaluating water removal performance.

Design, fabrication and test of a pneumatically controlled, renewable, microfluidic bead trapping device for sequential injection analysis applications

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

Shao, Guocheng; Lu, Donglai; Fu, Zhifeng

This paper describes the design, fabrication, and testing of a pneumatically controlled,renewable, microfluidic device for conducting bead-based assays in an automated sequential injection analysis system. The device used a “brick wall”-like pillar array (pillar size: 20 μm length X 50 μm width X 45 μm height) with 5 μm gaps between the pillars serving as the micro filter. The flow channel where bead trapping occurred is 500 μm wide X 75 μm deep. An elastomeric membrane and an air chamber were located underneath the flow channel. By applying pressure to the air chamber, the membrane is deformed and pushed upwardmore » against the filter structure. This effectively traps beads larger than 5 μm and creates a “bed” or micro column of beads that can be perfused and washed with liquid samples and reagents. Upon completion of the assay process, the pressure is released and the beads are flushed out from underneath the filter structure to renew the device. Mouse IgG was used as a model analyte to test the feasibility of using the proposed device for immunoassay applications. Resulting microbeads from an on-chip fluorescent immunoassay were individually examined using flow cytometry. The results show that the fluorescence signal intensity distribution is fairly narrow indicating high chemical reaction uniformity among the beads population. Electrochemical onchip assay was also conducted. A detection limit of 0.1 ng/mL1 ppb was achieved and good device reliability and repeatability were demonstrated. The novel microfluidic-based beadstrapping device thus opens up a new pathway to design micro-bead based biosensor immunoassays for clinical and othervarious applications.« less

Microfluidic immunomagnetic cell separation from whole blood.

PubMed

Bhuvanendran Nair Gourikutty, Sajay; Chang, Chia-Pin; Puiu, Poenar Daniel

2016-02-01

Immunomagnetic-based separation has become a viable technique for the separation of cells and biomolecules. Here we report on the design and analysis of a simple and efficient microfluidic device for high throughput and high efficiency capture of cells tagged with magnetic particles. This is made possible by using a microfluidic chip integrated with customized arrays of permanent magnets capable of creating large magnetic field gradients, which determine the effective capturing of the tagged cells. This method is based on manipulating the cells which are under the influence of a combination of magnetic and fluid dynamic forces in a fluid under laminar flow through a microfluidic chip. A finite element analysis (FEA) model is developed to analyze the cell separation process and predict its behavior, which is validated subsequently by the experimental results. The magnetic field gradients created by various arrangements of magnetic arrays have been simulated using FEA and the influence of these field gradients on cell separation has been studied with the design of our microfluidic chip. The proof-of-concept for the proposed technique is demonstrated by capturing white blood cells (WBCs) from whole human blood. CD45-conjugated magnetic particles were added into whole blood samples to label WBCs and the mixture was flown through our microfluidic device to separate the labeled cells. After the separation process, the remaining WBCs in the elute were counted to determine the capture efficiency, and it was found that more than 99.9% WBCs have been successfully separated from whole blood. The proposed design can be used for positive selection as well as for negative enrichment of rare cells. Copyright © 2015 Elsevier B.V. All rights reserved.

Attractive design: an elution solvent optimization platform for magnetic-bead-based fractionation using digital microfluidics and design of experiments.

PubMed

Lafrenière, Nelson M; Mudrik, Jared M; Ng, Alphonsus H C; Seale, Brendon; Spooner, Neil; Wheeler, Aaron R

2015-04-07

There is great interest in the development of integrated tools allowing for miniaturized sample processing, including solid phase extraction (SPE). We introduce a new format for microfluidic SPE relying on C18-functionalized magnetic beads that can be manipulated in droplets in a digital microfluidic platform. This format provides the opportunity to tune the amount (and potentially the type) of stationary phase on-the-fly, and allows the removal of beads after the extraction (to enable other operations in same device-space), maintaining device reconfigurability. Using the new method, we employed a design of experiments (DOE) operation to enable automated on-chip optimization of elution solvent composition for reversed phase SPE of a model system. Further, conditions were selected to enable on-chip fractionation of multiple analytes. Finally, the method was demonstrated to be useful for online cleanup of extracts from dried blood spot (DBS) samples. We anticipate this combination of features will prove useful for separating a wide range of analytes, from small molecules to peptides, from complex matrices.

Fully chip-embedded automation of a multi-step lab-on-a-chip process using a modularized timer circuit.

PubMed

Kang, Junsu; Lee, Donghyeon; Heo, Young Jin; Chung, Wan Kyun

2017-11-07

For highly-integrated microfluidic systems, an actuation system is necessary to control the flow; however, the bulk of actuation devices including pumps or valves has impeded the broad application of integrated microfluidic systems. Here, we suggest a microfluidic process control method based on built-in microfluidic circuits. The circuit is composed of a fluidic timer circuit and a pneumatic logic circuit. The fluidic timer circuit is a serial connection of modularized timer units, which sequentially pass high pressure to the pneumatic logic circuit. The pneumatic logic circuit is a NOR gate array designed to control the liquid-controlling process. By using the timer circuit as a built-in signal generator, multi-step processes could be done totally inside the microchip without any external controller. The timer circuit uses only two valves per unit, and the number of process steps can be extended without limitation by adding timer units. As a demonstration, an automation chip has been designed for a six-step droplet treatment, which entails 1) loading, 2) separation, 3) reagent injection, 4) incubation, 5) clearing and 6) unloading. Each process was successfully performed for a pre-defined step-time without any external control device.

Systematic Prevention of Bubble Formation and Accumulation for Long-Term Culture of Pancreatic Islet Cells in Microfluidic Device

PubMed Central

Wang, Yong; Lee, Dongyoung; Zhang, Lisa; Jeon, Hyojin; Mendoza-Elias, Joshua E.; Harvat, Tricia A.; Hassan, Sarah Z.; Zhou, Amanda; Eddington, David T.; Oberholzer, José

2012-01-01

Reliable long-term cell culture in microfluidic system is limited by air bubble formation and accumulation. In this study, we developed a bubble removal system capable of both trapping and discharging air bubbles in a consistent and reliable manner. Combined with PDMS (Polydimethylsiloxane) hydrophilic surface treatment and vacuum filling, a microfluidic perifusion system equipped with the bubble trap was successfully applied for long-term culture of mouse pancreatic islets with no bubble formation and no flow interruption. In addition to demonstrating normal cell viability and islet morphology, post-cultured islets exhibited normal insulin secretion kinetics, intracellular calcium signaling, and changes in mitochondrial potentials in response to glucose challenge. This design could be easily adapted by other microfluidic systems due to its simple design, ease of fabrication, and portability. PMID:22252566

Polymer microfluidic device replacing fluids using only capillary force

NASA Astrophysics Data System (ADS)

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

2005-02-01

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

Dynamics of blood flow in a microfluidic ladder network

NASA Astrophysics Data System (ADS)

Maddala, Jeevan; Zilberman-Rudenko, Jevgenia; McCarty, Owen

The dynamics of a complex mixture of cells and proteins, such as blood, in perturbed shear flow remains ill-defined. Microfluidics is a promising technology for improving the understanding of blood flow under complex conditions of shear; as found in stent implants and in tortuous blood vessels. We model the fluid dynamics of blood flow in a microfluidic ladder network with dimensions mimicking venules. Interaction of blood cells was modeled using multiagent framework, where cells of different diameters were treated as spheres. This model served as the basis for predicting transition regions, collision pathways, re-circulation zones and residence times of cells dependent on their diameters and device architecture. Based on these insights from the model, we were able to predict the clot formation configurations at various locations in the device. These predictions were supported by the experiments using whole blood. To facilitate platelet aggregation, the devices were coated with fibrillar collagen and tissue factor. Blood was perfused through the microfluidic device for 9 min at a physiologically relevant venous shear rate of 600 s-1. Using fluorescent microscopy, we observed flow transitions near the channel intersections and at the areas of blood flow obstruction, which promoted larger thrombus formation. This study of integrating model predictions with experimental design, aids in defining the dynamics of blood flow in microvasculature and in development of novel biomedical devices.

A polymeric master replication technology for mass fabrication of poly(dimethylsiloxane) microfluidic devices.

PubMed

Li, Hai-Fang; Lin, Jin-Ming; Su, Rong-Guo; Cai, Zong Wei; Uchiyama, Katsumi

2005-05-01

A protocol of producing multiple polymeric masters from an original glass master mold has been developed, which enables the production of multiple poly(dimethylsiloxane) (PDMS)-based microfluidic devices in a low-cost and efficient manner. Standard wet-etching techniques were used to fabricate an original glass master with negative features, from which more than 50 polymethylmethacrylate (PMMA) positive replica masters were rapidly created using the thermal printing technique. The time to replicate each PMMA master was as short as 20 min. The PMMA replica masters have excellent structural features and could be used to cast PDMS devices for many times. An integration geometry designed for laser-induced fluorescence (LIF) detection, which contains normal deep microfluidic channels and a much deeper optical fiber channel, was successfully transferred into PDMS devices. The positive relief on seven PMMA replica masters is replicated with regard to the negative original glass master, with a depth average variation of 0.89% for 26-microm deep microfluidic channels and 1.16% for the 90 mum deep fiber channel. The imprinted positive relief in PMMA from master-to-master is reproducible with relative standard deviations (RSDs) of 1.06% for the maximum width and 0.46% for depth in terms of the separation channel. The PDMS devices fabricated from the PMMA replica masters were characterized and applied to the separation of a fluorescein isothiocyanate (FITC)-labeled epinephrine sample.

Rapid identification and susceptibility testing of uropathogenic microbes via immunosorbent ATP-bioluminescence assay on a microfluidic simulator for antibiotic therapy.

PubMed

Dong, Tao; Zhao, Xinyan

2015-02-17

The incorporation of pathogen identification with antimicrobial susceptibility testing (AST) was implemented on a concept microfluidic simulator, which is well suited for personalizing antibiotic treatment of urinary tract infections (UTIs). The microfluidic device employs a fiberglass membrane sandwiched between two polypropylene components, with capture antibodies immobilized on the membrane. The chambers in the microfluidic device share the same geometric distribution as the wells in a standard 384-well microplate, resulting in compatibility with common microplate readers. Thirteen types of common uropathogenic microbes were selected as the analytes in this study. The microbes can be specifically captured by various capture antibodies and then quantified via an ATP bioluminescence assay (ATP-BLA) either directly or after a variety of follow-up tests, including urine culture, antibiotic treatment, and personalized antibiotic therapy simulation. Owing to the design of the microfluidic device, as well as the antibody specificity and the ATP-BLA sensitivity, the simulator was proven to be able to identify UTI pathogen species in artificial urine samples within 20 min and to reliably and simultaneously verify the antiseptic effects of eight antibiotic drugs within 3-6 h. The measurement range of the device spreads from 1 × 10(3) to 1 × 10(5) cells/mL in urine samples. We envision that the medical simulator might be broadly employed in UTI treatment and could serve as a model for the diagnosis and treatment of other diseases.

Microfluidic devices for cell culture and handling in organ-on-a-chip applications

NASA Astrophysics Data System (ADS)

Becker, Holger; Schulz, Ingo; Mosig, Alexander; Jahn, Tobias; Gärtner, Claudia

2014-03-01

For many problems in system biology or pharmacology, in-vivo-like models of cell-cell interactions or organ functions are highly sought after. Conventional stationary cell culture in 2D plates quickly reaches its limitations with respect to an in-vivo like expression and function of individual cell types. Microfabrication technologies and microfluidics offer an attractive solution to these problems. The ability to generate flow as well as geometrical conditions for cell culture and manipulation close to the in-vivo situation allows for an improved design of experiments and the modeling of organ-like functionalities. Furthermore, reduced internal volumes lead to a reduction in reagent volumes necessary as well as an increased assay sensitivity. In this paper we present a range of microfluidic devices designed for the co-culturing of a variety of cells. The influence of substrate materials and surface chemistry on the cell morphology and viability for long-term cell culture has been investigated as well as strategies and medium supply for on-chip cell cultivation.

Inertial focusing of spherical particles in rectangular microchannels over a wide range of Reynolds numbers.

PubMed

Liu, Chao; Hu, Guoqing; Jiang, Xingyu; Sun, Jiashu

2015-02-21

Inertial microfluidics has emerged as an important tool for manipulating particles and cells. For a better design of inertial microfluidic devices, we conduct 3D direct numerical simulations (DNS) and experiments to determine the complicated dependence of focusing behaviour on the particle size, channel aspect ratio, and channel Reynolds number. We find that the well-known focusing of the particles at the two centers of the long channel walls occurs at a relatively low Reynolds number, whereas additional stable equilibrium positions emerge close to the short walls with increasing Reynolds number. Based on the numerically calculated trajectories of particles, we propose a two-stage particle migration which is consistent with experimental observations. We further present a general criterion to secure good focusing of particles for high flow rates. This work thus provides physical insight into the multiplex focusing of particles in rectangular microchannels with different geometries and Reynolds numbers, and paves the way for efficiently designing inertial microfluidic devices.

Design of a compact disk-like microfluidic platform for enzyme-linked immunosorbent assay.

PubMed

Lai, Siyi; Wang, Shengnian; Luo, Jun; Lee, L James; Yang, Shang-Tian; Madou, Marc J

2004-04-01

This paper presents an integrated microfluidic device on a compact disk (CD) that performs an enzyme-linked immunosorbent assay (ELISA) for rat IgG from a hybridoma cell culture. Centrifugal and capillary forces were used to control the flow sequence of different solutions involved in the ELISA process. The microfluidic device was fabricated on a plastic CD. Each step of the ELISA process was carried out automatically by controlling the rotation speed of the CD. The work on analysis of rat IgG from hybridoma culture showed that the microchip-based ELISA has the same detection range as the conventional method on the 96-well microtiter plate but has advantages such as less reagent consumption and shorter assay time over the conventional method.

Optothermally actuated capillary burst valve

NASA Astrophysics Data System (ADS)

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

2017-04-01

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

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.

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.

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.

Characterization of three-dimensional cancer cell migration in mixed collagen-Matrigel scaffolds using microfluidics and image analysis

PubMed Central

Maška, Martin; Ederra, Cristina; Peláez, Rafael; Morales, Xabier; Muñoz-Arrieta, Gorka; Mujika, Maite; Kozubek, Michal; Muñoz-Barrutia, Arrate; Rouzaut, Ana; Arana, Sergio; Garcia-Aznar, José Manuel; Ortiz-de-Solorzano, Carlos

2017-01-01

Microfluidic devices are becoming mainstream tools to recapitulate in vitro the behavior of cells and tissues. In this study, we use microfluidic devices filled with hydrogels of mixed collagen-Matrigel composition to study the migration of lung cancer cells under different cancer invasion microenvironments. We present the design of the microfluidic device, characterize the hydrogels morphologically and mechanically and use quantitative image analysis to measure the migration of H1299 lung adenocarcinoma cancer cells in different experimental conditions. Our results show the plasticity of lung cancer cell migration, which turns from mesenchymal in collagen only matrices, to lobopodial in collagen-Matrigel matrices that approximate the interface between a disrupted basement membrane and the underlying connective tissue. Our quantification of migration speed confirms a biphasic role of Matrigel. At low concentration, Matrigel facilitates migration, most probably by providing a supportive and growth factor retaining environment. At high concentration, Matrigel slows down migration, possibly due excessive attachment. Finally, we show that antibody-based integrin blockade promotes a change in migration phenotype from mesenchymal or lobopodial to amoeboid and analyze the effect of this change in migration dynamics, in regards to the structure of the matrix. In summary, we describe and characterize a robust microfluidic platform and a set of software tools that can be used to study lung cancer cell migration under different microenvironments and experimental conditions. This platform could be used in future studies, thus benefitting from the advantages introduced by microfluidic devices: precise control of the environment, excellent optical properties, parallelization for high throughput studies and efficient use of therapeutic drugs. PMID:28166248

Paper-based microfluidics with an erodible polymeric bridge giving controlled release and timed flow shutoff.

PubMed

Jahanshahi-Anbuhi, Sana; Henry, Aleah; Leung, Vincent; Sicard, Clémence; Pennings, Kevin; Pelton, Robert; Brennan, John D; Filipe, Carlos D M

2014-01-07

Water soluble pullulan films were formatted into paper-based microfluidic devices, serving as a controlled time shutoff valve. The utility of the valve was demonstrated by a one-step, fully automatic implementation of a complex pesticide assay requiring timed, sequential exposure of an immobilized enzyme layer to separate liquid streams. Pullulan film dissolution and the capillary wicking of aqueous solutions through the device were measured and modeled providing valve design criteria. The films dissolve mainly by surface erosion, meaning the film thickness mainly controls the shutoff time. This method can also provide time-dependent sequential release of reagents without compromising the simplicity and low cost of paper-based devices.

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.

Design and validation of a microfluidic device for blood-brain barrier monitoring and transport studies

NASA Astrophysics Data System (ADS)

Ugolini, Giovanni Stefano; Occhetta, Paola; Saccani, Alessandra; Re, Francesca; Krol, Silke; Rasponi, Marco; Redaelli, Alberto

2018-04-01

In vitro blood-brain barrier models are highly relevant for drug screening and drug development studies, due to the challenging task of understanding the transport mechanism of drug molecules through the blood-brain barrier towards the brain tissue. In this respect, microfluidics holds potential for providing microsystems that require low amounts of cells and reagent and can be potentially multiplexed for increasing the ease and throughput of the drug screening process. We here describe the design, development and validation of a microfluidic device for endothelial blood-brain barrier cell transport studies. The device comprises of two microstructured layers (top culture chamber and bottom collection chamber) sandwiching a porous membrane for the cell culture. Microstructured layers include two pairs of physical electrodes, embedded into the device layers by geometrically defined guiding channels with computationally optimized positions. These electrodes allow the use of commercial electrical measurement systems for monitoring trans-endothelial electrical resistance (TEER). We employed the designed device for performing preliminary assessment of endothelial barrier formation with murine brain endothelial cells (Br-bEnd5). Results demonstrate that cellular junctional complexes effectively form in the cultures (expression of VE-Cadherin and ZO-1) and that the TEER monitoring systems effectively detects an increase of resistance of the cultured cell layers indicative of tight junction formation. Finally, we validate the use of the described microsystem for drug transport studies demonstrating that Br-bEnd5 cells significantly hinder the transport of molecules (40 kDa and 4 kDa dextran) from the top culture chamber to the bottom collection chamber.

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.

Concurrent DNA Preconcentration and Separation in Bipolar Electrode-Based Microfluidic Device

PubMed Central

Song, Hongjun; Wang, Yi; Garson, Charles; Pant, Kapil

2015-01-01

This paper presents a bipolar electrode (BPE) device in a microfluidic dual-channel design for concurrent preconcentration and separation of composite DNA containing samples. The novelty of the present effort relies on the combination of BPE-induced ion concentration polarization (ICP) and end-labeled free-solution electrophoresis (ELFSE). The ion concentration polarization effect arising from the faradaic reaction on the BPE is utilized to exert opposing electrophoretic and electroosmotic forces on the DNA samples. Meanwhile, end-labeled free-solution electrophoresis alters the mass-charge ratio to enable simultaneous DNA separation in free solution. The microfluidic device was fabricated using standard and soft lithography techniques to form gold-on-glass electrode capped with a PDMS microfluidic channel. Experimental testing with various DNA samples was carried out over a range of applied electric field. Concentration ratios up to 285× within 5 minutes for a 102-mer DNA, and concurrent preconcentration and free-solution separation of binary mixture of free and bound 102-mer DNA within 6 minutes was demonstrated. The effect of applied electric field was also interrogated with respect to pertinent performance metrics of preconcentration and separation. PMID:26005497

A Soft, Wearable Microfluidic Device for the Capture, Storage, and Colorimetric Sensing of Sweat

PubMed Central

Koh, Ahyeon; Kang, Daeshik; Xue, Yeguang; Lee, Seungmin; Pielak, Rafal M.; Kim, Jeonghyun; Hwang, Taehwan; Min, Seunghwan; Banks, Anthony; Bastien, Philippe; Manco, Megan C.; Wang, Liang; Ammann, Kaitlyn R.; Jang, Kyung-In; Won, Phillip; Han, Seungyong; Ghaffari, Roozbeh; Paik, Ungyu; Slepian, Marvin J.; Balooch, Guive; Huang, Yonggang; Rogers, John A.

2017-01-01

Capabilities in health monitoring via capture and quantitative chemical analysis of sweat could complement, or potentially obviate the need for, approaches based on sporadic assessment of blood samples. Established sweat monitoring technologies use simple fabric swatches and are limited to basic analysis in controlled laboratory or hospital settings. We present a collection of materials and device designs for soft, flexible and stretchable microfluidic systems, including embodiments that integrate wireless communication electronics, which can intimately and robustly bond to the surface of skin without chemical and mechanical irritation. This integration defines access points for a small set of sweat glands such that perspiration spontaneously initiates routing of sweat through a microfluidic network and set of reservoirs. Embedded chemical analyses respond in colorimetric fashion to markers such as chloride and hydronium ions, glucose and lactate. Wireless interfaces to digital image capture hardware serve as a means for quantitation. Human studies demonstrated the functionality of this microfluidic device during fitness cycling in a controlled environment and during long-distance bicycle racing in arid, outdoor conditions. The results include quantitative values for sweat rate, total sweat loss, pH and concentration of both chloride and lactate. PMID:27881826

Optical measurement of transverse molecular diffusion in a microchannel.

PubMed Central

Kamholz, A E; Schilling, E A; Yager, P

2001-01-01

Quantitative analysis of molecular diffusion is a necessity for the efficient design of most microfluidic devices as well as an important biophysical method in its own right. This study demonstrates the rapid measurement of diffusion coefficients of large and small molecules in a microfluidic device, the T-sensor, by means of conventional epifluorescence microscopy. Data were collected by monitoring the transverse flux of analyte from a sample stream into a second stream flowing alongside it. As indicated by the low Reynolds numbers of the system (< 1), flow is laminar, and molecular transport between streams occurs only by diffusion. Quantitative determinations were made by fitting data with predictions of a one-dimensional model. Analysis was made of the flow development and its effect on the distribution of diffusing analyte using a three-dimensional modeling software package. Diffusion coefficients were measured for four fluorescently labeled molecules: fluorescein-biotin, insulin, ovalbumin, and streptavidin. The resulting values differed from accepted results by an average of 2.4%. Microfluidic system parameters can be selected to achieve accurate diffusion coefficient measurements and to optimize other microfluidic devices that rely on precise transverse transport of molecules. PMID:11259309

Design of portable ultraminiature flow cytometers for medical diagnostics

NASA Astrophysics Data System (ADS)

Leary, James F.

2018-02-01

Design of portable microfluidic flow/image cytometry devices for measurements in the field (e.g. initial medical diagnostics) requires careful design in terms of power requirements and weight to allow for realistic portability. True portability with high-throughput microfluidic systems also requires sampling systems without the need for sheath hydrodynamic focusing both to avoid the need for sheath fluid and to enable higher volumes of actual sample, rather than sheath/sample combinations. Weight/power requirements dictate use of super-bright LEDs with top-hat excitation beam architectures and very small silicon photodiodes or nanophotonic sensors that can both be powered by small batteries. Signal-to-noise characteristics can be greatly improved by appropriately pulsing the LED excitation sources and sampling and subtracting noise in between excitation pulses. Microfluidic cytometry also requires judicious use of small sample volumes and appropriate statistical sampling by microfluidic cytometry or imaging for adequate statistical significance to permit real-time (typically in less than 15 minutes) initial medical decisions for patients in the field. This is not something conventional cytometry traditionally worries about, but is very important for development of small, portable microfluidic devices with small-volume throughputs. It also provides a more reasonable alternative to conventional tubes of blood when sampling geriatric and newborn patients for whom a conventional peripheral blood draw can be problematical. Instead one or two drops of blood obtained by pin-prick should be able to provide statistically meaningful results for use in making real-time medical decisions without the need for blood fractionation, which is not realistic in the doctor's office or field.

Comparison of capacitive and radio frequency resonator sensors for monitoring parallelized droplet microfluidic production.

PubMed

Conchouso, David; McKerricher, Garret; Arevalo, Arpys; Castro, David; Shamim, Atif; Foulds, Ian G

2016-08-16

Scaled-up production of microfluidic droplets, through the parallelization of hundreds of droplet generators, has received a lot of attention to bring novel multiphase microfluidics research to industrial applications. However, apart from droplet generation, other significant challenges relevant to this goal have never been discussed. Examples include monitoring systems, high-throughput processing of droplets and quality control procedures among others. In this paper, we present and compare capacitive and radio frequency (RF) resonator sensors as two candidates that can measure the dielectric properties of emulsions in microfluidic channels. By placing several of these sensors in a parallelization device, the stability of the droplet generation at different locations can be compared, and potential malfunctions can be detected. This strategy enables for the first time the monitoring of scaled-up microfluidic droplet production. Both sensors were prototyped and characterized using emulsions with droplets of 100-150 μm in diameter, which were generated in parallelization devices at water-in-oil volume fractions (φ) between 11.1% and 33.3%.Using these sensors, we were able to measure accurately increments as small as 2.4% in the water volume fraction of the emulsions. Although both methods rely on the dielectric properties of the emulsions, the main advantage of the RF resonator sensors is the fact that they can be designed to resonate at multiple frequencies of the broadband transmission line. Consequently with careful design, two or more sensors can be parallelized and read out by a single signal. Finally, a comparison between these sensors based on their sensitivity, readout cost and simplicity, and design flexibility is also discussed.

A microfluidic device for the continuous culture and analysis of Caenorhabditis elegans in a toxic aqueous environment

NASA Astrophysics Data System (ADS)

Jung, Jaehoon; Nakajima, Masahiro; Tajima, Hirotaka; Huang, Qiang; Fukuda, Toshio

2013-08-01

The nematode Caenorhabditis elegans (C. elegans) receives attention as a bioindicator, and the C. elegans condition has been recently analyzed using microfluidic devices equipped with an imaging system. To establish a method without an imaging system, we have proposed a novel microfluidic device with which to analyze the condition of C. elegans from the capacitance change using a pair of micro-electrodes. The device was designed to culture C. elegans, to expose C. elegans to an external stimulus, such as a chemical or toxicant, and to measure the capacitance change which indicates the condition of C. elegans. In this study, to demonstrate the capability of our device in a toxic aqueous environment, the device was applied to examine the effect of cadmium on C. elegans. Thirty L4 larval stage C. elegans were divided into three groups. One group was a control group and the other groups were exposed to cadmium solutions with concentrations of 5% and 10% LC50 for 24 h. The capacitance change and the body volume of C. elegans as a reference were measured four times and we confirmed the correlation between them. It shows that our device can analyze the condition of C. elegans without an imaging system.

Multilayer Microfluidic Devices Created From A Single Photomask

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

Kelly, Ryan T.; Sheen, Allison M.; Jambovane, Sachin R.

2013-08-28

The time and expense associated with high quality photomask production can discourage the creation of multilayer microfluidic devices, as each layer currently requires a separate photomask. Here we describe an approach in which multilayer microfabricated devices can be created from a single photomask. The separate layers and their corresponding alignment marks are arranged in separate halves of the mask for two layer devices or quadrants for four layer devices. Selective exposure of the photomask features and rotation of the device substrate between exposures result in multiple copies of the devices on each wafer. Subsequent layers are aligned to patterned featuresmore » on the substrate with the same alignment accuracy as when multiple photomasks are used. We demonstrate this approach for fabricating devices employing multilayer soft lithography (MSL) for pneumatic valving. MSL devices containing as many as 5 layers (4 aligned fluidic layers plus a manually aligned control layer) were successfully created using this approach. Device design is also modularized, enabling the presence or absence of features as well as channel heights to be selected independently from one another. The use of a single photomask to create multilayer devices results in a dramatic savings of time and/or money required to advance from device design to completed prototype.« less

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

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.

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

NASA Astrophysics Data System (ADS)

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

2013-03-01

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

Microfluidic Biochip Design

NASA Technical Reports Server (NTRS)

Panzarella, Charles

2004-01-01

As humans prepare for the exploration of our solar system, there is a growing need for miniaturized medical and environmental diagnostic devices for use on spacecrafts, especially during long-duration space missions where size and power requirements are critical. In recent years, the biochip (or Lab-on-a- Chip) has emerged as a technology that might be able to satisfy this need. In generic terms, a biochip is a miniaturized microfluidic device analogous to the electronic microchip that ushered in the digital age. It consists of tiny microfluidic channels, pumps and valves that transport small amounts of sample fluids to biosensors that can perform a variety of tests on those fluids in near real time. It has the obvious advantages of being small, lightweight, requiring less sample fluids and reagents and being more sensitive and efficient than larger devices currently in use. Some of the desired space-based applications would be to provide smaller, more robust devices for analyzing blood, saliva and urine and for testing water and food supplies for the presence of harmful contaminants and microorganisms. Our group has undertaken the goal of adapting as well as improving upon current biochip technology for use in long-duration microgravity environments. In addition to developing computational models of the microfluidic channels, valves and pumps that form the basis of every biochip, we are also trying to identify potential problems that could arise in reduced gravity and develop solutions to these problems. One such problem is due to the prevalence of bubbly sample fluids in microgravity. A bubble trapped in a microfluidic channel could be detrimental to the operation of a biochip. Therefore, the process of bubble formation in microgravity needs to be studied, and a model of this process has been developed and used to understand how bubbles develop and move through biochip components. It is clear that some type of bubble filter would be necessary in Space, and several bubble filter designs are being evaluated.

Simulation analysis of rectifying microfluidic mixing with field-effect-tunable electrothermal induced flow.

PubMed

Liu, Weiyu; Ren, Yukun; Tao, Ye; Yao, Bobin; Li, You

2018-03-01

We report herein field-effect control on in-phase electrothermal streaming from a theoretical point of view, a phenomenon termed "alternating-current electrothermal-flow field effect transistor" (ACET-FFET), in the context of a new technology for handing analytes in microfluidics. Field-effect control through a gate terminal endows ACET-FFET the ability to generate arbitrary symmetry breaking in the transverse vortex flow pattern, which makes it attractive for mixing microfluidic samples. A computational model is developed to study the feasibility of this new microfluidic device design for micromixing. The influence of various parameters on developing an efficient mixer is investigated, and an integrated layout of discrete electrode array is suggested for achieving high-throughput mixing. Our physical demonstration with field-effect electrothermal flow control using a simple electrode structure proves invaluable for designing active micromixers for modern micro total analytical system. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Slopes To Prevent Trapping of Bubbles in Microfluidic Channels

NASA Technical Reports Server (NTRS)

Greer, Harold E.; Lee, Michael C.; Smith, J. Anthony; Willis, Peter A.

2010-01-01

The idea of designing a microfluidic channel to slope upward along the direction of flow of the liquid in the channel has been conceived to help prevent trapping of gas bubbles in the channel. In the original application that gave rise to this idea, the microfluidic channels are parts of micro-capillary electrophoresis (microCE) devices undergoing development for use on Mars in detecting compounds indicative of life. It is necessary to prevent trapping of gas bubbles in these devices because uninterrupted liquid pathways are essential for sustaining the electrical conduction and flows that are essential for CE. The idea is also applicable to microfluidic devices that may be developed for similar terrestrial microCE biotechnological applications or other terrestrial applications in which trapping of bubbles in microfluidic channels cannot be tolerated. A typical microCE device in the original application includes, among other things, multiple layers of borosilicate float glass wafers. Microfluidic channels are formed in the wafers, typically by use of wet chemical etching. The figure presents a simplified cross section of part of such a device in which the CE channel is formed in the lowermost wafer (denoted the channel wafer) and, according to the present innovation, slopes upward into a via hole in another wafer (denoted the manifold wafer) lying immediately above the channel wafer. Another feature of the present innovation is that the via hole in the manifold wafer is made to taper to a wider opening at the top to further reduce the tendency to trap bubbles. At the time of reporting the information for this article, an effort to identify an optimum technique for forming the slope and the taper was in progress. Of the techniques considered thus far, the one considered to be most promising is precision milling by use of femtosecond laser pulses. Other similar techniques that may work equally well are precision milling using a focused ion beam, or a small diamond-tipped drill bit.

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.

An optical manometer-on-a-chip

NASA Astrophysics Data System (ADS)

Jin, Yuhang; Crozier, Kenneth B.

2011-10-01

The rapid development of microfluidic devices in recent years has led to a huge number of applications in chemistry, biology and interdisciplinary areas. This is because they act as miniaturized platforms in which sorting, mixing, reaction and measurement can be achieved in a precise and rapid manner. Being able to both understand and measure the pressure of fluids inside these devices is very important, especially in the cases where multiphase flows are involved. For example, certain advanced micromixing technologies demand accurate evaluations of bubble-induced extra pressure, since the pressure contribution from one bubble is likely to impact the velocity and residence time of others, affecting the mixing efficiency and quality in a complicated manner. Similarly, in some microfluidics-based biochemical analysis, extra pressure brought about by droplets is a critical factor in the design of on-chip pumping, as high throughput experiments involving continuous supply of large numbers of droplets often require a considerable enhancement in the pumping pressure necessary to maintain the droplet flow3. Last, state-of-the-art microfluidic logic devices rely heavily on the pressure distribution inside the channels, which automatically controls the paths of each droplet in the microfluidic network and as a result determines the "on" and "off" of each switch. A few techniques to measure pressure change or pressure drop in microfluidic channels have been developed. Examples include connecting the device to commercially available pressure sensors and comparing pressures of different areas by analyzing the position of fluid-fluid interface. However, all of those methods have intrinsic drawbacks in one or more aspects that considerably limit their applications. A significant one is that they are primarily aiming at measuring or comparing pressures over relatively long channels (~10 mm), and are hence only designed to work in the highpressure range, i.e. to detect a pressure change on the order of tens or hundreds of Pascals. Moreover, the long channels make it rather challenging to look into the detailed dynamics of pressure variations caused by inhomogeneous emulsions, since such a long section invariably contains multiple elements, for instance droplets, of the emulsion flow, and the measurements average out the behavior of one single element. Consequently, to further reveal the characteristics of flows in microfluidics, it is highly desirable for a pressure measurement device to work in the low-pressure range, and to resolve pressure changes "locally", i.e. within small spatial regions.

A microfluidic-based lid device for conventional cell culture dishes to automatically control oxygen level.

PubMed

Lee, Seung Yeob; Yang, Sung

2018-04-25

Most conventional hypoxic cell culture systems undergo reoxygenation during experimental manipulations, resulting in undesirable effects including the reduction of cell viability. A lid device was developed herein for conventional cell culture dishes to resolve this limitation. The integration of multilayered microfluidic channels inside a thin membrane was designed to prevent the reoxygenation caused by reagent infusion and automatically control the oxygen level. The experimental data clearly show the reducibility of the dissolved oxygen in the infusing reagent and the controllability of the oxygen level inside the dish. The feasibility of the device for hypoxia studies was confirmed by HIF-1α experiments. Therefore, the device could be used as a compact and convenient hypoxic cell culture system to prevent reoxygenation-related issues.

Microfluidic fuel cell systems

NASA Astrophysics Data System (ADS)

Ho, Bernard; Kjeang, Erik

2011-06-01

A microfluidic fuel cell is a microfabricated device that produces electrical power through electrochemical reactions involving a fuel and an oxidant. Microfluidic fuel cell systems exploit co-laminar flow on the microscale to separate the fuel and oxidant species, in contrast to conventional fuel cells employing an ion exchange membrane for this function. Since 2002 when the first microfluidic fuel cell was invented, many different fuels, oxidants, and architectures have been investigated conceptually and experimentally. In this mini-review article, recent advancements in the field of microfluidic fuel cell systems are documented, with particular emphasis on design, operation, and performance. The present microfluidic fuel cell systems are categorized by the fluidic phases of the fuel and oxidant streams, featuring gaseous/gaseous, liquid/gaseous, and liquid/liquid systems. The typical cell configurations and recent contributions in each category are analyzed. Key research challenges and opportunities are highlighted and recommendations for further work are provided.

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

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.

Microfluidics: a transformational tool for nanomedicine development and production.

PubMed

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

2016-11-01

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

Optimization of multiplexed PCR on an integrated microfluidic forensic platform for rapid DNA analysis.

PubMed

Estes, Matthew D; Yang, Jianing; Duane, Brett; Smith, Stan; Brooks, Carla; Nordquist, Alan; Zenhausern, Frederic

2012-12-07

This study reports the design, prototyping, and assay development of multiplexed polymerase chain reaction (PCR) on a plastic microfluidic device. Amplification of 17 DNA loci is carried out directly on-chip as part of a system for continuous workflow processing from sample preparation (SP) to capillary electrophoresis (CE). For enhanced performance of on-chip PCR amplification, improved control systems have been developed making use of customized Peltier assemblies, valve actuators, software, and amplification chemistry protocols. Multiple enhancements to the microfluidic chip design have been enacted to improve the reliability of sample delivery through the various on-chip modules. This work has been enabled by the encapsulation of PCR reagents into a solid phase material through an optimized Solid Phase Encapsulating Assay Mix (SPEAM) bead-based hydrogel fabrication process. SPEAM bead technology is reliably coupled with precise microfluidic metering and dispensing for efficient amplification and subsequent DNA short tandem repeat (STR) fragment analysis. This provides a means of on-chip reagent storage suitable for microfluidic automation, with the long shelf-life necessary for point-of-care (POC) or field deployable applications. This paper reports the first high quality 17-plex forensic STR amplification from a reference sample in a microfluidic chip with preloaded solid phase reagents, that is designed for integration with up and downstream processing.

A microfluidic device for study of the effect of tumor vascular structures on the flow field and HepG2 cellular flow behaviors.

PubMed

Ke, Ming; Cai, Shaoxi; Zou, Misha; Zhao, Yi; Li, Bo; Chen, Sijia; Chen, Longcong

2018-01-29

To build a microfluidic device with various morphological features of the tumor vasculature for study of the effects of tumor vascular structures on the flow field and tumor cellular flow behaviors. The designed microfluidic device was able to approximatively simulate the in vivo structures of tumor vessels and the flow within it. In this models, the influences of the angle of bifurcation, the number of branches, and the narrow channels on the flow field and the influence of vorticity on the retention of HepG2 cells were significant. Additionally, shear stress below physiological conditions of blood circulation has considerable effect on the formation of the lumen-like structures (LLSs) of HepG2 cells. These results can provide some data and reference in the understanding of the interaction between hemorheological properties and tumor vascular structures in solid tumors. Copyright © 2018. Published by Elsevier Inc.

Development of paper-based microfluidic analytical device for iron assay using photomask printed with 3D printer for fabrication of hydrophilic and hydrophobic zones on paper by photolithography.

PubMed

Asano, Hitoshi; Shiraishi, Yukihide

2015-07-09

This paper describes a paper-based microfluidic analytical device for iron assay using a photomask printed with a 3D printer for fabrication of hydrophilic and hydrophobic zones on the paper by photolithography. Several designed photomasks for patterning paper-based microfluidic analytical devices can be printed with a 3D printer easily, rapidly and inexpensively. A chromatography paper was impregnated with the octadecyltrichlorosilane n-hexane solution and hydrophobized. After the hydrophobic zone of the paper was exposed to the UV light through the photomask, the hydrophilic zone was generated. The smallest functional hydrophilic channel and hydrophobic barrier were ca. 500 μm and ca. 100 μm in width, respectively. The fabrication method has high stability, resolution and precision for hydrophilic channel and hydrophobic barrier. This test paper was applied to the analysis of iron in water samples using a colorimetry with phenanthroline. Copyright © 2015 Elsevier B.V. All rights reserved.

Microfluidics meets metabolomics to reveal the impact of Campylobacter jejuni infection on biochemical pathways.

PubMed

Mortensen, Ninell P; Mercier, Kelly A; McRitchie, Susan; Cavallo, Tammy B; Pathmasiri, Wimal; Stewart, Delisha; Sumner, Susan J

2016-06-01

Microfluidic devices that are currently being used in pharmaceutical research also have a significant potential for utilization in investigating exposure to infectious agents. We have established a microfluidic device cultured with Caco-2 cells, and utilized metabolomics to investigate the biochemical responses to the bacterial pathogen Campylobacter jejuni. In the microfluidic devices, Caco-2 cells polarize at day 5, are uniform, have defined brush borders and tight junctions, and form a mucus layer. Metabolomics analysis of cell culture media collected from both Caco-2 cell culture systems demonstrated a more metabolic homogenous biochemical profile in the media collected from microfluidic devices, compared with media collected from transwells. GeneGo pathway mapping indicated that aminoacyl-tRNA biosynthesis was perturbed by fluid flow, suggesting that fluid dynamics and shear stress impacts the cells translational quality control. Both microfluidic device and transwell culturing systems were used to investigate the impact of Campylobacter jejuni infection on biochemical processes. Caco-2 cells cultured in either system were infected at day 5 with C. jejuni 81-176 for 48 h. Metabolomics analysis clearly differentiated C. jejuni 81-176 infected and non-infected medias collected from the microfluidic devices, and demonstrated that C. jejuni 81-176 infection in microfluidic devices impacts branched-chain amino acid metabolism, glycolysis, and gluconeogenesis. In contrast, no distinction was seen in the biochemical profiles of infected versus non-infected media collected from cells cultured in transwells. Microfluidic culturing conditions demonstrated a more metabolically homogenous cell population, and present the opportunity for studying host-pathogen interactions for extended periods of time.

Microfluidics Meets Metabolomics to Reveal the Impact of Campylobacter jejuni Infection on Biochemical Pathways

PubMed Central

Mortensen, Ninell P.; Mercier, Kelly A.; McRitchie, Susan; Cavallo, Tammy B.; Pathmasiri, Wimal; Stewart, Delisha; Sumner, Susan J.

2016-01-01

Microfluidic devices that are currently being used in pharmaceutical research also have a significant potential for utilization in investigating exposure to infectious agents. We have established a microfluidic device cultured with Caco-2 cells, and utilized metabolomics to investigate the biochemical responses to the bacterial pathogen Campylobacter jejuni. In the microfluidic devices, Caco-2 cells polarize at day 5, are uniform, have defined brush borders and tight junctions, and form a mucus layer. Metabolomics analysis of cell culture media collected from both Caco-2 cell culture systems demonstrated a more metabolic homogenous biochemical profile in the media collected from microfluidic devices, compared with media collected from transwells. GeneGo pathway mapping indicated that aminoacyl-tRNA biosynthesis was perturbed by fluid flow, suggesting that fluid dynamics and shear stress impacts the cells translational quality control. Both microfluidic device and transwell culturing systems were used to investigate the impact of Campylobacter jejuni infection on biochemical processes. Caco-2 cells cultured in either system were infected at day 5 with C. jejuni 81-176 for 48 hours. Metabolomics analysis clearly differentiated C. jejuni 81-176 infected and non-infected medias collected from the microfluidic devices, and demonstrated that C. jejuni 81-176 infection in microfluidic devices impacts branched-chain amino acid metabolism, glycolysis, and gluconeogenesis. In contrast, no distinction was seen in the biochemical profiles of infected versus non-infected media collected from cells cultured in transwells. Microfluidic culturing conditions demonstrated a more metabolically homogenous cell population, and present the opportunity for studying host-pathogen interactions for extended periods of time. PMID:27231016

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

PubMed

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

2011-02-07

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

Microfluidic Devices in Advanced Caenorhabditis elegans Research.

PubMed

Muthaiyan Shanmugam, Muniesh; Subhra Santra, Tuhin

2016-08-02

The study of model organisms is very important in view of their potential for application to human therapeutic uses. One such model organism is the nematode worm, Caenorhabditis elegans. As a nematode, C. elegans have ~65% similarity with human disease genes and, therefore, studies on C. elegans can be translated to human, as well as, C. elegans can be used in the study of different types of parasitic worms that infect other living organisms. In the past decade, many efforts have been undertaken to establish interdisciplinary research collaborations between biologists, physicists and engineers in order to develop microfluidic devices to study the biology of C. elegans. Microfluidic devices with the power to manipulate and detect bio-samples, regents or biomolecules in micro-scale environments can well fulfill the requirement to handle worms under proper laboratory conditions, thereby significantly increasing research productivity and knowledge. The recent development of different kinds of microfluidic devices with ultra-high throughput platforms has enabled researchers to carry out worm population studies. Microfluidic devices primarily comprises of chambers, channels and valves, wherein worms can be cultured, immobilized, imaged, etc. Microfluidic devices have been adapted to study various worm behaviors, including that deepen our understanding of neuromuscular connectivity and functions. This review will provide a clear account of the vital involvement of microfluidic devices in worm biology.

Controlled evacuation using the biocompatible and energy efficient microfluidic ejector.

PubMed

Lad, V N; Ralekar, Swati

2016-10-01

Development of controlled vacuum is having many applications in the realm of biotechnology, cell transfer, gene therapy, biomedical engineering and other engineering activities involving separation or chemical reactions. Here we show the controlled vacuum generation through a biocompatible, energy efficient, low-cost and flexible miniature device. We have designed and fabricated microfluidic devices from polydimethylsiloxane which are capable of producing vacuum at a highly controlled rate by using water as a motive fluid. Scrupulous removal of infected fluid/body fluid from the internal hemorrhage affected parts during surgical operations, gene manipulation, cell sorting, and other biomedical activities require complete isolation of the delicate cells or tissues adjacent to the targeted location. We demonstrate the potential of the miniature device to obtain controlled evacuation without the use of highly pressurized motive fluids. Water has been used as a motive liquid to eject vapor and liquid at ambient conditions through the microfluidic devices prepared using a low-cost fabrication method. The proposed miniature device may find applications in vacuum generation especially where the controlled rate of evacuation, and limited vacuum generation are of utmost importance in order to precisely protect the cells in the nearby region of the targeted evacuated area.

Numerical and experimental evaluation of microfluidic sorting devices.

PubMed

Taylor, Jay K; Ren, Carolyn L; Stubley, G D

2008-01-01

The development of lab-on-a-chip devices calls for the isolation or separation of specific bioparticles or cells. The design of a miniaturized cell-sorting device for handheld operation must follow the strict parameters associated with lab-on-a-chip technology. The limitations include applied voltage, high efficiency of cell-separation, reliability, size, flow control, and cost, among others. Currently used designs have achieved successful levels of cell isolation; however, further improvements in the microfluidic chip design are important to incorporate into larger systems. This study evaluates specific design modifications that contribute to the reduction of required applied potential aiming for developing portable devices, improved operation reliability by minimizing induced pressure disturbance when electrokinetic pumping is employed, and improved flow control by incorporating directing streams achieving dynamic sorting and counting. The chip designs fabricated in glass and polymeric materials include asymmetric channel widths for sample focusing, nonuniform channel depth for minimizing induced pressure disturbance, directing streams to assist particle flow control, and online filters for reducing channel blockage. Fluorescence-based visualization experimental results of electrokinetic focusing, flow field phenomena, and dynamic sorting demonstrate the advantages of the chip design. Numerical simulations in COMSOL are validated by the experimental data and used to investigate the effects of channel geometry and fluid properties on the flow field.

A microfluidic platform for precision small-volume sample processing and its use to size separate biological particles with an acoustic microdevice [Precision size separation of biological particles in small-volume samples by an acoustic microfluidic system

DOE PAGES

Fong, Erika J.; Huang, Chao; Hamilton, Julie; ...

2015-11-23

Here, a major advantage of microfluidic devices is the ability to manipulate small sample volumes, thus reducing reagent waste and preserving precious sample. However, to achieve robust sample manipulation it is necessary to address device integration with the macroscale environment. To realize repeatable, sensitive particle separation with microfluidic devices, this protocol presents a complete automated and integrated microfluidic platform that enables precise processing of 0.15–1.5 ml samples using microfluidic devices. Important aspects of this system include modular device layout and robust fixtures resulting in reliable and flexible world to chip connections, and fully-automated fluid handling which accomplishes closed-loop sample collection,more » system cleaning and priming steps to ensure repeatable operation. Different microfluidic devices can be used interchangeably with this architecture. Here we incorporate an acoustofluidic device, detail its characterization, performance optimization, and demonstrate its use for size-separation of biological samples. By using real-time feedback during separation experiments, sample collection is optimized to conserve and concentrate sample. Although requiring the integration of multiple pieces of equipment, advantages of this architecture include the ability to process unknown samples with no additional system optimization, ease of device replacement, and precise, robust sample processing.« less

Principles of transverse flow fractionation of microparticles in superhydrophobic channels.

PubMed

Asmolov, Evgeny S; Dubov, Alexander L; Nizkaya, Tatiana V; Kuehne, Alexander J C; Vinogradova, Olga I

2015-07-07

We propose a concept of fractionation of micron-sized particles in a microfluidic device with a bottom wall decorated by superhydrophobic stripes. The stripes are oriented at an angle α to the direction of a driving force, G, which generally includes an applied pressure gradient and gravity. Separation relies on the initial sedimentation of particles under gravity in the main forward flow, and their subsequent lateral deflection near a superhydrophobic wall due to generation of a secondary flow transverse to G. We provide some theoretical arguments allowing us to quantify the transverse displacement of particles in the microfluidic channel, and confirm the validity of theoretical predictions in test experiments with monodisperse fractions of microparticles. Our results can guide the design of superhydrophobic microfluidic devices for efficient sorting of microparticles with a relatively small difference in size and density.

Microfluidics-to-Mass Spectrometry: A review of coupling methods and applications

PubMed Central

Wang, Xue; Yi, Lian; Mukhitov, Nikita; Schrell, Adrian M.; Dhumpa, Raghuram; Roper, Michael G.

2014-01-01

Microfluidic devices offer great advantages in integrating sample processes, minimizing sample and reagent volumes, and increasing analysis speed, while mass spectrometry detection provides high information content, is sensitive, and can be used in quantitative analyses. The coupling of microfluidic devices to mass spectrometers is becoming more common with the strengths of both systems being combined to analyze precious and complex samples. This review summarizes select achievements published between 2010 – July 2014 in novel coupling between microfluidic devices and mass spectrometers. The review is subdivided by the types of ionization sources employed, and the different microfluidic systems used. PMID:25458901

Fabrication, Metrology, and Transport Characteristics of Single Polymeric Nanopores in Three-Dimensional Hybrid Microfluidic/Nanofluidic Devices

ERIC Educational Resources Information Center

King, Travis L.

2009-01-01

The incorporation of nanofluidic elements between microfluidic channels to form hybrid microfluidic/nanofluidic architectures allows the extension of microfluidic systems into the third dimension, thus removing the constraints imposed by planarity. Measuring and understanding the behavior of these devices creates new analytical challenges due to…

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.

In vitro development of donated frozen-thawed human embryos in a prototype static microfluidic device: a randomized controlled trial.

PubMed

Kieslinger, Dorit C; Hao, Zhenxia; Vergouw, Carlijn G; Kostelijk, Elisabeth H; Lambalk, Cornelis B; Le Gac, Séverine

2015-03-01

To compare the development of human embryos in microfluidic devices with culture in standard microdrop dishes, both under static conditions. Prospective randomized controlled trial. In vitro fertilization laboratory. One hundred eighteen donated frozen-thawed human day-4 embryos. Random allocation of embryos that fulfilled the inclusion criteria to single-embryo culture in a microfluidics device (n = 58) or standard microdrop dish (n = 60). Blastocyst formation rate and quality after 24, 28, 48, and 72 hours of culture. The percentage of frozen-thawed day-4 embryos that developed to the blastocyst stage did not differ significantly in the standard microdrop dishes and microfluidic devices after 28 hours of culture (53.3% vs. 58.6%) or at any of the other time points. The proportion of embryos that would have been suitable for embryo transfer was comparable after 28 hours of culture in the control dishes and microfluidic devices (90.0% vs. 93.1%). Furthermore, blastocyst quality was similar in the two study groups. This study shows that a microfluidic device can successfully support human blastocyst development in vitro under static culture conditions. Future studies need to clarify whether earlier stage embryos will benefit from the culture in microfluidic devices more than the tested day-4 embryos because many important steps in the development of human embryos already take place before day 4. Further improvements of the microfluidic device will include parallel culture of single embryos, application of medium refreshment, and built-in sensors. NTR3867. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Using an Adapted Microfluidic Olfactory Chip for the Imaging of Neuronal Activity in Response to Pheromones in Male C. Elegans Head Neurons

PubMed Central

Reilly, Douglas K.; Lawler, Daniel E.; Albrecht, Dirk R.; Srinivasan, Jagan

2017-01-01

The use of calcium indicators has greatly enhanced our understanding of neural dynamics and regulation. The nematode Caenorhabditis elegans, with its completely mapped nervous system and transparent anatomy, presents an ideal model for understanding real-time neural dynamics using calcium indicators. In combination with microfluidic technologies and experimental designs, calcium-imaging studies using these indicators are performed in both free-moving and trapped animals. However, most previous studies utilizing trapping devices, such as the olfactory chip described in Chronis et al., have devices designed for use in the more common hermaphrodite, as the less common male is both morphologically and structurally dissimilar. An adapted olfactory chip was designed and fabricated for increased efficiency in male neuronal imaging with using young adult animals. A turn was incorporated into the worm loading port to rotate the animals and to allow for the separation of the individual neurons within a bilateral pair in 2D imaging. Worms are exposed to a controlled flow of odorant within the microfluidic device, as described in previous hermaphrodite studies. Calcium transients are then analyzed using the open-source software ImageJ. The procedure described herein should allow for an increased amount of male-based C. elegans calcium imaging studies, deepening our understanding of the mechanisms of sex-specific neuronal signaling. PMID:28930991

Commercialization of microfluidic devices.

PubMed

Volpatti, Lisa R; Yetisen, Ali K

2014-07-01

Microfluidic devices offer automation and high-throughput screening, and operate at low volumes of consumables. Although microfluidics has the potential to reduce turnaround times and costs for analytical devices, particularly in medical, veterinary, and environmental sciences, this enabling technology has had limited diffusion into consumer products. This article analyzes the microfluidics market, identifies issues, and highlights successful commercialization strategies. Addressing niche markets and establishing compatibility with existing workflows will accelerate market penetration. Copyright © 2014 Elsevier Ltd. All rights reserved.

A Student-Made Microfluidic Device for Electrophoretic Separation of Food Dyes

ERIC Educational Resources Information Center

Teerasong, Saowapak; McClain, Robert L.

2011-01-01

We have developed an undergraduate laboratory activity to introduce students to microfluidics. In the activity, each student constructs their own microfluidic device using simple photolithographic techniques and then uses the device to separate a food dye mixture by electrophoresis. Dyes are used so that students are able to visually observe the…

Design of organic 3D microresonators with microfluidics coupled to thin-film processes for photonic applications

NASA Astrophysics Data System (ADS)

Huby, N.; Pluchon, D.; Coulon, N.; Belloul, M.; Moreac, A.; Gaviot, E.; Panizza, P.; Bêche, B.

2010-06-01

We report on the design and realization of photonic integrated devices based on 3D organic microresonators (MR) shaped by an applied fluid mechanism technique. Such an interdisciplinary approach has been judiciously achieved by combining microfluidics techniques and thin-film processes, respectively, for the realizations of microfluidic and optical chips. The microfluidic framework with flow rates control allows the fabrication of microresonators with diameters ranging from 30 to 160 μm. The resonance of an isolated sphere in air has been demonstrated by way of a modified Raman spectroscopy devoted to the excitation of Whispering Gallery Modes (WGM). Then the 3D-MR have been integrated onto an organic chip and positioned either close to the extremity of a taper or alongside a rib waveguide. Both devices have proved efficient evanescent coupling mechanisms leading to the excitation of the WGM confined at the surface of the organic 3D-MR. Finally, a band-stop filter has been used to detect the resonance spectra of organic resonators once being integrated. Such spectral resonances have been observed with an integrated configuration and characterized with a Δ λ = 1.4 nm free spectral range (FSR), appearing as stemming from a 78 μm-radius MR structure.

The Separation of Blood Components Using Standing Surface Acoustic Waves (SSAWs) Microfluidic Devices: Analysis and Simulation.

PubMed

Soliman, Ahmed M; Eldosoky, Mohamed A; Taha, Taha E

2017-03-29

The separation of blood components (WBCs, RBCs, and platelets) is important for medical applications. Recently, standing surface acoustic wave (SSAW) microfluidic devices are used for the separation of particles. In this paper, the design analysis of SSAW microfluidics is presented. Also, the analysis of SSAW force with Rayleigh angle effect and its attenuation in liquid-loaded substrate, viscous drag force, hydrodynamic force, and diffusion force are explained and analyzed. The analyses are provided for selecting the piezoelectric material, width of the main microchannel, working area of SAW, wavelength, minimum input power required for the separation process, and widths of outlet collecting microchannels. The design analysis of SSAW microfluidics is provided for determining the minimum input power required for the separation process with appropriated the displacement contrast of the particles.The analyses are applied for simulation the separation of blood components. The piezoelectric material, width of the main microchannel, working area of SAW, wavelength, and minimum input power required for the separation process are selected as LiNbO₃, 120 μm, 1.08 mm², 300 μm, 371 mW. The results are compared to other published results. The results of these simulations achieve minimum power consumption, less complicated setup, and high collecting efficiency. All simulation programs are built by MATLAB.

The Separation of Blood Components Using Standing Surface Acoustic Waves (SSAWs) Microfluidic Devices: Analysis and Simulation

PubMed Central

Soliman, Ahmed M.; Eldosoky, Mohamed A.; Taha, Taha E.

2017-01-01

The separation of blood components (WBCs, RBCs, and platelets) is important for medical applications. Recently, standing surface acoustic wave (SSAW) microfluidic devices are used for the separation of particles. In this paper, the design analysis of SSAW microfluidics is presented. Also, the analysis of SSAW force with Rayleigh angle effect and its attenuation in liquid-loaded substrate, viscous drag force, hydrodynamic force, and diffusion force are explained and analyzed. The analyses are provided for selecting the piezoelectric material, width of the main microchannel, working area of SAW, wavelength, minimum input power required for the separation process, and widths of outlet collecting microchannels. The design analysis of SSAW microfluidics is provided for determining the minimum input power required for the separation process with appropriated the displacement contrast of the particles.The analyses are applied for simulation the separation of blood components. The piezoelectric material, width of the main microchannel, working area of SAW, wavelength, and minimum input power required for the separation process are selected as LiNbO3, 120 μm, 1.08 mm2, 300 μm, 371 mW. The results are compared to other published results. The results of these simulations achieve minimum power consumption, less complicated setup, and high collecting efficiency. All simulation programs are built by MATLAB. PMID:28952506

Protein Crystal Growth With the Aid of Microfluidics

NASA Technical Reports Server (NTRS)

vanderWoerd, Mark

2003-01-01

Protein crystallography is one of three well-known methods to obtain the structure of proteins. A major rate limiting step in protein crystallography is protein crystal nucleation and growth, which is still largely a process conducted by trial-and-error methods. Many attempts have been made to improve protein crystal growth by performing growth in microgravity. Although the use of microgravity appears to improve crystal quality in some attempts, this method has been inefficient because several reasons: we lack a fundamental understanding of macromolecular crystal growth in general and of the influence of microgravity in particular, we have to start with crystal growth conditions in microgravity based on conditions on the ground and finally the hardware does not allow for experimental iteration without reloading samples on the ground. To partially accommodate the disadvantages of the current hardware, we have used microfluidic technology (Lab-on-a-Chip devices) to design the concept of a more efficient crystallization device, suitable for use on the International Space Station and in high-throughput applications on the ground. The concept and properties of microfluidics, the application design process, and the advances in protein crystal growth hardware will be discussed in this presentation. Some examples of proteins crystallized in the new hardware will be discussed, including the differences between conventional crystallization versus crystallization in microfluidics.

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.

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.

Control of microtubule trajectory within an electric field by altering surface charge density

PubMed Central

Isozaki, Naoto; Ando, Suguru; Nakahara, Tasuku; Shintaku, Hirofumi; Kotera, Hidetoshi; Meyhöfer, Edgar; Yokokawa, Ryuji

2015-01-01

One of challenges for using microtubules (MTs) driven by kinesin motors in microfluidic environments is to control their direction of movement. Although applying physical biases to rectify MTs is prevalent, it has not been established as a design methodology in conjunction with microfluidic devices. In the future, the methodology is expected to achieve functional motor-driven nanosystems. Here, we propose a method to guide kinesin-propelled MTs in multiple directions under an electric field by designing a charged surface of MT minus ends labeled with dsDNA via a streptavidin-biotin interaction. MTs labeled with 20-bp or 50-bp dsDNA molecules showed significantly different trajectories according to the DNA length, which were in good agreement with values predicted from electrophoretic mobilities measured for their minus ends. Since the effective charge of labeled DNA molecules was equal to that of freely dispersed DNA molecules in a buffer solution, MT trajectory could be estimated by selecting labeling molecules with known charges. Moreover, the estimated trajectory enables to define geometrical sizes of a microfluidic device. This rational molecular design and prediction methodology allows MTs to be guided in multiple directions, demonstrating the feasibility of using molecular sorters driven by motor proteins. PMID:25567007

Control of microtubule trajectory within an electric field by altering surface charge density.

PubMed

Isozaki, Naoto; Ando, Suguru; Nakahara, Tasuku; Shintaku, Hirofumi; Kotera, Hidetoshi; Meyhöfer, Edgar; Yokokawa, Ryuji

2015-01-08

One of challenges for using microtubules (MTs) driven by kinesin motors in microfluidic environments is to control their direction of movement. Although applying physical biases to rectify MTs is prevalent, it has not been established as a design methodology in conjunction with microfluidic devices. In the future, the methodology is expected to achieve functional motor-driven nanosystems. Here, we propose a method to guide kinesin-propelled MTs in multiple directions under an electric field by designing a charged surface of MT minus ends labeled with dsDNA via a streptavidin-biotin interaction. MTs labeled with 20-bp or 50-bp dsDNA molecules showed significantly different trajectories according to the DNA length, which were in good agreement with values predicted from electrophoretic mobilities measured for their minus ends. Since the effective charge of labeled DNA molecules was equal to that of freely dispersed DNA molecules in a buffer solution, MT trajectory could be estimated by selecting labeling molecules with known charges. Moreover, the estimated trajectory enables to define geometrical sizes of a microfluidic device. This rational molecular design and prediction methodology allows MTs to be guided in multiple directions, demonstrating the feasibility of using molecular sorters driven by motor proteins.

Benchtop fabrication of three-dimensional reconfigurable microfluidic devices from paper-polymer composite.

PubMed

Han, Yu Long; Wang, Wenqi; Hu, Jie; Huang, Guoyou; Wang, Shuqi; Lee, Won Gu; Lu, Tian Jian; Xu, Feng

2013-12-21

We presented a benchtop technique that can fabricate reconfigurable, three-dimensional (3D) microfluidic devices made from a soft paper-polymer composite. This fabrication approach can produce microchannels at a minimal width of 100 μm and can be used to prototype 3D microfluidic devices by simple bending and stretching. The entire fabrication process can be finished in 2 hours on a laboratory bench without the need for special equipment involved in lithography. Various functional microfluidic devices (e.g., droplet generator and reconfigurable electronic circuit) were prepared using this paper-polymer hybrid microfluidic system. The developed method can be applied in a wide range of standard applications and emerging technologies such as liquid-phase electronics.

Microfluidic model of the platelet-generating organ: beyond bone marrow biomimetics

NASA Astrophysics Data System (ADS)

Blin, Antoine; Le Goff, Anne; Magniez, Aurélie; Poirault-Chassac, Sonia; Teste, Bruno; Sicot, Géraldine; Nguyen, Kim Anh; Hamdi, Feriel S.; Reyssat, Mathilde; Baruch, Dominique

2016-02-01

We present a new, rapid method for producing blood platelets in vitro from cultured megakaryocytes based on a microfluidic device. This device consists in a wide array of VWF-coated micropillars. Such pillars act as anchors on megakaryocytes, allowing them to remain trapped in the device and subjected to hydrodynamic shear. The combined effect of anchoring and shear induces the elongation of megakaryocytes and finally their rupture into platelets and proplatelets. This process was observed with megakaryocytes from different origins and found to be robust. This original bioreactor design allows to process megakaryocytes at high throughput (millions per hour). Since platelets are produced in such a large amount, their extensive biological characterisation is possible and shows that platelets produced in this bioreactor are functional.

Microfluidic model of the platelet-generating organ: beyond bone marrow biomimetics.

PubMed

Blin, Antoine; Le Goff, Anne; Magniez, Aurélie; Poirault-Chassac, Sonia; Teste, Bruno; Sicot, Géraldine; Nguyen, Kim Anh; Hamdi, Feriel S; Reyssat, Mathilde; Baruch, Dominique

2016-02-22

We present a new, rapid method for producing blood platelets in vitro from cultured megakaryocytes based on a microfluidic device. This device consists in a wide array of VWF-coated micropillars. Such pillars act as anchors on megakaryocytes, allowing them to remain trapped in the device and subjected to hydrodynamic shear. The combined effect of anchoring and shear induces the elongation of megakaryocytes and finally their rupture into platelets and proplatelets. This process was observed with megakaryocytes from different origins and found to be robust. This original bioreactor design allows to process megakaryocytes at high throughput (millions per hour). Since platelets are produced in such a large amount, their extensive biological characterisation is possible and shows that platelets produced in this bioreactor are functional.

Fabrication of zein nanostructure

NASA Astrophysics Data System (ADS)

Luecha, Jarupat

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

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.

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.

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.

Review of microfluidic cell culture devices for the control of gaseous microenvironments in vitro

NASA Astrophysics Data System (ADS)

Wu, H.-M.; Lee, T.-A.; Ko, P.-L.; Chiang, H.-J.; Peng, C.-C.; Tung, Y.-C.

2018-04-01

Gaseous microenvironments play important roles in various biological activities in vivo. However, it is challenging to precisely control gaseous microenvironments in vitro for cell culture due to the high diffusivity nature of gases. In recent years, microfluidics has paved the way for the development of new types of cell culture devices capable of manipulating cellular microenvironments, and provides a powerful tool for in vitro cell studies. This paper reviews recent developments of microfluidic cell culture devices for the control of gaseous microenvironments, and discusses the advantages and limitations of current devices. We conclude with suggestions for the future development of microfluidic cell culture devices for the control of gaseous microenvironments.

Magnetic Nickel iron Electroformed Trap (MagNET): a master/replica fabrication strategy for ultra-high throughput (>100 mL h−1) immunomagnetic sorting†

PubMed Central

Ko, Jina; Yelleswarapu, Venkata; Singh, Anup; Shah, Nishal

2016-01-01

Microfluidic devices can sort immunomagnetically labeled cells with sensitivity and specificity much greater than that of conventional methods, primarily because the size of microfluidic channels and micro-scale magnets can be matched to that of individual cells. However, these small feature sizes come at the expense of limited throughput (ϕ < 5 mL h−1) and susceptibility to clogging, which have hindered current microfluidic technology from processing relevant volumes of clinical samples, e.g. V > 10 mL whole blood. Here, we report a new approach to micromagnetic sorting that can achieve highly specific cell separation in unprocessed complex samples at a throughput (ϕ > 100 mL h−1) 100× greater than that of conventional microfluidics. To achieve this goal, we have devised a new approach to micromagnetic sorting, the magnetic nickel iron electroformed trap (MagNET), which enables high flow rates by having millions of micromagnetic traps operate in parallel. Our design rotates the conventional microfluidic approach by 90° to form magnetic traps at the edges of pores instead of in channels, enabling millions of the magnetic traps to be incorporated into a centimeter sized device. Unlike previous work, where magnetic structures were defined using conventional microfabrication, we take inspiration from soft lithography and create a master from which many replica electroformed magnetic micropore devices can be economically manufactured. These free-standing 12 µm thick permalloy (Ni80Fe20) films contain micropores of arbitrary shape and position, allowing the device to be tailored for maximal capture efficiency and throughput. We demonstrate MagNET's capabilities by fabricating devices with both circular and rectangular pores and use these devices to rapidly (ϕ = 180 mL h−1) and specifically sort rare tumor cells from white blood cells. PMID:27170379

An integrated cell culture lab on a chip: modular microdevices for cultivation of mammalian cells and delivery into microfluidic microdroplets.

PubMed

Hufnagel, Hansjörg; Huebner, Ansgar; Gülch, Carina; Güse, Katharina; Abell, Chris; Hollfelder, Florian

2009-06-07

We present a modular system of microfluidic PDMS devices designed to incorporate the steps necessary for cell biological assays based on mammalian tissue culture 'on-chip'. The methods described herein include the on-chip immobilization and culturing of cells as well as their manipulation by transfection. Assessment of cell viability by flow cytrometry suggests low attrition rates (<3%) and excellent growth properties in the device for up to 7 days for CHO-K1 cells. To demonstrate that key procedures from the repertoire of cell biology are possible in this format, transfection of a reporter gene (encoding green fluorescent protein) was carried out. The modular design enables efficient detachment and recollection of cells and allows assessment of the success of transfection achieved on-chip. The transfection levels (20%) are comparable to standard large scale procedures and more than 500 cells could be transfected. Finally, cells are transferred into microfluidic microdoplets, where in principle a wide range of subsequent assays can be carried out at the single cell level in droplet compartments. The procedures developed for this modular device layout further demonstrate that commonly used methods in cell biology involving mammalian cells can be reliably scaled down to allow single cell investigations in picolitre volumes.

Expanding Imaging Capabilities for Microfluidics: Applicability of Darkfield Internal Reflection Illumination (DIRI) to Observations in Microfluidics

PubMed Central

Kawano, Yoshihiro; Otsuka, Chino; Sanzo, James; Higgins, Christopher; Nirei, Tatsuo; Schilling, Tobias; Ishikawa, Takuji

2015-01-01

Microfluidics is used increasingly for engineering and biomedical applications due to recent advances in microfabrication technologies. Visualization of bubbles, tracer particles, and cells in a microfluidic device is important for designing a device and analyzing results. However, with conventional methods, it is difficult to observe the channel geometry and such particles simultaneously. To overcome this limitation, we developed a Darkfield Internal Reflection Illumination (DIRI) system that improved the drawbacks of a conventional darkfield illuminator. This study was performed to investigate its utility in the field of microfluidics. The results showed that the developed system could clearly visualize both microbubbles and the channel wall by utilizing brightfield and DIRI illumination simultaneously. The methodology is useful not only for static phenomena, such as clogging, but also for dynamic phenomena, such as the detection of bubbles flowing in a channel. The system was also applied to simultaneous fluorescence and DIRI imaging. Fluorescent tracer beads and channel walls were observed clearly, which may be an advantage for future microparticle image velocimetry (μPIV) analysis, especially near a wall. Two types of cell stained with different colors, and the channel wall, can be recognized using the combined confocal and DIRI system. Whole-slide imaging was also conducted successfully using this system. The tiling function significantly expands the observing area of microfluidics. The developed system will be useful for a wide variety of engineering and biomedical applications for the growing field of microfluidics. PMID:25748425

Expanding imaging capabilities for microfluidics: applicability of darkfield internal reflection illumination (DIRI) to observations in microfluidics.

PubMed

Kawano, Yoshihiro; Otsuka, Chino; Sanzo, James; Higgins, Christopher; Nirei, Tatsuo; Schilling, Tobias; Ishikawa, Takuji

2015-01-01

Microfluidics is used increasingly for engineering and biomedical applications due to recent advances in microfabrication technologies. Visualization of bubbles, tracer particles, and cells in a microfluidic device is important for designing a device and analyzing results. However, with conventional methods, it is difficult to observe the channel geometry and such particles simultaneously. To overcome this limitation, we developed a Darkfield Internal Reflection Illumination (DIRI) system that improved the drawbacks of a conventional darkfield illuminator. This study was performed to investigate its utility in the field of microfluidics. The results showed that the developed system could clearly visualize both microbubbles and the channel wall by utilizing brightfield and DIRI illumination simultaneously. The methodology is useful not only for static phenomena, such as clogging, but also for dynamic phenomena, such as the detection of bubbles flowing in a channel. The system was also applied to simultaneous fluorescence and DIRI imaging. Fluorescent tracer beads and channel walls were observed clearly, which may be an advantage for future microparticle image velocimetry (μPIV) analysis, especially near a wall. Two types of cell stained with different colors, and the channel wall, can be recognized using the combined confocal and DIRI system. Whole-slide imaging was also conducted successfully using this system. The tiling function significantly expands the observing area of microfluidics. The developed system will be useful for a wide variety of engineering and biomedical applications for the growing field of microfluidics.

Rapid mask prototyping for microfluidics.

PubMed

Maisonneuve, B G C; Honegger, T; Cordeiro, J; Lecarme, O; Thiry, T; Fuard, D; Berton, K; Picard, E; Zelsmann, M; Peyrade, D

2016-03-01

With the rise of microfluidics for the past decade, there has come an ever more pressing need for a low-cost and rapid prototyping technology, especially for research and education purposes. In this article, we report a rapid prototyping process of chromed masks for various microfluidic applications. The process takes place out of a clean room, uses a commercially available video-projector, and can be completed in less than half an hour. We quantify the ranges of fields of view and of resolutions accessible through this video-projection system and report the fabrication of critical microfluidic components (junctions, straight channels, and curved channels). To exemplify the process, three common devices are produced using this method: a droplet generation device, a gradient generation device, and a neuro-engineering oriented device. The neuro-engineering oriented device is a compartmentalized microfluidic chip, and therefore, required the production and the precise alignment of two different masks.

Rapid mask prototyping for microfluidics

PubMed Central

Maisonneuve, B. G. C.; Honegger, T.; Cordeiro, J.; Lecarme, O.; Thiry, T.; Fuard, D.; Berton, K.; Picard, E.; Zelsmann, M.; Peyrade, D.

2016-01-01

With the rise of microfluidics for the past decade, there has come an ever more pressing need for a low-cost and rapid prototyping technology, especially for research and education purposes. In this article, we report a rapid prototyping process of chromed masks for various microfluidic applications. The process takes place out of a clean room, uses a commercially available video-projector, and can be completed in less than half an hour. We quantify the ranges of fields of view and of resolutions accessible through this video-projection system and report the fabrication of critical microfluidic components (junctions, straight channels, and curved channels). To exemplify the process, three common devices are produced using this method: a droplet generation device, a gradient generation device, and a neuro-engineering oriented device. The neuro-engineering oriented device is a compartmentalized microfluidic chip, and therefore, required the production and the precise alignment of two different masks. PMID:27014396

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

PubMed

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

2014-01-01

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

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

Magnetoresistive immunosensor for the detection of Escherichia coli O157:H7 including a microfluidic network.

PubMed

Mujika, M; Arana, S; Castaño, E; Tijero, M; Vilares, R; Ruano-López, J M; Cruz, A; Sainz, L; Berganza, J

2009-01-01

A hand held device has been designed for the immunomagnetic detection and quantification of the pathogen Escherichia coli O157:H7 in food and clinical samples. In this work, a technology to manufacture a Lab on a Chip that integrates a 3D microfluidic network with a microfabricated biosensor has been developed. With this aim, the sensing film optimization, the design of the microfluidic circuitry, the development of the biological protocols involved in the measurements and, finally, the packaging needed to carry out the assays in a safe and straightforward way have been completed. The biosensor is designed to be capable to detect and quantify small magnetic field variations caused by the presence of superparamagnetic beads bound to the antigens previously immobilized on the sensor surface via an antibody-antigen reaction. The giant magnetoresistive multilayer structure implemented as sensing film consists of 20[Cu(5.10nm)/Co(2.47 nm)] with a magnetoresistance of 3.20% at 235Oe and a sensitivity up to 0.06 Omega/Oe between 150Oe and 230Oe. Silicon nitride has been selected as optimum sensor surface coating due to its suitability for antibody immobilization. In order to guide the biological samples towards the sensing area, a microfluidic network made of SU-8 photoresist has been included. Finally, a novel packaging design has been fabricated employing 3D stereolithographic techniques. The microchannels are connected to the outside using standard tubing. Hence, this packaging allows an easy replacement of the used devices.

Constant flow-driven microfluidic oscillator for different duty cycles

PubMed Central

Kim, Sung-Jin; Yokokawa, Ryuji; Lesher-Perez, Sasha Cai; Takayama, Shuichi

2012-01-01

This paper presents microfluidic devices that autonomously convert two constant flow inputs into an alternating oscillatory flow output. We accomplish this hardware embedded self-control programming using normally closed membrane valves that have an inlet, an outlet, and a membrane-pressurization chamber connected to a third terminal. Adjustment of threshold opening pressures in these 3-terminal flow switching valves enabled adjustment of oscillation periods to between 57–360 s with duty cycles of 0.2–0.5. These values are in relatively good agreement with theoretical values, providing the way for rational design of an even wider range of different waveform oscillations. We also demonstrate the ability to use these oscillators to perform temporally patterned delivery of chemicals to living cells. The device only needs a syringe pump, thus removing the use of complex, expensive external actuators. These tunable waveform microfluidic oscillators are envisioned to facilitate cell-based studies that require temporal stimulation. PMID:22206453

Droplet Velocity Measurement Based on Dielectric Layer Thickness Variation Using Digital Microfluidic Devices.

PubMed

Zulkepli, Siti Noor Idora Syafinaz; Hamid, Nor Hisham; Shukla, Vineeta

2018-05-08

In recent years, the number of interdisciplinary research works related to the development of miniaturized systems with integrated chemical and biological analyses is increasing. Digital microfluidic biochips (DMFBs) are one kind of miniaturized systems designed for conducting inexpensive, fast, convenient and reliable biochemical assay procedures focusing on basic scientific research and medical diagnostics. The role of a dielectric layer in the digital microfluidic biochips is prominent as it helps in actuating microliter droplets based on the electrowetting-on-dielectric (EWOD) technique. The advantages of using three different material layers of dielectric such as parafilm, polytetrafluoroethylene (PTFE) and ethylene tetrafluoroethylene (ETFE) were reported in the current work. A simple fabrication process of a digital microfluidic device was performed and good results were obtained. The threshold of the actuation voltage was determined for all dielectric materials of varying thicknesses. Additionally, the OpenDrop device was tested by utilizing a single-plate system to transport microliter droplets for a bioassay operation. With the newly proposed fabrication methods, these dielectric materials showed changes in contact angle and droplet velocity when the actuation voltage was applied. The threshold actuation voltage for the dielectric layers of 10⁻13 μm was 190 V for the open plate DMFBs.

Development and Applications of Portable Biosensors.

PubMed

Srinivasan, Balaji; Tung, Steve

2015-08-01

The significance of microfluidics-based and microelectromechanical systems-based biosensors has been widely acknowledged, and many reviews have explored their potential applications in clinical diagnostics, personalized medicine, global health, drug discovery, food safety, and forensics. Because health care costs are increasing, there is an increasing need to remotely monitor the health condition of patients by point-of-care-testing. The demand for biosensors for detection of biological warfare agents has increased, and research is focused on ways of producing small portable devices that would allow fast, accurate, and on-site detection. In the past decade, the demand for rapid and accurate on-site detection of plant disease diagnosis has increased due to emerging pathogens with resistance to pesticides, increased human mobility, and regulations limiting the application of toxic chemicals to prevent spread of diseases. The portability of biosensors for on-site diagnosis is limited due to various issues, including sample preparation techniques, fluid-handling techniques, the limited lifetime of biological reagents, device packaging, integrating electronics for data collection/analysis, and the requirement of external accessories and power. Many microfluidic, electronic, and biological design strategies, such as handling liquids in biosensors without pumps/valves, the application of droplet-based microfluidics, paper-based microfluidic devices, and wireless networking capabilities for data transmission, are being explored. © 2015 Society for Laboratory Automation and Screening.

A soft, wearable microfluidic device for the capture, storage, and colorimetric sensing of sweat.

PubMed

Koh, Ahyeon; Kang, Daeshik; Xue, Yeguang; Lee, Seungmin; Pielak, Rafal M; Kim, Jeonghyun; Hwang, Taehwan; Min, Seunghwan; Banks, Anthony; Bastien, Philippe; Manco, Megan C; Wang, Liang; Ammann, Kaitlyn R; Jang, Kyung-In; Won, Phillip; Han, Seungyong; Ghaffari, Roozbeh; Paik, Ungyu; Slepian, Marvin J; Balooch, Guive; Huang, Yonggang; Rogers, John A

2016-11-23

Capabilities in health monitoring enabled by capture and quantitative chemical analysis of sweat could complement, or potentially obviate the need for, approaches based on sporadic assessment of blood samples. Established sweat monitoring technologies use simple fabric swatches and are limited to basic analysis in controlled laboratory or hospital settings. We present a collection of materials and device designs for soft, flexible, and stretchable microfluidic systems, including embodiments that integrate wireless communication electronics, which can intimately and robustly bond to the surface of the skin without chemical and mechanical irritation. This integration defines access points for a small set of sweat glands such that perspiration spontaneously initiates routing of sweat through a microfluidic network and set of reservoirs. Embedded chemical analyses respond in colorimetric fashion to markers such as chloride and hydronium ions, glucose, and lactate. Wireless interfaces to digital image capture hardware serve as a means for quantitation. Human studies demonstrated the functionality of this microfluidic device during fitness cycling in a controlled environment and during long-distance bicycle racing in arid, outdoor conditions. The results include quantitative values for sweat rate, total sweat loss, pH, and concentration of chloride and lactate. Copyright © 2016, American Association for the Advancement of Science.

Non-perturbative manipulation through a 3D microfluidic treadmill

NASA Astrophysics Data System (ADS)

Gonzalez, Jeremias; Liu, Bin

2017-11-01

Our capabilities of micromanipulation have evolved with advances in contact-free trapping techniques under various disciplines, such as optical, magnetic, and microfluidic traps. In these techniques, a microscale particle is held in place under compression due to electromagnetic or hydrodynamic forces. In this work, we present a trap-free design of a microfluidic ``treadmill'' (MFC), realized by a uniform flow along arbitrary directions in a 3D microfluidic device, which is composed of a central chamber and pairs of x - and y - channels at different elevations. Through boundary element simulations, we demonstrate that 3D background flows along any direction can be generated in the middle of the chamber, controlled by a set of syringe pumps. By tuning the detailed geometry of the MFC, we show the optimized shape of the device that leads to minimized strain rate, allowing for manipulation of the suspended particles with negligible perturbations. We also show an experimental realization of the MFC device, using laser stereolithography. The x - , y - , and z - manipulation modes are obtained independently by a syringe pump with push/pull mechanisms, and are compared with the above simulation results. The authors thank the support of National Science Foundation CREST: Center for Cellular and Biomolecular Machines at UC Merced (NSF-HRD-1547848).

Self-Powered Viscosity and Pressure Sensing in Microfluidic Systems Based on the Piezoelectric Energy Harvesting of Flowing Droplets.

PubMed

Wang, Zhao; Tan, Lun; Pan, Xumin; Liu, Gao; He, Yahua; Jin, Wenchao; Li, Meng; Hu, Yongming; Gu, Haoshuang

2017-08-30

The rapid development of microscaled piezoelectric energy harvesters has provided a simple and highly efficient way for building self-powered sensor systems through harvesting the mechanical energy from the ambient environment. In this work, a self-powered microfluidic sensor that can harvest the mechanical energy of the fluid and simultaneously monitor their characteristics was fabricated by integrating the flexible piezoelectric poly(vinylidene fluoride) (PVDF) nanofibers with the well-designed microfluidic chips. Those devices could generate open-circuit high output voltage up to 1.8 V when a droplet of water is flowing past the suspended PVDF nanofibers and result in their periodical deformations. The impulsive output voltage signal allowed them to be utilized for droplets or bubbles counting in the microfluidic systems. Furthermore, the devices also exhibited self-powered sensing behavior due to the decreased voltage amplitude with increasing input pressure and liquid viscosity. The drop of output voltage could be attributed to the variation of flow condition and velocity of the droplets, leading to the reduced deformation of the piezoelectric PVDF layer and the decrease of the generated piezoelectric potential.

Additive manufacturing of microfluidic glass chips

NASA Astrophysics Data System (ADS)

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

2018-02-01

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

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.

Production of nanoparticle drug delivery systems with microfluidics tools.

PubMed

Khan, Ikram Ullah; Serra, Christophe A; Anton, Nicolas; Vandamme, Thierry F

2015-04-01

Nowadays the development of composite nano- and microparticles is an extensively studied area of research. This interest is growing because of the potential use of such particles in drug delivery systems. Indeed they can be used in various medical disciplines depending upon their sizes and their size distribution, which determine their final biomedical applications. Amongst the different techniques to produce nanoparticles, microfluidic techniques allow preparing particles having a specific size, a narrow size distribution and high encapsulation efficiency with ease. This review covers the general description of microfluidics, its techniques, advantages and disadvantages with focus on the encapsulation of active principles in polymeric nanoparticles as well as on pure drug nanoparticles. Polymeric nanoparticles constitute the majority of the examples reported; however lipid nanoparticulate systems (DNA, SiRNA nanocarriers) are very comparable and their formulation processes are in most cases exactly similar. Accordingly this review focuses also on active ingredient nanoparticles formulated by nanoprecipitation processes in microfluidic devices in general. It also provides detailed description of the different geometries of most common microfluidic devices and the crucial parameters involved in techniques designed to obtain the desired properties. Although the classical fabrication of nanoparticles drug delivery systems in batch is extremely well-described and developed, their production with microfluidic tools arises today as an emerging field with much more potential. In this review we present and discuss these new possibilities for biomedical applications through the current emerging developments.

Evaluation of peristaltic micromixers for highly integrated microfluidic systems

PubMed Central

Kim, Duckjong; Rho, Hoon Suk; Jambovane, Sachin; Shin, Soojeong; Hong, Jong Wook

2016-01-01

Microfluidic devices based on the multilayer soft lithography allow accurate manipulation of liquids, handling reagents at the sub-nanoliter level, and performing multiple reactions in parallel processors by adapting micromixers. Here, we have experimentally evaluated and compared several designs of micromixers and operating conditions to find design guidelines for the micromixers. We tested circular, triangular, and rectangular mixing loops and measured mixing performance according to the position and the width of the valves that drive nanoliters of fluids in the micrometer scale mixing loop. We found that the rectangular mixer is best for the applications of highly integrated microfluidic platforms in terms of the mixing performance and the space utilization. This study provides an improved understanding of the flow behaviors inside micromixers and design guidelines for micromixers that are critical to build higher order fluidic systems for the complicated parallel bio/chemical processes on a chip. PMID:27036809

Evaluation of peristaltic micromixers for highly integrated microfluidic systems

NASA Astrophysics Data System (ADS)

Kim, Duckjong; Rho, Hoon Suk; Jambovane, Sachin; Shin, Soojeong; Hong, Jong Wook

2016-03-01

Microfluidic devices based on the multilayer soft lithography allow accurate manipulation of liquids, handling reagents at the sub-nanoliter level, and performing multiple reactions in parallel processors by adapting micromixers. Here, we have experimentally evaluated and compared several designs of micromixers and operating conditions to find design guidelines for the micromixers. We tested circular, triangular, and rectangular mixing loops and measured mixing performance according to the position and the width of the valves that drive nanoliters of fluids in the micrometer scale mixing loop. We found that the rectangular mixer is best for the applications of highly integrated microfluidic platforms in terms of the mixing performance and the space utilization. This study provides an improved understanding of the flow behaviors inside micromixers and design guidelines for micromixers that are critical to build higher order fluidic systems for the complicated parallel bio/chemical processes on a chip.

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…

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.

Microfluidic Biochip Design

NASA Technical Reports Server (NTRS)

Panzarella, Charles

2004-01-01

As humans prepare for the exploration of our solar system, there is a growing need for miniaturized medical and environmental diagnostic devices for use on spacecrafts, especially during long-duration space missions where size and power requirements are critical. In recent years, the biochip (or Lab-on-a-Chip) has emerged as a technology that might be able to satisfy this need. In generic terms, a biochip is a miniaturized microfluidic device analogous to the electronic microchip that ushered in the digital age. It consists of tiny microfluidic channels, pumps and valves that transport small amounts of sample fluids to biosensors that can perform a variety of tests on those fluids in near real time. It has the obvious advantages of being small, lightweight, requiring less sample fluids and reagents and being more sensitive and efficient than larger devices currently in use. Some of the desired space-based applications would be to provide smaller, more robust devices for analyzing blood, saliva and urine and for testing water and food supplies for the presence of harmful contaminants and microorganisms. Our group has undertaken the goal of adapting as well as improving upon current biochip technology for use in long-duration microgravity environments.

A Microfluidic Love-Wave Biosensing Device for PSA Detection Based on an Aptamer Beacon Probe.

PubMed

Zhang, Feng; Li, Shuangming; Cao, Kang; Wang, Pengjuan; Su, Yan; Zhu, Xinhua; Wan, Ying

2015-06-11

A label-free and selective aptamer beacon-based Love-wave biosensing device was developed for prostate specific antigen (PSA) detection. The device consists of the following parts: LiTaO3 substrate with SiO2 film as wave guide layer, two set of inter-digital transducers (IDT), gold film for immobilization of the biorecongniton layer and a polydimethylsiloxane (PDMS) microfluidic channels. DNA aptamer, or "artificial antibody", was used as the specific biorecognition probe for PSA capture. Some nucleotides were added to the 3'-end of the aptamer to form a duplex with the 3'-end, turning the aptamer into an aptamer-beacon. Taking advantage of the selective target-induced assembly changes arising from the "aptamer beacon", highly selective and specific detection of PSA was achieved. Furthermore, PDMS microfluidic channels were designed and fabricated to realize automated quantitative sample injection. After optimization of the experimental conditions, the established device showed good performance for PSA detection between 10 ng/mL to 1 μg/mL, with a detection limit of 10 ng/mL. The proposed sensor might be a promising alternative for point of care diagnostics.

Batch-reactor microfluidic device: first human use of a microfluidically produced PET radiotracer†

PubMed Central

Miraghaie, Reza; Kotta, Kishore; Ball, Carroll E.; Zhang, Jianzhong; Buchsbaum, Monte S.; Kolb, Hartmuth C.; Elizarov, Arkadij

2013-01-01

The very first microfluidic device used for the production of 18F-labeled tracers for clinical research is reported along with the first human Positron Emission Tomography scan obtained with a microfluidically produced radiotracer. The system integrates all operations necessary for the transformation of [18F]fluoride in irradiated cyclotron target water to a dose of radiopharmaceutical suitable for use in clinical research. The key microfluidic technologies developed for the device are a fluoride concentration system and a microfluidic batch reactor assembly. Concentration of fluoride was achieved by means of absorption of the fluoride anion on a micro ion-exchange column (5 μL of resin) followed by release of the radioactivity with 45 μL of the release solution (95 ± 3% overall efficiency). The reactor assembly includes an injection-molded reactor chip and a transparent machined lid press-fitted together. The resulting 50 μL cavity has a unique shape designed to minimize losses of liquid during reactor filling and liquid evaporation. The cavity has 8 ports for gases and liquids, each equipped with a 2-way on-chip mechanical valve rated for pressure up to 20.68 bar (300 psi). The temperature is controlled by a thermoelectric heater capable of heating the reactor up to 180 °C from RT in 150 s. A camera captures live video of the processes in the reactor. HPLC-based purification and reformulation units are also integrated in the device. The system is based on “split-box architecture”, with reagents loaded from outside of the radiation shielding. It can be installed either in a standard hot cell, or as a self-shielded unit. Along with a high level of integration and automation, split-box architecture allowed for multiple production runs without the user being exposed to radiation fields. The system was used to support clinical trials of [18F]fallypride, a neuroimaging radiopharmaceutical under IND Application #109,880. PMID:23135409

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.

Novel microfluidic device for the continuous separation of cancer cells using dielectrophoresis.

PubMed

Alazzam, Anas; Mathew, Bobby; Alhammadi, Falah

2017-03-01

We describe the design, microfabrication, and testing of a microfluidic device for the separation of cancer cells based on dielectrophoresis. Cancer cells, specifically green fluorescent protein-labeled MDA-MB-231, are successfully separated from a heterogeneous mixture of the same and normal blood cells. MDA-MB-231 cancer cells are separated with an accuracy that enables precise detection and counting of circulating tumor cells present among normal blood cells. The separation is performed using a set of planar interdigitated transducer electrodes that are deposited on the surface of a glass wafer and slightly protrude into the separation microchannel at one side. The device includes two parts, namely, a glass wafer and polydimethylsiloxane element. The device is fabricated using standard microfabrication techniques. All experiments are conducted with low conductivity sucrose-dextrose isotonic medium. The variation in response between MDA-MB-231 cancer cells and normal cells to a certain band of alternating-current frequencies is used for continuous separation of cells. The fabrication of the microfluidic device, preparation of cells and medium, and flow conditions are detailed. The proposed microdevice can be used to detect and separate malignant cells from heterogeneous mixture of cells for the purpose of early screening for cancer. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

[Fabrications of a poly (methyl methacrylate) (PMMA) microfluidic chip-based DNA analysis device].

PubMed

Du, Xiao-Guang

2009-12-01

A DNA analysis device based on poly(methyl methacrylate) (PMMA) microfluidic chips was developed. A PMMA chip with cross microchannels was fabricated by a simple hot embossing. Microchannels were modified with a static adsorptive coating method using 2% hydroxyethyl cellulose. A high-voltage power unit, variable in the range 0-1 800 V, was used for on-chip DNA sample injection and gel electrophoretic separation. High speed, high resolution DNA analysis was obtained with the home-built PMMA chip in a sieving matrix containing 2% hydroxyethyl cellulose with a blue intercalating dye, TO-PRO-3 (TP3), by using diode laser induced fluorescence detection based on optical fibers with a 670 nm long-pass filter. The DNA analysis device was applied for the separation of phiX-174/HaeIII DNA digest sample with 11 fragments ranging from 72 to 1 353 bp. A separation efficiency of 1.14 x 10(6) plates/m was obtained for the 603 bp fragments, while the R of 271/281 bp fragments was 1.2. The device was characterized by simple design, low cost for fabrication and operation, reusable PMMA chips, and good reproducibility. A portable microfluidic device for DNA analysis can be developed for clinical diagnosis and disease screening.

Self-powered Imbibing Microfluidic Pump by Liquid Encapsulation: SIMPLE.

PubMed

Kokalj, Tadej; Park, Younggeun; Vencelj, Matjaž; Jenko, Monika; Lee, Luke P

2014-11-21

Reliable, autonomous, internally self-powered microfluidic pumps are in critical demand for rapid point-of-care (POC) devices, integrated molecular-diagnostic platforms, and drug delivery systems. Here we report on a Self-powered Imbibing Microfluidic Pump by Liquid Encapsulation (SIMPLE), which is disposable, autonomous, easy to use and fabricate, robust, and cost efficient, as a solution for self-powered microfluidic POC devices. The imbibition pump introduces the working liquid which is sucked into a porous material (paper) upon activation. The suction of the working liquid creates a reduced pressure in the analytical channel and induces the sequential sample flow into the microfluidic circuits. It requires no external power or control and can be simply activated by a fingertip press. The flow rate can be programmed by defining the shape of utilized porous material: by using three different paper shapes with circular section angles 20°, 40° and 60°, three different volume flow rates of 0.07 μL s(-1), 0.12 μL s(-1) and 0.17 μL s(-1) are demonstrated at 200 μm × 600 μm channel cross-section. We established the SIMPLE pumping of 17 μL of sample; however, the sample volume can be increased to several hundreds of μL. To demonstrate the design, fabrication, and characterization of SIMPLE, we used a simple, robust and cheap foil-laminating fabrication technique. The SIMPLE can be integrated into hydrophilic or hydrophobic materials-based microfluidic POC devices. Since it is also applicable to large-scale manufacturing processes, we anticipate that a new chapter of a cost effective, disposable, autonomous POC diagnostic chip is addressed with this technical innovation.

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

A microfluidic device for the automated derivatization of free fatty acids to fatty acid methyl esters.

PubMed

Duong, Cindy T; Roper, Michael G

2012-02-21

Free fatty acid (FFA) compositions are examined in feedstock for biodiesel production, as source-specific markers in soil, and because of their role in cellular signaling. However, sample preparation of FFAs for gas chromatography-mass spectrometry (GC-MS) analysis can be time and labor intensive. Therefore, to increase sample preparation throughput, a glass microfluidic device was developed to automate derivatization of FFAs to fatty acid methyl esters (FAMEs). FFAs were delivered to one input of the device and methanolic-HCl was delivered to a second input. FAME products were produced as the reagents traversed a 29 μL reaction channel held at 55 °C. A Design of Experiment protocol was used to determine the combination of derivatization time (T(der)) and ratio of methanolic-HCl:FFA (R(der)) that maximized the derivatization efficiencies of tridecanoic acid and stearic acid to their methyl ester forms. The combination of T(der) = 0.8 min and R(der) = 4.9 that produced optimal derivatization conditions for both FFAs within a 5 min total sample preparation time was determined. This combination of T(der) and R(der) was used to derivatize 12 FFAs with a range of derivatization efficiencies from 18% to 93% with efficiencies of 61% for tridecanoic acid and 84% for stearic acid. As compared to a conventional macroscale derivatization of FFA to FAME, the microfluidic device decreased the volume of methanolic-HCl and FFA by 20- and 1300-fold, respectively. The developed microfluidic device can be used for automated preparation of FAMEs to analyze the FFA compositions of volume-limited samples.

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

PubMed

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

2008-07-09

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

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

PubMed Central

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

2008-01-01

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

Microfluidic model of the platelet-generating organ: beyond bone marrow biomimetics

PubMed Central

Blin, Antoine; Le Goff, Anne; Magniez, Aurélie; Poirault-Chassac, Sonia; Teste, Bruno; Sicot, Géraldine; Nguyen, Kim Anh; Hamdi, Feriel S.; Reyssat, Mathilde; Baruch, Dominique

2016-01-01

We present a new, rapid method for producing blood platelets in vitro from cultured megakaryocytes based on a microfluidic device. This device consists in a wide array of VWF-coated micropillars. Such pillars act as anchors on megakaryocytes, allowing them to remain trapped in the device and subjected to hydrodynamic shear. The combined effect of anchoring and shear induces the elongation of megakaryocytes and finally their rupture into platelets and proplatelets. This process was observed with megakaryocytes from different origins and found to be robust. This original bioreactor design allows to process megakaryocytes at high throughput (millions per hour). Since platelets are produced in such a large amount, their extensive biological characterisation is possible and shows that platelets produced in this bioreactor are functional. PMID:26898346

Flexible planar microfluidic chip employing a light emitting diode and a PIN-photodiode for portable flow cytometers.

PubMed

Kettlitz, Siegfried W; Valouch, Sebastian; Sittel, Wiebke; Lemmer, Uli

2012-01-07

Detection of fluorescence particles is a key method of flow cytometry. We evaluate the performance of a design for a microfluidic fluorescence particle detection device. Due to the planar design with low layer thicknesses, we avoid optical components such as lenses or dichroic mirrors and substitute them with a shadow mask and colored film filters. A commercially available LED is used as the light source and a PIN-photodiode as detector. This design approach reduces component cost and power consumption and enables supplying the device with power from a standard USB port. From evaluation of this design, we obtain a maximum particle detection frequency of up to 600 particles per second at a sensitivity of better than 4.7 × 10(5) MESF (molecules of equivalent soluble fluorochrome) measured with particles for FITC sensitivity calibration. Lowering the flow rate increases the instrument sensitivity by an order of magnitude enabling the detection of particles with 4.5 × 10(4) MESF.

Monolithic microfluidic concentrators and mixers

DOEpatents

Frechet, Jean M.; Svec, Frantisek; Yu, Cong; Rohr, Thomas

2005-05-03

Microfluidic devices comprising porous monolithic polymer for concentration, extraction or mixing of fluids. A method for in situ preparation of monolithic polymers by in situ initiated polymerization of polymer precursors within microchannels of a microfluidic device and their use for solid phase extraction (SPE), preconcentration, concentration and mixing.

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.

Hydrogen peroxide concentration by pervaporation of a ternary liquid solution in microfluidics.

PubMed

Ziemecka, Iwona; Haut, Benoît; Scheid, Benoit

2015-01-21

Pervaporation in a microfluidic device is performed on liquid ternary solutions of hydrogen peroxide-water-methanol in order to concentrate hydrogen peroxide (H2O2) by removing methanol. The quantitative analysis of the pervaporation of solutions with different initial compositions is performed, varying the operating temperature of the microfluidic device. Experimental results together with a mathematical model of the separation process are used to understand the effect of the operating conditions on the microfluidic device efficiency. The parameters influencing significantly the performance of pervaporation in the microfluidic device are determined and the limitations of the process are discussed. For the analysed system, the operating temperature of the chip has to be below the temperature at which H2O2 decomposes. Therefore, the choice of an adequate reduced operating pressure is required, depending on the expected separation efficiency.

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.

Microfluidics and thin-film processes: a recipe for organic integrated photonics based on 3D microresonators

NASA Astrophysics Data System (ADS)

Huby, N.; Pluchon, D.; Belloul, M.; Moreac, A.; Coulon, N.; Gaviot, E.; Panizza, P.; B"che, B.

2010-02-01

We report on the design and realization of photonic integrated devices based on 3D organic microresonators. This has been achieved by combining microfluidics techniques and thin-film processes. The microfluidic device and the control of the flow rates of the continuous and dispersed phases allow the fabrication of organic microresonators with diameter ranging from 30 to 200 μm. The resonance of the sphere in air has been first investigated by using the Raman spectroscopy set-up demonstrating the appropriate photonic properties. Then the microresonators have been integrated on an organic chip made of the photosensitive resin SU-8 and positioned at the extremity of a taper and alongside a rib waveguide. The realization of these structures by thin-film processes needs one step UV-lithography leading to 6μm width and 30μm height. Both devices have proved the efficient evanescent coupling leading to the excitation of the whispering gallery modes confined at the surface of the organic 3D microresonators. Finally, a band-stop filter has been used to detect the resonance spectra of the resonators once integrated.

A cell sorting and trapping microfluidic device with an interdigital channel

NASA Astrophysics Data System (ADS)

Tu, Jing; Qiao, Yi; Xu, Minghua; Li, Junji; Liang, Fupeng; Duan, Mengqin; Ju, An; Lu, Zuhong

2016-12-01

The growing interest in cell sorting and trapping is driving the demand for high performance technologies. Using labeling techniques or external forces, cells can be identified by a series of methods. However, all of these methods require complicated systems with expensive devices. Based on inherent differences in cellular morphology, cells can be sorted by specific structures in microfluidic devices. The weir filter is a basic and efficient cell sorting and trapping structure. However, in some existing weir devices, because of cell deformability and high flow velocity in gaps, trapped cells may become stuck or even pass through the gaps. Here, we designed and fabricated a microfluidic device with interdigital channels for cell sorting and trapping. The chip consisted of a sheet of silicone elastomer polydimethylsiloxane and a sheet of glass. A square-wave-like weir was designed in the middle of the channel, comprising the interdigital channels. The square-wave pattern extended the weir length by three times with the channel width remaining constant. Compared with a straight weir, this structure exhibited a notably higher trapping capacity. Interdigital channels provided more space to slow down the rate of the pressure decrease, which prevented the cells from becoming stuck in the gaps. Sorting a mixture K562 and blood cells to trap cells demonstrated the efficiency of the chip with the interdigital channel to sort and trap large and less deformable cells. With stable and efficient cell sorting and trapping abilities, the chip with an interdigital channel may be widely applied in scientific research fields.

Label-free viscosity measurement of complex fluids using reversal flow switching manipulation in a microfluidic channel

PubMed Central

Jun Kang, Yang; Ryu, Jeongeun; Lee, Sang-Joon

2013-01-01

The accurate viscosity measurement of complex fluids is essential for characterizing fluidic behaviors in blood vessels and in microfluidic channels of lab-on-a-chip devices. A microfluidic platform that accurately identifies biophysical properties of blood can be used as a promising tool for the early detections of cardiovascular and microcirculation diseases. In this study, a flow-switching phenomenon depending on hydrodynamic balancing in a microfluidic channel was adopted to conduct viscosity measurement of complex fluids with label-free operation. A microfluidic device for demonstrating this proposed method was designed to have two inlets for supplying the test and reference fluids, two side channels in parallel, and a junction channel connected to the midpoint of the two side channels. According to this proposed method, viscosities of various fluids with different phases (aqueous, oil, and blood) in relation to that of reference fluid were accurately determined by measuring the switching flow-rate ratio between the test and reference fluids, when a reverse flow of the test or reference fluid occurs in the junction channel. An analytical viscosity formula was derived to measure the viscosity of a test fluid in relation to that of the corresponding reference fluid using a discrete circuit model for the microfluidic device. The experimental analysis for evaluating the effects of various parameters on the performance of the proposed method revealed that the fluidic resistance ratio (RJL/RL, fluidic resistance in the junction channel (RJL) to fluidic resistance in the side channel (RL)) strongly affects the measurement accuracy. The microfluidic device with smaller RJL/RL values is helpful to measure accurately the viscosity of the test fluid. The proposed method accurately measured the viscosities of various fluids, including single-phase (Glycerin and plasma) and oil-water phase (oil vs. deionized water) fluids, compared with conventional methods. The proposed method was also successfully applied to measure viscosities of blood with varying hematocrits, chemically fixed RBCS, and channel sizes. Based on these experimental results, the proposed method can be effectively used to measure the viscosities of various fluids easily, without any fluorescent labeling and tedious calibration procedures. PMID:24404040

Partially filled electrodes for digital microfluidic devices

NASA Astrophysics Data System (ADS)

Pyne, D. G.; Salman, W. M.; Abdelgawad, M.; Sun, Y.

2013-07-01

As digital microfluidics technology evolves, the need for integrating additional elements (e.g., sensing/detection and heating elements) on the electrode increases. Consequently, electrode area for droplet actuation is reduced to create space for accommodating these additional elements, which undesirably affects force generation. Electrodes cannot simply be scaled larger to compensate for this loss of force, as this would also increase droplet volume and thereby compromise the advantages thought in miniaturization. Here, we present a study evaluating, numerically with preliminary experimental verification, different partially filled electrode designs and suggesting designs that combine high actuation forces with a large reduction in electrode area.

Design and Optimization of Coin-Shaped Microreactor Chips for PET Radiopharmaceutical Synthesis

PubMed Central

Elizarov, Arkadij M.; van Dam, R. Michael; Shin, Young Shik; Kolb, Hartmuth C.; Padgett, Henry C.; Stout, David; Shu, Jenny; Huang, Jiang; Daridon, Antoine; Heath, James R.

2010-01-01

An integrated elastomeric microfluidic device, with a footprint the size of a postage stamp, has been designed and optimized for multistep radiosynthesis of PET tracers. Methods The unique architecture of the device is centered around a 5-μL coin-shaped reactor, which yields reaction efficiency and speed from a combination of high reagent concentration, pressurized reactions, and rapid heat and mass transfer. Its novel features facilitate mixing, solvent exchange, and product collection. New mixing mechanisms assisted by vacuum, pressure, and chemical reactions are exploited. Results The architecture of the reported reactor is the first that has allowed batch-mode microfluidic devices to produce radiopharmaceuticals of sufficient quality and quantity to be validated by in vivo imaging. Conclusion The reactor has the potential to produce multiple human doses of 18F-FDG; the most impact, however, is expected in the synthesis of PET radiopharmaceuticals that can be made only with low yields by currently available equipment. PMID:20124050

Generation and precise control of dynamic biochemical gradients for cellular assays

NASA Astrophysics Data System (ADS)

Saka, Yasushi; MacPherson, Murray; Giuraniuc, Claudiu V.

2017-03-01

Spatial gradients of diffusible signalling molecules play crucial roles in controlling diverse cellular behaviour such as cell differentiation, tissue patterning and chemotaxis. In this paper, we report the design and testing of a microfluidic device for diffusion-based gradient generation for cellular assays. A unique channel design of the device eliminates cross-flow between the source and sink channels, thereby stabilizing gradients by passive diffusion. The platform also enables quick and flexible control of chemical concentration that makes highly dynamic gradients in diffusion chambers. A model with the first approximation of diffusion and surface adsorption of molecules recapitulates the experimentally observed gradients. Budding yeast cells cultured in a gradient of a chemical inducer expressed a reporter fluorescence protein in a concentration-dependent manner. This microfluidic platform serves as a versatile prototype applicable to a broad range of biomedical investigations.

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.

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.

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

Fong, Erika J.; Huang, Chao; Hamilton, Julie

Here, a major advantage of microfluidic devices is the ability to manipulate small sample volumes, thus reducing reagent waste and preserving precious sample. However, to achieve robust sample manipulation it is necessary to address device integration with the macroscale environment. To realize repeatable, sensitive particle separation with microfluidic devices, this protocol presents a complete automated and integrated microfluidic platform that enables precise processing of 0.15–1.5 ml samples using microfluidic devices. Important aspects of this system include modular device layout and robust fixtures resulting in reliable and flexible world to chip connections, and fully-automated fluid handling which accomplishes closed-loop sample collection,more » system cleaning and priming steps to ensure repeatable operation. Different microfluidic devices can be used interchangeably with this architecture. Here we incorporate an acoustofluidic device, detail its characterization, performance optimization, and demonstrate its use for size-separation of biological samples. By using real-time feedback during separation experiments, sample collection is optimized to conserve and concentrate sample. Although requiring the integration of multiple pieces of equipment, advantages of this architecture include the ability to process unknown samples with no additional system optimization, ease of device replacement, and precise, robust sample processing.« less

Aqueous gradient by balancing diffusive and convective mass transport (Conference Presentation)

NASA Astrophysics Data System (ADS)

Habhab, Mohammed-Baker I.; Ismail, Tania; Lo, Joe F.; Haque, Arefa

2016-03-01

In wounds, cells secret biomolecules such as vascular endothelial growth factor (VEGF), a protein that controls many processes in healing. VEGF protein is expressed in a gradient in tissue, and its shape will be affected by the tissue injury sustained during wounding. In order to study the responses of keratinocyte cell migration to VEGF gradients and the geometric factors on wound healing, we designed a microfluidic gradient device that can generate large area gradients (1.5 cm in diameter) capable of mimicking arbitrary wound shapes. Microfluidic devices offer novel techniques to address biological and biomedical issues. Different from other gradient microfluidics, our device balances diffusion of biomolecules versus the convective clearance by a buffer flow on the opposite ends of the gradient. This allows us to create a large area gradient within shorter time scales by actively driving mass transport. In addition, the microfluidic device makes use of a porous filter membrane to create this balance as well as to deliver the resulting gradient to a culture of cells. The culture of cells are seeded above the gradient in a gasket chamber. However, Keratinocytes do not migrate effectively on filter paper. Therefore, in order to improve the motility of cells on the surface, we coated the filter paper with a 30m thick layer of gelatin type B. after observation under the microscope we found that the gelatin coated sample showed cells with more spread out morphology, with 97% viability, suggesting better adhesion than the non-coated sample.

Discrete elements for 3D microfluidics.

PubMed

Bhargava, Krisna C; Thompson, Bryant; Malmstadt, Noah

2014-10-21

Microfluidic systems are rapidly becoming commonplace tools for high-precision materials synthesis, biochemical sample preparation, and biophysical analysis. Typically, microfluidic systems are constructed in monolithic form by means of microfabrication and, increasingly, by additive techniques. These methods restrict the design and assembly of truly complex systems by placing unnecessary emphasis on complete functional integration of operational elements in a planar environment. Here, we present a solution based on discrete elements that liberates designers to build large-scale microfluidic systems in three dimensions that are modular, diverse, and predictable by simple network analysis techniques. We develop a sample library of standardized components and connectors manufactured using stereolithography. We predict and validate the flow characteristics of these individual components to design and construct a tunable concentration gradient generator with a scalable number of parallel outputs. We show that these systems are rapidly reconfigurable by constructing three variations of a device for generating monodisperse microdroplets in two distinct size regimes and in a high-throughput mode by simple replacement of emulsifier subcircuits. Finally, we demonstrate the capability for active process monitoring by constructing an optical sensing element for detecting water droplets in a fluorocarbon stream and quantifying their size and frequency. By moving away from large-scale integration toward standardized discrete elements, we demonstrate the potential to reduce the practice of designing and assembling complex 3D microfluidic circuits to a methodology comparable to that found in the electronics industry.

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.

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.

A practical guide for the fabrication of microfluidic devices using glass and silicon

PubMed Central

Iliescu, Ciprian; Taylor, Hayden; Avram, Marioara; Miao, Jianmin; Franssila, Sami

2012-01-01

This paper describes the main protocols that are used for fabricating microfluidic devices from glass and silicon. Methods for micropatterning glass and silicon are surveyed, and their limitations are discussed. Bonding methods that can be used for joining these materials are summarized and key process parameters are indicated. The paper also outlines techniques for forming electrical connections between microfluidic devices and external circuits. A framework is proposed for the synthesis of a complete glass/silicon device fabrication flow. PMID:22662101

A microfluidic device integrating dual CMOS polysilicon nanowire sensors for on-chip whole blood processing and simultaneous detection of multiple analytes.

PubMed

Kuan, Da-Han; Wang, I-Shun; Lin, Jiun-Rue; Yang, Chao-Han; Huang, Chi-Hsien; Lin, Yen-Hung; Lin, Chih-Ting; Huang, Nien-Tsu

2016-08-02

The hemoglobin-A1c test, measuring the ratio of glycated hemoglobin (HbA1c) to hemoglobin (Hb) levels, has been a standard assay in diabetes diagnosis that removes the day-to-day glucose level variation. Currently, the HbA1c test is restricted to hospitals and central laboratories due to the laborious, time-consuming whole blood processing and bulky instruments. In this paper, we have developed a microfluidic device integrating dual CMOS polysilicon nanowire sensors (MINS) for on-chip whole blood processing and simultaneous detection of multiple analytes. The micromachined polymethylmethacrylate (PMMA) microfluidic device consisted of a serpentine microchannel with multiple dam structures designed for non-lysed cells or debris trapping, uniform plasma/buffer mixing and dilution. The CMOS-fabricated polysilicon nanowire sensors integrated with the microfluidic device were designed for the simultaneous, label-free electrical detection of multiple analytes. Our study first measured the Hb and HbA1c levels in 11 clinical samples via these nanowire sensors. The results were compared with those of standard Hb and HbA1c measurement methods (Hb: the sodium lauryl sulfate hemoglobin detection method; HbA1c: cation-exchange high-performance liquid chromatography) and showed comparable outcomes. Finally, we successfully demonstrated the efficacy of the MINS device's on-chip whole blood processing followed by simultaneous Hb and HbA1c measurement in a clinical sample. Compared to current Hb and HbA1c sensing instruments, the MINS platform is compact and can simultaneously detect two analytes with only 5 μL of whole blood, which corresponds to a 300-fold blood volume reduction. The total assay time, including the in situ sample processing and analyte detection, was just 30 minutes. Based on its on-chip whole blood processing and simultaneous multiple analyte detection functionalities with a lower sample volume requirement and shorter process time, the MINS device can be effectively applied to real-time diabetes diagnostics and monitoring in point-of-care settings.

Tissue culture on a chip: Developmental biology applications of self-organized capillary networks in microfluidic devices.

PubMed

Miura, Takashi; Yokokawa, Ryuji

2016-08-01

Organ culture systems are used to elucidate the mechanisms of pattern formation in developmental biology. Various organ culture techniques have been used, but the lack of microcirculation in such cultures impedes the long-term maintenance of larger tissues. Recent advances in microfluidic devices now enable us to utilize self-organized perfusable capillary networks in organ cultures. In this review, we will overview past approaches to organ culture and current technical advances in microfluidic devices, and discuss possible applications of microfluidics towards the study of developmental biology. © 2016 Japanese Society of Developmental Biologists.

Electrodes for microfluidic applications

DOEpatents

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

2006-08-22

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

Nanolaminate microfluidic device for mobility selection of particles

DOEpatents

Surh, Michael P [Livermore, CA; Wilson, William D [Pleasanton, CA; Barbee, Jr., Troy W.; Lane, Stephen M [Oakland, CA

2006-10-10

A microfluidic device made from nanolaminate materials that are capable of electrophoretic selection of particles on the basis of their mobility. Nanolaminate materials are generally alternating layers of two materials (one conducting, one insulating) that are made by sputter coating a flat substrate with a large number of layers. Specific subsets of the conducting layers are coupled together to form a single, extended electrode, interleaved with other similar electrodes. Thereby, the subsets of conducting layers may be dynamically charged to create time-dependent potential fields that can trap or transport charge colloidal particles. The addition of time-dependence is applicable to all geometries of nanolaminate electrophoretic and electrochemical designs from sinusoidal to nearly step-like.

A microfluidic two-pump system inspired by liquid feeding in mosquitoes

NASA Astrophysics Data System (ADS)

Marino, Andrew; Goad, Angela; Stremler, Mark; Socha, John; Jung, Sunghwan

Mosquitoes feed on nectar and blood using a two-pump system in the head-a smaller cibarial pump in line with a larger a pharyngeal pump, with a valve in between. To suck, mosquitoes transport the liquid (which may be a multi-component viscous fluid, blood) through a long micro-channel, the proboscis. In the engineering realm, microfluidic devices in biomedical applications, such as lab-on-a-chip technology, necessitate implementing a robust pump design to handle clogging and increase flow control compared to a single-pump system. In this talk, we introduce a microfluidic pump design inspired by the mosquito's two-pump system. The pumping performance (flow rate) in presence of impurities (air bubbles, soft clogs) is quantified as a function of phase difference and volume expansion of the pumps, and the elasticity of the valve.

Detachably assembled microfluidic device for perfusion culture and post-culture analysis of a spheroid array.

PubMed

Sakai, Yusuke; Hattori, Koji; Yanagawa, Fumiki; Sugiura, Shinji; Kanamori, Toshiyuki; Nakazawa, Kohji

2014-07-01

Microfluidic devices permit perfusion culture of three-dimensional (3D) tissue, mimicking the flow of blood in vascularized 3D tissue in our body. Here, we report a microfluidic device composed of a two-part microfluidic chamber chip and multi-microwell array chip able to be disassembled at the culture endpoint. Within the microfluidic chamber, an array of 3D tissue aggregates (spheroids) can be formed and cultured under perfusion. Subsequently, detailed post-culture analysis of the spheroids collected from the disassembled device can be performed. This device facilitates uniform spheroid formation, growth analysis in a high-throughput format, controlled proliferation via perfusion flow rate, and post-culture analysis of spheroids. We used the device to culture spheroids of human hepatocellular carcinoma (HepG2) cells under two controlled perfusion flow rates. HepG2 spheroids exhibited greater cell growth at higher perfusion flow rates than at lower perfusion flow rates, and exhibited different metabolic activity and mRNA and protein expression under the different flow rate conditions. These results show the potential of perfusion culture to precisely control the culture environment in microfluidic devices. The construction of spheroid array chambers allows multiple culture conditions to be tested simultaneously, with potential applications in toxicity and drug screening. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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.

Surface acoustic wave microfluidics

PubMed Central

Ding, Xiaoyun; Li, Peng; Lin, Sz-Chin Steven; Stratton, Zackary S.; Nama, Nitesh; Guo, Feng; Slotcavage, Daniel; Mao, Xiaole; Shi, Jinjie; Costanzo, Francesco; Huang, Tony Jun

2014-01-01

The recent introduction of surface acoustic wave (SAW) technology onto lab-on-a-chip platforms has opened a new frontier in microfluidics. The advantages provided by such SAW microfluidics are numerous: simple fabrication, high biocompatibility, fast fluid actuation, versatility, compact and inexpensive devices and accessories, contact-free particle manipulation, and compatibility with other microfluidic components. We believe that these advantages enable SAW microfluidics to play a significant role in a variety of applications in biology, chemistry, engineering, and medicine. In this review article, we discuss the theory underpinning SAWs and their interactions with particles and the contacting fluids in which they are suspended. We then review the SAW-enabled microfluidic devices demonstrated to date, starting with devices that accomplish fluid mixing and transport through the use of travelling SAW; we follow that by reviewing the more recent innovations achieved with standing SAW that enable such actions as particle/cell focusing, sorting, and patterning. Finally, we look forward and appraise where the discipline of SAW microfluidics could go next. PMID:23900527

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

PubMed

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

2018-04-15

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

Microfluidic assembly blocks.

PubMed

Rhee, Minsoung; Burns, Mark A

2008-08-01

An assembly approach for microdevice construction using prefabricated microfluidic components is presented. Although microfluidic systems are convenient platforms for biological assays, their use in the life sciences is still limited mainly due to the high-level fabrication expertise required for construction. This approach involves prefabrication of individual microfluidic assembly blocks (MABs) in PDMS that can be readily assembled to form microfluidic systems. Non-expert users can assemble the blocks on glass slides to build their devices in minutes without any fabrication steps. In this paper, we describe the construction and assembly of the devices using the MAB methodology, and demonstrate common microfluidic applications including laminar flow development, valve control, and cell culture.

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.

Inventions Utilizing Microfluidics and Colloidal Particles

NASA Technical Reports Server (NTRS)

Marr, David W.; Gong, Tieying; Oakey, John; Terray, Alexander V.; Wu, David T.

2009-01-01

Several related inventions pertain to families of devices that utilize microfluidics and/or colloidal particles to obtain useful physical effects. The families of devices can be summarized as follows: (1) Microfluidic pumps and/or valves wherein colloidal-size particles driven by electrical, magnetic, or optical fields serve as the principal moving parts that propel and/or direct the affected flows. (2) Devices that are similar to the aforementioned pumps and/or valves except that they are used to manipulate light instead of fluids. The colloidal particles in these devices are substantially constrained to move in a plane and are driven to spatially order them into arrays that function, variously, as waveguides, filters, or switches for optical signals. (3) Devices wherein the ultra-laminar nature of microfluidic flows is exploited to effect separation, sorting, or filtering of colloidal particles or biological cells in suspension. (4) Devices wherein a combination of confinement and applied electrical and/or optical fields forces the colloidal particles to become arranged into three-dimensional crystal lattices. Control of the colloidal crystalline structures could be exploited to control diffraction of light. (5) Microfluidic devices, incorporating fluid waveguides, wherein switching of flows among different paths would be accompanied by switching of optical signals.

Microfluidic device, and related methods

NASA Technical Reports Server (NTRS)

Wong, Eric W. (Inventor)

2010-01-01

A method of making a microfluidic device is provided. The method features patterning a permeable wall on a substrate, and surrounding the permeable wall with a solid, non-permeable boundary structure to establish a microfluidic channel having a cross-sectional dimension less than 5,000 microns and a cross-sectional area at least partially filled with the permeable wall so that fluid flowing through the microfluidic channel at least partially passes through the permeable wall.

Advances in microfluidic devices made from thermoplastics used in cell biology and analyses.

PubMed

Gencturk, Elif; Mutlu, Senol; Ulgen, Kutlu O

2017-09-01

Silicon and glass were the main fabrication materials of microfluidic devices, however, plastics are on the rise in the past few years. Thermoplastic materials have recently been used to fabricate microfluidic platforms to perform experiments on cellular studies or environmental monitoring, with low cost disposable devices. This review describes the present state of the development and applications of microfluidic systems used in cell biology and analyses since the year 2000. Cultivation, separation/isolation, detection and analysis, and reaction studies are extensively discussed, considering only microorganisms (bacteria, yeast, fungi, zebra fish, etc.) and mammalian cell related studies in the microfluidic platforms. The advantages/disadvantages, fabrication methods, dimensions, and the purpose of creating the desired system are explained in detail. An important conclusion of this review is that these microfluidic platforms are still open for research and development, and solutions need to be found for each case separately.

Microfluidics and Coagulation Biology

PubMed Central

Colace, Thomas V.; Tormoen, Garth W.

2014-01-01

The study of blood ex vivo can occur in closed or open systems, with or without flow. Microfluidic devices facilitate measurements of platelet function, coagulation biology, cellular biorheology, adhesion dynamics, pharmacology, and clinical diagnostics. An experimental session can accommodate 100s to 1000s of unique clotting events. Using microfluidics, thrombotic events can be studied on defined surfaces of biopolymers, matrix proteins, and tissue factor under constant flow rate or constant pressure drop conditions. Distinct shear rates can be created on a device with a single perfusion pump. Microfluidic devices facilitated the determination of intraluminal thrombus permeability and the discovery that platelet contractility can be activated by a sudden decrease in flow. Microfluidics are ideal for multicolor imaging of platelets, fibrin, and phosphatidylserine and provide a human blood analog to the mouse injury models. Overall, microfluidic advances offer many opportunities for research, drug testing under relevant hemodynamic conditions, and clinical diagnostics. PMID:23642241

Microfluidic chip for non-invasive analysis of tumor cells interaction with anti-cancer drug doxorubicin by AFM and Raman spectroscopy.

PubMed

Zhang, Han; Xiao, Lifu; Li, Qifei; Qi, Xiaojun; Zhou, Anhong

2018-03-01

Raman spectroscopy has been playing an increasingly significant role for cell classification. Here, we introduce a novel microfluidic chip for non-invasive Raman cell natural fingerprint collection. Traditional Raman spectroscopy measurement of the cells grown in a Polydimethylsiloxane (PDMS) based microfluidic device suffers from the background noise from the substrate materials of PDMS when intended to apply as an in vitro cell assay. To overcome this disadvantage, the current device is designed with a middle layer of PDMS layer sandwiched by two MgF 2 slides which minimize the PDMS background signal in Raman measurement. Three cancer cell lines, including a human lung cancer cell A549, and human breast cancer cell lines MDA-MB-231 and MDA-MB-231/BRMS1, were cultured in this microdevice separately for a period of three days to evaluate the biocompatibility of the microfluidic system. In addition, atomic force microscopy (AFM) was used to measure the Young's modulus and adhesion force of cancer cells at single cell level. The AFM results indicated that our microchannel environment did not seem to alter the cell biomechanical properties. The biochemical responses of cancer cells exposed to anti-cancer drug doxorubicin (DOX) up to 24 h were assessed by Raman spectroscopy. Principal component analysis over the Raman spectra indicated that cancer cells untreated and treated with DOX can be distinguished. This PDMS microfluidic device offers a non-invasive and reusable tool for in vitro Raman measurement of living cells, and can be potentially applied for anti-cancer drug screening.

Use of Vacuum Bagging for Fabricating Thermoplastic Microfluidic Devices

PubMed Central

Cassano, Christopher L.; Simon, Andrew J.; Liu, Wei; Fredrickson, Carl; Fan, Z. Hugh

2014-01-01

In this work we present a novel thermal bonding method for thermoplastic microfluidic devices. This simple method employs a modified vacuum bagging technique, a concept borrowed from the aerospace industry, to produce conventional thick substrate microfluidic devices, as well as multi-layer film devices. The bonds produced using this method are superior to those obtained using conventional thermal bonding methods, including thermal lamination, and are capable of sustaining burst pressures in excess of 550 kPa. To illustrate the utility of this method, thick substrate devices were produced, as well as a six-layer film device that incorporated several complex features. PMID:25329244

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

PubMed

Koo, Hyung-Jun; Velev, Orlin D

2013-05-09

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

Vapor-fed microfluidic hydrogen generator.

PubMed

Modestino, M A; Dumortier, M; Hosseini Hashemi, S M; Haussener, S; Moser, C; Psaltis, D

2015-05-21

Water-splitting devices that operate with humid air feeds are an attractive alternative for hydrogen production as the required water input can be obtained directly from ambient air. This article presents a novel proof-of-concept microfluidic platform that makes use of polymeric ion conductor (Nafion®) thin films to absorb water from air and performs the electrochemical water-splitting process. Modelling and experimental tools are used to demonstrate that these microstructured devices can achieve the delicate balance between water, gas, and ionic transport processes required for vapor-fed devices to operate continuously and at steady state, at current densities above 3 mA cm(-2). The results presented here show that factors such as the thickness of the Nafion films covering the electrodes, convection of air streams, and water content of the ionomer can significantly affect the device performance. The insights presented in this work provide important guidelines for the material requirements and device designs that can be used to create practical electrochemical hydrogen generators that work directly under ambient air.

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.

Optimization of Surface-Enhanced Raman Spectroscopy Conditions for Implementation into a Microfluidic Device for Drug Detection.

PubMed

Kline, Neal D; Tripathi, Ashish; Mirsafavi, Rustin; Pardoe, Ian; Moskovits, Martin; Meinhart, Carl; Guicheteau, Jason A; Christesen, Steven D; Fountain, Augustus W

2016-11-01

A microfluidic device is being developed by University of California-Santa Barbara as part of a joint effort with the United States Army to develop a portable, rapid drug detection device. Surface-enhanced Raman spectroscopy (SERS) is used to provide a sensitive, selective detection technique within the microfluidic platform employing metallic nanoparticles as the SERS medium. Using several illicit drugs as analytes, the work presented here describes the efforts of the Edgewood Chemical Biological Center to optimize the microfluidic platform by investigating the role of nanoparticle material, nanoparticle size, excitation wavelength, and capping agents on the performance, and drug concentration detection limits achievable with Ag and Au nanoparticles that will ultimately be incorporated into the final design. This study is particularly important as it lays out a systematic comparison of limits of detection and potential interferences from working with several nanoparticle capping agents-such as tannate, citrate, and borate-which does not seem to have been done previously as the majority of studies only concentrate on citrate as the capping agent. Morphine, cocaine, and methamphetamine were chosen as test analytes for this study and were observed to have limits of detection (LOD) in the range of (1.5-4.7) × 10 -8 M (4.5-13 ng/mL), with the borate capping agent having the best performance.

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

PubMed

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

2018-03-26

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

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.

Comparison of separation performance of laser-ablated and wet-etched microfluidic devices

PubMed Central

Baker, Christopher A.; Bulloch, Rayford; Roper, Michael G.

2010-01-01

Laser ablation of glass allows for production of microfluidic devices without the need of hydrofluoric acid and photolithography. The goal of this study was to compare the separation performance of microfluidic devices produced using a low-cost laser ablation system and conventional wet etching. During laser ablation, cracking of the glass substrate was prevented by heating the glass to 300°C. A range of laser energy densities was found to produce channel depths ranging from 4 – 35 μm and channel widths from 118 – 162 μm. The electroosmotic flow velocity was lower in laser-ablated devices, 0.110 ± 0.005 cm s−1, as compared to wet-etched microfluidic chips, 0.126 ± 0.003 cm s−1. Separations of both small and large molecules performed on both wet- and laser-ablated devices were compared by examining limits of detection, theoretical plate count, and peak asymmetry. Laser-induced fluorescence detection limits were 10 pM fluorescein for both types of devices. Laser-ablated and wet-etched microfluidic chips had reproducible migration times with ≤ 2.8% RSD and peak asymmetries ranging from 1.0 – 1.8. Numbers of theoretical plates were between 2.8- and 6.2-fold higher on the wet-etched devices compared to laser-ablated devices. Nevertheless, resolution between small and large analytes was accomplished, which indicates that laser ablation may find an application in pedagogical studies of electrophoresis or microfluidic devices, or in settings where hydrofluoric acid cannot be used. PMID:20827468

About Small Streams and Shiny Rocks: Macromolecular Crystal Growth in Microfluidics

NASA Technical Reports Server (NTRS)

vanderWoerd, Mark; Ferree, Darren; Spearing, Scott; Monaco, Lisa; Molho, Josh; Spaid, Michael; Brasseur, Mike; Curreri, Peter A. (Technical Monitor)

2002-01-01

We are developing a novel technique with which we have grown diffraction quality protein crystals in very small volumes, utilizing chip-based, microfluidic ("LabChip") technology. With this technology volumes smaller than achievable with any laboratory pipette can be dispensed with high accuracy. We have performed a feasibility study in which we crystallized several proteins with the aid of a LabChip device. The protein crystals are of excellent quality as shown by X-ray diffraction. The advantages of this new technology include improved accuracy of dispensing for small volumes, complete mixing of solution constituents without bubble formation, highly repeatable recipe and growth condition replication, and easy automation of the method. We have designed a first LabChip device specifically for protein crystallization in batch mode and can reliably dispense and mix from a range of solution constituents. We are currently testing this design. Upon completion additional crystallization techniques, such as vapor diffusion and liquid-liquid diffusion will be accommodated. Macromolecular crystallization using microfluidic technology is envisioned as a fully automated system, which will use the 'tele-science' concept of remote operation and will be developed into a research facility aboard the International Space Station.

Non-invasive paper-based microfluidic device for ultra-low detection of urea through enzyme catalysis

NASA Astrophysics Data System (ADS)

Suresh, Vignesh; Qunya, Ong; Kanta, Bera Lakshmi; Yuh, Lee Yeong; Chong, Karen S. L.

2018-03-01

This work describes the design, fabrication and characterization of a paper-based microfluidic device for ultra-low detection of urea through enzyme catalysis. The microfluidic system comprises an entry port, a fluidic channel, a reaction zone and two electrodes (contacts). Wax printing was used to create fluidic channels on the surface of a chromatography paper. Pre-conceptualized designs of the fluidic channel are wax-printed on the paper substrate while the electrodes are screen-printed. The paper printed with wax is heated to cause the wax reflow along the thickness of the paper that selectively creates hydrophilic and hydrophobic zones inside the paper. Urease immobilized in the reaction zone catalyses urea into releasing ions and, thereby, generating a current flow between the electrodes. A measure of current with respect to time at a fixed potential enables the detection of urea. The methodology enabled urea concentration down to 1 pM to be detected. The significance of this work lies in the use of simple and inexpensive paper-based substrates to achieve detection of ultra-low concentrations of analytes such as urea. The process is non-invasive and employs a less cumbersome two-electrode assembly.

Microfluidic Devices for Forensic DNA Analysis: A Review.

PubMed

Bruijns, Brigitte; van Asten, Arian; Tiggelaar, Roald; Gardeniers, Han

2016-08-05

Microfluidic devices may offer various advantages for forensic DNA analysis, such as reduced risk of contamination, shorter analysis time and direct application at the crime scene. Microfluidic chip technology has already proven to be functional and effective within medical applications, such as for point-of-care use. In the forensic field, one may expect microfluidic technology to become particularly relevant for the analysis of biological traces containing human DNA. This would require a number of consecutive steps, including sample work up, DNA amplification and detection, as well as secure storage of the sample. This article provides an extensive overview of microfluidic devices for cell lysis, DNA extraction and purification, DNA amplification and detection and analysis techniques for DNA. Topics to be discussed are polymerase chain reaction (PCR) on-chip, digital PCR (dPCR), isothermal amplification on-chip, chip materials, integrated devices and commercially available techniques. A critical overview of the opportunities and challenges of the use of chips is discussed, and developments made in forensic DNA analysis over the past 10-20 years with microfluidic systems are described. Areas in which further research is needed are indicated in a future outlook.

Fast selective trapping and release of picoliter droplets in a 3D microfluidic PDMS multi-trap system with bubbles.

PubMed

Rambach, Richard W; Biswas, Preetika; Yadav, Ashutosh; Garstecki, Piotr; Franke, Thomas

2018-02-12

The selective manipulation and incubation of individual picoliter drops in high-throughput droplet based microfluidic devices still remains challenging. We used a surface acoustic wave (SAW) to induce a bubble in a 3D designed multi-trap polydimethylsiloxane (PDMS) device to manipulate multiple droplets and demonstrate the selection, incubation and on-demand release of aqueous droplets from a continuous oil flow. By controlling the position of the acoustic actuation, individual droplets are addressed and selectively released from a droplet stream of 460 drops per s. A complete trapping and releasing cycle can be as short as 70 ms and has no upper limit for incubation time. We characterize the fluidic function of the hybrid device in terms of electric power, pulse duration and acoustic path.

Method And Apparatus For Reducing Sample Dispersion In Turns And Junctions Of Micro-Channel Systems

DOEpatents

Griffiths, Stewart K. , Nilson, Robert H.

2004-05-11

What is disclosed pertains to improvement in the performance of microchannel devices by providing turns, wyes, tees, and other junctions that produce little dispersion of a sample as it traverses the turn or junction. The reduced dispersion results from contraction and expansion regions that reduce the cross-sectional area over some portion of the turn or junction. By carefully designing the geometries of these regions, sample dispersion in turns and junctions is reduced to levels comparable to the effects of ordinary diffusion. The low dispersion features are particularly suited for microfluidic devices and systems using either electromotive force, pressure, or combinations thereof as the principle of fluid transport. Such microfluidic devices and systems are useful for separation of components, sample transport, reaction, mixing, dilution or synthesis, or combinations thereof.

A vacuum manifold for rapid world-to-chip connectivity of complex PDMS microdevices.

PubMed

Cooksey, Gregory A; Plant, Anne L; Atencia, Javier

2009-05-07

The lack of simple interfaces for microfluidic devices with a large number of inlets significantly limits production and utilization of these devices. In this article, we describe the fabrication of a reusable manifold that provides rapid world-to-chip connectivity. A vacuum network milled into a rigid manifold holds microdevices and prevents leakage of fluids injected into the device from ports in the manifold. A number of different manifold designs were explored, and all performed similarly, yielding an average of 100 kPa (15 psi) fluid holding pressure. The wide applicability of this manifold concept is demonstrated by interfacing with a 51-inlet microfluidic chip containing 144 chambers and hundreds of embedded pneumatic valves. Due to the speed of connectivity, the manifolds are ideal for rapid prototyping and are well suited to serve as "universal" interfaces.

Tunable organic transistors that use microfluidic source and drain electrodes

NASA Astrophysics Data System (ADS)

Maltezos, George; Nortrup, Robert; Jeon, Seokwoo; Zaumseil, Jana; Rogers, John A.

2003-09-01

This letter describes a type of transistor that uses conducting fluidic source and drain electrodes of mercury which flow on top of a thin film of the organic semiconductor pentacene. Pumping the mercury through suitably designed microchannels changes the width of the transistor channel and, therefore, the electrical characteristics of the device. Measurements on transistors with a range of channel lengths reveal low contact resistances between mercury and pentacene. Data collected before, during, and after pumping the mercury through the microchannels demonstrate reversible and systematic tuning of the devices. This unusual type of organic transistor has the potential to be useful in plastic microfluidic devices that require active elements for pumps, sensors, or other components. It also represents a noninvasive way to build transistor test structures that incorporate certain classes of chemically and mechanically fragile organic semiconductors.

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.

Flow control using audio tones in resonant microfluidic networks: towards cell-phone controlled lab-on-a-chip devices.

PubMed

Phillips, Reid H; Jain, Rahil; Browning, Yoni; Shah, Rachana; Kauffman, Peter; Dinh, Doan; Lutz, Barry R

2016-08-16

Fluid control remains a challenge in development of portable lab-on-a-chip devices. Here, we show that microfluidic networks driven by single-frequency audio tones create resonant oscillating flow that is predicted by equivalent electrical circuit models. We fabricated microfluidic devices with fluidic resistors (R), inductors (L), and capacitors (C) to create RLC networks with band-pass resonance in the audible frequency range available on portable audio devices. Microfluidic devices were fabricated from laser-cut adhesive plastic, and a "buzzer" was glued to a diaphragm (capacitor) to integrate the actuator on the device. The AC flowrate magnitude was measured by imaging oscillation of bead tracers to allow direct comparison to the RLC circuit model across the frequency range. We present a systematic build-up from single-channel systems to multi-channel (3-channel) networks, and show that RLC circuit models predict complex frequency-dependent interactions within multi-channel networks. Finally, we show that adding flow rectifying valves to the network creates pumps that can be driven by amplified and non-amplified audio tones from common audio devices (iPod and iPhone). This work shows that RLC circuit models predict resonant flow responses in multi-channel fluidic networks as a step towards microfluidic devices controlled by audio tones.

Microfluidic device for chemical and mechanical manipulation of suspended cells

NASA Astrophysics Data System (ADS)

Rezvani, Samaneh; Shi, Nan; Squires, Todd M.; Schmidt, Christoph F.

2018-01-01

Microfluidic devices have proven to be useful and versatile for cell studies. We here report on a method to adapt microfluidic stickers made from UV-curable optical adhesive with inserted permeable hydrogel membrane micro-windows for mechanical studies of suspended cells. The windows were fabricated by optical projection lithography using scanning confocal microscopy. The device allows us to rapidly exchange embedding medium while observing and probing the cells. We characterize the device and demonstrate the function by exposing cultured fibroblasts to varying osmotic conditions. Cells can be shrunk reversibly under osmotic compression.

Theory of a microfluidic serial dilution bioreactor for growth of planktonic and biofilm populations.

PubMed

Hsu, Sze-Bi; Yang, Ya-Tang

2016-04-01

We present the theory of a microfluidic bioreactor with a two-compartment growth chamber and periodic serial dilution. In the model, coexisting planktonic and biofilm populations exchange by adsorption and detachment. The criteria for coexistence and global extinction are determined by stability analysis of the global extinction state. Stability analysis yields the operating diagram in terms of the dilution and removal ratios, constrained by the plumbing action of the bioreactor. The special case of equal uptake function and logistic growth is analytically solved and explicit growth curves are plotted. The presented theory is applicable to generic microfluidic bioreactors with discrete growth chambers and periodic dilution at discrete time points. Therefore, the theory is expected to assist the design of microfluidic devices for investigating microbial competition and microbial biofilm growth under serial dilution conditions.

Microfluidic redox battery.

PubMed

Lee, Jin Wook; Goulet, Marc-Antoni; Kjeang, Erik

2013-07-07

A miniaturized microfluidic battery is proposed, which is the first membraneless redox battery demonstrated to date. This unique concept capitalizes on dual-pass flow-through porous electrodes combined with stratified, co-laminar flow to generate electrical power on-chip. The fluidic design is symmetric to allow for both charging and discharging operations in forward, reverse, and recirculation modes. The proof-of-concept device fabricated using low-cost materials integrated in a microfluidic chip is shown to produce competitive power levels when operated on a vanadium redox electrolyte. A complete charge/discharge cycle is performed to demonstrate its operation as a rechargeable battery, which is an important step towards providing sustainable power to lab-on-a-chip and microelectronic applications.

A microfluidic flow-through device for high throughput electrical lysis of bacterial cells based on continuous dc voltage.

PubMed

Wang, Hsiang-Yu; Bhunia, Arun K; Lu, Chang

2006-12-15

Interest in electrical lysis of biological cells on a microfludic platform has increased because it allows for the rapid recovery of intracellular contents without introducing lytic agents. In this study we demonstrated a simple microfluidic flow-through device which lysed Escherichia coli cells under a continuous dc voltage. The E. coli cells had previously been modified to express green fluorescent protein (GFP). In our design, the cell lysis only happened in a defined section of a microfluidic channel due to the local field amplification by geometric modification. The geometric modification also effectively decreased the required voltage for lysis by several folds. We found that local field strength of 1000-1500 V/cm was required for nearly 100% cell death. This threshold field strength was considerably lower than the value reported in the literature, possibly due to the longer duration of the field [Lee, S.W., Tai, Y.C., 1999. Sens. Actuators A: Phys. 73, 74-79]. Cell lysis was detected by both plate count and fluorescence spectroscopy. The cell membrane was completely disintegrated in the lysis section of the microfluidic device, when the field strength was higher than 2000 V/cm. The devices were fabricated using low-cost soft lithography with channel widths considerably larger than the cell size to avoid clogging and ensure stable performance. Our tool will be ideal for high throughput processing of bacterial cells for chemical analysis of intracellular contents such as DNA and proteins. The application of continuous dc voltage greatly simplified the instrumentation compared to devices using electrical pulses for similar purposes. In principle, the same approach can also be applied for lysis of mammalian cells and electroporative transfection.

Microfluidic transwell inserts for generation of tissue culture-friendly gradients in well plates

PubMed Central

Sip, Christopher G.; Bhattacharjee, Nirveek; Folch, Albert

2015-01-01

Gradients of biochemical molecules play a key role in many physiological processes such as axon growth, tissue morphogenesis, and trans-epithelium nutrient transport, as well as in pathophysiological phenomena such as wound healing, immune response, bacterial invasion, and cancer metastasis. In this paper, we report a microfluidic transwell insert for generating quantifiable concentration gradients in a user-friendly and modular format that is compatible with conventional cell cultures and with tissue explant cultures. The device is simply inserted into a standard 6-well plate, where it hangs self-supported at a distance of ~250 μm above the cell culture surface. The gradient is created by small microflows from the device, through an integrated track-etched porous membrane, into the cell culture well. The microfluidic transwell can deliver stable, quantifiable gradients over a large area with extremely low fluid shear stress to dissociated cells or tissue explants cultured independently on the surface of a 6-well plate. We used finite-element modeling to describe the porous membrane flow and molecular transport and to predict gradients generated by the device. Using the device, we applied a gradient of the chemotactic peptide N-Formyl-Met-Leu-Phe (fMLP) to a large population of HL-60 cells (a neutrophil cell line) and directly observed the migration with time-lapse microscopy. On quantification of the chemotactic response with an automated tracking algorithm, we found 74% of the cells moving towards the gradient. Additionally, the modular design and low fluid shear stress made it possible to apply gradients of growth factors and second messengers to mouse retinal explant cultures. With a simplified interface and well-defined gradients, the microfluidic transwell device has potential for broad applications to gradient-sensing biology. PMID:24225908

Systematic characterization of degas-driven flow for poly(dimethylsiloxane) microfluidic devices

DOE PAGES

Liang, David Y.; Tentori, Augusto M.; Dimov, Ivan K.; ...

2011-01-01

Degas-driven flow is a novel phenomenon used to propel fluids in poly(dimethylsiloxane) (PDMS)-based microfluidic devices without requiring any external power. This method takes advantage of the inherently high porosity and air solubility of PDMS by removing air molecules from the bulk PDMS before initiating the flow. The dynamics of degas-driven flow are dependent on the channel and device geometries and are highly sensitive to temporal parameters. These dependencies have not been fully characterized, hindering broad use of degas-driven flow as a microfluidic pumping mechanism. Here, we characterize, for the first time, the effect of various parameters on the dynamics ofmore » degas-driven flow, including channel geometry, PDMS thickness, PDMS exposure area, vacuum degassing time, and idle time at atmospheric pressure before loading. We investigate the effect of these parameters on flow velocity as well as channel fill time for the degas-driven flow process. Using our devices, we achieved reproducible flow with a standard deviation of less than 8% for flow velocity, as well as maximum flow rates of up to 3 nL/s and mean flow rates of approximately 1-1.5 nL/s. Parameters such as channel surface area and PDMS chip exposure area were found to have negligible impact on degas-driven flow dynamics, whereas channel cross-sectional area, degas time, PDMS thickness, and idle time were found to have a larger impact. In addition, we develop a physical model that can predict mean flow velocities within 6% of experimental values and can be used as a tool for future design of PDMS-based microfluidic devices that utilize degas-driven flow.« less

Rapid and cheap prototyping of a microfluidic cell sorter.

PubMed

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

2011-05-01

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

Limiting factors in the production of deep microstructures

NASA Astrophysics Data System (ADS)

Tolfree, David W. L.; O'Neill, William; Tunna, Leslie; Sutcliffe, Christopher

1999-10-01

Microsystems increasingly require precision deep microstructures that can be cost-effectively designed and manufactured. New products must be able to meet the demands of the rapidly growing markets for microfluidic, micro- optical and micromechanical devices in industrial sectors which include chemicals, pharmaceuticals, biosciences, medicine and food. The realization of such products, first requires an effective process to design and manufacture prototypes. Two process methods used for the fabrication of high aspect-ratio microstructures are based on X-ray beam lithography with electroforming processes and direct micromachining with a frequency multiplied Nd:YAG laser using nanosecond pulse widths. Factors which limit the efficiency and precision obtainable using such processes are important parameters when deciding on the best fabrication method to use. A basic microstructure with narrow channels suitable for a microfluidic mixer have been fabricated using both these techniques and comparisons made of the limitations and suitability of the processes in respect of fast prototyping and manufacture or working devices.

Incorporation of prefabricated screw, pneumatic, and solenoid valves into microfluidic devices

PubMed Central

Hulme, S. Elizabeth; Shevkoplyas, Sergey S.

2011-01-01

This paper describes a method for prefabricating screw, pneumatic, and solenoid valves and embedding them in microfluidic devices. This method of prefabrication and embedding is simple, requires no advanced fabrication, and is compatible with soft lithography. Because prefabrication allows many identical valves to be made at one time, the performance across different valves made in the same manner is reproducible. In addition, the performance of a single valve is reproducible over many cycles of opening and closing: an embedded solenoid valve opened and closed a microfluidic channel more than 100,000 times with no apparent deterioration in its function. It was possible to combine all three types of prefabricated valves in a single microfluidic device to control chemical gradients in a microfluidic channel temporally and spatially. PMID:19209338

Incorporation of prefabricated screw, pneumatic, and solenoid valves into microfluidic devices.

PubMed

Hulme, S Elizabeth; Shevkoplyas, Sergey S; Whitesides, George M

2009-01-07

This paper describes a method for prefabricating screw, pneumatic, and solenoid valves and embedding them in microfluidic devices. This method of prefabrication and embedding is simple, requires no advanced fabrication, and is compatible with soft lithography. Because prefabrication allows many identical valves to be made at one time, the performance across different valves made in the same manner is reproducible. In addition, the performance of a single valve is reproducible over many cycles of opening and closing: an embedded solenoid valve opened and closed a microfluidic channel more than 100,000 times with no apparent deterioration in its function. It was possible to combine all three types of prefabricated valves in a single microfluidic device to control chemical gradients in a microfluidic channel temporally and spatially.

How cutting-edge technologies impact the design of electrochemical (bio)sensors for environmental analysis. A review.

PubMed

Arduini, Fabiana; Cinti, Stefano; Scognamiglio, Viviana; Moscone, Danila; Palleschi, Giuseppe

2017-03-22

Through the years, scientists have developed cutting-edge technologies to make (bio)sensors more convenient for environmental analytical purposes. Technological advancements in the fields of material science, rational design, microfluidics, and sensor printing, have radically shaped biosensor technology, which is even more evident in the continuous development of sensing systems for the monitoring of hazardous chemicals. These efforts will be crucial in solving some of the problems constraining biosensors to reach real environmental applications, such as continuous analyses in field by means of multi-analyte portable devices. This review (with 203 refs.) covers the progress between 2010 and 2015 in the field of technologies enabling biosensor applications in environmental analysis, including i) printing technology, ii) nanomaterial technology, iii) nanomotors, iv) biomimetic design, and (v) microfluidics. Next section describes futuristic cutting-edge technologies that are gaining momentum in recent years, which furnish highly innovative aspects to biosensing devices. Copyright © 2016 Elsevier B.V. All rights reserved.

Microfluidic T-form mixer utilizing switching electroosmotic flow.

PubMed

Lin, Che-Hsin; Fu, Lung-Ming; Chien, Yu-Sheng

2004-09-15

This paper presents a microfluidic T-form mixer utilizing alternatively switching electroosmotic flow. The microfluidic device is fabricated on low-cost glass slides using a simple and reliable fabrication process. A switching DC field is used to generate an electroosmotic force which simultaneously drives and mixes the fluid samples. The proposed design eliminates the requirements for moving parts within the microfluidic device and delicate external control systems. Two operation modes, namely, a conventional switching mode and a novel pinched switching mode, are presented. Computer simulation is employed to predict the mixing performance attainable in both operation modes. The simulation results are then compared to those obtained experimentally. It is shown that a mixing performance as high as 97% can be achieved within a mixing distance of 1 mm downstream from the T-junction when a 60 V/cm driving voltage and a 2-Hz switching frequency are applied in the pinched switching operation mode. This study demonstrates how the driving voltage and switching frequency can be optimized to yield an enhanced mixing performance. The novel methods presented in this study provide a simple solution to mixing problems in the micro-total-analysis-systems field.

Phospholipid Polymer Biointerfaces for Lab-on-a-Chip Devices.

PubMed

Xu, Yan; Takai, Madoka; Ishihara, Kazuhiko

2010-06-01

This review summarizes recent achievements and progress in the development of various functional 2-methacryloyloxyethyl phosphorylcholine (MPC) polymer biointerfaces for lab-on-a-chip devices and applications. As phospholipid polymers, MPC polymers can form cell-membrane-like surfaces by surface chemistry and physics and thereby provide biointerfaces capable of suppressing protein adsorption and many subsequent biological responses. In order to enable application to microfluidic devices, a number of MPC polymers with diverse functions have been specially designed and synthesized by incorporating functional units such as charge and active ester for generating the microfluidic flow and conjugating biomolecules, respectively. Furthermore, these polymers were incorporated with silane or hydrophobic moiety to construct stable interfaces on various substrate materials such as glass, quartz, poly(methyl methacrylate), and poly(dimethylsiloxane), via a silane-coupling reaction or hydrophobic interactions. The basic interfacial properties of these interfaces have been characterized from multiple aspects of chemistry, physics, and biology, and the suppression of nonspecific bioadsorption and control of microfluidic flow have been successfully achieved using these biointerfaces on a chip. Further, many chip-based biomedical applications such as immunoassays and DNA separation have been accomplished by integrating these biointerfaces on a chip. Therefore, functional phospholipid polymer interfaces are promising and useful for application to lab-on-a-chip devices in biomedicine.

Volumetric flow rate in simulations of microfluidic devices+

NASA Astrophysics Data System (ADS)

Kovalčíková, KristÍna; Slavík, Martin; Bachratá, Katarína; Bachratý, Hynek; Bohiniková, Alžbeta

2018-06-01

In this work, we examine the volumetric flow rate of microfluidic devices. The volumetric flow rate is a parameter which is necessary to correctly set up a simulation of a real device and to check the conformity of a simulation and a laboratory experiments [1]. Instead of defining the volumetric rate at the beginning as a simulation parameter, a parameter of external force is set. The proposed hypothesis is that for a fixed set of other parameters (topology, viscosity of the liquid, …) the volumetric flow rate is linearly dependent on external force in typical ranges of fluid velocity used in our simulations. To confirm this linearity hypothesis and to find numerical limits of this approach, we test several values of the external force parameter. The tests are designed for three different topologies of simulation box and for various haematocrits. The topologies of the microfluidic devices are inspired by existing laboratory experiments [3 - 6]. The linear relationship between the external force and the volumetric flow rate is verified in orders of magnitudes similar to the values obtained from laboratory experiments. Supported by the Slovak Research and Development Agency under the contract No. APVV-15-0751 and by the Ministry of Education, Science, Research and Sport of the Slovak Republic under the contract No. VEGA 1/0643/17.

Microfabrication and Applications of Opto-Microfluidic Sensors

PubMed Central

Zhang, Daiying; Men, Liqiu; Chen, Qiying

2011-01-01

A review of research activities on opto-microfluidic sensors carried out by the research groups in Canada is presented. After a brief introduction of this exciting research field, detailed discussion is focused on different techniques for the fabrication of opto-microfluidic sensors, and various applications of these devices for bioanalysis, chemical detection, and optical measurement. Our current research on femtosecond laser microfabrication of optofluidic devices is introduced and some experimental results are elaborated. The research on opto-microfluidics provides highly sensitive opto-microfluidic sensors for practical applications with significant advantages of portability, efficiency, sensitivity, versatility, and low cost. PMID:22163904

Design and simulation of a microfluidic device for acoustic cell separation.

PubMed

Shamloo, Amir; Boodaghi, Miad

2018-03-01

Experimental acoustic cell separation methods have been widely used to perform separation for different types of blood cells. However, numerical simulation of acoustic cell separation has not gained enough attention and needs further investigation since by using numerical methods, it is possible to optimize different parameters involved in the design of an acoustic device and calculate particle trajectories in a simple and low cost manner before spending time and effort for fabricating these devices. In this study, we present a comprehensive finite element-based simulation of acoustic separation of platelets, red blood cells and white blood cells, using standing surface acoustic waves (SSAWs). A microfluidic channel with three inlets, including the middle inlet for sheath flow and two symmetrical tilted angle inlets for the cells were used to drive the cells through the channel. Two interdigital transducers were also considered in this device and by implementing an alternating voltage to the transducers, an acoustic field was created which can exert the acoustic radiation force to the cells. Since this force is dependent to the size of the cells, the cells are pushed towards the midline of the channel with different path lines. Particle trajectories for different cells were obtained and compared with a theoretical equation. Two types of separations were observed as a result of varying the amplitude of the acoustic field. In the first mode of separation, white blood cells were sorted out through the middle outlet and in the second mode of separation, platelets were sorted out through the side outlets. Depending on the clinical needs and by using the studied microfluidic device, each of these modes can be applied to separate the desired cells. Copyright © 2017 Elsevier B.V. All rights reserved.

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

Clear Castable Polyurethane Elastomer for Fabrication of Microfluidic Devices

PubMed Central

Domansky, Karel; Leslie, Daniel C.; McKinney, James; Fraser, Jacob P.; Sliz, Josiah D.; Hamkins-Indik, Tiama; Hamilton, Geraldine A.; Bahinski, Anthony; Ingber, Donald E.

2013-01-01

Polydimethylsiloxane (PDMS) has numerous desirable properties for fabricating microfluidic devices, including optical transparency, flexibility, biocompatibility, and fabrication by casting; however, partitioning of small hydrophobic molecules into the bulk of PDMS hinders industrial acceptance of PDMS microfluidic devices for chemical processing and drug development applications. Here we describe an attractive alternative material that is similar to PDMS in terms of optical transparency, flexibility and castability, but that is also resistant to absorption of small hydrophobic molecules. PMID:23954953

Microfluidic chemical reaction circuits

DOEpatents

Lee, Chung-cheng [Irvine, CA; Sui, Guodong [Los Angeles, CA; Elizarov, Arkadij [Valley Village, CA; Kolb, Hartmuth C [Playa del Rey, CA; Huang, Jiang [San Jose, CA; Heath, James R [South Pasadena, CA; Phelps, Michael E [Los Angeles, CA; Quake, Stephen R [Stanford, CA; Tseng, Hsian-rong [Los Angeles, CA; Wyatt, Paul [Tipperary, IE; Daridon, Antoine [Mont-Sur-Rolle, CH

2012-06-26

New microfluidic devices, useful for carrying out chemical reactions, are provided. The devices are adapted for on-chip solvent exchange, chemical processes requiring multiple chemical reactions, and rapid concentration of reagents.

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

NASA Astrophysics Data System (ADS)

Amoyav, Benzion; Benny, Ofra

2018-04-01

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

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.

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.

Experimental and numerical studies of a microfluidic device with compliant chambers for flow stabilization

NASA Astrophysics Data System (ADS)

Iyer, V.; Raj, A.; Annabattula, R. K.; Sen, A. K.

2015-07-01

This paper reports experimental and numerical studies of a passive microfluidic device that stabilizes a pulsating incoming flow and delivers a steady flow at the outlet. The device employs a series of chambers along the flow direction with a thin polymeric membrane (of thickness 75-250 µm) serving as the compliant boundary. The deformation of the membrane allows accumulation of fluid during an overflow and discharge of fluid during an underflow for flow stabilization. Coupled fluid-structure simulations are performed using Mooney-Rivlin formulations to account for a thin hyperelastic membrane material undergoing large deformations to accurately predict the device performance. The device was fabricated with PDMS as the substrate material and thin PDMS membrane as the compliant boundary. The performance of the device is defined in terms of a parameter called ‘Attenuation Factor (AF)’. The effect of various design parameters including membrane thickness, elastic modulus, chamber size and number of chambers in series as well as operating conditions including the outlet pressure, mean input flow rate, fluctuation amplitude and frequency on the device performance were studied using experiments and simulations. The simulation results successfully confront the experimental data (within 10%) which validates the numerical simulations. The device was used at the exit of a PZT actuated valveless micropump to take pulsating flow at the upstream and deliver steady flow downstream. The amplitude of the pulsating flow delivered by the micropump was significantly reduced (AF = 0.05 for a device with three 4 mm chambers) but at the expense of a reduction in the pressure capability (<20%). The proposed device could potentially be used for reducing flow pulsations in practical microfluidic circuits.

Nature-inspired polymer actuators for micro-fluidic mixing.

NASA Astrophysics Data System (ADS)

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

2007-11-01

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

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

NASA Astrophysics Data System (ADS)

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

2017-12-01

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

Rapid Protein Separations in Microfluidic Devices

NASA Technical Reports Server (NTRS)

Fan, Z. H.; Das, Champak; Xia, Zheng; Stoyanov, Alexander V.; Fredrickson, Carl K.

2004-01-01

This paper describes fabrication of glass and plastic microfluidic devices for protein separations. Although the long-term goal is to develop a microfluidic device for two-dimensional gel electrophoresis, this paper focuses on the first dimension-isoelectric focusing (IEF). A laser-induced fluorescence (LIF) imaging system has been built for imaging an entire channel in an IEF device. The whole-channel imaging eliminates the need to migrate focused protein bands, which is required if a single-point detector is used. Using the devices and the imaging system, we are able to perform IEF separations of proteins within minutes rather than hours in traditional bench-top instruments.

Microfluidics: a groundbreaking technology for PET tracer production?

PubMed

Rensch, Christian; Jackson, Alexander; Lindner, Simon; Salvamoser, Ruben; Samper, Victor; Riese, Stefan; Bartenstein, Peter; Wängler, Carmen; Wängler, Björn

2013-07-05

Application of microfluidics to Positron Emission Tomography (PET) tracer synthesis has attracted increasing interest within the last decade. The technical advantages of microfluidics, in particular the high surface to volume ratio and resulting fast thermal heating and cooling rates of reagents can lead to reduced reaction times, increased synthesis yields and reduced by-products. In addition automated reaction optimization, reduced consumption of expensive reagents and a path towards a reduced system footprint have been successfully demonstrated. The processing of radioactivity levels required for routine production, use of microfluidic-produced PET tracer doses in preclinical and clinical imaging as well as feasibility studies on autoradiolytic decomposition have all given promising results. However, the number of microfluidic synthesizers utilized for commercial routine production of PET tracers is very limited. This study reviews the state of the art in microfluidic PET tracer synthesis, highlighting critical design aspects, strengths, weaknesses and presenting several characteristics of the diverse PET market space which are thought to have a significant impact on research, development and engineering of microfluidic devices in this field. Furthermore, the topics of batch- and single-dose production, cyclotron to quality control integration as well as centralized versus de-centralized market distribution models are addressed.

High spatial and temporal resolution cell manipulation techniques in microchannels.

PubMed

Novo, Pedro; Dell'Aica, Margherita; Janasek, Dirk; Zahedi, René P

2016-03-21

The advent of microfluidics has enabled thorough control of cell manipulation experiments in so called lab on chips. Lab on chips foster the integration of actuation and detection systems, and require minute sample and reagent amounts. Typically employed microfluidic structures have similar dimensions as cells, enabling precise spatial and temporal control of individual cells and their local environments. Several strategies for high spatio-temporal control of cells in microfluidics have been reported in recent years, namely methods relying on careful design of the microfluidic structures (e.g. pinched flow), by integration of actuators (e.g. electrodes or magnets for dielectro-, acousto- and magneto-phoresis), or integrations thereof. This review presents the recent developments of cell experiments in microfluidics divided into two parts: an introduction to spatial control of cells in microchannels followed by special emphasis in the high temporal control of cell-stimulus reaction and quenching. In the end, the present state of the art is discussed in line with future perspectives and challenges for translating these devices into routine applications.

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

PubMed

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

2010-08-07

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

Rapid Detection of Microbial Contamination Using a Microfluidic Device.

PubMed

Al-Adhami, Mustafa; Tilahun, Dagmawi; Rao, Govind; Gurramkonda, Chandrasekhar; Kostov, Yordan

2017-01-01

A portable kinetics fluorometer is developed to detect viable cells which may be contaminating various samples. The portable device acts as a single-excitation, single-emission photometer that continuously measures fluorescence intensity of an indicator dye and plots it. The slope of the plot depends on the number of colony forming units per milliliter. The device uses resazurin as the indicator dye. Viable cells reduce resazurin to resorufin, which is more fluorescent. Photodiode is used to detect fluorescence change. The photodiode generated current proportional to the intensity of the light that reached it, and an op-amp is used in a transimpedance differential configuration to ensure amplification of the photodiode's signal. A microfluidic chip is designed specifically for the device. It acts as a fully enclosed cuvette, which enhances the resazurin reduction rate. In tests, the E. coli-containing media are injected into the microfluidic chip and the device is able to detect the presence of E. coli in LB media based on the fluorescence change that occurred in the indicator dye. The device provides fast, accurate, and inexpensive means to optical detection of the presence of viable cells and could be used in the field in place of more complex methods, i.e., loop-meditated isothermal amplification of DNA (LAMP) to detect bacteria in pharmaceutical samples (Jimenez et al., J Microbiol Methods 41(3):259-265, 2000) or measuring the intrinsic fluorescence of the bacterial or yeast chromophores (Estes et al., Biosens Bioelectron 18(5):511-519, 2003).

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

3D printed microfluidics for biological applications.

PubMed

Ho, Chee Meng Benjamin; Ng, Sum Huan; Li, King Ho Holden; Yoon, Yong-Jin

2015-01-01

The term "Lab-on-a-Chip," is synonymous with describing microfluidic devices with biomedical applications. Even though microfluidics have been developing rapidly over the past decade, the uptake rate in biological research has been slow. This could be due to the tedious process of fabricating a chip and the absence of a "killer application" that would outperform existing traditional methods. In recent years, three dimensional (3D) printing has been drawing much interest from the research community. It has the ability to make complex structures with high resolution. Moreover, the fast building time and ease of learning has simplified the fabrication process of microfluidic devices to a single step. This could possibly aid the field of microfluidics in finding its "killer application" that will lead to its acceptance by researchers, especially in the biomedical field. In this paper, a review is carried out of how 3D printing helps to improve the fabrication of microfluidic devices, the 3D printing technologies currently used for fabrication and the future of 3D printing in the field of microfluidics.

Paper-based microfluidic system for tear electrolyte analysis† †We declare no competing financial interests. ‡ ‡Electronic supplementary information (ESI) available: Microscopic images of G1 paper and G41 paper under brightfield; optimization of CO2 laser radiation fluence and beam speed for ablating filter paper-G1; photographs of DI water diffusion in microfluidic channels with different lengths, different widths, different viscosities of fluid and different numbers of channels; fluorescence intensity readouts of Na+ and K+ ions with varied concentrations of fluorescent probes; effect of variations in temperature on fluorescence intensity; photographs of DMSO on G1 paper dried in the air; calibration curves of electrolyte sensing on G1 paper using microplate reader measurement; calculation of sensitivity of the fluorescent sensors based on International Union of Pure and Applied Chemistry (IUPAC) guidelines; quantification of ion interference in buffer solution and artificial tear fluid; light attenuation of LED lights using different optical filters; the design of the sample collection device and its potential clinical use; calibration curves of electrolyte sensors using the paper-based microfluidic system; quantifications of evaporation effect on sampling process; design of the sample collection device and its potential clinical use; batch-to-batch variation experiments; equation for background subtraction; movies of sample collection and measurements. See DOI: 10.1039/c6lc01450j Click here for additional data file. Click here for additional data file. Click here for additional data file. Click here for additional data file.

PubMed Central

Jiang, Nan; Tamayol, Ali; Ruiz-Esparza, Guillermo U.; Zhang, Yu Shrike; Medina-Pando, Sofía; Gupta, Aditi; Wolffsohn, James S.; Butt, Haider; Khademhosseini, Ali

2017-01-01

The analysis of tear constituents at point-of-care settings has a potential for early diagnosis of ocular disorders such as dry eye disease, low-cost screening, and surveillance of at-risk subjects. However, current minimally-invasive rapid tear analysis systems for point-of-care settings have been limited to assessment of osmolarity or inflammatory markers and cannot differentiate between dry eye subclassifications. Here, we demonstrate a portable microfluidic system that allows quantitative analysis of electrolytes in the tear fluid that is suited for point-of-care settings. The microfluidic system consists of a capillary tube for sample collection, a reservoir for sample dilution, and a paper-based microfluidic device for electrolyte analysis. The sensing regions are functionalized with fluorescent crown ethers, o-acetanisidide, and seminaphtorhodafluor that are sensitive to mono- and divalent electrolytes, and their fluorescence outputs are measured with a smartphone readout device. The measured sensitivity values of Na+, K+, Ca2+ ions and pH in artificial tear fluid were matched with the known ion concentrations within the physiological range. The microfluidic system was tested with samples having different ionic concentrations, demonstrating the feasibility for the detection of early-stage dry eye, differential diagnosis of dry eye sub-types, and their severity staging. PMID:28207920

A Microfluidic Device for Continuous Sensing of Systemic Acute Toxicants in Drinking Water

PubMed Central

Zhao, Xinyan; Dong, Tao

2013-01-01

A bioluminescent-cell-based microfluidic device for sensing toxicants in drinking water was designed and fabricated. The system employed Vibrio fischeri cells as broad-spectrum sensors to monitor potential systemic cell toxicants in water, such as heavy metal ions and phenol. Specifically, the chip was designed for continuous detection. The chip design included two counter-flow micromixers, a T-junction droplet generator and six spiral microchannels. The cell suspension and water sample were introduced into the micromixers and dispersed into droplets in the air flow. This guaranteed sufficient oxygen supply for the cell sensors. Copper (Cu2+), zinc (Zn2+), potassium dichromate and 3,5-dichlorophenol were selected as typical toxicants to validate the sensing system. Preliminary tests verified that the system was an effective screening tool for acute toxicants although it could not recognize or quantify specific toxicants. A distinct non-linear relationship was observed between the zinc ion concentration and the Relative Luminescence Units (RLU) obtained during testing. Thus, the concentration of simple toxic chemicals in water can be roughly estimated by this system. The proposed device shows great promise for an early warning system for water safety. PMID:24300075

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

PubMed

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

2016-01-21

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

Microfluidic diffusion diluter: bulging of PDMS microchannels under pressure-driven flow

NASA Astrophysics Data System (ADS)

Holden, Matthew A.; Kumar, Saurabh; Beskok, Ali; Cremer, Paul S.

2003-05-01

The bulging of microfluidic systems during pressure-driven flow is potentially a major consideration for polydimethylsiloxane (PDMS)-based devices. Microchannel cross-sectional areas can change drastically as a function of flow rate and downstream microchannel position. Such geometrical flexibility leads to difficulties in predicting convective/diffusive transport for these systems. We have previously introduced a non-dimensional parameter, kappa, for characterizing convection and diffusion behavior for pressure-driven flow in rigid all-glass systems. This paper describes a modification of that concept for application to non-rigid systems, which is accomplished by incorporating an experimental step to account for the bulging in PDMS/glass microsystems. Specifically, an experimental measurement of channel height by fluorescence microscopy is combined with the aforementioned theory to characterize convective/diffusive behavior at a single location in the device. This allowed the parameter kappa to be determined at that point and applied to predict fluid flow in the subsequent portion of the PDMS microsystem. This procedure was applied to a PDMS/glass microfluidic diffusion dilution (muDD) device designed for generating concentration gradients. Theoretically predicted and experimentally measured distributions of concentrations within the microsystem matched well.

Imaging the Root Hair Morphology of Arabidopsis Seedlings in a Two-layer Microfluidic Platform

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

Aufrecht, Jayde A.; Ryan, Jennifer M.; Hasim, Sahar

Root hairs increase root surface area for better water uptake and nutrient absorption by the plant. Because they are small in size and often obscured by their natural environment, root hair morphology and function are difficult to study and often excluded from plant research. In recent years, microfluidic platforms have offered a way to visualize root systems at high resolution without disturbing the roots during transfer to an imaging system. The microfluidic platform presented here builds on previous plant-on-a-chip research by incorporating a two-layer device to confine the Arabidopsis thaliana main root to the same optical plane as the rootmore » hairs. This design enables the quantification of root hairs on a cellular and organelle level and also prevents z-axis drifting during the addition of experimental treatments. We describe how to store the devices in a contained and hydrated environment, without the need for fluidic pumps, while maintaining a gnotobiotic environment for the seedling. After the optical imaging experiment, the device may be disassembled and used as a substrate for atomic force or scanning electron microscopy while keeping fine root structures intact.« less

Imaging the Root Hair Morphology of Arabidopsis Seedlings in a Two-layer Microfluidic Platform

DOE PAGES

Aufrecht, Jayde A.; Ryan, Jennifer M.; Hasim, Sahar; ...

2017-08-01

Root hairs increase root surface area for better water uptake and nutrient absorption by the plant. Because they are small in size and often obscured by their natural environment, root hair morphology and function are difficult to study and often excluded from plant research. In recent years, microfluidic platforms have offered a way to visualize root systems at high resolution without disturbing the roots during transfer to an imaging system. The microfluidic platform presented here builds on previous plant-on-a-chip research by incorporating a two-layer device to confine the Arabidopsis thaliana main root to the same optical plane as the rootmore » hairs. This design enables the quantification of root hairs on a cellular and organelle level and also prevents z-axis drifting during the addition of experimental treatments. We describe how to store the devices in a contained and hydrated environment, without the need for fluidic pumps, while maintaining a gnotobiotic environment for the seedling. After the optical imaging experiment, the device may be disassembled and used as a substrate for atomic force or scanning electron microscopy while keeping fine root structures intact.« less

Modelling and simulation of passive Lab-on-a-Chip (LoC) based micromixer for clinical application

NASA Astrophysics Data System (ADS)

Saikat, Chakraborty; Sharath, M.; Srujana, M.; Narayan, K.; Pattnaik, Prasant Kumar

2016-03-01

In biomedical application, micromixer is an important component because of many processes requires rapid and efficient mixing. At micro scale, the flow is Laminar due to small channel size which enables controlled rapid mixing. The reduction in analysis time along with high throughput can be achieved with the help of rapid mixing. In LoC application, micromixer is used for mixing of fluids especially for the devices which requires efficient mixing. Micromixer of this type of microfluidic devices with a rapid mixing is useful in application such as DNA/RNA synthesis, drug delivery system & biological agent detection. In this work, we design and simulate a microfluidic based passive rapid micromixer for lab-on-a-chip application.

A multi-channel clogging-resistant lab-on-a-chip cell counter and analyzer

NASA Astrophysics Data System (ADS)

Dai, Jie; Chiu, Yu-Jui; Lian, Ian; Wu, Tsung-Feng; Yang, Kecheng; Lo, Yu-Hwa

2016-02-01

Early signs of diseases can be revealed from cell detection in biofluids, such as detection of white blood cells (WBCs) in the peritoneal fluid for peritonitis. A lab-on-a-chip microfluidic device offers an attractive platform for such applications because of its small size, low cost, and ease of use provided the device can meet the performance requirements which many existing LoC devices fail to satisfy. We report an integrated microfluidic device capable of accurately counting low concentration of white blood cells in peritoneal fluid at 150 μl min-1 to offer an accurate (<3% error) and fast (~10 min/run) WBC count. Utilizing the self-regulating hydrodynamic properties and a unique architecture in the design, the device can achieve higher flow rate (500-1000 μl min-1), continuous running for over 5 h without clogging, as well as excellent signal quality for unambiguous WBC count and WBC classification for certain diseases. These properties make the device a promising candidate for point-of-care applications.

Streamline-based microfluidic device

NASA Technical Reports Server (NTRS)

Tai, Yu-Chong (Inventor); Zheng, Siyang (Inventor); Kasdan, Harvey (Inventor)

2013-01-01

The present invention provides a streamline-based device and a method for using the device for continuous separation of particles including cells in biological fluids. The device includes a main microchannel and an array of side microchannels disposed on a substrate. The main microchannel has a plurality of stagnation points with a predetermined geometric design, for example, each of the stagnation points has a predetermined distance from the upstream edge of each of the side microchannels. The particles are separated and collected in the side microchannels.

Dynamical phase separation using a microfluidic device: experiments and modeling

NASA Astrophysics Data System (ADS)

Aymard, Benjamin; Vaes, Urbain; Radhakrishnan, Anand; Pradas, Marc; Gavriilidis, Asterios; Kalliadasis, Serafim; Complex Multiscale Systems Team

2017-11-01

We study the dynamical phase separation of a binary fluid by a microfluidic device both from the experimental and from the modeling points of view. The experimental device consists of a main channel (600 μm wide) leading into an array of 276 trapezoidal capillaries of 5 μm width arranged on both sides and separating the lateral channels from the main channel. Due to geometrical effects as well as wetting properties of the substrate, and under well chosen pressure boundary conditions, a multiphase flow introduced into the main channel gets separated at the capillaries. Understanding this dynamics via modeling and numerical simulation is a crucial step in designing future efficient micro-separators. We propose a diffuse-interface model, based on the classical Cahn-Hilliard-Navier-Stokes system, with a new nonlinear mobility and new wetting boundary conditions. We also propose a novel numerical method using a finite-element approach, together with an adaptive mesh refinement strategy. The complex geometry is captured using the same computer-aided design files as the ones adopted in the fabrication of the actual device. Numerical simulations reveal a very good qualitative agreement between model and experiments, demonstrating also a clear separation of phases.

Microfluidic filtration and extraction of pathogens from food samples by hydrodynamic focusing and inertial lateral migration.

PubMed

Clime, Liviu; Hoa, Xuyen D; Corneau, Nathalie; Morton, Keith J; Luebbert, Christian; Mounier, Maxence; Brassard, Daniel; Geissler, Matthias; Bidawid, Sabah; Farber, Jeff; Veres, Teodor

2015-02-01

Detecting pathogenic bacteria in food or other biological samples with lab-on-a-chip (LOC) devices requires several sample preparation steps prior to analysis which commonly involves cleaning complex sample matrices of large debris. This often underestimated step is important to prevent these larger particles from clogging devices and to preserve initial concentrations when LOC techniques are used to concentrate or isolate smaller target microorganisms for downstream analysis. In this context, we developed a novel microfluidic system for membrane-free cleaning of biological samples from debris particles by combining hydrodynamic focusing and inertial lateral migration effects. The microfluidic device is fabricated using thermoplastic elastomers being compatible with thermoforming fabrication techniques leading to low-cost single-use devices. Microfluidic chip design and pumping protocols are optimized by investigating diffusive losses numerically with coupled Navier-Stokes and convective-diffusion theoretical models. Stability of inertial lateral migration and separation of debris is assessed through fluorescence microscopy measurements with labelled particles serving as a model system. Efficiency of debris cleaning is experimentally investigated by monitoring microchip outlets with in situ optical turbidity sensors, while retention of targeted pathogens (i.e., Listeria monocytogenes) within the sample stream is assessed through bacterial culture techniques. Optimized pumping protocols can remove up to 50 % of debris from ground beef samples while percentage for preserved microorganisms can account for 95 % in relatively clean samples. However, comparison between inoculated turbid and clean samples (i.e., with and without ground beef debris) indicate some degree of interference between debris inertial lateral migration and hydrodynamic focusing of small microorganisms. Although this interference can lead to significant decrease in chip performance through loss of target bacteria, it remains possible to reach 70 % for sample recovery and more than 50 % for debris removal even in the most turbid samples tested. Due to the relatively simple design, the robustness of the inertial migration effect itself, the high operational flow rates and fabrication methods that leverage low-cost materials, the proposed device can have an impact on a wide range of applications where high-throughput separation of particles and biological species is of interest.

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.

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.

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

Principles, Techniques, and Applications of Tissue Microfluidics

NASA Technical Reports Server (NTRS)

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

2011-01-01

The principle of tissue microfluidics and its resultant techniques has been applied to cell analysis. Building microfluidics to suit a particular tissue sample would allow the rapid, reliable, inexpensive, highly parallelized, selective extraction of chosen regions of tissue for purposes of further biochemical analysis. Furthermore, the applicability of the techniques ranges beyond the described pathology application. For example, they would also allow the posing and successful answering of new sets of questions in many areas of fundamental research. The proposed integration of microfluidic techniques and tissue slice samples is called "tissue microfluidics" because it molds the microfluidic architectures in accordance with each particular structure of each specific tissue sample. Thus, microfluidics can be built around the tissues, following the tissue structure, or alternatively, the microfluidics can be adapted to the specific geometry of particular tissues. By contrast, the traditional approach is that microfluidic devices are structured in accordance with engineering considerations, while the biological components in applied devices are forced to comply with these engineering presets.

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.

Dean Flow Dynamics in Low-Aspect Ratio Spiral Microchannels

PubMed Central

Nivedita, Nivedita; Ligrani, Phillip; Papautsky, Ian

2017-01-01

A wide range of microfluidic cell-sorting devices has emerged in recent years, based on both passive and active methods of separation. Curvilinear channel geometries are often used in these systems due to presence of secondary flows, which can provide high throughput and sorting efficiency. Most of these devices are designed on the assumption of two counter rotating Dean vortices present in the curved rectangular channels and existing in the state of steady rotation and amplitude. In this work, we investigate these secondary flows in low aspect ratio spiral rectangular microchannels and define their development with respect to the channel aspect ratio and Dean number. This work is the first to experimentally and numerically investigate Dean flows in microchannels for Re > 100, and show presence of secondary Dean vortices beyond a critical Dean number. We further demonstrate the impact of these multiple vortices on particle and cell focusing. Ultimately, this work offers new insights into secondary flow instabilities for low-aspect ratio, spiral microchannels, with improved flow models for design of more precise and efficient microfluidic devices for applications such as cell sorting and micromixing. PMID:28281579

Microfluidic Devices for Forensic DNA Analysis: A Review

PubMed Central

Bruijns, Brigitte; van Asten, Arian; Tiggelaar, Roald; Gardeniers, Han

2016-01-01

Microfluidic devices may offer various advantages for forensic DNA analysis, such as reduced risk of contamination, shorter analysis time and direct application at the crime scene. Microfluidic chip technology has already proven to be functional and effective within medical applications, such as for point-of-care use. In the forensic field, one may expect microfluidic technology to become particularly relevant for the analysis of biological traces containing human DNA. This would require a number of consecutive steps, including sample work up, DNA amplification and detection, as well as secure storage of the sample. This article provides an extensive overview of microfluidic devices for cell lysis, DNA extraction and purification, DNA amplification and detection and analysis techniques for DNA. Topics to be discussed are polymerase chain reaction (PCR) on-chip, digital PCR (dPCR), isothermal amplification on-chip, chip materials, integrated devices and commercially available techniques. A critical overview of the opportunities and challenges of the use of chips is discussed, and developments made in forensic DNA analysis over the past 10–20 years with microfluidic systems are described. Areas in which further research is needed are indicated in a future outlook. PMID:27527231

Biomimetic postcapillary expansions for enhancing rare blood cell separation on a microfluidic chip†

PubMed Central

Jain, Abhishek

2013-01-01

Blood cells naturally auto-segregate in postcapillary venules, with the erythrocytes (red blood cells, RBCs) aggregating near the axis of flow and the nucleated cells (NCs)—which include leukocytes, progenitor cells and, in cancer patients, circulating tumor cells—marginating toward the vessel wall. We have used this principle to design a microfluidic device that extracts nucleated cells (NCs) from whole blood. Fabricated using polydimethylsiloxane (PDMS) soft lithography, the biomimetic cell extraction device consists of rectangular microchannels that are 20–400 μm wide, 11 μm deep and up to 2 cm long. The key design feature is the use of repeated expansions/contractions of triangular geometry mimicking postcapillary venules, which enhance margination and optimize the extraction. The device operates on unprocessed whole blood and is able to extract 94 ± 4.5% of NCs with 45.75 ± 2.5-fold enrichment in concentration at a rate of 5 nl s−1. The device eliminates the need to preprocess blood via centrifugation or RBC lysis, and is ready to be implemented as the initial stage of lab-on-a-chip devices that require enriched nucleated cells. The potential downstream applications are numerous, encompassing all preclinical and clinical assays that operate on enriched NC populations and include on-chip flow cytometry PMID:21773633

Macromolecular Crystal Growth by Means of Microfluidics

NASA Technical Reports Server (NTRS)

vanderWoerd, Mark; Ferree, Darren; Spearing, Scott; Monaco, Lisa; Molho, Josh; Spaid, Michael; Brasseur, Mike; Curreri, Peter A. (Technical Monitor)

2002-01-01

We have performed a feasibility study in which we show that chip-based, microfluidic (LabChip(TM)) technology is suitable for protein crystal growth. This technology allows for accurate and reliable dispensing and mixing of very small volumes while minimizing bubble formation in the crystallization mixture. The amount of (protein) solution remaining after completion of an experiment is minimal, which makes this technique efficient and attractive for use with proteins, which are difficult or expensive to obtain. The nature of LabChip(TM) technology renders it highly amenable to automation. Protein crystals obtained in our initial feasibility studies were of excellent quality as determined by X-ray diffraction. Subsequent to the feasibility study, we designed and produced the first LabChip(TM) device specifically for protein crystallization in batch mode. It can reliably dispense and mix from a range of solution constituents into two independent growth wells. We are currently testing this design to prove its efficacy for protein crystallization optimization experiments. In the near future we will expand our design to incorporate up to 10 growth wells per LabChip(TM) device. Upon completion, additional crystallization techniques such as vapor diffusion and liquid-liquid diffusion will be accommodated. Macromolecular crystallization using microfluidic technology is envisioned as a fully automated system, which will use the 'tele-science' concept of remote operation and will be developed into a research facility for the International Space Station as well as on the ground.

Microfluidic model of the platelet-generating organ: beyond bone marrow biomimetics

NASA Astrophysics Data System (ADS)

Reyssat, Mathilde; Blin, Antoine; Le Goff, Anne; Magniez, Aurelie; Poirault-Chassac, Sonia; Teste, Bruno; Sicot, Geraldine; Nguyen, Kim Anh; Hamdi, Feriel S.; Baruch, Dominique

2015-11-01

We present a new, rapid method for producing blood platelets in vitro from cultured megakaryocytes based on a microfluidic device. This device consists in a wide array of VWF coated micropillars. Such pillars act as anchors on megakaryocytes, allowing them to remain trapped in the device and subjected to hydrodynamic shear. The combined effect of anchoring and shear induces the elongation of megakaryocytes and finally their rupture into platelets and proplatelets. This process was observed with megakaryocytes from different origins and found to be robust. This original bioreactor design allows to process megakaryocytes at high throughput (millions per hour), with a platelet yield increasing four times in comparison with control experiments. Since platelets are produced in such a large amount, their extensive biological characterization is possible. Fluorescent microscopy observations, flow cytometry, aggregometry results indicate that platelets produced in this bioreactor are functional.

Matrix-Assisted Three-Dimensional Printing of Cellulose Nanofibers for Paper Microfluidics.

PubMed

Shin, Sungchul; Hyun, Jinho

2017-08-09

A cellulose nanofiber (CNF), one of the most attractive green bioresources, was adopted for construction of microfluidic devices using matrix-assisted three-dimensional (3D) printing. CNF hydrogels can support structures printed using CAD design in a 3D hydrogel environment with the appropriate combination of rheological properties between the CNF hydrogel and ink materials. Amazingly, the structure printed freely in the bulky CNF hydrogels was able to retain its highly resolved 3D features in an ultrathin two-dimensional (2D) paper using a simple drying process. The dimensional change in the CNF hydrogels from 3D to 2D resulted from simple dehydration of the CNFs and provided transparent, stackable paper-based 3D channel devices. As a proof of principle, the rheological properties of the CNF hydrogels, the 3D structure of the ink, the formation of channels by evacuation of the ink, and the highly localized selectivity of the devices are described.

Hybrid electro-optical nanosystem for neurons investigation

NASA Astrophysics Data System (ADS)

Miu, Mihaela; Kleps, Irina; Craciunoiu, Florea; Simion, Monica; Bragaru, Adina; Ignat, Teodora

2010-11-01

The scope of this paper is development of a new laboratory-on-a-chip (LOC) device for biomedical studies consisting of a microfluidic system coupled to microelectronic/optical transducers with nanometric features, commonly called biosensors. The proposed device is a hybrid system with sensing element on silicon (Si) chip and microfluidic system on polydimethylsiloxane (PDMS) substrates, taking into accounts their particular advantages. Different types of nanoelectrode arrays, positioned in the reactor, have been investigated as sensitive elements for electrical detection and the recording of neuron extracellular electric activity has been monitorized in parallel with whole-cell patch-clamp membrane current. Moreover, using an additional porosification process the sensing element became efficient for optical detection also. The preliminary test results demonstrate the functionality of the proposed design and also the fabrication technology, the devices bringing advantages in terms enhancement of sensitivity in both optoelectronic detection schemes.

A semi-automated, field-portable microscopy platform for clinical diagnostic applications

NASA Astrophysics Data System (ADS)

Jagannadh, Veerendra Kalyan; Srinivasan, Rajesh; Gorthi, Sai Siva

2015-08-01

Clinical microscopy is a versatile diagnostic platform used for diagnosis of a multitude of diseases. In the recent past, many microfluidics based point-of-care diagnostic devices have been developed, which serve as alternatives to microscopy. However, these point-of-care devices are not as multi-functional and versatile as clinical microscopy. With the use of custom designed optics and microfluidics, we have developed a versatile microscopy-based cellular diagnostic platform, which can be used at the point of care. The microscopy platform presented here is capable of detecting infections of very low parasitemia level (in a very small quantity of sample), without the use of any additional computational hardware. Such a cost-effective and portable diagnostic device, would greatly impact the quality of health care available to people living in rural locations of the world. Apart from clinical diagnostics, it's applicability to field research in environmental microbiology has also been outlined.

A microfluidic device to study neuronal and motor responses to acute chemical stimuli in zebrafish.

PubMed

Candelier, Raphaël; Murmu, Meena Sriti; Romano, Sebastián Alejo; Jouary, Adrien; Debrégeas, Georges; Sumbre, Germán

2015-07-21

Zebrafish larva is a unique model for whole-brain functional imaging and to study sensory-motor integration in the vertebrate brain. To take full advantage of this system, one needs to design sensory environments that can mimic the complex spatiotemporal stimulus patterns experienced by the animal in natural conditions. We report on a novel open-ended microfluidic device that delivers pulses of chemical stimuli to agarose-restrained larvae with near-millisecond switching rate and unprecedented spatial and concentration accuracy and reproducibility. In combination with two-photon calcium imaging and recordings of tail movements, we found that stimuli of opposite hedonic values induced different circuit activity patterns. Moreover, by precisely controlling the duration of the stimulus (50-500 ms), we found that the probability of generating a gustatory-induced behavior is encoded by the number of neurons activated. This device may open new ways to dissect the neural-circuit principles underlying chemosensory perception.

Big insights from small volumes: deciphering complex leukocyte behaviors using microfluidics

PubMed Central

Irimia, Daniel; Ellett, Felix

2016-01-01

Inflammation is an indispensable component of the immune response, and leukocytes provide the first line of defense against infection. Although the major stereotypic leukocyte behaviors in response to infection are well known, the complexities and idiosyncrasies of these phenotypes in conditions of disease are still emerging. Novel tools are indispensable for gaining insights into leukocyte behavior, and in the past decade, microfluidic technologies have emerged as an exciting development in the field. Microfluidic devices are readily customizable, provide tight control of experimental conditions, enable high precision of ex vivo measurements of individual as well as integrated leukocyte functions, and have facilitated the discovery of novel leukocyte phenotypes. Here, we review some of the most interesting insights resulting from the application of microfluidic approaches to the study of the inflammatory response. The aim is to encourage leukocyte biologists to integrate these new tools into increasingly more sophisticated experimental designs for probing complex leukocyte functions. PMID:27194799

Microfluidic etching and oxime-based tailoring of biodegradable polyketoesters.

PubMed

Barrett, Devin G; Lamb, Brian M; Yousaf, Muhammad N

2008-09-02

A straightforward, flexible, and inexpensive method to etch biodegradable poly(1,2,6-hexanetriol alpha-ketoglutarate) films is reported. Microfluidic delivery of the etchant, a solution of NaOH, can create micron-scale channels through local hydrolysis of the polyester film. In addition, the presence of a ketone in the repeat unit allows for prior or post chemoselective modifications, enabling the design of functionalized microchannels. Delivery of oxyamine tethered ligands react with ketone groups on the polyketoester to generate covalent oxime linkages. By thermally sealing an etched film to a second flat surface, poly(1,2,6-hexanetriol alpha-ketoglutarate) can be used to create biodegradable microfluidic devices. In order to determine the versatility of the microfluidic etch technique, poly(epsilon-caprolactone) was etched with acetone. This strategy provides a facile method for the direct patterning of biodegradable materials, both through etching and chemoselective ligand immobilization.

Microfluidics-based integrated airborne pathogen detection systems

NASA Astrophysics Data System (ADS)

Northrup, M. Allen; Alleman-Sposito, Jennifer; Austin, Todd; Devitt, Amy; Fong, Donna; Lin, Phil; Nakao, Brian; Pourahmadi, Farzad; Vinas, Mary; Yuan, Bob

2006-09-01

Microfluidic Systems is focused on building microfluidic platforms that interface front-end mesofluidics to handle real world sample volumes for optimal sensitivity coupled to microfluidic circuitry to process small liquid volumes for complex reagent metering, mixing, and biochemical analysis, particularly for pathogens. MFSI is the prime contractor on two programs for the US Department of Homeland Security: BAND (Bioagent Autonomous Networked Detector) and IBADS (Instantaneous Bio-Aerosol Detection System). The goal of BAND is to develop an autonomous system for monitoring the air for known biological agents. This consists of air collection, sample lysis, sample purification, detection of DNA, RNA, and toxins, and a networked interface to report the results. For IBADS, MFSI is developing the confirmatory device which must verify the presence of a pathogen with 5 minutes of an air collector/trigger sounding an alarm. Instrument designs and biological assay results from both BAND and IBADS will be presented.

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.

An integrated microfluidic cell for detection, manipulation, and sorting of single micron-sized magnetic beads

NASA Astrophysics Data System (ADS)

Jiang, Z.; Llandro, J.; Mitrelias, T.; Bland, J. A. C.

2006-04-01

A lab-on-a-chip integrated microfluidic cell has been developed for magnetic biosensing, which is comprised of anisotropic magnetoresistance (AMR) sensors optimized for the detection of single magnetic beads and electrodes to manipulate and sort the beads, integrated into a microfluidic channel. The device is designed to read out the real-time signal from 9 μm diameter magnetic beads moving over AMR sensors patterned into 18×4.5 μm rectangles and 10 μm diameter rings and arranged in Wheatstone bridges. The beads are moved over the sensors along a 75×75 μm wide channel patterned in SU8. Beads of different magnetic moments can be sorted through a magnetostatic sorting gate into different branches of the microfluidic channel using a magnetic field gradient applied by lithographically defined 120 nm thick Cu striplines carrying 0.2 A current.

Microfluidic Device

NASA Technical Reports Server (NTRS)

Tai, Yu-Chong (Inventor); Kasdan, Harvey L. (Inventor); Zheng, Siyang (Inventor); Lin, Jeffrey Chun-Hui (Inventor)

2016-01-01

Described herein are particular embodiments relating to a microfluidic device that may be utilized for cell sensing, counting, and/or sorting. Particular aspects relate to a microfabricated device that is capable of differentiating single cell types from dense cell populations. One particular embodiment relates a device and methods of using the same for sensing, counting, and/or sorting leukocytes from whole, undiluted blood samples.

Microfluidic Device

NASA Technical Reports Server (NTRS)

Zheng, Siyang (Inventor); Lin, Jeffrey Chun-Hui (Inventor); Kasdan, Harvey (Inventor); Tai, Yu-Chong (Inventor)

2015-01-01

Described herein are particular embodiments relating to a microfluidic device that may be utilized for cell sensing, counting, and/or sorting. Particular aspects relate to a microfabricated device that is capable of differentiating single cell types from dense cell populations. One particular embodiment relates a device and methods of using the same for sensing, counting, and/or sorting leukocytes from whole, undiluted blood samples.

Microfluidic Device

NASA Technical Reports Server (NTRS)

Tai, Yu-Chong (Inventor); Zheng, Siyang (Inventor); Lin, Jeffrey Chun-Hui (Inventor); Kasdan, Harvey L. (Inventor)

2017-01-01

Described herein are particular embodiments relating to a microfluidic device that may be utilized for cell sensing, counting, and/or sorting. Particular aspects relate to a microfabricated device that is capable of differentiating single cell types from dense cell populations. One particular embodiment relates a device and methods of using the same for sensing, counting, and/or sorting leukocytes from whole, undiluted blood samples.

Multivariate Analysis To Quantify Species in the Presence of Direct Interferents: Micro-Raman Analysis of HNO 3 in Microfluidic Devices

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

Lines, Amanda M.; Nelson, Gilbert L.; Casella, Amanda J.

Microfluidic devices are a growing field with significant potential for application to small scale processing of solutions. Much like large scale processing, fast, reliable, and cost effective means of monitoring the streams during processing are needed. Here we apply a novel Micro-Raman probe to the on-line monitoring of streams within a microfluidic device. For either macro or micro scale process monitoring via spectroscopic response, there is the danger of interfering or confounded bands obfuscating results. By utilizing chemometric analysis, a form of multivariate analysis, species can be accurately quantified in solution despite the presence of overlapping or confounded spectroscopic bands.more » This is demonstrated on solutions of HNO 3 and NaNO 3 within micro-flow and microfluidic devices.« less

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.

Design of a single-step immunoassay principle based on the combination of an enzyme-labeled antibody release coating and a hydrogel copolymerized with a fluorescent enzyme substrate in a microfluidic capillary device.

PubMed

Wakayama, Hideki; Henares, Terence G; Jigawa, Kaede; Funano, Shun-ichi; Sueyoshi, Kenji; Endo, Tatsuro; Hisamoto, Hideaki

2013-11-21

A combination of an enzyme-labeled antibody release coating and a novel fluorescent enzyme substrate-copolymerized hydrogel in a microchannel for a single-step, no-wash microfluidic immunoassay is demonstrated. This hydrogel discriminates the free enzyme-conjugated antibody from an antigen-enzyme-conjugated antibody immunocomplex based on the difference in molecular size. A selective and sensitive immunoassay, with 10-1000 ng mL(-1) linear range, is reported.

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.

Microfabrication of plastic-PDMS microfluidic devices using polyimide release layer and selective adhesive bonding

DOE PAGES

Wang, Shuyu; Yu, Shifeng; Lu, Ming; ...

2017-03-15

In this study, we present an improved method to bond poly(dimethylsiloxane) (PDMS) with polyimide (PI) to develop flexible substrate microfluidic devices. The PI film was separately fabricated on a silicon wafer by spin coating followed by thermal treatment to avoid surface unevenness of the flexible substrate. In this way, we could also integrate flexible substrate into standard micro-electromechanical systems (MEMS) fabrication. Meanwhile, the adhesive epoxy was selectively transferred to the PDMS microfluidic device by a stamp-and-stick method to avoid epoxy clogging the microfluidic channels. To spread out the epoxy evenly on the transferring substrate, we used superhydrophilic vanadium oxide filmmore » coated glass as the transferring substrate. After the bonding process, the flexible substrate could easily be peeled off from the rigid substrate. Contact angle measurement was used to characterize the hydrophicity of the vanadium oxide film. X-ray photoelectron spectroscopy analysis was conducted to study the surface of the epoxy. We further evaluated the bonding quality by peeling tests, which showed a maximum bonding strength of 100 kPa. By injecting with black ink, the plastic microfluidic device was confirmed to be well bonded with no leakage for a day under 1 atm. Finally, this proposed versatile method could bond the microfluidic device and plastic substrate together and be applied in the fabrication of some biosensors and lab-on-a-chip systems.« less

Microfabrication of plastic-PDMS microfluidic devices using polyimide release layer and selective adhesive bonding

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

Wang, Shuyu; Yu, Shifeng; Lu, Ming

In this study, we present an improved method to bond poly(dimethylsiloxane) (PDMS) with polyimide (PI) to develop flexible substrate microfluidic devices. The PI film was separately fabricated on a silicon wafer by spin coating followed by thermal treatment to avoid surface unevenness of the flexible substrate. In this way, we could also integrate flexible substrate into standard micro-electromechanical systems (MEMS) fabrication. Meanwhile, the adhesive epoxy was selectively transferred to the PDMS microfluidic device by a stamp-and-stick method to avoid epoxy clogging the microfluidic channels. To spread out the epoxy evenly on the transferring substrate, we used superhydrophilic vanadium oxide filmmore » coated glass as the transferring substrate. After the bonding process, the flexible substrate could easily be peeled off from the rigid substrate. Contact angle measurement was used to characterize the hydrophicity of the vanadium oxide film. X-ray photoelectron spectroscopy analysis was conducted to study the surface of the epoxy. We further evaluated the bonding quality by peeling tests, which showed a maximum bonding strength of 100 kPa. By injecting with black ink, the plastic microfluidic device was confirmed to be well bonded with no leakage for a day under 1 atm. Finally, this proposed versatile method could bond the microfluidic device and plastic substrate together and be applied in the fabrication of some biosensors and lab-on-a-chip systems.« less

Microfluidic sieve valves

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

Quake, Stephen R; Marcus, Joshua S; Hansen, Carl L

2015-01-13

Sieve valves for use in microfluidic device are provided. The valves are useful for impeding the flow of particles, such as chromatography beads or cells, in a microfluidic channel while allowing liquid solution to pass through the valve. The valves find particular use in making microfluidic chromatography modules.

A microfluidic device for simultaneous measurement of viscosity and flow rate of blood in a complex fluidic network

PubMed Central

Jun Kang, Yang; Yeom, Eunseop; Lee, Sang-Joon

2013-01-01

Blood viscosity has been considered as one of important biophysical parameters for effectively monitoring variations in physiological and pathological conditions of circulatory disorders. Standard previous methods make it difficult to evaluate variations of blood viscosity under cardiopulmonary bypass procedures or hemodialysis. In this study, we proposed a unique microfluidic device for simultaneously measuring viscosity and flow rate of whole blood circulating in a complex fluidic network including a rat, a reservoir, a pinch valve, and a peristaltic pump. To demonstrate the proposed method, a twin-shaped microfluidic device, which is composed of two half-circular chambers, two side channels with multiple indicating channels, and one bridge channel, was carefully designed. Based on the microfluidic device, three sequential flow controls were applied to identify viscosity and flow rate of blood, with label-free and sensorless detection. The half-circular chamber was employed to achieve mechanical membrane compliance for flow stabilization in the microfluidic device. To quantify the effect of flow stabilization on flow fluctuations, a formula of pulsation index (PI) was analytically derived using a discrete fluidic circuit model. Using the PI formula, the time constant contributed by the half-circular chamber is estimated to be 8 s. Furthermore, flow fluctuations resulting from the peristaltic pumps are completely removed, especially under periodic flow conditions within short periods (T < 10 s). For performance demonstrations, the proposed method was applied to evaluate blood viscosity with respect to varying flow rate conditions [(a) known blood flow rate via a syringe pump, (b) unknown blood flow rate via a peristaltic pump]. As a result, the flow rate and viscosity of blood can be simultaneously measured with satisfactory accuracy. In addition, the proposed method was successfully applied to identify the viscosity of rat blood, which circulates in a complex fluidic network. These observations confirm that the proposed method can be used for simultaneous measurement of viscosity and flow rate of whole blood circulating in the complex fluid network, with sensorless and label-free detection. Furthermore, the proposed method will be used in evaluating variations in the viscosity of human blood during cardiopulmonary bypass procedures or hemodialysis. PMID:24404074

A microfluidic device for simultaneous measurement of viscosity and flow rate of blood in a complex fluidic network.

PubMed

Jun Kang, Yang; Yeom, Eunseop; Lee, Sang-Joon

2013-01-01

Blood viscosity has been considered as one of important biophysical parameters for effectively monitoring variations in physiological and pathological conditions of circulatory disorders. Standard previous methods make it difficult to evaluate variations of blood viscosity under cardiopulmonary bypass procedures or hemodialysis. In this study, we proposed a unique microfluidic device for simultaneously measuring viscosity and flow rate of whole blood circulating in a complex fluidic network including a rat, a reservoir, a pinch valve, and a peristaltic pump. To demonstrate the proposed method, a twin-shaped microfluidic device, which is composed of two half-circular chambers, two side channels with multiple indicating channels, and one bridge channel, was carefully designed. Based on the microfluidic device, three sequential flow controls were applied to identify viscosity and flow rate of blood, with label-free and sensorless detection. The half-circular chamber was employed to achieve mechanical membrane compliance for flow stabilization in the microfluidic device. To quantify the effect of flow stabilization on flow fluctuations, a formula of pulsation index (PI) was analytically derived using a discrete fluidic circuit model. Using the PI formula, the time constant contributed by the half-circular chamber is estimated to be 8 s. Furthermore, flow fluctuations resulting from the peristaltic pumps are completely removed, especially under periodic flow conditions within short periods (T < 10 s). For performance demonstrations, the proposed method was applied to evaluate blood viscosity with respect to varying flow rate conditions [(a) known blood flow rate via a syringe pump, (b) unknown blood flow rate via a peristaltic pump]. As a result, the flow rate and viscosity of blood can be simultaneously measured with satisfactory accuracy. In addition, the proposed method was successfully applied to identify the viscosity of rat blood, which circulates in a complex fluidic network. These observations confirm that the proposed method can be used for simultaneous measurement of viscosity and flow rate of whole blood circulating in the complex fluid network, with sensorless and label-free detection. Furthermore, the proposed method will be used in evaluating variations in the viscosity of human blood during cardiopulmonary bypass procedures or hemodialysis.

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

PubMed

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

2016-01-21

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

Laser tweezer actuated microphotonic array devices for high resolution imaging and analysis in chip-based biosystems

NASA Astrophysics Data System (ADS)

Birkbeck, Aaron L.

A new technology is developed that functionally integrates arrays of lasers and micro-optics into microfluidic systems for the purpose of imaging, analyzing, and manipulating objects and biological cells. In general, the devices and technologies emerging from this area either lack functionality through the reliance on mechanical systems or provide a serial-based, time consuming approach. As compared to the current state of art, our all-optical design methodology has several distinguishing features, such as parallelism, high efficiency, low power, auto-alignment, and high yield fabrication methods, which all contribute to minimizing the cost of the integration process. The potential use of vertical cavity surface emitting lasers (VCSELs) for the creation of two-dimensional arrays of laser optical tweezers that perform independently controlled, parallel capture, and transport of large numbers of individual objects and biological cells is investigated. One of the primary biological applications for which VCSEL array sourced laser optical tweezers are considered is the formation of engineered tissues through the manipulation and spatial arrangement of different types of cells in a co-culture. Creating devices that combine laser optical tweezers with select micro-optical components permits optical imaging and analysis functions to take place inside the microfluidic channel. One such device is a micro-optical spatial filter whose motion and alignment is controlled using a laser optical tweezer. Unlike conventional spatial filter systems, our device utilizes a refractive optical element that is directly incorporated onto the lithographically patterned spatial filter. This allows the micro-optical spatial filter to automatically align itself in three-dimensions to the focal point of the microscope objective, where it then filters out the higher frequency additive noise components present in the laser beam. As a means of performing high resolution imaging in the microfluidic channel, we developed a novel technique that integrates the capacity of a laser tweezer to optically trap and manipulate objects in three-dimensions with the resolution-enhanced imaging capabilities of a solid immersion lens (SIL). In our design, the SIL is a free-floating device whose imaging beam, motion control and alignment is provided by a laser optical tweezer, which allows the microfluidic SIL to image in areas that are inaccessible to traditional solid immersion microscopes.

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.

Microfluidic Devices for Drug Delivery Systems and Drug Screening

PubMed Central

Kompella, Uday B.; Damiati, Safa A.

2018-01-01

Microfluidic devices present unique advantages for the development of efficient drug carrier particles, cell-free protein synthesis systems, and rapid techniques for direct drug screening. Compared to bulk methods, by efficiently controlling the geometries of the fabricated chip and the flow rates of multiphase fluids, microfluidic technology enables the generation of highly stable, uniform, monodispersed particles with higher encapsulation efficiency. Since the existing preclinical models are inefficient drug screens for predicting clinical outcomes, microfluidic platforms might offer a more rapid and cost-effective alternative. Compared to 2D cell culture systems and in vivo animal models, microfluidic 3D platforms mimic the in vivo cell systems in a simple, inexpensive manner, which allows high throughput and multiplexed drug screening at the cell, organ, and whole-body levels. In this review, the generation of appropriate drug or gene carriers including different particle types using different configurations of microfluidic devices is highlighted. Additionally, this paper discusses the emergence of fabricated microfluidic cell-free protein synthesis systems for potential use at point of care as well as cell-, organ-, and human-on-a-chip models as smart, sensitive, and reproducible platforms, allowing the investigation of the effects of drugs under conditions imitating the biological system. PMID:29462948

Design and Modelling of a Microfluidic Electro-Lysis Device with Controlling Plates

NASA Technical Reports Server (NTRS)

Jenkins, A.; Chen, C. P.; Spearing, S.; Monaco, L. A.; Steele, A.; Flores, G.

2006-01-01

Many Lab-on-Chip applications require sample pre-treatment systems. Using electric fields to perform cell-lysis in bio-MEMS systems has provided a powerful tool which can be integrated into Lab-on-a-Chip platforms. The major design considerations for electro-lysis devices include optimal geometry and placement of micro-electrodes, cell concentration, flow rates, optimal electric field (e.g. pulsed DC vs. AC), etc. To avoid electrolysis of the flowing solution at the exposed electrode surfaces, magnitudes and the applied voltages and duration of the DC pulse, or the AC frequency of the AC, have to be optimized for a given configuration. Using simulation tools for calculation of electric fields has proved very useful, for exploring alternative configurations and operating conditions for achieving electro cell-lysis. To alleviate the problem associated with low electric fields within the microfluidics channel and the high voltage demand on the contact electrode strips, two "control plates" are added to the microfluidics configuration. The principle of placing the two controlling plate-electrodes is based on the electric fields generated by a combined insulator/dielectric (gladwater) media. Surface charges are established at the insulator/dielectric interface. This paper discusses the effects of this interface charge on the modification of the electric field of the flowing liquid/cell solution.

OpenDrop: An Integrated Do-It-Yourself Platform for Personal Use of Biochips

PubMed Central

Alistar, Mirela; Gaudenz, Urs

2017-01-01

Biochips, or digital labs-on-chip, are developed with the purpose of being used by laboratory technicians or biologists in laboratories or clinics. In this article, we expand this vision with the goal of enabling everyone, regardless of their expertise, to use biochips for their own personal purposes. We developed OpenDrop, an integrated electromicrofluidic platform that allows users to develop and program their own bio-applications. We address the main challenges that users may encounter: accessibility, bio-protocol design and interaction with microfluidics. OpenDrop consists of a do-it-yourself biochip, an automated software tool with visual interface and a detailed technique for at-home operations of microfluidics. We report on two years of use of OpenDrop, released as an open-source platform. Our platform attracted a highly diverse user base with participants originating from maker communities, academia and industry. Our findings show that 47% of attempts to replicate OpenDrop were successful, the main challenge remaining the assembly of the device. In terms of usability, the users managed to operate their platforms at home and are working on designing their own bio-applications. Our work provides a step towards a future in which everyone will be able to create microfluidic devices for their personal applications, thereby democratizing parts of health care. PMID:28952524

Design and Modelling of a Microfluidic Electro-Lysis Device with Controlling Plates

NASA Astrophysics Data System (ADS)

Jenkins, A.; Chen, C. P.; Spearing, S.; Monaco, L. A.; Steele, A.; Flores, G.

2006-04-01

Many Lab-on-Chip applications require sample pre-treatment systems. Using electric fields to perform cell lysis in bio-MEMS systems has provided a powerful tool which can be integrated into Lab-on-a- Chip platforms. The major design considerations for electro-lysis devices include optimal geometry and placement of micro-electrodes, cell concentration, flow rates, optimal electric field (e.g. pulsed DC vs. AC), etc. To avoid electrolysis of the flowing solution at the exposed electrode surfaces, magnitudes and the applied voltages and duration of the DC pulse, or the AC frequency of the AC, have to be optimized for a given configuration. Using simulation tools for calculation of electric fields has proved very useful, for exploring alternative configurations and operating conditions for achieving electro cell-lysis. To alleviate the problem associated with low electric fields within the microfluidics channel and the high voltage demand on the contact electrode strips, two ''control plates'' are added to the microfluidics configuration. The principle of placing the two controlling plate-electrodes is based on the electric fields generated by a combined insulator/dielectric (glass/water) media. Surface charges are established at the insulator/dielectric interface. This paper discusses the effects of this interface charge on the modification of the electric field of the flowing liquid/cell solution.

Effects of surface properties on droplet formation inside a microfluidic device

NASA Astrophysics Data System (ADS)

Steinhaus, Ben; Shen, Amy

2004-11-01

Micro-fluidic devices offer a unique method of creating and controlling droplets on small length scales. A microfluidic device is used to study the effects of surface properties on droplet formation of a 2-phase flow system. Four phase diagrams are generated to compare the dynamics of the 2 immiscible fluid system (silicone oil and water) inside microchannels with different surface properties. Results show that the channel surface plays an important role in determining the flow patterns and the droplet formation of the 2-phase fluid system.

"Off-the-shelf" 3-D microfluidic nozzle.

PubMed

Terray, Alex; Hart, Sean J

2010-07-07

We present the construction and operation of a microfluidic nozzle created using several standard fluidic parts available commercially. By elegantly combining several pieces from a standard assembly, a capillary and a few other standard parts, we were able to develop a novel device. Using this device, precise axisymmetric flow focusing of particles was achieved and observed at the exit of the nozzle and within a connected microfluidic device several centimetres away. Sheath and core flow rates were varied to show influence and control over the width of the focused particles.

Fabricating biomedical origami: a state-of-the-art review

PubMed Central

Johnson, Meredith; Chen, Yue; Hovet, Sierra; Xu, Sheng; Wood, Bradford; Ren, Hongliang; Tokuda, Junichi; Tse, Zion Tsz Ho

2018-01-01

Purpose Origami-based biomedical device design is an emerging technology due to its ability to be deployed from a minimal foldable pattern to a larger volume. This paper aims to review state-of-the-art origami structures applied in the medical device field. Methods Publications and reports of origami structure related to medical device design from the past 10 years are reviewed and categorized according to engineering specifications, including the application field, fabrication material, size/volume, deployment method, manufacturability, and advantages. Results This paper presents an overview of the biomedical applications of devices based on origami structures, including disposable sterilization covers, cardiac catheterization, stent grafts, encapsulation and microsurgery, gastrointestinal microsurgery, laparoscopic surgical grippers, microgrippers, microfluidic devices, and drug delivery. Challenges in terms of materials and fabrication, assembly, modeling and computation design, and clinical adoptability are discussed at the end of this paper to provide guidance for future origami-based design in the medical device field. Conclusion Concepts from origami can be used to design and develop novel medical devices. Origami-based medical device design is currently progressing, with researchers improving design methods, materials, fabrication techniques, and folding efficiency. PMID:28260164

Fabricating biomedical origami: a state-of-the-art review.

PubMed

Johnson, Meredith; Chen, Yue; Hovet, Sierra; Xu, Sheng; Wood, Bradford; Ren, Hongliang; Tokuda, Junichi; Tse, Zion Tsz Ho

2017-11-01

Origami-based biomedical device design is an emerging technology due to its ability to be deployed from a minimal foldable pattern to a larger volume. This paper aims to review state-of-the-art origami structures applied in the medical device field. Publications and reports of origami structure related to medical device design from the past 10 years are reviewed and categorized according to engineering specifications, including the application field, fabrication material, size/volume, deployment method, manufacturability, and advantages. This paper presents an overview of the biomedical applications of devices based on origami structures, including disposable sterilization covers, cardiac catheterization, stent grafts, encapsulation and microsurgery, gastrointestinal microsurgery, laparoscopic surgical grippers, microgrippers, microfluidic devices, and drug delivery. Challenges in terms of materials and fabrication, assembly, modeling and computation design, and clinical adoptability are discussed at the end of this paper to provide guidance for future origami-based design in the medical device field. Concepts from origami can be used to design and develop novel medical devices. Origami-based medical device design is currently progressing, with researchers improving design methods, materials, fabrication techniques, and folding efficiency.

Packaging of electro-microfluidic devices

DOEpatents

Benavides, Gilbert L.; Galambos, Paul C.; Emerson, John A.; Peterson, Kenneth A.; Giunta, Rachel K.; Zamora, David Lee; Watson, Robert D.

2003-04-15

A new architecture for packaging surface micromachined electro-microfluidic devices is presented. This architecture relies on two scales of packaging to bring fluid to the device scale (picoliters) from the macro-scale (microliters). The architecture emulates and utilizes electronics packaging technology. The larger package consists of a circuit board with embedded fluidic channels and standard fluidic connectors (e.g. Fluidic Printed Wiring Board). The embedded channels connect to the smaller package, an Electro-Microfluidic Dual-Inline-Package (EMDIP) that takes fluid to the microfluidic integrated circuit (MIC). The fluidic connection is made to the back of the MIC through Bosch-etched holes that take fluid to surface micromachined channels on the front of the MIC. Electrical connection is made to bond pads on the front of the MIC.

Packaging of electro-microfluidic devices

DOEpatents

Benavides, Gilbert L.; Galambos, Paul C.; Emerson, John A.; Peterson, Kenneth A.; Giunta, Rachel K.; Watson, Robert D.

2002-01-01

A new architecture for packaging surface micromachined electro-microfluidic devices is presented. This architecture relies on two scales of packaging to bring fluid to the device scale (picoliters) from the macro-scale (microliters). The architecture emulates and utilizes electronics packaging technology. The larger package consists of a circuit board with embedded fluidic channels and standard fluidic connectors (e.g. Fluidic Printed Wiring Board). The embedded channels connect to the smaller package, an Electro-Microfluidic Dual-Inline-Package (EMDIP) that takes fluid to the microfluidic integrated circuit (MIC). The fluidic connection is made to the back of the MIC through Bosch-etched holes that take fluid to surface micromachined channels on the front of the MIC. Electrical connection is made to bond pads on the front of the MIC.

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

PubMed

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

2014-04-15

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

Configurable 3D-Printed millifluidic and microfluidic 'lab on a chip' reactionware devices.

PubMed

Kitson, Philip J; Rosnes, Mali H; Sans, Victor; Dragone, Vincenza; Cronin, Leroy

2012-09-21

We utilise 3D design and 3D printing techniques to fabricate a number of miniaturised fluidic 'reactionware' devices for chemical syntheses in just a few hours, using inexpensive materials producing reliable and robust reactors. Both two and three inlet reactors could be assembled, as well as one-inlet devices with reactant 'silos' allowing the introduction of reactants during the fabrication process of the device. To demonstrate the utility and versatility of these devices organic (reductive amination and alkylation reactions), inorganic (large polyoxometalate synthesis) and materials (gold nanoparticle synthesis) processes were efficiently carried out in the printed devices.

Single step sequential polydimethylsiloxane wet etching to fabricate a microfluidic channel with various cross-sectional geometries

NASA Astrophysics Data System (ADS)

Wang, C.-K.; Liao, W.-H.; Wu, H.-M.; Lo, Y.-H.; Lin, T.-R.; Tung, Y.-C.

2017-11-01

Polydimethylsiloxane (PDMS) has become a widely used material to construct microfluidic devices for various biomedical and chemical applications due to its desirable material properties and manufacturability. PDMS microfluidic devices are usually fabricated using soft lithography replica molding methods with master molds made of photolithogrpahy patterned photoresist layers on silicon wafers. The fabricated microfluidic channels often have rectangular cross-sectional geometries with single or multiple heights. In this paper, we develop a single step sequential PDMS wet etching process that can be used to fabricate microfluidic channels with various cross-sectional geometries from single-layer PDMS microfluidic channels. The cross-sections of the fabricated channel can be non-rectangular, and varied along the flow direction. Furthermore, the fabricated cross-sectional geometries can be numerically simulated beforehand. In the experiments, we fabricate microfluidic channels with various cross-sectional geometries using the developed technique. In addition, we fabricate a microfluidic mixer with alternative mirrored cross-sectional geometries along the flow direction to demonstrate the practical usage of the developed technique.

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

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.

Implementation of poly(ε-caprolactone) sheet-based shape-memory polymer microvalves into plastic-based microfluidic devices

NASA Astrophysics Data System (ADS)

Jiang, Chenyang; Uto, Koichiro; Ebara, Mitsuhiro; Aoyagi, Takao; Ichiki, Takanori

2015-06-01

Implementation of shape-memory polymer (SMP) sheet-based microvalves into plastic-based microfluidic devices has been studied toward the use in disposable and mass producible micro total analysis devices. Poly(ε-caprolactone) (PCL) and poly(methyl methacrylate-co-styrene) (MS) were used as SMP and main substrate materials, respectively. Bonding between PCL sheets and MS plates was the critical issue in the practical implementation. We found the pristine PCL sheet has relatively rough surface with Ra of 85.14 nm, which is the cause of poor bonding. Hence, by introducing the post-anneal treatment with sandwiched between two flat glass plates, the PCL surface could be smoothed to Ra of 12.50 nm, and tight bonding could be obtained. Consequently, microfluidic devices consisting of plastic/PCL/plastic layers were successfully fabricated and therein the actuation of SMP valves without any leakage was demonstrated. The present technology is expected to be applicable to disposable microfluidic devices as required for point-of-care testing.

Microfluidic devices with permeable polymer barriers for capture and transport of biomolecules and cells.

PubMed

Lee, Ho Suk; Chu, Wai Keung; Zhang, Kun; Huang, Xiaohua

2013-09-07

We report a method for fabricating permeable polymer microstructure barriers in polydimethylsiloxane (PDMS) microfluidic devices and the use of the devices to capture and transport DNA and cells. The polymer microstructure in a desired location in a fluidic channel is formed in situ by the polymerization of acrylamide and polyethylene diacrylate cross-linker (PEG-DA) monomer in a solution which is trapped in the location using a pair of PDMS valves. The porous polymer microstructure provides a mechanical barrier to convective fluid flow in the channel or between two microfluidic chambers while it still conducts ions or small charged species under an electric field, allowing for the rapid capture and transport of biomolecules and cells by electrophoresis. We have demonstrated the application of the devices for the rapid capture and efficient release of bacteriophage λ genomic DNA, solution exchange and for the transport and capture of HeLa cells. Our devices will enable the multi-step processing of biomolecules and cells or individual cells within a single microfluidic chamber.

Microfluidic device and method for focusing, segmenting, and dispensing of a fluid stream

DOEpatents

Jacobson, Stephen C [Knoxville, TN; Ramsey, J Michael [Knoxville, TN

2008-09-09

A microfluidic device and method for forming and dispensing minute volume segments of a material are described. In accordance with the present invention, a microfluidic device and method are provided for spatially confining the material in a focusing element. The device is also adapted for segmenting the confined material into minute volume segments, and dispensing a volume segment to a waste or collection channel. The device further includes means for driving the respective streams of sample and focusing fluids through respective channels into a chamber, such that the focusing fluid streams spatially confine the sample material. The device may also include additional means for driving a minute volume segment of the spatially confined sample material into a collection channel in fluid communication with the waste reservoir.

Microfluidic device and method for focusing, segmenting, and dispensing of a fluid stream

DOEpatents

Jacobson, Stephen C.; Ramsey, J. Michael

2004-09-14

A microfluidic device for forming and/or dispensing minute volume segments of a material is described. In accordance with one aspect of the present invention, a microfluidic device and method is provided for spatially confining the material in a focusing element. The device is also capable of segmenting the confined material into minute volume segments, and dispensing a volume segment to a waste or collection channel. The device further includes means for driving the respective streams of sample and focusing fluids through respective channels into a chamber, such that the focusing fluid streams spatially confine the sample material. The device may also include additional means for driving a minute volume segment of the spatially confined sample material into a collection channel in fluid communication with the waste reservoir.

Digital Microfluidics for Nucleic Acid Amplification

PubMed Central

Veigas, Bruno; Fortunato, Elvira; Martins, Rodrigo; Águas, Hugo; Igreja, Rui; Baptista, Pedro V.

2017-01-01

Digital Microfluidics (DMF) has emerged as a disruptive methodology for the control and manipulation of low volume droplets. In DMF, each droplet acts as a single reactor, which allows for extensive multiparallelization of biological and chemical reactions at a much smaller scale. DMF devices open entirely new and promising pathways for multiplex analysis and reaction occurring in a miniaturized format, thus allowing for healthcare decentralization from major laboratories to point-of-care with accurate, robust and inexpensive molecular diagnostics. Here, we shall focus on DMF platforms specifically designed for nucleic acid amplification, which is key for molecular diagnostics of several diseases and conditions, from pathogen identification to cancer mutations detection. Particular attention will be given to the device architecture, materials and nucleic acid amplification applications in validated settings. PMID:28672827

3D-templated, fully automated microfluidic input/output multiplexer for endocrine tissue culture and secretion sampling.

PubMed

Li, Xiangpeng; Brooks, Jessica C; Hu, Juan; Ford, Katarena I; Easley, Christopher J

2017-01-17

A fully automated, 16-channel microfluidic input/output multiplexer (μMUX) has been developed for interfacing to primary cells and to improve understanding of the dynamics of endocrine tissue function. The device utilizes pressure driven push-up valves for precise manipulation of nutrient input and hormone output dynamics, allowing time resolved interrogation of the cells. The ability to alternate any of the 16 channels from input to output, and vice versa, provides for high experimental flexibility without the need to alter microchannel designs. 3D-printed interface templates were custom designed to sculpt the above-channel polydimethylsiloxane (PDMS) in microdevices, creating millimeter scale reservoirs and confinement chambers to interface primary murine islets and adipose tissue explants to the μMUX sampling channels. This μMUX device and control system was first programmed for dynamic studies of pancreatic islet function to collect ∼90 minute insulin secretion profiles from groups of ∼10 islets. The automated system was also operated in temporal stimulation and cell imaging mode. Adipose tissue explants were exposed to a temporal mimic of post-prandial insulin and glucose levels, while simultaneous switching between labeled and unlabeled free fatty acid permitted fluorescent imaging of fatty acid uptake dynamics in real time over a ∼2.5 hour period. Application with varying stimulation and sampling modes on multiple murine tissue types highlights the inherent flexibility of this novel, 3D-templated μMUX device. The tissue culture reservoirs and μMUX control components presented herein should be adaptable as individual modules in other microfluidic systems, such as organ-on-a-chip devices, and should be translatable to different tissues such as liver, heart, skeletal muscle, and others.

Microfluidic engineering of neural stem cell niches for fate determination

PubMed Central

Ma, Jingyun; Li, Na; Wang, Liang; Shen, Liming; Sun, Yu; Wang, Yajun; Zhao, Jingyuan; Wei, Wenjuan; Ren, Yan; Liu, Jing

2017-01-01

Neural stem cell (NSC) transplantation has great therapeutic potential for neurodegenerative diseases and central nervous system injuries. Successful NSC replacement therapy requires precise control over the cellular behaviors. However, the regulation of NSC fate is largely unclear, which severely restricts the potential clinical applications. To develop an effective model, we designed an assembled microfluidic system to engineer NSC niches and assessed the effects of various culture conditions on NSC fate determination. Five types of NSC microenvironments, including two-dimensional (2D) cellular monolayer culture, 2D cellular monolayer culture on the extracellular matrix (ECM), dispersed cells in the ECM, three-dimensional (3D) spheroid aggregates, and 3D spheroids cultured in the ECM, were constructed within an integrated microfluidic chip simultaneously. In addition, we evaluated the influence of static and perfusion culture on NSCs. The efficiency of this approach was evaluated comprehensively by characterization of NSC viability, self-renewal, proliferation, and differentiation into neurons, astrocytes, or oligodendrocytes. Differences in the status and fate of NSCs governed by the culture modes and micro-niches were analyzed. NSCs in the microfluidic device demonstrated good viability, the 3D culture in the ECM facilitated NSC self-renewal and proliferation, and 2D culture in the static state and spheroid culture under perfusion conditions benefited NSC differentiation. Regulation of NSC self-renewal and differentiation on this microfluidic device could provide NSC-based medicinal products and references for distinct nerve disease therapy. PMID:28798841

Measurement of microchannel fluidic resistance with a standard voltage meter.

PubMed

Godwin, Leah A; Deal, Kennon S; Hoepfner, Lauren D; Jackson, Louis A; Easley, Christopher J

2013-01-03

A simplified method for measuring the fluidic resistance (R(fluidic)) of microfluidic channels is presented, in which the electrical resistance (R(elec)) of a channel filled with a conductivity standard solution can be measured and directly correlated to R(fluidic) using a simple equation. Although a slight correction factor could be applied in this system to improve accuracy, results showed that a standard voltage meter could be used without calibration to determine R(fluidic) to within 12% error. Results accurate to within 2% were obtained when a geometric correction factor was applied using these particular channels. When compared to standard flow rate measurements, such as meniscus tracking in outlet tubing, this approach provided a more straightforward alternative and resulted in lower measurement error. The method was validated using 9 different fluidic resistance values (from ∼40 to 600kPa smm(-3)) and over 30 separately fabricated microfluidic devices. Furthermore, since the method is analogous to resistance measurements with a voltage meter in electrical circuits, dynamic R(fluidic) measurements were possible in more complex microfluidic designs. Microchannel R(elec) was shown to dynamically mimic pressure waveforms applied to a membrane in a variable microfluidic resistor. The variable resistor was then used to dynamically control aqueous-in-oil droplet sizes and spacing, providing a unique and convenient control system for droplet-generating devices. This conductivity-based method for fluidic resistance measurement is thus a useful tool for static or real-time characterization of microfluidic systems. Copyright © 2012 Elsevier B.V. All rights reserved.

Measurement of Microchannel Fluidic Resistance with a Standard Voltage Meter

PubMed Central

Godwin, Leah A.; Deal, Kennon S.; Hoepfner, Lauren D.; Jackson, Louis A.; Easley, Christopher J.

2012-01-01

A simplified method for measuring the fluidic resistance (Rfluidic) of microfluidic channels is presented, in which the electrical resistance (Relec) of a channel filled with a conductivity standard solution can be measured and directly correlated to Rfluidic using a simple equation. Although a slight correction factor could be applied in this system to improve accuracy, results showed that a standard voltage meter could be used without calibration to determine Rfluidic to within 12% error. Results accurate to within 2% were obtained when a geometric correction factor was applied using these particular channels. When compared to standard flow rate measurements, such as meniscus tracking in outlet tubing, this approach provided a more straightforward alternative and resulted in lower measurement error. The method was validated using 9 different fluidic resistance values (from ~40 – 600 kPa s mm−3) and over 30 separately fabricated microfluidic devices. Furthermore, since the method is analogous to resistance measurements with a voltage meter in electrical circuits, dynamic Rfluidic measurements were possible in more complex microfluidic designs. Microchannel Relec was shown to dynamically mimic pressure waveforms applied to a membrane in a variable microfluidic resistor. The variable resistor was then used to dynamically control aqueous-in-oil droplet sizes and spacing, providing a unique and convenient control system for droplet-generating devices. This conductivity-based method for fluidic resistance measurement is thus a useful tool for static or real-time characterization of microfluidic systems. PMID:23245901

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.

Fabrication of polyimide based microfluidic channels for biosensor devices

NASA Astrophysics Data System (ADS)

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

2015-03-01

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

Double emulsions from a capillary array injection microfluidic device.

PubMed

Shang, Luoran; Cheng, Yao; Wang, Jie; Ding, Haibo; Rong, Fei; Zhao, Yuanjin; Gu, Zhongze

2014-09-21

A facile microfluidic device was developed by inserting an annular capillary array into a collection channel for single-step emulsification of double emulsions. By inserting multiple inner-phase solutions into the capillary array, multicomponent double emulsions or microcapsules with inner droplets of different content could also be obtained from the device.

Neural Stem Cell Differentiation Using Microfluidic Device-Generated Growth Factor Gradient.

PubMed

Kim, Ji Hyeon; Sim, Jiyeon; Kim, Hyun-Jung

2018-04-11

Neural stem cells (NSCs) have the ability to self-renew and differentiate into multiple nervous system cell types. During embryonic development, the concentrations of soluble biological molecules have a critical role in controlling cell proliferation, migration, differentiation and apoptosis. In an effort to find optimal culture conditions for the generation of desired cell types in vitro , we used a microfluidic chip-generated growth factor gradient system. In the current study, NSCs in the microfluidic device remained healthy during the entire period of cell culture, and proliferated and differentiated in response to the concentration gradient of growth factors (epithermal growth factor and basic fibroblast growth factor). We also showed that overexpression of ASCL1 in NSCs increased neuronal differentiation depending on the concentration gradient of growth factors generated in the microfluidic gradient chip. The microfluidic system allowed us to study concentration-dependent effects of growth factors within a single device, while a traditional system requires multiple independent cultures using fixed growth factor concentrations. Our study suggests that the microfluidic gradient-generating chip is a powerful tool for determining the optimal culture conditions.

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.

Microsphere integrated microfluidic disk: synergy of two techniques for rapid and ultrasensitive dengue detection.

PubMed

Hosseini, Samira; Aeinehvand, Mohammad M; Uddin, Shah M; Benzina, Abderazak; Rothan, Hussin A; Yusof, Rohana; Koole, Leo H; Madou, Marc J; Djordjevic, Ivan; Ibrahim, Fatimah

2015-11-09

The application of microfluidic devices in diagnostic systems is well-established in contemporary research. Large specific surface area of microspheres, on the other hand, has secured an important position for their use in bioanalytical assays. Herein, we report a combination of microspheres and microfluidic disk in a unique hybrid platform for highly sensitive and selective detection of dengue virus. Surface engineered polymethacrylate microspheres with carefully designed functional groups facilitate biorecognition in a multitude manner. In order to maximize the utility of the microspheres' specific surface area in biomolecular interaction, the microfluidic disk was equipped with a micromixing system. The mixing mechanism (microballoon mixing) enhances the number of molecular encounters between spheres and target analyte by accessing the entire sample volume more effectively, which subsequently results in signal amplification. Significant reduction of incubation time along with considerable lower detection limits were the prime motivations for the integration of microspheres inside the microfluidic disk. Lengthy incubations of routine analytical assays were reduced from 2 hours to 5 minutes while developed system successfully detected a few units of dengue virus. Obtained results make this hybrid microsphere-microfluidic approach to dengue detection a promising avenue for early detection of this fatal illness.

Macro to Nano: A Simple Method for Transporting Cultured Cells from Milliliter Scale to Nanoliter Scale

PubMed Central

Seale, Kevin T.; Faley, Shannon L.; Chamberlain, Jeff; Wikswo, John P.

2013-01-01

Microfluidic devices are well suited for the study of metabolism and paracrine and autocrine signaling because they allow steady or intermittent perfusion of biological cells at cell densities that approach those in living tissue. They also enable the study of small populations of rare cells. However, it can be difficult to introduce the cells into a microfluidic device to achieve and control such densities without damaging or clumping the cells. We describe simple procedures that address the problem of efficient introduction of cells and cell culture media into microfluidic devices using small bore polyetheretherketone (PEEK) tubing and Hamilton gastight syringes. Suspension or adherent cells grown in cell culture flasks are centrifuged and extracted directly from the centrifuge pellet into the end of the PEEK tubing by aspiration. The tube end is then coupled to pre-punched channels in the polydimethylsiloxane (PDMS) microfluidic device by friction fitting. Controlled depression of the syringe plunger expels the cells into the microfluidic device only seconds following aspiration. The gastight syringes and PEEK tubing with PEEK fittings provide a noncompliant source of pressure and suction with a rapid response time that is well suited for short-term intra-microfluidic cellular studies. The benefits of this method are its simplicity, modest expense, the short preparation time required for loading appropriate numbers of cells, and the applicability of the technique to small quantities of rare or expensive cells. This should in turn lead to new applications of microfludic devices to biology and medicine. PMID:20511682

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.

Microfluidic electrochemical reactors

DOEpatents

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

2011-03-22

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

In-air microfluidics: Drop and jet coalescence enables rapid multi-phase 3D printing

NASA Astrophysics Data System (ADS)

Visser, Claas Willem; Kamperman, Tom; Lohse, Detlef; Karperien, Marcel; University of Twente Collaboration

2016-11-01

For the first time, we connect and integrate the fields of microfluidics and additive manufacturing, by presenting a unifying technology that we call In-air microfluidics (IAMF). We impact two liquid jets or a jet and a droplet train while flying in-air, and control their coalescence and solidification. This approach enables producing monodisperse emulsions, particles, and fibers with controlled shape and size (10 to 300 µm) and production rates 100x higher than droplet microfluidics. A single device is sufficient to process a variety of materials, and to produce different particle or fiber shapes, in marked contrast to current microfluidic devices or printers. In-air microfluidics also enables rapid deposition onto substrates, for example to form 3D printed (bio)materials which are partly-liquid but still shape-stable.

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.

Over a century of neuron culture: from the hanging drop to microfluidic devices.

PubMed

Millet, Larry J; Gillette, Martha U

2012-12-01

The brain is the most intricate, energetically active, and plastic organ in the body. These features extend to its cellular elements, the neurons and glia. Understanding neurons, or nerve cells, at the cellular and molecular levels is the cornerstone of modern neuroscience. The complexities of neuron structure and function require unusual methods of culture to determine how aberrations in or between cells give rise to brain dysfunction and disease. Here we review the methods that have emerged over the past century for culturing neurons in vitro, from the landmark finding by Harrison (1910) - that neurons can be cultured outside the body - to studies utilizing culture vessels, micro-islands, Campenot and brain slice chambers, and microfluidic technologies. We conclude with future prospects for neuronal culture and considerations for advancement. We anticipate that continued innovation in culture methods will enhance design capabilities for temporal control of media and reagents (chemotemporal control) within sub-cellular environments of three-dimensional fluidic spaces (microfluidic devices) and materials (e.g., hydrogels). They will enable new insights into the complexities of neuronal development and pathology.

Over a Century of Neuron Culture: From the Hanging Drop to Microfluidic Devices

PubMed Central

Millet, Larry J.; Gillette, Martha U.

2012-01-01

The brain is the most intricate, energetically active, and plastic organ in the body. These features extend to its cellular elements, the neurons and glia. Understanding neurons, or nerve cells, at the cellular and molecular levels is the cornerstone of modern neuroscience. The complexities of neuron structure and function require unusual methods of culture to determine how aberrations in or between cells give rise to brain dysfunction and disease. Here we review the methods that have emerged over the past century for culturing neurons in vitro, from the landmark finding by Harrison (1910) — that neurons can be cultured outside the body — to studies utilizing culture vessels, micro-islands, Campenot and brain slice chambers, and microfluidic technologies. We conclude with future prospects for neuronal culture and considerations for advancement. We anticipate that continued innovation in culture methods will enhance design capabilities for temporal control of media and reagents (chemotemporal control) within sub-cellular environments of three-dimensional fluidic spaces (microfluidic devices) and materials (e.g., hydrogels). They will enable new insights into the complexities of neuronal development and pathology. PMID:23239951

Blood Perfusion in Microfluidic Models of Pulmonary Capillary Networks: Role of Geometry and Hematocrit

NASA Astrophysics Data System (ADS)

Stauber, Hagit; Waisman, Dan; Sznitman, Josue; Technion-IIT Team; Department of Neonatology Carmel Medical Center; Faculty of Medicine-Technion IIT Collaboration

2015-11-01

Microfluidic platforms are increasingly used to study blood microflows at true physiological scale due to their ability to overcome manufacturing obstacle of complex anatomical morphologies, such as the organ-specific architectures of the microcirculation. In the present work, we utilize microfluidic platforms to devise in vitro models of the underlying pulmonary capillary networks (PCN), where capillary lengths and diameters are similar to the size of RBCs (~ 5-10 μm). To better understand flow characteristics and dispersion of red blood cells (RBCs) in PCNs, we have designed microfluidic models of alveolar capillary beds inspired by the seminal ``sheet flow'' model of Fung and Sobin (1969). Our microfluidic PCNs feature confined arrays of staggered pillars with diameters of ~ 5,7 and 10 μm, mimicking the dense structure of pulmonary capillary meshes. The devices are perfused with suspensions of RBCs at varying hematocrit levels under different flow rates. Whole-field velocity patterns using micro-PIV and single-cell tracking using PTV are obtained with fluorescently-labelled RBCs and discussed. Our experiments deliver a real-scale quantitative description of RBC perfusion characteristics across the pulmonary capillary microcirculation.

Rare cell isolation and analysis in microfluidics

PubMed Central

Chen, Yuchao; Li, Peng; Huang, Po-Hsun; Xie, Yuliang; Mai, John D.; Wang, Lin; Nguyen, Nam-Trung; Huang, Tony Jun

2014-01-01

Rare cells are low-abundance cells in a much larger population of background cells. Conventional benchtop techniques have limited capabilities to isolate and analyze rare cells because of their generally low selectivity and significant sample loss. Recent rapid advances in microfluidics have been providing robust solutions to the challenges in the isolation and analysis of rare cells. In addition to the apparent performance enhancements resulting in higher efficiencies and sensitivity levels, microfluidics provides other advanced features such as simpler handling of small sample volumes and multiplexing capabilities for high-throughput processing. All of these advantages make microfluidics an excellent platform to deal with the transport, isolation, and analysis of rare cells. Various cellular biomarkers, including physical properties, dielectric properties, as well as immunoaffinities, have been explored for isolating rare cells. In this Focus article, we discuss the design considerations of representative microfluidic devices for rare cell isolation and analysis. Examples from recently published works are discussed to highlight the advantages and limitations of the different techniques. Various applications of these techniques are then introduced. Finally, a perspective on the development trends and promising research directions in this field are proposed. PMID:24406985

Multiphase flow microfluidics for the production of single or multiple emulsions for drug delivery.

PubMed

Zhao, Chun-Xia

2013-11-01

Considerable effort has been directed towards developing novel drug delivery systems. Microfluidics, capable of generating monodisperse single and multiple emulsion droplets, executing precise control and operations on these droplets, is a powerful tool for fabricating complex systems (microparticles, microcapsules, microgels) with uniform size, narrow size distribution and desired properties, which have great potential in drug delivery applications. This review presents an overview of the state-of-the-art multiphase flow microfluidics for the production of single emulsions or multiple emulsions for drug delivery. The review starts with a brief introduction of the approaches for making single and multiple emulsions, followed by presentation of some potential drug delivery systems (microparticles, microcapsules and microgels) fabricated in microfluidic devices using single or multiple emulsions as templates. The design principles, manufacturing processes and properties of these drug delivery systems are also discussed and compared. Furthermore, drug encapsulation and drug release (including passive and active controlled release) are provided and compared highlighting some key findings and insights. Finally, site-targeting delivery using multiphase flow microfluidics is also briefly introduced. Copyright © 2013 Elsevier B.V. All rights reserved.

Microfluidic Approaches to Synchrotron Radiation-Based Fourier Transform Infrared (SR-FTIR) Spectral Microscopy of Living Biosystems

PubMed Central

Loutherback, Kevin; Birarda, Giovanni; Chen, Liang; Holman, Hoi-Ying N.

2016-01-01

A long-standing desire in biological and biomedical sciences is to be able to probe cellular chemistry as biological processes are happening inside living cells. Synchrotron radiation-based Fourier transform infrared (SR-FTIR) spectral microscopy is a label-free and nondestructive analytical technique that can provide spatiotemporal distributions and relative abundances of biomolecules of a specimen by their characteristic vibrational modes. Despite great progress in recent years, SR-FTIR imaging of living biological systems remains challenging because of the demanding requirements on environmental control and strong infrared absorption of water. To meet this challenge, microfluidic devices have emerged as a method to control the water thickness while providing a hospitable environment to measure cellular processes and responses over many hours or days. This paper will provide an overview of microfluidic device development for SR-FTIR imaging of living biological systems, provide contrast between the various techniques including closed and open-channel designs, and discuss future directions of development within this area. Even as the fundamental science and technological demonstrations develop, other ongoing issues must be addressed; for example, choosing applications whose experimental requirements closely match device capabilities, and developing strategies to efficiently complete the cycle of development. These will require imagination, ingenuity and collaboration. PMID:26732243

Microfluidic approaches to synchrotron radiation-based Fourier transform infrared (SR-FTIR) spectral microscopy of living biosystems

DOE PAGES

Loutherback, Kevin; Birarda, Giovanni; Chen, Liang; ...

2016-02-15

A long-standing desire in biological and biomedical sciences is to be able to probe cellular chemistry as biological processes are happening inside living cells. Synchrotron radiation-based Fourier transform infrared (SR-FTIR) spectral microscopy is a label-free and nondestructive analytical technique that can provide spatiotemporal distributions and relative abundances of biomolecules of a specimen by their characteristic vibrational modes. Despite great progress in recent years, SR-FTIR imaging of living biological systems remains challenging because of the demanding requirements on environmental control and strong infrared absorption of water. To meet this challenge, microfluidic devices have emerged as a method to control the watermore » thickness while providing a hospitable environment to measure cellular processes and responses over many hours or days. This paper will provide an overview of microfluidic device development for SR-FTIR imaging of living biological systems, provide contrast between the various techniques including closed and open-channel designs, and discuss future directions of development within this area. Even as the fundamental science and technological demonstrations develop, other ongoing issues must be addressed; for example, choosing applications whose experimental requirements closely match device capabilities, and developing strategies to efficiently complete the cycle of development. These will require imagination, ingenuity and collaboration.« 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.

Microfluidic approaches to synchrotron radiation-based Fourier transform infrared (SR-FTIR) spectral microscopy of living biosystems

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

Loutherback, Kevin; Birarda, Giovanni; Chen, Liang

A long-standing desire in biological and biomedical sciences is to be able to probe cellular chemistry as biological processes are happening inside living cells. Synchrotron radiation-based Fourier transform infrared (SR-FTIR) spectral microscopy is a label-free and nondestructive analytical technique that can provide spatiotemporal distributions and relative abundances of biomolecules of a specimen by their characteristic vibrational modes. Despite great progress in recent years, SR-FTIR imaging of living biological systems remains challenging because of the demanding requirements on environmental control and strong infrared absorption of water. To meet this challenge, microfluidic devices have emerged as a method to control the watermore » thickness while providing a hospitable environment to measure cellular processes and responses over many hours or days. This paper will provide an overview of microfluidic device development for SR-FTIR imaging of living biological systems, provide contrast between the various techniques including closed and open-channel designs, and discuss future directions of development within this area. Even as the fundamental science and technological demonstrations develop, other ongoing issues must be addressed; for example, choosing applications whose experimental requirements closely match device capabilities, and developing strategies to efficiently complete the cycle of development. These will require imagination, ingenuity and collaboration.« less

Microfluidic Cold-Finger Device for the Investigation of Ice-Binding Proteins.

PubMed

Haleva, Lotem; Celik, Yeliz; Bar-Dolev, Maya; Pertaya-Braun, Natalya; Kaner, Avigail; Davies, Peter L; Braslavsky, Ido

2016-09-20

Ice-binding proteins (IBPs) bind to ice crystals and control their structure, enlargement, and melting, thereby helping their host organisms to avoid injuries associated with ice growth. IBPs are useful in applications where ice growth control is necessary, such as cryopreservation, food storage, and anti-icing. The study of an IBP's mechanism of action is limited by the technological difficulties of in situ observations of molecules at the dynamic interface between ice and water. We describe herein a new, to our knowledge, apparatus designed to generate a controlled temperature gradient in a microfluidic chip, called a microfluidic cold finger (MCF). This device allows growth of a stable ice crystal that can be easily manipulated with or without IBPs in solution. Using the MCF, we show that the fluorescence signal of IBPs conjugated to green fluorescent protein is reduced upon freezing and recovers at melting. This finding strengthens the evidence for irreversible binding of IBPs to their ligand, ice. We also used the MCF to demonstrate the basal-plane affinity of several IBPs, including a recently described IBP from Rhagium inquisitor. Use of the MCF device, along with a temperature-controlled setup, provides a relatively simple and robust technique that can be widely used for further analysis of materials at the ice/water interface. Copyright © 2016. Published by Elsevier Inc.

Controlling Capillary-Driven Fluid Transport in Paper-Based Microfluidic Devices Using a Movable Valve.

PubMed

Li, Bowei; Yu, Lijuan; Qi, Ji; Fu, Longwen; Zhang, Peiqing; Chen, Lingxin

2017-06-06

This paper describes a novel strategy for fabricating the movable valve on paper-based microfluidic devices to manipulate capillary-driven fluids. The movable valve fabrication is first realized using hollow rivets as the holding center to control the paper channel in different layer movement that results in the channel's connection or disconnection. The relatively simple valve fabrication procedure is robust, versatile, and compatible with microfluidic paper-based analytical devices (μPADs) with differing levels of complexity. It is remarkable that the movable valve can be convenient and free to control fluid without the timing setting, advantages that make it user-friendly for untrained users to carry out the complex multistep operations. For the performance of the movable valve to be verified, several different designs of μPADs were tested and obtained with satisfactory results. In addition, in the proof-of-concept enzyme-linked immunosorbent assay experiments, we demonstrate the use of these valves in μPADs for the successful analysis of samples of carcino-embryonic antigen, showing good sensitivity and reproducibility. We hope this technique will open new avenues for the fabrication of paper-based valves in an easily adoptable and widely available way on μPADs and provide potential point-of-care applications in the future.

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.

Method Of Packaging And Assembling Electro-Microfluidic Devices

DOEpatents

Benavides, Gilbert L.; Galambos, Paul C.; Emerson, John A.; Peterson, Kenneth A.; Giunta, Rachel K.; Zamora, David Lee; Watson, Robert D.

2004-11-23

A new architecture for packaging surface micromachined electro-microfluidic devices is presented. This architecture relies on two scales of packaging to bring fluid to the device scale (picoliters) from the macro-scale (microliters). The architecture emulates and utilizes electronics packaging technology. The larger package consists of a circuit board with embedded fluidic channels and standard fluidic connectors (e.g. Fluidic Printed Wiring Board). The embedded channels connect to the smaller package, an Electro-Microfluidic Dual-Inline-Package (EMDIP) that takes fluid to the microfluidic integrated circuit (MIC). The fluidic connection is made to the back of the MIC through Bosch-etched holes that take fluid to surface micromachined channels on the front of the MIC. Electrical connection is made to bond pads on the front of the MIC.

A modular and low­cost 3D­-printed microfluidic device with assembly of capillaries for droplet mass production

NASA Astrophysics Data System (ADS)

Aguirre-Pablo, A. A.; Zhang, J. M.; Li, E. Q.; Thoroddsen, S. T.

2015-11-01

We report a new 3D­-printed microfluidic system with assembly of capillaries for droplet generation. The system consists of the following parts: 3D­printed Droplet Generation Units (DGUs) with embedded capillaries and two 3D-printed pyramid distributors for supplying two different fluid phases into every DGU. A single DGU consists of four independent parts: a top channel, a bottom channel, a capillary and a sealing gasket. All components are produced by 3d­printing except the capillaries, which are formed in a glass-­puller. DGUs are independent of the distributor and from each other; they can easily be assembled, replaced and modified due to its modular design which is an advantage in case of a faulty part or clogging, eliminating the need to fabricate a complete new system which is cost and time demanding. We assessed the feasibility of producing droplets in this device varying different fluid parameters, such as liquid viscosity and flow rate, which affect droplet size and generation frequency. The design and fabrication of this device is simple and low­-cost with the 3D printing technology. Due to the modular design of independent parts, low-cost fabrication and easy parallelization of multiple DGU's, this system provides great flexibility for industrial applications.

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

PubMed

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

2011-10-01

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

A microfluidic device for dry sample preservation in remote settings.

PubMed

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

2013-11-21

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

Gravity-oriented microfluidic device for uniform and massive cell spheroid formation

PubMed Central

Lee, Kangsun; Kim, Choong; Young Yang, Jae; Lee, Hun; Ahn, Byungwook; Xu, Linfeng; Yoon Kang, Ji; Oh, Kwang W.

2012-01-01

We propose a simple method for forming massive and uniform three-dimensional (3-D) cell spheroids in a multi-level structured microfluidic device by gravitational force. The concept of orienting the device vertically has allowed spheroid formation, long-term perfusion, and retrieval of the cultured spheroids by user-friendly standard pipetting. We have successfully formed, perfused, and retrieved uniform, size-controllable, well-conditioned spheroids of human embryonic kidney 293 cells (HEK 293) in the gravity-oriented microfluidic device. We expect the proposed method will be a useful tool to study in-vitro 3-D cell models for the proliferation, differentiation, and metabolism of embryoid bodies or tumours. PMID:22662098

Lifespan-on-a-chip: microfluidic chambers for performing lifelong observation of C. elegans†

PubMed Central

Hulme, S. Elizabeth; Shevkoplyas, Sergey S.; McGuigan, Alison P.; Apfeld, Javier; Fontana, Walter

2011-01-01

This article describes the fabrication of a microfluidic device for the liquid culture of many individual nematode worms (Caenorhabditis elegans) in separate chambers. Each chamber houses a single worm from the fourth larval stage until death, and enables examination of a population of individual worms for their entire adult lifespans. Adjacent to the chambers, the device includes microfluidic worm clamps, which enable periodic, temporary immobilization of each worm. The device made it possible to track changes in body size and locomotion in individual worms throughout their lifespans. This ability to perform longitudinal measurements within the device enabled the identification of age-related phenotypic changes that correlate with lifespan in C. elegans. PMID:20162234

Micro-Fluidic Chemical Reactor Systems: Development, Scale-Up and Demonstration

DTIC Science & Technology

2002-11-01

B) A ) Figure 1: Gas Phase Microreactor . ( A ) Photograph of device. (B) Top view schematic. (C) Side view across channel. ( D ) Side view along... Microreactor system showing controller, heater power, fluid mixing, and microreactor cards (as in Figure 14) in a PCI chassis... microreactor design used for gas-phase heterogeneous reactions is a microchannel device that can be integrated with a heat exchange layer for highly

Microfluidic structures and methods for integrating a functional component into a microfluidic device

DOEpatents

Simmons, Blake [San Francisco, CA; Domeier, Linda [Danville, CA; Woo, Noble [San Gabriet, CA; Shepodd, Timothy [Livermore, CA; Renzi, Ronald F [Tracy, CA

2008-04-01

Injection molding is used to form microfluidic devices with integrated functional components. One or more functional components are placed in a mold cavity which is then closed. Molten thermoplastic resin is injected into the mold and then cooled, thereby forming a solid substrate including the functional component(s). The solid substrate including the functional component(s) is then bonded to a second substrate which may include microchannels or other features.

Multi-depth valved microfluidics for biofilm segmentation

NASA Astrophysics Data System (ADS)

Meyer, M. T.; Subramanian, S.; Kim, Y. W.; Ben-Yoav, H.; Gnerlich, M.; Gerasopoulos, K.; Bentley, W. E.; Ghodssi, R.

2015-09-01

Bacterial biofilms present a societal challenge, as they occur in the majority of infections but are highly resistant to both immune mechanisms and traditional antibiotics. In the pursuit of better understanding biofilm biology for developing new treatments, there is a need for streamlined, controlled platforms for biofilm growth and evaluation. We leverage advantages of microfluidics to develop a system in which biofilms are formed and sectioned, allowing parallel assays on multiple sections of one biofilm. A microfluidic testbed with multiple depth profiles was developed to accommodate biofilm growth and sectioning by hydraulically actuated valves. In realization of the platform, a novel fabrication technique was developed for creating multi-depth microfluidic molds using sequentially patterned photoresist separated and passivated by conformal coatings using atomic layer deposition. Biofilm thickness variation within three separately tested devices was less than 13% of the average thickness in each device, while variation between devices was 23% of the average thickness. In a demonstration of parallel experiments performed on one biofilm within one device, integrated valves were used to trisect the uniform biofilms with one section maintained as a control, and two sections exposed to different concentrations of sodium dodecyl sulfate. The technology presented here for multi-depth microchannel fabrication can be used to create a host of microfluidic devices with diverse architectures. While this work focuses on one application of such a device in biofilm sectioning for parallel experimentation, the tailored architectures enabled by the fabrication technology can be used to create devices that provide new biological information.

An inkjet-printed microfluidic device for liquid-liquid extraction.

PubMed

Watanabe, Masashi

2011-04-07

A microfluidic device for liquid-liquid extraction was quickly produced using an office inkjet printer. An advantage of this method is that normal end users, who are not familiar with microfabrication, can produce their original microfluidic devices by themselves. In this method, the printer draws a line on a hydrophobic and oil repellent surface using hydrophilic ink. This line directs a fluid, such as water or xylene, to form a microchannel along the printed line. Using such channels, liquid-liquid extraction was successfully performed under concurrent and countercurrent flow conditions. © The Royal Society of Chemistry 2011

Membraneless seawater desalination

DOEpatents

Crooks, Richard A.; Knust, Kyle N.; Perdue, Robbyn K.

2018-04-03

Disclosed are microfluidic devices and systems for the desalination of water. The devices and systems can include an electrode configured to generate an electric field gradient in proximity to an intersection formed by the divergence of two microfluidic channels from an inlet channel. Under an applied bias and in the presence of a pressure driven flow of saltwater, the electric field gradient can preferentially direct ions in saltwater into one of the diverging microfluidic channels, while desalted water flows into second diverging channel. Also provided are methods of using the devices and systems described herein to decrease the salinity of water.

Microfluidic platform for single cell analysis under dynamic spatial and temporal stimulation.

PubMed

Song, Jiyoung; Ryu, Hyunryul; Chung, Minhwan; Kim, Youngtaek; Blum, Yannick; Lee, Sung Sik; Pertz, Olivier; Jeon, Noo Li

2018-05-01

Recent research on cellular responses is shifting from static observations recorded under static stimuli to real-time monitoring in a dynamic environment. Since cells sense and interact with their surrounding microenvironment, an experimental platform where dynamically changing cellular microenvironments should be recreated in vitro. There has been a lack of microfluidic devices to support spatial and temporal stimulations in a simple and robust manner. Here, we describe a microfluidic device that generates dynamic chemical gradients and pulses in both space and time using a single device. This microfluidic device provides at least 12h of continuous stimulations that can be used to observe responses from mammalian cells. Combination of the microfluidic de-vice with live-cell imaging facilitates real-time observation of dynamic cellular response at single cell level. Using stable HEK cells with biosensors, ERK (Extracellular signal-Regulated Kinase) activities were observed un-der the pulsatile and ramping stimulations of EGF (Epidermal Growth Factor). We quantified ERK activation even at extremely low EGF concentration (0.0625µg/ml), which can not be observed using conventional techniques such as western blot. Cytoskeleton re-arrangement of the 3T3 fibroblast (stable transfection with Lifeact-GFP) was compared under abrupt and gradually changing gradient of PDGF. Copyright © 2017 Elsevier B.V. All rights reserved.

Microfluidic platform for multiplexed detection in single cells and methods thereof

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

Wu, Meiye; Singh, Anup K.

The present invention relates to a microfluidic device and platform configured to conduct multiplexed analysis within the device. In particular, the device allows multiple targets to be detected on a single-cell level. Also provided are methods of performing multiplexed analyses to detect one or more target nucleic acids, proteins, and post-translational modifications.

Tissue Equivalents Based on Cell-Seeded Biodegradable Microfluidic Constructs

PubMed Central

Borenstein, Jeffrey T.; Megley, Katie; Wall, Kimberly; Pritchard, Eleanor M.; Truong, David; Kaplan, David L.; Tao, Sarah L.; Herman, Ira M.

2010-01-01

One of the principal challenges in the field of tissue engineering and regenerative medicine is the formation of functional microvascular networks capable of sustaining tissue constructs. Complex tissues and vital organs require a means to support oxygen and nutrient transport during the development of constructs both prior to and after host integration, and current approaches have not demonstrated robust solutions to this challenge. Here, we present a technology platform encompassing the design, construction, cell seeding and functional evaluation of tissue equivalents for wound healing and other clinical applications. These tissue equivalents are comprised of biodegradable microfluidic scaffolds lined with microvascular cells and designed to replicate microenvironmental cues necessary to generate and sustain cell populations to replace dermal and/or epidermal tissues lost due to trauma or disease. Initial results demonstrate that these biodegradable microfluidic devices promote cell adherence and support basic cell functions. These systems represent a promising pathway towards highly integrated three-dimensional engineered tissue constructs for a wide range of clinical applications.

A versatile valving toolkit for automating fluidic operations in paper microfluidic devices.

PubMed

Toley, Bhushan J; Wang, Jessica A; Gupta, Mayuri; Buser, Joshua R; Lafleur, Lisa K; Lutz, Barry R; Fu, Elain; Yager, Paul

2015-03-21

Failure to utilize valving and automation techniques has restricted the complexity of fluidic operations that can be performed in paper microfluidic devices. We developed a toolkit of paper microfluidic valves and methods for automatic valve actuation using movable paper strips and fluid-triggered expanding elements. To the best of our knowledge, this is the first functional demonstration of this valving strategy in paper microfluidics. After introduction of fluids on devices, valves can actuate automatically after a) a certain period of time, or b) the passage of a certain volume of fluid. Timing of valve actuation can be tuned with greater than 8.5% accuracy by changing lengths of timing wicks, and we present timed on-valves, off-valves, and diversion (channel-switching) valves. The actuators require ~30 μl fluid to actuate and the time required to switch from one state to another ranges from ~5 s for short to ~50 s for longer wicks. For volume-metered actuation, the size of a metering pad can be adjusted to tune actuation volume, and we present two methods - both methods can achieve greater than 9% accuracy. Finally, we demonstrate the use of these valves in a device that conducts a multi-step assay for the detection of the malaria protein PfHRP2. Although slightly more complex than devices that do not have moving parts, this valving and automation toolkit considerably expands the capabilities of paper microfluidic devices. Components of this toolkit can be used to conduct arbitrarily complex, multi-step fluidic operations on paper-based devices, as demonstrated in the malaria assay device.

A versatile valving toolkit for automating fluidic operations in paper microfluidic devices

PubMed Central

Toley, Bhushan J.; Wang, Jessica A.; Gupta, Mayuri; Buser, Joshua R.; Lafleur, Lisa K.; Lutz, Barry R.; Fu, Elain; Yager, Paul

2015-01-01

Failure to utilize valving and automation techniques has restricted the complexity of fluidic operations that can be performed in paper microfluidic devices. We developed a toolkit of paper microfluidic valves and methods for automatic valve actuation using movable paper strips and fluid-triggered expanding elements. To the best of our knowledge, this is the first functional demonstration of this valving strategy in paper microfluidics. After introduction of fluids on devices, valves can actuate automatically a) after a certain period of time, or b) after the passage of a certain volume of fluid. Timing of valve actuation can be tuned with greater than 8.5% accuracy by changing lengths of timing wicks, and we present timed on-valves, off-valves, and diversion (channel-switching) valves. The actuators require ~30 μl fluid to actuate and the time required to switch from one state to another ranges from ~5 s for short to ~50s for longer wicks. For volume-metered actuation, the size of a metering pad can be adjusted to tune actuation volume, and we present two methods – both methods can achieve greater than 9% accuracy. Finally, we demonstrate the use of these valves in a device that conducts a multi-step assay for the detection of the malaria protein PfHRP2. Although slightly more complex than devices that do not have moving parts, this valving and automation toolkit considerably expands the capabilities of paper microfluidic devices. Components of this toolkit can be used to conduct arbitrarily complex, multi-step fluidic operations on paper-based devices, as demonstrated in the malaria assay device. PMID:25606810

Magnetic Tethering of Microswimmers in Microfluidic Devices

NASA Astrophysics Data System (ADS)

Chawan, Aschvin; Jana, Saikat; Ghosh, Suvojit; Jung, Sunghwan; Puri, Ishwar

2013-03-01

Exercising control over animal locomotion is well known in the macro world. In the micro-scale world, such methods require more sophistication. We magnetize Paramecium multimicronucleatum by internalization of magnetite nanoparticles coated with bovine serum albumin (BSA). This enables control of their motion in a microfluidic device using a magnetic field. Miniature permanent magnets embedded within the device are used to tether the magnetized organisms to specific locations along a micro-channel. Ciliary beatings of the microswimmer generate shear flows nearby. We apply this setup to enhance cross-stream mixing in a microfluidic device by supplementing molecular diffusion. The device is similar to an active micromixer but requires no external power sources or artificial actuators. We optically characterize the effectiveness of the mechanism in a variety of flow situations.

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.

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

Development of a microfluidic device for cell concentration and blood cell-plasma separation.

PubMed

Maria, M Sneha; Kumar, B S; Chandra, T S; Sen, A K

2015-12-01

This work presents design, fabrication and test of a microfluidic device which employs Fahraeus-Lindqvist and Zweifach-Fung effects for cell concentration and blood cell-plasma separation. The device design comprises a straight main channel with a series of branched channels placed symmetrically on both sides of the main channel. The design implements constrictions before each junction (branching point) in order to direct cells that would have migrated closer to the wall (naturally or after liquid extraction at a junction) towards the centre of the main channel. Theoretical and numerical analysis are performed for design of the microchannel network to ensure that a minimum flow rate ratio (of 2.5:1, main channel-to-side channels) is maintained at each junction and predict flow rate at the plasma outlet. The dimensions and location of the constrictions were determined using numerical simulations. The effect of presence of constrictions before the junctions was demonstrated by comparing the performances of the device with and without constrictions. To demonstrate the performance of the device, initial experiments were performed with polystyrene microbeads (10 and 15 μm size) and droplets. Finally, the device was used for concentration of HL60 cells and separation of plasma and cells in diluted blood samples. The cell concentration and blood-plasma purification efficiency was quantified using Haemocytometer and Fluorescence-Activated Cell Sorter (FACS). A seven-fold cell concentration was obtained with HL60 cells and a purification efficiency of 70 % and plasma recovery of 80 % was observed for diluted (1:20) blood sample. FACS was used to identify cell lysis and the cell viability was checked using Trypan Blue test which showed that more than 99 % cells are alive indicating the suitability of the device for practical use. The proposed device has potential to be used as a sample preparation module in lab on chip based diagnostic platforms.