microfluidic device integrated: Topics by Science.gov

Sample records for microfluidic device integrated

Desktop aligner for fabrication of multilayer microfluidic devices.

PubMed

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

2015-07-01

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

PubMed Central

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

2015-01-01

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

PubMed

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

2010-01-12

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

PubMed

Sonker, Mukul; Knob, Radim; Sahore, Vishal; Woolley, Adam T

2017-07-01

Integration in microfluidics is important for achieving automation. Sample preconcentration integrated with separation in a microfluidic setup can have a substantial impact on rapid analysis of low-abundance disease biomarkers. Here, we have developed a microfluidic device that uses pH-mediated solid-phase extraction (SPE) for the enrichment and elution of preterm birth (PTB) biomarkers. Furthermore, this SPE module was integrated with microchip electrophoresis for combined enrichment and separation of multiple analytes, including a PTB peptide biomarker (P1). A reversed-phase octyl methacrylate monolith was polymerized as the SPE medium in polyethylene glycol diacrylate modified cyclic olefin copolymer microfluidic channels. Eluent for pH-mediated SPE of PTB biomarkers on the monolith was optimized using different pH values and ionic concentrations. Nearly 50-fold enrichment was observed in single channel SPE devices for a low nanomolar solution of P1, with great elution time reproducibility (<7% RSD). The monolith binding capacity was determined to be 400 pg (0.2 pmol). A mixture of a model peptide (FA) and a PTB biomarker (P1) was extracted, eluted, injected, and then separated by microchip electrophoresis in our integrated device with ∼15-fold enrichment. This device shows important progress towards an integrated electrokinetically operated platform for preconcentration and separation of biomarkers. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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 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.
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.
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.
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.
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.

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.
Optofluidic platforms based on surface-enhanced Raman scattering.

PubMed

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

2010-05-01

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

NASA Astrophysics Data System (ADS)

Liu, Robin H.; Grodzinski, Piotr

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

PubMed

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

2018-01-01

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

PubMed

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

2016-03-21

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

PubMed Central

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

2016-01-01

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

NASA Technical Reports Server (NTRS)

Culbertson, Christopher; Gonda, Steve; Ramsey, John Michael

2005-01-01

The ultimate goal of this project is to integrate microfluidic devices with NASA's space bioreactor systems. In such a system, the microfluidic device would provide realtime feedback control of the bioreactor by monitoring pH, glucose, and lactate levels in the cell media; and would provide an analytical capability to the bioreactor in exterrestrial environments for monitoring bioengineered cell products and health changes in cells due to environmental stressors. Such integrated systems could be used as biosentinels both in space and on planet surfaces. The objective is to demonstrate the ability of microfabricated devices to repeatedly and reproducibly perform bead cytometry experiments in micro, lunar, martian, and hypergravity (1.8g).
Irreversible, direct bonding of nanoporous polymer membranes to PDMS or glass microdevices.

PubMed

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

2010-03-07

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

PubMed

Zuo, Peng; Li, XiuJun; Dominguez, Delfina C; Ye, Bang-Ce

2013-10-07

Infectious pathogens often cause serious public health concerns throughout the world. There is an increasing demand for simple, rapid and sensitive approaches for multiplexed pathogen detection. In this paper we have developed a polydimethylsiloxane (PDMS)/paper/glass hybrid microfluidic system integrated with aptamer-functionalized graphene oxide (GO) nano-biosensors for simple, one-step, multiplexed pathogen detection. The paper substrate used in this hybrid microfluidic system facilitated the integration of aptamer biosensors on the microfluidic biochip, and avoided complicated surface treatment and aptamer probe immobilization in a PDMS or glass-only microfluidic system. Lactobacillus acidophilus was used as a bacterium model to develop the microfluidic platform with a detection limit of 11.0 cfu mL(-1). We have also successfully extended this method to the simultaneous detection of two infectious pathogens - Staphylococcus aureus and Salmonella enterica. This method is simple and fast. The one-step 'turn on' pathogen assay in a ready-to-use microfluidic device only takes ~10 min to complete on the biochip. Furthermore, this microfluidic device has great potential in rapid detection of a wide variety of different other bacterial and viral pathogens.
A PDMS/paper/glass hybrid microfluidic biochip integrated with aptamer-functionalized graphene oxide nano-biosensors for one-step multiplexed pathogen detection

PubMed Central

Zuo, Peng; Dominguez, Delfina C.; Ye, Bang-Ce

2014-01-01

Infectious pathogens often cause serious public health concerns throughout the world. There is an increasing demand for simple, rapid and sensitive approaches for multiplexed pathogen detection. In this paper we have developed a polydimethylsiloxane (PDMS)/paper/glass hybrid microfluidic system integrated with aptamer-functionalized graphene oxide (GO) nano-biosensors for simple, one-step, multiplexed pathogen detection. The paper substrate used in this hybrid microfluidic system facilitated the integration of aptamer biosensors on the microfluidic biochip, and avoided complicated surface treatment and aptamer probe immobilization in a PDMS or glass-only microfluidic system. Lactobacillus acidophilus was used as a bacterium model to develop the microfluidic platform with a detection limit of 11.0 cfu mL−1. We have also successfully extended this method to the simultaneous detection of two infectious pathogens - Staphylococcus aureus and Salmonella enterica. This method is simple and fast. The one-step ‘turn on’ pathogen assay in a ready-to-use microfluidic device only takes ~10 min to complete on the biochip. Furthermore, this microfluidic device has great potential in rapid detection of a wide variety of different other bacterial and viral pathogens. PMID:23929394

Biosensors-on-chip: a topical review

NASA Astrophysics Data System (ADS)

Chen, Sensen; Shamsi, Mohtashim H.

2017-08-01

This review will examine the integration of two fields that are currently at the forefront of science, i.e. biosensors and microfluidics. As a lab-on-a-chip (LOC) technology, microfluidics has been enriched by the integration of various detection tools for analyte detection and quantitation. The application of such microfluidic platforms is greatly increased in the area of biosensors geared towards point-of-care diagnostics. Together, the merger of microfluidics and biosensors has generated miniaturized devices for sample processing and sensitive detection with quantitation. We believe that microfluidic biosensors (biosensors-on-chip) are essential for developing robust and cost effective point-of-care diagnostics. This review is relevant to a variety of disciplines, such as medical science, clinical diagnostics, LOC technologies including MEMs/NEMs, and analytical science. Specifically, this review will appeal to scientists working in the two overlapping fields of biosensors and microfluidics, and will also help new scientists to find their directions in developing point-of-care devices.
Validation of long-term primary neuronal cultures and network activity through the integration of reversibly bonded microbioreactors and MEA substrates.

PubMed

Biffi, Emilia; Menegon, Andrea; Piraino, Francesco; Pedrocchi, Alessandra; Fiore, Gianfranco B; Rasponi, Marco

2012-01-01

In vitro recording of neuronal electrical activity is a widely used technique to understand brain functions and to study the effect of drugs on the central nervous system. The integration of microfluidic devices with microelectrode arrays (MEAs) enables the recording of networks activity in a controlled microenvironment. In this work, an integrated microfluidic system for neuronal cultures was developed, reversibly coupling a PDMS microfluidic device with a commercial flat MEA through magnetic forces. Neurons from mouse embryos were cultured in a 100 µm channel and their activity was followed up to 18 days in vitro. The maturation of the networks and their morphological and functional characteristics were comparable with those of networks cultured in macro-environments and described in literature. In this work, we successfully demonstrated the ability of long-term culturing of primary neuronal cells in a reversible bonded microfluidic device (based on magnetism) that will be fundamental for neuropharmacological studies. Copyright © 2011 Wiley Periodicals, Inc.
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.
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.
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
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.
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.
Microfluidic device for acoustic cell lysis

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

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

2015-08-04

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

PubMed Central

Bou Chakra, Elie; Hannes, Benjamin; Vieillard, Julien; Mansfield, Colin D.; Mazurczyk, Radoslav; Bouchard, Aude; Potempa, Jan; Krawczyk, Stanislas; Cabrera, Michel

2009-01-01

A novel approach to integrating biochip and microfluidic devices is reported in which microcontact printing is a key fabrication technique. The process is performed using an automated microcontact printer that has been developed as an application-specific tool. As proof-of-concept the instrument is used to consecutively and selectively graft patterns of antibodies at the bottom of a glass channel for use in microfluidic immunoassays. Importantly, feature collapse due to over compression of the PDMS stamp is avoided by fine control of the stamp’s compression during contact. The precise alignment of biomolecules at the intersection of microfluidic channel and integrated optical waveguides has been achieved, with antigen detection performed via fluorescence excitation. Thus, it has been demonstrated that this technology permits sequential microcontact printing of isolated features consisting of functional biomolecules at any position along a microfluidic channel and also that it is possible to precisely align these features with existing components. PMID:20161128
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.
Fabrication of a microfluidic chip by UV bonding at room temperature for integration of temperature-sensitive layers

NASA Astrophysics Data System (ADS)

Schlautmann, S.; Besselink, G. A. J.; Radhakrishna Prabhu, G.; Schasfoort, R. B. M.

2003-07-01

A method for the bonding of a microfluidic device at room temperature is presented. The wafer with the fluidic structures was bonded to a sensor wafer with gold pads by means of adhesive bonding, utilizing an UV-curable glue layer. To avoid filling the fluidic channels with the glue, a stamping process was developed which allows the selective application of a thin glue layer. In this way a microfluidic glass chip was fabricated that could be used for performing surface plasmon resonance measurements without signs of leakage. The advantage of this method is the possibility of integration of organic layers as well as other temperature-sensitive layers into a microfluidic glass device.
Spintronic microfluidic platform for biomedical and environmental applications

NASA Astrophysics Data System (ADS)

Cardoso, F. A.; Martins, V. C.; Fonseca, L. P.; Germano, J.; Sousa, L. A.; Piedade, M. S.; Freitas, P. P.

2010-09-01

Faster, more sensitive and easy to operate biosensing devices still are a need at important areas such as biomedical diagnostics, food control and environmental monitoring. Recently, spintronic-devices have emerged as a promising alternative to the existent technologies [1-3]. A number of advantages, namely high sensitivity, easy integration, miniaturization, scalability, robustness and low cost make these devices potentially capable of responding to the existent technological need. In parallel, the field of microfluidics has shown great advances [4]. Microfluidic systems allow the analysis of small sample volumes (from micro- down to pico-liters), often by automate sample processing with the ability to integrate several steps into a single device (analyte amplification, concentration, separation and/or labeling), all in a reduced assay time (minutes to hours) and affordable cost. The merging of these two technologies, magnetoresistive biochips and microfluidics, will enable the development of highly competitive devices. This work reports the integration of a magnetoresistive biochip with a microfluidic system inside a portable and autonomous electronic platform aiming for a fully integrated device. A microfluidic structure fabricated in polydimethylsiloxane with dimensions of W: 0.5mm, H: 0.1mm, L: 10mm, associated to a mechanical system to align and seal the channel by pressure is presented (Fig. 1) [5]. The goal is to perform sample loading and transportation over the chip and simultaneously control the stringency and uniformity of the wash-out process. The biochip output is acquired by an electronic microsystem incorporating the circuitry to control, address and read-out the 30 spin-valve sensors sequentially (Fig. 1) [2]. This platform is being applied to the detection of water-borne microbial pathogens (e.g. Salmonella and Escherichia coli) and genetic diseases diagnosis (e.g. cystic fibrosis) through DNA hybridization assays. Open chamber measurements were performed as described elsewhere [2]. Briefly, a 20 μl sample droplet is manually dispensed over the chip, limited by a polymeric frame. When using the microfluidic system for sample loading, a known volume of sample is introduced into the fluidic system through the help of a syringe pump at a controlled velocity.
Mixing in microfluidic devices and enhancement methods

PubMed Central

Ward, Kevin; Fan, Z Hugh

2015-01-01

Mixing in microfluidic devices presents a challenge due to laminar flows in microchannels, which result from low Reynolds numbers determined by the channel’s hydraulic diameter, flow velocity, and solution’s kinetic viscosity. To address this challenge, novel methods of mixing enhancement within microfluidic devices have been explored for a variety of applications. Passive mixing methods have been created, including those using ridges or slanted wells within the microchannels, as well as their variations with improved performance by varying geometry and patterns, by changing the properties of channel surfaces, and by optimization via simulations. In addition, active mixing methods including microstirrers, acoustic mixers, and flow pulsation have been investigated and integrated into microfluidic devices to enhance mixing in a more controllable manner. In general, passive mixers are easy to integrate, but difficult to control externally by users after fabrication. Active mixers usually take efforts to integrate within a device and they require external components (e.g. power sources) to operate. However, they can be controlled by users to a certain degree for tuned mixing. In this article, we provide a general overview of a number of passive and active mixers, discuss their advantages and disadvantages, and make suggestions on choosing a mixing method for a specific need as well as advocate possible integration of key elements of passive and active mixers to harness the advantages of both types. PMID:26549938
Mixing in microfluidic devices and enhancement methods.

PubMed

Ward, Kevin; Fan, Z Hugh

2015-09-01

Mixing in microfluidic devices presents a challenge due to laminar flows in microchannels, which result from low Reynolds numbers determined by the channel's hydraulic diameter, flow velocity, and solution's kinetic viscosity. To address this challenge, novel methods of mixing enhancement within microfluidic devices have been explored for a variety of applications. Passive mixing methods have been created, including those using ridges or slanted wells within the microchannels, as well as their variations with improved performance by varying geometry and patterns, by changing the properties of channel surfaces, and by optimization via simulations. In addition, active mixing methods including microstirrers, acoustic mixers, and flow pulsation have been investigated and integrated into microfluidic devices to enhance mixing in a more controllable manner. In general, passive mixers are easy to integrate, but difficult to control externally by users after fabrication. Active mixers usually take efforts to integrate within a device and they require external components (e.g. power sources) to operate. However, they can be controlled by users to a certain degree for tuned mixing. In this article, we provide a general overview of a number of passive and active mixers, discuss their advantages and disadvantages, and make suggestions on choosing a mixing method for a specific need as well as advocate possible integration of key elements of passive and active mixers to harness the advantages of both types.
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.
Integrated microelectrode array and microfluidics for temperature clamp of sensory neurons in culture.

PubMed

Pearce, Thomas M; Wilson, J Adam; Oakes, S George; Chiu, Shing-Yan; Williams, Justin C

2005-01-01

A device for cell culture is presented that combines MEMS technology and liquid-phase photolithography to create a microfluidic chip that influences and records electrical cellular activity. A photopolymer channel network is formed on top of a multichannel microelectrode array. Preliminary results indicated successful local thermal control within microfluidic channels and control of lamina position over the electrode array. To demonstrate the biological application of such a device, adult dissociated dorsal root ganglion neurons with a subpopulation of thermally-sensitive cells are attached onto the electrode array. Using laminar flow, dynamic control of local temperature of the neural cells was achieved while maintaining a constant chemical culture medium. Recording the expected altered cellular activity confirms the success of the integrated device.
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.

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

PubMed Central

Rhee, Minsoung

2010-01-01

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

DOEpatents

Simmons, Blake; Domeier, Linda; Woo, Noble; Shepodd, Timothy; Renzi, Ronald F.

2014-08-19

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.
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
Lab-on-CMOS Integration of Microfluidics and Electrochemical Sensors

PubMed Central

Huang, Yue; Mason, Andrew J.

2013-01-01

This paper introduces a CMOS-microfluidics integration scheme for electrochemical microsystems. A CMOS chip was embedded into a micro-machined silicon carrier. By leveling the CMOS chip and carrier surface to within 100 nm, an expanded obstacle-free surface suitable for photolithography was achieved. Thin film metal planar interconnects were microfabricated to bridge CMOS pads to the perimeter of the carrier, leaving a flat and smooth surface for integrating microfluidic structures. A model device containing SU-8 microfluidic mixers and detection channels crossing over microelectrodes on a CMOS integrated circuit was constructed using the chip-carrier assembly scheme. Functional integrity of microfluidic structures and on-CMOS electrodes was verified by a simultaneous sample dilution and electrochemical detection experiment within multi-channel microfluidics. This lab-on-CMOS integration process is capable of high packing density, is suitable for wafer-level batch production, and opens new opportunities to combine the performance benefits of on-CMOS sensors with lab-on-chip platforms. PMID:23939616
Lab-on-CMOS integration of microfluidics and electrochemical sensors.

PubMed

Huang, Yue; Mason, Andrew J

2013-10-07

This paper introduces a CMOS-microfluidics integration scheme for electrochemical microsystems. A CMOS chip was embedded into a micro-machined silicon carrier. By leveling the CMOS chip and carrier surface to within 100 nm, an expanded obstacle-free surface suitable for photolithography was achieved. Thin film metal planar interconnects were microfabricated to bridge CMOS pads to the perimeter of the carrier, leaving a flat and smooth surface for integrating microfluidic structures. A model device containing SU-8 microfluidic mixers and detection channels crossing over microelectrodes on a CMOS integrated circuit was constructed using the chip-carrier assembly scheme. Functional integrity of microfluidic structures and on-CMOS electrodes was verified by a simultaneous sample dilution and electrochemical detection experiment within multi-channel microfluidics. This lab-on-CMOS integration process is capable of high packing density, is suitable for wafer-level batch production, and opens new opportunities to combine the performance benefits of on-CMOS sensors with lab-on-chip platforms.
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.
Integrated optical detection of autonomous capillary microfluidic immunoassays:a hand-held point-of-care prototype.

PubMed

Novo, P; Chu, V; Conde, J P

2014-07-15

The miniaturization of biosensors using microfluidics has potential in enabling the development of point-of-care devices, with the added advantages of reduced time and cost of analysis with limits-of-detection comparable to those obtained through traditional laboratory techniques. Interfacing microfluidic devices with the external world can be difficult especially in aspects involving fluid handling and the need for simple sample insertion that avoids special equipment or trained personnel. In this work we present a point-of-care prototype system by integrating capillary microfluidics with a microfabricated photodiode array and electronic instrumentation into a hand-held unit. The capillary microfluidic device is capable of autonomous and sequential fluid flow, including control of the average fluid velocity at any given point of the analysis. To demonstrate the functionality of the prototype, a model chemiluminescence ELISA was performed. The performance of the integrated optical detection in the point-of-care prototype is equal to that obtained with traditional bench-top instrumentation. The photodiode signals were acquired, displayed and processed by a simple graphical user interface using a computer connected to the microcontroller through USB. The prototype performed integrated chemiluminescence ELISA detection in about 15 min with a limit-of-detection of ≈2 nM with an antibody-antigen affinity constant of ≈2×10(7) M(-1). Copyright © 2014 Elsevier B.V. All rights reserved.
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.
Nano-islands integrated evanescence-based lab-on-a-chip on silica-on-silicon and polydimethylsiloxane hybrid platform for detection of recombinant growth hormone

PubMed Central

Ozhikandathil, J.; Packirisamy, M.

2012-01-01

Integration of nano-materials in optical microfluidic devices facilitates the realization of miniaturized analytical systems with enhanced sensing abilities for biological and chemical substances. In this work, a novel method of integration of gold nano-islands in a silica-on-silicon-polydimethylsiloxane microfluidic device is reported. The device works based on the nano-enhanced evanescence technique achieved by interacting the evanescent tail of propagating wave with the gold nano-islands integrated on the core of the waveguide resulting in the modification of the propagating UV-visible spectrum. The biosensing ability of the device is investigated by finite-difference time-domain simulation with a simplified model of the device. The performance of the proposed device is demonstrated for the detection of recombinant growth hormone based on antibody-antigen interaction. PMID:24106526
Integration of minisolenoids in microfluidic device for magnetic bead-based immunoassays

NASA Astrophysics Data System (ADS)

Liu, Yan-Jun; Guo, Shi-Shang; Zhang, Zhi-Ling; Huang, Wei-Hua; Baigl, Damien; Chen, Yong; Pang, Dai-Wen

2007-10-01

Microfluidic devices with integrated minisolenoids, microvalves, and channels have been fabricated for fast and low-volume immunoassay using superparamagnetic beads and well-known surface bioengineering protocols. A magnetic reaction area can be formed in the microchannel, featuring a high surface-to-volume ratio and low diffusion distances for the reagents to the bead surface. Such a method has the obvious advantage of easy implementation at low cost. Moreover, the minisolenoids can be switched on or off and the magnetic field intensity can be tuned on demand. Fluids can be manipulated by controlling the integrated air-pressure-actuated microvalves. Accordingly, magnetic bead-based immunoassay, as a typical example of biochemical detection and analysis, has been successfully performed on the integrated microfluidic device automatically in longitudinal mode. With a sample consumption of 0.5μl and a total assay time of less than 15min, goat immunoglobulin G was detected and the method exhibited a detection limit of 4.7ng/ml.
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.
Integrated microchip incorporating atomic magnetometer and microfluidic channel for NMR and MRI

DOEpatents

Ledbetter, Micah P [Oakland, CA; Savukov, Igor M [Los Alamos, NM; Budker, Dmitry [El Cerrito, CA; Shah, Vishal K [Plainsboro, NJ; Knappe, Svenja [Boulder, CO; Kitching, John [Boulder, CO; Michalak, David J [Berkeley, CA; Xu, Shoujun [Houston, TX; Pines, Alexander [Berkeley, CA

2011-08-09

An integral microfluidic device includes an alkali vapor cell and microfluidic channel, which can be used to detect magnetism for nuclear magnetic resonance (NMR) and magnetic resonance imaging (MRI). Small magnetic fields in the vicinity of the vapor cell can be measured by optically polarizing and probing the spin precession in the small magnetic field. This can then be used to detect the magnetic field of in encoded analyte in the adjacent microfluidic channel. The magnetism in the microfluidic channel can be modulated by applying an appropriate series of radio or audio frequency pulses upstream from the microfluidic chip (the remote detection modality) to yield a sensitive means of detecting NMR and MRI.
An integrated microfludic device for culturing and screening of Giardia lamblia.

PubMed

Zheng, Guo-Xia; Zhang, Xue-Mei; Yang, Yu-Suo; Zeng, Shu-Rui; Wei, Jun-Feng; Wang, Yun-Hua; Li, Ya-Jie

2014-02-01

In vitro culturing of trophozoites was important for research of Giardia lamblia (G. lamblia), especially in discovery of anti-Giardia agents. The current culture methods mainly suffer from lab-intension or the obstacle in standardizing the gas condition. Thus, it could benefit from a more streamlined and integrated approach. Microfluidics offers a way to accomplish this goal. Here we presented an integrated microfluidic device for culturing and screening of G. lamblia. The device consisted of a polydimethylsiloxane (PDMS) microchip with an aerobic culture system. In the microchip, the functionality of integrated concentration gradient generator (CGG) with micro-scale cell culture enables dose-response experiment to be performed in a simple and reagent-saving way. The diffusion-based culture chambers allowed growing G. lamblia at the in vivo like environment. It notable that the highly air permeable material of parallel chambers maintain uniform anaerobic environment in different chambers easily. Using this device, G. lamblia were successfully cultured and stressed on-chip. In all cases, a dose-related inhibitory response was detected. The application of this device for these purposes represents the first step in developing a completely integrated microfluidic platform for high-throughput screening and might be expanded to other assays based on in vitro culture of G. lamblia with further tests. Copyright © 2013 Elsevier Inc. All rights reserved.
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
Laser-induced fluorescence detection platform for point-of-care testing

NASA Astrophysics Data System (ADS)

Berner, Marcel; Hilbig, Urs; Schubert, Markus B.; Gauglitz, Günter

2017-08-01

Point-of-care testing (POCT) devices for continuous low-cost monitoring of critical patient parameters require miniaturized and integrated setups for performing quick high-sensitivity analyses, away from central clinical laboratories. This work presents a novel and promising laser-induced fluorescence platform for measurements in direct optical test formats that leads towards such powerful POCT devices based on fluorescence-labeled immunoassays. Ultimate sensitivity of thin film photodetectors, integrated with microfluidics, and a comprehensive optimization of all system components aim at low-level signal detection in the targeted biosensor application. The setup acquires fluorescence signals from the volume of a microfluidic channel. An innovative sandwiching process forms a flow channel in the microfluidic chips by embedding laser-cut double-sided adhesive tapes. The custom fit of amorphous silicon based photodiode arrays to the geometry of the flow channel enables miniaturization, fully adequate for POCT devices. A free-beam laser excitation with line focus provides excellent alignment stability, allows for easy and reliable swapping of the disposable microfluidic chips, and therewith greatly improves the ease of use of the resulting integrated device. As a proof-of-concept of this novel in-volume measurement approach, the limit of detection for the dye DY636-COOH in pure water as a model fluorophore is examined and found to be 26 nmol l-1 .
Optical fiber loops and helices: tools for integrated photonic device characterization and microfluidic trapping

NASA Astrophysics Data System (ADS)

Ren, Yundong; Zhang, Rui; Ti, Chaoyang; Liu, Yuxiang

2016-09-01

Tapered optical fibers can deliver guided light into and carry light out of micro/nanoscale systems with low loss and high spatial resolution, which makes them ideal tools in integrated photonics and microfluidics. Special geometries of tapered fibers are desired for probing monolithic devices in plane as well as optical manipulation of micro particles in fluids. However, for many specially shaped tapered fibers, it remains a challenge to fabricate them in a straightforward, controllable, and repeatable way. In this work, we fabricated and characterized two special geometries of tapered optical fibers, namely fiber loops and helices, that could be switched between one and the other. The fiber loops in this work are distinct from previous ones in terms of their superior mechanical stability and high optical quality factors in air, thanks to a post-annealing process. We experimentally measured an intrinsic optical quality factor of 32,500 and a finesse of 137 from a fiber loop. A fiber helix was used to characterize a monolithic cavity optomechanical device. Moreover, a microfluidic "roller coaster" was demonstrated, where microscale particles in water were optically trapped and transported by a fiber helix. Tapered fiber loops and helices can find various applications ranging from on-the-fly characterization of integrated photonic devices to particle manipulation and sorting in microfluidics.
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.
Universal microfluidic automaton for autonomous sample processing: application to the Mars Organic Analyzer.

PubMed

Kim, Jungkyu; Jensen, Erik C; Stockton, Amanda M; Mathies, Richard A

2013-08-20

A fully integrated multilayer microfluidic chemical analyzer for automated sample processing and labeling, as well as analysis using capillary zone electrophoresis is developed and characterized. Using lifting gate microfluidic control valve technology, a microfluidic automaton consisting of a two-dimensional microvalve cellular array is fabricated with soft lithography in a format that enables facile integration with a microfluidic capillary electrophoresis device. The programmable sample processor performs precise mixing, metering, and routing operations that can be combined to achieve automation of complex and diverse assay protocols. Sample labeling protocols for amino acid, aldehyde/ketone and carboxylic acid analysis are performed automatically followed by automated transfer and analysis by the integrated microfluidic capillary electrophoresis chip. Equivalent performance to off-chip sample processing is demonstrated for each compound class; the automated analysis resulted in a limit of detection of ~16 nM for amino acids. Our microfluidic automaton provides a fully automated, portable microfluidic analysis system capable of autonomous analysis of diverse compound classes in challenging environments.

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.
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.
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.
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.
Microfluidic devices with thick-film electrochemical detection

DOEpatents

Wang, Joseph; Tian, Baomin; Sahlin, Eskil

2005-04-12

An apparatus for conducting a microfluidic process and analysis, including at least one elongated microfluidic channel, fluidic transport means for transport of fluids through the microfluidic channel, and at least one thick-film electrode in fluidic connection with the outlet end of the microfluidic channel. The present invention includes an integrated on-chip combination reaction, separation and thick-film electrochemical detection microsystem, for use in detection of a wide range of analytes, and methods for the use thereof.
Integrated printed circuit board device for cell lysis and nucleic acid extraction.

PubMed

Marshall, Lewis A; Wu, Liang Li; Babikian, Sarkis; Bachman, Mark; Santiago, Juan G

2012-11-06

Preparation of raw, untreated biological samples remains a major challenge in microfluidics. We present a novel microfluidic device based on the integration of printed circuit boards and an isotachophoresis assay for sample preparation of nucleic acids from biological samples. The device has integrated resistive heaters and temperature sensors as well as a 70 μm × 300 μm × 3.7 cm microfluidic channel connecting two 15 μL reservoirs. We demonstrated this device by extracting pathogenic nucleic acids from 1 μL dispensed volume of whole blood spiked with Plasmodium falciparum. We dispensed whole blood directly onto an on-chip reservoir, and the system's integrated heaters simultaneously lysed and mixed the sample. We used isotachophoresis to extract the nucleic acids into a secondary buffer via isotachophoresis. We analyzed the convective mixing action with micro particle image velocimetry (micro-PIV) and verified the purity and amount of extracted nucleic acids using off-chip quantitative polymerase chain reaction (PCR). We achieved a clinically relevant limit of detection of 500 parasites per microliter. The system has no moving parts, and the process is potentially compatible with a wide range of on-chip hybridization or amplification assays.
Femtosecond Laser Fabrication of Monolithically Integrated Microfluidic Sensors in Glass

PubMed Central

He, Fei; Liao, Yang; Lin, Jintian; Song, Jiangxin; Qiao, Lingling; Cheng, Ya; Sugioka, Koji

2014-01-01

Femtosecond lasers have revolutionized the processing of materials, since their ultrashort pulse width and extremely high peak intensity allows high-quality micro- and nanofabrication of three-dimensional (3D) structures. This unique capability opens up a new route for fabrication of microfluidic sensors for biochemical applications. The present paper presents a comprehensive review of recent advancements in femtosecond laser processing of glass for a variety of microfluidic sensor applications. These include 3D integration of micro-/nanofluidic, optofluidic, electrofluidic, surface-enhanced Raman-scattering devices, in addition to fabrication of devices for microfluidic bioassays and lab-on-fiber sensors. This paper describes the unique characteristics of femtosecond laser processing and the basic concepts involved in femtosecond laser direct writing. Advanced spatiotemporal beam shaping methods are also discussed. Typical examples of microfluidic sensors fabricated using femtosecond lasers are then highlighted, and their applications in chemical and biological sensing are described. Finally, a summary of the technology is given and the outlook for further developments in this field is considered. PMID:25330047
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
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.
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
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.
Fabrication of microfluidic architectures for optimal flow rate and concentration measurement for lab on chip application

NASA Astrophysics Data System (ADS)

Adam, Tijjani; Hashim, U.

2017-03-01

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

PubMed

Zhang, Chenchu; Hu, Yanlei; Du, Wenqiang; Wu, Peichao; Rao, Shenglong; Cai, Ze; Lao, Zhaoxin; Xu, Bing; Ni, Jincheng; Li, Jiawen; Zhao, Gang; Wu, Dong; Chu, Jiaru; Sugioka, Koji

2016-09-13

Rapid integration of high-quality functional devices in microchannels is in highly demand for miniature lab-on-a-chip applications. This paper demonstrates the embellishment of existing microfluidic devices with integrated micropatterns via femtosecond laser MRAF-based holographic patterning (MHP) microfabrication, which proves two-photon polymerization (TPP) based on spatial light modulator (SLM) to be a rapid and powerful technology for chip functionalization. Optimized mixed region amplitude freedom (MRAF) algorithm has been used to generate high-quality shaped focus field. Base on the optimized parameters, a single-exposure approach is developed to fabricate 200 × 200 μm microstructure arrays in less than 240 ms. Moreover, microtraps, QR code and letters are integrated into a microdevice by the advanced method for particles capture and device identification. These results indicate that such a holographic laser embellishment of microfluidic devices is simple, flexible and easy to access, which has great potential in lab-on-a-chip applications of biological culture, chemical analyses and optofluidic devices.
Optimized holographic femtosecond laser patterning method towards rapid integration of high-quality functional devices in microchannels

NASA Astrophysics Data System (ADS)

Zhang, Chenchu; Hu, Yanlei; Du, Wenqiang; Wu, Peichao; Rao, Shenglong; Cai, Ze; Lao, Zhaoxin; Xu, Bing; Ni, Jincheng; Li, Jiawen; Zhao, Gang; Wu, Dong; Chu, Jiaru; Sugioka, Koji

2016-09-01

Rapid integration of high-quality functional devices in microchannels is in highly demand for miniature lab-on-a-chip applications. This paper demonstrates the embellishment of existing microfluidic devices with integrated micropatterns via femtosecond laser MRAF-based holographic patterning (MHP) microfabrication, which proves two-photon polymerization (TPP) based on spatial light modulator (SLM) to be a rapid and powerful technology for chip functionalization. Optimized mixed region amplitude freedom (MRAF) algorithm has been used to generate high-quality shaped focus field. Base on the optimized parameters, a single-exposure approach is developed to fabricate 200 × 200 μm microstructure arrays in less than 240 ms. Moreover, microtraps, QR code and letters are integrated into a microdevice by the advanced method for particles capture and device identification. These results indicate that such a holographic laser embellishment of microfluidic devices is simple, flexible and easy to access, which has great potential in lab-on-a-chip applications of biological culture, chemical analyses and optofluidic devices.
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.

Single-use thermoplastic microfluidic burst valves enabling on-chip reagent storage

PubMed Central

Rahmanian, Omid D.

2014-01-01

A simple and reliable method for fabricating single-use normally closed burst valves in thermoplastic microfluidic devices is presented, using a process flow that is readily integrated into established workflows for the fabrication of thermoplastic microfluidics. An experimental study of valve performance reveals the relationships between valve geometry and burst pressure. The technology is demonstrated in a device employing multiple valves engineered to actuate at different inlet pressures that can be generated using integrated screw pumps. On-chip storage and reconstitution of fluorescein salt sealed within defined reagent chambers are demonstrated. By taking advantage of the low gas and water permeability of cyclic olefin copolymer, the robust burst valves allow on-chip hermetic storage of reagents, making the technology well suited for the development of integrated and disposable assays for use at the point of care. PMID:25972774
Wirelessly powered microfluidic dielectrophoresis devices using printable RF circuits.

PubMed

Qiao, Wen; Cho, Gyoujin; Lo, Yu-Hwa

2011-03-21

We report the first microfluidic device integrated with a printed RF circuit so the device can be wirelessly powered by a commercially available RFID reader. For conventional dielectrophoresis devices, electrical wires are needed to connect the electric components on the microchip to external equipment such as power supplies, amplifiers, function generators, etc. Such a procedure is unfamiliar to most clinicians and pathologists who are used to working with a microscope for examination of samples on microscope slides. The wirelessly powered device reported here eliminates the entire need for wire attachments and external instruments so the operators can use the device in essentially the same manner as they do with microscope slides. The integrated circuit can be fabricated on a flexible plastic substrate at very low cost using a roll-to-roll printing method. Electrical power at 13.56 MHz transmitted by a radio-frequency identification (RFID) reader is inductively coupled to the printed RFIC and converted into 10 V DC (direct current) output, which provides sufficient power to drive a microfluidic device to manipulate biological particles such as beads and proteins via the DC dielectrophoresis (DC-DEP) effect. To our best knowledge, this is the first wirelessly powered microfluidic dielectrophoresis device. Although the work is preliminary, the device concept, the architecture, and the core technology are expected to stimulate many efforts in the future and transform the technology to a wide range of clinical and point-of-care applications. This journal is © The Royal Society of Chemistry 2011
Graphene-based inline pressure sensor integrated with microfluidic elastic tube

NASA Astrophysics Data System (ADS)

Inoue, Nagisa; Onoe, Hiroaki

2018-01-01

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

NASA Astrophysics Data System (ADS)

Perozziello, Gerardo; Candeloro, Patrizio; Coluccio, Maria Laura; Di Fabrizio, Enzo

2017-11-01

Optofluidics is a field with important applications in areas such as biotechnology, chemical synthesis and analytical chemistry. Optofluidic devices combine optical elements into microfluidic devices in ways that increase portability and sensitivity of analysis for diagnostic or screening purposes .In fact in these devices fluids give fine adaptability, mobility and accessibility to nanoscale photonic devices which otherwise could not be realized using conventional devices. This review describes several cases inwhich optical or microfluidic approaches are used to trap single cells in proximity of integrated optical sensor for being analysed.
Microfluidics Integrated Biosensors: A Leading Technology towards Lab-on-a-Chip and Sensing Applications

PubMed Central

Luka, George; Ahmadi, Ali; Najjaran, Homayoun; Alocilja, Evangelyn; DeRosa, Maria; Wolthers, Kirsten; Malki, Ahmed; Aziz, Hassan; Althani, Asmaa; Hoorfar, Mina

2015-01-01

A biosensor can be defined as a compact analytical device or unit incorporating a biological or biologically derived sensitive recognition element immobilized on a physicochemical transducer to measure one or more analytes. Microfluidic systems, on the other hand, provide throughput processing, enhance transport for controlling the flow conditions, increase the mixing rate of different reagents, reduce sample and reagents volume (down to nanoliter), increase sensitivity of detection, and utilize the same platform for both sample preparation and detection. In view of these advantages, the integration of microfluidic and biosensor technologies provides the ability to merge chemical and biological components into a single platform and offers new opportunities for future biosensing applications including portability, disposability, real-time detection, unprecedented accuracies, and simultaneous analysis of different analytes in a single device. This review aims at representing advances and achievements in the field of microfluidic-based biosensing. The review also presents examples extracted from the literature to demonstrate the advantages of merging microfluidic and biosensing technologies and illustrate the versatility that such integration promises in the future biosensing for emerging areas of biological engineering, biomedical studies, point-of-care diagnostics, environmental monitoring, and precision agriculture. PMID:26633409
Tunable Microfluidic Devices for Hydrodynamic Fractionation of Cells and Beads: A Review

PubMed Central

Alvankarian, Jafar; Majlis, Burhanuddin Yeop

2015-01-01

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

PubMed

Ozhikandathil, Jayan; Badilescu, Simona; Packirisamy, Muthukumaran

2017-01-01

Lab-on-chip technology is attracting great interest due to its potential as miniaturized devices that can automate and integrate many sample-handling steps, minimize consumption of reagent and samples, have short processing time and enable multiplexed analysis. Microfluidic devices have demonstrated their potential for a broad range of applications in life sciences, including point-of-care diagnostics and personalized medicine, based on the routine diagnosis of levels of hormones, cancer markers, and various metabolic products in blood, serum, etc. Microfluidics offers an adaptable platform that can facilitate cell culture as well as monitor their activity and control the cellular environment. Signaling molecules released from cells such as neurotransmitters and hormones are important in assessing the health of cells and the effect of drugs on their functions. In this review, we provide an insight into the state-of-art applications of microfluidics for monitoring of hormones released by cells. In our works, we have demonstrated efficient detection methods for bovine growth hormones using nano and microphotonics integrated microfluidics devices. The bovine growth hormone can be used as a growth promoter in dairy farming to enhance the milk and meat production. In the recent years, a few attempts have been reported on developing very sensitive, fast and low-cost methods of detection of bovine growth hormone using micro devices. This paper reviews the current state-of-art of detection and analysis of hormone using integrated optical micro and nanofluidics systems. In addition, the paper also focuses on various lab-on-a-chip technologies reported recently, and their benefits for screening growth hormones in milk.
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.
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.
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.
Contact-lens type of micromachined hydrogenated amorphous Si fluorescence detector coupled with microfluidic electrophoresis devices

NASA Astrophysics Data System (ADS)

Kamei, Toshihiro; Wada, Takehito

2006-09-01

A 5.8-μm-thick SiO2/Ta2O5 multilayer optical interference filter was monolithically integrated and micromachined on a hydrogenated amorphous Si (a-Si :H) pin photodiode to form a fluorescence detector. A microfluidic electrophoresis device was mounted on a detection platform comprising a fluorescence-collecting half-ball lens and the micromachined fluorescence detector. The central aperture of the fluorescence detector allows semiconductor laser light to pass up through the detector and to irradiate an electrophoretic separation channel. The limit of detection is as low as 7nM of the fluorescein solution, and high-speed DNA fragment sizing can be achieved with high separation efficiency. The micromachined a-Si :H fluorescence detector exhibits high sensitivity for practical fluorescent labeling dyes as well as integration flexibility on various substances, making it ideal for application to portable microfluidic bioanalysis devices.
Monolithic Integration of Two-Dimensional Liquid Chromatography-Capillary Electrophoresis and Electrospray Ionization on a Microfluidic Device

PubMed Central

Chambers, Andrew G.; Mellors, J. Scott; Henley, W. Hampton; Ramsey, J. Michael

2011-01-01

A microfluidic device capable of two-dimensional reversed-phase liquid chromatography-capillary electrophoresis with integrated electrospray ionization (LC-CE-ESI) for mass spectrometry (MS)-based proteomic applications is described. Traditional instrumentation was used for the LC sample injection and delivery of the LC mobile phase. The glass microfabricated device incorporated a sample-trapping region and an LC channel packed with reversed-phase particles. Rapid electrokinetic injections of the LC effluent into the CE dimension were performed at a cross channel intersection. The CE separation channel terminated at a corner of the square device, which functioned as an integrated electrospray tip. In addition to LC-CE-ESI, this device was used for LC-ESI without any instrumental modifications. To evaluate the system, LC-MS and LC-CE-MS analysis of protein digests were performed and compared. PMID:21214194
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.
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
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
Fluid control structures in microfluidic devices

DOEpatents

Mathies, Richard A.; Grover, William H.; Skelley, Alison; Lagally, Eric; Liu, Chung N.

2008-11-04

Methods and apparatus for implementing microfluidic analysis devices are provided. A monolithic elastomer membrane associated with an integrated pneumatic manifold allows the placement and actuation of a variety of fluid control structures, such as structures for pumping, isolating, mixing, routing, merging, splitting, preparing, and storing volumes of fluid. The fluid control structures can be used to implement a variety of sample introduction, preparation, processing, and storage techniques.
Fluid control structures in microfluidic devices

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

Mathies, Richard A.; Grover, William H.; Skelley, Alison

2017-05-09

Methods and apparatus for implementing microfluidic analysis devices are provided. A monolithic elastomer membrane associated with an integrated pneumatic manifold allows the placement and actuation of a variety of fluid control structures, such as structures for pumping, isolating, mixing, routing, merging, splitting, preparing, and storing volumes of fluid. The fluid control structures can be used to implement a variety of sample introduction, preparation, processing, and storage techniques.
Fluid control structures in microfluidic devices

NASA Technical Reports Server (NTRS)

Skelley, Alison (Inventor); Mathies, Richard A. (Inventor); Lagally, Eric (Inventor); Grover, William H. (Inventor); Liu, Chung N. (Inventor)

2008-01-01

Methods and apparatus for implementing microfluidic analysis devices are provided. A monolithic elastomer membrane associated with an integrated pneumatic manifold allows the placement and actuation of a variety of fluid control structures, such as structures for pumping, isolating, mixing, routing, merging, splitting, preparing, and storing volumes of fluid. The fluid control structures can be used to implement a variety of sample introduction, preparation, processing, and storage techniques.
A high-performance polydimethylsiloxane electrospun membrane for cell culture in lab-on-a-chip.

PubMed

Moghadas, Hajar; Saidi, Mohammad Said; Kashaninejad, Navid; Nguyen, Nam-Trung

2018-03-01

Thin porous membranes are important components in a microfluidic device, serving as separators, filters, and scaffolds for cell culture. However, the fabrication and the integration of these membranes possess many challenges, which restrict their widespread applications. This paper reports a facile technique to fabricate robust membrane-embedded microfluidic devices. We integrated an electrospun membrane into a polydimethylsiloxane (PDMS) device using the simple plasma-activated bonding technique. To increase the flexibility of the membrane and to address the leakage problem, the electrospun membrane was fabricated with the highest weight ratio of PDMS to polymethylmethacrylate (i.e., 6:1 w/w). The membrane-integrated microfluidic device could withstand a flow rate of up to 50 μ l/min. As a proof of concept, we demonstrated that such a compartmentalized microfluidic platform could be successfully used for cell culture with the capability of providing a more realistic in vivo -like condition. Human lung cancer epithelial cells (A549) were seeded on the membrane from the top microchannel, while the continuous flow of the culture medium through the bottom microchannel provided a shear-free cell culture condition. The tortuous micro-/nanofibers of the membrane immobilized the cells within the hydrophobic micropores and with no need of extracellular matrix for cell adhesion and cell growth. The hydrophobic surface conditions of the membrane were suitable for anchorage-independent cell types. To further extend the application of the device, we qualitatively showed that rinsing the membrane with ethanol prior to cell seeding could temporarily render the membrane hydrophilic and the platform could also be used for anchorage-dependent cells. Due to the three-dimensional (3D) topography of the membranes, three different configurations were observed, including individual single cells, monolayer cells, and 3D cell clusters. This cost-effective and robust compartmentalized microfluidic device may open up new avenues in translational medicine and pharmacodynamics research.

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.
A programmable microfluidic static droplet array for droplet generation, transportation, fusion, storage, and retrieval.

PubMed

Jin, Si Hyung; Jeong, Heon-Ho; Lee, Byungjin; Lee, Sung Sik; Lee, Chang-Soo

2015-01-01

We present a programmable microfluidic static droplet array (SDA) device that can perform user-defined multistep combinatorial protocols. It combines the passive storage of aqueous droplets without any external control with integrated microvalves for discrete sample dispensing and dispersion-free unit operation. The addressable picoliter-volume reaction is systematically achieved by consecutively merging programmable sequences of reagent droplets. The SDA device is remarkably reusable and able to perform identical enzyme kinetic experiments at least 30 times via automated cross-contamination-free removal of droplets from individual hydrodynamic traps. Taking all these features together, this programmable and reusable universal SDA device will be a general microfluidic platform that can be reprogrammed for multiple applications.
Optimization of monolithic columns for microfluidic devices

NASA Astrophysics Data System (ADS)

Pagaduan, Jayson V.; Yang, Weichun; Woolley, Adam T.

2011-06-01

Monolithic columns offer advantages as solid-phase extractors because they offer high surface area that can be tailored to a specific function, fast mass transport, and ease of fabrication. Porous glycidyl methacrylate-ethylene glycol dimethacrylate monoliths were polymerized in-situ in microfluidic devices, without pre-treatment of the poly(methyl methacrylate) channel surface. Cyclohexanol, 1-dodecanol and Tween 20 were used to control the pore size of the monoliths. The epoxy groups on the monolith surface can be utilized to immobilize target-specific probes such as antibodies, aptamers, or DNA for biomarker detection. Microfluidic devices integrated with solid-phase extractors should be useful for point-of-care diagnostics in detecting specific biomarkers from complex biological fluids.
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.
Integration of a Miniature Quartz Crystal Microbalance with a Microfluidic Chip for Amyloid Beta-Aβ42 Quantitation

PubMed Central

Tao, Wenyan; Xie, Qingji; Wang, Hairui; Ke, Shanming; Lin, Peng; Zeng, Xierong

2015-01-01

A miniature quartz crystal microbalance (mQCM) was integrated with a polydimethylsiloxane (PDMS) microfluidic device for on-chip determination of amyloid polypeptide–Aβ42. The integration techniques included photolithography and plasma coupling. Aβ42 antibody was immobilized on the mQCM surface using a cross-linker method, and the resonance frequency of mQCM shifted negatively due to antibody-antigen binding. A linear range from 0.1 µM to 3.2 µM was achieved. By using matrix elimination buffer, i.e., matrix phosphate buffer containing 500 µg/mL dextran and 0.5% Tween 20, Aβ42 could be successfully detected in the presence of 75% human serum. Additionally, high temperature treatments at 150 °C provided a valid method to recover mQCM, and PDMS-mQCM microfluidic device could be reused to some extent. Since the detectable Aβ42 concentration could be as low as 0.1 µM, which is close to cut-off value for Alzheimer patients, the PDMS-mQCM device could be applied in early Alzheimer’s disease diagnosis. PMID:26473864
Three-dimensional fit-to-flow microfluidic assembly.

PubMed

Chen, Arnold; Pan, Tingrui

2011-12-01

Three-dimensional microfluidics holds great promise for large-scale integration of versatile, digitalized, and multitasking fluidic manipulations for biological and clinical applications. Successful translation of microfluidic toolsets to these purposes faces persistent technical challenges, such as reliable system-level packaging, device assembly and alignment, and world-to-chip interface. In this paper, we extended our previously established fit-to-flow (F2F) world-to-chip interconnection scheme to a complete system-level assembly strategy that addresses the three-dimensional microfluidic integration on demand. The modular F2F assembly consists of an interfacial chip, pluggable alignment modules, and multiple monolithic layers of microfluidic channels, through which convoluted three-dimensional microfluidic networks can be easily assembled and readily sealed with the capability of reconfigurable fluid flow. The monolithic laser-micromachining process simplifies and standardizes the fabrication of single-layer pluggable polymeric modules, which can be mass-produced as the renowned Lego(®) building blocks. In addition, interlocking features are implemented between the plug-and-play microfluidic chips and the complementary alignment modules through the F2F assembly, resulting in facile and secure alignment with average misalignment of 45 μm. Importantly, the 3D multilayer microfluidic assembly has a comparable sealing performance as the conventional single-layer devices, providing an average leakage pressure of 38.47 kPa. The modular reconfigurability of the system-level reversible packaging concept has been demonstrated by re-routing microfluidic flows through interchangeable modular microchannel layers.
Optimized holographic femtosecond laser patterning method towards rapid integration of high-quality functional devices in microchannels

PubMed Central

Zhang, Chenchu; Hu, Yanlei; Du, Wenqiang; Wu, Peichao; Rao, Shenglong; Cai, Ze; Lao, Zhaoxin; Xu, Bing; Ni, Jincheng; Li, Jiawen; Zhao, Gang; Wu, Dong; Chu, Jiaru; Sugioka, Koji

2016-01-01

Rapid integration of high-quality functional devices in microchannels is in highly demand for miniature lab-on-a-chip applications. This paper demonstrates the embellishment of existing microfluidic devices with integrated micropatterns via femtosecond laser MRAF-based holographic patterning (MHP) microfabrication, which proves two-photon polymerization (TPP) based on spatial light modulator (SLM) to be a rapid and powerful technology for chip functionalization. Optimized mixed region amplitude freedom (MRAF) algorithm has been used to generate high-quality shaped focus field. Base on the optimized parameters, a single-exposure approach is developed to fabricate 200 × 200 μm microstructure arrays in less than 240 ms. Moreover, microtraps, QR code and letters are integrated into a microdevice by the advanced method for particles capture and device identification. These results indicate that such a holographic laser embellishment of microfluidic devices is simple, flexible and easy to access, which has great potential in lab-on-a-chip applications of biological culture, chemical analyses and optofluidic devices. PMID:27619690
Use of Ice-Nucleating Proteins To Improve the Performance of Freeze-Thaw Valves in Microfluidic Devices.

PubMed

Gaiteri, Joseph C; Henley, W Hampton; Siegfried, Nathan A; Linz, Thomas H; Ramsey, J Michael

2017-06-06

Currently, reliable valving on integrated microfluidic devices fabricated from rigid materials is confined to expensive and complex methods. Freeze-thaw valves (FTVs) can provide a low cost, low complexity valving mechanism, but reliable implementation of them has been greatly hindered by the lack of ice nucleation sites within the valve body's small volume. Work to date has required very low temperatures (on the order of -40 °C or colder) to induce freezing without nucleation sites, making FTVs impractical due to instrument engineering challenges. Here, we report the use of ice-nucleating proteins (INPs) to induce ice formation at relatively warm temperatures in microfluidic devices. Microfluidic channels were filled with buffers containing femtomolar INP concentrations from Pseudomonas syringae. The channels were cooled externally with simple, small-footprint Peltier thermoelectric coolers (TECs), and the times required for channel freezing (valve closure) and thawing (valve opening) were measured. Under optimized conditions in plastic chips, INPs made sub-10 s actuations possible at TEC temperatures as warm as -13 °C. Additionally, INPs were found to have no discernible inhibitory effects in model enzyme-linked immunosorbent assays or polymerase chain reactions, indicating their compatibility with microfluidic systems that incorporate these widely used bioassays. FTVs with INPs provide a much needed reliable valving scheme for rigid plastic devices with low complexity, low cost, and no moving parts on the device or instrument. The reduction in freeze time, accessible actuation temperatures, chemical compatibility, and low complexity make the implementation of compact INP-based FTV arrays practical and attractive for the control of integrated biochemical assays.
Integrative Utilization of Microenvironments, Biomaterials and Computational Techniques for Advanced Tissue Engineering.

PubMed

Shamloo, Amir; Mohammadaliha, Negar; Mohseni, Mina

2015-10-20

This review aims to propose the integrative implementation of microfluidic devices, biomaterials, and computational methods that can lead to a significant progress in tissue engineering and regenerative medicine researches. Simultaneous implementation of multiple techniques can be very helpful in addressing biological processes. Providing controllable biochemical and biomechanical cues within artificial extracellular matrix similar to in vivo conditions is crucial in tissue engineering and regenerative medicine researches. Microfluidic devices provide precise spatial and temporal control over cell microenvironment. Moreover, generation of accurate and controllable spatial and temporal gradients of biochemical factors is attainable inside microdevices. Since biomaterials with tunable properties are a worthwhile option to construct artificial extracellular matrix, in vitro platforms that simultaneously utilize natural, synthetic, or engineered biomaterials inside microfluidic devices are phenomenally advantageous to experimental studies in the field of tissue engineering. Additionally, collaboration between experimental and computational methods is a useful way to predict and understand mechanisms responsible for complex biological phenomena. Computational results can be verified by using experimental platforms. Computational methods can also broaden the understanding of the mechanisms behind the biological phenomena observed during experiments. Furthermore, computational methods are powerful tools to optimize the fabrication of microfluidic devices and biomaterials with specific features. Here we present a succinct review of the benefits of microfluidic devices, biomaterial, and computational methods in the case of tissue engineering and regeneration medicine. Furthermore, some breakthroughs in biological phenomena including the neuronal axon development, cancerous cell migration and blood vessel formation via angiogenesis by virtue of the aforementioned approaches are discussed. Copyright © 2015 Elsevier B.V. All rights reserved.
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
Fabricating PFPE Membranes for Microfluidic Valves and Pumps

NASA Technical Reports Server (NTRS)

Greer, Frank; White, Victor E.; Lee, Michael C.; Willis, Peter A.; Grunthaner, Frank J.; Rolland, Jason; Rolland, Jason

2009-01-01

A process has been developed for fabricating membranes of a perfluoropolyether (PFPE) and integrating them into valves and pumps in laboratory-on-achip microfluidic devices. Membranes of poly(tetrafluoroethylene) [PTFE] and poly(dimethylsilane) [PDMS] have been considered for this purpose and found wanting. By making it possible to use PFPE instead of PTFE or PDMS, the present process expands the array of options for further development of microfluidic devices for diverse applications that could include detection of biochemicals of interest, detection of toxins and biowarfare agents, synthesis and analysis of proteins, medical diagnosis, and synthesis of fuels.
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
A Versatile Microfluidic Device for Automating Synthetic Biology.

PubMed

Shih, Steve C C; Goyal, Garima; Kim, Peter W; Koutsoubelis, Nicolas; Keasling, Jay D; Adams, Paul D; Hillson, Nathan J; Singh, Anup K

2015-10-16

New microbes are being engineered that contain the genetic circuitry, metabolic pathways, and other cellular functions required for a wide range of applications such as producing biofuels, biobased chemicals, and pharmaceuticals. Although currently available tools are useful in improving the synthetic biology process, further improvements in physical automation would help to lower the barrier of entry into this field. We present an innovative microfluidic platform for assembling DNA fragments with 10× lower volumes (compared to that of current microfluidic platforms) and with integrated region-specific temperature control and on-chip transformation. Integration of these steps minimizes the loss of reagents and products compared to that with conventional methods, which require multiple pipetting steps. For assembling DNA fragments, we implemented three commonly used DNA assembly protocols on our microfluidic device: Golden Gate assembly, Gibson assembly, and yeast assembly (i.e., TAR cloning, DNA Assembler). We demonstrate the utility of these methods by assembling two combinatorial libraries of 16 plasmids each. Each DNA plasmid is transformed into Escherichia coli or Saccharomyces cerevisiae using on-chip electroporation and further sequenced to verify the assembly. We anticipate that this platform will enable new research that can integrate this automated microfluidic platform to generate large combinatorial libraries of plasmids and will help to expedite the overall synthetic biology process.
Multiwell capillarity-based microfluidic device for the study of 3D tumour tissue-2D endothelium interactions and drug screening in co-culture models.

PubMed

Virumbrales-Muñoz, María; Ayuso, José María; Olave, Marta; Monge, Rosa; de Miguel, Diego; Martínez-Lostao, Luis; Le Gac, Séverine; Doblare, Manuel; Ochoa, Ignacio; Fernandez, Luis J

2017-09-20

The tumour microenvironment is very complex, and essential in tumour development and drug resistance. The endothelium is critical in the tumour microenvironment: it provides nutrients and oxygen to the tumour and is essential for systemic drug delivery. Therefore, we report a simple, user-friendly microfluidic device for co-culture of a 3D breast tumour model and a 2D endothelium model for cross-talk and drug delivery studies. First, we demonstrated the endothelium was functional, whereas the tumour model exhibited in vivo features, e.g., oxygen gradients and preferential proliferation of cells with better access to nutrients and oxygen. Next, we observed the endothelium structure lost its integrity in the co-culture. Following this, we evaluated two drug formulations of TRAIL (TNF-related apoptosis inducing ligand): soluble and anchored to a LUV (large unilamellar vesicle). Both diffused through the endothelium, LUV-TRAIL being more efficient in killing tumour cells, showing no effect on the integrity of endothelium. Overall, we have developed a simple capillary force-based microfluidic device for 2D and 3D cell co-cultures. Our device allows high-throughput approaches, patterning different cell types and generating gradients without specialised equipment. We anticipate this microfluidic device will facilitate drug screening in a relevant microenvironment thanks to its simple, effective and user-friendly operation.
Microfluidic Devices for Chemical and Biochemical Analysis in Microgravity

NASA Technical Reports Server (NTRS)

Roman, Gregory T.; Culbertson, Christopher T.; Meyer, Amanda; Ramsey, J. Michael; Gonda, Steven R.

2004-01-01

One often touted benefit of "Lab-on-a-Chip" devices is their potential for use in remote environments. The ultimate remote environment is outer space, and NASA has multiple needs in the area of analytical sensing capability in such an environment. In particular, we are interested in integrating microfluidic devices with NASA bioreactor systems. In such an integrated system, the microfluidic device will serve as a biosensor and be used for both feedback control and for detecting various bioproducts produced by cells cultured in the NASA bioreactors. As a first step in demonstrating the ability of microfluidic devices to operate under the extreme environmental conditions found in outer space, we constructed a portable, battery operated platform for testing under reduced gravity conditions on a NASA KC-135 reduced gravity research aircraft, (AKA "the vomit comet"). The test platform consisted of a microchip, two 0-8kV high voltage power supplies, a high voltage switch, a solid-state diode-pumped green laser, a channel photomultiplier, and an inertial mass measurement unit, all under the control of a laptop computer and powered by 10 D-cell alkaline batteries. Over the course of 4 KC-135 flights, 1817 fast electrophoretic separations of 4 amino acids and/or proteins were performed in a variety of gravitational environments including zero-G, Martian-G, lunar-G, and 2-G. Results from these experiments will be presented and discussed.
High-pressure microfluidic control in lab-on-a-chip devices using mobile polymer monoliths.

PubMed

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

2002-10-01

We have developed a nonstick polymer formulation for creating moving parts inside of microfluidic channels and have applied the technique to create piston-based devices that overcome several microfluidic flow control challenges. The parts were created bycompletely filling the channels of a glass microfluidic chip with the monomer/ solvent/initiator components of a nonstick photopolymer and then selectively exposing the chip to UV light in order to define mobile pistons (or other quasi-two-dimensional shapes) inside the channels. Stops defined in the substrate prevent the part from flushing out of the device but also provide sealing surfaces so that valves and other flow control devices are possible. Sealing against pressures greater than 30 MPa (4,500 psi) and actuation times less than 33 ms are observed. An on-chip check valve, a diverter valve, and a 10-nL pipet are demonstrated. This valving technology, coupled with high-pressure electrokinetic pumps, should make it possible to create a completely integrated HPLC system on a chip.
Microfluidic devices to enrich and isolate circulating tumor cells

PubMed Central

Myung, J. H.; Hong, S.

2015-01-01

Given the potential clinical impact of circulating tumor cells (CTCs) in blood as a clinical biomarker for diagnosis and prognosis of various cancers, a myriad of detection methods for CTCs have been recently introduced. Among those, a series of microfluidic devices are particularly promising as these uniquely offer micro-scale analytical systems that are highlighted by low consumption of samples and reagents, high flexibility to accommodate other cutting-edge technologies, precise and well-defined flow behaviors, and automation capability, presenting significant advantages over the conventional larger scale systems. In this review, we highlight the advantages of microfluidic devices and their translational potential into CTC detection methods, categorized by miniaturization of bench-top analytical instruments, integration capability with nanotechnologies, and in situ or sequential analysis of captured CTCs. This review provides a comprehensive overview of recent advances in the CTC detection achieved through application of microfluidic devices and their challenges that these promising technologies must overcome to be clinically impactful. PMID:26549749
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.
Single nanopore transport of synthetic and biological polyelectrolytes in three-dimensional hybrid microfluidic/nanofluidic devices

DOE PAGES

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

2009-01-02

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

Highly integrated autonomous lab-on-a-chip device for on-line and in situ determination of environmental chemical parameters.

PubMed

Martinez-Cisneros, Cynthia; da Rocha, Zaira; Seabra, Antonio; Valdés, Francisco; Alonso-Chamarro, Julián

2018-06-05

The successful integration of sample pretreatment stages, sensors, actuators and electronics in microfluidic devices enables the attainment of complete micro total analysis systems, also known as lab-on-a-chip devices. In this work, we present a novel monolithic autonomous microanalyzer that integrates microfluidics, electronics, a highly sensitive photometric detection system and a sample pretreatment stage consisting on an embedded microcolumn, all in the same device, for on-line determination of relevant environmental parameters. The microcolumn can be filled/emptied with any resin or powder substrate whenever required, paving the way for its application to several analytical processes: separation, pre-concentration or ionic-exchange. To promote its autonomous operation, avoiding issues caused by bubbles in photometric detection systems, an efficient monolithic bubble removal structure was also integrated. To demonstrate its feasibility, the microanalyzer was successfully used to determine nitrate and nitrite in continuous flow conditions, providing real time and continuous information.
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
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
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.
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.
Ionic electroactive polymer actuators as active microfluidic mixers

DOE PAGES

Meis, Catherine; Montazami, Reza; Hashemi, Nastaran

2015-11-06

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

DOEpatents

Van Dam, R. Michael; Shah, Gaurav; Keng, Pei-Yuin

2017-05-16

The present disclosure sets forth incorporating microfluidic chips interfaces for use with digital microfluidic processes. Methods and devices according to the present disclosure utilize compact, integrated platforms that interface with a chip upstream and downstream of the reaction, as well as between intermediate reaction steps if needed. In some embodiments these interfaces are automated, including automation of a multiple reagent process. Various reagent delivery systems and methods are also disclosed.
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.
Characterization of light-controlled Volvox as movable microvalve element assembled in multilayer microfluidic device

NASA Astrophysics Data System (ADS)

Nagai, Moeto; Oguri, Michihito; Shibata, Takayuki

2015-06-01

We report a model of a light-controlled microvalve driven by Volvox and characterization of Volvox as a movable microvalve element in a multilayer microfluidic device for development of the valve. First, a three-layer microfluidic device having a single through-hole was fabricated by a replica molding process. The fabricated devices met the requirements for experiments using Volvox. Second, we used the phototactic behavior of V. carteri and controlled its motions in a microchannel by illuminating light. V. carteri migrated to the light source in the channel. Third, a colony of V. carteri was placed on a microhole, and the colony was found to stop the flow compared to the flow without Volvox on the hole. The integration of all of the obtained findings is expected to lead to the fabrication of the proposed microvalve.
Microfluidic White Organic Light-Emitting Diode Based on Integrated Patterns of Greenish-Blue and Yellow Solvent-Free Liquid Emitters

NASA Astrophysics Data System (ADS)

Kobayashi, Naofumi; Kasahara, Takashi; Edura, Tomohiko; Oshima, Juro; Ishimatsu, Ryoichi; Tsuwaki, Miho; Imato, Toshihiko; Shoji, Shuichi; Mizuno, Jun

2015-10-01

We demonstrated a novel microfluidic white organic light-emitting diode (microfluidic WOLED) based on integrated sub-100-μm-wide microchannels. Single-μm-thick SU-8-based microchannels, which were sandwiched between indium tin oxide (ITO) anode and cathode pairs, were fabricated by photolithography and heterogeneous bonding technologies. 1-Pyrenebutyric acid 2-ethylhexyl ester (PLQ) was used as a solvent-free greenish-blue liquid emitter, while 2,8-di-tert-butyl-5,11-bis(4-tert-butylphenyl)-6,12-diphenyltetracene (TBRb)-doped PLQ was applied as a yellow liquid emitter. In order to form the liquid white light-emitting layer, the greenish-blue and yellow liquid emitters were alternately injected into the integrated microchannels. The fabricated electro-microfluidic device successfully exhibited white electroluminescence (EL) emission via simultaneous greenish-blue and yellow emissions under an applied voltage of 100 V. A white emission with Commission Internationale de l’Declairage (CIE) color coordinates of (0.40, 0.42) was also obtained; the emission corresponds to warm-white light. The proposed device has potential applications in subpixels of liquid-based microdisplays and for lighting.
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.
Note: A microfluidic freezer based on evaporative cooling of atomized aqueous microdroplets

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

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

2015-01-15

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

NASA Astrophysics Data System (ADS)

Etxebarria, Ikerne; Elizalde, Jorge; Pacios, Roberto

2016-08-01

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

PubMed Central

Tehranirokh, Masoomeh; Kouzani, Abbas Z.; Francis, Paul S.; Kanwar, Jagat R.

2013-01-01

Microfluidic technology provides precise, controlled-environment, cost-effective, compact, integrated, and high-throughput microsystems that are promising substitutes for conventional biological laboratory methods. In recent years, microfluidic cell culture devices have been used for applications such as tissue engineering, diagnostics, drug screening, immunology, cancer studies, stem cell proliferation and differentiation, and neurite guidance. Microfluidic technology allows dynamic cell culture in microperfusion systems to deliver continuous nutrient supplies for long term cell culture. It offers many opportunities to mimic the cell-cell and cell-extracellular matrix interactions of tissues by creating gradient concentrations of biochemical signals such as growth factors, chemokines, and hormones. Other applications of cell cultivation in microfluidic systems include high resolution cell patterning on a modified substrate with adhesive patterns and the reconstruction of complicated tissue architectures. In this review, recent advances in microfluidic platforms for cell culturing and proliferation, for both simple monolayer (2D) cell seeding processes and 3D configurations as accurate models of in vivo conditions, are examined. PMID:24273628
Recent Advancements towards Full-System Microfluidics

PubMed Central

Miled, Amine

2017-01-01

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

PubMed

de la Rosa, Carlos; Prakash, Ranjit; Tilley, Peter A; Fox, Julie D; Kaler, Karan V i S

2007-01-01

An integrated microfluidic system for combined manipulation, pre-concentration, and lysis of samples containing Bordetella pertussis by dielectrophoresis and electroporation has been developed and implemented. The microfluidic device was able to pre-concentrate the amount of B. pertussis cells present in 200 microl of a B. pertussis suspension stock into a 20 microl volume. The device exhibited optimal sample pre-concentration of 6.7x at a stock value of 10(3) cfu/ml and at a flow rate of 250 microl/h. Electro-disruption experiments showed that on-chip-based electroporation is an effective solution for lysis of B. pertussis cells that is easily integrated with dielectrophoresis assisted pre-concentration procedures. Pulsed voltage applied, number of pulses, and presence of potassium chloride in a B. pertussis suspension showed a reduction in B. pertussis cell viability by electroporation; and transmission electron microscopy confirmed B. pertussis cell disruption by electroporation. Genetic amplification and detection of the pre-concentrated sample employing an integrated chip-based system demonstrated a complete chip approach for pathogen detection.

Construction of oxygen and chemical concentration gradients in a single microfluidic device for studying tumor cell-drug interactions in a dynamic hypoxia microenvironment.

PubMed

Wang, Lei; Liu, Wenming; Wang, Yaolei; Wang, Jian-chun; Tu, Qin; Liu, Rui; Wang, Jinyi

2013-02-21

Recent microfluidic advancements in oxygen gradients have greatly promoted controllable oxygen-sensitive cellular investigations at microscale resolution. However, multi-gradient integration in a single microfluidic device for tissue-mimicking cell investigation is not yet well established. In this study, we describe a method that can generate oxygen and chemical concentration gradients in a single microfluidic device via the formation of an oxygen gradient in a chamber and a chemical concentration gradient between adjacent chambers. The oxygen gradient dynamics were systematically investigated, and were quantitatively controlled using simple exchange between the aerial oxygen and the oxygen-free conditions in the gas-permeable polydimethylsiloxane channel. Meanwhile, the chemical gradient dynamics was generated using a special channel-branched device. For potential medical applications of the established oxygen and chemical concentration gradients, a tumor cell therapy assessment was performed using two antitumor drugs (tirapazamine and bleomycin) and two tumor cell lines (human lung adenocarcinoma A549 cells and human cervical carcinoma HeLa cells). The results of the proof-of-concept experiment indicate the dose-dependent antitumor effect of the drugs and hypoxia-induced cytotoxicity of tirapazamine. We demonstrate that the integration of oxygen and chemical concentration gradients in a single device can be applied to investigating oxygen- and chemical-sensitive cell events, which can also be valuable in the development of multi-gradient generating procedures and specific drug screening.
Integration and application of optical chemical sensors in microbioreactors.

PubMed

Gruber, Pia; Marques, Marco P C; Szita, Nicolas; Mayr, Torsten

2017-08-08

The quantification of key variables such as oxygen, pH, carbon dioxide, glucose, and temperature provides essential information for biological and biotechnological applications and their development. Microfluidic devices offer an opportunity to accelerate research and development in these areas due to their small scale, and the fine control over the microenvironment, provided that these key variables can be measured. Optical sensors are well-suited for this task. They offer non-invasive and non-destructive monitoring of the mentioned variables, and the establishment of time-course profiles without the need for sampling from the microfluidic devices. They can also be implemented in larger systems, facilitating cross-scale comparison of analytical data. This tutorial review presents an overview of the optical sensors and their technology, with a view to support current and potential new users in microfluidics and biotechnology in the implementation of such sensors. It introduces the benefits and challenges of sensor integration, including, their application for microbioreactors. Sensor formats, integration methods, device bonding options, and monitoring options are explained. Luminescent sensors for oxygen, pH, carbon dioxide, glucose and temperature are showcased. Areas where further development is needed are highlighted with the intent to guide future development efforts towards analytes for which reliable, stable, or easily integrated detection methods are not yet available.
Microfluidics-Based Lab-on-Chip Systems in DNA-Based Biosensing: An Overview

PubMed Central

Dutse, Sabo Wada; Yusof, Nor Azah

2011-01-01

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

PubMed Central

Tentori, Augusto M.; Herr, Amy E.

2011-01-01

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

PubMed

Wu, Liang; Chen, Pu; Dong, Yingsong; Feng, Xiaojun; Liu, Bi-Feng

2013-06-01

Encapsulation of single cells is a challenging task in droplet microfluidics due to the random compartmentalization of cells dictated by Poisson statistics. In this paper, a microfluidic device was developed to improve the single-cell encapsulation rate by integrating droplet generation with fluorescence-activated droplet sorting. After cells were loaded into aqueous droplets by hydrodynamic focusing, an on-flight fluorescence-activated sorting process was conducted to isolate droplets containing one cell. Encapsulation of fluorescent polystyrene beads was investigated to evaluate the developed method. A single-bead encapsulation rate of more than 98 % was achieved under the optimized conditions. Application to encapsulate single HeLa cells was further demonstrated with a single-cell encapsulation rate of 94.1 %, which is about 200 % higher than those obtained by random compartmentalization. We expect this new method to provide a useful platform for encapsulating single cells, facilitating the development of high-throughput cell-based assays.
Low-temperature bonded glass-membrane microfluidic device for in vitro organ-on-a-chip cell culture models

NASA Astrophysics Data System (ADS)

Pocock, Kyall J.; Gao, Xiaofang; Wang, Chenxi; Priest, Craig; Prestidge, Clive A.; Mawatari, Kazuma; Kitamori, Takehiko; Thierry, Benjamin

2015-12-01

The integration of microfluidics with living biological systems has paved the way to the exciting concept of "organson- a-chip", which aims at the development of advanced in vitro models that replicate the key features of human organs. Glass based devices have long been utilised in the field of microfluidics but the integration of alternative functional elements within multi-layered glass microdevices, such as polymeric membranes, remains a challenge. To this end, we have extended a previously reported approach for the low-temperature bonding of glass devices that enables the integration of a functional polycarbonate porous membrane. The process was initially developed and optimised on specialty low-temperature bonding equipment (μTAS2001, Bondtech, Japan) and subsequently adapted to more widely accessible hot embosser units (EVG520HE Hot Embosser, EVG, Austria). The key aspect of this method is the use of low temperatures compatible with polymeric membranes. Compared to borosilicate glass bonding (650 °C) and quartz/fused silica bonding (1050 °C) processes, this method maintains the integrity and functionality of the membrane (Tg 150 °C for polycarbonate). Leak tests performed showed no damage or loss of integrity of the membrane for up to 150 hours, indicating sufficient bond strength for long term cell culture. A feasibility study confirmed the growth of dense and functional monolayers of Caco-2 cells within 5 days.
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 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 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
Microfluidics and microbial engineering.

PubMed

Kou, Songzi; Cheng, Danhui; Sun, Fei; Hsing, I-Ming

2016-02-07

The combination of microbial engineering and microfluidics is synergistic in nature. For example, microfluidics is benefiting from the outcome of microbial engineering and many reported point-of-care microfluidic devices employ engineered microbes as functional parts for the microsystems. In addition, microbial engineering is facilitated by various microfluidic techniques, due to their inherent strength in high-throughput screening and miniaturization. In this review article, we firstly examine the applications of engineered microbes for toxicity detection, biosensing, and motion generation in microfluidic platforms. Secondly, we look into how microfluidic technologies facilitate the upstream and downstream processes of microbial engineering, including DNA recombination, transformation, target microbe selection, mutant characterization, and microbial function analysis. Thirdly, we highlight an emerging concept in microbial engineering, namely, microbial consortium engineering, where the behavior of a multicultural microbial community rather than that of a single cell/species is delineated. Integrating the disciplines of microfluidics and microbial engineering opens up many new opportunities, for example in diagnostics, engineering of microbial motors, development of portable devices for genetics, high throughput characterization of genetic mutants, isolation and identification of rare/unculturable microbial species, single-cell analysis with high spatio-temporal resolution, and exploration of natural microbial communities.
Novel concept of washing for microfluidic paper-based analytical devices based on capillary force of paper substrates.

PubMed

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

2016-11-01

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

DOE PAGES

Wu, Meiye

2015-03-23

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

PubMed

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

2016-09-15

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

PubMed

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

2018-04-01

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

PubMed

Hyun, Kyung-A; Jung, Hyo-Il

2013-04-01

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

NASA Astrophysics Data System (ADS)

Chen, Q. L.; Ho, H. P.; Jin, L.; Chu, B. W.-K.; Li, M. J.; Yam, V. W.-W.

2008-02-01

This work primarily aims to integrate dissolved oxygen sensing capability with a microfluidic platform containing arrays of micro bio-reactors or bio-activity indicators. The measurement of oxygen concentration is of significance for a variety of bio-related applications such as cell culture and gene expression. Optical oxygen sensors based on luminescence quenching are gaining much interest in light of their low power consumption, quick response and high analyte sensitivity in comparison to similar oxygen sensing devices. In our microfluidic oxygen sensor device, a thin layer of oxygen-sensitive luminescent organometallic dye is covalently bonded to a glass slide. Micro flow channels are formed on the glass slide using patterned PDMS (Polydimethylsiloxane). Dissolved oxygen sensing is then performed by directing an optical excitation probe beam to the area of interest within the microfluidic channel. The covalent bonding approach for sensor layer formation offers many distinct advantages over the physical entrapment method including minimizing dye leaching, ensuring good stability and fabrication simplicity. Experimental results confirm the feasibility of the device.
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.

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

PubMed Central

Xing, Yanlong; Dittrich, Petra S.

2018-01-01

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

PubMed

Kazayama, Yuki; Teshima, Tetsuhiko; Osaki, Toshihisa; Takeuchi, Shoji; Toyota, Taro

2016-01-19

Vesicles composed of phospholipids (liposomes) have attracted interest as artificial cell models and have been widely studied to explore lipid-lipid and lipid-protein interactions. However, the size dispersity of liposomes prepared by conventional methods was a major problem that inhibited their use in high-throughput analyses based on monodisperse liposomes. In this study, we developed an integrative microfluidic device that enables both the size-based selection and trapping of liposomes. This device consists of hydrodynamic selection and trapping channels in series, which made it possible to successfully produce an array of more than 60 monodisperse liposomes from a polydisperse liposome suspension with a narrow size distribution (the coefficient of variation was less than 12%). We successfully observed a size-dependent response of the liposomes to sequential osmotic stimuli, which had not clarified so far, by using this device. Our device will be a powerful tool to facilitate the statistical analysis of liposome dynamics.
Selective filling for patterning in microfluidic channels and integration of chromatography in "lab-on-a-chip" devices using sol-gel technology

NASA Astrophysics Data System (ADS)

Jindal, Rohit

The last decade has seen tremendous advancement in the development of miniaturized chemical analysis system also known as "lab-on-a-chip". It is believed that the true potential of these devices will be achieved by integrating various functions such as separation, reaction, sensing, mixing, pumping, injection and detection onto a single chip. The ability to pattern different functionalities is indispensable for the development of highly integrated devices. In this work, a simple method based on the concept of selective filling is described for patterning in the microfluidic channels. It is based on the difference in the free energy of filling between an open and a covered part of the channel. This method was used for the integration of chromatography in the microfluidic devices. A chromatographic column was realized by utilizing sol-gel as an immobilization matrix for entrapping reversed phase chromatographic particles. Localization of the stationary phase was achieved using the selective filling technique. Channels were fabricated in quartz using photolithography and wet etching. Electroosmotic flow was used for manipulating fluid movement in the channels. Cross channel design was used for making a pulse injection of the solutes in the separation channel. An optical fiber setup was developed for carrying out on-chip UV absorbance detection. Stationary phase was created under different sol-gel synthesis conditions. It was established that the sol-gel synthesis carried out under acidic conditions provides the optimum synthesis conditions for creating separation column. Chromatographic performance of the stationary phase material was demonstrated by separating peptides present in a mixture. The sol-gel immobilization method was extended for the integration of micropump in the chip. The micropump enables pumping of the fluid in field free channels. Preliminary results, demonstrating the potential of carbon nanotubes as a support material in the microfluidic channels, were obtained using CVD (chemical vapor deposition) grown tubes in the channel. Results obtained in this work demonstrate the potential of selective filling technique along with sol-gel technology as a useful tool for the fabrication of multifunctional "lab-on-a-chip" devices.
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.
A Two-Stage Microfluidic Device for the Isolation and Capture of Circulating Tumor Cells

NASA Astrophysics Data System (ADS)

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

2014-11-01

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

PubMed Central

Johnson, Alicia S.; Anderson, Kari B.; Halpin, Stephen T.; Kirkpatrick, Douglas C.; Spence, Dana M.; Martin, R. Scott

2012-01-01

In Part I of a two-part series, we describe a simple, and inexpensive approach to fabricate polystyrene devices that is based upon melting polystyrene (from either a Petri dish or powder form) against PDMS molds or around electrode materials. The ability to incorporate microchannels in polystyrene and integrate the resulting device with standard laboratory equipment such as an optical plate reader for analyte readout and micropipettors for fluid propulsion is first described. A simple approach for sample and reagent delivery to the device channels using a standard, multi-channel micropipette and a PDMS-based injection block is detailed. Integration of the microfluidic device with these off-chip functions (sample delivery and readout) enables high throughput screens and analyses. An approach to fabricate polystyrene-based devices with embedded electrodes is also demonstrated, thereby enabling the integration of microchip electrophoresis with electrochemical detection through the use of a palladium electrode (for a decoupler) and carbon-fiber bundle (for detection). The device was sealed against a PDMS-based microchannel and used for the electrophoretic separation and amperometric detection of dopamine, epinephrine, catechol, and 3,4-dihydroxyphenylacetic acid. Finally, these devices were compared against PDMS-based microchips in terms of their optical transparency and absorption of an anti-platelet drug, clopidogrel. Part I of this series lays the foundation for Part II, where these devices were utilized for various on-chip cellular analysis. PMID:23120747
Microfluidic Organ/Body-on-a-Chip Devices at the Convergence of Biology and Microengineering.

PubMed

Perestrelo, Ana Rubina; Águas, Ana C P; Rainer, Alberto; Forte, Giancarlo

2015-12-10

Recent advances in biomedical technologies are mostly related to the convergence of biology with microengineering. For instance, microfluidic devices are now commonly found in most research centers, clinics and hospitals, contributing to more accurate studies and therapies as powerful tools for drug delivery, monitoring of specific analytes, and medical diagnostics. Most remarkably, integration of cellularized constructs within microengineered platforms has enabled the recapitulation of the physiological and pathological conditions of complex tissues and organs. The so-called "organ-on-a-chip" technology, which represents a new avenue in the field of advanced in vitro models, with the potential to revolutionize current approaches to drug screening and toxicology studies. This review aims to highlight recent advances of microfluidic-based devices towards a body-on-a-chip concept, exploring their technology and broad applications in the biomedical field.
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
Modular microfluidic valve structures based on reversible thermoresponsive ionogel actuators.

PubMed

Benito-Lopez, Fernando; Antoñana-Díez, Marta; Curto, Vincenzo F; Diamond, Dermot; Castro-López, Vanessa

2014-09-21

This paper reports for the first time the use of a cross-linked poly(N-isopropylacrylamide) ionogel encapsulating the ionic liquid 1-ethyl-3-methylimidazolium ethyl sulphate as a thermoresponsive and modular microfluidic valve. The ionogel presents superior actuation behaviour to its equivalent hydrogel. Ionogel swelling and shrinking mechanisms and kinetics are investigated as well as the performance of the ionogel when integrated as a valve in a microfluidic device. The modular microfluidic valve demonstrates fully a reversible on-off behaviour without failure for up to eight actuation cycles and a pressure resistance of 1100 mbar.
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
Optics-Integrated Microfluidic Platforms for Biomolecular Analyses

PubMed Central

Bates, Kathleen E.; Lu, Hang

2016-01-01

Compared with conventional optical methods, optics implemented on microfluidic chips provide small, and often much cheaper ways to interrogate biological systems from the level of single molecules up to small model organisms. The optical probing of single molecules has been used to investigate the mechanical properties of individual biological molecules; however, multiplexing of these measurements through microfluidics and nanofluidics confers many analytical advantages. Optics-integrated microfluidic systems can significantly simplify sample processing and allow a more user-friendly experience; alignments of on-chip optical components are predetermined during fabrication and many purely optical techniques are passively controlled. Furthermore, sample loss from complicated preparation and fluid transfer steps can be virtually eliminated, a particularly important attribute for biological molecules at very low concentrations. Excellent fluid handling and high surface area/volume ratios also contribute to faster detection times for low abundance molecules in small sample volumes. Although integration of optical systems with classical microfluidic analysis techniques has been limited, microfluidics offers a ready platform for interrogation of biophysical properties. By exploiting the ease with which fluids and particles can be precisely and dynamically controlled in microfluidic devices, optical sensors capable of unique imaging modes, single molecule manipulation, and detection of minute changes in concentration of an analyte are possible. PMID:27119629
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.
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.
Fully solution-processed organic light-emitting electrochemical cells (OLEC) with inkjet-printed micro-lenses for disposable lab-on-chip applications at ambient conditions

NASA Astrophysics Data System (ADS)

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

2016-02-01

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

PubMed

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

2013-11-07

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

PubMed

Chen, Chang-Yu; Tu, Ting-Yuan; Jong, De-Shien; Wo, Andrew M

2011-06-01

Planar patch clamp has revolutionized characterization of ion channel behavior in drug discovery primarily via advancement in high throughput. Lab use of planar technology, however, addresses different requirements and suffers from inflexibility to enable wide range of interrogation via a single cell. This work presents integration of planar patch clamp with microfluidics, achieving multiple solution exchanges for tailor-specific measurement and allowing rapid replacement of the cell-contacting aperture. Studies via endogenously expressed ion channels in HEK 293T cells were commenced to characterize the device. Results reveal the microfluidic concentration generator produces distinct solution/drug combination/concentrations on-demand. Volume-regulated chloride channel and voltage-gated potassium channels in HEK 293T cells immersed in generated solutions under various osmolarities or drug concentrations show unique channel signature under specific condition. Excitation and blockage of ion channels in a single cell was demonstrated via serial solution exchange. Robustness of the reversible bonding and ease of glass substrate replacement were proven via repeated usage of the integrated device. The present approach reveals the capability and flexibility of integrated microfluidic planar patch-clamp system for ion channel assays. Copyright © 2011 Wiley Periodicals, Inc.
3D printed Lego®-like modular microfluidic devices based on capillary driving.

PubMed

Nie, Jing; Gao, Qing; Qiu, Jing-Jiang; Sun, Miao; Liu, An; Shao, Lei; Fu, Jian-Zhong; Zhao, Peng; He, Yong

2018-03-12

The field of how to rapidly assemble microfluidics with modular components continuously attracts researchers' attention, however, extra efforts must be devoted to solving the problems of leaking and aligning between individual modules. This paper presents a novel type of modular microfluidic device, driven by capillary force. There is no necessity for a strict seal or special alignment, and its open structures make it easy to integrate various stents and reactants. The key rationale for this method is to print different functional modules with a low-cost three-dimensional (3D) printer, then fill the channels with capillary materials and assemble them with plugs like Lego ® bricks. This rapidly reconstructed modular microfluidic device consists of a variety of common functional modules and other personalized modules, each module having a unified standard interface for easy assembly. As it can be printed by a desktop 3D printer, the manufacturing process is simple and efficient, with controllable regulation of the flow channel scale. Through diverse combinations of different modules, a variety of different functions can be achieved, without duplicating the manufacturing process. A single module can also be taken out for testing and analysis. What's more, combined with basic circuit components, it can serve as a low-cost Lego ® -like modular microfluidic circuits. As a proof of concept, the modular microfluidic device has been successfully demonstrated and used for stent degradation and cell cultures, revealing the potential use of this method in both chemical and biological research.
Colloidal core-seeded semiconductor nanorods as fluorescent labels for in-vitro diagnostics (Conference Presentation)

NASA Astrophysics Data System (ADS)

Chan, YinThai

2016-03-01

Colloidal semiconductor nanocrystals are ideal fluorophores for clinical diagnostics, therapeutics, and highly sensitive biochip applications due to their high photostability, size-tunable color of emission and flexible surface chemistry. The relatively recent development of core-seeded semiconductor nanorods showed that the presence of a rod-like shell can confer even more advantageous physicochemical properties than their spherical counterparts, such as large multi-photon absorption cross-sections and facet-specific chemistry that can be exploited to deposit secondary nanoparticles. It may be envisaged that these highly fluorescent nanorods can be integrated with large scale integrated (LSI) microfluidic systems that allow miniaturization and integration of multiple biochemical processes in a single device at the nanoliter scale, resulting in a highly sensitive and automated detection platform. In this talk, I will describe a LSI microfluidic device that integrates RNA extraction, reverse transcription to cDNA, amplification and target pull-down to detect histidine decarboxylase (HDC) gene directly from human white blood cells samples. When anisotropic colloidal semiconductor nanorods (NRs) were used as the fluorescent readout, the detection limit was found to be 0.4 ng of total RNA, which was much lower than that obtained using spherical quantum dots (QDs) or organic dyes. This was attributed to the large action cross-section of NRs and their high probability of target capture in a pull-down detection scheme. The combination of large scale integrated microfluidics with highly fluorescent semiconductor NRs may find widespread utility in point-of-care devices and multi-target diagnostics.
Various on-chip sensors with microfluidics for biological applications.

PubMed

Lee, Hun; Xu, Linfeng; Koh, Domin; Nyayapathi, Nikhila; Oh, Kwang W

2014-09-12

In this paper, we review recent advances in on-chip sensors integrated with microfluidics for biological applications. Since the 1990s, much research has concentrated on developing a sensing system using optical phenomena such as surface plasmon resonance (SPR) and surface-enhanced Raman scattering (SERS) to improve the sensitivity of the device. The sensing performance can be significantly enhanced with the use of microfluidic chips to provide effective liquid manipulation and greater flexibility. We describe an optical image sensor with a simpler platform for better performance over a larger field of view (FOV) and greater depth of field (DOF). As a new trend, we review consumer electronics such as smart phones, tablets, Google glasses, etc. which are being incorporated in point-of-care (POC) testing systems. In addition, we discuss in detail the current optical sensing system integrated with a microfluidic chip.
Thermally driven microfluidic pumping via reversible shape memory polymers

NASA Astrophysics Data System (ADS)

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

2016-08-01

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

PubMed Central

Perestrelo, Ana Rubina; Águas, Ana C. P.; Rainer, Alberto; Forte, Giancarlo

2015-01-01

Recent advances in biomedical technologies are mostly related to the convergence of biology with microengineering. For instance, microfluidic devices are now commonly found in most research centers, clinics and hospitals, contributing to more accurate studies and therapies as powerful tools for drug delivery, monitoring of specific analytes, and medical diagnostics. Most remarkably, integration of cellularized constructs within microengineered platforms has enabled the recapitulation of the physiological and pathological conditions of complex tissues and organs. The so-called “organ-on-a-chip” technology, which represents a new avenue in the field of advanced in vitro models, with the potential to revolutionize current approaches to drug screening and toxicology studies. This review aims to highlight recent advances of microfluidic-based devices towards a body-on-a-chip concept, exploring their technology and broad applications in the biomedical field. PMID:26690442
High frequency acoustic on-chip integration for particle characterization and manipulation in microfluidics

NASA Astrophysics Data System (ADS)

Li, Sizhe; Carlier, Julien; Toubal, Malika; Liu, Huiqin; Campistron, Pierre; Callens, Dorothée; Nassar, Georges; Nongaillard, Bertrand; Guo, Shishang

2017-10-01

This letter presents a microfluidic device that integrates high frequency (650 MHz) bulk acoustic waves for the realization of particle handling on-chip. The core structure of the microfluidic chip is made up of a confocal lens, a vertical reflection wall, and a ZnO film transducer coupled with a silicon substrate for exciting acoustic beams. The excited acoustic waves propagate in bulk silicon and are then guided by a 45° silicon mirror into the suspensions in the microchannel; afterwards, the acoustic energy is focused on particles by the confocal lens and reflected by a reflection wall. Parts of the reflected acoustic energy backtrack into the transducer, and acoustic attenuation measurements are characterized for particle detection. Meanwhile, a strong acoustic streaming phenomenon can be seen around the reflection wall, which is used to implement particle manipulation. This platform opens a frontier for on-chip integration of high sensitivity acoustic characterization and localized acoustic manipulation in microfluidics.
Flexible manipulation of microfluids using optically regulated adsorption/desorption of hydrophobic materials.

PubMed

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

2007-04-15

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

PubMed

Parker, Richard M; Gates, James C; Wales, Dominic J; Smith, Peter G R; Grossel, Martin C

2013-02-07

A planar Bragg grating device has been developed that is capable of detecting changes in the refractive index of a wide range of fluids including solvents, acids and bases. The integration of this high precision refractive index sensor within a chemically resistant microfluidic flow system has enabled the investigation of diverse fluid interactions. By cycling between different solvents, both miscible and immiscible, within the microfluidic system it is shown that the previous solvent determines the nature of the refractive index profile across the transition in composition. This solvent dispersion effect is investigated with particular attention to the methanol-water transition, where transients in refractive index are observed that are an order of magnitude larger in amplitude than the difference between the bulk fluids. The potential complications of such phenomenon are discussed together with an example of a device that exploits this effect for the unambiguous composition measurement of a binary solvent system.
Resolution improvement of 3D stereo-lithography through the direct laser trajectory programming: Application to microfluidic deterministic lateral displacement device.

PubMed

Juskova, Petra; Ollitrault, Alexis; Serra, Marco; Viovy, Jean-Louis; Malaquin, Laurent

2018-02-13

The vast majority of current microfluidic devices are produced using soft lithography, a technique with strong limitations regarding the fabrication of three-dimensional architectures. Additive manufacturing holds great promises to overcome these limitations, but conventional machines still lack the resolution required by most microfluidic applications. 3D printing machines based on two-photon lasers, in contrast, have the needed resolution but are too limited in speed and size of the global device. Here we demonstrate how the resolution of conventional stereolithographic machines can be improved by a direct programming of the laser path and can contribute to bridge the gap between the two above technologies, allowing the direct printing of features between 10 and 100 μm, corresponding to a large fraction of microfluidic applications. This strategy allows to achieve resolutions limited only by the physical size of the laser beam, decreasing by a factor at least 2× the size of the smallest features printable, and increasing their reproducibility by a factor 5. The approach was applied to produce an open microfluidic device with the reversible seal, integrating periodical patterns using the simple motifs, and validated by the fabrication of a deterministic lateral displacement particles sorting device. The sorting of polystyrene beads (diameter: 20 μm and 45 μm) was achieved with a specificity >95%, comparable with that achieved with arrays prepared by microlithography. Copyright © 2017 Elsevier B.V. All rights reserved.
Plasmofluidics: Merging Light and Fluids at the Micro-/Nano-Scale

PubMed Central

Wang, Mingsong; Zhao, Chenglong; Miao, Xiaoyu; Zhao, Yanhui; Rufo, Joseph

2016-01-01

Plasmofluidics is the synergistic integration of plasmonics and micro/nano fluidics in devices and applications in order to enhance performance. There has been significant progress in the emerging field of plasmofluidics in recent years. By utilizing the capability of plasmonics to manipulate light at the nanoscale, combined with the unique optical properties of fluids, and precise manipulation via micro/nano fluidics, plasmofluidic technologies enable innovations in lab-on-a-chip systems, reconfigurable photonic devices, optical sensing, imaging, and spectroscopy. In this review article, we examine and categorize the most recent advances in plasmofluidics into plasmon-enhanced functionalities in microfluidics and microfluidics-enhanced plasmonic devices. The former focuses on plasmonic manipulations of fluids, bubbles, particles, biological cells, and molecules at the micro-/nano-scale. The latter includes technological advances that apply microfluidic principles to enable reconfigurable plasmonic devices and performance-enhanced plasmonic sensors. We conclude with our perspectives on the upcoming challenges, opportunities, and the possible future directions of the emerging field of plasmofluidics. PMID:26140612
Plasmofluidics: Merging Light and Fluids at the Micro-/Nanoscale.

PubMed

Wang, Mingsong; Zhao, Chenglong; Miao, Xiaoyu; Zhao, Yanhui; Rufo, Joseph; Liu, Yan Jun; Huang, Tony Jun; Zheng, Yuebing

2015-09-16

Plasmofluidics is the synergistic integration of plasmonics and micro/nanofluidics in devices and applications in order to enhance performance. There has been significant progress in the emerging field of plasmofluidics in recent years. By utilizing the capability of plasmonics to manipulate light at the nanoscale, combined with the unique optical properties of fluids and precise manipulation via micro/nanofluidics, plasmofluidic technologies enable innovations in lab-on-a-chip systems, reconfigurable photonic devices, optical sensing, imaging, and spectroscopy. In this review article, the most recent advances in plasmofluidics are examined and categorized into plasmon-enhanced functionalities in microfluidics and microfluidics-enhanced plasmonic devices. The former focuses on plasmonic manipulations of fluids, bubbles, particles, biological cells, and molecules at the micro/nanoscale. The latter includes technological advances that apply microfluidic principles to enable reconfigurable plasmonic devices and performance-enhanced plasmonic sensors. The article is concluded with perspectives on the upcoming challenges, opportunities, and possible future directions of the emerging field of plasmofluidics. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
PDMS free-flow electrophoresis chips with integrated partitioning bars for bubble segregation.

PubMed

Köhler, Stefan; Weilbeer, Claudia; Howitz, Steffen; Becker, Holger; Beushausen, Volker; Belder, Detlev

2011-01-21

In this work, a microfluidic free-flow electrophoresis device with a novel approach for preventing gas bubbles from entering the separation area is presented. This is achieved by integrating partitioning bars to reduce the channel depth between electrode channels and separation chamber in order to obtain electrical contact and simultaneously prevent bubbles from entering the separation area. The three-layer sandwich chip features a reusable carrier plate with integrated ports for fluidic connection combined with a softlithographically cast microfluidic PDMS layer and a sealing glass slide. This design allows for a straightforward and rapid chip prototyping process. The performance of the device is demonstrated by free-flow zone electrophoretic separations of fluorescent dye mixtures as well as by the separation of labeled amines and amino acids with separation voltages up to 297 V.
An integrated double-filtration microfluidic device for isolation, enrichment and quantification of urinary extracellular vesicles for detection of bladder cancer

PubMed Central

Liang, Li-Guo; Kong, Meng-Qi; Zhou, Sherry; Sheng, Ye-Feng; Wang, Ping; Yu, Tao; Inci, Fatih; Kuo, Winston Patrick; Li, Lan-Juan; Demirci, Utkan; Wang, ShuQi

2017-01-01

Extracellular vesicles (EVs), including exosomes and microvesicles, are present in a variety of bodily fluids, and the concentration of these sub-cellular vesicles and their associated biomarkers (proteins, nucleic acids, and lipids) can be used to aid clinical diagnosis. Although ultracentrifugation is commonly used for isolation of EVs, it is highly time-consuming, labor-intensive and instrument-dependent for both research laboratories and clinical settings. Here, we developed an integrated double-filtration microfluidic device that isolated and enriched EVs with a size range of 30–200 nm from urine, and subsequently quantified the EVs via a microchip ELISA. Our results showed that the concentration of urinary EVs was significantly elevated in bladder cancer patients (n = 16) compared to healthy controls (n = 8). Receiver operating characteristic (ROC) analysis demonstrated that this integrated EV double-filtration device had a sensitivity of 81.3% at a specificity of 90% (16 bladder cancer patients and 8 healthy controls). Thus, this integrated device has great potential to be used in conjunction with urine cytology and cystoscopy to improve clinical diagnosis of bladder cancer in clinics and at point-of-care (POC) settings. PMID:28436447
Digital hydraulic drive for microfluidics and miniaturized cell culture devices based on shape memory alloy actuators

NASA Astrophysics Data System (ADS)

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

2018-08-01

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

PubMed

Ben-Yoav, Hadar; Dykstra, Peter H; Bentley, William E; Ghodssi, Reza

2017-01-01

A microfluidic electrochemical lab-on-a-chip (LOC) device for DNA hybridization detection has been developed. The device comprises a 3 × 3 array of microelectrodes integrated with a dual layer microfluidic valved manipulation system that provides controlled and automated capabilities for high throughput analysis of microliter volume samples. The surface of the microelectrodes is functionalized with single-stranded DNA (ssDNA) probes which enable specific detection of complementary ssDNA targets. These targets are detected by a capacitive technique which measures dielectric variation at the microelectrode-electrolyte interface due to DNA hybridization events. A quantitative analysis of the hybridization events is carried out based on a sensing modeling that includes detailed analysis of energy storage and dissipation components. By calculating these components during hybridization events the device is able to demonstrate specific and dose response sensing characteristics. The developed microfluidic LOC for DNA hybridization detection offers a technology for real-time and label-free assessment of genetic markers outside of laboratory settings, such as at the point-of-care or in-field environmental monitoring.

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

NASA Astrophysics Data System (ADS)

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

2017-02-01

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

PubMed Central

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

2010-01-01

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

PubMed Central

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

2016-01-01

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

NASA Astrophysics Data System (ADS)

Chen, Binyu; Han, Xiaoming; Su, Zhen; Liu, Quanjun

2018-05-01

In microfluidic detection technology, because of the universality of optical methods in laboratory, optical detection is an attractive solution for microfluidic chip laboratory equipment. In addition, the equipment with high stability and low cost can be realized by integrating appropriate optical detection technology on the chip. This paper reports a detection system for microfluidic droplets. Photomultiplier tubes (PMT) is used as a detection device to improve the sensitivity of detection. This system improves the signal to noise ratio by software filtering and spatial filter. The fluorescence intensity is proportional to the concentration of the fluorescence and intensity of the laser. The fluorescence micro droplets of different concentrations can be distinguished by this system.
Torque-actuated valves for microfluidics.

PubMed

Weibel, Douglas B; Kruithof, Maarten; Potenta, Scott; Sia, Samuel K; Lee, Andrew; Whitesides, George M

2005-08-01

This paper describes torque-actuated valves for controlling the flow of fluids in microfluidic channels. The valves consist of small machine screws (> or =500 microm) embedded in a layer of polyurethane cast above microfluidic channels fabricated in poly(dimethylsiloxane) (PDMS). The polyurethane is cured photochemically with the screws in place; on curing, it bonds to the surrounding layer of PDMS and forms a stiff layer that retains an impression of the threads of the screws. The valves were separated from the ceiling of microfluidic channels by a layer of PDMS and were integrated into channels using a simple procedure compatible with soft lithography and rapid prototyping. Turning the screws actuated the valves by collapsing the PDMS layer between the valve and channel, controlling the flow of fluids in the underlying channels. These valves have the useful characteristic that they do not require power to retain their setting (on/off). They also allow settings between "on" and "off" and can be integrated into portable, disposable microfluidic devices for carrying out sandwich immunoassays.
Capillary electrophoresis-electrochemistry microfluidic system for the determination of organic peroxides

NASA Technical Reports Server (NTRS)

Wang, Joseph; Escarpa, Alberto; Pumera, Martin; Feldman, Jason; Svehla, D. (Principal Investigator)

2002-01-01

A microfluidic analytical system for the separation and detection of organic peroxides, based on a microchip capillary electrophoresis device with an integrated amperometric detector, was developed. The new microsystem relies on the reductive detection of both organic acid peroxides and hydroperoxides at -700 mV (vs. Ag wire/AgCl). Factors influencing the separation and detection processes were examined and optimized. The integrated microsystem offers rapid measurements (within 130 s) of these organic-peroxide compounds, down to micromolar levels. A highly stable response for repetitive injections (RSD 0.35-3.12%; n = 12) reflects the negligible electrode passivation. Such a "lab-on-a-chip" device should be attractive for on-site analysis of organic peroxides, as desired for environmental screening and industrial monitoring.
Dual-nozzle microfluidic droplet generator

NASA Astrophysics Data System (ADS)

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

2018-05-01

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

PubMed

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

2016-04-05

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

PubMed

Araci, Ismail Emre; Brisk, Philip

2014-02-01

In 2002, Thorsen et al. integrated thousands of micromechanical valves on a single microfluidic chip and demonstrated that the control of the fluidic networks can be simplified through multiplexors [1]. This enabled realization of highly parallel and automated fluidic processes with substantial sample economy advantage. Moreover, the fabrication of these devices by multilayer soft lithography was easy and reliable hence contributed to the power of the technology; microfluidic large scale integration (mLSI). Since then, mLSI has found use in wide variety of applications in biology and chemistry. In the meantime, efforts to improve the technology have been ongoing. These efforts mostly focus on; novel materials, components, micromechanical valve actuation methods, and chip architectures for mLSI. In this review, these technological advances are discussed and, recent examples of the mLSI applications are summarized. Copyright © 2013 Elsevier Ltd. All rights reserved.
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.
Various On-Chip Sensors with Microfluidics for Biological Applications

PubMed Central

Lee, Hun; Xu, Linfeng; Koh, Domin; Nyayapathi, Nikhila; Oh, Kwang W.

2014-01-01

In this paper, we review recent advances in on-chip sensors integrated with microfluidics for biological applications. Since the 1990s, much research has concentrated on developing a sensing system using optical phenomena such as surface plasmon resonance (SPR) and surface-enhanced Raman scattering (SERS) to improve the sensitivity of the device. The sensing performance can be significantly enhanced with the use of microfluidic chips to provide effective liquid manipulation and greater flexibility. We describe an optical image sensor with a simpler platform for better performance over a larger field of view (FOV) and greater depth of field (DOF). As a new trend, we review consumer electronics such as smart phones, tablets, Google glasses, etc. which are being incorporated in point-of-care (POC) testing systems. In addition, we discuss in detail the current optical sensing system integrated with a microfluidic chip. PMID:25222033
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
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.
Bio-functionalized silk hydrogel microfluidic systems.

PubMed

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

2016-07-01

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

PubMed Central

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

2015-01-01

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

PubMed

Kirschbaum, Stefanie E K; Baeumner, Antje J

2015-05-01

The concept and realization of microfluidic total analysis systems (microTAS) have revolutionized the analytical process by integrating the whole breadth of analytical techniques into miniaturized systems. Paramount for efficient and competitive microTAS are integrated detection strategies, which lead to low limits of detection while reducing the sample volume. The concept of electrochemiluminescence (ECL) has been intriguing ever since its introduction based on Ru(bpy)3 (2+) by Tokel and Bard [1] (J Am Chem Soc 1853:2862-2863, 1972), especially because of its immense sensitivity, nonexistent auto-luminescent background signal, and simplicity in experimental design. Therefore, integrating ECL detection into microTAS is a logical consequence to achieve simple, yet highly sensitive, sensors. However, published microanalytical devices employing ECL detection focus in general on traditional ECL chemistry and have yet to take advantage of advances made in standard bench-top ECL strategies. This review will therefore focus on the most recent advancements in microfluidic ECL approaches, but also evaluate the potential impact of bench-top ECL research progress that would further improve performance and lower limits of detection of micro analytical ECL systems, ensuring their desirability as detection principle for microTAS applications.
An integrated fluorescence detection system in poly(dimethylsiloxane) for microfluidic applications.

PubMed

Chabinyc, M L; Chiu, D T; McDonald, J C; Stroock, A D; Christian, J F; Karger, A M; Whitesides, G M

2001-09-15

This paper describes a prototype of an integrated fluorescence detection system that uses a microavalanche photodiode (microAPD) as the photodetector for microfluidic devices fabricated in poly(dimethylsiloxane) (PDMS). The prototype device consisted of a reusable detection system and a disposable microfluidic system that was fabricated using rapid prototyping. The first step of the procedure was the fabrication of microfluidic channels in PDMS and the encapsulation of a multimode optical fiber (100-microm core diameter) in the PDMS; the tip of the fiber was placed next to the side wall of one of the channels. The optical fiber was used to couple light into the microchannel for the excitation of fluorescent analytes. The photodetector, a prototype solid-state microAPD array, was embedded in a thick slab (1 cm) of PDMS. A thin (80 microm) colored polycarbonate filter was placed on the top of the embedded microAPD to absorb scattered excitation light before it reached the detector. The microAPD was placed below the microchannel and orthogonal to the axis of the optical fiber. The close proximity (approximately 200 microm) of the microAPD to the microchannel made it unnecessary to incorporate transfer optics; the pixel size of the microAPD (30 microm) matched the dimensions of the channels (50 microm). A blue light-emitting diode was used for fluorescence excitation. The microAPD was operated in Geiger mode to detect the fluorescence. The detection limit of the prototype (approximately 25 nM) was determined by finding the minimum detectable concentration of a solution of fluorescein. The device was used to detect the separation of a mixture of proteins and small molecules by capillary electrophoresis; the separation illustrated the suitability of this integrated fluorescence detection system for bioanalytical applications.

Differentially photo-crosslinked polymers enable self-assembling microfluidics

PubMed Central

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

2012-01-01

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

PubMed

Kim, Samuel C; Clark, Iain C; Shahi, Payam; Abate, Adam R

2018-01-16

Droplet microfluidics can identify and sort cells using digital reverse transcription polymerase chain reaction (RT-PCR) signals from individual cells. However, current methods require multiple microfabricated devices for enzymatic cell lysis and PCR reagent addition, making the process complex and prone to failure. Here, we describe a new approach that integrates all components into a single device. The method enables controlled exposure of isolated single cells to a high pH buffer, which lyses cells and inactivates reaction inhibitors but can be instantly neutralized with RT-PCR buffer. Using our chemical lysis approach, we distinguish individual cells' gene expression with data quality equivalent to more complex two-step workflows. Our system accepts cells and produces droplets ready for amplification, making single-cell droplet RT-PCR faster and more reliable.
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.
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
Organ/body-on-a-chip based on microfluidic technology for drug discovery.

PubMed

Kimura, Hiroshi; Sakai, Yasuyuki; Fujii, Teruo

2018-02-01

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

PubMed

van den Brink, Floris T G; Wigger, Tina; Ma, Liwei; Odijk, Mathieu; Olthuis, Wouter; Karst, Uwe; van den Berg, Albert

2016-10-05

Reactive xenobiotic metabolites and their adduct formation with biomolecules such as proteins are important to study as they can be detrimental to human health. Here, we present a microfluidic electrochemical cell with integrated micromixer to study phase I and phase II metabolism as well as protein adduct formation of xenobiotics in a purely instrumental approach. The newly developed microfluidic device enables both the generation of reactive metabolites through electrochemical oxidation and subsequent adduct formation with biomolecules in a chemical microreactor. This allows us to study the detoxification of reactive species with glutathione and to predict potential toxicity of xenobiotics as a result of protein modification. Efficient mixing in microfluidic systems is a slow process due to the typically laminar flow conditions in shallow channels. Therefore, a passive gradient rotation micromixer has been designed that is capable of mixing liquids efficiently in a 790 pL volume within tens of milliseconds. The mixing principle relies on turning the concentration gradient that is initially established by bringing together two streams of liquid, to take advantage of the short diffusion distances in the shallow microchannels of thin-layer flow cells. The mixer is located immediately downstream of the working electrode of an electrochemical cell with integrated boron doped diamond electrodes. In conjunction with mass spectrometry, the two microreactors integrated in a single device provide a powerful tool to study the metabolism and toxicity of xenobiotics, which was demonstrated by the investigation of the model compound 1-hydroxypyrene.
Oxygen-induced cell migration and on-line monitoring biomarkers modulation of cervical cancers on a microfluidic system

PubMed Central

Lin, Xuexia; Chen, Qiushui; Liu, Wu; Zhang, Jie; Wang, Shiqi; Lin, Zhixiong; Lin, Jin-Ming

2015-01-01

In this work, we report an integrated microfluidic device for cell co-culture under different concentrations of oxygen, in which the secreted protein VEGF165 was on-line qualitatively and semi-quantitatively analyzed by functional nucleic acid, hemin, ABTS and peroxide system. This microfluidic platform allowed investigation of various oxygen and distances effect on cell-to-cell communication. Besides, the microfluidic device was used for real-time analysis of VEGF165 protein by aptamer-functionalized microchannels. Under 5% O2 condition, we found that the migration of CaSki cells was faster than the migration of human umbilical vein endothelial cells. However, the migration of CaSki cells was slower than the migration of HUVECs under 15% O2 condition. Moreover, the shorter intercellular distances, the quicker cells migration. Furthermore, HIF-1α and VEGF165 genes, ROS were analyzed, and the results would provide new perspectives for the diagnosis and medical treatment of cervical cancer. PMID:25905434
Integrated Micro-Optics for Microfluidic Detection.

PubMed

Kazama, Yuto; Hibara, Akihide

2016-01-01

A method of embedding micro-optics into a microfluidic device was proposed and demonstrated. First, the usefulness of embedded right-angle prisms was demonstrated in microscope observation. Lateral-view microscopic observation of an aqueous dye flow in a 100-μm-sized microchannel was demonstrated. Then, the embedded right-angle prisms were utilized for multi-beam laser spectroscopy. Here, crossed-beam thermal lens detection of a liquid sample was applied to glucose detection.
Microfluidic devices for sample preparation and rapid detection of foodborne pathogens.

PubMed

Kant, Krishna; Shahbazi, Mohammad-Ali; Dave, Vivek Priy; Ngo, Tien Anh; Chidambara, Vinayaka Aaydha; Than, Linh Quyen; Bang, Dang Duong; Wolff, Anders

2018-03-10

Rapid detection of foodborne pathogens at an early stage is imperative for preventing the outbreak of foodborne diseases, known as serious threats to human health. Conventional bacterial culturing methods for foodborne pathogen detection are time consuming, laborious, and with poor pathogen diagnosis competences. This has prompted researchers to call the current status of detection approaches into question and leverage new technologies for superior pathogen sensing outcomes. Novel strategies mainly rely on incorporating all the steps from sample preparation to detection in miniaturized devices for online monitoring of pathogens with high accuracy and sensitivity in a time-saving and cost effective manner. Lab on chip is a blooming area in diagnosis, which exploits different mechanical and biological techniques to detect very low concentrations of pathogens in food samples. This is achieved through streamlining the sample handling and concentrating procedures, which will subsequently reduce human errors and enhance the accuracy of the sensing methods. Integration of sample preparation techniques into these devices can effectively minimize the impact of complex food matrix on pathogen diagnosis and improve the limit of detections. Integration of pathogen capturing bio-receptors on microfluidic devices is a crucial step, which can facilitate recognition abilities in harsh chemical and physical conditions, offering a great commercial benefit to the food-manufacturing sector. This article reviews recent advances in current state-of-the-art of sample preparation and concentration from food matrices with focus on bacterial capturing methods and sensing technologies, along with their advantages and limitations when integrated into microfluidic devices for online rapid detection of pathogens in foods and food production line. Copyright © 2018. Published by Elsevier Inc.
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.
Cell stimulus and lysis in a microfluidic device with segmented gas-liquid flow.

PubMed

El-Ali, Jamil; Gaudet, Suzanne; Günther, Axel; Sorger, Peter K; Jensen, Klavs F

2005-06-01

We describe a microfluidic device with rapid stimulus and lysis of mammalian cells for resolving fast transient responses in cell signaling networks. The device uses segmented gas-liquid flow to enhance mixing and has integrated thermoelectric heaters and coolers to control the temperature during cell stimulus and lysis. Potential negative effects of segmented flow on cell responses are investigated in three different cell types, with no morphological changes and no activation of the cell stress-sensitive mitogen activated protein kinases observed. Jurkat E6-1 cells are stimulated in the device using alpha-CD3, and the resulting activations of ERK and JNK are presented for different time points. Stimulation of cells performed on chip results in pathway activation identical to that of conventionally treated cells under the same conditions.
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.
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 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
Isothermal Amplification Methods for the Detection of Nucleic Acids in Microfluidic Devices

PubMed Central

Zanoli, Laura Maria; Spoto, Giuseppe

2012-01-01

Diagnostic tools for biomolecular detection need to fulfill specific requirements in terms of sensitivity, selectivity and high-throughput in order to widen their applicability and to minimize the cost of the assay. The nucleic acid amplification is a key step in DNA detection assays. It contributes to improving the assay sensitivity by enabling the detection of a limited number of target molecules. The use of microfluidic devices to miniaturize amplification protocols reduces the required sample volume and the analysis times and offers new possibilities for the process automation and integration in one single device. The vast majority of miniaturized systems for nucleic acid analysis exploit the polymerase chain reaction (PCR) amplification method, which requires repeated cycles of three or two temperature-dependent steps during the amplification of the nucleic acid target sequence. In contrast, low temperature isothermal amplification methods have no need for thermal cycling thus requiring simplified microfluidic device features. Here, the use of miniaturized analysis systems using isothermal amplification reactions for the nucleic acid amplification will be discussed. PMID:25587397
Tape transfer atomization patterning of liquid alloys for microfluidic stretchable wireless power transfer.

PubMed

Jeong, Seung Hee; Hjort, Klas; Wu, Zhigang

2015-02-12

Stretchable electronics offers unsurpassed mechanical compliance on complex or soft surfaces like the human skin and organs. To fully exploit this great advantage, an autonomous system with a self-powered energy source has been sought for. Here, we present a new technology to pattern liquid alloys on soft substrates, targeting at fabrication of a hybrid-integrated power source in microfluidic stretchable electronics. By atomized spraying of a liquid alloy onto a soft surface with a tape transferred adhesive mask, a universal fabrication process is provided for high quality patterns of liquid conductors in a meter scale. With the developed multilayer fabrication technique, a microfluidic stretchable wireless power transfer device with an integrated LED was demonstrated, which could survive cycling between 0% and 25% strain over 1,000 times.
Tape Transfer Atomization Patterning of Liquid Alloys for Microfluidic Stretchable Wireless Power Transfer

PubMed Central

Jeong, Seung Hee; Hjort, Klas; Wu, Zhigang

2015-01-01

Stretchable electronics offers unsurpassed mechanical compliance on complex or soft surfaces like the human skin and organs. To fully exploit this great advantage, an autonomous system with a self-powered energy source has been sought for. Here, we present a new technology to pattern liquid alloys on soft substrates, targeting at fabrication of a hybrid-integrated power source in microfluidic stretchable electronics. By atomized spraying of a liquid alloy onto a soft surface with a tape transferred adhesive mask, a universal fabrication process is provided for high quality patterns of liquid conductors in a meter scale. With the developed multilayer fabrication technique, a microfluidic stretchable wireless power transfer device with an integrated LED was demonstrated, which could survive cycling between 0% and 25% strain over 1,000 times. PMID:25673261
In-House fabrication and Electrical characterization of planner si-nanogap

NASA Astrophysics Data System (ADS)

Dhahi, Th. S.; Adam, Tijjani; Hashim, U.

2017-10-01

Nanogap is increasingly known to be beneficial, dependable and higher sensing technology. Another possible purpose is to examine a bioactivity and study the reaction of single molecule. It is important to carefully recognize the differences between the sensor surface and electrode in order to incorporate the biological system with nanogap. Also, it crucial to examine the dielectric properties between the planar nanogap with and without a sample. Electrical concentration between the electrodes could be increased due to integrating of microfluidic channel when the sample is being used. This paper is a report on an electrical point of view of planar nanogap capacitor device with comparison of different excitation frequency with and without microfluidic channel. By using 40 nm Si nanogap devices, the sensitivity of nanogap was compared by dropping deionized water and pH 7 onto the target. Experiments were carried out in wide range of frequencies from 1 Hz to 1 MHz at room temperature with 30 mV input signal (0 V, DC, Offset). Both effects of excitation frequency on capacitance sampling with 10 µm microfluidic integration were analyzed.
Reconfigurable microfluidic pump enabled by opto-electrical-thermal transduction

NASA Astrophysics Data System (ADS)

Takeuchi, Masaru; Hagiwara, Masaya; Haulot, Gauvain; Ho, Chih-Ming

2013-10-01

Flexible integration of a microfluidic system comprising pumps, valves, and microchannels was realized by an optoelectronic reconfigurable microchannels (OERM) technique. Projecting a low light fluidic device pattern—e.g., pumps, valves, and channels—onto an OERM platform generates Joule heating and melts the substrate in the bright area on the platform; thus, the fluidic system can be reconfigured by changing the projected light pattern. Hexadecane was used as the substrate of the microfluidic system. The volume change of hexadecane during the liquid-solid phase transition was utilized to generate pumping pressure. The system can pump nanoliters of water within several seconds.

Computational analysis of integrated biosensing and shear flow in a microfluidic vascular model

NASA Astrophysics Data System (ADS)

Wong, Jeremy F.; Young, Edmond W. K.; Simmons, Craig A.

2017-11-01

Fluid flow and flow-induced shear stress are critical components of the vascular microenvironment commonly studied using microfluidic cell culture models. Microfluidic vascular models mimicking the physiological microenvironment also offer great potential for incorporating on-chip biomolecular detection. In spite of this potential, however, there are few examples of such functionality. Detection of biomolecules released by cells under flow-induced shear stress is a significant challenge due to severe sample dilution caused by the fluid flow used to generate the shear stress, frequently to the extent where the analyte is no longer detectable. In this work, we developed a computational model of a vascular microfluidic cell culture model that integrates physiological shear flow and on-chip monitoring of cell-secreted factors. Applicable to multilayer device configurations, the computational model was applied to a bilayer configuration, which has been used in numerous cell culture applications including vascular models. Guidelines were established that allow cells to be subjected to a wide range of physiological shear stress while ensuring optimal rapid transport of analyte to the biosensor surface and minimized biosensor response times. These guidelines therefore enable the development of microfluidic vascular models that integrate cell-secreted factor detection while addressing flow constraints imposed by physiological shear stress. Ultimately, this work will result in the addition of valuable functionality to microfluidic cell culture models that further fulfill their potential as labs-on-chips.
Printed microfluidic filter for heparinized blood.

PubMed

Bilatto, Stanley E R; Adly, Nouran Y; Correa, Daniel S; Wolfrum, Bernhard; Offenhäusser, Andreas; Yakushenko, Alexey

2017-05-01

A simple lab-on-a-chip method for blood plasma separation was developed by combining stereolithographic 3D printing with inkjet printing, creating a completely sealed microfluidic device. In some approaches, one dilutes the blood sample before separation, reducing the concentration of a target analyte and increasing a contamination risk. In this work, a single drop (8 μ l) of heparinized whole blood could be efficiently filtered using a capillary effect without any external driving forces and without dilution. The blood storage in heparin tubes during 24 h at 4 °C initiated the formation of small crystals that formed auto-filtration structures in the sample upon entering the 3D-printed device, with pores smaller than the red blood cells, separating plasma from the cellular content. The total filtration process took less than 10 s. The presented printed plasma filtration microfluidics fabricated with a rapid prototyping approach is a miniaturized, fast and easy-to-operate device that can be integrated into healthcare/portable systems for point-of-care diagnostics.
Microfluidic integration of parallel solid-phase liquid chromatography.

PubMed

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

2013-03-05

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

PubMed

Lazar, Iulia M; Trisiripisal, Phichet; Sarvaiya, Hetal A

2006-08-01

A microfluidic liquid chromatography (LC) system for proteomic investigations that integrates all the necessary components for stand-alone operation, i.e., pump, valve, separation column, and electrospray interface, is described in this paper. The overall size of the LC device is small enough to enable the integration of two fully functional separation systems on a 3 in. x 1 in. glass microchip. A multichannel architecture that uses electroosmotic pumping principles provides the necessary functionality for eluent propulsion and sample valving. The flow rates generated within these chips are fully consistent with the requirements of nano-LC platforms that are routinely used in proteomic applications. The microfluidic device was evaluated for the analysis of a protein digest obtained from the MCF7 breast cancer cell line. The cytosolic protein extract was processed according to a shotgun protocol, and after tryptic digestion and prefractionation using strong cation exchange chromatography (SCX), selected sample subfractions were analyzed with conventional and microfluidic LC platforms. Using similar experimental conditions, the performance of the microchip LC was comparable to that obtained with benchtop instrumentation, providing an overlap of 75% in proteins that were identified by more than two unique peptides. The microfluidic LC analysis of a protein-rich SCX fraction enabled the confident identification of 77 proteins by using conventional data filtering parameters, of 39 proteins with p < 0.001, and of 5 proteins that are known to be cancer-specific biomarkers, demonstrating thus the potential applicability of these chips for future high-throughput biomarker screening applications.
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.
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.
Microfluidics as a new tool in radiation biology

PubMed Central

Lacombe, Jerome; Phillips, Shanna Leslie; Zenhausern, Frederic

2016-01-01

Ionizing radiations interact with molecules at the cellular and molecular levels leading to several biochemical modifications that may be responsible for biological effects on tissue or whole organisms. The study of these changes is difficult because of the complexity of the biological response(s) to radiations and the lack of reliable models able to mimic the whole molecular phenomenon and different communications between the various cell networks, from the cell activation to the macroscopic effect at the tissue or organismal level. Microfluidics, the science and technology of systems that can handle small amounts of fluids in confined and controlled environment, has been an emerging field for several years. Some microfluidic devices, even at early stages of development, may already help radiobiological research by proposing new approaches to study cellular, tissue and total-body behavior upon irradiation. These devices may also be used in clinical biodosimetry since microfluidic technology is frequently developed for integrating complex bioassay chemistries into automated user-friendly, reproducible and sensitive analyses. In this review, we discuss the use, numerous advantages, and possible future of microfluidic technology in the field of radiobiology. We will also examine the disadvantages and required improvements for microfluidics to be fully practical in radiation research and to become an enabling tool for radiobiologists and radiation oncologists. PMID:26704304
Microfluidics as a new tool in radiation biology.

PubMed

Lacombe, Jerome; Phillips, Shanna Leslie; Zenhausern, Frederic

2016-02-28

Ionizing radiations interact with molecules at the cellular and molecular levels leading to several biochemical modifications that may be responsible for biological effects on tissue or whole organisms. The study of these changes is difficult because of the complexity of the biological response(s) to radiations and the lack of reliable models able to mimic the whole molecular phenomenon and different communications between the various cell networks, from the cell activation to the macroscopic effect at the tissue or organismal level. Microfluidics, the science and technology of systems that can handle small amounts of fluids in confined and controlled environment, has been an emerging field for several years. Some microfluidic devices, even at early stages of development, may already help radiobiological research by proposing new approaches to study cellular, tissue and total-body behavior upon irradiation. These devices may also be used in clinical biodosimetry since microfluidic technology is frequently developed for integrating complex bioassay chemistries into automated user-friendly, reproducible and sensitive analyses. In this review, we discuss the use, numerous advantages, and possible future of microfluidic technology in the field of radiobiology. We will also examine the disadvantages and required improvements for microfluidics to be fully practical in radiation research and to become an enabling tool for radiobiologists and radiation oncologists. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
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.
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.
Open-source, community-driven microfluidics with Metafluidics.

PubMed

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

2017-06-07

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

PubMed Central

Hamon, Morgan; Hong, Jong Wook

2013-01-01

Recent advances in applied physics and chemistry have led to the development of novel microfluidic systems. Microfluidic systems allow minute amounts of reagents to be processed using μm-scale channels and offer several advantages over conventional analytical devices for use in biological sciences: faster, more accurate and more reproducible analytical performance, reduced cell and reagent consumption, portability, and integration of functional components in a single chip. In this review, we introduce how microfluidics has been applied to biological sciences. We first present an overview of the fabrication of microfluidic systems and describe the distinct technologies available for biological research. We then present examples of microsystems used in biological sciences, focusing on applications in molecular and cellular biology. PMID:24305843
A Microfluidic Cytometer for Complete Blood Count With a 3.2-Megapixel, 1.1- μm-Pitch Super-Resolution Image Sensor in 65-nm BSI CMOS.

PubMed

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

2017-08-01

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

PubMed Central

Lucklum, Ralf; Zubtsov, Mikhail; Schmidt, Marc-Peter; Mukhin, Nikolay V.; Hirsch, Soeren

2017-01-01

The current work demonstrates a novel surface acoustic wave (SAW) based phononic crystal sensor approach that allows the integration of a velocimetry-based sensor concept into single chip integrated solutions, such as Lab-on-a-Chip devices. The introduced sensor platform merges advantages of ultrasonic velocimetry analytic systems and a microacoustic sensor approach. It is based on the analysis of structural resonances in a periodic composite arrangement of microfluidic channels confined within a liquid analyte. Completed theoretical and experimental investigations show the ability to utilize periodic structure localized modes for the detection of volumetric properties of liquids and prove the efficacy of the proposed sensor concept. PMID:28946609
SAW-Based Phononic Crystal Microfluidic Sensor-Microscale Realization of Velocimetry Approaches for Integrated Analytical Platform Applications.

PubMed

Oseev, Aleksandr; Lucklum, Ralf; Zubtsov, Mikhail; Schmidt, Marc-Peter; Mukhin, Nikolay V; Hirsch, Soeren

2017-09-23

The current work demonstrates a novel surface acoustic wave (SAW) based phononic crystal sensor approach that allows the integration of a velocimetry-based sensor concept into single chip integrated solutions, such as Lab-on-a-Chip devices. The introduced sensor platform merges advantages of ultrasonic velocimetry analytic systems and a microacoustic sensor approach. It is based on the analysis of structural resonances in a periodic composite arrangement of microfluidic channels confined within a liquid analyte. Completed theoretical and experimental investigations show the ability to utilize periodic structure localized modes for the detection of volumetric properties of liquids and prove the efficacy of the proposed sensor concept.
Microbioreactors with microfluidic control and a user-friendly connection to the actuator hardware

NASA Astrophysics Data System (ADS)

Buchenauer, A.; Funke, M.; Büchs, J.; Mokwa, W.; Schnakenberg, U.

2009-07-01

In this study, an array of microbioreactors based on the format of 48-well microtiter plates (MTPs) is presented. The process parameters pH and biomass are monitored online using commercially available optical sensor technology. A microfluidic device dispenses acid or base individually into each well for controlling the pH of fermentations. Fluid volumes from 72 nL to 940 nL can be supplied with valve opening times between 10 ms and 200 ms. One microfluidic device is capable of supplying four wells from two reservoirs. Up to four microfluidic devices can be integrated on the area of a prototype MTP. The devices are fabricated in polydimethylsiloxane (PDMS) using soft lithographic techniques and utilize pneumatically actuated microvalves. During fermentations, the microbioreactor is clamped to an orbital shaker and a temporary pneumatic connection guides the externally controlled pressurized air to the microfluidic device. Finally, fermentations of Escherichia coli in the presence and absence of pH control are carried out in the microbioreactor system over 18 h. During the fermentation the pH of the cultures is continuously monitored by means of optodes. An ammonia solution or phosphoric acid is dispensed to adjust the pH if it differs from the set point of 7.2. In a controlled culture, the pH can be sustained within 7.0 to 7.3 while the pH in an uncontrolled culture ranges between 6.5 and 9.0. This microbioreactor demonstrates the possibility of pH-controlled fermentations in micro-scale. The process control and the user friendly connection to the actuation hardware provide an easy handling comparable to standard MTPs.
A rapid, straightforward, and print house compatible mass fabrication method for integrating 3D paper-based microfluidics.

PubMed

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

2013-11-01

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

PubMed

Wang, Yao-Nan; Liu, Chan-Chiung; Yang, Ruey-Jen; Ju, Wei-Jhong; Fu, Lung-Ming

2016-03-17

An integrated microfluidic distillation system is proposed for separating a mixed ethanol-methanol-water solution into its constituent components. The microfluidic chip is fabricated using a CO2 laser system and comprises a serpentine channel, a boiling zone, a heating zone, and a cooled collection chamber filled with de-ionized (DI) water. In the proposed device, the ethanol-methanol-water solution is injected into the microfluidic chip and driven through the serpentine channel and into the collection chamber by means of a nitrogen carrier gas. Following the distillation process, the ethanol-methanol vapor flows into the collection chamber and condenses into the DI water. The resulting solution is removed from the collection tank and reacted with a mixed indicator. Finally, the methanol concentration is inversely derived from the absorbance measurements obtained using a spectrophotometer. The experimental results show the proposed microfluidic system achieves an average methanol distillation efficiency of 97%. The practicality of the proposed device is demonstrated by detecting the methanol concentrations of two commercial fruit wines. It is shown that the measured concentration values deviate by no more than 3% from those obtained using a conventional bench top system. Copyright © 2016 Elsevier B.V. All rights reserved.
Integrated Microfluidic Membrane Transistor Utilizing Chemical Information for On-Chip Flow Control.

PubMed

Frank, Philipp; Schreiter, Joerg; Haefner, Sebastian; Paschew, Georgi; Voigt, Andreas; Richter, Andreas

2016-01-01

Microfluidics is a great enabling technology for biology, biotechnology, chemistry and general life sciences. Despite many promising predictions of its progress, microfluidics has not reached its full potential yet. To unleash this potential, we propose the use of intrinsically active hydrogels, which work as sensors and actuators at the same time, in microfluidic channel networks. These materials transfer a chemical input signal such as a substance concentration into a mechanical output. This way chemical information is processed and analyzed on the spot without the need for an external control unit. Inspired by the development electronics, our approach focuses on the development of single transistor-like components, which have the potential to be used in an integrated circuit technology. Here, we present membrane isolated chemical volume phase transition transistor (MIS-CVPT). The device is characterized in terms of the flow rate from source to drain, depending on the chemical concentration in the control channel, the source-drain pressure drop and the operating temperature.

Microfluidic Serial Dilution Circuit

PubMed Central

Paegel, Brian M.; Grover, William H.; Skelley, Alison M.; Mathies, Richard A.; Joyce, Gerald F.

2008-01-01

In vitro evolution of RNA molecules requires a method for executing many consecutive serial dilutions. To solve this problem, a microfluidic circuit has been fabricated in a three-layer glass-PDMS-glass device. The 400-nL serial dilution circuit contains five integrated membrane valves: three two-way valves arranged in a loop to drive cyclic mixing of the diluent and carryover, and two bus valves to control fluidic access to the circuit through input and output channels. By varying the valve placement in the circuit, carryover fractions from 0.04 to 0.2 were obtained. Each dilution process, which is comprised of a diluent flush cycle followed by a mixing cycle, is carried out with no pipeting, and a sample volume of 400 nL is sufficient for conducting an arbitrary number of serial dilutions. Mixing is precisely controlled by changing the cyclic pumping rate, with a minimum mixing time of 22 s. This microfluidic circuit is generally applicable for integrating automated serial dilution and sample preparation in almost any microfluidic architecture. PMID:17073422
Integrated Microfluidic Membrane Transistor Utilizing Chemical Information for On-Chip Flow Control

PubMed Central

Frank, Philipp; Schreiter, Joerg; Haefner, Sebastian; Paschew, Georgi; Voigt, Andreas; Richter, Andreas

2016-01-01

Microfluidics is a great enabling technology for biology, biotechnology, chemistry and general life sciences. Despite many promising predictions of its progress, microfluidics has not reached its full potential yet. To unleash this potential, we propose the use of intrinsically active hydrogels, which work as sensors and actuators at the same time, in microfluidic channel networks. These materials transfer a chemical input signal such as a substance concentration into a mechanical output. This way chemical information is processed and analyzed on the spot without the need for an external control unit. Inspired by the development electronics, our approach focuses on the development of single transistor-like components, which have the potential to be used in an integrated circuit technology. Here, we present membrane isolated chemical volume phase transition transistor (MIS-CVPT). The device is characterized in terms of the flow rate from source to drain, depending on the chemical concentration in the control channel, the source-drain pressure drop and the operating temperature. PMID:27571209
Study on the photocatalytic reaction kinetics in a TiO2 nanoparticles coated microreactor integrated microfluidics device.

PubMed

Liu, Ai-Lin; Li, Zhong-Qiu; Wu, Zeng-Qiang; Xia, Xing-Hua

2018-05-15

For study of the photocatalytic reaction kinetics in a confined microsystem, a photocatalysis microreactor integrated on a microfluidic device has been fabricated using an on-line UV/vis detector. The performance of the photocatalysis microreactor is evaluated by the photocatalytic degradation of Rhodamine B chosen as model target by using commercial titanium dioxide (Degussa P25, TiO 2 ) nanoparticles as a photocatalyst. Results show that the photocatalytic reaction occurs via the Langmuir-Hinshelwood mechanism and the photocatalysis kinetics in the confined microsystem (r = 0.359 min -1 ) is about 10 times larger than that in macrosystem (r = 0.033 min -1 ). In addition, the photocatalysis activity of the immobilized TiO 2 nanoparticles in the microreactor exhibits good stability under flowing conditions. The present microchip device offers an interesting platform for screening of photocatalysts and exploration of photocatalysis mechanisms and kinetics. Copyright © 2018 Elsevier B.V. All rights reserved.
A lab-on-chip for biothreat detection using single-molecule DNA mapping.

PubMed

Meltzer, Robert H; Krogmeier, Jeffrey R; Kwok, Lisa W; Allen, Richard; Crane, Bryan; Griffis, Joshua W; Knaian, Linda; Kojanian, Nanor; Malkin, Gene; Nahas, Michelle K; Papkov, Vyacheslav; Shaikh, Saad; Vyavahare, Kedar; Zhong, Qun; Zhou, Yi; Larson, Jonathan W; Gilmanshin, Rudolf

2011-03-07

Rapid, specific, and sensitive detection of airborne bacteria, viruses, and toxins is critical for biodefense, yet the diverse nature of the threats poses a challenge for integrated surveillance, as each class of pathogens typically requires different detection strategies. Here, we present a laboratory-on-a-chip microfluidic device (LOC-DLA) that integrates two unique assays for the detection of airborne pathogens: direct linear analysis (DLA) with unsurpassed specificity for bacterial threats and Digital DNA for toxins and viruses. The LOC-DLA device also prepares samples for analysis, incorporating upstream functions for concentrating and fractionating DNA. Both DLA and Digital DNA assays are single molecule detection technologies, therefore the assay sensitivities depend on the throughput of individual molecules. The microfluidic device and its accompanying operation protocols have been heavily optimized to maximize throughput and minimize the loss of analyzable DNA. We present here the design and operation of the LOC-DLA device, demonstrate multiplex detection of rare bacterial targets in the presence of 100-fold excess complex bacterial mixture, and demonstrate detection of picogram quantities of botulinum toxoid.
Microfluidic paper-based biomolecule preconcentrator based on ion concentration polarization.

PubMed

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

2016-06-21

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

PubMed

Fernandes, Ana C; Gernaey, Krist V; Krühne, Ulrich

From its birth, microfluidics has been referenced as a revolutionary technology and the solution to long standing technological and sociological issues, such as detection of dilute compounds and personalized healthcare. Microfluidics has for example been envisioned as: (1) being capable of miniaturizing industrial production plants, thereby increasing their automation and operational safety at low cost; (2) being able to identify rare diseases by running bioanalytics directly on the patient's skin; (3) allowing health diagnostics in point-of-care sites through cheap lab-on-a-chip devices. However, the current state of microfluidics, although technologically advanced, has so far failed to reach the originally promised widespread use. In this paper, some of the aspects are identified and discussed that have prevented microfluidics from reaching its full potential, especially in the chemical engineering and biotechnology fields, focusing mainly on the specialization on a single target of most microfluidic devices and offering a perspective on the alternate, multi-use, "plug and play" approach. Increasing the flexibility of microfluidic platforms, by increasing their compatibility with different substrates, reactions and operation conditions, and other microfluidic systems is indeed of surmount importance and current academic and industrial approaches to modular microfluidics are presented. Furthermore, two views on the commercialization of plug-and-play microfluidics systems, leading towards improved acceptance and more widespread use, are introduced. A brief review of the main materials and fabrication strategies used in these fields, is also presented. Finally, a step-wise guide towards the development of microfluidic systems is introduced with special focus on the integration of sensors in microfluidics. The proposed guidelines are then applied for the development of two different example platforms, and to three examples taken from literature. With this work, we aim to provide an interesting perspective on the field of microfluidics when applied to chemical engineering and biotechnology studies, as well as to contribute with potential solutions to some of its current challenges. Copyright © 2018 Elsevier Inc. All rights reserved.
High efficiency integration of three-dimensional functional microdevices inside a microfluidic chip by using femtosecond laser multifoci parallel microfabrication

NASA Astrophysics Data System (ADS)

Xu, Bing; Du, Wen-Qiang; Li, Jia-Wen; Hu, Yan-Lei; Yang, Liang; Zhang, Chen-Chu; Li, Guo-Qiang; Lao, Zhao-Xin; Ni, Jin-Cheng; Chu, Jia-Ru; Wu, Dong; Liu, Su-Ling; Sugioka, Koji

2016-01-01

High efficiency fabrication and integration of three-dimension (3D) functional devices in Lab-on-a-chip systems are crucial for microfluidic applications. Here, a spatial light modulator (SLM)-based multifoci parallel femtosecond laser scanning technology was proposed to integrate microstructures inside a given ‘Y’ shape microchannel. The key novelty of our approach lies on rapidly integrating 3D microdevices inside a microchip for the first time, which significantly reduces the fabrication time. The high quality integration of various 2D-3D microstructures was ensured by quantitatively optimizing the experimental conditions including prebaking time, laser power and developing time. To verify the designable and versatile capability of this method for integrating functional 3D microdevices in microchannel, a series of microfilters with adjustable pore sizes from 12.2 μm to 6.7 μm were fabricated to demonstrate selective filtering of the polystyrene (PS) particles and cancer cells with different sizes. The filter can be cleaned by reversing the flow and reused for many times. This technology will advance the fabrication technique of 3D integrated microfluidic and optofluidic chips.
Microfluidic array platform for simultaneous lipid bilayer membrane formation.

PubMed

Zagnoni, M; Sandison, M E; Morgan, H

2009-01-01

In recent years, protein array technologies have found widespread applications in proteomics. However, new methods for high-throughput analysis of protein-protein and protein-compound interactions are still required. In this paper, an array of lipid bilayer membranes formed within a microfluidic system with integrated electrodes is presented. The system is comprised of three layers that are clamped together, thus rendering the device cleanable and reusable. The device microfluidics enable the simultaneous formation of an array of lipid bilayers using a previously developed air-exposure technique, thereby avoiding the need to manually form individual bilayers. The Ag/AgCl electrodes allow for ion channel measurements, each of the sites being independently addressable. Typically, a 50% yield in simultaneous lipid bilayer formation over 12 sites was obtained and ion channel recordings have been acquired over multiple sites. This system has great potential for the development of an automatable platform of suspended lipid bilayer arrays.
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.
Acoustic biosensors.

PubMed

Fogel, Ronen; Limson, Janice; Seshia, Ashwin A

2016-06-30

Resonant and acoustic wave devices have been researched for several decades for application in the gravimetric sensing of a variety of biological and chemical analytes. These devices operate by coupling the measurand (e.g. analyte adsorption) as a modulation in the physical properties of the acoustic wave (e.g. resonant frequency, acoustic velocity, dissipation) that can then be correlated with the amount of adsorbed analyte. These devices can also be miniaturized with advantages in terms of cost, size and scalability, as well as potential additional features including integration with microfluidics and electronics, scaled sensitivities associated with smaller dimensions and higher operational frequencies, the ability to multiplex detection across arrays of hundreds of devices embedded in a single chip, increased throughput and the ability to interrogate a wider range of modes including within the same device. Additionally, device fabrication is often compatible with semiconductor volume batch manufacturing techniques enabling cost scalability and a high degree of precision and reproducibility in the manufacturing process. Integration with microfluidics handling also enables suitable sample pre-processing/separation/purification/amplification steps that could improve selectivity and the overall signal-to-noise ratio. Three device types are reviewed here: (i) bulk acoustic wave sensors, (ii) surface acoustic wave sensors, and (iii) micro/nano-electromechanical system (MEMS/NEMS) sensors. © 2016 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.
A critical insight into the development pipeline of microfluidic immunoassay devices for the sensitive quantitation of protein biomarkers at the point of care.

PubMed

Barbosa, Ana I; Reis, Nuno M

2017-03-13

The latest clinical procedures for the timely and cost-effective diagnosis of chronic and acute clinical conditions, such as cardiovascular diseases, cancer, chronic respiratory diseases, diabetes or sepsis (i.e. the biggest causes of death worldwide), involve the quantitation of specific protein biomarkers released into the blood stream or other physiological fluids (e.g. urine or saliva). The clinical thresholds are usually in the femtomolar to picolomar range, and consequently the measurement of these protein biomarkers heavily relies on highly sophisticated, bulky and automated equipment in centralised pathology laboratories. The first microfluidic devices capable of measuring protein biomarkers in miniaturised immunoassays were presented nearly two decades ago and promised to revolutionise point-of-care (POC) testing by offering unmatched sensitivity and automation in a compact POC format; however, the development and adoption of microfluidic protein biomarker tests has fallen behind expectations. This review presents a detailed critical overview into the pipeline of microfluidic devices developed in the period 2005-2016 capable of measuring protein biomarkers from the pM to fM range in formats compatible with POC testing, with a particular focus on the use of affordable microfluidic materials and compact low-cost signal interrogation. The integration of these two important features (essential unique selling points for the successful microfluidic diagnostic products) has been missed in previous review articles and explain the poor adoption of microfluidic technologies in this field. Most current miniaturised devices compromise either on the affordability, compactness and/or performance of the test, making current tests unsuitable for the POC measurement of protein biomarkers. Seven core technical areas, including (i) the selected strategy for antibody immobilisation, (ii) the surface area and surface-area-to-volume ratio, (iii) surface passivation, (iv) the biological matrix interference, (v) fluid control, (vi) the signal detection modes and (vii) the affordability of the manufacturing process and detection system, were identified as the key to the effective development of a sensitive and affordable microfluidic protein biomarker POC test.
Photodamage and the importance of photoprotection in biomolecular-powered device applications.

PubMed

Vandelinder, Virginia; Bachand, George D

2014-01-07

In recent years, an enhanced understanding of the mechanisms underlying photobleaching and photoblinking of fluorescent dyes has led to improved photoprotection strategies, such as reducing and oxidizing systems (ROXS) that reduce blinking and oxygen scavenging systems to reduce bleaching. Excitation of fluorescent dyes can also result in damage to catalytic proteins (e.g., biomolecular motors), affecting the performance of integrated devices. Here, we characterized the motility of microtubules driven by kinesin motor proteins using various photoprotection strategies, including a microfluidic deoxygenation device. Impaired motility of microtubules was observed at high excitation intensities in the absence of photoprotection as well as in the presence of an enzymatic oxygen scavenging system. In contrast, using a polydimethylsiloxane (PDMS) microfluidic deoxygenation device and ROXS, not only were the fluorophores slower to bleach but also moving the velocity and fraction of microtubules over time remained unaffected even at high excitation intensities. Further, we demonstrate the importance of photoprotection by examining the effect of photodamage on the behavior of a switchable mutant of kinesin. Overall, these results demonstrate that improved photoprotection strategies may have a profound impact on functional fluorescently labeled biomolecules in integrated devices.
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.
Transient deformation of a droplet near a microfluidic constriction: A quantitative analysis

NASA Astrophysics Data System (ADS)

Trégouët, Corentin; Salez, Thomas; Monteux, Cécile; Reyssat, Mathilde

2018-05-01

We report on experiments that consist of deforming a collection of monodisperse droplets produced by a microfluidic chip through a flow-focusing device. We show that a proper numerical modeling of the flow is necessary to access the stress applied by the latter on the droplet along its trajectory through the chip. This crucial step enables the full integration of the differential equation governing the dynamical deformation, and consequently the robust measurement of the interfacial tension by fitting the experiments with the calculated deformation. Our study thus demonstrates the feasibility of quantitative in situ rheology in microfluidic flows involving, e.g., droplets, capsules, or cells.
Ultrasensitive Nanoelectrospray Ionization-Mass Spectrometry using Poly(dimethylsiloxane) Microchips with Monolithically Integrated Emitters

PubMed Central

Sun, Xuefei; Kelly, Ryan T.; Tang, Keqi; Smith, Richard D.

2010-01-01

Summary Poly(dimethylsiloxane) (PDMS) is a widely used substrate for microfluidic devices, as it enables facile fabrication and has other distinctive properties. However, for applications requiring highly sensitive nanoelectrospray ionization mass spectrometry (nanoESI-MS) detection, the use of PDMS microdevices has been hindered by a large chemical background in the mass spectra that originates from the leaching of uncross-linked oligomers and other contaminants from the substrate. A more general challenge is that microfluidic devices containing monolithically integrated electrospray emitters are frequently unable to operate stably in the nanoflow regime where the best sensitivity is achieved. In this report, we extracted the contaminants from PDMS substrates using a series of solvents, eliminating the background observed when untreated PDMS microchips are used for nanoESI-MS, such that peptides at concentrations of 1 nM were readily detected. Optimization of the integrated emitter geometry enabled stable operation at flow rates as low as 10 nL/min. PMID:20617264
Microfluidic droplet sorting using integrated bilayer micro-valves

NASA Astrophysics Data System (ADS)

Chen, Yuncong; Tian, Yang; Xu, Zhen; Wang, Xinran; Yu, Sicong; Dong, Liang

2016-10-01

This paper reports on a microfluidic device capable of sorting microfluidic droplets utilizing conventional bilayer pneumatic micro-valves as sorting controllers. The device consists of two micro-valves placed symmetrically on two sides of a sorting area, each on top of a branching channel at an inclined angle with respect to the main channel. Changes in transmitted light intensity, induced by varying light absorbance by each droplet, are used to divert the droplet from the sorting area into one of the three outlet channels. When no valve is activated, the droplet flows into the outlet channel in the direction of the main channel. When one of the valves is triggered, the flexible membrane of valve will first be deflected. Once the droplet leaves the detection point, the deflected membrane will immediately return to its default flattened position, thereby exerting a drawing pressure on the droplet and deviating it from its original streamline to the outlet on the same side as the valve. This sorting method will be particularly suitable for numerous large-scale integrated microfluidic systems, where pneumatic micro-valves are already used. Only few structural modifications are needed to achieve droplet sorting capabilities in these systems. Due to the mechanical nature of diverting energy applied to droplets, the proposed sorting method may induce only minimal interference to biological species or microorganisms encapsulated inside the droplets that may accompany electrical, optical and magnetic-based techniques.
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.
Pneumatic oscillator circuits for timing and control of integrated microfluidics.

PubMed

Duncan, Philip N; Nguyen, Transon V; Hui, Elliot E

2013-11-05

Frequency references are fundamental to most digital systems, providing the basis for process synchronization, timing of outputs, and waveform synthesis. Recently, there has been growing interest in digital logic systems that are constructed out of microfluidics rather than electronics, as a possible means toward fully integrated laboratory-on-a-chip systems that do not require any external control apparatus. However, the full realization of this goal has not been possible due to the lack of on-chip frequency references, thus requiring timing signals to be provided from off-chip. Although microfluidic oscillators have been demonstrated, there have been no reported efforts to characterize, model, or optimize timing accuracy, which is the fundamental metric of a clock. Here, we report pneumatic ring oscillator circuits built from microfluidic valves and channels. Further, we present a compressible-flow analysis that differs fundamentally from conventional circuit theory, and we show the utility of this physically based model for the optimization of oscillator stability. Finally, we leverage microfluidic clocks to demonstrate circuits for the generation of phase-shifted waveforms, self-driving peristaltic pumps, and frequency division. Thus, pneumatic oscillators can serve as on-chip frequency references for microfluidic digital logic circuits. On-chip clocks and pumps both constitute critical building blocks on the path toward achieving autonomous laboratory-on-a-chip devices.
Microsphere integrated microfluidic disk: synergy of two techniques for rapid and ultrasensitive dengue detection

PubMed Central

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

2015-01-01

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. PMID:26548806

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.
Enabling liquid solvent structure analysis using hard x-ray absorption spectroscopy with a transferrable microfluidic reactor.

PubMed

Zheng, Jian; Zhang, Wei; Wang, Feng; Yu, Xiao-Ying

2018-05-10

In this paper, a vacuum compatible microfluidic device, system for analysis at the liquid vacuum interface, is integrated to hard x-ray absorption spectroscopy to obtain the local structure of K 3 [Fe(CN) 6 ] in aqueous solutions with three concentrations of 0.5 M, 0.05 M, and 0.005 M. The solutions were sealed in a microchannel 500 µm wide and 300 µm deep in a portable microfluidic device. The Fe K-edge x-ray absorption spectra indicate a presence of Fe(III) in the complex in water, with an octahedral geometry coordinated with 6 C atoms in the first shell with a distance of ~1.92 Å and 6 N atoms in the second shell with a distance of ~3.10 Å. Varying the concentration has no observable influence on the structure of K 3 [Fe(CN) 6 ]. Our results demonstrate the feasibility of using microfluidic based liquid cells in large synchrotron facilities. Using portable microfludic reactors provides a viable approach to enable multifaceted measurements of liquids in the future.
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.
Perspective use of direct human blood as an energy source in air-breathing hybrid microfluidic fuel cells

NASA Astrophysics Data System (ADS)

Dector, A.; Escalona-Villalpando, R. A.; Dector, D.; Vallejo-Becerra, V.; Chávez-Ramírez, A. U.; Arriaga, L. G.; Ledesma-García, J.

2015-08-01

This work presents a flexible and light air-breathing hybrid microfluidic fuel cell (HμFC) operated under biological conditions. A mixture of glucose oxidase, glutaraldehyde, multi-walled carbon nanotubes and vulcan carbon (GOx/VC-MWCNT-GA) was used as the bioanode. Meanwhile, integrating an air-exposed electrode (Pt/C) as the cathode enabled direct oxygen delivery from air. The microfluidic fuel cell performance was evaluated using glucose obtained from three different sources as the fuel: 5 mM glucose in phosphate buffer, human serum and human blood. For the last fuel, an open circuit voltage and maximum power density of 0.52 V and 0.20 mW cm-2 (at 0.38 V) were obtained respectively; meanwhile the maximum current density was 1.1 mA cm-2. Furthermore, the stability of the device was measured in terms of recovery after several polarization curves, showing excellent results. Although this air-breathing HμFC requires technological improvements before being tested in a biomedical device, it represents the best performance to date for a microfluidic fuel cell using human blood as glucose source.
Enabling liquid solvent structure analysis using hard x-ray absorption spectroscopy with a transferrable microfluidic reactor

NASA Astrophysics Data System (ADS)

Zheng, Jian; Zhang, Wei; Wang, Feng; Yu, Xiao-Ying

2018-05-01

In this paper, a vacuum compatible microfluidic device, system for analysis at the liquid vacuum interface, is integrated to hard x-ray absorption spectroscopy to obtain the local structure of K3[Fe(CN)6] in aqueous solutions with three concentrations of 0.5 M, 0.05 M, and 0.005 M. The solutions were sealed in a microchannel 500 µm wide and 300 µm deep in a portable microfluidic device. The Fe K-edge x-ray absorption spectra indicate a presence of Fe(III) in the complex in water, with an octahedral geometry coordinated with 6 C atoms in the first shell with a distance of ~1.92 Å and 6 N atoms in the second shell with a distance of ~3.10 Å. Varying the concentration has no observable influence on the structure of K3[Fe(CN)6]. Our results demonstrate the feasibility of using microfluidic based liquid cells in large synchrotron facilities. Using portable microfludic reactors provides a viable approach to enable multifaceted measurements of liquids in the future.
Enabling liquid solvent structure analysis using hard x-ray absorption spectroscopy with a transferrable microfluidic reactor

DOE PAGES

Zheng, Jian; Zhang, Wei; Wang, Feng; ...

2018-04-11

In this study, a vacuum compatible microfluidic device, system for analysis at the liquid vacuum interface, is integrated to hard x-ray absorption spectroscopy to obtain the local structure of K 3[Fe(CN) 6] in aqueous solutions with three concentrations of 0.5 M, 0.05 M, and 0.005 M. The solutions were sealed in a microchannel 500 µm wide and 300 µm deep in a portable microfluidic device. The Fe K-edge x-ray absorption spectra indicate a presence of Fe(III) in the complex in water, with an octahedral geometry coordinated with 6 C atoms in the first shell with a distance of ~1.92 Åmore » and 6 N atoms in the second shell with a distance of ~3.10 Å. Varying the concentration has no observable influence on the structure of K 3[Fe(CN) 6]. Our results demonstrate the feasibility of using microfluidic based liquid cells in large synchrotron facilities. Using portable microfludic reactors provides a viable approach to enable multifaceted measurements of liquids in the future.« less
Enabling liquid solvent structure analysis using hard x-ray absorption spectroscopy with a transferrable microfluidic reactor

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

Zheng, Jian; Zhang, Wei; Wang, Feng

In this study, a vacuum compatible microfluidic device, system for analysis at the liquid vacuum interface, is integrated to hard x-ray absorption spectroscopy to obtain the local structure of K 3[Fe(CN) 6] in aqueous solutions with three concentrations of 0.5 M, 0.05 M, and 0.005 M. The solutions were sealed in a microchannel 500 µm wide and 300 µm deep in a portable microfluidic device. The Fe K-edge x-ray absorption spectra indicate a presence of Fe(III) in the complex in water, with an octahedral geometry coordinated with 6 C atoms in the first shell with a distance of ~1.92 Åmore » and 6 N atoms in the second shell with a distance of ~3.10 Å. Varying the concentration has no observable influence on the structure of K 3[Fe(CN) 6]. Our results demonstrate the feasibility of using microfluidic based liquid cells in large synchrotron facilities. Using portable microfludic reactors provides a viable approach to enable multifaceted measurements of liquids in the future.« less
Enabling liquid solvent structure analysis using hard x-ray absorption spectroscopy with a transferrable microfluidic reactor

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

Zheng, Jian; Zhang, Wei; Wang, Feng

In this paper, a vacuum compatible microfluidic device, System for Analysis at the Liquid Vacuum Interface (SALVI), is integrated to hard x-ray absorption spectroscopy (XAS) to obtain the local structure of K3[Fe(CN)6] in aqueous solutions with three concentrations of 0.5 M, 0.05 M, and 0.005 M. The solutions were sealed in a microchannel of 500 μm wide and 300 µm deep in a portable microfluidic device. The Fe K-edge x-ray absorption spectra show that the complex in water is Fe(III). The complex is present with octahedral geometry coordinated with 6 C atoms in the first shell with a distance ofmore » ~1.92 Å and 6 N atoms in the second shell with a distance of ~3.10 Å. Varying the concentration has no observable influence on the structure of K3[Fe(CN)6]. Our results demonstrate the feasibility of using microfluidic based liquid cells in large synchrotron facilities and it is a viable approach to enable multifaceted measurements of liquids in the future.« less
High-throughput particle manipulation by hydrodynamic, electrokinetic, and dielectrophoretic effects in an integrated microfluidic chip

PubMed Central

Li, Shunbo; Li, Ming; Bougot-Robin, Kristelle; Cao, Wenbin; Yeung Yeung Chau, Irene; Li, Weihua; Wen, Weijia

2013-01-01

Integrating different steps on a chip for cell manipulations and sample preparation is of foremost importance to fully take advantage of microfluidic possibilities, and therefore make tests faster, cheaper and more accurate. We demonstrated particle manipulation in an integrated microfluidic device by applying hydrodynamic, electroosmotic (EO), electrophoretic (EP), and dielectrophoretic (DEP) forces. The process involves generation of fluid flow by pressure difference, particle trapping by DEP force, and particle redirect by EO and EP forces. Both DC and AC signals were applied, taking advantages of DC EP, EO and AC DEP for on-chip particle manipulation. Since different types of particles respond differently to these signals, variations of DC and AC signals are capable to handle complex and highly variable colloidal and biological samples. The proposed technique can operate in a high-throughput manner with thirteen independent channels in radial directions for enrichment and separation in microfluidic chip. We evaluated our approach by collecting Polystyrene particles, yeast cells, and E. coli bacteria, which respond differently to electric field gradient. Live and dead yeast cells were separated successfully, validating the capability of our device to separate highly similar cells. Our results showed that this technique could achieve fast pre-concentration of colloidal particles and cells and separation of cells depending on their vitality. Hydrodynamic, DC electrophoretic and DC electroosmotic forces were used together instead of syringe pump to achieve sufficient fluid flow and particle mobility for particle trapping and sorting. By eliminating bulky mechanical pumps, this new technique has wide applications for in situ detection and analysis. PMID:24404011
High-throughput particle manipulation by hydrodynamic, electrokinetic, and dielectrophoretic effects in an integrated microfluidic chip.

PubMed

Li, Shunbo; Li, Ming; Bougot-Robin, Kristelle; Cao, Wenbin; Yeung Yeung Chau, Irene; Li, Weihua; Wen, Weijia

2013-01-01

Integrating different steps on a chip for cell manipulations and sample preparation is of foremost importance to fully take advantage of microfluidic possibilities, and therefore make tests faster, cheaper and more accurate. We demonstrated particle manipulation in an integrated microfluidic device by applying hydrodynamic, electroosmotic (EO), electrophoretic (EP), and dielectrophoretic (DEP) forces. The process involves generation of fluid flow by pressure difference, particle trapping by DEP force, and particle redirect by EO and EP forces. Both DC and AC signals were applied, taking advantages of DC EP, EO and AC DEP for on-chip particle manipulation. Since different types of particles respond differently to these signals, variations of DC and AC signals are capable to handle complex and highly variable colloidal and biological samples. The proposed technique can operate in a high-throughput manner with thirteen independent channels in radial directions for enrichment and separation in microfluidic chip. We evaluated our approach by collecting Polystyrene particles, yeast cells, and E. coli bacteria, which respond differently to electric field gradient. Live and dead yeast cells were separated successfully, validating the capability of our device to separate highly similar cells. Our results showed that this technique could achieve fast pre-concentration of colloidal particles and cells and separation of cells depending on their vitality. Hydrodynamic, DC electrophoretic and DC electroosmotic forces were used together instead of syringe pump to achieve sufficient fluid flow and particle mobility for particle trapping and sorting. By eliminating bulky mechanical pumps, this new technique has wide applications for in situ detection and analysis.
From functional structure to packaging: full-printing fabrication of a microfluidic chip.

PubMed

Zheng, Fengyi; Pu, Zhihua; He, Enqi; Huang, Jiasheng; Yu, Bocheng; Li, Dachao; Li, Zhihong

2018-05-24

This paper presents a concept of a full-printing methodology aiming at convenient and fast fabrication of microfluidic devices. For the first time, we achieved a microfluidic biochemical sensor with all functional structures fabricated by inkjet printing, including electrodes, immobilized enzymes, microfluidic components and packaging. With the cost-effective and rapid process, this method provides the possibility of quick model validation of a novel lab-on-chip system. In this study, a three-electrode electrochemical system was integrated successfully with glucose oxidase immobilization gel and sealed in an ice channel, forming a disposable microfluidic sensor for glucose detection. This fully-printed chip was characterized and showed good sensitivity and a linear section at a low-level concentration of glucose (0-10 mM). With the aid of automatic equipment, the fully-printed sensor can be massively produced with low cost.
"Hot-wire" microfluidic flowmeter based on a microfiber coupler.

PubMed

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

2016-12-15

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

PubMed

Cheong, Raymond; Paliwal, Saurabh; Levchenko, Andre

2010-08-01

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

PubMed

Fu, Xiaotong; Mavrogiannis, Nicholas; Ibo, Markela; Crivellari, Francesca; Gagnon, Zachary R

2017-01-01

We present a new type of free-flow electrophoresis (FFE) device for performing on-chip microfluidic isotachophoresis and zone electrophoresis. FFE is performed using metal gallium electrodes, which are isolated from a main microfluidic flow channel using thin micron-scale polydimethylsiloxane/carbon black (PDMS/CB) composite membranes integrated directly into the sidewalls of the microfluidic channel. The thin membrane allows for field penetration and effective electrophoresis, but serves to prevent bubble generation at the electrodes from electrolysis. We experimentally demonstrate the ability to use this platform to perform on-chip free-flow electrophoretic separation and isotachophoretic concentration. Due to the small size and simple fabrication procedure, this PDMS/CB platform could be used as a part of an on-chip upstream sample preparation toolkit for portable microfluidic diagnostic applications. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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.
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 microfluidic platform with integrated arrays for immunologic assays for biological pathogen detection

NASA Astrophysics Data System (ADS)

Klemm, Richard; Becker, Holger; Hlawatsch, Nadine; Julich, Sandra; Miethe, Peter; Moche, Christian; Schattschneider, Sebastian; Tomaso, Herbert; Gärtner, Claudia

2014-05-01

The ability to integrate complete assays on a microfluidic chip helps to greatly simplify instrument requirements and allows the use of lab-on-a-chip technology in the field. A core application for such field-portable systems is the detection of pathogens in a CBRN scenario such as permanent monitoring of airborne pathogens, e.g. in subway stations or hospitals etc. An immunological assay was chosen as method for the pathogen identification. The conceptual approach was its realization as a lab-on-a-chip system, enabling an easy handling of the sample in an automated manner. The immunological detection takes place on an antibody array directly implemented in the microfluidic network. Different immobilization strategies will be presented showing the performance of the system. Central elements of the disposable microfluidic device like fluidic interface, turning valves, liquid introduction and waste storage, as well as the architecture of measurement and control fluidic network, will be introduced. Overall process times of about 30 minutes were achieved and assays for the detection of Francisella tularensis and Yersinia pestis are presented. An important feature of the integrated lab-on-a-chip approach is that all waste liquids remain on-chip and contamination risks can be avoided.
[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.
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.

Monolithic integration of microfluidic channels and semiconductor lasers.

PubMed

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

2006-08-21

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

NASA Astrophysics Data System (ADS)

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

2006-08-01

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

PubMed

Mauk, Michael G; Liu, Changchun; Qiu, Xianbo; Chen, Dafeng; Song, Jinzhao; Bau, Haim H

2017-01-01

Microfluidic cassettes ("chips") for processing and analysis of clinical specimens and other sample types facilitate point-of-care (POC) immunoassays and nucleic acid based amplification tests. These single-use test chips can be self-contained and made amenable to autonomous operation-reducing or eliminating supporting instrumentation-by incorporating laminated, pliable "pouch" and membrane structures for fluid storage, pumping, mixing, and flow control. Materials and methods for integrating flexible pouch compartments and diaphragm valves into hard plastic (e.g., acrylic and polycarbonate) microfluidic "chips" for reagent storage, fluid actuation, and flow control are described. We review several versions of these pouch chips for immunoassay and nucleic acid amplification tests, and describe related fabrication techniques. These protocols thus offer a "toolbox" of methods for storage, pumping, and flow control functions in microfluidic devices.
Integrated microfluidic system with simultaneous emulsion generation and concentration.

PubMed

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

2016-03-15

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

DOEpatents

Herr, Amy E; Singh, Anup K; Throckmorton, Daniel J

2015-02-24

A micro-analytical platform for performing electrophoresis-based immunoassays was developed by integrating photopolymerized cross-linked polyacrylamide gels within a microfluidic device. The microfluidic immunoassays are performed by gel electrophoretic separation and quantifying analyte concentration based upon conventional polyacrylamide gel electrophoresis (PAGE). To retain biological activity of proteins and maintain intact immune complexes, native PAGE conditions were employed. Both direct (non-competitive) and competitive immunoassay formats are demonstrated in microchips for detecting toxins and biomarkers (cytokines, c-reactive protein) in bodily fluids (serum, saliva, oral fluids). Further, a description of gradient gels fabrication is included, in an effort to describe methods we have developed for further optimization of on-chip PAGE immunoassays. The described chip-based PAGE immunoassay method enables immunoassays that are fast (minutes) and require very small amounts of sample (less than a few microliters). Use of microfabricated chips as a platform enables integration, parallel assays, automation and development of portable devices.
Microchannel gel electrophoretic separation systems and methods for preparing and using

DOEpatents

Herr, Amy; Singh, Anup K; Throckmorton, Daniel J

2013-09-03

A micro-analytical platform for performing electrophoresis-based immunoassays was developed by integrating photopolymerized cross-linked polyacrylamide gels within a microfluidic device. The microfluidic immunoassays are performed by gel electrophoretic separation and quantifying analyte concentration based upon conventional polyacrylamide gel electrophoresis (PAGE). To retain biological activity of proteins and maintain intact immune complexes, native PAGE conditions were employed. Both direct (non-competitive) and competitive immunoassay formats are demonstrated in microchips for detecting toxins and biomarkers (cytokines, c-reactive protein) in bodily fluids (serum, saliva, oral fluids). Further, a description of gradient gels fabrication is included, in an effort to describe methods we have developed for further optimization of on-chip PAGE immunoassays. The described chip-based PAGE immunoassay method enables immunoassays that are fast (minutes) and require very small amounts of sample (less than a few microliters). Use of microfabricated chips as a platform enables integration, parallel assays, automation and development of portable devices.
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.
Simple and inexpensive microfluidic devices for the generation of monodisperse multiple emulsions

NASA Astrophysics Data System (ADS)

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

2014-01-01

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

NASA Astrophysics Data System (ADS)

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

2012-03-01

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

NASA Astrophysics Data System (ADS)

Evstrapov, A. A.

2017-11-01

The use of micro- and nanofluidic systems in modern analytical instruments allow you to implement a number of unique opportunities and achieve ultra-high measurement sensitivity. The possibility of manipulation of the individual biological objects (cells, bacteria, viruses, proteins, nucleic acids) in a liquid medium caused the development of devices on microchip platform for methods: chromatographic and electrophoretic analyzes; polymerase chain reaction; sequencing of nucleic acids; immunoassay; cytometric studies. Development of micro and nano fabrication technologies, materials science, surface chemistry, analytical chemistry, cell engineering have led to the creation of a unique systems such as “lab-on-a-chip”, “human-on-a-chip” and other. This article discusses common in microfluidics materials and methods of making functional structures. Examples of integration of nanoscale structures in microfluidic devices for the implementation of new features and improve the technical characteristics of devices and systems are shown.
Droplet Microfluidics for Chip-Based Diagnostics

PubMed Central

Kaler, Karan V. I. S.; Prakash, Ravi

2014-01-01

Droplet microfluidics (DMF) is a fluidic handling technology that enables precision control over dispensing and subsequent manipulation of droplets in the volume range of microliters to picoliters, on a micro-fabricated device. There are several different droplet actuation methods, all of which can generate external stimuli, to either actively or passively control the shape and positioning of fluidic droplets over patterned substrates. In this review article, we focus on the operation and utility of electro-actuation-based DMF devices, which utilize one or more micro-/nano-patterned substrates to facilitate electric field-based handling of chemical and/or biological samples. The underlying theory of DMF actuations, device fabrication methods and integration of optical and opto-electronic detectors is discussed in this review. Example applications of such electro-actuation-based DMF devices have also been included, illustrating the various actuation methods and their utility in conducting chip-based laboratory and clinical diagnostic assays. PMID:25490590
Autonomous microfluidic system for phosphate detection.

PubMed

McGraw, Christina M; Stitzel, Shannon E; Cleary, John; Slater, Conor; Diamond, Dermot

2007-02-28

Miniaturization of analytical devices through the advent of microfluidics and micro total analysis systems is an important step forward for applications such as medical diagnostics and environmental monitoring. The development of field-deployable instruments requires that the entire system, including all necessary peripheral components, be miniaturized and packaged in a portable device. A sensor for long-term monitoring of phosphate levels has been developed that incorporates sampling, reagent and waste storage, detection, and wireless communication into a complete, miniaturized system. The device employs a low-power detection and communication system, so the entire instrument can operate autonomously for 7 days on a single rechargeable, 12V battery. In addition, integration of a wireless communication device allows the instrument to be controlled and results to be downloaded remotely. This autonomous system has a limit of detection of 0.3mg/L and a linear dynamic range between 0 and 20mg/L.
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.
Technologies for autonomous integrated lab-on-chip systems for space missions

NASA Astrophysics Data System (ADS)

Nascetti, A.; Caputo, D.; Scipinotti, R.; de Cesare, G.

2016-11-01

Lab-on-chip devices are ideal candidates for use in space missions where experiment automation, system compactness, limited weight and low sample and reagent consumption are required. Currently, however, most microfluidic systems require external desktop instrumentation to operate and interrogate the chip, thus strongly limiting their use as stand-alone systems. In order to overcome the above-mentioned limitations our research group is currently working on the design and fabrication of "true" lab-on-chip systems that integrate in a single device all the analytical steps from the sample preparation to the detection without the need for bulky external components such as pumps, syringes, radiation sources or optical detection systems. Three critical points can be identified to achieve 'true' lab-on-chip devices: sample handling, analytical detection and signal transduction. For each critical point, feasible solutions are presented and evaluated. Proposed microfluidic actuation and control is based on electrowetting on dielectrics, autonomous capillary networks and active valves. Analytical detection based on highly specific chemiluminescent reactions is used to avoid external radiation sources. Finally, the integration on the same chip of thin film sensors based on hydrogenated amorphous silicon is discussed showing practical results achieved in different sensing tasks.
Rapid PCR amplification using a microfluidic device with integrated microwave heating and air impingement cooling.

PubMed

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

2010-07-07

A microwave heating system is described for performing polymerase chain reaction (PCR) in a microfluidic device. The heating system, in combination with air impingement cooling, provided rapid thermal cycling with heating and cooling rates of up to 65 degrees C s(-1) and minimal over- or under-shoot (+/-0.1 degrees C) when reaching target temperatures. In addition, once the required temperature was reached it could be maintained with an accuracy of +/-0.1 degrees C. To demonstrate the functionality of the system, PCR was successfully performed for the amplification of the Amelogenin locus using heating rates and quantities an order of magnitude faster and smaller than current commercial instruments.
Skin-inspired hydrogel-elastomer hybrids with robust interfaces and functional microstructures

NASA Astrophysics Data System (ADS)

Yuk, Hyunwoo; Zhang, Teng; Parada, German Alberto; Liu, Xinyue; Zhao, Xuanhe

2016-06-01

Inspired by mammalian skins, soft hybrids integrating the merits of elastomers and hydrogels have potential applications in diverse areas including stretchable and bio-integrated electronics, microfluidics, tissue engineering, soft robotics and biomedical devices. However, existing hydrogel-elastomer hybrids have limitations such as weak interfacial bonding, low robustness and difficulties in patterning microstructures. Here, we report a simple yet versatile method to assemble hydrogels and elastomers into hybrids with extremely robust interfaces (interfacial toughness over 1,000 Jm-2) and functional microstructures such as microfluidic channels and electrical circuits. The proposed method is generally applicable to various types of tough hydrogels and diverse commonly used elastomers including polydimethylsiloxane Sylgard 184, polyurethane, latex, VHB and Ecoflex. We further demonstrate applications enabled by the robust and microstructured hydrogel-elastomer hybrids including anti-dehydration hydrogel-elastomer hybrids, stretchable and reactive hydrogel-elastomer microfluidics, and stretchable hydrogel circuit boards patterned on elastomer.
Modular microfluidics for point-of-care protein purifications

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

Millet, L. J.; Lucheon, J. D.; Standaert, R. F.

Biochemical separations are the heart of diagnostic assays and purification methods for biologics. On-chip miniaturization and modularization of separation procedures will enable the development of customized, portable devices for personalized health-care diagnostics and point-of-use production of treatments. In this report, we describe the design and fabrication of miniature ion exchange, size exclusion and affinity chromatography modules for on-chip clean-up of recombinantly-produced proteins. Our results demonstrate that these common separations techniques can be implemented in microfluidic modules with performance comparable to conventional approaches. We introduce embedded 3-D microfluidic interconnects for integrating micro-scale separation modules that can be arranged and reconfigured tomore » suit a variety of fluidic operations or biochemical processes. In conclusion, we demonstrate the utility of the modular approach with a platform for the enrichment of enhanced green fluorescent protein (eGFP) from Escherichia coli lysate through integrated affinity and size-exclusion chromatography modules.« less

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
Integrated microfluidic systems for cell lysis, mixing/pumping and DNA amplification

NASA Astrophysics Data System (ADS)

Lee, Chia-Yen; Lee, Gwo-Bin; Lin, Jr-Lung; Huang, Fu-Chun; Liao, Chia-Sheng

2005-06-01

The present paper reports a fully automated microfluidic system for the DNA amplification process by integrating an electroosmotic pump, an active micromixer and an on-chip temperature control system. In this DNA amplification process, the cell lysis is initially performed in a micro cell lysis reactor. Extracted DNA samples, primers and reagents are then driven electroosmotically into a mixing region where they are mixed by the active micromixer. The homogeneous mixture is then thermally cycled in a micro-PCR (polymerase chain reaction) chamber to perform DNA amplification. Experimental results show that the proposed device can successfully automate the sample pretreatment operation for DNA amplification, thereby delivering significant time and effort savings. The new microfluidic system, which facilitates cell lysis, sample driving/mixing and DNA amplification, could provide a significant contribution to ongoing efforts to miniaturize bio-analysis systems by utilizing a simple fabrication process and cheap materials.
Droplet-based Biosensing for Lab-on-a-Chip, Open Microfluidics Platforms

PubMed Central

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

2016-01-01

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

PubMed

Millet, L J; Lucheon, J D; Standaert, R F; Retterer, S T; Doktycz, M J

2015-04-21

Biochemical separations are the heart of diagnostic assays and purification methods for biologics. On-chip miniaturization and modularization of separation procedures will enable the development of customized, portable devices for personalized health-care diagnostics and point-of-use production of treatments. In this report, we describe the design and fabrication of miniature ion exchange, size exclusion and affinity chromatography modules for on-chip clean-up of recombinantly-produced proteins. Our results demonstrate that these common separations techniques can be implemented in microfluidic modules with performance comparable to conventional approaches. We introduce embedded 3-D microfluidic interconnects for integrating micro-scale separation modules that can be arranged and reconfigured to suit a variety of fluidic operations or biochemical processes. We demonstrate the utility of the modular approach with a platform for the enrichment of enhanced green fluorescent protein (eGFP) from Escherichia coli lysate through integrated affinity and size-exclusion chromatography modules.
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.
Modular microfluidics for point-of-care protein purifications

DOE PAGES

Millet, L. J.; Lucheon, J. D.; Standaert, R. F.; ...

2015-01-01

Biochemical separations are the heart of diagnostic assays and purification methods for biologics. On-chip miniaturization and modularization of separation procedures will enable the development of customized, portable devices for personalized health-care diagnostics and point-of-use production of treatments. In this report, we describe the design and fabrication of miniature ion exchange, size exclusion and affinity chromatography modules for on-chip clean-up of recombinantly-produced proteins. Our results demonstrate that these common separations techniques can be implemented in microfluidic modules with performance comparable to conventional approaches. We introduce embedded 3-D microfluidic interconnects for integrating micro-scale separation modules that can be arranged and reconfigured tomore » suit a variety of fluidic operations or biochemical processes. In conclusion, we demonstrate the utility of the modular approach with a platform for the enrichment of enhanced green fluorescent protein (eGFP) from Escherichia coli lysate through integrated affinity and size-exclusion chromatography modules.« less
Droplet-based Biosensing for Lab-on-a-Chip, Open Microfluidics Platforms.

PubMed

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

2016-04-14

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

PubMed

Doonan, Steven R; Bailey, Ryan C

2017-04-04

By rapidly creating libraries of thousands of unique, miniaturized reactors, droplet microfluidics provides a powerful method for automating high-throughput chemical analysis. In order to engineer in-droplet assays, microfluidic devices must add reagents into droplets, remove fluid from droplets, and perform other necessary operations, each typically provided by a unique, specialized geometry. Unfortunately, modifying device performance or changing operations usually requires re-engineering the device among these specialized geometries, a time-consuming and costly process when optimizing in-droplet assays. To address this challenge in implementing droplet chemistry, we have developed the "K-channel," which couples a cross-channel flow to the segmented droplet flow to enable a range of operations on passing droplets. K-channels perform reagent injection (0-100% of droplet volume), fluid extraction (0-50% of droplet volume), and droplet splitting (1:1-1:5 daughter droplet ratio). Instead of modifying device dimensions or channel configuration, adjusting external conditions, such as applied pressure and electric field, selects the K-channel process and tunes its magnitude. Finally, interfacing a device-embedded magnet allows selective capture of 96% of droplet-encapsulated superparamagnetic beads during 1:1 droplet splitting events at ∼400 Hz. Addition of a second K-channel for injection (after the droplet splitting K-channel) enables integrated washing of magnetic beads within rapidly moving droplets. Ultimately, the K-channel provides an exciting opportunity to perform many useful droplet operations across a range of magnitudes without requiring architectural modifications. Therefore, we envision the K-channel as a versatile, easy to use microfluidic component enabling diverse, in-droplet (bio)chemical manipulations.
Beyond isolated cells: microfluidic transport of large tissue for pancreatic cancer diagnosis

NASA Astrophysics Data System (ADS)

Das, Ronnie; Murphy, Rachel G.; Seibel, Eric J.

2015-03-01

For cancer diagnoses, core biopsies (CBs) obtained from patients using coring needles (CNs) are traditionally visualized and assessed on microscope slides by pathologists after samples are processed and sectioned. A fundamental gain in optical information (i.e., diagnosis/staging) may be achieved when whole, unsectioned CBs (L = 5-20, D = 0.5-2.0 mm) are analyzed in 3D. This approach preserves CBs for traditional pathology and maximizes the diagnostic potential of patient samples. To bridge CNs/CBs with imaging, our group developed a microfluidic device that performs biospecimen preparation on unsectioned CBs for pathology. The ultimate goal is an automated and rapid point-of-care system that aids pathologists by processing tissue for advanced 3D imaging platforms. An inherent, but essential device feature is the microfluidic transport of CBs, which has not been previously investigated. Early experiments demonstrated proof-of-concept: pancreas CBs (D = 0.3-2.0 mm) of set lengths were transported in straight/curved microchannels, but dimensional tolerance and flow rates were variable, and preservation of CB integrity was uncontrolled. A second study used metal cylinder substitutes (L = 10, D = 1 mm) in microchannels to understand the transport mechanism. However, CBs are imperfectly shaped, rough, porous and viscoelastic. In this study, fresh/formalin-fixed porcine and human pancreas CBs were deposited into our device through a custom interface using clinical CNs. CB integrity (i.e., sample viability) may be assessed at every stage using an optomechanical metric: physical breaks were determined when specimen intensity profile data deviated beyond xavg + 2σ. Flow rates for human CBs were determined for several CNs, and microfluidic transport of fresh and formalin-fixed CBs was analyzed.
Acoustically and Electrokinetically Driven Transport in Microfluidic Devices

NASA Astrophysics Data System (ADS)

Sayar, Ersin

Electrokinetically driven flows are widely employed as a primary method for liquid pumping in micro-electromechanical systems. Mixing of analytes and reagents is limited in microfluidic devices due to the low Reynolds number of the flows. Acoustic excitations have recently been suggested to promote mixing in the microscale flow systems. Electrokinetic flows through straight microchannels were investigated using the Poisson-Boltzmann and Nernst-Planck models. The acoustic wave/fluid flow interactions in a microchannel were investigated via the development of two and three-dimensional dynamic predictive models for flows with field couplings of the electrical, mechanical and fluid flow quantities. The effectiveness and applicability of electrokinetic augmentation in flexural plate wave micropumps for enhanced capabilities were explored. The proposed concept can be exploited to integrate micropumps into complex microfluidic chips improving the portability of micro-total-analysis systems along with the capabilities of actively controlling acoustics and electrokinetics for micro-mixer applications. Acoustically excited flows in microchannels consisting of flexural plate wave devices and thin film resonators were considered. Compressible flow fields were considered to accommodate the acoustic excitations produced by a vibrating wall. The velocity and pressure profiles for different parameters including frequency, channel height, wave amplitude and length were investigated. Coupled electrokinetics and acoustics cases were investigated while the electric field intensity of the electrokinetic body forces and actuation frequency of acoustic excitations were varied. Multifield analysis of a piezoelectrically actuated valveless micropump was also presented. The effect of voltage and frequency on membrane deflection and flow rate were investigated. Detailed fluid/solid deformation coupled simulations of piezoelectric valveless micropump have been conducted to predict the generated time averaged flow rates. Developed coupled solid and fluid mechanics models can be utilized to integrate flow-through sensors with microfluidic chips.
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.
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.
Characterization and optimization of low cost microfluidic thread based electroanalytical device for micro flow injection analysis.

PubMed

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

2017-01-25

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

PubMed

Hu, Jie; Cui, Xingye; Gong, Yan; Xu, Xiayu; Gao, Bin; Wen, Ting; Lu, Tian Jian; Xu, Feng

2016-01-01

Cardiovascular diseases (CVDs) are the main causes of morbidity and mortality in the world where about 4 in every 5 CVD deaths happen in low- and middle-income countries (LMICs). Most CVDs are preventable and curable, which is largely dependent on timely and effective interventions, including diagnosis, prognosis and therapeutic monitoring. However, these interventions are high-cost in high income countries and are usually lacking in LMICs. Thanks to the rapid development of microfluidics and nanotechnology, lots of portable analytical devices are developed for detection of CVDs at the point-of-care (POC). In the meantime, smartphone, as a versatile and powerful handheld tool, has been employed not only as a reader for microfluidic assays, but also as an analyzer for physiological indexes. In this review, we present a comprehensive introduction of the current status and potential development direction on POC diagnostics for CVDs. First of all, we introduce some main facts about CVDs and their standard diagnostic procedures and methods. Second, we discuss about both commercially available POC devices and developed prototypes for detection of CVDs via immunoassays. Subsequently, we report the advances in smartphone-based readout for microfluidic assays. Finally, we present some examples using smartphone, individually or combined with other components or devices, for CVD monitoring. We envision an integrated smartphone-based system capable of functioning blood tests, disease examination, and imaging will come in the future. Copyright © 2016 Elsevier Inc. All rights reserved.
Low-temperature bonding process for the fabrication of hybrid glass-membrane organ-on-a-chip devices

NASA Astrophysics Data System (ADS)

Pocock, Kyall J.; Gao, Xiaofang; Wang, Chenxi; Priest, Craig; Prestidge, Clive A.; Mawatari, Kazuma; Kitamori, Takehiko; Thierry, Benjamin

2016-10-01

The integration of microfluidics with living biological systems has paved the way to the exciting concept of "organs-on-a-chip," which aims at the development of advanced in vitro models that replicate the key features of human organs. Glass-based devices have long been utilized in the field of microfluidics but the integration of alternative functional elements within multilayered glass microdevices, such as polymeric membranes, remains a challenge. To this end, we have extended a previously reported approach for the low-temperature bonding of glass devices that enables the integration of a functional polycarbonate porous membrane. The process was initially developed and optimized on specialty low-temperature bonding equipment (μTAS2001, Bondtech, Japan) and subsequently adapted to more widely accessible hot embosser units (EVG520HE Hot Embosser, EVG, Austria). The key aspect of this method is the use of low temperatures compatible with polymeric membranes. Compared to borosilicate glass bonding (650°C) and quartz/fused silica bonding (1050°C) processes, this method maintains the integrity and functionality of the membrane (Tg 150°C for polycarbonate). Leak tests performed showed no damage or loss of integrity of the membrane for up to 150 h, indicating sufficient bond strength for long-term cell culture. A feasibility study confirmed the growth of dense and functional monolayers of Caco-2 cells within 5 days.
Materials for microfluidic chip fabrication.

PubMed

Ren, Kangning; Zhou, Jianhua; Wu, Hongkai

2013-11-19

Through manipulating fluids using microfabricated channel and chamber structures, microfluidics is a powerful tool to realize high sensitive, high speed, high throughput, and low cost analysis. In addition, the method can establish a well-controlled microenivroment for manipulating fluids and particles. It also has rapid growing implementations in both sophisticated chemical/biological analysis and low-cost point-of-care assays. Some unique phenomena emerge at the micrometer scale. For example, reactions are completed in a shorter amount of time as the travel distances of mass and heat are relatively small; the flows are usually laminar; and the capillary effect becomes dominant owing to large surface-to-volume ratios. In the meantime, the surface properties of the device material are greatly amplified, which can lead to either unique functions or problems that we would not encounter at the macroscale. Also, each material inherently corresponds with specific microfabrication strategies and certain native properties of the device. Therefore, the material for making the device plays a dominating role in microfluidic technologies. In this Account, we address the evolution of materials used for fabricating microfluidic chips, and discuss the application-oriented pros and cons of different materials. This Account generally follows the order of the materials introduced to microfluidics. Glass and silicon, the first generation microfluidic device materials, are perfect for capillary electrophoresis and solvent-involved applications but expensive for microfabriaction. Elastomers enable low-cost rapid prototyping and high density integration of valves on chip, allowing complicated and parallel fluid manipulation and in-channel cell culture. Plastics, as competitive alternatives to elastomers, are also rapid and inexpensive to microfabricate. Their broad variety provides flexible choices for different needs. For example, some thermosets support in-situ fabrication of arbitrary 3D structures, while some perfluoropolymers are extremely inert and antifouling. Chemists can use hydrogels as highly permeable structural material, which allows diffusion of molecules without bulk fluid flows. They are used to support 3D cell culture, to form diffusion gradient, and to serve as actuators. Researchers have recently introduced paper-based devices, which are extremely low-cost to prepare and easy to use, thereby promising in commercial point-of-care assays. In general, the evolution of chip materials reflects the two major trends of microfluidic technology: powerful microscale research platforms and low-cost portable analyses. For laboratory research, chemists choosing materials generally need to compromise the ease in prototyping and the performance of the device. However, in commercialization, the major concerns are the cost of production and the ease and reliability in use. There may be new growth in the combination of surface engineering, functional materials, and microfluidics, which is possibly accomplished by the utilization of composite materials or hybrids for advanced device functions. Also, significant expanding of commercial applications can be predicted.
Integrated sample-to-detection chip for nucleic acid test assays.

PubMed

Prakash, R; Pabbaraju, K; Wong, S; Tellier, R; Kaler, K V I S

2016-06-01

Nucleic acid based diagnostic techniques are routinely used for the detection of infectious agents. Most of these assays rely on nucleic acid extraction platforms for the extraction and purification of nucleic acids and a separate real-time PCR platform for quantitative nucleic acid amplification tests (NATs). Several microfluidic lab on chip (LOC) technologies have been developed, where mechanical and chemical methods are used for the extraction and purification of nucleic acids. Microfluidic technologies have also been effectively utilized for chip based real-time PCR assays. However, there are few examples of microfluidic systems which have successfully integrated these two key processes. In this study, we have implemented an electro-actuation based LOC micro-device that leverages multi-frequency actuation of samples and reagents droplets for chip based nucleic acid extraction and real-time, reverse transcription (RT) PCR (qRT-PCR) amplification from clinical samples. Our prototype micro-device combines chemical lysis with electric field assisted isolation of nucleic acid in a four channel parallel processing scheme. Furthermore, a four channel parallel qRT-PCR amplification and detection assay is integrated to deliver the sample-to-detection NAT chip. The NAT chip combines dielectrophoresis and electrostatic/electrowetting actuation methods with resistive micro-heaters and temperature sensors to perform chip based integrated NATs. The two chip modules have been validated using different panels of clinical samples and their performance compared with standard platforms. This study has established that our integrated NAT chip system has a sensitivity and specificity comparable to that of the standard platforms while providing up to 10 fold reduction in sample/reagent volumes.
Mkit: A Cell Migration Assay Based on Microfluidic Device and Smartphone

PubMed Central

Yang, Ke; Wu, Jiandong; Peretz-Soroka, Hagit; Zhu, Ling; Li, Zhigang; Sang, Yaoshuo; Hipolito, Jolly; Zhang, Michael; Santos, Susy; Hillier, Craig; de Faria, Ricardo Lobato; Liu, Yong; Lin, Francis

2017-01-01

Mobile sensing based on the integration of microfluidic device and smartphone, so-called MS2 technology, has enabled many applications over recent years, and continues to stimulate growing interest in both research communities and industries. In particular, it has been envisioned that MS2 technology can be developed for various cell functional assays to enable basic research and clinical applications. Toward this direction, in this paper, we describe the development of a MS2-based cell functional assay for testing cell migration (the Mkit). The system is constructed as an integrated test kit, which includes microfluidic chips, a smartphone-based imaging platform, the phone apps for image capturing and data analysis, and a set of reagent and accessories for performing the cell migration assay. We demonstrated that the Mkit can effectively measure purified neutrophil and cancer cell chemotaxis. Furthermore, neutrophil chemotaxis can be tested from a drop of whole blood using the Mkit with red blood cell (RBC) lysis. The effects of chemoattractant dose and gradient profile on neutrophil chemotaxis were also tested using the Mkit. In addition to research applications, we demonstrated the effective use of the Mkit for on-site test at the hospital and for testing clinical samples from chronic obstructive pulmonary disease patient. Thus, this developed Mkit provides an easy and integrated experimental platform for cell migration related research and potential medical diagnostic applications. PMID:28772229
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.
Bioprinting of Micro-Organ Tissue Analog for Drug Metabolism Study

NASA Astrophysics Data System (ADS)

Sun, Wei

An evolving application of tissue engineering is to develop in vitro 3D cell/tissue models for drug screening and pharmacological study. In order to test in space, these in vitro models are mostly manufactured through micro-fabrication techniques and incorporate living cells with MEMS or microfluidic devices. These cell-integrated microfluidic devices, or referred as microorgans, are effective in furnishing reliable and inexpensive drug metabolism and toxicity studies [1-3]. This paper will present an on-going research collaborated between Drexel University and NASA JSC Radiation Physics Laboratory for applying a direct cell printing technique to freeform fabrication of 3D liver tissue analog in drug metabolism study. The paper will discuss modeling, design, and solid freeform fabrication of micro-fluidic flow patterns and bioprinting of 3D micro-liver chamber that biomimics liver physiological microenvironment for enhanced drug metabolization. Technical details to address bioprinting of 3D liver tissue analog, integration with a microfluidic device, and basic drug metabolism study for NASA's interests will presented. 1. Holtorf H. Leslie J. Chang R, Nam J, Culbertson C, Sun W, Gonda S, "Development of a Three-Dimensional Tissue-on-a-Chip Micro-Organ Device for Pharmacokinetic Analysis", the 47th Annual Meeting of the American Society for Cell Biology, Washington, DC, December 1-5, 2007. 2. Chang, R., Nam, J., Culbertson C., Holtorf, H., Jeevarajan, A., Gonda, S. and Sun, W., "Bio-printing and Modeling of Flow Patterns for Cell Encapsulated 3D Liver Chambers For Pharmacokinetic Study", TERMIS North America 2007 Conference and Exposition, Westin Harbour Castle, Toronto, Canada, June 13-16, 2007. 3.Starly, B., Chang, R., Sun, W., Culbertson, C., Holtorf, H. and Gonda, S., "Bioprinted Tissue-on-chip Application for Pharmacokinetic Studies", Proceedings of World Congress on Tissue Engineering and Regenerative Medicine, Pittsburgh, PA, USA, April 24-27, 2006.

Bioanalysis in microfluidic devices.

PubMed

Khandurina, Julia; Guttman, András

2002-01-18

Microfabricated bioanalytical devices (also referred to as laboratory-on-a-chip or micro-TAS) offer highly efficient platforms for simultaneous analysis of a large number of biologically important molecules, possessing great potential for genome, proteome and metabolome studies. Development and implementation of microfluidic-based bioanalytical tools involves both established and evolving technologies, including microlithography, micromachining, micro-electromechanical systems technology and nanotechnology. This article provides an overview of the latest developments in the key device subject areas and the basic interdisciplinary technologies. Important aspects of DNA and protein analysis, interfacing issues and system integration are all thoroughly discussed, along with applications for this novel "synergized" technology in high-throughput separations of biologically important molecules. This review also gives a better understanding of how to utilize these technologies as well as to provide appropriate technical solutions to problems perceived as being more fundamental.
Thermoplastic microfluidic devices and their applications in protein and DNA analysis

PubMed Central

Liu, Ke; Fan, Z. Hugh

2013-01-01

Microfluidics is a platform technology that has been used for genomics, proteomics, chemical synthesis, environment monitoring, cellular studies, and other applications. The fabrication materials of microfluidic devices have traditionally included silicon and glass, but plastics have gained increasing attention in the past few years. We focus this review on thermoplastic microfluidic devices and their applications in protein and DNA analysis. We outline the device design and fabrication methods, followed by discussion on the strategies of surface treatment. We then concentrate on several significant advancements in applying thermoplastic microfluidic devices to protein separation, immunoassays, and DNA analysis. Comparison among numerous efforts, as well as the discussion on the challenges and innovation associated with detection, is presented. PMID:21274478
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.
Microfluidic immunosensor with integrated liquid core waveguides for sensitive Mie scattering detection of avian influenza antigens in a real biological matrix.

PubMed

Heinze, Brian C; Gamboa, Jessica R; Kim, Keesung; Song, Jae-Young; Yoon, Jeong-Yeol

2010-11-01

This work presents the use of integrated, liquid core, optical waveguides for measuring immunoagglutination-induced light scattering in a microfluidic device, towards rapid and sensitive detection of avian influenza (AI) viral antigens in a real biological matrix (chicken feces). Mie scattering simulations were performed and tested to optimize the scattering efficiency of the device through proper scatter angle waveguide geometry. The detection limit is demonstrated to be 1 pg mL(-1) in both clean buffer and real biological matrix. This low detection limit is made possible through on-chip diffusional mixing of AI target antigens and high acid content microparticle assay reagents, coupled with real-time monitoring of immunoagglutination-induced forward Mie scattering via high refractive index liquid core optical waveguides in close proximity (100 μm) to the sample chamber. The detection time for the assay is <2 min. This device could easily be modified to detect trace levels of any biological molecules that antibodies are available for, moving towards a robust platform for point-of-care disease diagnostics.
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.
Electrofluidic Circuit-Based Microfluidic Viscometer for Analysis of Newtonian and Non-Newtonian Liquids under Different Temperatures.

PubMed

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

2018-02-06

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

PubMed Central

Fraser, Graham M.; Goldman, Daniel; Ellis, Christopher G.

2016-01-01

Red blood cells play a crucial role in the local regulation of oxygen supply in the microcirculation through the oxygen dependent release of ATP. Since red blood cells serve as an oxygen sensor for the circulatory system, the dynamics of ATP release determine the effectiveness of red blood cells to relate the oxygen levels to the vessels. Previous work has focused on the feasibility of developing a microfluidic system to measure the dynamics of ATP release. The objective was to determine if a steep oxygen gradient could be developed in the channel to cause a rapid decrease in hemoglobin oxygen saturation in order to measure the corresponding levels of ATP released from the red blood cells. In the present study, oxygen transport simulations were used to optimize the geometric design parameters for a similar system which is easier to fabricate. The system is composed of a microfluidic device stacked on top of a large, gas impermeable flow channel with a hole to allow gas exchange. The microfluidic device is fabricated using soft lithography in polydimethyl-siloxane, an oxygen permeable material. Our objective is twofold: (1) optimize the parameters of our system and (2) develop a method to assess the oxygen distribution in complex 3D microfluidic device geometries. 3D simulations of oxygen transport were performed to simulate oxygen distribution throughout the device. The simulations demonstrate that microfluidic device geometry plays a critical role in molecule exchange, for instance, changing the orientation of the short wide microfluidic channel results in a 97.17% increase in oxygen exchange. Since microfluidic devices have become a more prominent tool in biological studies, understanding the transport of oxygen and other biological molecules in microfluidic devices is critical for maintaining a physiologically relevant environment. We have also demonstrated a method to assess oxygen levels in geometrically complex microfluidic devices. PMID:27829071
Finite Element Model of Oxygen Transport for the Design of Geometrically Complex Microfluidic Devices Used in Biological Studies.

PubMed

Sové, Richard J; Fraser, Graham M; Goldman, Daniel; Ellis, Christopher G

2016-01-01

Red blood cells play a crucial role in the local regulation of oxygen supply in the microcirculation through the oxygen dependent release of ATP. Since red blood cells serve as an oxygen sensor for the circulatory system, the dynamics of ATP release determine the effectiveness of red blood cells to relate the oxygen levels to the vessels. Previous work has focused on the feasibility of developing a microfluidic system to measure the dynamics of ATP release. The objective was to determine if a steep oxygen gradient could be developed in the channel to cause a rapid decrease in hemoglobin oxygen saturation in order to measure the corresponding levels of ATP released from the red blood cells. In the present study, oxygen transport simulations were used to optimize the geometric design parameters for a similar system which is easier to fabricate. The system is composed of a microfluidic device stacked on top of a large, gas impermeable flow channel with a hole to allow gas exchange. The microfluidic device is fabricated using soft lithography in polydimethyl-siloxane, an oxygen permeable material. Our objective is twofold: (1) optimize the parameters of our system and (2) develop a method to assess the oxygen distribution in complex 3D microfluidic device geometries. 3D simulations of oxygen transport were performed to simulate oxygen distribution throughout the device. The simulations demonstrate that microfluidic device geometry plays a critical role in molecule exchange, for instance, changing the orientation of the short wide microfluidic channel results in a 97.17% increase in oxygen exchange. Since microfluidic devices have become a more prominent tool in biological studies, understanding the transport of oxygen and other biological molecules in microfluidic devices is critical for maintaining a physiologically relevant environment. We have also demonstrated a method to assess oxygen levels in geometrically complex microfluidic devices.
Fully 3D printed integrated reactor array for point-of-care molecular diagnostics.

PubMed

Kadimisetty, Karteek; Song, Jinzhao; Doto, Aoife M; Hwang, Young; Peng, Jing; Mauk, Michael G; Bushman, Frederic D; Gross, Robert; Jarvis, Joseph N; Liu, Changchun

2018-06-30

Molecular diagnostics that involve nucleic acid amplification tests (NAATs) are crucial for prevention and treatment of infectious diseases. In this study, we developed a simple, inexpensive, disposable, fully 3D printed microfluidic reactor array that is capable of carrying out extraction, concentration and isothermal amplification of nucleic acids in variety of body fluids. The method allows rapid molecular diagnostic tests for infectious diseases at point of care. A simple leak-proof polymerization strategy was developed to integrate flow-through nucleic acid isolation membranes into microfluidic devices, yielding a multifunctional diagnostic platform. Static coating technology was adopted to improve the biocompatibility of our 3D printed device. We demonstrated the suitability of our device for both end-point colorimetric qualitative detection and real-time fluorescence quantitative detection. We applied our diagnostic device to detection of Plasmodium falciparum in plasma samples and Neisseria meningitides in cerebrospinal fluid (CSF) samples by loop-mediated, isothermal amplification (LAMP) within 50 min. The detection limits were 100 fg for P. falciparum and 50 colony-forming unit (CFU) for N. meningitidis per reaction, which are comparable to that of benchtop instruments. This rapid and inexpensive 3D printed device has great potential for point-of-care molecular diagnosis of infectious disease in resource-limited settings. Copyright © 2018 Elsevier B.V. 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.
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.
A neuron-in-capillary platform for facile collection and mass spectrometric characterization of a secreted neuropeptide

PubMed Central

Lee, Chang Young; Fan, Yi; Rubakhin, Stanislav S.; Yoon, Sook; Sweedler, Jonathan V.

2016-01-01

The integration of microfluidic devices—which efficiently handle small liquid volumes—with separations/mass spectrometry (MS) is an effective approach for profiling the neurochemistry occurring in selected neurons. Interfacing the microfluidic cell culture to the mass spectrometer is challenging because of geometric and scaling issues. Here we demonstrate the hyphenation of a neuron-in-capillary platform to a solid phase extraction device and off-line MS. A primary neuronal culture of Aplysia californica neurons was established directly inside a cylindrical polyimide capillary. The approach also uses a particle-embedded monolith to condition neuropeptide releasates collected from several Aplysia neurons cultured in the capillary, with the subsequent characterization of released peptides via MS. This system presents a number of advances compared to more traditional microfluidic devices fabricated with polydimethylsiloxane. These include low cost, easy access to cell culture, rigidity, ease of transport, and minimal fluid handling. The cylindrical geometry of the platform allows convenient interface with a wide range of analytical tools that utilize capillary columns. PMID:27245782
Tunable Liquid Gradient Refractive Index (L-GRIN) lens with two degrees of freedom.

PubMed

Mao, Xiaole; Lin, Sz-Chin Steven; Lapsley, Michael Ian; Shi, Jinjie; Juluri, Bala Krishna; Huang, Tony Jun

2009-07-21

We report a tunable optofluidic microlens configuration named the Liquid Gradient Refractive Index (L-GRIN) lens for focusing light within a microfluidic device. The focusing of light was achieved through the gradient refractive index (GRIN) within the liquid medium, rather than via curved refractive lens surfaces. The diffusion of solute (CaCl(2)) between side-by-side co-injected microfluidic laminar flows was utilized to establish a hyperbolic secant (HS) refractive index profile to focus light. Tailoring the refractive index profile by adjusting the flow conditions enables not only tuning of the focal distance (translation mode), but also shifting of the output light direction (swing mode), a second degree of freedom that to our knowledge has yet to be accomplished for in-plane tunable microlenses. Advantages of the L-GRIN lens also include a low fluid consumption rate, competitive focusing performance, and high compatibility with existing microfluidic devices. This work provides a new strategy for developing integrative tunable microlenses for a variety of lab-on-a-chip applications.
A Versatile PDMS/Paper Hybrid Microfluidic Platform for Sensitive Infectious Disease Diagnosis

PubMed Central

2015-01-01

Bacterial meningitis is a serious health concern worldwide. Given that meningitis can be fatal and many meningitis cases occurred in high-poverty areas, a simple, low-cost, highly sensitive method is in great need for immediate and early diagnosis of meningitis. Herein, we report a versatile and cost-effective polydimethylsiloxane (PDMS)/paper hybrid microfluidic device integrated with loop-mediated isothermal amplification (LAMP) for the rapid, sensitive, and instrument-free detection of the main meningitis-causing bacteria, Neisseria meningitidis (N. meningitidis). The introduction of paper into the microfluidic device for LAMP reactions enables stable test results over a much longer period of time than a paper-free microfluidic system. This hybrid system also offers versatile functions, by providing not only on-site qualitative diagnostic analysis (i.e., a yes or no answer), but also confirmatory testing and quantitative analysis in laboratory settings. The limit of detection of N. meningitidis is about 3 copies per LAMP zone within 45 min, close to single-bacterium detection sensitivity. In addition, we have achieved simple pathogenic microorganism detection without a laborious sample preparation process and without the use of centrifuges. This low-cost hybrid microfluidic system provides a simple and highly sensitive approach for fast instrument-free diagnosis of N. meningitidis in resource-limited settings. This versatile PDMS/paper microfluidic platform has great potential for the point of care (POC) diagnosis of a wide range of infectious diseases, especially for developing nations. PMID:25019330
Microfluidics meets metabolomics to reveal the impact of Campylobacter jejuni infection on biochemical pathways.

PubMed

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

2016-06-01

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

PubMed Central

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

2016-01-01

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

PubMed

Muthaiyan Shanmugam, Muniesh; Subhra Santra, Tuhin

2016-08-02

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

PubMed

Bithi, Swastika S; Vanapalli, Siva A

2017-02-02

Drug assays with patient-derived cells such as circulating tumor cells requires manipulating small sample volumes without loss of rare disease-causing cells. Here, we report an effective technology for isolating and analyzing individual tumor cells and their clusters from minute sample volumes using an optimized microfluidic device integrated with pipettes. The method involves using hand pipetting to create an array of cell-laden nanoliter-sized droplets immobilized in a microfluidic device without loss of tumor cells during the pipetting process. Using this technology, we demonstrate single-cell analysis of tumor cell response to the chemotherapy drug doxorubicin. We find that even though individual tumor cells display diverse uptake profiles of the drug, the onset of apoptosis is determined by accumulation of a critical intracellular concentration of doxorubicin. Experiments with clusters of tumor cells compartmentalized in microfluidic drops reveal that cells within a cluster have higher viability than their single-cell counterparts when exposed to doxorubicin. This result suggests that circulating tumor cell clusters might be able to better survive chemotherapy drug treatment. Our technology is a promising tool for understanding tumor cell-drug interactions in patient-derived samples including rare cells.
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.
High content screening in microfluidic devices

PubMed Central

Cheong, Raymond; Paliwal, Saurabh; Levchenko, Andre

2011-01-01

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

Immobilization of pH-sensitive CdTe Quantum Dots in a Poly(acrylate) Hydrogel for Microfluidic Applications

NASA Astrophysics Data System (ADS)

Franke, M.; Leubner, S.; Dubavik, A.; George, A.; Savchenko, T.; Pini, C.; Frank, P.; Melnikau, D.; Rakovich, Y.; Gaponik, N.; Eychmüller, A.; Richter, A.

2017-04-01

Microfluidic devices present the basis of modern life sciences and chemical information processing. To control the flow and to allow optical readout, a reliable sensor material that can be easily utilized for microfluidic systems is in demand. Here, we present a new optical readout system for pH sensing based on pH sensitive, photoluminescent glutathione capped cadmium telluride quantum dots that are covalently immobilized in a poly(acrylate) hydrogel. For an applicable pH sensing the generated hybrid material is integrated in a microfluidic sensor chip setup. The hybrid material not only allows in situ readout, but also possesses valve properties due to the swelling behavior of the poly(acrylate) hydrogel. In this work, the swelling property of the hybrid material is utilized in a microfluidic valve seat, where a valve opening process is demonstrated by a fluid flow change and in situ monitored by photoluminescence quenching. This discrete photoluminescence detection (ON/OFF) of the fluid flow change (OFF/ON) enables upcoming chemical information processing.
Microfluidic rectifier based on poly(dimethylsiloxane) membrane and its application to a micropump

PubMed Central

Wang, Yao-Nan; Tsai, Chien-Hsiung; Fu, Lung-Ming; Lin Liou, Lung-Kai

2013-01-01

A microfluidic rectifier incorporating an obstructed microchannel and a PDMS membrane is proposed. During forward flow, the membrane deflects in the upward direction; thereby allowing the fluid to pass over the obstacle. Conversely, during reverse flow, the membrane seals against the obstacle, thereby closing the channel and preventing flow. It is shown that the proposed device can operate over a wide pressure range by increasing or decreasing the membrane thickness as required. A microfluidic pump is realized by integrating the rectifier with a simple stepper motor mechanism. The experimental results show that the pump can achieve a vertical left height of more than 2 m. Moreover, it is shown that a maximum flow rate of 6.3 ml/min can be obtained given a membrane thickness of 200 μm and a motor velocity of 80 rpm. In other words, the proposed microfluidic rectifier not only provides an effective means of preventing reverse flow but also permits the realization of a highly efficient microfluidic pump. PMID:24404051
Microfluidic rectifier based on poly(dimethylsiloxane) membrane and its application to a micropump.

PubMed

Wang, Yao-Nan; Tsai, Chien-Hsiung; Fu, Lung-Ming; Lin Liou, Lung-Kai

2013-01-01

A microfluidic rectifier incorporating an obstructed microchannel and a PDMS membrane is proposed. During forward flow, the membrane deflects in the upward direction; thereby allowing the fluid to pass over the obstacle. Conversely, during reverse flow, the membrane seals against the obstacle, thereby closing the channel and preventing flow. It is shown that the proposed device can operate over a wide pressure range by increasing or decreasing the membrane thickness as required. A microfluidic pump is realized by integrating the rectifier with a simple stepper motor mechanism. The experimental results show that the pump can achieve a vertical left height of more than 2 m. Moreover, it is shown that a maximum flow rate of 6.3 ml/min can be obtained given a membrane thickness of 200 μm and a motor velocity of 80 rpm. In other words, the proposed microfluidic rectifier not only provides an effective means of preventing reverse flow but also permits the realization of a highly efficient microfluidic pump.
Approaching near real-time biosensing: microfluidic microsphere based biosensor for real-time analyte detection.

PubMed

Cohen, Noa; Sabhachandani, Pooja; Golberg, Alexander; Konry, Tania

2015-04-15

In this study we describe a simple lab-on-a-chip (LOC) biosensor approach utilizing well mixed microfluidic device and a microsphere-based assay capable of performing near real-time diagnostics of clinically relevant analytes such cytokines and antibodies. We were able to overcome the adsorption kinetics reaction rate-limiting mechanism, which is diffusion-controlled in standard immunoassays, by introducing the microsphere-based assay into well-mixed yet simple microfluidic device with turbulent flow profiles in the reaction regions. The integrated microsphere-based LOC device performs dynamic detection of the analyte in minimal amount of biological specimen by continuously sampling micro-liter volumes of sample per minute to detect dynamic changes in target analyte concentration. Furthermore we developed a mathematical model for the well-mixed reaction to describe the near real time detection mechanism observed in the developed LOC method. To demonstrate the specificity and sensitivity of the developed real time monitoring LOC approach, we applied the device for clinically relevant analytes: Tumor Necrosis Factor (TNF)-α cytokine and its clinically used inhibitor, anti-TNF-α antibody. Based on the reported results herein, the developed LOC device provides continuous sensitive and specific near real-time monitoring method for analytes such as cytokines and antibodies, reduces reagent volumes by nearly three orders of magnitude as well as eliminates the washing steps required by standard immunoassays. Copyright © 2014 Elsevier B.V. All rights reserved.
3D-printed Microfluidic Devices: Fabrication, Advantages and Limitations—a Mini Review

PubMed Central

Chen, Chengpeng; Mehl, Benjamin T.; Munshi, Akash S.; Townsend, Alexandra D.; Spence, Dana M.; Martin, R. Scott

2016-01-01

A mini-review with 79 references. In this review, the most recent trends in 3D-printed microfluidic devices are discussed. In addition, a focus is given to the fabrication aspects of these devices, with the supplemental information containing detailed instructions for designing a variety of structures including: a microfluidic channel, threads to accommodate commercial fluidic fittings, a flow splitter; a well plate, a mold for PDMS channel casting; and how to combine multiple designs into a single device. The advantages and limitations of 3D-printed microfluidic devices are thoroughly discussed, as are some future directions for the field. PMID:27617038
3D-printed Microfluidic Devices: Fabrication, Advantages and Limitations-a Mini Review.

PubMed

Chen, Chengpeng; Mehl, Benjamin T; Munshi, Akash S; Townsend, Alexandra D; Spence, Dana M; Martin, R Scott

2016-08-21

A mini-review with 79 references. In this review, the most recent trends in 3D-printed microfluidic devices are discussed. In addition, a focus is given to the fabrication aspects of these devices, with the supplemental information containing detailed instructions for designing a variety of structures including: a microfluidic channel, threads to accommodate commercial fluidic fittings, a flow splitter; a well plate, a mold for PDMS channel casting; and how to combine multiple designs into a single device. The advantages and limitations of 3D-printed microfluidic devices are thoroughly discussed, as are some future directions for the field.
Self-powered integrated microfluidic point-of-care low-cost enabling (SIMPLE) chip

PubMed Central

Yeh, Erh-Chia; Fu, Chi-Cheng; Hu, Lucy; Thakur, Rohan; Feng, Jeffrey; Lee, Luke P.

2017-01-01

Portable, low-cost, and quantitative nucleic acid detection is desirable for point-of-care diagnostics; however, current polymerase chain reaction testing often requires time-consuming multiple steps and costly equipment. We report an integrated microfluidic diagnostic device capable of on-site quantitative nucleic acid detection directly from the blood without separate sample preparation steps. First, we prepatterned the amplification initiator [magnesium acetate (MgOAc)] on the chip to enable digital nucleic acid amplification. Second, a simplified sample preparation step is demonstrated, where the plasma is separated autonomously into 224 microwells (100 nl per well) without any hemolysis. Furthermore, self-powered microfluidic pumping without any external pumps, controllers, or power sources is accomplished by an integrated vacuum battery on the chip. This simple chip allows rapid quantitative digital nucleic acid detection directly from human blood samples (10 to 105 copies of methicillin-resistant Staphylococcus aureus DNA per microliter, ~30 min, via isothermal recombinase polymerase amplification). These autonomous, portable, lab-on-chip technologies provide promising foundations for future low-cost molecular diagnostic assays. PMID:28345028
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.
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
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.
Paper-based analytical devices for clinical diagnosis: recent advances in the fabrication techniques and sensing mechanisms

PubMed Central

Sher, Mazhar; Zhuang, Rachel; Demirci, Utkan; Asghar, Waseem

2017-01-01

Introduction There is a significant interest in developing inexpensive portable biosensing platforms for various applications including disease diagnostics, environmental monitoring, food safety, and water testing at the point-of-care (POC) settings. Current diagnostic assays available in the developed world require sophisticated laboratory infrastructure and expensive reagents. Hence, they are not suitable for resource-constrained settings with limited financial resources, basic health infrastructure, and few trained technicians. Cellulose and flexible transparency paper-based analytical devices have demonstrated enormous potential for developing robust, inexpensive and portable devices for disease diagnostics. These devices offer promising solutions to disease management in resource-constrained settings where the vast majority of the population cannot afford expensive and highly sophisticated treatment options. Areas covered In this review, the authors describe currently developed cellulose and flexible transparency paper-based microfluidic devices, device fabrication techniques, and sensing technologies that are integrated with these devices. The authors also discuss the limitations and challenges associated with these devices and their potential in clinical settings. Expert commentary In recent years, cellulose and flexible transparency paper-based microfluidic devices have demonstrated the potential to become future healthcare options despite a few limitations such as low sensitivity and reproducibility. PMID:28103450
Paper-based analytical devices for clinical diagnosis: recent advances in the fabrication techniques and sensing mechanisms.

PubMed

Sher, Mazhar; Zhuang, Rachel; Demirci, Utkan; Asghar, Waseem

2017-04-01

There is a significant interest in developing inexpensive portable biosensing platforms for various applications including disease diagnostics, environmental monitoring, food safety, and water testing at the point-of-care (POC) settings. Current diagnostic assays available in the developed world require sophisticated laboratory infrastructure and expensive reagents. Hence, they are not suitable for resource-constrained settings with limited financial resources, basic health infrastructure, and few trained technicians. Cellulose and flexible transparency paper-based analytical devices have demonstrated enormous potential for developing robust, inexpensive and portable devices for disease diagnostics. These devices offer promising solutions to disease management in resource-constrained settings where the vast majority of the population cannot afford expensive and highly sophisticated treatment options. Areas covered: In this review, the authors describe currently developed cellulose and flexible transparency paper-based microfluidic devices, device fabrication techniques, and sensing technologies that are integrated with these devices. The authors also discuss the limitations and challenges associated with these devices and their potential in clinical settings. Expert commentary: In recent years, cellulose and flexible transparency paper-based microfluidic devices have demonstrated the potential to become future healthcare options despite a few limitations such as low sensitivity and reproducibility.
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.
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
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.
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…
3D cardiac μ tissues within a microfluidic device with real-time contractile stress readout

PubMed Central

Aung, Aereas; Bhullar, Ivneet Singh; Theprungsirikul, Jomkuan; Davey, Shruti Krishna; Lim, Han Liang; Chiu, Yu-Jui; Ma, Xuanyi; Dewan, Sukriti; Lo, Yu-Hwa; McCulloch, Andrew; Varghese, Shyni

2015-01-01

We present the development of three-dimensional (3D) cardiac microtissues within a microfluidic device with the ability to quantify real-time contractile stress measurements in situ. Using a 3D patterning technology that allows for the precise spatial distribution of cells within the device, we created an array of 3D cardiac microtissues from neonatal mouse cardiomyocytes. We integrated the 3D micropatterning technology with microfluidics to achieve perfused cell-laden structures. The cells were encapsulated within a degradable gelatin methacrylate hydrogel, which was sandwiched between two polyacrylamide hydrogels. The polyacrylamide hydrogels were used as “stress sensors” to acquire the contractile stresses generated by the beating cardiac cells. The cardiac-specific response of the engineered 3D system was examined by exposing it to epinephrine, an adrenergic neurotransmitter known to increase the magnitude and frequency of cardiac contractions. In response to exogenous epinephrine the engineered cardiac tissues exhibited an increased beating frequency and stress magnitude. Such cost-effective and easy-to-adapt 3D cardiac systems with real-time functional readout could be an attractive technological platform for drug discovery and development. PMID:26588203
Microfluidic separation of motile sperm with millilitre-scale sample capacity

NASA Astrophysics Data System (ADS)

Nosrati, Reza; Vollmer, Marion; Eamer, Lise; Zeidan, Krista; San Gabriel, Maria C.; Zini, Armand; Sinton, David

2012-11-01

Isolating motile from non-motile spermatozoa has been a challenge since the establishment of in vitro fertilization. Microfluidic approaches have been employed for this purpose, but current devices are limited by low sample volume. Here, we present a high-throughput microfluidic device that separates spermatozoa from one millilitre of raw semen sample based on the hydrodynamic characteristics of swimming sperm in a confined geometry. The device consists of two layers: an outer injection ring on top aligned with a network of radial microchannels at the bottom guiding motile sperm into an inner collection chamber. This approach (1) maximizes exposure of the sperm to the fluid channels, (2) maximizes surface area density (3) prevents fluid flow bias, and (4) employs a non-Newtonian viscoelastic medium consistent with the in vivo environment. Tests with human and bull spermatozoa indicate an increase in motile sperm concentration from 62.2% in raw semen to 99.2% in separated sample combined with a higher incidence of normal morphology. DNA integrity testing is currently underway. In conclusion, we present an effective one-step procedure to perform semen purification and separation on a millilitre-scale with clinically relevant numbers.

Microfluidic device with integrated microfilter of conical-shaped holes for high efficiency and high purity capture of circulating tumor cells

NASA Astrophysics Data System (ADS)

Tang, Yadong; Shi, Jian; Li, Sisi; Wang, Li; Cayre, Yvon E.; Chen, Yong

2014-08-01

Capture of circulating tumor cells (CTCs) from peripheral blood of cancer patients has major implications for metastatic detection and therapy analyses. Here we demonstrated a microfluidic device for high efficiency and high purity capture of CTCs. The key novelty of this approach lies on the integration of a microfilter with conical-shaped holes and a micro-injector with cross-flow components for size dependent capture of tumor cells without significant retention of non-tumor cells. Under conditions of constant flow rate, tumor cells spiked into phosphate buffered saline could be recovered and then cultured for further analyses. When tumor cells were spiked in blood of healthy donors, they could also be recovered at high efficiency and high clearance efficiency of white blood cells. When the same device was used for clinical validation, CTCs could be detected in blood samples of cancer patients but not in that of healthy donors. Finally, the capture efficiency of tumor cells is cell-type dependent but the hole size of the filter should be more closely correlated to the nuclei size of the tumor cells. Together with the advantage of easy operation, low-cost and high potential of integration, this approach offers unprecedented opportunities for metastatic detection and cancer treatment monitoring.
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.
Preliminary assessment for DNA extraction on microfluidic channel

NASA Astrophysics Data System (ADS)

Gopinath, Subash C. B.; Hashim, Uda; Uda, M. N. A.

2017-03-01

The aim of this research is to extract, purify and yield DNA in mushroom from solid state mushroom sample by using fabricated continuous high-capacity sample delivery microfluidic through integrated solid state extraction based amino-coated silica bead. This device is made to specifically extract DNA in mushroom sample in continuous inflow process with energy and cost consumption. In this project, we present two methods of DNA extraction and purification which are by using centrifuge (complex and conventional method) and by using microfluidic biosensor (new and fast method). DNA extracted can be determined by using ultraviolet-visible spectroscopy (UV-VIS). The peak obtained at wavelength 260nm after measuring the absorbance of sample proves that DNA is successfully extracted from the mushroom.
Photonic crystal beads from gravity-driven microfluidics.

PubMed

Gu, Hongcheng; Rong, Fei; Tang, Baocheng; Zhao, Yuanjin; Fu, Degang; Gu, Zhongze

2013-06-25

This Letter reports a simple method for the mass production of 3D colloidal photonic crystal beads (PCBs) by using a gravity-driven microfluidic device and online droplet drying method. Compared to traditional methods, the droplet templates of the PCBs are generated by using the ultrastable gravity as the driving force for the microfluidics, thus the PCBs are formed with minimal polydispersity. Moreover, drying of the droplet templates is integrated into the production process, and the nanoparticles in the droplets self-assemble online. Overall, this process results in PCBs with good morphology, low polydispersity, brilliant structural colors, and narrow stop bands. PCBs could be bulk generated by this process for many practical applications, such as multiplex-encoded assays and the construction of novel optical materials.
Comparative analysis of fabrication methods for achieving rounded microchannels in PDMS

NASA Astrophysics Data System (ADS)

Bartlett, Nicholas W.; Wood, Robert J.

2016-11-01

Many microfluidic applications demand control over channel cross-sectional geometry. In particular, rounded microchannels are essential to the function of microfluidic valves, which have played an integral part in the success of microfluidics over the past fifteen years. Here we investigate the relative strengths and weaknesses of different strategies for fabricating rounded microchannels in PDMS, systematically examining five common strategies. We consider the appropriateness of the fabrication strategies for microchannels of differing sizes and aspect ratios, and evaluate these various strategies on a number of metrics ranging from microchannel resolution to fabrication difficulty. We discuss the merits of the different strategies for a range of applications, and make recommendations on which strategy to use based on the driving constraints of the device.
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.
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.
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.
Isothermal circular-strand-displacement polymerization of DNA and microRNA in digital microfluidic devices.

PubMed

Giuffrida, Maria Chiara; Zanoli, Laura Maria; D'Agata, Roberta; Finotti, Alessia; Gambari, Roberto; Spoto, Giuseppe

2015-02-01

Nucleic-acid amplification is a crucial step in nucleic-acid-sequence-detection assays. The use of digital microfluidic devices to miniaturize amplification techniques reduces the required sample volume and the analysis time and offers new possibilities for process automation and integration in a single device. The recently introduced droplet polymerase-chain-reaction (PCR) amplification methods require repeated cycles of two or three temperature-dependent steps during the amplification of the nucleic-acid target sequence. In contrast, low-temperature isothermal-amplification methods have no need for thermal cycling, thus requiring simplified microfluidic-device features. Here, the combined use of digital microfluidics and molecular-beacon (MB)-assisted isothermal circular-strand-displacement polymerization (ICSDP) to detect microRNA-210 sequences is described. MicroRNA-210 has been described as the most consistently and predominantly upregulated hypoxia-inducible factor. The nmol L(-1)-pmol L(-1) detection capabilities of the method were first tested by targeting single-stranded DNA sequences from the genetically modified Roundup Ready soybean. The ability of the droplet-ICSDP method to discriminate between full-matched, single-mismatched, and unrelated sequences was also investigated. The detection of a range of nmol L(-1)-pmol L(-1) microRNA-210 solutions compartmentalized in nanoliter-sized droplets was performed, establishing the ability of the method to detect as little as 10(-18) mol of microRNA target sequences compartmentalized in 20 nL droplets. The suitability of the method for biological samples was tested by detecting microRNA-210 from transfected K562 cells.
Electrochemical immunoassay on a microfluidic device with sequential injection and flushing functions.

PubMed

Nashida, Norihiro; Satoh, Wataru; Fukuda, Junji; Suzuki, Hiroaki

2007-06-15

An integrated microfluidic device with injecting, flushing, and sensing functions was realized using valves that operate based on direct electrowetting. The device consisted of two substrates: a glass substrate with driving and sensing electrodes and a poly(dimethylsiloxane) (PDMS) substrate. Microfluidic transport was achieved using the spontaneous movement of solutions in hydrophilic flow channels formed with a dry-film photoresist layer. The injection and flushing of solutions were controlled by gold working electrodes, which functioned as valves. The valves were formed either in the channels or in a through-hole in the glass substrate. To demonstrate the system's applicability to an immunoassay, the detection of immobilized antigens was performed as a partial simulation of a sandwich immunoassay. Human alpha-fetoprotein (AFP) or an anti-human AFP antibody was immobilized on a platinum working electrode in the chamber using a plasma-polymerized film (PPF). By applying a potential to the injection valves, necessary solutions were injected one by one through the channels into a reaction chamber at the center of the chip and incubated for reasonable periods of time. The solutions were then flushed through the flushing valve and absorbed in a filter paper placed under the device. After incubation with the corresponding antibodies labeled with glucose oxidase (GOD), electrochemical detection was conducted. In both cases, the obtained current depended on the amount of immobilized antigen. The calibration curves were sigmoidal, and the detection limit was 0.1 ng. The developed microfluidic system could potentially be a fundamental component for a micro immunoassay of the next generation.
Recent advances in low-cost microfluidic platforms for diagnostic applications.

PubMed

Tomazelli Coltro, Wendell Karlos; Cheng, Chao-Min; Carrilho, Emanuel; de Jesus, Dosil Pereira

2014-08-01

The use of inexpensive materials and cost-effective manufacturing processes for mass production of microfluidic devices is very attractive and has spurred a variety of approaches. Such devices are particularly suited for diagnostic applications in limited resource settings. This review describes the recent and remarkable advances in the use of low-cost substrates for the development of microfluidic devices for diagnostics and clinical assays. Thus, a plethora of new and improved fabrication methods, designs, capabilities, detections, and applications of microfluidic devices fabricated with paper, plastic, and threads are covered. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Polymer-based microfluidic chips for isothermal amplification of nucleic acids

NASA Astrophysics Data System (ADS)

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

2017-11-01

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

PubMed

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

2007-09-01

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

PubMed Central

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

2009-01-01

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

PubMed Central

Moussavi-Haramic, S. F.; Pezzi, H. M.; Huttenlocher, A.; Beebe, D. J.

2016-01-01

Chemotaxis is a fundamental biological process where complex chemotactic gradients are integrated and prioritized to guide cell migration toward specific locations. To understand the mechanisms of gradient dependent cell migration, it is important to develop in vitro models that recapitulate key attributes of the chemotactic cues present in vivo. Current in vitro tools for studying cell migration are not amenable to easily study the response of neutrophils to dual gradients. Many of these systems require external pumps and complex setups to establish and maintain the gradients. Here we report a simple yet innovative microfluidic device for studying cell migration in the presence of dual chemotactic gradients through a 3-dimensional substrate. The device is tested and validated by studying the migration of the neutrophil-like cell line PLB-985 to gradients of fMLP. Furthermore, the device is expanded and used with heparinised whole blood, whereupon neutrophils were observed to migrate from whole blood towards gradients of fMLP eliminating the need for any neutrophil purification or capture steps. PMID:25893484
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.
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
Mkit: A cell migration assay based on microfluidic device and smartphone.

PubMed

Yang, Ke; Wu, Jiandong; Peretz-Soroka, Hagit; Zhu, Ling; Li, Zhigang; Sang, Yaoshuo; Hipolito, Jolly; Zhang, Michael; Santos, Susy; Hillier, Craig; de Faria, Ricardo Lobato; Liu, Yong; Lin, Francis

2018-01-15

Mobile sensing based on the integration of microfluidic device and smartphone, so-called MS 2 technology, has enabled many applications over recent years, and continues to stimulate growing interest in both research communities and industries. In particular, it has been envisioned that MS 2 technology can be developed for various cell functional assays to enable basic research and clinical applications. Toward this direction, in this paper, we describe the development of a MS 2 -based cell functional assay for testing cell migration (the M kit ). The system is constructed as an integrated test kit, which includes microfluidic chips, a smartphone-based imaging platform, the phone apps for image capturing and data analysis, and a set of reagent and accessories for performing the cell migration assay. We demonstrated that the M kit can effectively measure purified neutrophil and cancer cell chemotaxis. Furthermore, neutrophil chemotaxis can be tested from a drop of whole blood using the M kit with red blood cell (RBC) lysis. The effects of chemoattractant dose and gradient profile on neutrophil chemotaxis were also tested using the M kit . In addition to research applications, we demonstrated the effective use of the M kit for on-site test at the hospital and for testing clinical samples from chronic obstructive pulmonary disease patient. Thus, this developed M kit provides an easy and integrated experimental platform for cell migration related research and potential medical diagnostic applications. Copyright © 2017 Elsevier B.V. All rights reserved.

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.
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.
Real-time isothermal RNA amplification of toxic marine microalgae using preserved reagents on an integrated microfluidic platform.

PubMed

Tsaloglou, Maria-Nefeli; Laouenan, Florian; Loukas, Christos-Moritz; Monsalve, Lisandro Gabriel; Thanner, Christine; Morgan, Hywel; Ruano-López, Jesus M; Mowlem, Matthew C

2013-01-21

Quantitation of specific RNA sequences is a useful technique in marine biology that can elucidate cell abundance, speciation and viability, especially for early detection of harmful algal blooms. We are thus developing an integrated microfluidic system for cell concentration and lysis, RNA extraction/purification and quantitative RNA detection for environmental applications. The portable system is based on a microfluidic cartridge, or "lab-card", using a low-cost injection moulded device, with a laminated lid. Here we present real-time isothermal RNA amplification using reagent master-mixes preserved on-chip in a gel at 4 °C for up to eight months. We demonstrate quantitation by reference to an internal control in a competitive assay with 500 cell equivalents of the toxic microalga Karenia brevis. Annealing of primers, amplification at 41 °C and real-time fluorescence detection of the internal control and target using sequence-specific molecular beacons were all performed on-chip.
Integrated bioassays in microfluidic devices: botulinum toxin assays.

PubMed

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

2005-12-01

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

NASA Astrophysics Data System (ADS)

Sugioka, Koji; Cheng, Ya

2014-12-01

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

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

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

2014-12-15

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

PubMed

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

2016-08-19

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

PubMed

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

2016-03-01

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

PubMed Central

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

2016-01-01

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

NASA Astrophysics Data System (ADS)

Caputo, Domenico; de Cesare, Giampiero; Nascetti, Augusto; Scipinotti, Riccardo

2013-05-01

In this paper, we present the first integration of an amorphous silicon balanced photosensor with a microfluidic network to perform on-chip detection for biomedical applications, where rejection of large background light intensity is needed. This solution allows to achieve high resolution readout without the need of high dynamic range electronics. The balanced photodiode is constituted by two series-connected a-Si:H/a-SiC:H n-i-p stacked junctions, deposited on a glass substrate. The structure is a three terminal device where two electrodes bias the two diodes in reverse conditions while the third electrode (i.e. the connection point of the two diodes) provides the output signal given by the differential current. The microfluidic network is composed of two channels made in PolyDimetilSiloxane (PDMS) positioned over the glass substrate on the photodiode-side aligning each channel with a diode. This configuration guarantees an optimal optical coupling between luminescence events occurring in the channels and the photosensors. The experiments have been carried out measuring the differential current in identical and different conditions for the two channels. We have found that: the measurement dynamic range can be increased by at least an order of magnitude with respect to conventional photodiodes; the balanced photodiode is able to detect the presence or absence of water in the channel; the presence of fluorescent molecules in the channel can be successful detected by our device without any need of optical filter for the excitation light. These preliminary results demonstrate the successful integration of a microfluidic network with a-Si:H photosensor for on-chip detection in biomedical applications.
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
Soft tubular microfluidics for 2D and 3D applications

PubMed Central

Xi, Wang; Kong, Fang; Yeo, Joo Chuan; Yu, Longteng; Sonam, Surabhi; Dao, Ming; Gong, Xiaobo; Lim, Chwee Teck

2017-01-01

Microfluidics has been the key component for many applications, including biomedical devices, chemical processors, microactuators, and even wearable devices. This technology relies on soft lithography fabrication which requires cleanroom facilities. Although popular, this method is expensive and labor-intensive. Furthermore, current conventional microfluidic chips precludes reconfiguration, making reiterations in design very time-consuming and costly. To address these intrinsic drawbacks of microfabrication, we present an alternative solution for the rapid prototyping of microfluidic elements such as microtubes, valves, and pumps. In addition, we demonstrate how microtubes with channels of various lengths and cross-sections can be attached modularly into 2D and 3D microfluidic systems for functional applications. We introduce a facile method of fabricating elastomeric microtubes as the basic building blocks for microfluidic devices. These microtubes are transparent, biocompatible, highly deformable, and customizable to various sizes and cross-sectional geometries. By configuring the microtubes into deterministic geometry, we enable rapid, low-cost formation of microfluidic assemblies without compromising their precision and functionality. We demonstrate configurable 2D and 3D microfluidic systems for applications in different domains. These include microparticle sorting, microdroplet generation, biocatalytic micromotor, triboelectric sensor, and even wearable sensing. Our approach, termed soft tubular microfluidics, provides a simple, cheaper, and faster solution for users lacking proficiency and access to cleanroom facilities to design and rapidly construct microfluidic devices for their various applications and needs. PMID:28923968
Soft tubular microfluidics for 2D and 3D applications

NASA Astrophysics Data System (ADS)

Xi, Wang; Kong, Fang; Yeo, Joo Chuan; Yu, Longteng; Sonam, Surabhi; Dao, Ming; Gong, Xiaobo; Teck Lim, Chwee

2017-10-01

Microfluidics has been the key component for many applications, including biomedical devices, chemical processors, microactuators, and even wearable devices. This technology relies on soft lithography fabrication which requires cleanroom facilities. Although popular, this method is expensive and labor-intensive. Furthermore, current conventional microfluidic chips precludes reconfiguration, making reiterations in design very time-consuming and costly. To address these intrinsic drawbacks of microfabrication, we present an alternative solution for the rapid prototyping of microfluidic elements such as microtubes, valves, and pumps. In addition, we demonstrate how microtubes with channels of various lengths and cross-sections can be attached modularly into 2D and 3D microfluidic systems for functional applications. We introduce a facile method of fabricating elastomeric microtubes as the basic building blocks for microfluidic devices. These microtubes are transparent, biocompatible, highly deformable, and customizable to various sizes and cross-sectional geometries. By configuring the microtubes into deterministic geometry, we enable rapid, low-cost formation of microfluidic assemblies without compromising their precision and functionality. We demonstrate configurable 2D and 3D microfluidic systems for applications in different domains. These include microparticle sorting, microdroplet generation, biocatalytic micromotor, triboelectric sensor, and even wearable sensing. Our approach, termed soft tubular microfluidics, provides a simple, cheaper, and faster solution for users lacking proficiency and access to cleanroom facilities to design and rapidly construct microfluidic devices for their various applications and needs.
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
Explosives detection in the marine environment using UUV-modified immunosensor

NASA Astrophysics Data System (ADS)

Charles, Paul T.; Adams, André A.; Deschamps, Jeffrey R.; Veitch, Scott P.; Hanson, Alfred; Kusterbeck, Anne W.

2011-05-01

Port and harbor security has rapidly become a point of interest and concern with the emergence of new improvised explosive devices (IEDs). The ability to provide physical surveillance and identification of IEDs and unexploded ordnances (UXO) at these entry points has led to an increased effort in the development of unmanned underwater vehicles (UUVs) equipped with sensing devices. Traditional sensors used to identify and locate potential threats are side scan sonar/acoustic methods and magnetometers. At the Naval Research Laboratory (NRL), we have developed an immunosensor capable of detecting trace levels of explosives that has been integrated into a REMUS payload for use in the marine environment. Laboratory tests using a modified PMMA microfluidic device with immobilized monoclonal antibodies specific for TNT and RDX have been conducted yielding detection levels in the low parts-per-billion (ppb) range. New designs and engineered improvements in microfluidic devices, fluorescence signal probes, and UUV internal fluidic and optical components have been investigated and integrated into the unmanned underwater prototype. Results from laboratory and recent field demonstrations using the prototype UUV immunosensor will be discussed. The immunosensor in combination with acoustic and other sensors could serve as a complementary characterization tool for the detection of IEDs, UXOs and other potential chemical or biological threats.
HANDHELD MICROFLUIDIC DEVICE FOR CYANOBACTERIA TOXIN DETECTION AND MONITORING - PHASE I

EPA Science Inventory

HJ Science & Technology, Inc., proposes to demonstrate the feasibility of an integrated “lab-on-a-chip” technology capable of rapid and real time detection and identification of a variety of toxins in drinking water, particularly microcystins and other toxins produced by cy...
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…
Passive Microfluidic device for Sub Millisecond Mixing

PubMed Central

McMahon, Jay; Mohamed, Hisham; Barnard, David; Shaikh, Tanvir R.; Mannella, Carmen A.; Wagenknecht, Terence; Lu, Toh-Ming

2009-01-01

We report the investigation of a novel microfluidic mixing device to achieve submillisecond mixing. The micromixer combines two fluid streams of several microliters per second into a mixing compartment integrated with two T- type premixers and 4 butterfly-shaped in-channel mixing elements. We have employed three dimensional fluidic simulations to evaluate the mixing efficiency, and have constructed physical devices utilizing conventional microfabrication techniques. The simulation indicated thorough mixing at flow rate as low as 6 µL/s. The corresponding mean residence time is 0.44 ms for 90% of the particles simulated, or 0.49 ms for 95% of the particles simulated, respectively. The mixing efficiency of the physical device was also evaluated using fluorescein dye solutions and FluoSphere-red nanoparticles suspensions. The constructed micromixers achieved thorough mixing at the same flow rate of 6 µL/s, with the mixing indices of 96% ± 1%, and 98% ± 1% for the dye and the nanoparticle, respectively. The experimental results are consistent with the simulation data. The device demonstrated promising capabilities for time resolved studies for macromolecular dynamics of biological macromolecules. PMID:20161619
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.

Paper-Plastic Hybrid Microfluidic Device for Smartphone-Based Colorimetric Analysis of Urine.

PubMed

Jalal, Uddin M; Jin, Gyeong Jun; Shim, Joon S

2017-12-19

In this work, a disposable paper-plastic hybrid microfluidic lab-on-a-chip (LOC) has been developed and successfully applied for the colorimetric measurement of urine by the smartphone-based optical platform using a "UrineAnalysis" Android app. The developed device was cost-effectively implemented as a stand-alone hybrid LOC by incorporating the paper-based conventional reagent test strip inside the plastic-based LOC microchannel. The LOC device quantitatively investigated the small volume (40 μL) of urine analytes for the colorimetric reaction of glucose, protein, pH, and red blood cell (RBC) in integration with the finger-actuating micropump. On the basis of our experiments, the conventional urine strip showed large deviation as the reaction time goes by, because dipping the strip sensor in a bottle of urine could not control the reaction volume. By integrating the strip sensor in the LOC device for urine analysis, our device significantly improves the time-dependent inconstancy of the conventional dipstick-based urine strip, and the smartphone app used for image analysis enhances the visual assessment of the test strip, which is a major user concern for the colorimetric analysis in point-of-care (POC) applications. As a result, the user-friendly LOC, which is successfully implemented in a disposable format with the smartphone-based optical platform, may be applicable as an effective tool for rapid and qualitative POC urinalysis.
Deformability and size-based cancer cell separation using an integrated microfluidic device.

PubMed

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

2015-11-07

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

PubMed Central

Camacho-Alanis, Fernanda; Gan, Lin; Ros, Alexandra

2012-01-01

Exploiting dielectrophoresis (DEP) to concentrate and separate biomolecules has recently shown large potential as a microscale bioanalytical tool. Such efforts however require tailored devices and knowledge of all interplaying transport mechanisms competing with dielectrophoresis (DEP). Specifically, a strong DEP contribution to the overall transport mechanism is necessary to exploit DEP of biomolecules for analytical applications such as separation and fractionation. Here, we present improved microfluidic devices combining optical lithography and focused ion beam milling (FIBM) for the manipulation of DNA and proteins using insulator-based dielectrophoresis (iDEP) and direct current (DC) electric fields. Experiments were performed on an elastomer platform forming the iDEP microfluidic device with integrated nanoposts and nanopost arrays. Microscale and nanoscale iDEP was studied for λ-DNA (48.5 kbp) and the protein bovine serum albumin (BSA). Numerical simulations were adapted to the various tested geometries revealing excellent qualitative agreement with experimental observations for streaming and trapping DEP. Both the experimental and simulation results indicate that DC iDEP trapping for λ-DNA occurs with tailored nanoposts fabricated via FIBM. Moreover, streaming iDEP concentration of BSA is improved with integrated nanopost arrays by a factor of 45 compared to microfabricated arrays. PMID:23441049
A Digital Microfluidics Platform for Loop-Mediated Isothermal Amplification Detection

PubMed Central

Veigas, Bruno; Águas, Hugo; Fortunato, Elvira; Martins, Rodrigo; Baptista, Pedro Viana; Igreja, Rui

2017-01-01

Digital microfluidics (DMF) arises as the next step in the fast-evolving field of operation platforms for molecular diagnostics. Moreover, isothermal schemes, such as loop-mediated isothermal amplification (LAMP), allow for further simplification of amplification protocols. Integrating DMF with LAMP will be at the core of a new generation of detection devices for effective molecular diagnostics at point-of-care (POC), providing simple, fast, and automated nucleic acid amplification with exceptional integration capabilities. Here, we demonstrate for the first time the role of coupling DMF and LAMP, in a dedicated device that allows straightforward mixing of LAMP reagents and target DNA, as well as optimum temperature control (reaction droplets undergo a temperature variation of just 0.3 °C, for 65 °C at the bottom plate). This device is produced using low-temperature and low-cost production processes, adaptable to disposable and flexible substrates. DMF-LAMP is performed with enhanced sensitivity without compromising reaction efficacy or losing reliability and efficiency, by LAMP-amplifying 0.5 ng/µL of target DNA in just 45 min. Moreover, on-chip LAMP was performed in 1.5 µL, a considerably lower volume than standard bench-top reactions. PMID:29144379
Developing a protocol for creating microfluidic devices with a 3D printer, PDMS, and glass

NASA Astrophysics Data System (ADS)

Collette, Robyn; Novak, Eric; Shirk, Kathryn

2015-03-01

Microfluidics research requires the design and fabrication of devices that have the ability to manipulate small volumes of fluid, typically ranging from microliters to picoliters. These devices are used for a wide range of applications including the assembly of materials and testing of biological samples. Many methods have been previously developed to create microfluidic devices, including traditional nanolithography techniques. However, these traditional techniques are cost-prohibitive for many small-scale laboratories. This research explores a relatively low-cost technique using a 3D printed master, which is used as a template for the fabrication of polydimethylsiloxane (PDMS) microfluidic devices. The masters are designed using computer aided design (CAD) software and can be printed and modified relatively quickly. We have developed a protocol for creating simple microfluidic devices using a 3D printer and PDMS adhered to glass. This relatively simple and lower-cost technique can now be scaled to more complicated device designs and applications. Funding provided by the Undergraduate Research Grant Program at Shippensburg University and the Student/Faculty Research Engagement Grants from the College of Arts and Sciences at Shippensburg University.
Enhanced biocompatibility of neural probes by integrating microstructures and delivering anti-inflammatory agents via microfluidic channels

NASA Astrophysics Data System (ADS)

Liu, Bin; Kim, Eric; Meggo, Anika; Gandhi, Sachin; Luo, Hao; Kallakuri, Srinivas; Xu, Yong; Zhang, Jinsheng

2017-04-01

Objective. Biocompatibility is a major issue for chronic neural implants, involving inflammatory and wound healing responses of neurons and glial cells. To enhance biocompatibility, we developed silicon-parylene hybrid neural probes with open architecture electrodes, microfluidic channels and a reservoir for drug delivery to suppress tissue responses. Approach. We chronically implanted our neural probes in the rat auditory cortex and investigated (1) whether open architecture electrode reduces inflammatory reaction by measuring glial responses; and (2) whether delivery of antibiotic minocycline reduces inflammatory and tissue reaction. Four weeks after implantation, immunostaining for glial fibrillary acid protein (astrocyte marker) and ionizing calcium-binding adaptor molecule 1 (macrophages/microglia cell marker) were conducted to identify immunoreactive astrocyte and microglial cells, and to determine the extent of astrocytes and microglial cell reaction/activation. A comparison was made between using traditional solid-surface electrodes and newly-designed electrodes with open architecture, as well as between deliveries of minocycline and artificial cerebral-spinal fluid diffused through microfluidic channels. Main results. The new probes with integrated micro-structures induced minimal tissue reaction compared to traditional electrodes at 4 weeks after implantation. Microcycline delivered through integrated microfluidic channels reduced tissue response as indicated by decreased microglial reaction around the neural probes implanted. Significance. The new design will help enhance the long-term stability of the implantable devices.
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.
Challenges and trends in magnetic sensor integration with microfluidics for biomedical applications

NASA Astrophysics Data System (ADS)

Cardoso, S.; Leitao, D. C.; Dias, T. M.; Valadeiro, J.; Silva, M. D.; Chicharo, A.; Silverio, V.; Gaspar, J.; Freitas, P. P.

2017-06-01

Magnetoresistive (MR) sensors have been successfully applied in many technologies, in particular readout electronics and smart systems for multiple signal addressing and readout. When single sensors are used, the requirements relate to spatial resolution and localized field sources. The integration of MR sensors in adaptable media (e.g. flexible, stretchable substrates) offers the possibility to merge the magnetic detection with mechanical functionalities. In addition, the precision of a micrometric needle can benefit greatly from the integration of MR sensors with submicrometric resolution. In this paper, we demonstrate through several detailed examples how advanced MR sensors can be integrated with the systems described above, and also with microfluidic technologies. Here, the challenges of handling liquids over a chip combine with those for miniaturization of microelectronics for MR readout. However, when these are overcome, the result is an integrated system with added functionalities, capable of answering the demand in biomedicine and biochemistry for lab-on-a-chip devices.
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.
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 fluorescence-based centrifugal microfluidic system for parallel detection of multiple allergens

NASA Astrophysics Data System (ADS)

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

2010-02-01

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

PubMed Central

Jiang, Huawei; Ali, Md. Azahar; Xu, Zhen; Halverson, Larry J.; Dong, Liang

2017-01-01

This paper reports on a miniaturized microbial fuel cell with a microfluidic flow-through configuration: a porous anolyte chamber is formed by filling a microfluidic chamber with three-dimensional graphene foam as anode, allowing nutritional medium to flow through the chamber to intimately interact with the colonized microbes on the scaffolds of the anode. No nutritional media flow over the anode. This allows sustaining high levels of nutrient utilization, minimizing consumption of nutritional substrates, and reducing response time of electricity generation owing to fast mass transport through pressure-driven flow and rapid diffusion of nutrients within the anode. The device provides a volume power density of 745 μW/cm3 and a surface power density of 89.4 μW/cm2 using Shewanella oneidensis as a model biocatalyst without any optimization of bacterial culture. The medium consumption and the response time of the flow-through device are reduced by 16.4 times and 4.2 times, respectively, compared to the non-flow-through counterpart with its freeway space volume six times the volume of graphene foam anode. The graphene foam enabled microfluidic flow-through approach will allow efficient microbial conversion of carbon-containing bioconvertible substrates to electricity with smaller space, less medium consumption, and shorter start-up time. PMID:28120875
Integrated Microfluidic Flow-Through Microbial Fuel Cells

NASA Astrophysics Data System (ADS)

Jiang, Huawei; Ali, Md. Azahar; Xu, Zhen; Halverson, Larry J.; Dong, Liang

2017-01-01

This paper reports on a miniaturized microbial fuel cell with a microfluidic flow-through configuration: a porous anolyte chamber is formed by filling a microfluidic chamber with three-dimensional graphene foam as anode, allowing nutritional medium to flow through the chamber to intimately interact with the colonized microbes on the scaffolds of the anode. No nutritional media flow over the anode. This allows sustaining high levels of nutrient utilization, minimizing consumption of nutritional substrates, and reducing response time of electricity generation owing to fast mass transport through pressure-driven flow and rapid diffusion of nutrients within the anode. The device provides a volume power density of 745 μW/cm3 and a surface power density of 89.4 μW/cm2 using Shewanella oneidensis as a model biocatalyst without any optimization of bacterial culture. The medium consumption and the response time of the flow-through device are reduced by 16.4 times and 4.2 times, respectively, compared to the non-flow-through counterpart with its freeway space volume six times the volume of graphene foam anode. The graphene foam enabled microfluidic flow-through approach will allow efficient microbial conversion of carbon-containing bioconvertible substrates to electricity with smaller space, less medium consumption, and shorter start-up time.
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.
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.
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.
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.
Merging microfluidics and sonochemistry: towards greener and more efficient micro-sono-reactors.

PubMed

Fernandez Rivas, David; Cintas, Pedro; Gardeniers, Han J G E

2012-11-18

Microfluidics enable the manipulation of chemical reactions using very small amounts of fluid, in channels with dimensions of tens to hundreds of micrometers; so-called microstructured devices, from which the iconic image of chips emerges. The immediate attraction of microfluidics lies in its greenness: use of small quantities of reagents and solvents, and hence less waste, a precise control of reaction conditions, integration of functionality for process intensification, safer and often faster protocols, reliable scale-up, and possibility of performing multiphase reactions. Among the limitations found in microfluidics the facile formation of precipitating products should be highlighted, and in this context, the search for efficient mass and energy transfers is a must. Such limitations have been partially overcome with the aid of ultrasound in conventional flow systems, and can now be successfully used in microreactors, which provide new capabilities. Novel applications and a better understanding of the physical and chemical aspects of sonochemistry can certainly be achieved by combining microfluidics and ultrasound. We will review this nascent area of research, paying attention to the latest developments and showing future directions, which benefit both from the existing microfluidic technology and sonochemistry itself.
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.

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

NASA Astrophysics Data System (ADS)

Brecher, Christian; Baum, Christoph; Bastuck, Thomas

2015-03-01

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

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

Sommer, Gregory Jon; Tentori, Augusto M.; Schaff, Ulrich Y.

We present a method for counting white blood cells that is uniquely compatible with centrifugation based microfluidics. Blood is deposited on top of one or more layers of density media within a microfluidic disk. Spinning the disk causes the cell populations within whole blood to settle through the media, reaching an equilibrium based on the density of each cell type. Separation and fluorescence measurement of cell types stained with a DNA dye is demonstrated using this technique. The integrated signal from bands of fluorescent microspheres is shown to be proportional to their initial concentration in suspension. Among the current generationmore » of medical diagnostics are devices based on the principle of centrifuging a CD sized disk functionalized with microfluidics. These portable 'lab on a disk' devices are capable of conducting multiple assays directly from a blood sample, embodied by platforms developed by Gyros, Samsung, and Abaxis. [1,2] However, no centrifugal platform to date includes a differential white blood cell count, which is an important metric complimentary to diagnostic assays. Measuring the differential white blood cell count (the relative fraction of granulocytes, lymphocytes, and monocytes) is a standard medical diagnostic technique useful for identifying sepsis, leukemia, AIDS, radiation exposure, and a host of other conditions that affect the immune system. Several methods exist for measuring the relative white blood cell count including flow cytometry, electrical impedance, and visual identification from a stained drop of blood under a microscope. However, none of these methods is easily incorporated into a centrifugal microfluidic diagnostic platform.« less
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
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.
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.
Optofluidic UV-Vis spectrophotometer for online monitoring of photocatalytic reactions

NASA Astrophysics Data System (ADS)

Wang, Ning; Tan, Furui; Zhao, Yu; Tsoi, Chi Chung; Fan, Xudong; Yu, Weixing; Zhang, Xuming

2016-06-01

On-chip integration of optical detection units into the microfluidic systems for online monitoring is highly desirable for many applications and is also well in line with the spirit of optofluidics technology-fusion of optics and microfluidics for advanced functionalities. This paper reports the construction of a UV-Vis spectrophotometer on a microreactor, and demonstrates the online monitoring of the photocatalytic degradations of methylene blue and methyl orange under different flow rates and different pH values by detecting the intensity change and/or the peak shift. The integrated device consists of a TiO2-coated glass substrate, a PDMS micro-sized reaction chamber and two flow cells. By comparing with the results of commercial equipment, we have found that the measuring range and the sensitivity are acceptable, especially when the transmittance is in the range of 0.01-0.9. This integrated optofluidic device can significantly cut down the test time and the sample volume, and would provide a versatile platform for real-time characterization of photochemical performance. Moreover, its online monitoring capability may enable to access the usually hidden information in biochemical reactions like intermediate products, time-dependent processes and reaction kinetics.
Strategy for signaling molecule detection by using an integrated microfluidic device coupled with mass spectrometry to study cell-to-cell communication.

PubMed

Mao, Sifeng; Zhang, Jie; Li, Haifang; Lin, Jin-Ming

2013-01-15

Cell-to-cell communication is a very important physiological behavior in life entity, and most of human behaviors are related to it. Although cell-to-cell communications are attracting much attention and financial support, rare methods have been successfully developed for in vitro cell-to-cell communication study. In this work, we developed a novel method for cell-to-cell communication study on an integrated microdevice, and signaling molecule and metabolites were online-detected by an electrospray ionization-quadrupole-time-of-flight-mass spectrometer (ESI-Q-TOF-MS) after on-chip solid-phase extraction. Moreover, we presented a "Surface Tension Plug" on a microchip to control cell-to-cell communication. The microdevice consists of three functional sections: cell coculture channel, targets pretreatment, and targets detection sections. To verify the feasibility of cell-to-cell communications on the integrated microdevice, we studied the communication between the 293 and the L-02 cells. Epinephrine and glucose were successfully detected using an ESI-Q-TOF-MS with short analysis time (<10 min). The results demonstrated that the developed microfluidic device is a potentially useful tool for high throughput cell-to-cell communication study.
Optofluidic UV-Vis spectrophotometer for online monitoring of photocatalytic reactions

PubMed Central

Wang, Ning; Tan, Furui; Zhao, Yu; Tsoi, Chi Chung; Fan, Xudong; Yu, Weixing; Zhang, Xuming

2016-01-01

On-chip integration of optical detection units into the microfluidic systems for online monitoring is highly desirable for many applications and is also well in line with the spirit of optofluidics technology–fusion of optics and microfluidics for advanced functionalities. This paper reports the construction of a UV-Vis spectrophotometer on a microreactor, and demonstrates the online monitoring of the photocatalytic degradations of methylene blue and methyl orange under different flow rates and different pH values by detecting the intensity change and/or the peak shift. The integrated device consists of a TiO2-coated glass substrate, a PDMS micro-sized reaction chamber and two flow cells. By comparing with the results of commercial equipment, we have found that the measuring range and the sensitivity are acceptable, especially when the transmittance is in the range of 0.01–0.9. This integrated optofluidic device can significantly cut down the test time and the sample volume, and would provide a versatile platform for real-time characterization of photochemical performance. Moreover, its online monitoring capability may enable to access the usually hidden information in biochemical reactions like intermediate products, time-dependent processes and reaction kinetics. PMID:27352840
Optofluidic UV-Vis spectrophotometer for online monitoring of photocatalytic reactions.

PubMed

Wang, Ning; Tan, Furui; Zhao, Yu; Tsoi, Chi Chung; Fan, Xudong; Yu, Weixing; Zhang, Xuming

2016-06-29

On-chip integration of optical detection units into the microfluidic systems for online monitoring is highly desirable for many applications and is also well in line with the spirit of optofluidics technology-fusion of optics and microfluidics for advanced functionalities. This paper reports the construction of a UV-Vis spectrophotometer on a microreactor, and demonstrates the online monitoring of the photocatalytic degradations of methylene blue and methyl orange under different flow rates and different pH values by detecting the intensity change and/or the peak shift. The integrated device consists of a TiO2-coated glass substrate, a PDMS micro-sized reaction chamber and two flow cells. By comparing with the results of commercial equipment, we have found that the measuring range and the sensitivity are acceptable, especially when the transmittance is in the range of 0.01-0.9. This integrated optofluidic device can significantly cut down the test time and the sample volume, and would provide a versatile platform for real-time characterization of photochemical performance. Moreover, its online monitoring capability may enable to access the usually hidden information in biochemical reactions like intermediate products, time-dependent processes and reaction kinetics.
Microfluidic-based Broadband Measurements of Fluid Permittivity and Permeability to 100 GHz

NASA Astrophysics Data System (ADS)

Little, Charles A. E.

This dissertation concerns the development of unique microfluidic microwave devices and associated microwave calibrations to quantitatively extract the broadband permittivity and permeability of fluids between 100 kHz and 110 GHz. The devices presented here consist of SU-8- and PDMS-based microfluidic channels integrated lithographically with coplanar waveguides (CPWs), measured via an external vector network analyzer (VNA). By applying our hybrid set of microwave calibrations to the raw data we extract distributed circuit parameters, representative of the electromagnetic response of the microfluidic channel. We then correlate these parameters to the permittivity and permeability of the fluid within the channels. We are primarily focused on developing devices, calibrations, and analyses to characterize various chemical and biological systems. The small fluid volumes and overall scale of our devices lends the technique to point-of-care blood and cell analysis, as well as to the analysis of high-value chemicals. Broadband microwave microfluidics is sensitive to three primary categories of phenomena: Ionic, dipolar, and magnetic resonances. All three can occur in complex fluids such as blood, proteins and particle suspensions. In order to make quantitative measurements, we need to be able to model and separate all three types of responses. Here we first measure saline solutions (NaCl and water) as an ideal system to better understanding both the ionic and dipolar response. Specifically, we are targeting the electrical double-layer (EDL) response, an ionic effect, which dominates over the intrinsic fluid response at lower frequencies. We have found that the EDL response for saline obeys a strict Debye-type relaxation model, the frequency response of which is dependent solely on the conductivity of the solution. To develop a better understanding of the magnetic response, we first measure magnetic nanoparticles; showing it is possible to detect the magnetic resonances of magnetic nanoparticle in a fluid environment using the broad-band approach, and that the response matches cavity-based measurements. In addition, we demonstrate the complicated intermixing that occurs between magnetic and electrical responses in CPW-type measurements through both numerical modeling, and empirical measurements of impeded embedded permalloy devices.
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
Microfluidic viscometers for shear rheology of complex fluids and biofluids

PubMed Central

Wang, William S.; Vanapalli, Siva A.

2016-01-01

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

NASA Astrophysics Data System (ADS)

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

2018-04-01

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

PubMed

Abdel Fattah, Abdel Rahman; Ghosh, Suvojit; Puri, Ishwar K

2016-08-01

Microfluidics has advanced magnetic blood fractionation by making integrated miniature devices possible. A ferromagnetic microstructure array that is integrated with a microfluidic channel rearranges an applied magnetic field to create a high gradient magnetic field (HGMF). By leveraging the differential magnetic susceptibilities of cell types contained in a host medium, such as paramagnetic red blood cells (RBCs) and diamagnetic white blood cells (WBCs), the resulting HGMF can be used to continuously separate them without attaching additional labels, such as magnetic beads, to them. We describe the effect of these ferromagnetic microstructure geometries have on the blood separation efficacy by numerically simulating the influence of microstructure height and pitch on the HGMF characteristics and resulting RBC separation. Visualizations of RBC trajectories provide insight into how arrays can be optimized to best separate these cells from a host fluid. Periodic microstructures are shown to moderate the applied field due to magnetic interference between the adjacent teeth of an array. Since continuous microstructures do not similarly weaken the resultant HGMF, they facilitate significantly higher RBC separation. Nevertheless, periodic arrays are more appropriate for relatively deep microchannels since, unlike continuous microstructures, their separation effectiveness is independent of depth. The results are relevant to the design of microfluidic devices that leverage HGMFs to fractionate blood by separating RBCs and WBCs. Copyright © 2016 Elsevier B.V. All rights reserved.
Miniature enzyme-based electrodes for detection of hydrogen peroxide release from alcohol-injured hepatocytes.

PubMed

Matharu, Zimple; Enomoto, James; Revzin, Alexander

2013-01-15

Alcohol insult to the liver sets off a complex sequence of inflammatory and fibrogenic responses. There is increasing evidence that hepatocytes play a key role in triggering these responses by producing inflammatory signals such as cytokines and reactive oxygen species (ROS). In the present study, we employed a cell culture/biosensor platform consisting of electrode arrays integrated with microfluidics to monitor extracellular H(2)O(2), one of the major ROS types, produced by primary rat hepatocytes during alcohol injury. The biosensor consisted of hydrogel microstructures with entrapped horseradish peroxidase (HRP) immobilized on an array of miniature gold electrodes. These arrays of sensing electrodes were integrated into microfluidic devices and modified with collagen (I) to promote hepatocyte adhesion. Once seeded into the microfluidic devices, hepatocytes were exposed to 100 mM ethanol and the signal at the working electrode was monitored by cyclic voltammetry (CV) over the course of 4 h. The CV experiments revealed that hepatocytes secreted up to 1.16 μM H(2)O(2) after 3 h of stimulation. Importantly, when hepatocytes were incubated with antioxidants or alcohol dehydrogenase inhibitor prior to alcohol exposure, the H(2)O(2) signal was decreased by ~5-fold. These experiments further confirmed that the biosensor was indeed monitoring oxidative stress generated by the hepatocytes and also pointed to one future use of this technology for screening hepatoprotective effects of antioxidants.
Microfluidic stretchable RF electronics.

PubMed

Cheng, Shi; Wu, Zhigang

2010-12-07

Stretchable electronics is a revolutionary technology that will potentially create a world of radically different electronic devices and systems that open up an entirely new spectrum of possibilities. This article proposes a microfluidic based solution for stretchable radio frequency (RF) electronics, using hybrid integration of active circuits assembled on flex foils and liquid alloy passive structures embedded in elastic substrates, e.g. polydimethylsiloxane (PDMS). This concept was employed to implement a 900 MHz stretchable RF radiation sensor, consisting of a large area elastic antenna and a cluster of conventional rigid components for RF power detection. The integrated radiation sensor except the power supply was fully embedded in a thin elastomeric substrate. Good electrical performance of the standalone stretchable antenna as well as the RF power detection sub-module was verified by experiments. The sensor successfully detected the RF radiation over 5 m distance in the system demonstration. Experiments on two-dimensional (2D) stretching up to 15%, folding and twisting of the demonstrated sensor were also carried out. Despite the integrated device was severely deformed, no failure in RF radiation sensing was observed in the tests. This technique illuminates a promising route of realizing stretchable and foldable large area integrated RF electronics that are of great interest to a variety of applications like wearable computing, health monitoring, medical diagnostics, and curvilinear electronics.
A Low-Noise Transimpedance Amplifier for BLM-Based Ion Channel Recording.

PubMed

Crescentini, Marco; Bennati, Marco; Saha, Shimul Chandra; Ivica, Josip; de Planque, Maurits; Morgan, Hywel; Tartagni, Marco

2016-05-19

High-throughput screening (HTS) using ion channel recording is a powerful drug discovery technique in pharmacology. Ion channel recording with planar bilayer lipid membranes (BLM) is scalable and has very high sensitivity. A HTS system based on BLM ion channel recording faces three main challenges: (i) design of scalable microfluidic devices; (ii) design of compact ultra-low-noise transimpedance amplifiers able to detect currents in the pA range with bandwidth >10 kHz; (iii) design of compact, robust and scalable systems that integrate these two elements. This paper presents a low-noise transimpedance amplifier with integrated A/D conversion realized in CMOS 0.35 μm technology. The CMOS amplifier acquires currents in the range ±200 pA and ±20 nA, with 100 kHz bandwidth while dissipating 41 mW. An integrated digital offset compensation loop balances any voltage offsets from Ag/AgCl electrodes. The measured open-input input-referred noise current is as low as 4 fA/√Hz at ±200 pA range. The current amplifier is embedded in an integrated platform, together with a microfluidic device, for current recording from ion channels. Gramicidin-A, α-haemolysin and KcsA potassium channels have been used to prove both the platform and the current-to-digital converter.

A Low-Noise Transimpedance Amplifier for BLM-Based Ion Channel Recording

PubMed Central

Crescentini, Marco; Bennati, Marco; Saha, Shimul Chandra; Ivica, Josip; de Planque, Maurits; Morgan, Hywel; Tartagni, Marco

2016-01-01

High-throughput screening (HTS) using ion channel recording is a powerful drug discovery technique in pharmacology. Ion channel recording with planar bilayer lipid membranes (BLM) is scalable and has very high sensitivity. A HTS system based on BLM ion channel recording faces three main challenges: (i) design of scalable microfluidic devices; (ii) design of compact ultra-low-noise transimpedance amplifiers able to detect currents in the pA range with bandwidth >10 kHz; (iii) design of compact, robust and scalable systems that integrate these two elements. This paper presents a low-noise transimpedance amplifier with integrated A/D conversion realized in CMOS 0.35 μm technology. The CMOS amplifier acquires currents in the range ±200 pA and ±20 nA, with 100 kHz bandwidth while dissipating 41 mW. An integrated digital offset compensation loop balances any voltage offsets from Ag/AgCl electrodes. The measured open-input input-referred noise current is as low as 4 fA/√Hz at ±200 pA range. The current amplifier is embedded in an integrated platform, together with a microfluidic device, for current recording from ion channels. Gramicidin-A, α-haemolysin and KcsA potassium channels have been used to prove both the platform and the current-to-digital converter. PMID:27213382
Sample injection and electrophoretic separation on a simple laminated paper based analytical device.

PubMed

Xu, Chunxiu; Zhong, Minghua; Cai, Longfei; Zheng, Qingyu; Zhang, Xiaojun

2016-02-01

We described a strategy to perform multistep operations on a simple laminated paper-based separation device by using electrokinetic flow to manipulate the fluids. A laminated crossed-channel paper-based separation device was fabricated by cutting a filter paper sheet followed by lamination. Multiple function units including sample loading, sample injection, and electrophoretic separation were integrated on a single paper based analytical device for the first time, by applying potential at different reservoirs for sample, sample waste, buffer, and buffer waste. As a proof-of-concept demonstration, mixed sample solution containing carmine and sunset yellow were loaded in the sampling channel, and then injected into separation channel followed by electrophoretic separation, by adjusting the potentials applied at the four terminals of sampling and separation channel. The effects of buffer pH, buffer concentration, channel width, and separation time on resolution of electrophoretic separation were studied. This strategy may be used to perform multistep operations such as reagent dilution, sample injection, mixing, reaction, and separation on a single microfluidic paper based analytical device, which is very attractive for building micro total analysis systems on microfluidic paper based analytical devices. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Combined Microfluidic-Eectric Diffused Mixing of Living Cells in Continuous Flow

NASA Astrophysics Data System (ADS)

Ming-Wen Wang,

2010-02-01

The mixing process is a crucially important stage in the operation of biological and chemical microfluidic devices. If the mixing is inadequate, reactants do not fully interact with each other, and the device may not operate properly. This paper describes a simplified microfluidic mixer (different from a chaotic mixer) which can uniformly mix a buffer solution with living cells by applying an AC electric charge. Diffusion of the living cells into the buffer solution occurs rapidly following the interface of the flow stream with the electric charge; no further agitating step is needed. To accomplish this, an asymmetric pair of electrodes was integrated at the inlets of the buffer solution and the cells fluid. When the buffer solution and the cells fluid were introduced into one flow path, they remained limited to that flow stream. When the electrodes were charged, however, the cells in a short distance were efficiently moved into the solution flow, and the original fluids were mixed. The mixing efficiency depends on the polarizability of the cells, and this in turn is governed by the dielectric properties of the cells, the medium, and the solvent. This micro device, capable of efficiently mixing living cells with a buffer solution, may potentially allow biological mixing to be done outside of hospitals, in facilities without biological analyzing instruments.
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.
Thermoelectric ELISA for quantification of 8OHdG in a microfluidic device

NASA Astrophysics Data System (ADS)

Nestorova, Gergana

This research demonstrates the feasibility of a novel method for performing thermoelectric enzyme-linked immunosorbent assay (ELISA) in a microfluidic device. The feasibility of the thermoelectric ELISA is demonstrated by measuring the concentration of 8-hydroxy 2-deoxyguanosine (8OHdG) in urine samples from amyloid precursor protein (APP) transgenic mice. The detection method is based on formation of a complex between 8OHdG and anti-8OHdG capture antibody conjugated to biotin. The complex is immobilized over the measuring junctions of a thermopile via biotin streptavidin interaction. The concentration of the analyte is determined by using enzyme linked secondary IgG antibody specific to the primary one. The concentration of 8OHdG is determined by the initiation of an enzymatic reaction between glucose and glucose oxidase that is conjugated to the secondary IgG antibody. The heat released by the reaction of glucose and glucose oxidase is measured using an antimony-bismuth thermopile integrated in a microfluidic device. The amount of heat detected by the sensor is inversely proportional to the concentration of 8OHdG. A standard calibration curve using known concentrations of synthetic 8OHdG is generated and used to determine the concentration of the oxidized guanine in mouse urine samples.
A microfluidics-based technique for automated and rapid labeling of cells for flow cytometry

NASA Astrophysics Data System (ADS)

Patibandla, Phani K.; Estrada, Rosendo; Kannan, Manasaa; Sethu, Palaniappan

2014-03-01

Flow cytometry is a powerful technique capable of simultaneous multi-parametric analysis of heterogeneous cell populations for research and clinical applications. In recent years, the flow cytometer has been miniaturized and made portable for application in clinical- and resource-limited settings. The sample preparation procedure, i.e. labeling of cells with antibodies conjugated to fluorescent labels, is a time consuming (˜45 min) and labor-intensive procedure. Microfluidics provides enabling technologies to accomplish rapid and automated sample preparation. Using an integrated microfluidic device consisting of a labeling and washing module, we demonstrate a new protocol that can eliminate sample handling and accomplish sample and reagent metering, high-efficiency mixing, labeling and washing in rapid automated fashion. The labeling module consists of a long microfluidic channel with an integrated chaotic mixer. Samples and reagents are precisely metered into this device to accomplish rapid and high-efficiency mixing. The mixed sample and reagents are collected in a holding syringe and held for up to 8 min following which the mixture is introduced into an inertial washing module to obtain ‘analysis-ready’ samples. The washing module consists of a high aspect ratio channel capable of focusing cells to equilibrium positions close to the channel walls. By introducing the cells and labeling reagents in a narrow stream at the center of the channel flanked on both sides by a wash buffer, the elution of cells into the wash buffer away from the free unbound antibodies is accomplished. After initial calibration experiments to determine appropriate ‘holding time’ to allow antibody binding, both modules were used in conjunction to label MOLT-3 cells (T lymphoblast cell line) with three different antibodies simultaneously. Results confirm no significant difference in mean fluorescence intensity values for all three antibodies labels (p < 0.01) between the conventional procedure (45 min) and our microfluidic approach (12 min).
Microfluidic vascularized bone tissue model with hydroxyapatite-incorporated extracellular matrix.

PubMed

Jusoh, Norhana; Oh, Soojung; Kim, Sudong; Kim, Jangho; Jeon, Noo Li

2015-10-21

Current in vitro systems mimicking bone tissues fail to fully integrate the three-dimensional (3D) microvasculature and bone tissue microenvironments, decreasing their similarity to in vivo conditions. Here, we propose 3D microvascular networks in a hydroxyapatite (HA)-incorporated extracellular matrix (ECM) for designing and manipulating a vascularized bone tissue model in a microfluidic device. Incorporation of HA of various concentrations resulted in ECM with varying mechanical properties. Sprouting angiogenesis was affected by mechanically modulated HA-extracellular matrix interactions, generating a model of vascularized bone microenvironment. Using this platform, we observed that hydroxyapatite enhanced angiogenic properties such as sprout length, sprouting speed, sprout number, and lumen diameter. This new platform integrates fibrin ECM with the synthetic bone mineral HA to provide in vivo-like microenvironments for bone vessel sprouting.
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.
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.
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.
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 portable and integrated instrument for cell manipulation by dielectrophoresis.

PubMed

Burgarella, Sarah; Di Bari, Marco

2015-07-01

The physical manipulation of biological cells is a key point in the development of miniaturized systems for point-of-care analyses. Dielectrophoresis (DEP) has been reported by several laboratories as a promising method in biomedical research for label-free cell manipulation without physical contact, by exploiting the dielectric properties of cells suspended in a microfluidic sample, under the action of high-gradient electric fields. In view of a more extended use of DEP phenomena in lab-on-chip devices for point-of-care settings, we have developed a portable instrument, integrating on the same device the microfluidic biochip for cell manipulation and all the laboratory functions (i.e., DEP electric signal generation, microscopic observation of the biological sample under test and image acquisition) that are normally obtained by combining different nonportable standard laboratory instruments. The nonuniform electric field for cell manipulation on the biochip is generated by microelectrodes, patterned on the silicon substrate of microfluidic channels, using standard microfabrication techniques. Numerical modeling was performed to simulate the electric field distribution, quantify the DEP force, and optimize the geometry of the microelectrodes. The developed instrument includes an electronic board, which allows the control of the electric signal applied to electrodes necessary for DEP, and a miniaturized optical microscope system that allows visual inspection and eventually cell counting, as well as image and video recording. The system also includes the control software. The portable and integrated platform described in this work therefore represents a complete and innovative solution of applied research, suitable for many biological applications. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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.
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.
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.
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
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

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