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

PubMed Central

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

2018-01-01

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

Interplay between materials and microfluidics

NASA Astrophysics Data System (ADS)

Hou, Xu; Zhang, Yu Shrike; Santiago, Grissel Trujillo-De; Alvarez, Mario Moisés; Ribas, João; Jonas, Steven J.; Weiss, Paul S.; Andrews, Anne M.; Aizenberg, Joanna; Khademhosseini, Ali

2017-04-01

Developments in the field of microfluidics have triggered technological revolutions in many disciplines, including chemical synthesis, electronics, diagnostics, single-cell analysis, micro- and nanofabrication, and pharmaceutics. In many of these areas, rapid growth is driven by the increasing synergy between fundamental materials development and new microfluidic capabilities. In this Review, we critically evaluate both how recent advances in materials fabrication have expanded the frontiers of microfluidic platforms and how the improved microfluidic capabilities are, in turn, furthering materials design. We discuss how various inorganic and organic materials enable the fabrication of systems with advanced mechanical, optical, chemical, electrical and biointerfacial properties — in particular, when these materials are combined into new hybrids and modular configurations. The increasing sophistication of microfluidic techniques has also expanded the range of resources available for the fabrication of new materials, including particles and fibres with specific functionalities, 3D (bio)printed composites and organoids. Together, these advances lead to complex, multifunctional systems, which have many interesting potential applications, especially in the biomedical and bioengineering domains. Future exploration of the interactions between materials science and microfluidics will continue to enrich the diversity of applications across engineering as well as the physical and biomedical sciences.

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.

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

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

A modular microfluidic architecture for integrated biochemical analysis.

PubMed

Shaikh, Kashan A; Ryu, Kee Suk; Goluch, Edgar D; Nam, Jwa-Min; Liu, Juewen; Thaxton, C Shad; Chiesl, Thomas N; Barron, Annelise E; Lu, Yi; Mirkin, Chad A; Liu, Chang

2005-07-12

Microfluidic laboratory-on-a-chip (LOC) systems based on a modular architecture are presented. The architecture is conceptualized on two levels: a single-chip level and a multiple-chip module (MCM) system level. At the individual chip level, a multilayer approach segregates components belonging to two fundamental categories: passive fluidic components (channels and reaction chambers) and active electromechanical control structures (sensors and actuators). This distinction is explicitly made to simplify the development process and minimize cost. Components belonging to these two categories are built separately on different physical layers and can communicate fluidically via cross-layer interconnects. The chip that hosts the electromechanical control structures is called the microfluidic breadboard (FBB). A single LOC module is constructed by attaching a chip comprised of a custom arrangement of fluid routing channels and reactors (passive chip) to the FBB. Many different LOC functions can be achieved by using different passive chips on an FBB with a standard resource configuration. Multiple modules can be interconnected to form a larger LOC system (MCM level). We demonstrated the utility of this architecture by developing systems for two separate biochemical applications: one for detection of protein markers of cancer and another for detection of metal ions. In the first case, free prostate-specific antigen was detected at 500 aM concentration by using a nanoparticle-based bio-bar-code protocol on a parallel MCM system. In the second case, we used a DNAzyme-based biosensor to identify the presence of Pb(2+) (lead) at a sensitivity of 500 nM in <1 nl of solution.

"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.

Modular microfluidic systems using reversibly attached PDMS fluid control modules

NASA Astrophysics Data System (ADS)

Skafte-Pedersen, Peder; Sip, Christopher G.; Folch, Albert; Dufva, Martin

2013-05-01

The use of soft lithography-based poly(dimethylsiloxane) (PDMS) valve systems is the dominating approach for high-density microscale fluidic control. Integrated systems enable complex flow control and large-scale integration, but lack modularity. In contrast, modular systems are attractive alternatives to integration because they can be tailored for different applications piecewise and without redesigning every element of the system. We present a method for reversibly coupling hard materials to soft lithography defined systems through self-aligning O-ring features thereby enabling easy interfacing of complex-valve-based systems with simpler detachable units. Using this scheme, we demonstrate the seamless interfacing of a PDMS-based fluid control module with hard polymer chips. In our system, 32 self-aligning O-ring features protruding from the PDMS fluid control module form chip-to-control module interconnections which are sealed by tightening four screws. The interconnection method is robust and supports complex fluidic operations in the reversibly attached passive chip. In addition, we developed a double-sided molding method for fabricating PDMS devices with integrated through-holes. The versatile system facilitates a wide range of applications due to the modular approach, where application specific passive chips can be readily attached to the flow control module.

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.

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

PubMed

Wardrip, Nathaniel C; Arnusch, Christopher J

2016-02-13

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

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

PubMed Central

Wardrip, Nathaniel C.; Arnusch, Christopher J.

2016-01-01

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

Finger-powered microfluidic systems using multilayer soft lithography and injection molding processes.

PubMed

Iwai, Kosuke; Shih, Kuan Cheng; Lin, Xiao; Brubaker, Thomas A; Sochol, Ryan D; Lin, Liwei

2014-10-07

Point-of-care (POC) and disposable biomedical applications demand low-power microfluidic systems with pumping components that provide controlled pressure sources. Unfortunately, external pumps have hindered the implementation of such microfluidic systems due to limitations associated with portability and power requirements. Here, we propose and demonstrate a 'finger-powered' integrated pumping system as a modular element to provide pressure head for a variety of advanced microfluidic applications, including finger-powered on-chip microdroplet generation. By utilizing a human finger for the actuation force, electrical power sources that are typically needed to generate pressure head were obviated. Passive fluidic diodes were designed and implemented to enable distinct fluids from multiple inlet ports to be pumped using a single actuation source. Both multilayer soft lithography and injection molding processes were investigated for device fabrication and performance. Experimental results revealed that the pressure head generated from a human finger could be tuned based on the geometric characteristics of the pumping system, with a maximum observed pressure of 7.6 ± 0.1 kPa. In addition to the delivery of multiple, distinct fluids into microfluidic channels, we also employed the finger-powered pumping system to achieve the rapid formation of both water-in-oil droplets (106.9 ± 4.3 μm in diameter) and oil-in-water droplets (75.3 ± 12.6 μm in diameter) as well as the encapsulation of endothelial cells in droplets without using any external or electrical controllers.

Modular high voltage power supply for chemical analysis

DOEpatents

Stamps, James F [Livermore, CA; Yee, Daniel D [Dublin, CA

2007-01-09

A high voltage power supply for use in a system such as a microfluidics system, uses a DC--DC converter in parallel with a voltage-controlled resistor. A feedback circuit provides a control signal for the DC--DC converter and voltage-controlled resistor so as to regulate the output voltage of the high voltage power supply, as well as, to sink or source current from the high voltage supply.

Modular high voltage power supply for chemical analysis

DOEpatents

Stamps, James F [Livermore, CA; Yee, Daniel D [Dublin, CA

2010-05-04

A high voltage power supply for use in a system such as a microfluidics system, uses a DC-DC converter in parallel with a voltage-controlled resistor. A feedback circuit provides a control signal for the DC-DC converter and voltage-controlled resistor so as to regulate the output voltage of the high voltage power supply, as well as, to sink or source current from the high voltage supply.

Modular high voltage power supply for chemical analysis

DOEpatents

Stamps, James F [Livermore, CA; Yee, Daniel D [Dublin, CA

2008-07-15

A high voltage power supply for use in a system such as a microfluidics system, uses a DC-DC converter in parallel with a voltage-controlled resistor. A feedback circuit provides a control signal for the DC-DC converter and voltage-controlled resistor so as to regulate the output voltage of the high voltage power supply, as well as, to sink or source current from the high voltage supply.

Towards a Multifunctional Electrochemical Sensing and Niosome Generation Lab-on-Chip Platform Based on a Plug-and-Play Concept.

PubMed

Kara, Adnane; Rouillard, Camille; Mathault, Jessy; Boisvert, Martin; Tessier, Frédéric; Landari, Hamza; Melki, Imene; Laprise-Pelletier, Myriam; Boisselier, Elodie; Fortin, Marc-André; Boilard, Eric; Greener, Jesse; Miled, Amine

2016-05-28

In this paper, we present a new modular lab on a chip design for multimodal neurotransmitter (NT) sensing and niosome generation based on a plug-and-play concept. This architecture is a first step toward an automated platform for an automated modulation of neurotransmitter concentration to understand and/or treat neurodegenerative diseases. A modular approach has been adopted in order to handle measurement or drug delivery or both measurement and drug delivery simultaneously. The system is composed of three fully independent modules: three-channel peristaltic micropumping system, a three-channel potentiostat and a multi-unit microfluidic system composed of pseudo-Y and cross-shape channels containing a miniature electrode array. The system was wirelessly controlled by a computer interface. The system is compact, with all the microfluidic and sensing components packaged in a 5 cm × 4 cm × 4 cm box. Applied to serotonin, a linear calibration curve down to 0.125 mM, with a limit of detection of 31 μ M was collected at unfunctionalized electrodes. Added sensitivity and selectivity was achieved by incorporating functionalized electrodes for dopamine sensing. Electrode functionalization was achieved with gold nanoparticles and using DNA and o-phenylene diamine polymer. The as-configured platform is demonstrated as a central component toward an "intelligent" drug delivery system based on a feedback loop to monitor drug delivery.

Towards a Multifunctional Electrochemical Sensing and Niosome Generation Lab-on-Chip Platform Based on a Plug-and-Play Concept

PubMed Central

Kara, Adnane; Rouillard, Camille; Mathault, Jessy; Boisvert, Martin; Tessier, Frédéric; Landari, Hamza; Melki, Imene; Laprise-Pelletier, Myriam; Boisselier, Elodie; Fortin, Marc-André; Boilard, Eric; Greener, Jesse; Miled, Amine

2016-01-01

In this paper, we present a new modular lab on a chip design for multimodal neurotransmitter (NT) sensing and niosome generation based on a plug-and-play concept. This architecture is a first step toward an automated platform for an automated modulation of neurotransmitter concentration to understand and/or treat neurodegenerative diseases. A modular approach has been adopted in order to handle measurement or drug delivery or both measurement and drug delivery simultaneously. The system is composed of three fully independent modules: three-channel peristaltic micropumping system, a three-channel potentiostat and a multi-unit microfluidic system composed of pseudo-Y and cross-shape channels containing a miniature electrode array. The system was wirelessly controlled by a computer interface. The system is compact, with all the microfluidic and sensing components packaged in a 5 cm × 4 cm × 4 cm box. Applied to serotonin, a linear calibration curve down to 0.125 mM, with a limit of detection of 31 μM was collected at unfunctionalized electrodes. Added sensitivity and selectivity was achieved by incorporating functionalized electrodes for dopamine sensing. Electrode functionalization was achieved with gold nanoparticles and using DNA and o-phenylene diamine polymer. The as-configured platform is demonstrated as a central component toward an “intelligent” drug delivery system based on a feedback loop to monitor drug delivery. PMID:27240377

Purification of complex samples: Implementation of a modular and reconfigurable droplet-based microfluidic platform with cascaded deterministic lateral displacement separation modules

PubMed Central

Pudda, Catherine; Boizot, François; Verplanck, Nicolas; Revol-Cavalier, Frédéric; Berthier, Jean; Thuaire, Aurélie

2018-01-01

Particle separation in microfluidic devices is a common problematic for sample preparation in biology. Deterministic lateral displacement (DLD) is efficiently implemented as a size-based fractionation technique to separate two populations of particles around a specific size. However, real biological samples contain components of many different sizes and a single DLD separation step is not sufficient to purify these complex samples. When connecting several DLD modules in series, pressure balancing at the DLD outlets of each step becomes critical to ensure an optimal separation efficiency. A generic microfluidic platform is presented in this paper to optimize pressure balancing, when DLD separation is connected either to another DLD module or to a different microfluidic function. This is made possible by generating droplets at T-junctions connected to the DLD outlets. Droplets act as pressure controllers, which perform at the same time the encapsulation of DLD sorted particles and the balance of output pressures. The optimized pressures to apply on DLD modules and on T-junctions are determined by a general model that ensures the equilibrium of the entire platform. The proposed separation platform is completely modular and reconfigurable since the same predictive model applies to any cascaded DLD modules of the droplet-based cartridge. PMID:29768490

Engineering of In Vitro 3D Capillary Beds by Self-Directed Angiogenic Sprouting

PubMed Central

Chan, Juliana M.; Zervantonakis, Ioannis K.; Rimchala, Tharathorn; Polacheck, William J.; Whisler, Jordan; Kamm, Roger D.

2012-01-01

In recent years, microfluidic systems have been used to study fundamental aspects of angiogenesis through the patterning of single-layered, linear or geometric vascular channels. In vivo, however, capillaries exist in complex, three-dimensional (3D) networks, and angiogenic sprouting occurs with a degree of unpredictability in all x,y,z planes. The ability to generate capillary beds in vitro that can support thick, biological tissues remains a key challenge to the regeneration of vital organs. Here, we report the engineering of 3D capillary beds in an in vitro microfluidic platform that is comprised of a biocompatible collagen I gel supported by a mechanical framework of alginate beads. The engineered vessels have patent lumens, form robust ∼1.5 mm capillary networks across the devices, and support the perfusion of 1 µm fluorescent beads through them. In addition, the alginate beads offer a modular method to encapsulate and co-culture cells that either promote angiogenesis or require perfusion for cell viability in engineered tissue constructs. This laboratory-constructed vascular supply may be clinically significant for the engineering of capillary beds and higher order biological tissues in a scalable and modular manner. PMID:23226527

Novel microfluidic system for online monitoring of biofilm dynamics by electrical impedance spectroscopy and amperometry

NASA Astrophysics Data System (ADS)

Bruchmann, Julia; Sachsenheimer, Kai; Schwartz, Thomas; Rapp, Bastian E.

2016-03-01

Biofilm formation is ubiquitous in nature where microorganisms attach to surfaces and form highly adapted and protected communities. In technical and industrial systems like drinking water supply, food production or shipping industry biofilms are a major cause of product contamination, biofouling, and biocorrosion. Therefore, understanding of biofilm formation and means of preventing biofilm formation is important to develop novel biofilm treatment strategies. A system allowing directly online detection and monitoring biofilm formation is necessary. However, until today, there are little to none technical systems featuring a non-destructive real-time characterization of biofilm formation in a highthroughput manner. This paper presents such a microfluidic system based on electrical impedance spectroscopy (EIS) and amperomertic current measurement. The sensor consists of four modules, each housing 24 independent electrodes within 12 microfluidic channels. Attached biomass on the electrodes is monitored as increased inhibition in charge transfer by EIS and a change in metabolic activity is measured as change in produced electric current by amperometry. This modular sensor system is highly adaptable and suitable for a broad range of microbiological applications. Among others, biofilm formation processes can be characterized online, biofilm manipulation like inactivation or destabilization can be monitored in real-time and gene expression can be analyzed in parallel. The use of different electrode designs allows effective biofilm studies during all biofilm phases. The whole system was recently extended by an integrated pneumatic microfluidic pump which enables easy handling procedures. Further developments of this pumping module will allow a fully- automated computer-controlled valving and pumping.

A Cost-Effective Fluorescence Mini-Microscope with Adjustable Magnifications for Biomedical Applications

PubMed Central

Zhang, Yu Shrike; Ribas, João; Nadhman, Akhtar; Aleman, Julio; Selimović, Šeila; Lesher-Perez, Sasha Cai; Wang, Ting; Manoharan, Vijayan; Shin, Su-Ryon; Damilano, Alessia; Annabi, Nasim; Dokmeci, Mehmet Remzi; Takayama, Shuichi; Khademhosseini, Ali

2015-01-01

We have designed and fabricated a miniature microscope from off-the-shelf components and webcam, with built-in fluorescence capability for biomedical applications. The mini-microscope was able to detect both biochemical parameters such as cell/tissue viability (e.g. Live/Dead assay), and biophysical properties of the microenvironment such as oxygen levels in microfabricated tissues based on an oxygen-sensitive fluorescent dye. This mini-microscope has adjustable magnifications from 8-60X, achieves a resolution as high as <2 μm, and possesses a long working distance of 4.5 mm (at a magnification of 8X). The mini-microscope was able to chronologically monitor cell migration and analyze beating of microfluidic liver and cardiac bioreactors in real time, respectively. The mini-microscope system is cheap, and its modularity allows convenient integration with a wide variety of pre-existing platforms including but not limited to, cell culture plates, microfluidic devices, and organs-on-a-chip systems. Therefore, we envision its widespread applications in cell biology, tissue engineering, biosensing, microfluidics, and organs-on-chips, which can potentially replace conventional bench-top microscopy where long-term in situ and large-scale imaging/analysis is required. PMID:26282117

A cost-effective fluorescence mini-microscope for biomedical applications.

PubMed

Zhang, Yu Shrike; Ribas, João; Nadhman, Akhtar; Aleman, Julio; Selimović, Šeila; Lesher-Perez, Sasha Cai; Wang, Ting; Manoharan, Vijayan; Shin, Su-Ryon; Damilano, Alessia; Annabi, Nasim; Dokmeci, Mehmet Remzi; Takayama, Shuichi; Khademhosseini, Ali

2015-01-01

We have designed and fabricated a miniature microscope from off-the-shelf components and a webcam, with built-in fluorescence capability for biomedical applications. The mini-microscope was able to detect both biochemical parameters, such as cell/tissue viability (e.g. live/dead assay), and biophysical properties of the microenvironment such as oxygen levels in microfabricated tissues based on an oxygen-sensitive fluorescent dye. This mini-microscope has adjustable magnifications from 8-60×, achieves a resolution as high as <2 μm, and possesses a long working distance of 4.5 mm (at a magnification of 8×). The mini-microscope was able to chronologically monitor cell migration and analyze beating of microfluidic liver and cardiac bioreactors in real time, respectively. The mini-microscope system is cheap, and its modularity allows convenient integration with a wide variety of pre-existing platforms including, but not limited to, cell culture plates, microfluidic devices, and organs-on-a-chip systems. Therefore, we envision its widespread application in cell biology, tissue engineering, biosensing, microfluidics, and organs-on-chips, which can potentially replace conventional bench-top microscopy where long-term in situ and large-scale imaging/analysis is required.

A Combined Fabrication and Instrumentation Platform for Sample Preparation.

PubMed

Guckenberger, David J; Thomas, Peter C; Rothbauer, Jacob; LaVanway, Alex J; Anderson, Meghan; Gilson, Dan; Fawcett, Kevin; Berto, Tristan; Barrett, Kevin; Beebe, David J; Berry, Scott M

2014-06-01

While potentially powerful, access to molecular diagnostics is substantially limited in the developing world. Here we present an approach to reduced cost molecular diagnostic instrumentation that has the potential to empower developing world communities by reducing costs through streamlining the sample preparation process. In addition, this instrument is capable of producing its own consumable devices on demand, reducing reliance on assay suppliers. Furthermore, this instrument is designed with an "open" architecture, allowing users to visually observe the assay process and make modifications as necessary (as opposed to traditional "black box" systems). This open environment enables integration of microfluidic fabrication and viral RNA purification onto an easy-to-use modular system via the use of interchangeable trays. Here we employ this system to develop a protocol to fabricate microfluidic devices and then use these devices to isolate viral RNA from serum for the measurement of human immunodeficiency virus (HIV) viral load. Results obtained from this method show significantly reduced error compared with similar nonautomated sample preparation processes. © 2014 Society for Laboratory Automation and Screening.

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

NASA Astrophysics Data System (ADS)

Chronopoulou, Laura; Sparago, Carolina; Palocci, Cleofe

2014-11-01

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

A Modular and Affordable Time-Lapse Imaging and Incubation System Based on 3D-Printed Parts, a Smartphone, and Off-The-Shelf Electronics

PubMed Central

Schwan, Emil; Fatsis-Kavalopoulos, Nikos; Kreuger, Johan

2016-01-01

Time-lapse imaging is a powerful tool for studying cellular dynamics and cell behavior over long periods of time to acquire detailed functional information. However, commercially available time-lapse imaging systems are expensive and this has limited a broader implementation of this technique in low-resource environments. Further, the availability of time-lapse imaging systems often present workflow bottlenecks in well-funded institutions. To address these limitations we have designed a modular and affordable time-lapse imaging and incubation system (ATLIS). The ATLIS enables the transformation of simple inverted microscopes into live cell imaging systems using custom-designed 3D-printed parts, a smartphone, and off-the-shelf electronic components. We demonstrate that the ATLIS provides stable environmental conditions to support normal cell behavior during live imaging experiments in both traditional and evaporation-sensitive microfluidic cell culture systems. Thus, the system presented here has the potential to increase the accessibility of time-lapse microscopy of living cells for the wider research community. PMID:28002463

A Modular and Affordable Time-Lapse Imaging and Incubation System Based on 3D-Printed Parts, a Smartphone, and Off-The-Shelf Electronics.

PubMed

Hernández Vera, Rodrigo; Schwan, Emil; Fatsis-Kavalopoulos, Nikos; Kreuger, Johan

2016-01-01

Time-lapse imaging is a powerful tool for studying cellular dynamics and cell behavior over long periods of time to acquire detailed functional information. However, commercially available time-lapse imaging systems are expensive and this has limited a broader implementation of this technique in low-resource environments. Further, the availability of time-lapse imaging systems often present workflow bottlenecks in well-funded institutions. To address these limitations we have designed a modular and affordable time-lapse imaging and incubation system (ATLIS). The ATLIS enables the transformation of simple inverted microscopes into live cell imaging systems using custom-designed 3D-printed parts, a smartphone, and off-the-shelf electronic components. We demonstrate that the ATLIS provides stable environmental conditions to support normal cell behavior during live imaging experiments in both traditional and evaporation-sensitive microfluidic cell culture systems. Thus, the system presented here has the potential to increase the accessibility of time-lapse microscopy of living cells for the wider research community.

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.

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

PubMed Central

Tangen, Uwe; Sharma, Abhishek

2015-01-01

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

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

PubMed

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

2015-01-01

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

Automated microfluidic platform for systematic studies of colloidal perovskite nanocrystals: towards continuous nano-manufacturing.

PubMed

Epps, Robert W; Felton, Kobi C; Coley, Connor W; Abolhasani, Milad

2017-11-21

Colloidal organic/inorganic metal-halide perovskite nanocrystals have recently emerged as a potential low-cost replacement for the semiconductor materials in commercial photovoltaics and light emitting diodes. However, unlike III-V and IV-VI semiconductor nanocrystals, studies of colloidal perovskite nanocrystals have yet to develop a fundamental and comprehensive understanding of nucleation and growth kinetics. Here, we introduce a modular and automated microfluidic platform for the systematic studies of room-temperature synthesized cesium-lead halide perovskite nanocrystals. With abundant data collection across the entirety of four orders of magnitude reaction time span, we comprehensively characterize nanocrystal growth within a modular microfluidic reactor. The developed high-throughput screening platform features a custom-designed three-port flow cell with translational capability for in situ spectral characterization of the in-flow synthesized perovskite nanocrystals along a tubular microreactor with an adjustable length, ranging from 3 cm to 196 cm. The translational flow cell allows for sampling of twenty unique residence times at a single equilibrated flow rate. The developed technique requires an average total liquid consumption of 20 μL per spectra and as little as 2 μL at the time of sampling. It may continuously sample up to 30 000 unique spectra per day in both single and multi-phase flow formats. Using the developed plug-and-play microfluidic platform, we study the growth of cesium lead trihalide perovskite nanocrystals through in situ monitoring of their absorption and emission band-gaps at residence times ranging from 100 ms to 17 min. The automated microfluidic platform enables a systematic study of the effect of mixing enhancement on the quality of the synthesized nanocrystals through a direct comparison between single- and multi-phase flow systems at similar reaction time scales. The improved mixing characteristics of the multi-phase flow format results in high-quality perovskite nanocrystals with kinetically tunable emission wavelength, ranging as much as 25 nm at equivalent residence times. Further application of this unique platform would allow rapid parameter optimization in the colloidal synthesis of a wide range of nanomaterials (e.g., metal or semiconductor), that is directly transferable to continuous manufacturing in a numbered-up platform with a similar characteristic length scale.

Predicting the behavior of microfluidic circuits made from discrete elements

PubMed Central

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

2015-01-01

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

Low-cost, disposable microfluidics device for blood plasma extraction using continuously alternating paramagnetic and diamagnetic capture modes

PubMed Central

Kim, Pilkee; Ong, Eng Hui; Yoon, Yong-Jin; Ng, Sum Huan Gary; Puttachat, Khuntontong

2016-01-01

Blood plasma contains biomarkers and substances that indicate the physiological state of an organism, and it can be used to diagnose various diseases or body condition. To improve the accuracy of diagnostic test, it is required to obtain the high purity of blood plasma. This paper presents a low-cost, disposable microfluidics device for blood plasma extraction using magnetophoretic behaviors of blood cells. This device uses alternating magnetophoretic capture modes to trap and separate paramagnetic and diamagnetic cells away from blood plasma. The device system is composed of two parts, a disposable microfluidics chip and a non-disposable (reusable) magnetic field source. Such modularized device helps the structure of the disposable part dramatically simplified, which is beneficial for low-cost mass production. A series of numerical simulation and parametric study have been performed to describe the mechanism of blood cell separation in the microchannel, and the results are discussed. Furthermore, experimental feasibility test has been carried out in order to demonstrate the blood plasma extraction process of the proposed device. In this experiment, pure blood plasma has been successfully extracted with yield of 21.933% from 75 μl 1:10 dilution of deoxygenated blood. PMID:27042252

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

PubMed Central

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

2013-01-01

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

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

PubMed

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

2012-05-01

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

Direct detection of cancer biomarkers in blood using a "place n play" modular polydimethylsiloxane pump.

PubMed

Zhang, Honglian; Li, Gang; Liao, Lingying; Mao, Hongju; Jin, Qinghui; Zhao, Jianlong

2013-01-01

Cancer biomarkers have significant potential as reliable tools for the early detection of the disease and for monitoring its recurrence. However, most current methods for biomarker detection have technical difficulties (such as sample preparation and specific detector requirements) which limit their application in point of care diagnostics. We developed an extremely simple, power-free microfluidic system for direct detection of cancer biomarkers in microliter volumes of whole blood. CEA and CYFRA21-1 were chosen as model cancer biomarkers. The system automatically extracted blood plasma from less than 3 μl of whole blood and performed a multiplex sample-to-answer assay (nano-ELISA (enzyme-linked immunosorbent assay) technique) without the use of external power or extra components. By taking advantage of the nano-ELISA technique, this microfluidic system detected CEA at a concentration of 50 pg/ml and CYFRA21-1 at a concentration of 60 pg/ml within 60 min. The combination of PnP polydimethylsiloxane (PDMS) pump and nano-ELISA technique in a single microchip system shows great promise for the detection of cancer biomarkers in a drop of blood.

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

Large scale micro-photometry for high resolution pH-characterization during electro-osmotic pumping and modular micro-swimming

NASA Astrophysics Data System (ADS)

Niu, Ran; Khodorov, Stanislav; Weber, Julian; Reinmüller, Alexander; Palberg, Thomas

2017-11-01

Micro-fluidic pumps as well as artificial micro-swimmers are conveniently realized exploiting phoretic solvent flows based on local gradients of temperature, electrolyte concentration or pH. We here present a facile micro-photometric method for monitoring pH gradients and demonstrate its performance and scope on different experimental situations including an electro-osmotic pump and modular micro-swimmers assembled from ion exchange resin beads and polystyrene colloids. In combination with the present microscope and DSLR camera our method offers a 2 μm spatial resolution at video frame rate over a field of view of 3920 × 2602 μm2. Under optimal conditions we achieve a pH-resolution of 0.05 with about equal contributions from statistical and systematical uncertainties. Our quantitative micro-photometric characterization of pH gradients which develop in time and reach out several mm is anticipated to provide valuable input for reliable modeling and simulations of a large variety of complex flow situations involving pH-gradients including artificial micro-swimmers, microfluidic pumping or even electro-convection.

NASA Tech Briefs, February 2006

NASA Technical Reports Server (NTRS)

2006-01-01

Topics discussed include: Nearly Direct Measurement of Relative Permittivity; DCS-Neural-Network Program for Aircraft Control and Testing; Dielectric Heaters for Testing Spacecraft Nuclear Reactors; Using Doppler Shifts of GPS Signals To Measure Angular Speed; Monitoring Temperatures of Tires Using Luminescent Materials; Highly Efficient Multilayer Thermoelectric Devices; Very High-Speed Digital Video Capability for In-Flight Use; MMIC DHBT Common-Base Amplifier for 172 GHz; Modular, Microprocessor-Controlled Flash Lighting System; Generic Environment for Simulating Launch Operations; Modular Aero-Propulsion System Simulation; X-Windows Socket Widget Class; Infrastructure for Rapid Development of Java GUI Programs; Processing Raman Spectra of High-Pressure Hydrogen Flames; X-Windows Information Sharing Protocol Widget Class; Simulating Humans as Integral Parts of Spacecraft Missions; Analyzing Power Supply and Demand on the ISS; Polyimides From a-BPDA and Aromatic Diamines; Making Plant-Support Structures From Waste Plant Fiber; Large Deployable Reflectarray Antenna; Periodically Discharging, Gas-Coalescing Filter; Ion Milling On Steps for Fabrication of Nanowires; Neuro-Prosthetic Implants With Adjustable Electrode Arrays; Microfluidic Devices for Studying Biomolecular Interactions; Studying Functions of All Yeast Genes Simultaneously; Polarization Phase-Compensating Coats for Metallic Mirrors; Tunable-Bandwidth Filter System; Methodology for Designing Fault-Protection Software; and Ground-Based Localization of Mars Rovers.

DynaMiTES - A dynamic cell culture platform for in vitro drug testing PART 1 - Engineering of microfluidic system and technical simulations.

PubMed

Mattern, Kai; Beißner, Nicole; Reichl, Stephan; Dietzel, Andreas

2018-05-01

Conventional safety and efficacy test models, such as animal experiments or static in vitro cell culture models, can often not reliably predict the most promising drug candidates. Therefore, a novel microfluidic cell culture platform, called Dynamic Micro Tissue Engineering System (DynaMiTES), was designed to allow online analysis of drugs permeating through barrier forming tissues under dynamic conditions combined with monitoring of the transepithelial electrical resistance (TEER) by electrodes optimized for homogeneous current distribution. A variety of pre-cultivated cell culture inserts can be integrated and exposed to well controlled dynamic micro flow conditions, resulting in a tightly regulated exposure of the cells to tested drugs, drug formulations and shear forces. With these qualities, the new system can provide more relevant information compared to static measurements. As a first in vitro model, a three-dimensional hemicornea construct consisting of human keratocytes (HCK-Ca) and epithelial cells (HCE-T) was successfully tested in the DynaMiTES. Thereby, we were able to demonstrate the functionality and cell compatibility of this new organ on chip test platform. The modular design of the DynaMiTES allows fast adaptation suitable for the investigation of drug permeation through other important cellular barriers. Copyright © 2017. Published by Elsevier B.V.

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

Electroacoustics: A New Mechanism for Driving Individually Addressable Jetting and Other Microfluidic Manipulations in Multiwell Arrays

NASA Astrophysics Data System (ADS)

Yeo, Leslie; Rezk, Amgad

2017-11-01

The low take-up of microfluidic technology at the laboratory bench despite 25 years of advances can be attributed to the reluctance of practitioners to adopt new and sophisticated technology, which requires substantial retraining, as well as the large investments that have already been made in the vast array of existing laboratory equipment. A way to circumvent this is to design microfluidic technology to retrofit existing laboratory technology such as microscope stages, microplate readers, etc. This is however not without challenge as existing microfluidic devices themselves often require large ancillary equipment to drive fluidic actuation/detection, which are not always amenable to integration into these existing laboratory formats. We have developed a low-cost and scalable modular plug-and-play microplatform that facilitates individual addressability of each well in a microarray plate for sample dispensing, mixing and preconcentration, as well as its ejection via jetting/nebulisation for subsequent analysis. As this cannot be achieved using standard acoustofluidics, we have developed a new electroacoustic mechanism that allows the transmission of high frequency sound waves into each well while uniquely confining the electric field off the piezoelectric chip.

Upgrading well plates using open microfluidic patterning.

PubMed

Berry, Samuel B; Zhang, Tianzi; Day, John H; Su, Xiaojing; Wilson, Ilham Z; Berthier, Erwin; Theberge, Ashleigh B

2017-12-05

Cellular communication between multiple cell types is a ubiquitous process that is responsible for vital physiological responses observed in vivo (e.g., immune response, organ function). Many in vitro coculture strategies have been developed, both in traditional culture and microscale systems, and have shown the potential to recreate some of the physiological behaviors of organs or groups of cells. A fundamental limitation of current systems is the difficulty of reconciling the additional engineering requirements for creating soluble factor signaling systems (e.g., segregated cell culture) with the use of well-characterized materials and platforms that have demonstrated successful results and biocompatibility in assays. We present a new open-microfluidic platform, the Monorail Device, that is placed in any existing well plate or Petri dish and enables patterning of segregated coculture regions, thereby allowing the direct upgrade of monoculture experiments into multiculture assays. Our platform patterns biocompatible hydrogel walls via microfluidic spontaneous capillary flow (SCF) along a rail insert set inside commercially available cultureware, creating customized pipette-accessible cell culture chambers that require fewer cells than standard macroscale culture. Importantly, the device allows the use of native surfaces without additional modification or treatments, while creating permeable dividers for the diffusion of soluble factors. Additionally, the ease of patterning afforded by our platform makes reconfiguration of the culture region as simple as changing the rail insert. We demonstrate the ability of the device to pattern flows on a variety of cell culture surfaces and create hydrogel walls in complex and precise shapes. We characterize the physical parameters that enable a reproducible SCF-driven flow and highlight specialized design features that increase the ease of use of the device and control of the open microfluidic flow. Further, we present the performance of our platform according to useful coculture criteria, including permeability and integrity of our hydrogel walls and surface-sensitive cell culture. Lastly, we show the potential of this type of platform to create modular multikingdom culture systems that can be used to study soluble factor signaling between mammalian cells, bacteria, and fungi, as well as the potential for adaptation of this technology by researchers across multiple fields.

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

PubMed

Silva, Ryan; Bhatia, Swapnil; Densmore, Douglas

2016-07-05

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

Digital Photonic Production of Micro Structures in Glass by In-Volume Selective Laser-Induced Etching using a High Speed Micro Scanner

NASA Astrophysics Data System (ADS)

Gottmann, Jens; Hermans, Martin; Ortmann, Jürgen

Digital photonic production of 3D microfluidic devices and assembled micro mechanics inside fused silica glass is carried out using ISLE directly from digital CAD data. To exploit the potential productivity of new high average power fs-lasers >150 W a modular high speed scanning system has been developed. Acousto-optical beam deflection, galvo-scanners and translation stages are controlled by CAM software. Using a lens with 10 mm focal length a focus radius of 1 μm is scanned with a velocity of 12 m/s on 400 μm track radius enabling the up-scaling of the ISLE- process using fs-laser radiation with up to 30 W.

Droplet microfluidic technology for single-cell high-throughput screening.

PubMed

Brouzes, Eric; Medkova, Martina; Savenelli, Neal; Marran, Dave; Twardowski, Mariusz; Hutchison, J Brian; Rothberg, Jonathan M; Link, Darren R; Perrimon, Norbert; Samuels, Michael L

2009-08-25

We present a droplet-based microfluidic technology that enables high-throughput screening of single mammalian cells. This integrated platform allows for the encapsulation of single cells and reagents in independent aqueous microdroplets (1 pL to 10 nL volumes) dispersed in an immiscible carrier oil and enables the digital manipulation of these reactors at a very high-throughput. Here, we validate a full droplet screening workflow by conducting a droplet-based cytotoxicity screen. To perform this screen, we first developed a droplet viability assay that permits the quantitative scoring of cell viability and growth within intact droplets. Next, we demonstrated the high viability of encapsulated human monocytic U937 cells over a period of 4 days. Finally, we developed an optically-coded droplet library enabling the identification of the droplets composition during the assay read-out. Using the integrated droplet technology, we screened a drug library for its cytotoxic effect against U937 cells. Taken together our droplet microfluidic platform is modular, robust, uses no moving parts, and has a wide range of potential applications including high-throughput single-cell analyses, combinatorial screening, and facilitating small sample analyses.

Miniaturised medium pressure capillary liquid chromatography system with flexible open platform design using off-the-shelf microfluidic components.

PubMed

Li, Yan; Dvořák, Miloš; Nesterenko, Pavel N; Stanley, Roger; Nuchtavorn, Nantana; Krčmová, Lenka Kujovská; Aufartová, Jana; Macka, Mirek

2015-10-08

Trends towards portable analytical instrumentation of the last decades have not been equally reflected in developments of portable liquid chromatography (LC) instrumentation for rapid on-site measurements. A miniaturised medium pressure capillary LC (MPLC) system with gradient elution capability has been designed based on a flexible modular microfluidic system using primarily off-the-shelf low cost components to ensure wide accessibility to other analysts. The microfluidic platform was assembled on a breadboard and contained microsyringe pumps and switch valves, complemented with an injection valve and on-capillary detectors, all controlled by a PC. Four miniaturised microsyringe pumps, with 5, 20 and 100 μL syringe volume options, formed the basis of the pumping system. Two pairs of pumps were used for each mobile phase to create gradient elution capability. The two microsyringe pumps in each pairs were linked by two electrically operated microfluidic switching valves and both pairs of pumps were connected through a zero void volume cross-connector, thus providing a low hold-up volume for gradient formation. Sample was injected by a 20 nL nano-LC sampling valve, directly connected to a 18 cm long 100 μm i.d. Chromolith CapRod RP-18 monolithic capillary column. On-capillary LED-based UV-vis photometric detection was conducted through a piece of equal diameter fused silica capillary connected after the column. The performance of the portable LC system was evaluated theoretically and experimentally, including the maximum operating pressure, gradient mixing performance, and the performance of the detectors. The 5 μL microsyringe pump offered the best performance, with typical maximum operating pressures up to 11.4 ± 0.4 MPa (water) and gradient pumping repeatability of between 4 and 9% for gradients between 0.10% s(-1) and 0.33% s(-1). Test analytes of charged and uncharged dyes and pharmaceuticals of varying hydrophobicity showed typical RSD values of 0.7-1.4% and 3.3-4.8% in isocratic mode and 1.2-4.6% and 3.2-6.4% in gradient mode, respectively for retention time and peak area repeatability. Crown Copyright © 2015. Published by Elsevier B.V. All rights reserved.

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

PubMed

Muluneh, Melaku; Issadore, David

2014-12-07

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

Modular development of a prototype point of care molecular diagnostic platform for sexually transmitted infections.

PubMed

Branavan, Manoharanehru; Mackay, Ruth E; Craw, Pascal; Naveenathayalan, Angel; Ahern, Jeremy C; Sivanesan, Tulasi; Hudson, Chris; Stead, Thomas; Kremer, Jessica; Garg, Neha; Baker, Mark; Sadiq, Syed T; Balachandran, Wamadeva

2016-08-01

This paper presents the design of a modular point of care test platform that integrates a proprietary sample collection device directly with a microfluidic cartridge. Cell lysis, within the cartridge, is conducted using a chemical method and nucleic acid purification is done on an activated cellulose membrane. The microfluidic device incorporates passive mixing of the lysis-binding buffers and sample using a serpentine channel. Results have shown extraction efficiencies for this new membrane of 69% and 57% compared to the commercial Qiagen extraction method of 85% and 59.4% for 0.1ng/µL and 100ng/µL salmon sperm DNA respectively spiked in phosphate buffered solution. Extraction experiments using the serpentine passive mixer cartridges incorporating lysis and nucleic acid purification showed extraction efficiency around 80% of the commercial Qiagen kit. Isothermal amplification was conducted using thermophillic helicase dependant amplification and recombinase polymerase amplification. A low cost benchtop real-time isothermal amplification platform has been developed capable of running six amplifications simultaneously. Results show that the platform is capable of detecting 1.32×10(6) of sample DNA through thermophillic helicase dependant amplification and 1×10(5) copy numbers Chlamydia trachomatis genomic DNA within 10min through recombinase polymerase nucleic acid amplification tests. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Future microfluidic and nanofluidic modular platforms for nucleic acid liquid biopsy in precision medicine

PubMed Central

Egatz-Gomez, Ana; Wang, Ceming; Klacsmann, Flora; Pan, Zehao; Marczak, Steve; Wang, Yunshan; Sun, Gongchen; Senapati, Satyajyoti; Chang, Hsueh-Chia

2016-01-01

Nucleic acid biomarkers have enormous potential in non-invasive diagnostics and disease management. In medical research and in the near future in the clinics, there is a great demand for accurate miRNA, mRNA, and ctDNA identification and profiling. They may lead to screening of early stage cancer that is not detectable by tissue biopsy or imaging. Moreover, because their cost is low and they are non-invasive, they can become a regular screening test during annual checkups or allow a dynamic treatment program that adjusts its drug and dosage frequently. We briefly review a few existing viral and endogenous RNA assays that have been approved by the Federal Drug Administration. These tests are based on the main nucleic acid detection technologies, namely, quantitative reverse transcription polymerase chain reaction (PCR), microarrays, and next-generation sequencing. Several of the challenges that these three technologies still face regarding the quantitative measurement of a panel of nucleic acids are outlined. Finally, we review a cluster of microfluidic technologies from our group with potential for point-of-care nucleic acid quantification without nucleic acid amplification, designed to overcome specific limitations of current technologies. We suggest that integration of these technologies in a modular design can offer a low-cost, robust, and yet sensitive/selective platform for a variety of precision medicine applications. PMID:27190565

A vertically-stacked, polymer, microfluidic point mutation analyzer: Rapid, high accuracy detection of low-abundance K-ras mutations

PubMed Central

Han, Kyudong; Lee, Tae Yoon; Nikitopoulos, Dimitris E.; Soper, Steven A.; Murphy, Michael C.

2011-01-01

Recognition of point mutations in the K-ras gene can be used for the clinical management of several types of cancers. Unfortunately, several assay and hardware concerns must be addressed to allow users not well-trained in performing molecular analyses the opportunity to undertake these measurements. To provide for a larger user-base for these types of molecular assays, a vertically-stacked microfluidic analyzer with a modular architecture and process automation was developed. The analyzer employed a primary PCR coupled to an allele-specific ligase detection reaction (LDR). Each functional device, including continuous flow thermal reactors for the PCR and LDR, passive micromixers and ExoSAP-IT® purification, was designed and tested. Individual devices were fabricated in polycarbonate using hot embossing and assembled using adhesive bonding for system assembly. The system produced LDR products from a DNA sample in ~1 h, an 80% reduction in time compared to conventional bench-top instrumentation. Purifying the post-PCR products with the ExoSAP-IT® enzyme led to optimized LDR performance minimizing false positive signals and producing reliable results. Mutant alleles in genomic DNA were quantified to the level of 0.25 ng of mutant DNA in 50 ng of wild-type DNA for a 25 μL sample, equivalent to DNA from 42 mutant cells. PMID:21771577

Rapid microfluidic thermal cycler for nucleic acid amplification

DOEpatents

Beer, Neil Reginald; Vafai, Kambiz

2015-10-27

A system for thermal cycling a material to be thermal cycled including a microfluidic heat exchanger; a porous medium in the microfluidic heat exchanger; a microfluidic thermal cycling chamber containing the material to be thermal cycled, the microfluidic thermal cycling chamber operatively connected to the microfluidic heat exchanger; a working fluid at first temperature; a first system for transmitting the working fluid at first temperature to the microfluidic heat exchanger; a working fluid at a second temperature, a second system for transmitting the working fluid at second temperature to the microfluidic heat exchanger; a pump for flowing the working fluid at the first temperature from the first system to the microfluidic heat exchanger and through the porous medium; and flowing the working fluid at the second temperature from the second system to the heat exchanger and through the porous medium.

Microfluidics and Raman microscopy: current applications and future challenges.

PubMed

Chrimes, Adam F; Khoshmanesh, Khashayar; Stoddart, Paul R; Mitchell, Arnan; Kalantar-Zadeh, Kourosh

2013-07-07

Raman microscopy systems are becoming increasingly widespread and accessible for characterising chemical species. Microfluidic systems are also progressively finding their way into real world applications. Therefore, it is anticipated that the integration of Raman systems with microfluidics will become increasingly attractive and practical. This review aims to provide an overview of Raman microscopy-microfluidics integrated systems for researchers who are actively interested in utilising these tools. The fundamental principles and application strengths of Raman microscopy are discussed in the context of microfluidics. Various configurations of microfluidics that incorporate Raman microscopy methods are presented, with applications highlighted. Data analysis methods are discussed, with a focus on assisting the interpretation of Raman-microfluidics data from complex samples. Finally, possible future directions of Raman-microfluidic systems are presented.

Microfluidic mixing for non-equilibrium single-molecule optical spectroscopy

NASA Astrophysics Data System (ADS)

Pfeil, Shawn H.

We describe a series of experiments made possible by the combination of single-molecule fluorescence spectroscopy and microfluidic mixing. To perform these measurements, a microfluidic sample handling system was developed and characterized. This system allows observation at times as early as 2.4 ms after a reaction is triggered, which is an more than an order of magnitude earlier than previous microfabricated devices. Dilutions as high as 1:19 (v/v) are achieved, allowing measurements of molecular refolding in native conditions. The interconversion of subpopulations, masked by averaging in ensemble measurements, is observed. This technology also facilitates ultra-sensitive chemiluminescence measurements, using only microliters of sample. Microfluidics are designed and fabricated to extend single-molecule measurements to samples out of equilibrium. The system is optimized for sensitive optical detection and experimental convenience. Channels are replica-molded in poly-dimethyl-siloxane (PDMS) elastomer and sealed to coverglass. The resulting devices are compatible with a broad range of chemicals, and exhibit low background fluorescence. The combination of continuous flow, which decouples reaction progress from measurement duration, with low background enables single molecules to be probed at well defined times after a reaction is triggered. Fluid delivery and pressure connections are made using an interface optimized for rapid assembly, rapid sample exchange, and modular device replacement, while providing access for high numerical aperture optics. The kinetics of Csp, the cold shock protein from Thermotoga maritima, are studied with the mixer. An order of magnitude decrease in deadtime puts a new upper limit of 4.6 ms on the time required for collapse after mixing. This result is in agreement with indirect measurements of chain reconfiguration time, which suggest collapse happens on the timescale of 10--100 ns. Measurements of the kinetics of a DNA sequence that binds cocaine put a lower bound on its folding rate of 100 s-1. Single-Molecule measurements at equilibrium, in conjunction with ensemble measurements, demonstrate that this system can be described thermodynamically with a two-state model. In addition, standard free energy changes for folding, in the presence and absence of 1 mM cocaine, are obtained. Ensemble chemiluminescence experiments demonstrate the broad applicability of themixing system. The luciferase-luciferin system from Photinus pyralis, the North American firefly, is studied. Kinetically resolved chemiluminescence measurements are performed using only 50 femtomoles of target, and microliters of sample. This compares favorably to stopped-flow, which requires milliliters of sample and picomoles of target.

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

PubMed Central

Muluneh, Melaku

2015-01-01

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

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.

Transforming nanomedicine manufacturing toward Quality by Design and microfluidics.

PubMed

Colombo, Stefano; Beck-Broichsitter, Moritz; Bøtker, Johan Peter; Malmsten, Martin; Rantanen, Jukka; Bohr, Adam

2018-04-05

Nanopharmaceuticals aim at translating the unique features of nano-scale materials into therapeutic products and consequently their development relies critically on the progression in manufacturing technology to allow scalable processes complying with process economy and quality assurance. The relatively high failure rate in translational nanopharmaceutical research and development, with respect to new products on the market, is at least partly due to immature bottom-up manufacturing development and resulting sub-optimal control of quality attributes in nanopharmaceuticals. Recently, quality-oriented manufacturing of pharmaceuticals has undergone an unprecedented change toward process and product development interaction. In this context, Quality by Design (QbD) aims to integrate product and process development resulting in an increased number of product applications to regulatory agencies and stronger proprietary defense strategies of process-based products. Although QbD can be applied to essentially any production approach, microfluidic production offers particular opportunities for QbD-based manufacturing of nanopharmaceuticals. Microfluidics provides unique design flexibility, process control and parameter predictability, and also offers ample opportunities for modular production setups, allowing process feedback for continuously operating production and process control. The present review aims at outlining emerging opportunities in the synergistic implementation of QbD strategies and microfluidic production in contemporary development and manufacturing of nanopharmaceuticals. In doing so, aspects of design and development, but also technology management, are reviewed, as is the strategic role of these tools for aligning nanopharmaceutical innovation, development, and advanced industrialization in the broader pharmaceutical field. Copyright © 2018 Elsevier B.V. All rights reserved.

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

NASA Astrophysics Data System (ADS)

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

2014-06-01

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

Self-contained microfluidic systems: a review.

PubMed

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

2016-08-16

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

Integrated Multi-process Microfluidic Systems for Automating Analysis

PubMed Central

Yang, Weichun; Woolley, Adam T.

2010-01-01

Microfluidic technologies have been applied extensively in rapid sample analysis. Some current challenges for standard microfluidic systems are relatively high detection limits, and reduced resolving power and peak capacity compared to conventional approaches. The integration of multiple functions and components onto a single platform can overcome these separation and detection limitations of microfluidics. Multiplexed systems can greatly increase peak capacity in multidimensional separations and can increase sample throughput by analyzing many samples simultaneously. On-chip sample preparation, including labeling, preconcentration, cleanup and amplification, can all serve to speed up and automate processes in integrated microfluidic systems. This paper summarizes advances in integrated multi-process microfluidic systems for automated analysis, their benefits and areas for needed improvement. PMID:20514343

A simple microfluidic platform for rapid and efficient production of the radiotracer [18F]fallypride.

PubMed

Zhang, Xin; Liu, Fei; Knapp, Karla-Anne; Nickels, Michael L; Manning, H Charles; Bellan, Leon M

2018-05-01

Herein, we report the development of a simple, high-throughput and efficient microfluidic system for synthesizing radioactive [18F]fallypride, a PET imaging radiotracer widely used in medical research. The microfluidic chip contains all essential modules required for the synthesis and purification of radioactive fallypride. The radiochemical yield of the tracer is sufficient for multiple animal injections for preclinical imaging studies. To produce the on-chip concentration and purification columns, we employ a simple "trapping" mechanism by inserting rows of square pillars with predefined gaps near the outlet of microchannel. Microspheres with appropriate functionality are suspended in solution and loaded into the microchannels to form columns for radioactivity concentration and product purification. Instead of relying on complicated flow control elements (e.g., micromechanical valves requiring complex external pneumatic actuation), external valves are utilized to control transfer of the reagents between different modules. The on-chip ion exchange column can efficiently capture [18F]fluoride with negligible loss (∼98% trapping efficiency), and subsequently release a burst of concentrated [18F]fluoride to the reaction cavity. A thin layer of PDMS with a small hole in the center facilitates rapid and reliable water evaporation (with the aid of azeotropic distillation and nitrogen flow) while reducing fluoride loss. During the solvent exchange and fluorination reaction, the entire chip is uniformly heated to the desired temperature using a hot plate. All aspects of the [18F]fallypride synthesis were monitored by high-performance liquid chromatography (HPLC) analysis, resulting in labelling efficiency in fluorination reaction ranging from 67-87% (n = 5). Moreover, after isolating unreacted [18F]fluoride, remaining fallypride precursor, and various by-products via an on-chip purification column, the eluted [18F]fallypride is radiochemically pure and of a sufficient quantity to allow for PET imaging (∼5 mCi). Finally, a positron emission tomography (PET) image of a rat brain injected with ∼300 μCi [18F]fallypride produced by our microfluidic chip is provided, demonstrating the utility of the product produced by the microfluidic reactor. With a short synthesis time (∼60 min) and a highly integrated on-chip modular configuration that allows for concentration, reaction, and product purification, our microfluidic chip offers numerous exciting advantages with the potential for applications in radiochemical research and clinical production. Moreover, due to its simplicity and potential for automation, we anticipate it may be easily integrated into a clinical environment.

AC electrothermal mixing for high conductive biofluids by arc-electrodes

NASA Astrophysics Data System (ADS)

Meng, Jiyu; Li, Shanshan; Li, Junwei; Yu, Chengzhuang; Wei, Chunyang; Dai, Shijie

2018-06-01

As a platform to mix the bioagents (i.e. serum, urine), we take advantage of the alternating current electrothermal (ACET) effect which is quite suitable for rapid pumping/mixing of high conductive biomicrofluids. Here we demonstrate the concept of a high-efficient mixing microfluidic chip as a basic unit to provide rapid mixing for lab-on-a-chip applications. As an active mixer, two streams are introduced into a ring-shape microchamber by a passive flow rate regulator, and then the microfluids in the chamber are actuated by a nonuniform electric field with a phase shift of 180°. It shows perfect mixing performance by arranging four arc-electrodes around the ring-shape microchamber subsequently. Taking the Joule heating and conductivity/permittivity changes into consideration, a temperature dependent fully coupled numerical model is presented. Then, the effects of applied voltages on mixing performance and temperature rise are provided to get an optimized design for ACET mixer. Moreover, the arrangement of the electrode array is analyzed to show the effects of electrode patterns on the swirls and mixing efficiencies. Since all the electrodes here are located along a ring-shape central microchamber, the ring-shape micromixer is quite suitable to function as a compact element modular for integrated microfluidic chips.

Microfluidic-Based Robotic Sampling System for Radioactive Solutions

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

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

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

Micropumps, microvalves, and micromixers within PCR microfluidic chips: Advances and trends.

PubMed

Zhang, Chunsun; Xing, Da; Li, Yuyuan

2007-01-01

This review surveys the advances of microvalves, micropumps, and micromixers within PCR microfluidic chips over the past ten years. First, the types of microvalves in PCR chips are discussed, including active and passive microvalves. The active microvalves are subdivided into mechanical (thermopneumatic and shape memory alloy), non-mechanical (hydrogel, sol-gel, paraffin, and ice), and external (modular built-in, pneumatic, and non-pneumatic) microvalves. The passive microvalves also include mechanical (in-line polymerized gel and passive plug) and non-mechanical (hydrophobic) microvalves. The review then discusses mechanical (piezoelectric, pneumatic, and thermopneumatic) and non-mechanical (electrokinetic, magnetohydrodynamic, electrochemical, acoustic-wave, surface tension and capillary, and ferrofluidic magnetic) micropumps in PCR chips. Next, different micromixers within PCR chips are presented, including passive (Y/T-type flow, recirculation flow, and drop) and active (electrokinetically-driven, acoustically-driven, magnetohydrodynamical-driven, microvalves/pumps) micromixers. Finally, general discussions on microvalves, micropumps, and micromixers for PCR chips are given. The microvalve/micropump/micromixers allow high levels of PCR chip integration and analytical throughput.

Improving Satellite Compatible Microdevices to Study Biology in Space

NASA Technical Reports Server (NTRS)

Kalkus, Trevor; Snyder, Jessica; Paulino-Lima, Ivan; Rothschild, Lynn

2017-01-01

The technology for biology in space lags far behind the gold standard for biological experiments on Earth. To remedy this disparity, the Rothschild lab works on proof of concept, prototyping, and developing of new sensors and devices to further the capabilities of biology research on satellites. One such device is the PowerCell Payload System. One goal for synthetic biology in aiding space travel and colonization is to genetically engineer living cells to produce biochemicals in space. However, such farming in space presupposes bacteria retain their functionality post-launch, bombarded by radiation, and without the 1G of Earth. Our questions is, does a co-culture of cyanobacteria and protein-synthesizing bacteria produce Earth-like yields of target proteins? Is the yield sensitive to variable gravitational forces? To answer these questions, a PowerCell Payload System will spend 1 year aboard the German Aerospace Center's Euglena and Combined Regenerative Organic-food Production In Space (Eu:CROPIS) mission satellite. The PowerCell system is a pair of two 48-well microfluidic cards, each well seeded with bacteria. The system integrates fluidic, thermal, optical, electronic, and control systems to germinate bacteria spores, then measure the protein synthesized for comparison to parallel experiments conducted on the Earth. In developing the PowerCell Payload, we gained insight into the shortcomings of biology experiments on satellites. To address these issues, we have started three new prototyping projects: 1) The development of an extremely stable and radiation resistant cell-free system, allowing for the construction of proteins utilizing only cell components instead of living cells. This can be lyophilized on a substrate, like paper. (2) Using paper as a microfluidic platform that is flexible, stable, cheap, and wicking. The capillary action eliminates the need for pumps, reducing volume, mass, and potential failing points. Electrodes can be printed on the paper to sense for biochemicals. (3) Developing a modular, semi-autonomous microfluidic device that can be easily adapted for a variety of common biological experiments. This versatility will allow for quicker and cheaper experimentation. These improvements to satellite experiment platforms have the potential to radically increase the return from NASA's biological and field studies with reduced development time, mass, and cost with increased robustness data and interpretation.

Efficient Computational Prototyping of Mixed Technology Microfluidic Components and Systems

DTIC Science & Technology

2002-08-01

AFRL-IF-RS-TR-2002-190 Final Technical Report August 2002 EFFICIENT COMPUTATIONAL PROTOTYPING OF MIXED TECHNOLOGY MICROFLUIDIC...SUBTITLE EFFICIENT COMPUTATIONAL PROTOTYPING OF MIXED TECHNOLOGY MICROFLUIDIC COMPONENTS AND SYSTEMS 6. AUTHOR(S) Narayan R. Aluru, Jacob White...Aided Design (CAD) tools for microfluidic components and systems were developed in this effort. Innovative numerical methods and algorithms for mixed

A Venturi microregulator array module for distributed pressure control

PubMed Central

Chang, Dustin S.; Langelier, Sean M.; Zeitoun, Ramsey I.

2010-01-01

Pressure-driven flow control systems are a critical component in many microfluidic devices. Compartmentalization of this functionality into a stand-alone module possessing a simple interface would allow reduction of the number of pneumatic interconnects required for fluidic control. Ideally, such a module would also be sufficiently compact for implementation in portable platforms. In our current work, we show the feasibility of using a modular array of Venturi pressure microregulators for coordinated droplet manipulation. The arrayed microregulators share a single pressure input and are capable of outputting electronically controlled pressures that can be independently set between ±1.3 kPa. Because the Venturi microregulator operates by thermal perturbation of a choked gas flow, this output range corresponds to a temperature variation between 20 and 95°C. Using the array, we demonstrate loading, splitting, merging, and independent movement of multiple droplets in a valveless microchannel network. PMID:20938490

Recent advances of controlled drug delivery using microfluidic platforms.

PubMed

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

2018-03-15

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

Multisensor-integrated organs-on-chips platform for automated and continual in situ monitoring of organoid behaviors

PubMed Central

Zhang, Yu Shrike; Aleman, Julio; Shin, Su Ryon; Kim, Duckjin; Mousavi Shaegh, Seyed Ali; Massa, Solange; Riahi, Reza; Chae, Sukyoung; Hu, Ning; Avci, Huseyin; Zhang, Weijia; Silvestri, Antonia; Sanati Nezhad, Amir; Manbohi, Ahmad; De Ferrari, Fabio; Polini, Alessandro; Calzone, Giovanni; Shaikh, Noor; Alerasool, Parissa; Budina, Erica; Kang, Jian; Bhise, Nupura; Pourmand, Adel; Skardal, Aleksander; Shupe, Thomas; Bishop, Colin E.; Dokmeci, Mehmet Remzi; Atala, Anthony; Khademhosseini, Ali

2017-01-01

Organ-on-a-chip systems are miniaturized microfluidic 3D human tissue and organ models designed to recapitulate the important biological and physiological parameters of their in vivo counterparts. They have recently emerged as a viable platform for personalized medicine and drug screening. These in vitro models, featuring biomimetic compositions, architectures, and functions, are expected to replace the conventional planar, static cell cultures and bridge the gap between the currently used preclinical animal models and the human body. Multiple organoid models may be further connected together through the microfluidics in a similar manner in which they are arranged in vivo, providing the capability to analyze multiorgan interactions. Although a wide variety of human organ-on-a-chip models have been created, there are limited efforts on the integration of multisensor systems. However, in situ continual measuring is critical in precise assessment of the microenvironment parameters and the dynamic responses of the organs to pharmaceutical compounds over extended periods of time. In addition, automated and noninvasive capability is strongly desired for long-term monitoring. Here, we report a fully integrated modular physical, biochemical, and optical sensing platform through a fluidics-routing breadboard, which operates organ-on-a-chip units in a continual, dynamic, and automated manner. We believe that this platform technology has paved a potential avenue to promote the performance of current organ-on-a-chip models in drug screening by integrating a multitude of real-time sensors to achieve automated in situ monitoring of biophysical and biochemical parameters. PMID:28265064

Microfluidic fuel cell systems

NASA Astrophysics Data System (ADS)

Ho, Bernard; Kjeang, Erik

2011-06-01

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

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.

Lab-on-Chip Cytometry Based on Magnetoresistive Sensors for Bacteria Detection in Milk

PubMed Central

Fernandes, Ana C.; Duarte, Carla M.; Cardoso, Filipe A.; Bexiga, Ricardo.; Cardoso, Susana.; Freitas, Paulo P.

2014-01-01

Flow cytometers have been optimized for use in portable platforms, where cell separation, identification and counting can be achieved in a compact and modular format. This feature can be combined with magnetic detection, where magnetoresistive sensors can be integrated within microfluidic channels to detect magnetically labelled cells. This work describes a platform for in-flow detection of magnetically labelled cells with a magneto-resistive based cell cytometer. In particular, we present an example for the validation of the platform as a magnetic counter that identifies and quantifies Streptococcus agalactiae in milk. PMID:25196163

Lab-on-chip cytometry based on magnetoresistive sensors for bacteria detection in milk.

PubMed

Fernandes, Ana C; Duarte, Carla M; Cardoso, Filipe A; Bexiga, Ricardo; Cardoso, Susana; Freitas, Paulo P

2014-08-21

Flow cytometers have been optimized for use in portable platforms, where cell separation, identification and counting can be achieved in a compact and modular format. This feature can be combined with magnetic detection, where magnetoresistive sensors can be integrated within microfluidic channels to detect magnetically labelled cells. This work describes a platform for in-flow detection of magnetically labelled cells with a magneto-resistive based cell cytometer. In particular, we present an example for the validation of the platform as a magnetic counter that identifies and quantifies Streptococcus agalactiae in milk.

CTC-Endothelial Cell Interactions during Metastasis

DTIC Science & Technology

2014-06-01

antibody. For these experiments, we first tested the Bioflux Microfluidics system. In our hands, the Bioflux microfluidic system was suboptimal for...indicated in the results, a subset of rolling assay experiments were also performed using Bioflux Microfluidics technologies (Fluxion Biosciences...behavior of MDA cells in the presence of neutralizing anti-E-selectin antibody. We performed these experiments using Bioflux Microfluidics technology

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

PubMed

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

2010-06-01

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

Suspended microfluidics.

PubMed

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

2013-06-18

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

Suspended microfluidics

PubMed Central

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

2013-01-01

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

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.

Microfluidic Devices for Drug Delivery Systems and Drug Screening

PubMed Central

Kompella, Uday B.; Damiati, Safa A.

2018-01-01

Microfluidic devices present unique advantages for the development of efficient drug carrier particles, cell-free protein synthesis systems, and rapid techniques for direct drug screening. Compared to bulk methods, by efficiently controlling the geometries of the fabricated chip and the flow rates of multiphase fluids, microfluidic technology enables the generation of highly stable, uniform, monodispersed particles with higher encapsulation efficiency. Since the existing preclinical models are inefficient drug screens for predicting clinical outcomes, microfluidic platforms might offer a more rapid and cost-effective alternative. Compared to 2D cell culture systems and in vivo animal models, microfluidic 3D platforms mimic the in vivo cell systems in a simple, inexpensive manner, which allows high throughput and multiplexed drug screening at the cell, organ, and whole-body levels. In this review, the generation of appropriate drug or gene carriers including different particle types using different configurations of microfluidic devices is highlighted. Additionally, this paper discusses the emergence of fabricated microfluidic cell-free protein synthesis systems for potential use at point of care as well as cell-, organ-, and human-on-a-chip models as smart, sensitive, and reproducible platforms, allowing the investigation of the effects of drugs under conditions imitating the biological system. PMID:29462948

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.

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.

Microfluidic process monitor for industrial solvent extraction system

DOEpatents

Gelis, Artem; Pereira, Candido; Nichols, Kevin Paul Flood

2016-01-12

The present invention provides a system for solvent extraction utilizing a first electrode with a raised area formed on its surface, which defines a portion of a microfluidic channel; a second electrode with a flat surface, defining another portion of the microfluidic channel that opposes the raised area of the first electrode; a reversibly deformable substrate disposed between the first electrode and second electrode, adapted to accommodate the raised area of the first electrode and having a portion that extends beyond the raised area of the first electrode, that portion defining the remaining portions of the microfluidic channel; and an electrolyte of at least two immiscible liquids that flows through the microfluidic channel. Also provided is a system for performing multiple solvent extractions utilizing several microfluidic chips or unit operations connected in series.

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

NASA Technical Reports Server (NTRS)

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

2011-01-01

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

System Integration - A Major Step toward Lab on a Chip

PubMed Central

2011-01-01

Microfluidics holds great promise to revolutionize various areas of biological engineering, such as single cell analysis, environmental monitoring, regenerative medicine, and point-of-care diagnostics. Despite the fact that intensive efforts have been devoted into the field in the past decades, microfluidics has not yet been adopted widely. It is increasingly realized that an effective system integration strategy that is low cost and broadly applicable to various biological engineering situations is required to fully realize the potential of microfluidics. In this article, we review several promising system integration approaches for microfluidics and discuss their advantages, limitations, and applications. Future advancements of these microfluidic strategies will lead toward translational lab-on-a-chip systems for a wide spectrum of biological engineering applications. PMID:21612614

Theory for the Emergence of Modularity in Complex Systems

NASA Astrophysics Data System (ADS)

Deem, Michael; Park, Jeong-Man

2013-03-01

Biological systems are modular, and this modularity evolves over time and in different environments. A number of observations have been made of increased modularity in biological systems under increased environmental pressure. We here develop a theory for the dynamics of modularity in these systems. We find a principle of least action for the evolved modularity at long times. In addition, we find a fluctuation dissipation relation for the rate of change of modularity at short times. We discuss a number of biological and social systems that can be understood with this framework. The modularity of the protein-protein interaction network increases when yeast are exposed to heat shock, and the modularity of the protein-protein networks in both yeast and E. coli appears to have increased over evolutionary time. Food webs in low-energy, stressful environments are more modular than those in plentiful environments, arid ecologies are more modular during droughts, and foraging of sea otters is more modular when food is limiting. The modularity of social networks changes over time: stock brokers instant messaging networks are more modular under stressful market conditions, criminal networks are more modular under increased police pressure, and world trade network modularity has decreased

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.

Micro-optics for microfluidic analytical applications.

PubMed

Yang, Hui; Gijs, Martin A M

2018-02-19

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

Microfluidic cell culture systems for drug research.

PubMed

Wu, Min-Hsien; Huang, Song-Bin; Lee, Gwo-Bin

2010-04-21

In pharmaceutical research, an adequate cell-based assay scheme to efficiently screen and to validate potential drug candidates in the initial stage of drug discovery is crucial. In order to better predict the clinical response to drug compounds, a cell culture model that is faithful to in vivo behavior is required. With the recent advances in microfluidic technology, the utilization of a microfluidic-based cell culture has several advantages, making it a promising alternative to the conventional cell culture methods. This review starts with a comprehensive discussion on the general process for drug discovery and development, the role of cell culture in drug research, and the characteristics of the cell culture formats commonly used in current microfluidic-based, cell-culture practices. Due to the significant differences in several physical phenomena between microscale and macroscale devices, microfluidic technology provides unique functionality, which is not previously possible by using traditional techniques. In a subsequent section, the niches for using microfluidic-based cell culture systems for drug research are discussed. Moreover, some critical issues such as cell immobilization, medium pumping or gradient generation in microfluidic-based, cell-culture systems are also reviewed. Finally, some practical applications of microfluidic-based, cell-culture systems in drug research particularly those pertaining to drug toxicity testing and those with a high-throughput capability are highlighted.

Ceramic microsystem incorporating a microreactor with immobilized biocatalyst for enzymatic spectrophotometric assays.

PubMed

Baeza, Mireia; López, Carmen; Alonso, Julián; López-Santín, Josep; Alvaro, Gregorio

2010-02-01

Low-temperature cofired ceramics (LTCC) technology is a versatile fabrication technique used to construct microflow systems. It permits the integration of several unitary operations (pretreatment, separation, (bio)chemical reaction, and detection stage) of an analytical process in a modular or monolithic way. Moreover, because of its compatibility with biological material, LTCC is adequate for analytical applications based on enzymatic reactions. Here we present the design, construction, and evaluation of a LTCC microfluidic system that integrates a microreactor (internal volume, 24.28 microL) with an immobilized beta-galactosidase from Escherichia coli (0.479 activity units) and an optical flow cell to measure the product of the enzymatic reaction. The enzyme was immobilized on a glyoxal-agarose support, maintaining its activity along the time of the study. As a proof of concept, the LTCC-beta-galactosidase system was tested by measuring the conversion of ortho-nitrophenyl beta-D-galactopyranoside, the substrate usually employed for activity determinations. Once packed in a monolithically integrated microcolumn, the miniaturized flow system was characterized, the operational conditions optimized (flow rate and injection volume), and its performance successfully evaluated by determining the beta-galactosidase substrate concentration at the millimolar level.

Microfluidic platform for optimization of crystallization conditions

NASA Astrophysics Data System (ADS)

Zhang, Shuheng; Gerard, Charline J. J.; Ikni, Aziza; Ferry, Gilles; Vuillard, Laurent M.; Boutin, Jean A.; Ferte, Nathalie; Grossier, Romain; Candoni, Nadine; Veesler, Stéphane

2017-08-01

We describe a universal, high-throughput droplet-based microfluidic platform for crystallization. It is suitable for a multitude of applications, due to its flexibility, ease of use, compatibility with all solvents and low cost. The platform offers four modular functions: droplet formation, on-line characterization, incubation and observation. We use it to generate droplet arrays with a concentration gradient in continuous long tubing, without using surfactant. We control droplet properties (size, frequency and spacing) in long tubing by using hydrodynamic empirical relations. We measure droplet chemical composition using both an off-line and a real-time on-line method. Applying this platform to a complicated chemical environment, membrane proteins, we successfully handle crystallization, suggesting that the platform is likely to perform well in other circumstances. We validate the platform for fine-gradient screening and optimization of crystallization conditions. Additional on-line detection methods may well be integrated into this platform in the future, for instance, an on-line diffraction technique. We believe this method could find applications in fields such as fluid interaction engineering, live cell study and enzyme kinetics.

Passive microfluidic array card and reader

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

Dugan, Lawrence Christopher; Coleman, Matthew A

A microfluidic array card and reader system for analyzing a sample. The microfluidic array card includes a sample loading section for loading the sample onto the microfluidic array card, a multiplicity of array windows, and a transport section or sections for transporting the sample from the sample loading section to the array windows. The microfluidic array card reader includes a housing, a receiving section for receiving the microfluidic array card, a viewing section, and a light source that directs light to the array window of the microfluidic array card and to the viewing section.

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

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

Microfluidic strategies for understanding the mechanics of cells and cell-mimetic systems

PubMed Central

Dahl, Joanna B.; Lin, Jung-Ming G.; Muller, Susan J.; Kumar, Sanjay

2016-01-01

Microfluidic systems are attracting increasing interest for the high-throughput measurement of cellular biophysical properties and for the creation of engineered cellular microenvironments. Here we review recent applications of microfluidic technologies to the mechanics of living cells and synthetic cell-mimetic systems. We begin by discussing the use of microfluidic devices to dissect the mechanics of cellular mimics such as capsules and vesicles. We then explore applications to circulating cells, including erythrocytes and other normal blood cells, and rare populations with potential disease diagnostic value, such as circulating tumor cells. We conclude by discussing how microfluidic devices have been used to investigate the mechanics, chemotaxis, and invasive migration of adherent cells. In these ways, microfluidic technologies represent an increasingly important toolbox for investigating cellular mechanics and motility at high throughput and in a format that lends itself to clinical translation. PMID:26134738

Gel integration for microfluidic applications.

PubMed

Zhang, Xuanqi; Li, Lingjun; Luo, Chunxiong

2016-05-21

Molecular diffusive membranes or materials are important for biological applications in microfluidic systems. Hydrogels are typical materials that offer several advantages, such as free diffusion for small molecules, biocompatibility with most cells, temperature sensitivity, relatively low cost, and ease of production. With the development of microfluidic applications, hydrogels can be integrated into microfluidic systems by soft lithography, flow-solid processes or UV cure methods. Due to their special properties, hydrogels are widely used as fluid control modules, biochemical reaction modules or biological application modules in different applications. Although hydrogels have been used in microfluidic systems for more than ten years, many hydrogels' properties and integrated techniques have not been carefully elaborated. Here, we systematically review the physical properties of hydrogels, general methods for gel-microfluidics integration and applications of this field. Advanced topics and the outlook of hydrogel fabrication and applications are also discussed. We hope this review can help researchers choose suitable methods for their applications using hydrogels.

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.

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.

Controllable Ag nanostructure patterning in a microfluidic channel for real-time SERS systems.

PubMed

Leem, Juyoung; Kang, Hyun Wook; Ko, Seung Hwan; Sung, Hyung Jin

2014-03-07

We present a microfluidic patterning system for fabricating nanostructured Ag thin films via a polyol method. The fabricated Ag thin films can be used immediately in a real-time SERS sensing system. The Ag thin films are formed on the inner surfaces of a microfluidic channel so that a Ag-patterned Si wafer and a Ag-patterned PDMS channel are produced by the fabrication. The optimum sensing region and fabrication duration for effective SERS detection were determined. As SERS active substrates, the patterned Ag thin films exhibit an enhancement factor (EF) of 4.25 × 10(10). The Ag-patterned polymer channel was attached to a glass substrate and used as a microfluidic sensing system for the real-time monitoring of biomolecule concentrations. This microfluidic patterning system provides a low-cost process for the fabrication of materials that are useful in medical and pharmaceutical detection and can be employed in mass production.

A multi-functional bubble-based microfluidic system

PubMed Central

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

2015-01-01

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

Rapid prototyping of microfluidic systems using a PDMS/polymer tape composite.

PubMed

Kim, Jungkyu; Surapaneni, Rajesh; Gale, Bruce K

2009-05-07

Rapid prototyping of microfluidic systems using a combination of double-sided tape and PDMS (polydimethylsiloxane) is introduced. PDMS is typically difficult to bond using adhesive tapes due to its hydrophobic nature and low surface energy. For this reason, PDMS is not compatible with the xurography method, which uses a knife plotter and various adhesive coated polymer tapes. To solve these problems, a PDMS/tape composite was developed and demonstrated in microfluidic applications. The PDMS/tape composite was created by spinning it to make a thin layer of PDMS over double-sided tape. Then the PDMS/tape composite was patterned to create channels using xurography, and bonded to a PDMS slab. After removing the backing paper from the tape, a complete microfluidic system could be created by placing the construct onto nearly any substrate; including glass, plastic or metal-coated glass/silicon substrates. The bond strength was shown to be sufficient for the pressures that occur in typical microfluidic channels used for chemical or biological analysis. This method was demonstrated in three applications: standard microfluidic channels and reactors, a microfluidic system with an integrated membrane, and an electrochemical biosensor. The PDMS/tape composite rapid prototyping technique provides a fast and cost effective fabrication method and can provide easy integration of microfluidic channels with sensors and other components without the need for a cleanroom facility.

Evaluation of cell lysis procedures and use of a micro fluidic system for an automated DNA-based cell identification in interplanetary missions

NASA Astrophysics Data System (ADS)

Hall, J. A.; Felnagle, E.; Fries, M.; Spearing, S.; Monaco, L.; Steele, A.

2006-12-01

A Modular Assay System for Solar System Exploration (MASSE) is being developed to include sample handling, pre-treatment, separation and analysis of biological target compounds by both DNA and protein microarrays. To better design sensitive and accurate initial upstream sample handling of the MASSE instrument, experiments investigating the sensitivity and potential extraction bias of commercially available DNA extraction kits between classes of environmentally relevant prokaryotes such as gram-negative bacteria ( Escherichia coli), gram-positive bacteria ( Bacillus megatarium), and Archaea ( Haloarcula marismortui) were performed. For extractions of both planktonic cultures and spiked Mars simulated regolith, FTA ® paper demonstrated the highest sensitivity, with detection as low as ˜1×10 1 cells and ˜3.3×10 2 cells, respectively. In addition to the highest sensitivity, custom modified application of FTA ® paper extraction protocol is the simplest in terms of incorporation into MASSE and displayed little bias in sensitivity with respect to prokaryotic cell type. The implementation of FTA paper for environmental microbiology investigations appears to be a viable and effective option potentially negating the need for other pre-concentration steps such as filtration and negating concerns regarding extraction efficiency of cells. In addition to investigations on useful technology for upstream sample handling in MASSE, we have also evaluated the potential for μTAS to be employed in the MASSE instrument by employing proprietary lab-on-a-chip development technology to investigate the potential for microfluidic cell lysis of different prokaryotic cells employing both chemical and biological lysis agents. Real-time bright-field microscopy and quantitative PMT detection indicated that that gram positive, gram negative and archaeal cells were effectively lyzed in a few seconds using the microfluidic chip protocol developed. This included employing a lysis buffer with components including lysozyme, Protease, Proteinase K, Tween-20 and TritonX-100. The effectiveness of antibiotics and other chemical lysis agents were also screened and demonstrated partial effectiveness on all three cell types. This work demonstrates a step wise approach to evaluating the efficacy and sensitivity of commercial macro-scale technology and state-of-the-art developmental microfluidic technology under consideration for incorporation into the remotely operated MASSE instrument currently under development at the Carnegie Institution of Washington.

Microfluidic systems and methods of transport and lysis of cells and analysis of cell lysate

DOEpatents

Culbertson, Christopher T.; Jacobson, Stephen C.; McClain, Maxine A.; Ramsey, J. Michael

2004-08-31

Microfluidic systems and methods are disclosed which are adapted to transport and lyse cellular components of a test sample for analysis. The disclosed microfluidic systems and methods, which employ an electric field to rupture the cell membrane, cause unusually rapid lysis, thereby minimizing continued cellular activity and resulting in greater accuracy of analysis of cell processes.

Microfluidic systems and methods for transport and lysis of cells and analysis of cell lysate

DOEpatents

Culbertson, Christopher T [Oak Ridge, TN; Jacobson, Stephen C [Knoxville, TN; McClain, Maxine A [Knoxville, TN; Ramsey, J Michael [Knoxville, TN

2008-09-02

Microfluidic systems and methods are disclosed which are adapted to transport and lyse cellular components of a test sample for analysis. The disclosed microfluidic systems and methods, which employ an electric field to rupture the cell membrane, cause unusually rapid lysis, thereby minimizing continued cellular activity and resulting in greater accuracy of analysis of cell processes.

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.

Development of Droplet Microfluidics Enabling High-Throughput Single-Cell Analysis.

PubMed

Wen, Na; Zhao, Zhan; Fan, Beiyuan; Chen, Deyong; Men, Dong; Wang, Junbo; Chen, Jian

2016-07-05

This article reviews recent developments in droplet microfluidics enabling high-throughput single-cell analysis. Five key aspects in this field are included in this review: (1) prototype demonstration of single-cell encapsulation in microfluidic droplets; (2) technical improvements of single-cell encapsulation in microfluidic droplets; (3) microfluidic droplets enabling single-cell proteomic analysis; (4) microfluidic droplets enabling single-cell genomic analysis; and (5) integrated microfluidic droplet systems enabling single-cell screening. We examine the advantages and limitations of each technique and discuss future research opportunities by focusing on key performances of throughput, multifunctionality, and absolute quantification.

Modular Power Standard for Space Explorations Missions

NASA Technical Reports Server (NTRS)

Oeftering, Richard C.; Gardner, Brent G.

2016-01-01

Future human space exploration will most likely be composed of assemblies of multiple modular spacecraft elements with interconnected electrical power systems. An electrical system composed of a standardized set modular building blocks provides significant development, integration, and operational cost advantages. The modular approach can also provide the flexibility to configure power systems to meet the mission needs. A primary goal of the Advanced Exploration Systems (AES) Modular Power System (AMPS) project is to establish a Modular Power Standard that is needed to realize these benefits. This paper is intended to give the space exploration community a "first look" at the evolving Modular Power Standard and invite their comments and technical contributions.

Terahertz microfluidic chips for detection of amino acids in aqueous solutions

NASA Astrophysics Data System (ADS)

Su, Bo; Zhang, Cong; Fan, Ning; Zhang, Cunlin

2016-11-01

Microfluidic technology can control the fluidic thickness accurately in less than 100 micrometers. So the combination of terahertz (THz) and microfluidic technology becomes one of the most interesting directions towards biological detection. We designed microfluidic chips for terahertz spectroscopy of biological samples in aqueous solutions. Using the terahertz time-domain spectroscopy (THz-TDS) system, we experimentally measured the transmittance of the chips and the THz absorption spectra of L-threonine and L-arginine, respectively. The results indicated the feasibility of performing high sensitivity THz spectroscopy of amino acids solutions. Therefore, the microfluidic chips can realize real-time and label-free measurement for biochemistry samples in THz-TDS system.

Finite Element Model of Oxygen Transport for the Design of Geometrically Complex Microfluidic Devices Used in Biological Studies

PubMed Central

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

2016-01-01

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

Finite Element Model of Oxygen Transport for the Design of Geometrically Complex Microfluidic Devices Used in Biological Studies.

PubMed

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

2016-01-01

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

Microfluidics on liquid handling stations (μF-on-LHS): a new industry-compatible microfluidic platform

NASA Astrophysics Data System (ADS)

Kittelmann, Jörg; Radtke, Carsten P.; Waldbaur, Ansgar; Neumann, Christiane; Hubbuch, Jürgen; Rapp, Bastian E.

2014-03-01

Since the early days microfluidics as a scientific discipline has been an interdisciplinary research field with a wide scope of potential applications. Besides tailored assays for point-of-care (PoC) diagnostics, microfluidics has been an important tool for large-scale screening of reagents and building blocks in organic chemistry, pharmaceutics and medical engineering. Furthermore, numerous potential marketable products have been described over the years. However, especially in industrial applications, microfluidics is often considered only an alternative technology for fluid handling, a field which is industrially mostly dominated by large-scale numerically controlled fluid and liquid handling stations. Numerous noteworthy products have dominated this field in the last decade and have been inhibited the widespread application of microfluidics technology. However, automated liquid handling stations and microfluidics do not have to be considered as mutually exclusive approached. We have recently introduced a hybrid fluidic platform combining an industrially established liquid handling station and a generic microfluidic interfacing module that allows probing a microfluidic system (such as an essay or a synthesis array) using the instrumentation provided by the liquid handling station. We term this technology "Microfluidic on Liquid Handling Stations (μF-on-LHS)" - a classical "best of both worlds"- approach that allows combining the highly evolved, automated and industry-proven LHS systems with any type of microfluidic assay. In this paper we show, to the best of our knowledge, the first droplet microfluidics application on an industrial LHS using the μF-on-LHS concept.

Microfluidic electronics.

PubMed

Cheng, Shi; Wu, Zhigang

2012-08-21

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

Plug-and-actuate on demand: multimodal individual addressability of microarray plates using modular hybrid acoustic wave technology.

PubMed

Rezk, Amgad R; Ramesan, Shwathy; Yeo, Leslie Y

2018-01-30

The microarray titre plate remains a fundamental workhorse in genomic, proteomic and cellomic analyses that underpin the drug discovery process. Nevertheless, liquid handling technologies for sample dispensing, processing and transfer have not progressed significantly beyond conventional robotic micropipetting techniques, which are not only at their fundamental sample size limit, but are also prone to mechanical failure and contamination. This is because alternative technologies to date suffer from a number of constraints, mainly their limitation to carry out only a single liquid operation such as dispensing or mixing at a given time, and their inability to address individual wells, particularly at high throughput. Here, we demonstrate the possibility for true sequential or simultaneous single- and multi-well addressability in a 96-well plate using a reconfigurable modular platform from which MHz-order hybrid surface and bulk acoustic waves can be coupled to drive a variety of microfluidic modes including mixing, sample preconcentration and droplet jetting/ejection in individual or multiple wells on demand, thus constituting a highly versatile yet simple setup capable of improving the functionality of existing laboratory protocols and processes.

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

PubMed

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

2014-09-01

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

Neural Stem Cell Differentiation Using Microfluidic Device-Generated Growth Factor Gradient.

PubMed

Kim, Ji Hyeon; Sim, Jiyeon; Kim, Hyun-Jung

2018-04-11

Neural stem cells (NSCs) have the ability to self-renew and differentiate into multiple nervous system cell types. During embryonic development, the concentrations of soluble biological molecules have a critical role in controlling cell proliferation, migration, differentiation and apoptosis. In an effort to find optimal culture conditions for the generation of desired cell types in vitro , we used a microfluidic chip-generated growth factor gradient system. In the current study, NSCs in the microfluidic device remained healthy during the entire period of cell culture, and proliferated and differentiated in response to the concentration gradient of growth factors (epithermal growth factor and basic fibroblast growth factor). We also showed that overexpression of ASCL1 in NSCs increased neuronal differentiation depending on the concentration gradient of growth factors generated in the microfluidic gradient chip. The microfluidic system allowed us to study concentration-dependent effects of growth factors within a single device, while a traditional system requires multiple independent cultures using fixed growth factor concentrations. Our study suggests that the microfluidic gradient-generating chip is a powerful tool for determining the optimal culture conditions.

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.

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…

Modular Fixturing System

NASA Technical Reports Server (NTRS)

Littell, Justin Anderson (Inventor); Street, Jon P. (Inventor)

2017-01-01

The modular fixturing system of the present invention is modular, reusable and capable of significant customization, both in terms of system radius and system height, allowing it to be arranged and rearranged in numerous unique configurations. The system includes multiple modular stanchions having stanchion shafts and stanchion feet that removably attach to apertures in a table. Angle brackets attached to the modular stanchions support shelves. These shelves in turn provide support to work pieces during fabrication processes such as welding.

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.

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

PubMed Central

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

2015-01-01

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

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

PubMed

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

2015-01-01

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

Smart and functional polymer materials for smart and functional microfluidic instruments

NASA Astrophysics Data System (ADS)

Gray, Bonnie L.

2014-04-01

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

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

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

Electrokinetic focusing injection methods on microfluidic devices.

PubMed

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

2003-04-15

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

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

PubMed Central

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

2016-01-01

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

Microfluidics-Enabled Diagnostic Systems: Markets, Challenges, and Examples.

PubMed

Becker, Holger; Gärtner, Claudia

2017-01-01

Microfluidics has become an important tool for the commercial product development in diagnostics. This article will focus on current technical demands during the development process such as material and integration challenges. Furthermore, we present data on the diagnostics market as well as examples of microfluidics-enabled systems currently under commercial development or already on the market.

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

PubMed Central

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

2012-01-01

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

Modular interdependency in complex dynamical systems.

PubMed

Watson, Richard A; Pollack, Jordan B

2005-01-01

Herbert A. Simon's characterization of modularity in dynamical systems describes subsystems as having dynamics that are approximately independent of those of other subsystems (in the short term). This fits with the general intuition that modules must, by definition, be approximately independent. In the evolution of complex systems, such modularity may enable subsystems to be modified and adapted independently of other subsystems, whereas in a nonmodular system, modifications to one part of the system may result in deleterious side effects elsewhere in the system. But this notion of modularity and its effect on evolvability is not well quantified and is rather simplistic. In particular, modularity need not imply that intermodule dependences are weak or unimportant. In dynamical systems this is acknowledged by Simon's suggestion that, in the long term, the dynamical behaviors of subsystems do interact with one another, albeit in an "aggregate" manner--but this kind of intermodule interaction is omitted in models of modularity for evolvability. In this brief discussion we seek to unify notions of modularity in dynamical systems with notions of how modularity affects evolvability. This leads to a quantifiable measure of modularity and a different understanding of its effect on evolvability.

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.

Recent Progress of Microfluidics in Translational Applications

PubMed Central

Liu, Zongbin; Han, Xin

2016-01-01

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

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

PubMed Central

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

2012-01-01

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

Studies on spectroscopy of glycerol in THz range using microfluidic chip-integrated micropump

NASA Astrophysics Data System (ADS)

Su, Bo; Han, Xue; Wu, Ying; Zhang, Cunlin

2014-11-01

Terahertz time-domain spectroscopy (THz-TDS) is a detection method of biological molecules with label-free, non-ionizing, non-intrusive, no pollution and real-time monitoring. But owing to the strong THz absorption by water, it is mainly used in the solid state detection of biological molecules. In this paper, we present a microfluidic chip technique for detecting biological liquid samples using the transmission type of THz-TDS system. The microfluidic channel of the microfluidic chip is fabricated in the quartz glass using Micro-Electro-Mechanical System (MEMS) technology and sealed with polydimethylsiloxane (PDMS) diaphragm. The length, width and depth of the microfluidic channel are 25mm, 100μm and 50μm, respectively. The diameter of THz detection zone in the microfluidic channel is 4mm. The thicknesses of quartz glass and PDMS diaphragm are 1mm and 250μm, individually. Another one of the same quartz glass is used to bond with the PDMS for the rigidity and air tightness of the microfluidic chip. In order to realize the automation of sampling and improve the control precise of fluid, a micropump, which comprises PDMS diaphragm, pump chamber, diffuser and nozzle and flat vibration motor, is integrated on the microfluidic chip. The diffuser and nozzle are fabricated on both sides of the pump chamber, which is covered with PDMS diaphragm. The flat vibration motor is stuck on the PDMS diaphragm as the actuator. We study the terahertz absorption spectroscopy characteristics of glycerol with the concentration of 98% in the microfluidic chip by the aid of the THz-TDS system, and the feasibility of the microfluidic chip for the detection of liquid samples is proved.

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

PubMed Central

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

2015-01-01

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

Microfluidic perfusion culture.

PubMed

Hattori, Koji; Sugiura, Shinji; Kanamori, Toshiyuki

2014-01-01

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

Microfluidic resonant waveguide grating biosensor system for whole cell sensing

NASA Astrophysics Data System (ADS)

Zaytseva, Natalya; Miller, William; Goral, Vasily; Hepburn, Jerry; Fang, Ye

2011-04-01

We report on a fluidic resonant waveguide grating (RWG) biosensor system that enables medium throughput measurements of cellular responses under microfluidics in a 32-well format. Dynamic mass redistribution assays under microfluidics differentiate the cross-desensitization process between the β2-adrenoceptor agonist epinephrine and the adenylate cyclase activator forskolin mediated signaling. This system opens new possibility to study cellular processes that are otherwise difficult to achieve using conventional RWG configurations.

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

High-throughput optofluidic system for the laser microsurgery of oocytes

NASA Astrophysics Data System (ADS)

Chandsawangbhuwana, Charlie; Shi, Linda Z.; Zhu, Qingyuan; Alliegro, Mark C.; Berns, Michael W.

2012-01-01

This study combines microfluidics with optical microablation in a microscopy system that allows for high-throughput manipulation of oocytes, automated media exchange, and long-term oocyte observation. The microfluidic component of the system transports oocytes from an inlet port into multiple flow channels. Within each channel, oocytes are confined against a microfluidic barrier using a steady fluid flow provided by an external computer-controlled syringe pump. This allows for easy media replacement without disturbing the oocyte location. The microfluidic and optical-laser microbeam ablation capabilities of the system were validated using surf clam (Spisula solidissima) oocytes that were immobilized in order to permit ablation of the 5 μm diameter nucleolinus within the oocyte nucleolus. Oocytes were the followed and assayed for polar body ejection.

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.

Hydrodynamic trapping for rapid assembly and in situ electrical characterization of droplet interface bilayer arrays

DOE PAGES

Nguyen, Mary -Anne; Srijanto, Bernadeta; Collier, C. Patrick; ...

2016-08-02

The droplet interface bilayer (DIB) is a modular technique for assembling planar lipid membranes between water droplets in oil. The DIB method thus provides a unique capability for developing digital, droplet-based membrane platforms for rapid membrane characterization, drug screening and ion channel recordings. This paper demonstrates a new, low-volume microfluidic system that automates droplet generation, sorting, and sequential trapping in designated locations to enable the rapid assembly of arrays of DIBs. The channel layout of the device is guided by an equivalent circuit model, which predicts that a serial arrangement of hydrodynamic DIB traps enables sequential droplet placement and minimizesmore » the hydrodynamic pressure developed across filled traps to prevent squeeze-through of trapped droplets. Furthermore, the incorporation of thin-film electrodes fabricated via evaporation metal deposition onto the glass substrate beneath the channels allows for the first time in situ, simultaneous electrical interrogation of multiple DIBs within a sealed device. Combining electrical measurements with imaging enables measurements of membrane capacitance and resistance and bilayer area, and our data show that DIBs formed in different trap locations within the device exhibit similar sizes and transport properties. Simultaneous, single channel recordings of ion channel gating in multiple membranes are obtained when alamethicin peptides are incorporated into the captured droplets, qualifying the thin-film electrodes as a means for measuring stimuli-responsive functions of membrane-bound biomolecules. Furthermore, this novel microfluidic-electrophysiology platform provides a reproducible, high throughput method for performing electrical measurements to study transmembrane proteins and biomembranes in low-volume, droplet-based membranes.« less

Hydrodynamic trapping for rapid assembly and in situ electrical characterization of droplet interface bilayer arrays

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

Nguyen, Mary -Anne; Srijanto, Bernadeta; Collier, C. Patrick

The droplet interface bilayer (DIB) is a modular technique for assembling planar lipid membranes between water droplets in oil. The DIB method thus provides a unique capability for developing digital, droplet-based membrane platforms for rapid membrane characterization, drug screening and ion channel recordings. This paper demonstrates a new, low-volume microfluidic system that automates droplet generation, sorting, and sequential trapping in designated locations to enable the rapid assembly of arrays of DIBs. The channel layout of the device is guided by an equivalent circuit model, which predicts that a serial arrangement of hydrodynamic DIB traps enables sequential droplet placement and minimizesmore » the hydrodynamic pressure developed across filled traps to prevent squeeze-through of trapped droplets. Furthermore, the incorporation of thin-film electrodes fabricated via evaporation metal deposition onto the glass substrate beneath the channels allows for the first time in situ, simultaneous electrical interrogation of multiple DIBs within a sealed device. Combining electrical measurements with imaging enables measurements of membrane capacitance and resistance and bilayer area, and our data show that DIBs formed in different trap locations within the device exhibit similar sizes and transport properties. Simultaneous, single channel recordings of ion channel gating in multiple membranes are obtained when alamethicin peptides are incorporated into the captured droplets, qualifying the thin-film electrodes as a means for measuring stimuli-responsive functions of membrane-bound biomolecules. Furthermore, this novel microfluidic-electrophysiology platform provides a reproducible, high throughput method for performing electrical measurements to study transmembrane proteins and biomembranes in low-volume, droplet-based membranes.« less

Polymer-based platform for microfluidic systems

DOEpatents

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

2009-10-13

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

Recent Progress of Microfluidics in Translational Applications.

PubMed

Liu, Zongbin; Han, Xin; Qin, Lidong

2016-04-20

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

The importance of microfluidics for the preparation of nanoparticles as advanced drug delivery systems.

PubMed

Martins, João Pedro; Torrieri, Giulia; Santos, Hélder A

2018-05-01

Nanoparticles are anticipated to overcome persistent challenges in efficient drug delivery, but the limitations associated with conventional methods of preparation are resulting in slow translation from research to clinical applications. Due to their enormous potential, microfluidic technologies have emerged as an advanced approach for the development of drug delivery systems with well-defined physicochemical characteristics and in a reproducible manner. Areas covered: This review provides an overview of microfluidic devices and materials used for their manufacturing, together with the flow patterns and regimes commonly used for nanoparticle preparation. Additionally, the different geometries used in droplet microfluidics are reviewed, with particular attention to the co-flow geometry used for the production of nanoparticles. Finally, this review summarizes the main and most recent nanoparticulate systems prepared using microfluidics, including drug nanosuspensions, polymeric, lipid, structured, and theranostic nanoparticles. Expert opinion: The production of nanoparticles at industrial scale is still a challenge, but the microfluidic technologies bring exciting opportunities to develop drug delivery systems that can be engineered in an easy, cost-effective and reproducible manner. As a highly interdisciplinary research field, more efforts and general acceptance are needed to allow for the translation of nanoparticulate drug delivery systems from academic research to the clinical practice.

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.

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

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

PubMed

Li, David; Jacobsen, Matthew M; Gyune Rim, Nae; Backman, Daniel; Kaplan, David L; Wong, Joyce Y

2017-05-31

Silkworm silk is an attractive biopolymer for biomedical applications due to its high mechanical strength and biocompatibility; as a result, there is increasing interest in scalable devices to spin silk and recombinant silk so as to improve and customize their properties for diverse biomedical purposes (Vepari and Kaplan 2007 Prog. Polym. Sci. 32 ). While artificial spinning of regenerated silk fibroins adds tunability to properties such as degradation rate and surface functionalization, the resulting fibers do not yet approach the mechanical strength of native silkworm silk. These drawbacks reduce the applicability and attractiveness of artificial silk (Kinahan et al 2011 Biomacromolecules 12 ). Here, we used computational fluid dynamic simulations to incorporate shear in tandem with biomimetic ion gradients by coupling a modular novel glass microfluidic device to our previous co-axial flow device. Fibers spun with this combined apparatus demonstrated a significant increase in mechanical strength compared to fibers spun with the basic apparatus alone, with a three-fold increase in Young's modulus and extensibility and a twelve-fold increase in toughness. These results thus demonstrate the critical importance of ionic milieu and shear stress in spinning strong fibers from solubilized silk fibroin.

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.

Quasispecies theory for evolution of modularity.

PubMed

Park, Jeong-Man; Niestemski, Liang Ren; Deem, Michael W

2015-01-01

Biological systems are modular, and this modularity evolves over time and in different environments. A number of observations have been made of increased modularity in biological systems under increased environmental pressure. We here develop a quasispecies theory for the dynamics of modularity in populations of these systems. We show how the steady-state fitness in a randomly changing environment can be computed. We derive a fluctuation dissipation relation for the rate of change of modularity and use it to derive a relationship between rate of environmental changes and rate of growth of modularity. We also find a principle of least action for the evolved modularity at steady state. Finally, we compare our predictions to simulations of protein evolution and find them to be consistent.

Functional maintenance of differentiated embryoid bodies in microfluidic systems: a platform for personalized medicine.

PubMed

Guven, Sinan; Lindsey, Jennifer S; Poudel, Ishwari; Chinthala, Sireesha; Nickerson, Michael D; Gerami-Naini, Behzad; Gurkan, Umut A; Anchan, Raymond M; Demirci, Utkan

2015-03-01

Hormone replacement therapies have become important for treating diseases such as premature ovarian failure or menopausal complications. The clinical use of bioidentical hormones might significantly reduce some of the potential risks reportedly associated with the use of synthetic hormones. In the present study, we demonstrate the utility and advantage of a microfluidic chip culture system to enhance the development of personalized, on-demand, treatment modules using embryoid bodies (EBs). Functional EBs cultured on microfluidic chips represent a platform for personalized, patient-specific treatment cassettes that can be cryopreserved until required for treatment. We assessed the viability, differentiation, and functionality of EBs cultured and cryopreserved in this system. During extended microfluidic culture, estradiol, progesterone, testosterone, and anti-müllerian hormone levels were measured, and the expression of differentiated steroidogenic cells was confirmed by immunocytochemistry assay for the ovarian tissue markers anti-müllerian hormone receptor type II, follicle-stimulating hormone receptor, and inhibin β-A and the estrogen biosynthesis enzyme aromatase. Our studies showed that under microfluidic conditions, differentiated steroidogenic EBs continued to secrete estradiol and progesterone at physiologically relevant concentrations (30-120 pg/ml and 150-450 pg/ml, respectively) for up to 21 days. Collectively, we have demonstrated for the first time the feasibility of using a microfluidic chip system with continuous flow for the differentiation and extended culture of functional steroidogenic stem cell-derived EBs, the differentiation of EBs into cells expressing ovarian antigens in a microfluidic system, and the ability to cryopreserve this system with restoration of growth and functionality on thawing. These results present a platform for the development of a new therapeutic system for personalized medicine. ©AlphaMed Press.

Microfluidic systems for stem cell-based neural tissue engineering.

PubMed

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

2016-07-05

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

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

Refractive multiple optical tweezers for parallel biochemical analysis in micro-fluidics

NASA Astrophysics Data System (ADS)

Merenda, Fabrice; Rohner, Johann; Pascoal, Pedro; Fournier, Jean-Marc; Vogel, Horst; Salathé, René-Paul

2007-02-01

We present a multiple laser tweezers system based on refractive optics. The system produces an array of 100 optical traps thanks to a refractive microlens array, whose focal plane is imaged into the focal plane of a high-NA microscope objective. This refractive multi-tweezers system is combined to micro-fluidics, aiming at performing simultaneous biochemical reactions on ensembles of free floating objects. Micro-fluidics allows both transporting the particles to the trapping area, and conveying biochemical reagents to the trapped particles. Parallel trapping in micro-fluidics is achieved with polystyrene beads as well as with native vesicles produced from mammalian cells. The traps can hold objects against fluid flows exceeding 100 micrometers per second. Parallel fluorescence excitation and detection on the ensemble of trapped particles is also demonstrated. Additionally, the system is capable of selectively and individually releasing particles from the tweezers array using a complementary steerable laser beam. Strategies for high-yield particle capture and individual particle release in a micro-fluidic environment are discussed. A comparison with diffractive optical tweezers enhances the pros and cons of refractive systems.

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.

Modular cathode assemblies and methods of using the same for electrochemical reduction

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

Wiedmeyer, Stanley G.; Barnes, Laurel A.; Williamson, Mark A.

Modular cathode assemblies are useable in electrolytic reduction systems and include a basket through which fluid electrolyte may pass and exchange charge with a material to be reduced in the basket. The basket can be divided into upper and lower sections to provide entry for the material. Example embodiment cathode assemblies may have any shape to permit modular placement at any position in reduction systems. Modular cathode assemblies include a cathode plate in the basket, to which unique and opposite electrical power may be supplied. Example embodiment modular cathode assemblies may have standardized electrical connectors. Modular cathode assemblies may bemore » supported by a top plate of an electrolytic reduction system. Electrolytic oxide reduction systems are operated by positioning modular cathode and anode assemblies at desired positions, placing a material in the basket, and charging the modular assemblies to reduce the metal oxide.« less

Modular cathode assemblies and methods of using the same for electrochemical reduction

DOEpatents

Wiedmeyer, Stanley G; Barnes, Laurel A; Williamson, Mark A; Willit, James L

2014-12-02

Modular cathode assemblies are useable in electrolytic reduction systems and include a basket through which fluid electrolyte may pass and exchange charge with a material to be reduced in the basket. The basket can be divided into upper and lower sections to provide entry for the material. Example embodiment cathode assemblies may have any shape to permit modular placement at any position in reduction systems. Modular cathode assemblies include a cathode plate in the basket, to which unique and opposite electrical power may be supplied. Example embodiment modular cathode assemblies may have standardized electrical connectors. Modular cathode assemblies may be supported by a top plate of an electrolytic reduction system. Electrolytic oxide reduction systems are operated by positioning modular cathode and anode assemblies at desired positions, placing a material in the basket, and charging the modular assemblies to reduce the metal oxide.

Microfluidic microarray systems and methods thereof

DOEpatents

West, Jay A. A. [Castro Valley, CA; Hukari, Kyle W [San Ramon, CA; Hux, Gary A [Tracy, CA

2009-04-28

Disclosed are systems that include a manifold in fluid communication with a microfluidic chip having a microarray, an illuminator, and a detector in optical communication with the microarray. Methods for using these systems for biological detection are also disclosed.

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.

Accelerated Biofluid Filling in Complex Microfluidic Networks by Vacuum-Pressure Accelerated Movement (V-PAM).

PubMed

Yu, Zeta Tak For; Cheung, Mei Ki; Liu, Shirley Xiaosu; Fu, Jianping

2016-09-01

Rapid fluid transport and exchange are critical operations involved in many microfluidic applications. However, conventional mechanisms used for driving fluid transport in microfluidics, such as micropumping and high pressure, can be inaccurate and difficult for implementation for integrated microfluidics containing control components and closed compartments. Here, a technology has been developed termed Vacuum-Pressure Accelerated Movement (V-PAM) capable of significantly enhancing biofluid transport in complex microfluidic environments containing dead-end channels and closed chambers. Operation of the V-PAM entails a pressurized fluid loading into microfluidic channels where gas confined inside can rapidly be dissipated through permeation through a thin, gas-permeable membrane sandwiched between microfluidic channels and a network of vacuum channels. Effects of different structural and operational parameters of the V-PAM for promoting fluid filling in microfluidic environments have been studied systematically. This work further demonstrates the applicability of V-PAM for rapid filling of temperature-sensitive hydrogels and unprocessed whole blood into complex irregular microfluidic networks such as microfluidic leaf venation patterns and blood circulatory systems. Together, the V-PAM technology provides a promising generic microfluidic tool for advanced fluid control and transport in integrated microfluidics for different microfluidic diagnosis, organs-on-chips, and biomimetic studies. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Digital biology and chemistry.

PubMed

Witters, Daan; Sun, Bing; Begolo, Stefano; Rodriguez-Manzano, Jesus; Robles, Whitney; Ismagilov, Rustem F

2014-09-07

This account examines developments in "digital" biology and chemistry within the context of microfluidics, from a personal perspective. Using microfluidics as a frame of reference, we identify two areas of research within digital biology and chemistry that are of special interest: (i) the study of systems that switch between discrete states in response to changes in chemical concentration of signals, and (ii) the study of single biological entities such as molecules or cells. In particular, microfluidics accelerates analysis of switching systems (i.e., those that exhibit a sharp change in output over a narrow range of input) by enabling monitoring of multiple reactions in parallel over a range of concentrations of signals. Conversely, such switching systems can be used to create new kinds of microfluidic detection systems that provide "analog-to-digital" signal conversion and logic. Microfluidic compartmentalization technologies for studying and isolating single entities can be used to reconstruct and understand cellular processes, study interactions between single biological entities, and examine the intrinsic heterogeneity of populations of molecules, cells, or organisms. Furthermore, compartmentalization of single cells or molecules in "digital" microfluidic experiments can induce switching in a range of reaction systems to enable sensitive detection of cells or biomolecules, such as with digital ELISA or digital PCR. This "digitizing" offers advantages in terms of robustness, assay design, and simplicity because quantitative information can be obtained with qualitative measurements. While digital formats have been shown to improve the robustness of existing chemistries, we anticipate that in the future they will enable new chemistries to be used for quantitative measurements, and that digital biology and chemistry will continue to provide further opportunities for measuring biomolecules, understanding natural systems more deeply, and advancing molecular and cellular analysis. Microfluidics will impact digital biology and chemistry and will also benefit from them if it becomes massively distributed.

An electrochemical albumin-sensing system utilizing microfluidic technology

NASA Astrophysics Data System (ADS)

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

2007-04-01

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

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.

Microfabricated Modular Scale-Down Device for Regenerative Medicine Process Development

PubMed Central

Reichen, Marcel; Macown, Rhys J.; Jaccard, Nicolas; Super, Alexandre; Ruban, Ludmila; Griffin, Lewis D.; Veraitch, Farlan S.; Szita, Nicolas

2012-01-01

The capacity of milli and micro litre bioreactors to accelerate process development has been successfully demonstrated in traditional biotechnology. However, for regenerative medicine present smaller scale culture methods cannot cope with the wide range of processing variables that need to be evaluated. Existing microfabricated culture devices, which could test different culture variables with a minimum amount of resources (e.g. expensive culture medium), are typically not designed with process development in mind. We present a novel, autoclavable, and microfabricated scale-down device designed for regenerative medicine process development. The microfabricated device contains a re-sealable culture chamber that facilitates use of standard culture protocols, creating a link with traditional small-scale culture devices for validation and scale-up studies. Further, the modular design can easily accommodate investigation of different culture substrate/extra-cellular matrix combinations. Inactivated mouse embryonic fibroblasts (iMEF) and human embryonic stem cell (hESC) colonies were successfully seeded on gelatine-coated tissue culture polystyrene (TC-PS) using standard static seeding protocols. The microfluidic chip included in the device offers precise and accurate control over the culture medium flow rate and resulting shear stresses in the device. Cells were cultured for two days with media perfused at 300 µl.h−1 resulting in a modelled shear stress of 1.1×10−4 Pa. Following perfusion, hESC colonies stained positively for different pluripotency markers and retained an undifferentiated morphology. An image processing algorithm was developed which permits quantification of co-cultured colony-forming cells from phase contrast microscope images. hESC colony sizes were quantified against the background of the feeder cells (iMEF) in less than 45 seconds for high-resolution images, which will permit real-time monitoring of culture progress in future experiments. The presented device is a first step to harness the advantages of microfluidics for regenerative medicine process development. PMID:23284952

Controlled droplet microfluidic systems for multistep chemical and biological assays.

PubMed

Kaminski, T S; Garstecki, P

2017-10-16

Droplet microfluidics is a relatively new and rapidly evolving field of science focused on studying the hydrodynamics and properties of biphasic flows at the microscale, and on the development of systems for practical applications in chemistry, biology and materials science. Microdroplets present several unique characteristics of interest to a broader research community. The main distinguishing features include (i) large numbers of isolated compartments of tiny volumes that are ideal for single cell or single molecule assays, (ii) rapid mixing and negligible thermal inertia that all provide excellent control over reaction conditions, and (iii) the presence of two immiscible liquids and the interface between them that enables new or exotic processes (the synthesis of new functional materials and structures that are otherwise difficult to obtain, studies of the functions and properties of lipid and polymer membranes and execution of reactions at liquid-liquid interfaces). The most frequent application of droplet microfluidics relies on the generation of large numbers of compartments either for ultrahigh throughput screens or for the synthesis of functional materials composed of millions of droplets or particles. Droplet microfluidics has already evolved into a complex field. In this review we focus on 'controlled droplet microfluidics' - a portfolio of techniques that provide convenient platforms for multistep complex reaction protocols and that take advantage of automated and passive methods of fluid handling on a chip. 'Controlled droplet microfluidics' can be regarded as a group of methods capable of addressing and manipulating droplets in series. The functionality and complexity of controlled droplet microfluidic systems can be positioned between digital microfluidics (DMF) addressing each droplet individually using 2D arrays of electrodes and ultrahigh throughput droplet microfluidics focused on the generation of hundreds of thousands or even millions of picoliter droplets that cannot be individually addressed by their location on a chip.

Analysis of Advanced Modular Power Systems (AMPS) for Deep Space Exploration

NASA Technical Reports Server (NTRS)

Oeftering, Richard; Soeder, James F.; Beach, Ray

2014-01-01

The Advanced Modular Power Systems (AMPS) project is developing a modular approach to spacecraft power systems for exploration beyond Earth orbit. AMPS is intended to meet the need of reducing the cost of design development, test and integration and also reducing the operational logistics cost of supporting exploration missions. AMPS seeks to establish modular power building blocks with standardized electrical, mechanical, thermal and data interfaces that can be applied across multiple exploration vehicles. The presentation discusses the results of a cost analysis that compares the cost of the modular approach against a traditional non-modular approach.

Parallel computation with molecular-motor-propelled agents in nanofabricated networks.

PubMed

Nicolau, Dan V; Lard, Mercy; Korten, Till; van Delft, Falco C M J M; Persson, Malin; Bengtsson, Elina; Månsson, Alf; Diez, Stefan; Linke, Heiner; Nicolau, Dan V

2016-03-08

The combinatorial nature of many important mathematical problems, including nondeterministic-polynomial-time (NP)-complete problems, places a severe limitation on the problem size that can be solved with conventional, sequentially operating electronic computers. There have been significant efforts in conceiving parallel-computation approaches in the past, for example: DNA computation, quantum computation, and microfluidics-based computation. However, these approaches have not proven, so far, to be scalable and practical from a fabrication and operational perspective. Here, we report the foundations of an alternative parallel-computation system in which a given combinatorial problem is encoded into a graphical, modular network that is embedded in a nanofabricated planar device. Exploring the network in a parallel fashion using a large number of independent, molecular-motor-propelled agents then solves the mathematical problem. This approach uses orders of magnitude less energy than conventional computers, thus addressing issues related to power consumption and heat dissipation. We provide a proof-of-concept demonstration of such a device by solving, in a parallel fashion, the small instance {2, 5, 9} of the subset sum problem, which is a benchmark NP-complete problem. Finally, we discuss the technical advances necessary to make our system scalable with presently available technology.

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

PubMed Central

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

2014-01-01

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

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

PubMed

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

2012-10-08

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

Plug-and-play, infrared, laser-mediated PCR in a microfluidic chip.

PubMed

Pak, Nikita; Saunders, D Curtis; Phaneuf, Christopher R; Forest, Craig R

2012-04-01

Microfluidic polymerase chain reaction (PCR) systems have set milestones for small volume (100 nL-5 μL), amplification speed (100-400 s), and on-chip integration of upstream and downstream sample handling including purification and electrophoretic separation functionality. In practice, the microfluidic chips in these systems require either insertion of thermocouples or calibration prior to every amplification. These factors can offset the speed advantages of microfluidic PCR and have likely hindered commercialization. We present an infrared, laser-mediated, PCR system that features a single calibration, accurate and repeatable precision alignment, and systematic thermal modeling and management for reproducible, open-loop control of PCR in 1 μL chambers of a polymer microfluidic chip. Total cycle time is less than 12 min: 1 min to fill and seal, 10 min to amplify, and 1 min to recover the sample. We describe the design, basis for its operation, and the precision engineering in the system and microfluidic chip. From a single calibration, we demonstrate PCR amplification of a 500 bp amplicon from λ-phage DNA in multiple consecutive trials on the same instrument as well as multiple identical instruments. This simple, relatively low-cost plug-and-play design is thus accessible to persons who may not be skilled in assembly and engineering.

Microfluidic opportunities in the field of nutrition

PubMed Central

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

2013-01-01

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

Testing of a Microfluidic Sampling System for High Temperature Electrochemical MC&A

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

Pereira, Candido; Nichols, Kevin

2013-11-27

This report describes the preliminary validation of a high-temperature microfluidic chip system for sampling of electrochemical process salt. Electroanalytical and spectroscopic techniques are attractive candidates for improvement through high-throughput sample analysis via miniaturization. Further, microfluidic chip systems are amenable to micro-scale chemical processing such as rapid, automated sample purification to improve sensor performance. The microfluidic chip was tested to determine the feasibility of the system for high temperature applications and conditions under which microfluidic systems can be used to generate salt droplets at process temperature to support development of material balance and control systems in a used fuel treatment facility.more » In FY13, the project focused on testing a quartz microchip device with molten salts at near process temperatures. The equipment was installed in glove box and tested up to 400°C using commercial thermal transfer fluids as the carrier phase. Preliminary tests were carried out with a low-melting halide salt to initially characterize the properties of this novel liquid-liquid system and to investigate the operating regimes for inducing droplet flow within candidate carrier fluids. Initial results show that the concept is viable for high temperature sampling but further development is required to optimize the system to operate with process relevant molten salts.« less

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.

Flexible packaging of solid-state integrated circuit chips with elastomeric microfluidics

PubMed Central

Zhang, Bowei; Dong, Quan; Korman, Can E.; Li, Zhenyu; Zaghloul, Mona E.

2013-01-01

A flexible technology is proposed to integrate smart electronics and microfluidics all embedded in an elastomer package. The microfluidic channels are used to deliver both liquid samples and liquid metals to the integrated circuits (ICs). The liquid metals are used to realize electrical interconnects to the IC chip. This avoids the traditional IC packaging challenges, such as wire-bonding and flip-chip bonding, which are not compatible with current microfluidic technologies. As a demonstration we integrated a CMOS magnetic sensor chip and associate microfluidic channels on a polydimethylsiloxane (PDMS) substrate that allows precise delivery of small liquid samples to the sensor. Furthermore, the packaged system is fully functional under bending curvature radius of one centimetre and uniaxial strain of 15%. The flexible integration of solid-state ICs with microfluidics enables compact flexible electronic and lab-on-a-chip systems, which hold great potential for wearable health monitoring, point-of-care diagnostics and environmental sensing among many other applications.

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

Portable modular detection system

DOEpatents

Brennan, James S [Rodeo, CA; Singh, Anup [Danville, CA; Throckmorton, Daniel J [Tracy, CA; Stamps, James F [Livermore, CA

2009-10-13

Disclosed herein are portable and modular detection devices and systems for detecting electromagnetic radiation, such as fluorescence, from an analyte which comprises at least one optical element removably attached to at least one alignment rail. Also disclosed are modular detection devices and systems having an integrated lock-in amplifier and spatial filter and assay methods using the portable and modular detection devices.

Modularity and the spread of perturbations in complex dynamical systems

NASA Astrophysics Data System (ADS)

Kolchinsky, Artemy; Gates, Alexander J.; Rocha, Luis M.

2015-12-01

We propose a method to decompose dynamical systems based on the idea that modules constrain the spread of perturbations. We find partitions of system variables that maximize "perturbation modularity," defined as the autocovariance of coarse-grained perturbed trajectories. The measure effectively separates the fast intramodular from the slow intermodular dynamics of perturbation spreading (in this respect, it is a generalization of the "Markov stability" method of network community detection). Our approach captures variation of modular organization across different system states, time scales, and in response to different kinds of perturbations: aspects of modularity which are all relevant to real-world dynamical systems. It offers a principled alternative to detecting communities in networks of statistical dependencies between system variables (e.g., "relevance networks" or "functional networks"). Using coupled logistic maps, we demonstrate that the method uncovers hierarchical modular organization planted in a system's coupling matrix. Additionally, in homogeneously coupled map lattices, it identifies the presence of self-organized modularity that depends on the initial state, dynamical parameters, and type of perturbations. Our approach offers a powerful tool for exploring the modular organization of complex dynamical systems.

Modularity and the spread of perturbations in complex dynamical systems.

PubMed

Kolchinsky, Artemy; Gates, Alexander J; Rocha, Luis M

2015-12-01

We propose a method to decompose dynamical systems based on the idea that modules constrain the spread of perturbations. We find partitions of system variables that maximize "perturbation modularity," defined as the autocovariance of coarse-grained perturbed trajectories. The measure effectively separates the fast intramodular from the slow intermodular dynamics of perturbation spreading (in this respect, it is a generalization of the "Markov stability" method of network community detection). Our approach captures variation of modular organization across different system states, time scales, and in response to different kinds of perturbations: aspects of modularity which are all relevant to real-world dynamical systems. It offers a principled alternative to detecting communities in networks of statistical dependencies between system variables (e.g., "relevance networks" or "functional networks"). Using coupled logistic maps, we demonstrate that the method uncovers hierarchical modular organization planted in a system's coupling matrix. Additionally, in homogeneously coupled map lattices, it identifies the presence of self-organized modularity that depends on the initial state, dynamical parameters, and type of perturbations. Our approach offers a powerful tool for exploring the modular organization of complex dynamical systems.

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

PubMed Central

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

2012-01-01

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

Reactions in Droplets in Microfluidic Channels

PubMed Central

Song, Helen; Chen, Delai L.; Ismagilov, Rustem F.

2006-01-01

Fundamental and applied research in chemistry and biology benefits from opportunities provided by droplet-based microfluidic systems. These systems enable the miniaturization of reactions by compartmentalizing reactions in droplets of femoliter to microliter volumes. Compartmentalization in droplets provides rapid mixing of reagents, control of the timing of reactions on timescales from milliseconds to months, control of interfacial properties, and the ability to synthesize and transport solid reagents and products. Droplet-based microfluidics can help to enhance and accelerate chemical and biochemical screening, protein crystallization, enzymatic kinetics, and assays. Moreover, the control provided by droplets in microfluidic devices can lead to new scientific methods and insights. PMID:17086584

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

NASA Astrophysics Data System (ADS)

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

2018-06-01

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

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.

Detection of Plasmodium Aldolase Using a Smartphone and Microfluidic Enzyme Linked Immunosorbent Assay

PubMed Central

2017-01-01

Background Malaria control efforts are limited in rural areas. A low-cost system to monitor response without the use of electricity is needed. Plasmodium aldolase is a malaria biomarker measured using enzyme linked immunosorbent assay (ELISA) techniques. A three-part system using ELISA was developed consisting of a microfluidic chip, hand crank centrifuge, and a smartphone. Methods A circular microfluidic chip was fabricated using clear acrylic and a CO2 laser. A series of passive valves released reagents at precise times based upon centrifugal force. Color change was measured via smartphone camera using an application programmed in Java. The microchip was compared to a standard 96-well sandwich ELISA. Results Results from standard ELISA were compared to microchip at varying concentrations (1–10 ng/mL). Over 15 different microfluidic patterns were tested, and a final prototype of the chip was created. The prototype microchip was compared to standard sandwich ELISA (n = 20) using samples of recombinant aldolase. Color readings of standard ELISA and microfluidic microchip showed similar results. Conclusion A low-cost microfluidic system could detect and follow therapeutic outcomes in rural areas and identify resistant strains. PMID:29057138

Multiphase flow microfluidics for the production of single or multiple emulsions for drug delivery.

PubMed

Zhao, Chun-Xia

2013-11-01

Considerable effort has been directed towards developing novel drug delivery systems. Microfluidics, capable of generating monodisperse single and multiple emulsion droplets, executing precise control and operations on these droplets, is a powerful tool for fabricating complex systems (microparticles, microcapsules, microgels) with uniform size, narrow size distribution and desired properties, which have great potential in drug delivery applications. This review presents an overview of the state-of-the-art multiphase flow microfluidics for the production of single emulsions or multiple emulsions for drug delivery. The review starts with a brief introduction of the approaches for making single and multiple emulsions, followed by presentation of some potential drug delivery systems (microparticles, microcapsules and microgels) fabricated in microfluidic devices using single or multiple emulsions as templates. The design principles, manufacturing processes and properties of these drug delivery systems are also discussed and compared. Furthermore, drug encapsulation and drug release (including passive and active controlled release) are provided and compared highlighting some key findings and insights. Finally, site-targeting delivery using multiphase flow microfluidics is also briefly introduced. Copyright © 2013 Elsevier B.V. All rights reserved.

System-level simulation of liquid filling in microfluidic chips.

PubMed

Song, Hongjun; Wang, Yi; Pant, Kapil

2011-06-01

Liquid filling in microfluidic channels is a complex process that depends on a variety of geometric, operating, and material parameters such as microchannel geometry, flow velocity∕pressure, liquid surface tension, and contact angle of channel surface. Accurate analysis of the filling process can provide key insights into the filling time, air bubble trapping, and dead zone formation, and help evaluate trade-offs among the various design parameters and lead to optimal chip design. However, efficient modeling of liquid filling in complex microfluidic networks continues to be a significant challenge. High-fidelity computational methods, such as the volume of fluid method, are prohibitively expensive from a computational standpoint. Analytical models, on the other hand, are primarily applicable to idealized geometries and, hence, are unable to accurately capture chip level behavior of complex microfluidic systems. This paper presents a parametrized dynamic model for the system-level analysis of liquid filling in three-dimensional (3D) microfluidic networks. In our approach, a complex microfluidic network is deconstructed into a set of commonly used components, such as reservoirs, microchannels, and junctions. The components are then assembled according to their spatial layout and operating rationale to achieve a rapid system-level model. A dynamic model based on the transient momentum equation is developed to track the liquid front in the microchannels. The principle of mass conservation at the junction is used to link the fluidic parameters in the microchannels emanating from the junction. Assembly of these component models yields a set of differential and algebraic equations, which upon integration provides temporal information of the liquid filling process, particularly liquid front propagation (i.e., the arrival time). The models are used to simulate the transient liquid filling process in a variety of microfluidic constructs and in a multiplexer, representing a complex microfluidic network. The accuracy (relative error less than 7%) and orders-of-magnitude speedup (30 000X-4 000 000X) of our system-level models are verified by comparison against 3D high-fidelity numerical studies. Our findings clearly establish the utility of our models and simulation methodology for fast, reliable analysis of liquid filling to guide the design optimization of complex microfluidic networks.

Future Concepts for Modular, Intelligent Aerospace Power Systems

NASA Technical Reports Server (NTRS)

Button, Robert M.; Soeder, James F.

2004-01-01

Nasa's resent commitment to Human and Robotic Space Exploration obviates the need for more affordable and sustainable systems and missions. Increased use of modularity and on-board intelligent technologies will enable these lofty goals. To support this new paradigm, an advanced technology program to develop modular, intelligent power management and distribution (PMAD) system technologies is presented. The many benefits to developing and including modular functionality in electrical power components and systems are shown to include lower costs and lower mass for highly reliable systems. The details of several modular technologies being developed by NASA are presented, broken down into hierarchical levels. Modularity at the device level, including the use of power electronic building blocks, is shown to provide benefits in lowering the development time and costs of new power electronic components.

Modular space station Phase B extension preliminary performance specification. Volume 2: Project

NASA Technical Reports Server (NTRS)

1971-01-01

The four systems of the modular space station project are described, and the interfaces between this project and the shuttle project, the tracking and data relay satellite project, and an arbitrarily defined experiment project are defined. The experiment project was synthesized from internal experiments, detached research and application modules, and attached research and application modules to derive a set of interface requirements which will support multiple combinations of these elements expected during the modular space station mission. The modular space station project element defines a 6-man orbital program capable of growth to a 12-man orbital program capability. The modular space station project element specification defines the modular space station system, the premission operations support system, the mission operations support system, and the cargo module system and their interfaces.

Numerical and experimental characterization of a novel modular passive micromixer.

PubMed

Pennella, Francesco; Rossi, Massimiliano; Ripandelli, Simone; Rasponi, Marco; Mastrangelo, Francesco; Deriu, Marco A; Ridolfi, Luca; Kähler, Christian J; Morbiducci, Umberto

2012-10-01

This paper reports a new low-cost passive microfluidic mixer design, based on a replication of identical mixing units composed of microchannels with variable curvature (clothoid) geometry. The micromixer presents a compact and modular architecture that can be easily fabricated using a simple and reliable fabrication process. The particular clothoid-based geometry enhances the mixing by inducing transversal secondary flows and recirculation effects. The role of the relevant fluid mechanics mechanisms promoting the mixing in this geometry were analysed using computational fluid dynamics (CFD) for Reynolds numbers ranging from 1 to 110. A measure of mixing potency was quantitatively evaluated by calculating mixing efficiency, while a measure of particle dispersion was assessed through the lacunarity index. The results show that the secondary flow arrangement and recirculation effects are able to provide a mixing efficiency equal to 80 % at Reynolds number above 70. In addition, the analysis of particles distribution promotes the lacunarity as powerful tool to quantify the dispersion of fluid particles and, in turn, the overall mixing. On fabricated micromixer prototypes the microscopic-Laser-Induced-Fluorescence (μLIF) technique was applied to characterize mixing. The experimental results confirmed the mixing potency of the microdevice.

Collective oscillations and coupled modes in confined microfluidic droplet arrays

NASA Astrophysics Data System (ADS)

Schiller, Ulf D.; Fleury, Jean-Baptiste; Seemann, Ralf; Gompper, Gerhard

Microfluidic droplets have a wide range of applications ranging from analytic assays in cellular biology to controlled mixing in chemical engineering. Ensembles of microfluidic droplets are interesting model systems for non-equilibrium many-body phenomena. When flowing in a microchannel, trains of droplets can form microfluidic crystals whose dynamics are governed by long-range hydrodynamic interactions and boundary effects. In this contribution, excitation mechanisms for collective waves in dense and confined microfluidic droplet arrays are investigated by experiments and computer simulations. We demonstrate that distinct modes can be excited by creating specific `defect' patterns in flowing droplet trains. While longitudinal modes exhibit a short-lived cascade of pairs of laterally displacing droplets, transversely excited modes form propagating waves that behave like microfluidic phonons. We show that the confinement induces a coupling between longitudinal and transverse modes. We also investigate the life time of the collective oscillations and discuss possible mechanisms for the onset of instabilities. Our results demonstrate that microfluidic phonons can exhibit effects beyond the linear theory, which can be studied particularly well in dense and confined systems. This work was supported by Deutsche Forschungsgemeinschaft under Grant No. SE 1118/4.

Development of a microfluidic perfusion 3D cell culture system

NASA Astrophysics Data System (ADS)

Park, D. H.; Jeon, H. J.; Kim, M. J.; Nguyen, X. D.; Morten, K.; Go, J. S.

2018-04-01

Recently, 3-dimensional in vitro cell cultures have gained much attention in biomedical sciences because of the closer relevance between in vitro cell cultures and in vivo environments. This paper presents a microfluidic perfusion 3D cell culture system with consistent control of long-term culture conditions to mimic an in vivo microenvironment. It consists of two sudden expansion reservoirs to trap incoming air bubbles, gradient generators to provide a linear concentration, and microchannel mixers. Specifically, the air bubbles disturb a flow in the microfluidic channel resulting in the instability of the perfusion cell culture conditions. For long-term stable operation, the sudden expansion reservoir is designed to trap air bubbles by using buoyancy before they enter the culture system. The performance of the developed microfluidic perfusion 3D cell culture system was examined experimentally and compared with analytical results. Finally, it was applied to test the cytotoxicity of cells infected with Ewing’s sarcoma. Cell death was observed for different concentrations of H2O2. For future work, the developed microfluidic perfusion 3D cell culture system can be used to examine the behavior of cells treated with various drugs and concentrations for high-throughput drug screening.

Closed-loop feedback control for microfluidic systems through automated capacitive fluid height sensing.

PubMed

Soenksen, L R; Kassis, T; Noh, M; Griffith, L G; Trumper, D L

2018-03-13

Precise fluid height sensing in open-channel microfluidics has long been a desirable feature for a wide range of applications. However, performing accurate measurements of the fluid level in small-scale reservoirs (<1 mL) has proven to be an elusive goal, especially if direct fluid-sensor contact needs to be avoided. In particular, gravity-driven systems used in several microfluidic applications to establish pressure gradients and impose flow remain open-loop and largely unmonitored due to these sensing limitations. Here we present an optimized self-shielded coplanar capacitive sensor design and automated control system to provide submillimeter fluid-height resolution (∼250 μm) and control of small-scale open reservoirs without the need for direct fluid contact. Results from testing and validation of our optimized sensor and system also suggest that accurate fluid height information can be used to robustly characterize, calibrate and dynamically control a range of microfluidic systems with complex pumping mechanisms, even in cell culture conditions. Capacitive sensing technology provides a scalable and cost-effective way to enable continuous monitoring and closed-loop feedback control of fluid volumes in small-scale gravity-dominated wells in a variety of microfluidic applications.

Simulation of value stream mapping and discrete optimization of energy consumption in modular construction

NASA Astrophysics Data System (ADS)

Chowdhury, Md Mukul

With the increased practice of modularization and prefabrication, the construction industry gained the benefits of quality management, improved completion time, reduced site disruption and vehicular traffic, and improved overall safety and security. Whereas industrialized construction methods, such as modular and manufactured buildings, have evolved over decades, core techniques used in prefabrication plants vary only slightly from those employed in traditional site-built construction. With a focus on energy and cost efficient modular construction, this research presents the development of a simulation, measurement and optimization system for energy consumption in the manufacturing process of modular construction. The system is based on Lean Six Sigma principles and loosely coupled system operation to identify the non-value adding tasks and possible causes of low energy efficiency. The proposed system will also include visualization functions for demonstration of energy consumption in modular construction. The benefits of implementing this system include a reduction in the energy consumption in production cost, decrease of energy cost in the production of lean-modular construction, and increase profit. In addition, the visualization functions will provide detailed information about energy efficiency and operation flexibility in modular construction. A case study is presented to validate the reliability of the system.

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.

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

NASA Astrophysics Data System (ADS)

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

2011-04-01

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

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

PubMed

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

2005-02-01

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

Effects of surface properties on droplet formation inside a microfluidic device

NASA Astrophysics Data System (ADS)

Steinhaus, Ben; Shen, Amy

2004-11-01

Micro-fluidic devices offer a unique method of creating and controlling droplets on small length scales. A microfluidic device is used to study the effects of surface properties on droplet formation of a 2-phase flow system. Four phase diagrams are generated to compare the dynamics of the 2 immiscible fluid system (silicone oil and water) inside microchannels with different surface properties. Results show that the channel surface plays an important role in determining the flow patterns and the droplet formation of the 2-phase fluid system.

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.

In Silico Investigation of a Surgical Interface for Remote Control of Modular Miniature Robots in Minimally Invasive Surgery

PubMed Central

Zygomalas, Apollon; Giokas, Konstantinos; Koutsouris, Dimitrios

2014-01-01

Aim. Modular mini-robots can be used in novel minimally invasive surgery techniques like natural orifice transluminal endoscopic surgery (NOTES) and laparoendoscopic single site (LESS) surgery. The control of these miniature assistants is complicated. The aim of this study is the in silico investigation of a remote controlling interface for modular miniature robots which can be used in minimally invasive surgery. Methods. The conceptual controlling system was developed, programmed, and simulated using professional robotics simulation software. Three different modes of control were programmed. The remote controlling surgical interface was virtually designed as a high scale representation of the respective modular mini-robot, therefore a modular controlling system itself. Results. With the proposed modular controlling system the user could easily identify the conformation of the modular mini-robot and adequately modify it as needed. The arrangement of each module was always known. The in silico investigation gave useful information regarding the controlling mode, the adequate speed of rearrangements, and the number of modules needed for efficient working tasks. Conclusions. The proposed conceptual model may promote the research and development of more sophisticated modular controlling systems. Modular surgical interfaces may improve the handling and the dexterity of modular miniature robots during minimally invasive procedures. PMID:25295187

In silico investigation of a surgical interface for remote control of modular miniature robots in minimally invasive surgery.

PubMed

Zygomalas, Apollon; Giokas, Konstantinos; Koutsouris, Dimitrios

2014-01-01

Aim. Modular mini-robots can be used in novel minimally invasive surgery techniques like natural orifice transluminal endoscopic surgery (NOTES) and laparoendoscopic single site (LESS) surgery. The control of these miniature assistants is complicated. The aim of this study is the in silico investigation of a remote controlling interface for modular miniature robots which can be used in minimally invasive surgery. Methods. The conceptual controlling system was developed, programmed, and simulated using professional robotics simulation software. Three different modes of control were programmed. The remote controlling surgical interface was virtually designed as a high scale representation of the respective modular mini-robot, therefore a modular controlling system itself. Results. With the proposed modular controlling system the user could easily identify the conformation of the modular mini-robot and adequately modify it as needed. The arrangement of each module was always known. The in silico investigation gave useful information regarding the controlling mode, the adequate speed of rearrangements, and the number of modules needed for efficient working tasks. Conclusions. The proposed conceptual model may promote the research and development of more sophisticated modular controlling systems. Modular surgical interfaces may improve the handling and the dexterity of modular miniature robots during minimally invasive procedures.

Microfluidics-Based PCR for Fusion Transcript Detection.

PubMed

Chen, Hui

2016-01-01

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

Real-Time Continuous Identification of Greenhouse Plant Pathogens Based on Recyclable Microfluidic Bioassay System.

PubMed

Qu, Xiangmeng; Li, Min; Zhang, Hongbo; Lin, Chenglie; Wang, Fei; Xiao, Mingshu; Zhou, Yi; Shi, Jiye; Aldalbahi, Ali; Pei, Hao; Chen, Hong; Li, Li

2017-09-20

The development of a real-time continuous analytical platform for the pathogen detection is of great scientific importance for achieving better disease control and prevention. In this work, we report a rapid and recyclable microfluidic bioassay system constructed from oligonucleotide arrays for selective and sensitive continuous identification of DNA targets of fungal pathogens. We employ the thermal denaturation method to effectively regenerate the oligonucleotide arrays for multiple sample detection, which could considerably reduce the screening effort and costs. The combination of thermal denaturation and laser-induced fluorescence detection technique enables real-time continuous identification of multiple samples (<10 min per sample). As a proof of concept, we have demonstrated that two DNA targets of fungal pathogens (Botrytis cinerea and Didymella bryoniae) can be sequentially analyzed using our rapid microfluidic bioassay system, which provides a new paradigm in the design of microfluidic bioassay system and will be valuable for chemical and biomedical analysis.

A Microfluidic Immunostaining System Enables Quality Assured and Standardized Immunohistochemical Biomarker Analysis

NASA Astrophysics Data System (ADS)

Kwon, Seyong; Cho, Chang Hyun; Kwon, Youngmee; Lee, Eun Sook; Park, Je-Kyun

2017-04-01

Immunohistochemistry (IHC) plays an important role in biomarker-driven cancer therapy. Although there has been a high demand for standardized and quality assured IHC, it has rarely been achieved due to the complexity of IHC testing and the subjective validation-based process flow of IHC quality control. We present here a microfluidic immunostaining system for the standardization of IHC by creating a microfluidic linearly graded antibody (Ab)-staining device and a reference cell microarray. Unlike conventional efforts, our system deals primarily with the screening of biomarker staining conditions for quantitative quality assurance testing in IHC. We characterized the microfluidic matching of Ab staining intensity using three HER2 Abs produced by different manufacturers. The quality of HER2 Ab was also validated using tissues of breast cancer patients, demonstrating that our system is an efficient and powerful tool for the standardization and quality assurance of IHC.

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.

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.

Advances in microfluidics for drug discovery.

PubMed

Lombardi, Dario; Dittrich, Petra S

2010-11-01

Microfluidics is considered as an enabling technology for the development of unconventional and innovative methods in the drug discovery process. The concept of micrometer-sized reaction systems in the form of continuous flow reactors, microdroplets or microchambers is intriguing, and the versatility of the technology perfectly fits with the requirements of drug synthesis, drug screening and drug testing. In this review article, we introduce key microfluidic approaches to the drug discovery process, highlighting the latest and promising achievements in this field, mainly from the years 2007 - 2010. Despite high expectations of microfluidic approaches to several stages of the drug discovery process, up to now microfluidic technology has not been able to significantly replace conventional drug discovery platforms. Our aim is to identify bottlenecks that have impeded the transfer of microfluidics into routine platforms for drug discovery and show some recent solutions to overcome these hurdles. Although most microfluidic approaches are still applied only for proof-of-concept studies, thanks to creative microfluidic research in the past years unprecedented novel capabilities of microdevices could be demonstrated, and general applicable, robust and reliable microfluidic platforms seem to be within reach.

Experimental Investigations on the Surface-Driven Capillary Flow of Aqueous Microparticle Suspensions in the Microfluidic Laboratory-On Systems

NASA Astrophysics Data System (ADS)

Mukhopadhyay, Subhadeep

In this work, total 1592 individual leakage-free polymethylmethacrylate (PMMA) microfluidic devices as laboratory-on-a-chip systems are fabricated by maskless lithography, hot embossing lithography, and direct bonding technique. Total 1094 individual Audio Video Interleave Files as experimental outputs related to the surface-driven capillary flow have been recorded and analyzed. The influence of effective viscosity, effect of surface wettability, effect of channel aspect ratio, and effect of centrifugal force on the surface-driven microfluidic flow of aqueous microparticle suspensions have been successfully and individually investigated in these laboratory-on-a-chip systems. Also, 5 micron polystyrene particles have been separated from the aqueous microparticle suspensions in the microfluidic lab-on-a-chip systems of modified design with 98% separation efficiency, and 10 micron polystyrene particles have been separated with 100% separation efficiency. About the novelty of this work, the experimental investigations have been performed on the surface-driven microfluidic flow of aqueous microparticle suspensions with the investigations on the separation time in particle-size based separation mechanism to control these suspensions in the microfluidic lab-on-a-chip systems. This research work contains a total of 10,112 individual experimental outputs obtained using total 30 individual instruments by author’s own hands-on completely during more than three years continuously. Author has performed the experimental investigations on both the fluid statics and fluid dynamics to develop an automated fluid machine.

Production of nanoparticle drug delivery systems with microfluidics tools.

PubMed

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

2015-04-01

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

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

PubMed

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

2013-11-05

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

A smartphone controlled handheld microfluidic liquid handling system.

PubMed

Li, Baichen; Li, Lin; Guan, Allan; Dong, Quan; Ruan, Kangcheng; Hu, Ronggui; Li, Zhenyu

2014-10-21

Microfluidics and lab-on-a-chip technologies have made it possible to manipulate small volume liquids with unprecedented resolution, automation and integration. However, most current microfluidic systems still rely on bulky off-chip infrastructures such as compressed pressure sources, syringe pumps and computers to achieve complex liquid manipulation functions. Here, we present a handheld automated microfluidic liquid handling system controlled by a smartphone, which is enabled by combining elastomeric on-chip valves and a compact pneumatic system. As a demonstration, we show that the system can automatically perform all the liquid handling steps of a bead-based HIV1 p24 sandwich immunoassay on a multi-layer PDMS chip without any human intervention. The footprint of the system is 6 × 10.5 × 16.5 cm, and the total weight is 829 g including battery. Powered by a 12.8 V 1500 mAh Li battery, the system consumed 2.2 W on average during the immunoassay and lasted for 8.7 h. This handheld microfluidic liquid handling platform is generally applicable to many biochemical and cell-based assays requiring complex liquid manipulation and sample preparation steps such as FISH, PCR, flow cytometry and nucleic acid sequencing. In particular, the integration of this technology with read-out biosensors may help enable the realization of the long-sought Tricorder-like handheld in vitro diagnostic (IVD) systems.

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

PubMed

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

2012-02-07

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

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

NASA Astrophysics Data System (ADS)

Chung, Daehan; Gray, Bonnie L.

2017-11-01

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

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.

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

NASA Astrophysics Data System (ADS)

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

2009-06-01

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

Gas diffusion as a new fluidic unit operation for centrifugal microfluidic platforms.

PubMed

Ymbern, Oriol; Sández, Natàlia; Calvo-López, Antonio; Puyol, Mar; Alonso-Chamarro, Julian

2014-03-07

A centrifugal microfluidic platform prototype with an integrated membrane for gas diffusion is presented for the first time. The centrifugal platform allows multiple and parallel analysis on a single disk and integrates at least ten independent microfluidic subunits, which allow both calibration and sample determination. It is constructed with a polymeric substrate material and it is designed to perform colorimetric determinations by the use of a simple miniaturized optical detection system. The determination of three different analytes, sulfur dioxide, nitrite and carbon dioxide, is carried out as a proof of concept of a versatile microfluidic system for the determination of analytes which involve a gas diffusion separation step during the analytical procedure.

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.

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

PubMed

Baigl, Damien

2012-10-07

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

Microfluidic and nanofluidic phase behaviour characterization for industrial CO2, oil and gas.

PubMed

Bao, Bo; Riordon, Jason; Mostowfi, Farshid; Sinton, David

2017-08-08

Microfluidic systems that leverage unique micro-scale phenomena have been developed to provide rapid, accurate and robust analysis, predominantly for biomedical applications. These attributes, in addition to the ability to access high temperatures and pressures, have motivated recent expanded applications in phase measurements relevant to industrial CO 2 , oil and gas applications. We here present a comprehensive review of this exciting new field, separating microfluidic and nanofluidic approaches. Microfluidics is practical, and provides similar phase properties analysis to established bulk methods with advantages in speed, control and sample size. Nanofluidic phase behaviour can deviate from bulk measurements, which is of particular relevance to emerging unconventional oil and gas production from nanoporous shale. In short, microfluidics offers a practical, compelling replacement of current bulk phase measurement systems, whereas nanofluidics is not practical, but uniquely provides insight into phase change phenomena at nanoscales. Challenges, trends and opportunities for phase measurements at both scales are highlighted.

A multiplexable, microfluidic platform for the rapid quantitation of a biomarker panel for early ovarian cancer detection at the point-of-care

PubMed Central

Shadfan, Basil H.; Simmons, Archana R.; Simmons, Glennon W.; Ho, Andy; Wong, Jorge; Lu, Karen H.; Bast, Robert C.; McDevitt, John T.

2015-01-01

Point-of-care (POC) diagnostic platforms have the potential to enable low-cost, large-scale screening. As no single biomarker is shed by all ovarian cancers, multiplexed biomarker panels promise improved sensitivity and specificity to address the unmet need for early detection of ovarian cancer. We have configured the programmable bio-nano-chip (p-BNC) - a multiplexable, microfluidic, modular platform - to quantify a novel multimarker panel comprising CA125, HE4, MMP-7 and CA72-4. The p-BNC is a bead-based immunoanalyzer system with a credit-card-sized footprint that integrates automated sample metering, bubble and debris removal, reagent storage and waste disposal, permitting POC analysis. Multiplexed p-BNC immunoassays demonstrated high specificity, low cross-reactivity, low limits of detection suitable for early detection, and a short analysis time of 43 minutes. Day-to-day variability, a critical factor for longitudinally monitoring biomarkers, ranged between 5.4–10.5%, well below the biological variation for all four markers. Biomarker concentrations for 31 late-stage sera correlated well (R2 = 0.71 to 0.93 for various biomarkers) with values obtained on the Luminex® platform. In a 31 patient cohort encompassing early- and late-stage ovarian cancers along with benign and healthy controls, the multiplexed p-BNC panel was able to distinguish cases from controls with 68.7% sensitivity at 80% specificity. Utility for longitudinal biomarker monitoring was demonstrated with pre-diagnostic sera from 2 cases and 4 controls. Taken together, the p-BNC shows strong promise as a diagnostic tool for large-scale screening that takes advantage of faster results and lower costs while leveraging possible improvement in sensitivity and specificity from biomarker panels. PMID:25388014

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

PubMed

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

2014-09-21

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

Microfluidic Liquid-Liquid Contactors

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

Mcculloch, Quinn

2017-07-25

This report describes progress made on the microfluidic contactor. A model was developed to predict its failure, a surrogate chemical system was selected to demonstrate mass transfer, and an all-optical system has been invented and implemented to monitor carryover and flowrates.

Bonded polyimide fuel cell package

DOEpatents

Morse, Jeffrey D.; Jankowski, Alan; Graff, Robert T.; Bettencourt, Kerry

2010-06-08

Described herein are processes for fabricating microfluidic fuel cell systems with embedded components in which micron-scale features are formed by bonding layers of DuPont Kapton.TM. polyimide laminate. A microfluidic fuel cell system fabricated using this process is also described.

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.

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

Liposome production by microfluidics: potential and limiting factors

PubMed Central

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

2016-01-01

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

Microfluidics for Drug Discovery and Development: From Target Selection to Product Lifecycle Management

PubMed Central

Kang, Lifeng; Chung, Bong Geun; Langer, Robert; Khademhosseini, Ali

2009-01-01

Microfluidic technologies’ ability to miniaturize assays and increase experimental throughput have generated significant interest in the drug discovery and development domain. These characteristics make microfluidic systems a potentially valuable tool for many drug discovery and development applications. Here, we review the recent advances of microfluidic devices for drug discovery and development and highlight their applications in different stages of the process, including target selection, lead identification, preclinical tests, clinical trials, chemical synthesis, formulations studies, and product management. PMID:18190858

Liposome production by microfluidics: potential and limiting factors.

PubMed

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

2016-05-19

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

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.

Microfluidic devices, systems, and methods for quantifying particles using centrifugal force

DOEpatents

Schaff, Ulrich Y.; Sommer, Gregory J.; Singh, Anup K.

2015-11-17

Embodiments of the present invention are directed toward microfluidic systems, apparatus, and methods for measuring a quantity of cells in a fluid. Examples include a differential white blood cell measurement using a centrifugal microfluidic system. A method may include introducing a fluid sample containing a quantity of cells into a microfluidic channel defined in part by a substrate. The quantity of cells may be transported toward a detection region defined in part by the substrate, wherein the detection region contains a density media, and wherein the density media has a density lower than a density of the cells and higher than a density of the fluid sample. The substrate may be spun such that at least a portion of the quantity of cells are transported through the density media. Signals may be detected from label moieties affixed to the cells.

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

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

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

2013-11-21

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

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.

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).

Macro- and microscale fluid flow systems for endothelial cell biology.

PubMed

Young, Edmond W K; Simmons, Craig A

2010-01-21

Recent advances in microfluidics have brought forth new tools for studying flow-induced effects on mammalian cells, with important applications in cardiovascular, bone and cancer biology. The plethora of microscale systems developed to date demonstrate the flexibility of microfluidic designs, and showcase advantages of the microscale that are simply not available at the macroscale. However, the majority of these systems will likely not achieve widespread use in the biological laboratory due to their complexity and lack of user-friendliness. To gain widespread acceptance in the biological research community, microfluidics engineers must understand the needs of cell biologists, while biologists must be made aware of available technology. This review provides a critical evaluation of cell culture flow (CCF) systems used to study the effects of mechanical forces on endothelial cells (ECs) in vitro. To help understand the need for various designs of CCF systems, we first briefly summarize main properties of ECs and their native environments. Basic principles of various macro- and microscale systems are described and evaluated. New opportunities are uncovered for developing technologies that have potential to both improve efficiency of experimentation as well as answer important biological questions that otherwise cannot be tackled with existing systems. Finally, we discuss some of the unresolved issues related to microfluidic cell culture, suggest possible avenues of investigation that could resolve these issues, and provide an outlook for the future of microfluidics in biological research.

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

PubMed

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

2015-10-21

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

Compartmental culture of embryonic stem cell-derived neurons in microfluidic devices for use in axonal biology.

PubMed

Shin, Hwa Sung; Kim, Hyung Joon; Min, Seul Ki; Kim, Sung Hoon; Lee, Byung Man; Jeon, Noo Li

2010-08-01

Axonal pathology has been clearly implicated in neurodegenerative diseases making the compartmental culture of neurons a useful research tool. Primary neurons have already been cultured in compartmental microfluidic devices but their derivation from an animal is a time-consuming and difficult work and has a limit in their sources. Embryonic stem cell (ESC)-derived neurons (ESC_Ns) overcome this limit, since ESCs can be renewed without limit and can be differentiated into ESC_Ns by robust and reproducible protocols. In this research, ESC_Ns were derived from mouse ESCs in compartmental microfluidic devices, and their axons were isolated from the somal cell bodies. Once embryoid bodies (EBs) were localized in the microfluidic culture chamber, ESC_Ns spread out from the EBs and occupied the cell culture chamber. Their axons traversed the microchannels and finally were isolated from the somata, providing an arrangement comparable to dissociated primary neurons. This ESC_N compartmental microfluidic culture system not only offers a substitute for the primary neuron counterpart system but also makes it possible to make comparisons between the two systems.

A single microfluidic chip with dual surface properties for protein drug delivery.

PubMed

Bokharaei, Mehrdad; Saatchi, Katayoun; Häfeli, Urs O

2017-04-15

Principles of double emulsion generation were incorporated in a glass microfluidic chip fabricated with two different surface properties in order to produce protein loaded polymer microspheres. The microspheres were produced by integrating two microfluidic flow focusing systems and a multi-step droplet splitting and mixing system into one chip. The chip consists of a hydrophobic and a hydrophilic section with two different heights, 12μm and 45μm, respectively. As a result, the protein is homogenously distributed throughout the polymer microsphere matrix, not just in its center (which has been studied before). In our work, the inner phase was bovine serum albumin (BSA) in phosphate buffered saline, the disperse phase was poly (lactic acid) in chloroform and the continuous phase was an aqueous solution of poly(vinyl alcohol). After solvent removal, BSA loaded microspheres with an encapsulation efficiency of up to 96% were obtained. Our results show the feasibility of producing microspheres loaded with a hydrophilic drug in a microfluidic system that integrates different microfluidic units into one chip. Copyright © 2017 Elsevier B.V. All rights reserved.

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

PubMed

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

2016-02-21

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

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

NASA Astrophysics Data System (ADS)

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

2008-02-01

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

QPatch: the past, present and future of automated patch clamp.

PubMed

Mathes, Chris

2006-04-01

The QPatch 16 significantly increases throughput for gigaseal patch clamp experiments, making direct measurements in ion channel drug discovery and safety testing feasible. Released to the market in the Autumn of 2004 by Sophion Bioscience, the QPatch originated from work done at NeuroSearch (Denmark) in the early days of automated patch clamp. Today, the QPatch provides many unique features. For example, only the QPatch includes an automated cell preparation station making several hours of unattended operation possible. The 16-channel electrode array, called the QPlate, includes glass-coated microfluidic channels for less compound absorption and, hence, more accurate IC(50) values. The microfluidic pathways also allow for very small amounts of compound used for each experiment ( approximately 5 microl per addition). Only the QPatch has four independent pipetting heads for more efficient liquid handling (especially for ligand-gated ion channel experiments). Patch clamp recordings with the QPatch match the high quality of conventional patch clamp and in some cases the results are even better. For example, only the QPatch includes 100% series resistance compensation for the elimination of false positives due to voltage errors. Finally, the modular QPatch 16 was designed with more channels in mind. The upgrade pathway to 48-channels (the QPatch HT) will be discussed.

Multilayer Microfluidic Devices Created From A Single Photomask

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

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

2013-08-28

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

Membraneless seawater desalination

DOEpatents

Crooks, Richard A.; Knust, Kyle N.; Perdue, Robbyn K.

2018-04-03

Disclosed are microfluidic devices and systems for the desalination of water. The devices and systems can include an electrode configured to generate an electric field gradient in proximity to an intersection formed by the divergence of two microfluidic channels from an inlet channel. Under an applied bias and in the presence of a pressure driven flow of saltwater, the electric field gradient can preferentially direct ions in saltwater into one of the diverging microfluidic channels, while desalted water flows into second diverging channel. Also provided are methods of using the devices and systems described herein to decrease the salinity of water.

Modularity: An Application of General Systems Theory to Military Force Development

DTIC Science & Technology

2005-01-01

1999). Context, modularity, and the cultural constitution of development. In P. Lloyd & C. Fernyhough (Eds.), Lev Vygotsky : Critical assessments...of General Systems Theory to Military Force Development 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT...Prescribed by ANSI Std Z39-18 MODULARITY: AN APPLICATION OF GENERAL SYSTEMS THEORY TO MILITARY FORCE DEVELOPMENT 279 R SEARCH MODULARITY: AN APPLICATION OF

Multi-kilowatt modularized spacecraft power processing system development

NASA Technical Reports Server (NTRS)

Andrews, R. E.; Hayden, J. H.; Hedges, R. T.; Rehmann, D. W.

1975-01-01

A review of existing information pertaining to spacecraft power processing systems and equipment was accomplished with a view towards applicability to the modularization of multi-kilowatt power processors. Power requirements for future spacecraft were determined from the NASA mission model-shuttle systems payload data study which provided the limits for modular power equipment capabilities. Three power processing systems were compared to evaluation criteria to select the system best suited for modularity. The shunt regulated direct energy transfer system was selected by this analysis for a conceptual design effort which produced equipment specifications, schematics, envelope drawings, and power module configurations.

Design of a rapid magnetic microfluidic mixer

NASA Astrophysics Data System (ADS)

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

2015-11-01

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

Shrinking microbubbles with microfluidics: mathematical modelling to control microbubble sizes.

PubMed

Salari, A; Gnyawali, V; Griffiths, I M; Karshafian, R; Kolios, M C; Tsai, S S H

2017-11-29

Microbubbles have applications in industry and life-sciences. In medicine, small encapsulated bubbles (<10 μm) are desirable because of their utility in drug/oxygen delivery, sonoporation, and ultrasound diagnostics. While there are various techniques for generating microbubbles, microfluidic methods are distinguished due to their precise control and ease-of-fabrication. Nevertheless, sub-10 μm diameter bubble generation using microfluidics remains challenging, and typically requires expensive equipment and cumbersome setups. Recently, our group reported a microfluidic platform that shrinks microbubbles to sub-10 μm diameters. The microfluidic platform utilizes a simple microbubble-generating flow-focusing geometry, integrated with a vacuum shrinkage system, to achieve microbubble sizes that are desirable in medicine, and pave the way to eventual clinical uptake of microfluidically generated microbubbles. A theoretical framework is now needed to relate the size of the microbubbles produced and the system's input parameters. In this manuscript, we characterize microbubbles made with various lipid concentrations flowing in solutions that have different interfacial tensions, and monitor the changes in bubble size along the microfluidic channel under various vacuum pressures. We use the physics governing the shrinkage mechanism to develop a mathematical model that predicts the resulting bubble sizes and elucidates the dominant parameters controlling bubble sizes. The model shows a good agreement with the experimental data, predicting the resulting microbubble sizes under different experimental input conditions. We anticipate that the model will find utility in enabling users of the microfluidic platform to engineer bubbles of specific sizes.

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

PubMed

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

2018-03-01

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

Bonded polyimide fuel cell package and method thereof

DOEpatents

Morse, Jeffrey D.; Jankowski, Alan; Graff, Robert T.; Bettencourt, Kerry

2005-11-01

Described herein are processes for fabricating microfluidic fuel cell systems with embedded components in which micron-scale features are formed by bonding layers of DuPont Kapton.TM. polyimide laminate. A microfluidic fuel cell system fabricated using this process is also described.

Method of preparation of bonded polyimide fuel cell package

DOEpatents

Morse, Jeffrey D [Martinez, CA; Jankowski, Alan [Livermore, CA; Graff, Robert T [Modesto, CA; Bettencourt, Kerry [Dublin, CA

2011-04-26

Described herein are processes for fabricating microfluidic fuel cell systems with embedded components in which micron-scale features are formed by bonding layers of DuPont Kapton.TM. polyimide laminate. A microfluidic fuel cell system fabricated using this process is also described.

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

PubMed

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

2016-04-01

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

Centrifugal Microfluidic System for Nucleic Acid Amplification and Detection

PubMed Central

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

2015-01-01

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

Droplet microfluidics for single-cell analysis.

PubMed

Brouzes, Eric

2012-01-01

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

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

Actuation of digital micro drops by electrowetting on open microfluidic chips fabricated in photolithography.

PubMed

Ko, Hyojin; Lee, Jeong Soo; Jung, Chan-Hee; Choi, Jae-Hak; Kwon, Oh-Sun; Shin, Kwanwoo

2014-08-01

Basic manipulations of discrete liquid drops on opened microfluidic chips based on electrowetting on dielectrics were described. While most developed microfluidic chips are closed systems equipped with a top plate to cover mechanically and to contact electrically to drop samples, our chips are opened systems with a single plate without any electric contact to drops directly. The chips consist of a linear array of patterned electrodes at 1.8 mm pitch was fabricated on a glass plate coated with thin hydrophobic and dielectric layers by using various methods including photolithography, spin coating and ion sputtering. Several actuations such as lateral oscillation, colliding mergence and translational motion for 3-10 μL water drops have been demonstrated satisfactory. All these kinetic performances of opened chips were similar to those of closed chip systems, indicating superiority of a none-contact method for the transport of drops on opened microfluidic chips actuated by using electrowetting technique.

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

PubMed

Lo, Shih-Jie; Yao, Da-Jeng

2015-07-23

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

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

PubMed Central

Lo, Shih-Jie; Yao, Da-Jeng

2015-01-01

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

Microfluidic technology for molecular diagnostics.

PubMed

Robinson, Tom; Dittrich, Petra S

2013-01-01

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

A Modular Robotic System with Applications to Space Exploration

NASA Technical Reports Server (NTRS)

Hancher, Matthew D.; Hornby, Gregory S.

2006-01-01

Modular robotic systems offer potential advantages as versatile, fault-tolerant, cost-effective platforms for space exploration, but a sufficiently mature system is not yet available. We describe the possible applications of such a system, and present prototype hardware intended as a step in the right direction. We also present elements of an automated design and optimization framework aimed at making modular robots easier to design and use, and discuss the results of applying the system to a gait optimization problem. Finally, we discuss the potential near-term applications of modular robotics to terrestrial robotics research.

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.

Army and Marine Corps Active Protection System (APS) Efforts

DTIC Science & Technology

2016-08-30

efforts—the Expedited, Non-Developmental Item (NDI) APS effort and the Modular Active Protection System (MAPS) effort. The Marines describe their...17 Modular Active Protection System (MAPS) Effort .......................................................... 18 The Marine Corps APS...Merkava Mark 4 tank was designed around the Trophy APS. 32 The Army’s Modular Active Protection System (MAPS) effort, described below, is intended to

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.

Digital Microfluidic Dynamic Culture of Mammalian Embryos on an Electrowetting on Dielectric (EWOD) Chip

PubMed Central

Huang, Hong-Yuan; Shen, Hsien-Hua; Tien, Chang-Hung; Li, Chin-Jung; Fan, Shih-Kang; Liu, Cheng-Hsien; Hsu, Wen-Syang; Yao, Da-Jeng

2015-01-01

Current human fertilization in vitro (IVF) bypasses the female oviduct and manually inseminates, fertilizes and cultivates embryos in a static microdrop containing appropriate chemical compounds. A microfluidic microchannel system for IVF is considered to provide an improved in-vivo-mimicking environment to enhance the development in a culture system for an embryo before implantation. We demonstrate a novel digitalized microfluidic device powered with electrowetting on a dielectric (EWOD) to culture an embryo in vitro in a single droplet in a microfluidic environment to mimic the environment in vivo for development of the embryo and to culture the embryos with good development and live births. Our results show that the dynamic culture powered with EWOD can manipulate a single droplet containing one mouse embryo and culture to the blastocyst stage. The rate of embryo cleavage to a hatching blastocyst with a dynamic culture is significantly greater than that with a traditional static culture (p<0.05). The EWOD chip enhances the culture of mouse embryos in a dynamic environment. To test the reproductive outcome of the embryos collected from an EWOD chip as a culture system, we transferred embryos to pseudo-pregnant female mice and produced live births. These results demonstrate that an EWOD-based microfluidic device is capable of culturing mammalian embryos in a microfluidic biological manner, presaging future clinical application. PMID:25933003

Digital Microfluidic Dynamic Culture of Mammalian Embryos on an Electrowetting on Dielectric (EWOD) Chip.

PubMed

Huang, Hong-Yuan; Shen, Hsien-Hua; Tien, Chang-Hung; Li, Chin-Jung; Fan, Shih-Kang; Liu, Cheng-Hsien; Hsu, Wen-Syang; Yao, Da-Jeng

2015-01-01

Current human fertilization in vitro (IVF) bypasses the female oviduct and manually inseminates, fertilizes and cultivates embryos in a static microdrop containing appropriate chemical compounds. A microfluidic microchannel system for IVF is considered to provide an improved in-vivo-mimicking environment to enhance the development in a culture system for an embryo before implantation. We demonstrate a novel digitalized microfluidic device powered with electrowetting on a dielectric (EWOD) to culture an embryo in vitro in a single droplet in a microfluidic environment to mimic the environment in vivo for development of the embryo and to culture the embryos with good development and live births. Our results show that the dynamic culture powered with EWOD can manipulate a single droplet containing one mouse embryo and culture to the blastocyst stage. The rate of embryo cleavage to a hatching blastocyst with a dynamic culture is significantly greater than that with a traditional static culture (p<0.05). The EWOD chip enhances the culture of mouse embryos in a dynamic environment. To test the reproductive outcome of the embryos collected from an EWOD chip as a culture system, we transferred embryos to pseudo-pregnant female mice and produced live births. These results demonstrate that an EWOD-based microfluidic device is capable of culturing mammalian embryos in a microfluidic biological manner, presaging future clinical application.

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

NASA Astrophysics Data System (ADS)

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

2018-04-01

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

Temperature-programmed natural convection for micromixing and biochemical reaction in a single microfluidic chamber.

PubMed

Kim, Sung-Jin; Wang, Fang; Burns, Mark A; Kurabayashi, Katsuo

2009-06-01

Micromixing is a crucial step for biochemical reactions in microfluidic networks. A critical challenge is that the system containing micromixers needs numerous pumps, chambers, and channels not only for the micromixing but also for the biochemical reactions and detections. Thus, a simple and compatible design of the micromixer element for the system is essential. Here, we propose a simple, yet effective, scheme that enables micromixing and a biochemical reaction in a single microfluidic chamber without using any pumps. We accomplish this process by using natural convection in conjunction with alternating heating of two heaters for efficient micromixing, and by regulating capillarity for sample transport. As a model application, we demonstrate micromixing and subsequent polymerase chain reaction (PCR) for an influenza viral DNA fragment. This process is achieved in a platform of a microfluidic cartridge and a microfabricated heating-instrument with a fast thermal response. Our results will significantly simplify micromixing and a subsequent biochemical reaction that involves reagent heating in microfluidic networks.

Parallel microfluidic synthesis of size-tunable polymeric nanoparticles using 3D flow focusing towards in vivo study

PubMed Central

Lim, Jong-Min; Bertrand, Nicolas; Valencia, Pedro M.; Rhee, Minsoung; Langer, Robert; Jon, Sangyong; Farokhzad, Omid C.; Karnik, Rohit

2014-01-01

Microfluidic synthesis of nanoparticles (NPs) can enhance the controllability and reproducibility in physicochemical properties of NPs compared to bulk synthesis methods. However, applications of microfluidic synthesis are typically limited to in vitro studies due to low production rates. Herein, we report the parallelization of NP synthesis by 3D hydrodynamic flow focusing (HFF) using a multilayer microfluidic system to enhance the production rate without losing the advantages of reproducibility, controllability, and robustness. Using parallel 3D HFF, polymeric poly(lactide-co-glycolide)-b-polyethyleneglycol (PLGA-PEG) NPs with sizes tunable in the range of 13–150 nm could be synthesized reproducibly with high production rate. As a proof of concept, we used this system to perform in vivo pharmacokinetic and biodistribution study of small (20 nm diameter) PLGA-PEG NPs that are otherwise difficult to synthesize. Microfluidic parallelization thus enables synthesis of NPs with tunable properties with production rates suitable for both in vitro and in vivo studies. PMID:23969105

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.

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

PubMed

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

2018-06-21

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

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

PubMed

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

2017-04-01

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

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

PubMed

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

2016-06-01

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

Lab-On-a-Chip Application Development (LOCAD): Bridging Technology Readiness for Exploration

NASA Technical Reports Server (NTRS)

Spearing, Scott F.; Jenkins, Andy

2004-01-01

At Marshall Space Flight Center we have established a capability to investigate the use of microfluidics for space flight. The Lab-On-a-Chip Application Development (LOCAD) team has created a program for advancing Technology Readiness Levels (TRL) of 1 and 2 to TRL 6 and 7, quickly and economically for Lab-On-a-Chip (LOC) applications. Scientists and engineers can utilize LOCAD'S process to efficiently learn about microfluidics and determine if microfluidics is applicable to their needs. Once the applicability has been determined, LOCAD can then perform tests to develop the new fluidic protocols which are different from macro-scale chemical reaction protocols. With this information new micro-fluidic devices can be created and tested. Currently, LOCAD is focused on using microfluidics for both Environmental Monitoring & Control, and Medical Systems. Eventually, handheld portable units utilizing LOC technology will perform rapid tests to determine water quality, and microbial contamination levels. Since LOC technology is drastically reduced in physical size, it thereby reduces power, weight, volume, and sample requirements, a big advantage considering the resource constraints associated with spaceflight. Another one of LOCAD's current activities is the development of a microfluidic system to aid in the search for life on Mars.

Machine vision for digital microfluidics

NASA Astrophysics Data System (ADS)

Shin, Yong-Jun; Lee, Jeong-Bong

2010-01-01

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

Spontaneous oscillations in microfluidic networks

NASA Astrophysics Data System (ADS)

Case, Daniel; Angilella, Jean-Regis; Motter, Adilson

2017-11-01

Precisely controlling flows within microfluidic systems is often difficult which typically results in systems being heavily reliant on numerous external pumps and computers. Here, I present a simple microfluidic network that exhibits flow rate switching, bistablity, and spontaneous oscillations controlled by a single pressure. That is, by solely changing the driving pressure, it is possible to switch between an oscillating and steady flow state. Such functionality does not rely on external hardware and may even serve as an on-chip memory or timing mechanism. I use an analytic model and rigorous fluid dynamics simulations to show these results.

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.

Magnetohydrodynamic pump with a system for promoting flow of fluid in one direction

DOEpatents

Lemoff, Asuncion V [Union City, CA; Lee, Abraham P [Irvine, CA

2010-07-13

A magnetohydrodynamic pump for pumping a fluid. The pump includes a microfluidic channel for channeling the fluid, a MHD electrode/magnet system operatively connected to the microfluidic channel, and a system for promoting flow of the fluid in one direction in the microfluidic channel. The pump has uses in the medical and biotechnology industries for blood-cell-separation equipment, biochemical assays, chemical synthesis, genetic analysis, drug screening, an array of antigen-antibody reactions, combinatorial chemistry, drug testing, medical and biological diagnostics, and combinatorial chemistry. The pump also has uses in electrochromatography, surface micromachining, laser ablation, inkjet printers, and mechanical micromilling.

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

PubMed

Jung, Taekeon; Yang, Sung

2015-05-21

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

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

PubMed Central

Jung, Taekeon; Yang, Sung

2015-01-01

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

An open-access microfluidic model for lung-specific functional studies at an air-liquid interface.

PubMed

Nalayanda, Divya D; Puleo, Christopher; Fulton, William B; Sharpe, Leilani M; Wang, Tza-Huei; Abdullah, Fizan

2009-10-01

In an effort to improve the physiologic relevance of existing in vitro models for alveolar cells, we present a microfluidic platform which provides an air-interface in a dynamic system combining microfluidic and suspended membrane culture systems. Such a system provides the ability to manipulate multiple parameters on a single platform along with ease in cell seeding and manipulation. The current study presents a comparison of the efficacy of the hybrid system with conventional platforms using assays analyzing the maintenance of function and integrity of A549 alveolar epithelial cell monolayer cultures. The hybrid system incorporates bio-mimetic nourishment on the basal side of the epithelial cells along with an open system on the apical side of the cells exposed to air allowing for easy access for assays.

Microfluidic Technology: Uncovering the Mechanisms of Nanocrystal Nucleation and Growth.

PubMed

Lignos, Ioannis; Maceiczyk, Richard; deMello, Andrew J

2017-05-16

The controlled and reproducible formation of colloidal semiconductor nanocrystals (or quantum dots) is of central importance in nanoscale science and technology. The tunable size- and shape-dependent properties of such materials make them ideal candidates for the development of efficient and low-cost displays, solar cells, light-emitting devices, and catalysts. The formidable difficulties associated with the macroscale preparation of semiconductor nanocrystals (possessing bespoke optical and chemical properties) result from the fact that underlying reaction mechanisms are complex and that the reactive environment is difficult to control. Automated microfluidic reactors coupled with monitoring systems and optimization algorithms aim to elucidate complex reaction mechanisms that govern both nucleation and growth of nanocrystals. Such platforms are ideally suited for the efficient optimization of reaction parameters, assuring the reproducible synthesis of nanocrystals with user-defined properties. This Account aims to inform the nanomaterials community about how microfluidic technologies can supplement flask experimentation for the ensemble investigation of formation mechanisms and design of semiconductor nanocrystals. We present selected studies outlining the preparation of quantum dots using microfluidic systems with integrated analytics. Such microfluidic reaction systems leverage the ability to extract real-time information regarding optical, structural, and compositional characteristics of quantum dots during nucleation and growth stages. The Account further highlights our recent research activities focused on the development and application of droplet-based microfluidics with integrated optical detection systems for the efficient and rapid screening of reaction conditions and a better understanding of the mechanisms of quantum dot synthesis. We describe the features and operation of fully automated microfluidic reactors and their subsequent application to high-throughput parametric screening of metal chalcogenides (CdSe, PbS, PbSe, CdSeTe), ternary and core/shell heavy metal-free quantum dots (CuInS 2 , CuInS 2 /ZnS), and all-inorganic perovskite nanocrystals (CsPbX 3 , X = Cl, Br, I) syntheses. Critically, concurrent absorption and photoluminescence measurements on millisecond to second time scales allow the extraction of basic parameters governing nanocrystal formation. Moreover, experimental data obtained from such microfluidic platforms can be directly supported by theoretical models of nucleation and growth. To this end, we also describe the use of metamodeling algorithms able to accurately predict optimized conditions of CdSe synthesis using a minimal number of sample parameters. Importantly, we discuss future challenges that must be addressed before microfluidic technologies are in a position to be widely adopted for the on-demand formation of nanocrystals. From a technology perspective, these challenges include the development of novel engineering platforms for the formation of complex architectures, the integration of monitoring systems able to harvest photophysical and structural information, the incorporation of continuous purification systems, and the application of optimization algorithms to multicomponent quantum dot systems.

High-Throughput Incubation and Quantification of Agglutination Assays in a Microfluidic System.

PubMed

Castro, David; Conchouso, David; Kodzius, Rimantas; Arevalo, Arpys; Foulds, Ian G

2018-06-04

In this paper, we present a two-phase microfluidic system capable of incubating and quantifying microbead-based agglutination assays. The microfluidic system is based on a simple fabrication solution, which requires only laboratory tubing filled with carrier oil, driven by negative pressure using a syringe pump. We provide a user-friendly interface, in which a pipette is used to insert single droplets of a 1.25-µL volume into a system that is continuously running and therefore works entirely on demand without the need for stopping, resetting or washing the system. These assays are incubated by highly efficient passive mixing with a sample-to-answer time of 2.5 min, a 5⁻10-fold improvement over traditional agglutination assays. We study system parameters such as channel length, incubation time and flow speed to select optimal assay conditions, using the streptavidin-biotin interaction as a model analyte quantified using optical image processing. We then investigate the effect of changing the concentration of both analyte and microbead concentrations, with a minimum detection limit of 100 ng/mL. The system can be both low- and high-throughput, depending on the rate at which assays are inserted. In our experiments, we were able to easily produce throughputs of 360 assays per hour by simple manual pipetting, which could be increased even further by automation and parallelization. Agglutination assays are a versatile tool, capable of detecting an ever-growing catalog of infectious diseases, proteins and metabolites. A system such as this one is a step towards being able to produce high-throughput microfluidic diagnostic solutions with widespread adoption. The development of analytical techniques in the microfluidic format, such as the one presented in this work, is an important step in being able to continuously monitor the performance and microfluidic outputs of organ-on-chip devices.

Paper pump for passive and programmable transport

PubMed Central

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

2013-01-01

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

Modular optical detector system

DOEpatents

Horn, Brent A [Livermore, CA; Renzi, Ronald F [Tracy, CA

2006-02-14

A modular optical detector system. The detector system is designed to detect the presence of molecules or molecular species by inducing fluorescence with exciting radiation and detecting the emitted fluorescence. Because the system is capable of accurately detecting and measuring picomolar concentrations it is ideally suited for use with microchemical analysis systems generally and capillary chromatographic systems in particular. By employing a modular design, the detector system provides both the ability to replace various elements of the detector system without requiring extensive realignment or recalibration of the components as well as minimal user interaction with the system. In addition, the modular concept provides for the use and addition of a wide variety of components, including optical elements (lenses and filters), light sources, and detection means, to fit particular needs.

Development of a Commercially Viable, Modular Autonomous Robotic Systems for Converting any Vehicle to Autonomous Control

NASA Technical Reports Server (NTRS)

Parish, David W.; Grabbe, Robert D.; Marzwell, Neville I.

1994-01-01

A Modular Autonomous Robotic System (MARS), consisting of a modular autonomous vehicle control system that can be retrofit on to any vehicle to convert it to autonomous control and support a modular payload for multiple applications is being developed. The MARS design is scalable, reconfigurable, and cost effective due to the use of modern open system architecture design methodologies, including serial control bus technology to simplify system wiring and enhance scalability. The design is augmented with modular, object oriented (C++) software implementing a hierarchy of five levels of control including teleoperated, continuous guidepath following, periodic guidepath following, absolute position autonomous navigation, and relative position autonomous navigation. The present effort is focused on producing a system that is commercially viable for routine autonomous patrolling of known, semistructured environments, like environmental monitoring of chemical and petroleum refineries, exterior physical security and surveillance, perimeter patrolling, and intrafacility transport applications.

The Rotary Zone Thermal Cycler: A Low-Power System Enabling Automated Rapid PCR

PubMed Central

Bartsch, Michael S.; Renzi, Ronald F.; Van de Vreugde, James L.; Kim, Hanyoup; Knight, Daniel L.; Sinha, Anupama; Branda, Steven S.; Patel, Kamlesh D.

2015-01-01

Advances in molecular biology, microfluidics, and laboratory automation continue to expand the accessibility and applicability of these methods beyond the confines of conventional, centralized laboratory facilities and into point of use roles in clinical, military, forensic, and field-deployed applications. As a result, there is a growing need to adapt the unit operations of molecular biology (e.g., aliquoting, centrifuging, mixing, and thermal cycling) to compact, portable, low-power, and automation-ready formats. Here we present one such adaptation, the rotary zone thermal cycler (RZTC), a novel wheel-based device capable of cycling up to four different fixed-temperature blocks into contact with a stationary 4-microliter capillary-bound sample to realize 1-3 second transitions with steady state heater power of less than 10 W. We demonstrate the utility of the RZTC for DNA amplification as part of a highly integrated rotary zone PCR (rzPCR) system that uses low-volume valves and syringe-based fluid handling to automate sample loading and unloading, thermal cycling, and between-run cleaning functionalities in a compact, modular form factor. In addition to characterizing the performance of the RZTC and the efficacy of different online cleaning protocols, we present preliminary results for rapid single-plex PCR, multiplex short tandem repeat (STR) amplification, and second strand cDNA synthesis. PMID:25826708

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.

Biochemical analysis with microfluidic systems.

PubMed

Bilitewski, Ursula; Genrich, Meike; Kadow, Sabine; Mersal, Gaber

2003-10-01

Microfluidic systems are capillary networks of varying complexity fabricated originally in silicon, but nowadays in glass and polymeric substrates. Flow of liquid is mainly controlled by use of electroosmotic effects, i.e. application of electric fields, in addition to pressurized flow, i.e. application of pressure or vacuum. Because electroosmotic flow rates depend on the charge densities on the walls of capillaries, they are influenced by substrate material, fabrication processes, surface pretreatment procedures, and buffer additives. Microfluidic systems combine the properties of capillary electrophoretic systems and flow-through analytical systems, and thus biochemical analytical assays have been developed utilizing and integrating both aspects. Proteins, peptides, and nucleic acids can be separated because of their different electrophoretic mobility; detection is achieved with fluorescence detectors. For protein analysis, in particular, interfaces between microfluidic chips and mass spectrometers were developed. Further levels of integration of required sample-treatment steps were achieved by integration of protein digestion by immobilized trypsin and amplification of nucleic acids by the polymerase chain reaction. Kinetic constants of enzyme reactions were determined by adjusting different degrees of dilution of enzyme substrates or inhibitors within a single chip utilizing mainly the properties of controlled dosing and mixing liquids within a chip. For analysis of kinase reactions, however, a combination of a reaction step (enzyme with substrate and inhibitor) and a separation step (enzyme substrate and reaction product) was required. Microfluidic chips also enable separation of analytes from sample matrix constituents, which can interfere with quantitative determination, if they have different electrophoretic mobilities. In addition to analysis of nucleic acids and enzymes, immunoassays are the third group of analytical assays performed in microfluidic chips. They utilize either affinity capillary electrophoresis as a homogeneous assay format, or immobilized antigens or antibodies in heterogeneous assays with serial supply of reagents and washing solutions.

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

PubMed

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

2008-11-01

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

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.

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

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

PubMed Central

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

2016-01-01

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

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.

Telepathology: design of a modular system.

PubMed

Brauchli, K; Christen, H; Meyer, P; Haroske, G; Meyer, W; Kunze, K D; Otto, R; Oberholzer, M

2000-01-01

Although telepathology systems have been developed for more than a decade, they are still not a widespread tool for routine diagnostic applications. Lacking interoperability, software that is not satisfying user needs as well as high costs have been identified as reasons. In this paper we would like to demonstrate that with a clear separation of the tasks required for a telepathology application, telepathology systems can be built in a modular way, where many modules can be implemented using standard software components. With such a modular design, systems can be easily adapted to changing user needs and new technological developments and it is easier to integrate modular systems into existing environments.

Systems, devices, and methods for agglutination assays using sedimentation

DOEpatents

Schaff, Ulrich Y.; Sommer, Gregory J.; Singh, Anup K.

2016-01-26

Embodiments of the present invention include methods for conducting agglutination assays using sedimentation. Aggregates may be exposed to sedimentation forces and travel through a density medium to a detection area. Microfluidic devices, such as microfluidic disks, are described for conducting the agglutination assays, as are systems for conducting the assays.

Giant Volume Change of Active Gels under Continuous Flow

DTIC Science & Technology

2014-04-21

harnessing chemical energy to produce motion, for example, using the energy released by ATP hydrolysis to power the directed movement of muscle fibers or micro ...microfluidic systems to generate capsules of biopolymer hydrogels, Herr demonstrated the use of gels for automated microfluidic protein blotting,13 Wu...active gels driven by the Belousov−Zhabotinsky reaction. These results demon- strate that microfluidics offers a useful and facile experimental

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

DTIC Science & Technology

2005-10-15

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

Multi-layer plastic/glass microfluidic systems containing electrical and mechanical functionality.

PubMed

Han, Arum; Wang, Olivia; Graff, Mason; Mohanty, Swomitra K; Edwards, Thayne L; Han, Ki-Ho; Bruno Frazier, A

2003-08-01

This paper describes an approach for fabricating multi-layer microfluidic systems from a combination of glass and plastic materials. Methods and characterization results for the microfabrication technologies underlying the process flow are presented. The approach is used to fabricate and characterize multi-layer plastic/glass microfluidic systems containing electrical and mechanical functionality. Hot embossing, heat staking of plastics, injection molding, microstenciling of electrodes, and stereolithography were combined with conventional MEMS fabrication techniques to realize the multi-layer systems. The approach enabled the integration of multiple plastic/glass materials into a single monolithic system, provided a solution for the integration of electrical functionality throughout the system, provided a mechanism for the inclusion of microactuators such as micropumps/valves, and provided an interconnect technology for interfacing fluids and electrical components between the micro system and the macro world.

A new approach for modular robot system behavioral modeling: Base on Petri net and category theory

NASA Astrophysics Data System (ADS)

Zhang, Yun; Wei, Hongxing; Yang, Bo

2018-04-01

To design modular robot system, Petri nets and category theory are combined and the ability of simulation of Petri net is discussed. According to category theory, the method of describing the category of components in the dynamic characteristics of the system is deduced. Moreover, a modular robot system is analyzed, which provides a verifiable description of the dynamic characteristics of the system.

A modular optical sensor

NASA Astrophysics Data System (ADS)

Conklin, John Albert

This dissertation presents the design of a modular, fiber-optic sensor and the results obtained from testing the modular sensor. The modular fiber-optic sensor is constructed in such manner that the sensor diaphragm can be replaced with different configurations to detect numerous physical phenomena. Additionally, different fiber-optic detection systems can be attached to the sensor. Initially, the modular sensor was developed to be used by university of students to investigate realistic optical sensors and detection systems to prepare for advance studies of micro-optical mechanical systems (MOMS). The design accomplishes this by doing two things. First, the design significantly lowers the costs associated with studying optical sensors by modularizing the sensor design. Second, the sensor broadens the number of physical phenomena that students can apply optical sensing techniques to in a fiber optics sensor course. The dissertation is divided into seven chapters covering the historical development of fiber-optic sensors, a theoretical overview of fiber-optic sensors, the design, fabrication, and the testing of the modular sensor developed in the course of this work. Chapter 1 discusses, in detail, how this dissertation is organized and states the purpose of the dissertation. Chapter 2 presents an historical overview of the development of optical fibers, optical pressure sensors, and fibers, optical pressure sensors, and optical microphones. Chapter 3 reviews the theory of multi-fiber optic detection systems, optical microphones, and pressure sensors. Chapter 4 presents the design details of the modular, optical sensor. Chapter 5 delves into how the modular sensor is fabricated and how the detection systems are constructed. Chapter 6 presents the data collected from the microphone and pressure sensor configurations of the modular sensor. Finally, Chapter 7 discusses the data collected and draws conclusions about the design based on the data collected. Chapter 7 also presents future work needed to expand the functionality and utility of the modular sensor.

On the role of sparseness in the evolution of modularity in gene regulatory networks

PubMed Central

2018-01-01

Modularity is a widespread property in biological systems. It implies that interactions occur mainly within groups of system elements. A modular arrangement facilitates adjustment of one module without perturbing the rest of the system. Therefore, modularity of developmental mechanisms is a major factor for evolvability, the potential to produce beneficial variation from random genetic change. Understanding how modularity evolves in gene regulatory networks, that create the distinct gene activity patterns that characterize different parts of an organism, is key to developmental and evolutionary biology. One hypothesis for the evolution of modules suggests that interactions between some sets of genes become maladaptive when selection favours additional gene activity patterns. The removal of such interactions by selection would result in the formation of modules. A second hypothesis suggests that modularity evolves in response to sparseness, the scarcity of interactions within a system. Here I simulate the evolution of gene regulatory networks and analyse diverse experimentally sustained networks to study the relationship between sparseness and modularity. My results suggest that sparseness alone is neither sufficient nor necessary to explain modularity in gene regulatory networks. However, sparseness amplifies the effects of forms of selection that, like selection for additional gene activity patterns, already produce an increase in modularity. That evolution of new gene activity patterns is frequent across evolution also supports that it is a major factor in the evolution of modularity. That sparseness is widespread across gene regulatory networks indicates that it may have facilitated the evolution of modules in a wide variety of cases. PMID:29775459

On the role of sparseness in the evolution of modularity in gene regulatory networks.

PubMed

Espinosa-Soto, Carlos

2018-05-01

Modularity is a widespread property in biological systems. It implies that interactions occur mainly within groups of system elements. A modular arrangement facilitates adjustment of one module without perturbing the rest of the system. Therefore, modularity of developmental mechanisms is a major factor for evolvability, the potential to produce beneficial variation from random genetic change. Understanding how modularity evolves in gene regulatory networks, that create the distinct gene activity patterns that characterize different parts of an organism, is key to developmental and evolutionary biology. One hypothesis for the evolution of modules suggests that interactions between some sets of genes become maladaptive when selection favours additional gene activity patterns. The removal of such interactions by selection would result in the formation of modules. A second hypothesis suggests that modularity evolves in response to sparseness, the scarcity of interactions within a system. Here I simulate the evolution of gene regulatory networks and analyse diverse experimentally sustained networks to study the relationship between sparseness and modularity. My results suggest that sparseness alone is neither sufficient nor necessary to explain modularity in gene regulatory networks. However, sparseness amplifies the effects of forms of selection that, like selection for additional gene activity patterns, already produce an increase in modularity. That evolution of new gene activity patterns is frequent across evolution also supports that it is a major factor in the evolution of modularity. That sparseness is widespread across gene regulatory networks indicates that it may have facilitated the evolution of modules in a wide variety of cases.

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.

A Modular Laser Graphics Projection System

NASA Astrophysics Data System (ADS)

Newswanger, Craig D.

1984-05-01

WED Enterprises has designed and built a modular projection system for the presentation of animated laser shows. This system was designed specifically for use in Disney theme shows. Its modular design allows it to be adapted to many show situations with simple hardware and software adjustments. The primary goals were superior animation, long life, low maintenance and stand alone operation.

Design of a modular digital computer system, DRL 4. [for meeting future requirements of spaceborne computers

NASA Technical Reports Server (NTRS)

1972-01-01

The design is reported of an advanced modular computer system designated the Automatically Reconfigurable Modular Multiprocessor System, which anticipates requirements for higher computing capacity and reliability for future spaceborne computers. Subjects discussed include: an overview of the architecture, mission analysis, synchronous and nonsynchronous scheduling control, reliability, and data transmission.

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.

Electric field-decoupled electroosmotic pump for microfluidic devices.

PubMed

Liu, Shaorong; Pu, Qiaosheng; Lu, Joann J

2003-09-26

An electric field-free electroosmotic pump has been constructed and its pumping rate has been measured under various experimental conditions. The key component of the pump is an ion-exchange membrane grounding joint that serves two major functions: (i) to maintain fluid continuity between pump channels and microfluidic conduit and (ii) to ground the solution in the microfluidic channel at the joint through an external electrode, and hence to decouple the electric field applied to the pump channels from the rest of the microfluidic system. A theoretical model has been developed to calculate the pumping rates and its validity has been demonstrated.

Large-scale modular biofiltration system for effective odor removal in a composting facility.

PubMed

Lin, Yueh-Hsien; Chen, Yu-Pei; Ho, Kuo-Ling; Lee, Tsung-Yih; Tseng, Ching-Ping

2013-01-01

Several different foul odors such as nitrogen-containing groups, sulfur-containing groups, and short-chain fatty-acids commonly emitted from composting facilities. In this study, an experimental laboratory-scale bioreactor was scaled up to build a large-scale modular biofiltration system that can process 34 m(3)min(-1)waste gases. This modular reactor system was proven effective in eliminating odors, with a 97% removal efficiency for 96 ppm ammonia, a 98% removal efficiency for 220 ppm amines, and a 100% removal efficiency of other odorous substances. The results of operational parameters indicate that this modular biofiltration system offers long-term operational stability. Specifically, a low pressure drop (<45 mmH2O m(-1)) was observed, indicating that the packing carrier in bioreactor units does not require frequent replacement. Thus, this modular biofiltration system can be used in field applications to eliminate various odors with compact working volume.

Microfluidics to Mimic Blood Flow in Health and Disease

NASA Astrophysics Data System (ADS)

Sebastian, Bernhard; Dittrich, Petra S.

2018-01-01

Throughout history, capillary systems have aided the establishment of the fundamental laws of blood flow and its non-Newtonian properties. The advent of microfluidics technology in the 1990s propelled the development of highly integrated lab-on-a-chip platforms that allow highly accurate replication of vascular systems' dimensions, mechanical properties, and biological complexity. Applications include the detection of pathological changes to red blood cells, white blood cells, and platelets at unparalleled sensitivity and the efficacy assessment of drug treatment. Recent efforts have aimed at the development of microfluidics-based tests usable in a clinial environment or the replication of more complex diseases such as thrombosis. These microfluidic disease models enable the study of onset and progression of disease as well as the identification of key players and risk factors, which have led to a spectrum of clinically relevant findings.

A dynamic bead-based microarray for parallel DNA detection

NASA Astrophysics Data System (ADS)

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

2011-05-01

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

Microfluidic bead-based diodes with targeted circular microchannels for low Reynolds number applications.

PubMed

Sochol, Ryan D; Lu, Albert; Lei, Jonathan; Iwai, Kosuke; Lee, Luke P; Lin, Liwei

2014-05-07

Self-regulating fluidic components are critical to the advancement of microfluidic processors for chemical and biological applications, such as sample preparation on chip, point-of-care molecular diagnostics, and implantable drug delivery devices. Although researchers have developed a wide range of components to enable flow rectification in fluidic systems, engineering microfluidic diodes that function at the low Reynolds number (Re) flows and smaller scales of emerging micro/nanofluidic platforms has remained a considerable challenge. Recently, researchers have demonstrated microfluidic diodes that utilize high numbers of suspended microbeads as dynamic resistive elements; however, using spherical particles to block fluid flow through rectangular microchannels is inherently limited. To overcome this issue, here we present a single-layer microfluidic bead-based diode (18 μm in height) that uses a targeted circular-shaped microchannel for the docking of a single microbead (15 μm in diameter) to rectify fluid flow under low Re conditions. Three-dimensional simulations and experimental results revealed that adjusting the docking channel geometry and size to better match the suspended microbead greatly increased the diodicity (Di) performance. Arraying multiple bead-based diodes in parallel was found to adversely affect system efficacy, while arraying multiple diodes in series was observed to enhance device performance. In particular, systems consisting of four microfluidic bead-based diodes with targeted circular-shaped docking channels in series revealed average Di's ranging from 2.72 ± 0.41 to 10.21 ± 1.53 corresponding to Re varying from 0.1 to 0.6.

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

Automatic sequential fluid handling with multilayer microfluidic sample isolated pumping

PubMed Central

Liu, Jixiao; Fu, Hai; Yang, Tianhang; Li, Songjing

2015-01-01

To sequentially handle fluids is of great significance in quantitative biology, analytical chemistry, and bioassays. However, the technological options are limited when building such microfluidic sequential processing systems, and one of the encountered challenges is the need for reliable, efficient, and mass-production available microfluidic pumping methods. Herein, we present a bubble-free and pumping-control unified liquid handling method that is compatible with large-scale manufacture, termed multilayer microfluidic sample isolated pumping (mμSIP). The core part of the mμSIP is the selective permeable membrane that isolates the fluidic layer from the pneumatic layer. The air diffusion from the fluidic channel network into the degassing pneumatic channel network leads to fluidic channel pressure variation, which further results in consistent bubble-free liquid pumping into the channels and the dead-end chambers. We characterize the mμSIP by comparing the fluidic actuation processes with different parameters and a flow rate range of 0.013 μl/s to 0.097 μl/s is observed in the experiments. As the proof of concept, we demonstrate an automatic sequential fluid handling system aiming at digital assays and immunoassays, which further proves the unified pumping-control and suggests that the mμSIP is suitable for functional microfluidic assays with minimal operations. We believe that the mμSIP technology and demonstrated automatic sequential fluid handling system would enrich the microfluidic toolbox and benefit further inventions. PMID:26487904

Verification of the Seismic Performance of a Rigidly Connected Modular System Depending on the Shape and Size of the Ceiling Bracket.

PubMed

Lee, Seungjae; Park, Jaeseong; Kwak, Euishin; Shon, Sudeok; Kang, Changhoon; Choi, Hosoon

2017-03-06

Modular systems have been mostly researched in relatively low-rise structures but, lately, their applications to mid- to high-rise structures began to be reviewed, and research interest in new modularization subjects has increased. The application of modular systems to mid- to high-rise structures requires the structural stability of the frame and connections that consist of units, and the evaluation of the stiffness of structures that are combined in units. However, the combination of general units causes loss of the cross-section of columns or beams, resulting in low seismic performance and hindering installation works in the field. In addition, the evaluation of a frame considering such a cross-sectional loss is not easy. Therefore, it is necessary to develop a joint that is stable and easy to install. In the study, a rigidly connected modular system was proposed as a moment-resisting frame for a unit modular system, and their joints were developed and their performances were compared. The proposed system changed the ceiling beam into a bracket type to fasten bolts. It can be merged with other seismic force-resisting systems. To verify the seismic performance of the proposed system, a cyclic loading test was conducted, and the rigidly connected joint performance and integrated behavior at the joint of modular units were investigated. From the experimental results, the maximum resisting force of the proposed connection exceeded the theoretical parameters, indicating that a rigid joint structural performance could be secured.

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.

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.

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.

Automatic Modeling and Simulation of Modular Robots

NASA Astrophysics Data System (ADS)

Jiang, C.; Wei, H.; Zhang, Y.

2018-03-01

The ability of reconfiguration makes modular robots have the ability of adaptable, low-cost, self-healing and fault-tolerant. It can also be applied to a variety of mission situations. In this manuscript, a robot platform which relied on the module library was designed, based on the screw theory and module theory. Then, the configuration design method of the modular robot was proposed. And the different configurations of modular robot system have been built, including industrial mechanical arms, the mobile platform, six-legged robot and 3D exoskeleton manipulator. Finally, the simulation and verification of one system among them have been made, using the analyses of screw kinematics and polynomial planning. The results of experiments demonstrate the feasibility and superiority of this modular system.

A microfluidic culture model of the human reproductive tract and 28-day menstrual cycle

PubMed Central

Xiao, Shuo; Coppeta, Jonathan R.; Rogers, Hunter B.; Isenberg, Brett C.; Zhu, Jie; Olalekan, Susan A.; McKinnon, Kelly E.; Dokic, Danijela; Rashedi, Alexandra S.; Haisenleder, Daniel J.; Malpani, Saurabh S.; Arnold-Murray, Chanel A.; Chen, Kuanwei; Jiang, Mingyang; Bai, Lu; Nguyen, Catherine T.; Zhang, Jiyang; Laronda, Monica M.; Hope, Thomas J.; Maniar, Kruti P.; Pavone, Mary Ellen; Avram, Michael J.; Sefton, Elizabeth C.; Getsios, Spiro; Burdette, Joanna E.; Kim, J. Julie; Borenstein, Jeffrey T.; Woodruff, Teresa K.

2017-01-01

The endocrine system dynamically controls tissue differentiation and homeostasis, but has not been studied using dynamic tissue culture paradigms. Here we show that a microfluidic system supports murine ovarian follicles to produce the human 28-day menstrual cycle hormone profile, which controls human female reproductive tract and peripheral tissue dynamics in single, dual and multiple unit microfluidic platforms (Solo-MFP, Duet-MFP and Quintet-MPF, respectively). These systems simulate the in vivo female reproductive tract and the endocrine loops between organ modules for the ovary, fallopian tube, uterus, cervix and liver, with a sustained circulating flow between all tissues. The reproductive tract tissues and peripheral organs integrated into a microfluidic platform, termed EVATAR, represents a powerful new in vitro tool that allows organ–organ integration of hormonal signalling as a phenocopy of menstrual cycle and pregnancy-like endocrine loops and has great potential to be used in drug discovery and toxicology studies. PMID:28350383

Drop mass transfer in a microfluidic chip compared to a centrifugal contactor

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

Nemer, Martin B.; Roberts, Christine C.; Hughes, Lindsey G.

2014-06-13

A model system was developed for enabling a multiscale understanding of centrifugal-contactor liquid–liquid extraction.The system consisted of Nd(III) + xylenol orange in the aqueous phase buffered to pH =5.5 by KHP, and dodecane + thenoyltrifluroroacetone (HTTA) + tributyphosphate (TBP) in the organic phase. Diffusion constants were measured for neodymium in both the organic and aqueous phases, and the Nd(III) partition coefficients were measured at various HTTA and TBP concentrations. A microfluidic channel was used as a high-shear model environment to observe mass-transfer on a droplet scale with xylenol orange as the aqueous-phase metal indicator; mass-transfer rates were measured quantitatively inmore » both diffusion and reaction limited regimes on the droplet scale. Lastly, the microfluidic results were comparable to observations made for the same system in a laboratory scale liquid–liquid centrifugal contactor, indicating that single drop microfluidic experiments can provide information on mass transfer in complicated flows and geometries.« less

Microfluidic Platform for Analyzing the Thermotaxis of C. elegans in a Linear Temperature Gradient.

PubMed

Yoon, Sunhee; Piao, Hailing; Jeon, Tae-Joon; Kim, Sun Min

2017-01-01

Caenorhabditis elegans (C. elegans), which shares a considerable amount of characteristics with human genes is one of the important model organisms for the study of behavioral responses. Thermotaxis is a representative behavior response of C. elegans; C. elegans stores the cultivation temperature in thermosensory neurons and moves to the cultivation temperature region in a temperature variation. In this study, we developed a microfluidic system for effective thermotaxis analysis of C. elegans. The microfluidic channel was fabricated using polydimethylsiloxane (PDMS) by soft lithography process. The temperature gradient (15 - 20°C) was generated in the microchannel and controlled by Peltier modules attached to the bottom of the channel. The thermotaxis of wild type (N2), tax-4(p678) and ttx-7(nj50) mutants were effectively analyzed using this microfluidic system. We believe that this system can be employed as a basic platform for studying the neural circuit of C. elegans responding to external stimuli.

Advanced Modular Power Approach to Affordable, Supportable Space Systems

NASA Technical Reports Server (NTRS)

Oeftering, Richard C.; Kimnach, Greg L.; Fincannon, James; Mckissock,, Barbara I.; Loyselle, Patricia L.; Wong, Edmond

2013-01-01

Recent studies of missions to the Moon, Mars and Near Earth Asteroids (NEA) indicate that these missions often involve several distinct separately launched vehicles that must ultimately be integrated together in-flight and operate as one unit. Therefore, it is important to see these vehicles as elements of a larger segmented spacecraft rather than separate spacecraft flying in formation. The evolution of large multi-vehicle exploration architecture creates the need (and opportunity) to establish a global power architecture that is common across all vehicles. The Advanced Exploration Systems (AES) Modular Power System (AMPS) project managed by NASA Glenn Research Center (GRC) is aimed at establishing the modular power system architecture that will enable power systems to be built from a common set of modular building blocks. The project is developing, demonstrating and evaluating key modular power technologies that are expected to minimize non-recurring development costs, reduce recurring integration costs, as well as, mission operational and support costs. Further, modular power is expected to enhance mission flexibility, vehicle reliability, scalability and overall mission supportability. The AMPS project not only supports multi-vehicle architectures but should enable multi-mission capability as well. The AMPS technology development involves near term demonstrations involving developmental prototype vehicles and field demonstrations. These operational demonstrations not only serve as a means of evaluating modular technology but also provide feedback to developers that assure that they progress toward truly flexible and operationally supportable modular power architecture.

Microsensor Technologies for Plant Growth System Monitoring

NASA Technical Reports Server (NTRS)

Kim, Chang-Soo

2004-01-01

This document covered the following: a) demonstration of feasibility of microsensor for tube and particulate growth systems; b) Dissolved oxygen; c)Wetness; d) Flexible microfluidic substrate with microfluidic channels and microsensor arrays; e)Dynamic root zone control/monitoring in microgravity; f)Rapid prototyping of phytoremediation; and g) A new tool for root physiology and pathology.

Magnetic water-in-water droplet microfluidics

NASA Astrophysics Data System (ADS)

Navi, Maryam; Abbasi, Niki; Tsai, Scott

2017-11-01

Aqueous two-phase systems (ATPS) have shown to be ideal candidates for replacing the conventional water-oil systems used in droplet microfluidics. We use an ATPS of Polyethylene Glycol (PEG) and Dextran (DEX) for microfluidic generation of magnetic water-in-water droplets. As ferrofluid partitions to DEX phase, there is no significant diffusion of ferrofluid at the interface of the droplets, rendering generation of magnetic DEX droplets in a non-magnetic continuous phase of PEG possible. In this system, both phases are water-based and highly biocompatible. We microfluidically generate magnetic DEX droplets at a flow-focusing junction in a jetting regime. We sort the droplets based on their size by placing a permanent magnet downstream of the droplet generation region, and show that the deflection of droplets is in good agreement with a mathematical model. We also show that the magnetic DEX droplets can be stabilized by lysozyme and be used for separation of single cell containing water-in-water droplets. This system of magnetic water-in-water droplet manipulation may find biomedical applications such as single-cell studies and drug delivery.

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

NASA Astrophysics Data System (ADS)

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

2006-07-01

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

Microfluidic Bead Suspension Hopper

PubMed Central

2014-01-01

Many high-throughput analytical platforms, from next-generation DNA sequencing to drug discovery, rely on beads as carriers of molecular diversity. Microfluidic systems are ideally suited to handle and analyze such bead libraries with high precision and at minute volume scales; however, the challenge of introducing bead suspensions into devices before they sediment usually confounds microfluidic handling and analysis. We developed a bead suspension hopper that exploits sedimentation to load beads into a microfluidic droplet generator. A suspension hopper continuously delivered synthesis resin beads (17 μm diameter, 112,000 over 2.67 h) functionalized with a photolabile linker and pepstatin A into picoliter-scale droplets of an HIV-1 protease activity assay to model ultraminiaturized compound screening. Likewise, trypsinogen template DNA-coated magnetic beads (2.8 μm diameter, 176,000 over 5.5 h) were loaded into droplets of an in vitro transcription/translation system to model a protein evolution experiment. The suspension hopper should effectively remove any barriers to using suspensions as sample inputs, paving the way for microfluidic automation to replace robotic library distribution. PMID:24761972

A Reduced Order Model for Whole-Chip Thermal Analysis of Microfluidic Lab-on-a-Chip Systems

PubMed Central

Wang, Yi; Song, Hongjun; Pant, Kapil

2013-01-01

This paper presents a Krylov subspace projection-based Reduced Order Model (ROM) for whole microfluidic chip thermal analysis, including conjugate heat transfer. Two key steps in the reduced order modeling procedure are described in detail, including (1) the acquisition of a 3D full-scale computational model in the state-space form to capture the dynamic thermal behavior of the entire microfluidic chip; and (2) the model order reduction using the Block Arnoldi algorithm to markedly lower the dimension of the full-scale model. Case studies using practically relevant thermal microfluidic chip are undertaken to establish the capability and to evaluate the computational performance of the reduced order modeling technique. The ROM is compared against the full-scale model and exhibits good agreement in spatiotemporal thermal profiles (<0.5% relative error in pertinent time scales) and over three orders-of-magnitude acceleration in computational speed. The salient model reusability and real-time simulation capability renders it amenable for operational optimization and in-line thermal control and management of microfluidic systems and devices. PMID:24443647

Endothelial cell culture in microfluidic devices for investigating microvascular processes.

PubMed

Mannino, Robert G; Qiu, Yongzhi; Lam, Wilbur A

2018-07-01

Numerous conditions and disease states such as sickle cell disease, malaria, thrombotic microangiopathy, and stroke significantly impact the microvasculature function and its role in disease progression. Understanding the role of cellular interactions and microvascular hemodynamic forces in the context of disease is crucial to understanding disease pathophysiology. In vivo models of microvascular disease using animal models often coupled with intravital microscopy have long been utilized to investigate microvascular phenomena. However, these methods suffer from some major drawbacks, including the inability to tightly and quantitatively control experimental conditions, the difficulty of imaging multiple microvascular beds within a living organism, and the inability to isolate specific microvascular geometries such as bifurcations. Thus, there exists a need for in vitro microvascular models that can mitigate the drawbacks associated with in vivo systems. To that end, microfluidics has been widely used to develop such models, as it allows for tight control of system inputs, facile imaging, and the ability to develop robust and repeatable systems with well-defined geometries. Incorporating endothelial cells to branching microfluidic models allows for the development of "endothelialized" systems that accurately recapitulate physiological microvessels. In this review, we summarize the field of endothelialized microfluidics, specifically focusing on fabrication methods, limitations, and applications of these systems. We then speculate on future directions and applications of these cutting edge technologies. We believe that this review of the field is of importance to vascular biologists and bioengineers who aim to utilize microfluidic technologies to solve vascular problems.

Modular entanglement.

PubMed

Gualdi, Giulia; Giampaolo, Salvatore M; Illuminati, Fabrizio

2011-02-04

We introduce and discuss the concept of modular entanglement. This is the entanglement that is established between the end points of modular systems composed by sets of interacting moduli of arbitrarily fixed size. We show that end-to-end modular entanglement scales in the thermodynamic limit and rapidly saturates with the number of constituent moduli. We clarify the mechanisms underlying the onset of entanglement between distant and noninteracting quantum systems and its optimization for applications to quantum repeaters and entanglement distribution and sharing.

Modular properties of 6d (DELL) systems

NASA Astrophysics Data System (ADS)

Aminov, G.; Mironov, A.; Morozov, A.

2017-11-01

If super-Yang-Mills theory possesses the exact conformal invariance, there is an additional modular invariance under the change of the complex bare charge [InlineMediaObject not available: see fulltext.]. The low-energy Seiberg-Witten prepotential ℱ( a), however, is not explicitly invariant, because the flat moduli also change a - → a D = ∂ℱ/∂ a. In result, the prepotential is not a modular form and depends also on the anomalous Eisenstein series E 2. This dependence is usually described by the universal MNW modular anomaly equation. We demonstrate that, in the 6 d SU( N) theory with two independent modular parameters τ and \\widehat{τ} , the modular anomaly equation changes, because the modular transform of τ is accompanied by an ( N -dependent!) shift of \\widehat{τ} and vice versa. This is a new peculiarity of double-elliptic systems, which deserves further investigation.

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.

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

PubMed

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

2014-03-07

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

Microfluidics-based in vivo mimetic systems for the study of cellular biology.

PubMed

Kim, Donghyuk; Wu, Xiaojie; Young, Ashlyn T; Haynes, Christy L

2014-04-15

The human body is a complex network of molecules, organelles, cells, tissues, and organs: an uncountable number of interactions and transformations interconnect all the system's components. In addition to these biochemical components, biophysical components, such as pressure, flow, and morphology, and the location of all of these interactions play an important role in the human body. Technical difficulties have frequently limited researchers from observing cellular biology as it occurs within the human body, but some state-of-the-art analytical techniques have revealed distinct cellular behaviors that occur only in the context of the interactions. These types of findings have inspired bioanalytical chemists to provide new tools to better understand these cellular behaviors and interactions. What blocks us from understanding critical biological interactions in the human body? Conventional approaches are often too naïve to provide realistic data and in vivo whole animal studies give complex results that may or may not be relevant for humans. Microfluidics offers an opportunity to bridge these two extremes: while these studies will not model the complexity of the in vivo human system, they can control the complexity so researchers can examine critical factors of interest carefully and quantitatively. In addition, the use of human cells, such as cells isolated from donated blood, captures human-relevant data and limits the use of animals in research. In addition, researchers can adapt these systems easily and cost-effectively to a variety of high-end signal transduction mechanisms, facilitating high-throughput studies that are also spatially, temporally, or chemically resolved. These strengths should allow microfluidic platforms to reveal critical parameters in the human body and provide insights that will help with the translation of pharmacological advances to clinical trials. In this Account, we describe selected microfluidic innovations within the last 5 years that focus on modeling both biophysical and biochemical interactions in cellular communication, such as flow and cell-cell networks. We also describe more advanced systems that mimic higher level biological networks, such as organ on-a-chip and animal on-a-chip models. Since the first papers in the early 1990s, interest in the bioanalytical use of microfluidics has grown significantly. Advances in micro-/nanofabrication technology have allowed researchers to produce miniaturized, biocompatible assay platforms suitable for microfluidic studies in biochemistry and chemical biology. Well-designed microfluidic platforms can achieve quick, in vitro analyses on pico- and femtoliter volume samples that are temporally, spatially, and chemically resolved. In addition, controlled cell culture techniques using a microfluidic platform have produced biomimetic systems that allow researchers to replicate and monitor physiological interactions. Pioneering work has successfully created cell-fluid, cell-cell, cell-tissue, tissue-tissue, even organ-like level interfaces. Researchers have monitored cellular behaviors in these biomimetic microfluidic environments, producing validated model systems to understand human pathophysiology and to support the development of new therapeutics.

Covalent Bonding of Thermoplastics to Rubbers for Printable, Reel-to-Reel Processing in Soft Robotics and Microfluidics.

PubMed

Taylor, Jay M; Perez-Toralla, Karla; Aispuro, Ruby; Morin, Stephen A

2018-02-01

The lamination of mechanically stiff structures to elastic materials is prevalent in biological systems and popular in many emerging synthetic systems, such as soft robotics, microfluidics, stretchable electronics, and pop-up assemblies. The disparate mechanical and chemical properties of these materials have made it challenging to develop universal synthetic procedures capable of reliably adhering to these classes of materials together. Herein, a simple and scalable procedure is described that is capable of covalently laminating a variety of commodity ("off-the-shelf") thermoplastic sheets to silicone rubber films. When combined with laser printing, the nonbonding sites can be "printed" onto the thermoplastic sheets, enabling the direct fabrication of microfluidic systems for actuation and liquid handling applications. The versatility of this approach in generating thin, multifunctional laminates is demonstrated through the fabrication of milliscale soft actuators and grippers with hinged articulation and microfluidic channels with built-in optical filtering and pressure-dependent geometries. This method of fabrication offers several advantages, including technical simplicity, process scalability, design versatility, and material diversity. The concepts and strategies presented herein are broadly applicable to the soft robotics, microfluidics, and advanced and additive manufacturing communities where hybrid rubber/plastic structures are prevalent. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The upcoming 3D-printing revolution in microfluidics.

PubMed

Bhattacharjee, Nirveek; Urrios, Arturo; Kang, Shawn; Folch, Albert

2016-05-21

In the last two decades, the vast majority of microfluidic systems have been built in poly(dimethylsiloxane) (PDMS) by soft lithography, a technique based on PDMS micromolding. A long list of key PDMS properties have contributed to the success of soft lithography: PDMS is biocompatible, elastomeric, transparent, gas-permeable, water-impermeable, fairly inexpensive, copyright-free, and rapidly prototyped with high precision using simple procedures. However, the fabrication process typically involves substantial human labor, which tends to make PDMS devices difficult to disseminate outside of research labs, and the layered molding limits the 3D complexity of the devices that can be produced. 3D-printing has recently attracted attention as a way to fabricate microfluidic systems due to its automated, assembly-free 3D fabrication, rapidly decreasing costs, and fast-improving resolution and throughput. Resins with properties approaching those of PDMS are being developed. Here we review past and recent efforts in 3D-printing of microfluidic systems. We compare the salient features of PDMS molding with those of 3D-printing and we give an overview of the critical barriers that have prevented the adoption of 3D-printing by microfluidic developers, namely resolution, throughput, and resin biocompatibility. We also evaluate the various forces that are persuading researchers to abandon PDMS molding in favor of 3D-printing in growing numbers.

Towards an integrated optofluidic system for highly sensitive detection of antibiotics in seawater incorporating bimodal waveguide photonic biosensors and complex, active microfluidics

NASA Astrophysics Data System (ADS)

Szydzik, C.; Gavela, A. F.; Roccisano, J.; Herranz de Andrés, S.; Mitchell, A.; Lechuga, L. M.

2016-12-01

We present recent results on the realisation and demonstration of an integrated optofluidic lab-on-a-chip measurement system. The system consists of an integrated on-chip automated microfluidic fluid handling subsystem, coupled with bimodal nano-interferometer waveguide technology, and is applied in the context of detection of antibiotics in seawater. The bimodal waveguide (BMWG) is a highly sensitive label-free biosensor. Integration of complex microfluidic systems with bimodal waveguide technology enables on-chip sample handling and fluid processing capabilities and allows for significant automation of experimental processes. The on-chip fluid-handling subsystem is realised through the integration of pneumatically actuated elastomer pumps and valves, enabling high temporal resolution sample and reagent delivery and facilitating multiplexed detection processes.

Hydrodynamic metamaterials: Microfabricated arrays to steer, refract, and focus streams of biomaterials

PubMed Central

Morton, Keith J.; Loutherback, Kevin; Inglis, David W.; Tsui, Ophelia K.; Sturm, James C.; Chou, Stephen Y.; Austin, Robert H.

2008-01-01

We show that it is possible to direct particles entrained in a fluid along trajectories much like rays of light in classical optics. A microstructured, asymmetric post array forms the core hydrodynamic element and is used as a building block to construct microfluidic metamaterials and to demonstrate refractive, focusing, and dispersive pathways for flowing beads and cells. The core element is based on the concept of deterministic lateral displacement where particles choose different paths through the asymmetric array based on their size: Particles larger than a critical size are displaced laterally at each row by a post and move along the asymmetric axis at an angle to the flow, while smaller particles move along streamline paths. We create compound elements with complex particle handling modes by tiling this core element using multiple transformation operations; we show that particle trajectories can be bent at an interface between two elements and that particles can be focused into hydrodynamic jets by using a single inlet port. Although particles propagate through these elements in a way that strongly resembles light rays propagating through optical elements, there are unique differences in the paths of our particles as compared with photons. The unusual aspects of these modular, microfluidic metamaterials form a rich design toolkit for mixing, separating, and analyzing cells and functional beads on-chip. PMID:18495920

A Modular Habitation System for Human Planetary and Space Exploration

NASA Technical Reports Server (NTRS)

Howe, A. Scott

2015-01-01

A small-diameter modular pressure vessel system is devised that can be applied to planetary surface and deep space human exploration missions. As one of the recommendations prepared for the NASA Human Spaceflight Architecture Team (HAT) Evolvable Mars Campaign (EMC), a compact modular system can provide a Mars-forward approach to a variety of missions and environments. Small cabins derived from the system can fit into the Space Launch System (SLS) Orion "trunk", or can be mounted with mobility systems to function as pressurized rovers, in-space taxis, ascent stage cabins, or propellant tanks. Larger volumes can be created using inflatable elements for long-duration deep space missions and planetary surface outposts. This paper discusses how a small-diameter modular system can address functional requirements, mass and volume constraints, and operational scenarios.

In Vitro Microfluidic Models for Neurodegenerative Disorders.

PubMed

Osaki, Tatsuya; Shin, Yoojin; Sivathanu, Vivek; Campisi, Marco; Kamm, Roger D

2018-01-01

Microfluidic devices enable novel means of emulating neurodegenerative disease pathophysiology in vitro. These organ-on-a-chip systems can potentially reduce animal testing and substitute (or augment) simple 2D culture systems. Reconstituting critical features of neurodegenerative diseases in a biomimetic system using microfluidics can thereby accelerate drug discovery and improve our understanding of the mechanisms of several currently incurable diseases. This review describes latest advances in modeling neurodegenerative diseases in the central nervous system and the peripheral nervous system. First, this study summarizes fundamental advantages of microfluidic devices in the creation of compartmentalized cell culture microenvironments for the co-culture of neurons, glial cells, endothelial cells, and skeletal muscle cells and in their recapitulation of spatiotemporal chemical gradients and mechanical microenvironments. Then, this reviews neurodegenerative-disease-on-a-chip models focusing on Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Finally, this study discusses about current drawbacks of these models and strategies that may overcome them. These organ-on-chip technologies can be useful to be the first line of testing line in drug development and toxicology studies, which can contribute significantly to minimize the phase of animal testing steps. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Characterization of size-dependent mechanical properties of tip-growing cells using a lab-on-chip device.

PubMed

Hu, Chengzhi; Munglani, Gautam; Vogler, Hannes; Ndinyanka Fabrice, Tohnyui; Shamsudhin, Naveen; Wittel, Falk K; Ringli, Christoph; Grossniklaus, Ueli; Herrmann, Hans J; Nelson, Bradley J

2016-12-20

Quantification of mechanical properties of tissues, living cells, and cellular components is crucial for the modeling of plant developmental processes such as mechanotransduction. Pollen tubes are tip-growing cells that provide an ideal system to study the mechanical properties at the single cell level. In this article, a lab-on-a-chip (LOC) device is developed to quantitatively measure the biomechanical properties of lily (Lilium longiflorum) pollen tubes. A single pollen tube is fixed inside the microfluidic chip at a specific orientation and subjected to compression by a soft membrane. By comparing the deformation of the pollen tube at a given external load (compressibility) and the effect of turgor pressure on the tube diameter (stretch ratio) with finite element modeling, its mechanical properties are determined. The turgor pressure and wall stiffness of the pollen tubes are found to decrease considerably with increasing initial diameter of the pollen tubes. This observation supports the hypothesis that tip-growth is regulated by a delicate balance between turgor pressure and wall stiffness. The LOC device is modular and adaptable to a variety of cells that exhibit tip-growth, allowing for the straightforward measurement of mechanical properties.

Optical cell monitoring system for underwater targets

NASA Astrophysics Data System (ADS)

Moon, SangJun; Manzur, Fahim; Manzur, Tariq; Demirci, Utkan

2008-10-01

We demonstrate a cell based detection system that could be used for monitoring an underwater target volume and environment using a microfluidic chip and charge-coupled-device (CCD). This technique allows us to capture specific cells and enumerate these cells on a large area on a microchip. The microfluidic chip and a lens-less imaging platform were then merged to monitor cell populations and morphologies as a system that may find use in distributed sensor networks. The chip, featuring surface chemistry and automatic cell imaging, was fabricated from a cover glass slide, double sided adhesive film and a transparent Polymethlymetacrylate (PMMA) slab. The optically clear chip allows detecting cells with a CCD sensor. These chips were fabricated with a laser cutter without the use of photolithography. We utilized CD4+ cells that are captured on the floor of a microfluidic chip due to the ability to address specific target cells using antibody-antigen binding. Captured CD4+ cells were imaged with a fluorescence microscope to verify the chip specificity and efficiency. We achieved 70.2 +/- 6.5% capturing efficiency and 88.8 +/- 5.4% specificity for CD4+ T lymphocytes (n = 9 devices). Bright field images of the captured cells in the 24 mm × 4 mm × 50 μm microfluidic chip were obtained with the CCD sensor in one second. We achieved an inexpensive system that rapidly captures cells and images them using a lens-less CCD system. This microfluidic device can be modified for use in single cell detection utilizing a cheap light-emitting diode (LED) chip instead of a wide range CCD system.

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.

Method for making electro-fluidic connections in microfluidic devices

DOEpatents

Frye-Mason, Gregory C.; Martinez, David; Manginell, Ronald P.; Heller, Edwin J.; Chanchani, Rajen

2004-08-10

A method for forming electro-fluidic interconnections in microfluidic devices comprises forming an electrical connection between matching bond pads on a die containing an active electrical element and a microfluidic substrate and forming a fluidic seal ring that circumscribes the active electrical element and a fluidic feedthrough. Preferably, the electrical connection and the seal ring are formed in a single bonding step. The simple method is particularly useful for chemical microanalytical systems wherein a plurality of microanalytical components, such as a chemical preconcentrator, a gas chromatography column, and a surface acoustic wave detector, are fluidically interconnected on a hybrid microfluidic substrate having electrical connection to external support electronics.

Application of Microfluidics in Experimental Ecology: The Importance of Being Spatial.

PubMed

Nagy, Krisztina; Ábrahám, Ágnes; Keymer, Juan E; Galajda, Péter

2018-01-01

Microfluidics is an emerging technology that is used more and more in biology experiments. Its capabilities of creating precisely controlled conditions in cellular dimensions make it ideal to explore cell-cell and cell-environment interactions. Thus, a wide spectrum of problems in microbial ecology can be studied using engineered microbial habitats. Moreover, artificial microfluidic ecosystems can serve as model systems to test ecology theories and principles that apply on a higher level in the hierarchy of biological organization. In this mini review we aim to demonstrate the versatility of microfluidics and the diversity of its applications that help the advance of microbiology, and in more general, experimental ecology.

Fast Computation on the Modern Battlefield

DTIC Science & Technology

2015-04-01

the performance of offloading systems in current and future scenarios. The modularity of this model allows system designers to replace model...goals were simplicity and modularity . We wanted the model to not necessarily answer every question for every scenario, but rather expose easy to...acquisitions for future systems. Again, because of the modularity of the model, it is possible for designers to substitute the most accurate value for

MOBS - A modular on-board switching system

NASA Astrophysics Data System (ADS)

Berner, W.; Grassmann, W.; Piontek, M.

The authors describe a multibeam satellite system that is designed for business services and for communications at a high bit rate. The repeater is regenerative with a modular onboard switching system. It acts not only as baseband switch but also as the central node of the network, performing network control and protocol evaluation. The hardware is based on a modular bus/memory architecture with associated processors.

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.

Microfluidics-assisted in vitro drug screening and carrier production

PubMed Central

Tsui, Jonathan H.; Lee, Woohyuk; Pun, Suzie H.; Kim, Jungkyu; Kim, Deok-Ho

2013-01-01

Microfluidic platforms provide several unique advantages for drug development. In the production of drug carriers, physical properties such as size and shape, and chemical properties such as drug composition and pharmacokinetic parameters, can be modified simply and effectively by tuning the flow rate and geometries. Large numbers of carriers can then be fabricated with minimal effort and with little to no batch-to-batch variation. Additionally, cell or tissue culture models in microfluidic systems can be used as in vitro drug screening tools. Compared to in vivo animal models, microfluidic drug screening platforms allow for high-throughput and reproducible screening at a significantly lower cost, and when combined with current advances in tissue engineering, are also capable of mimicking native tissues. In this review, various microfluidic platforms for drug and gene carrier fabrication are reviewed to provide guidelines for designing appropriate carriers. In vitro microfluidic drug screening platforms designed for high-throughput analysis and replication of in vivo conditions are also reviewed to highlight future directions for drug research and development. PMID:23856409

Microfluidic Dynamic Interfacial Tensiometry (μDIT).

PubMed

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

2014-05-07

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

The effect of contact angles and capillary dimensions on the burst frequency of super hydrophilic and hydrophilic centrifugal microfluidic platforms, a CFD study.

PubMed

Kazemzadeh, Amin; Ganesan, Poo; Ibrahim, Fatimah; He, Shuisheng; Madou, Marc J

2013-01-01

This paper employs the volume of fluid (VOF) method to numerically investigate the effect of the width, height, and contact angles on burst frequencies of super hydrophilic and hydrophilic capillary valves in centrifugal microfluidic systems. Existing experimental results in the literature have been used to validate the implementation of the numerical method. The performance of capillary valves in the rectangular and the circular microfluidic structures on super hydrophilic centrifugal microfluidic platforms is studied. The numerical results are also compared with the existing theoretical models and the differences are discussed. Our experimental and computed results show a minimum burst frequency occurring at square capillaries and this result is useful for designing and developing more sophisticated networks of capillary valves. It also predicts that in super hydrophilic microfluidics, the fluid leaks consistently from the capillary valve at low pressures which can disrupt the biomedical procedures in centrifugal microfluidic platforms.

The Effect of Contact Angles and Capillary Dimensions on the Burst Frequency of Super Hydrophilic and Hydrophilic Centrifugal Microfluidic Platforms, a CFD Study

PubMed Central

Kazemzadeh, Amin; Ganesan, Poo; Ibrahim, Fatimah; He, Shuisheng; Madou, Marc J.

2013-01-01

This paper employs the volume of fluid (VOF) method to numerically investigate the effect of the width, height, and contact angles on burst frequencies of super hydrophilic and hydrophilic capillary valves in centrifugal microfluidic systems. Existing experimental results in the literature have been used to validate the implementation of the numerical method. The performance of capillary valves in the rectangular and the circular microfluidic structures on super hydrophilic centrifugal microfluidic platforms is studied. The numerical results are also compared with the existing theoretical models and the differences are discussed. Our experimental and computed results show a minimum burst frequency occurring at square capillaries and this result is useful for designing and developing more sophisticated networks of capillary valves. It also predicts that in super hydrophilic microfluidics, the fluid leaks consistently from the capillary valve at low pressures which can disrupt the biomedical procedures in centrifugal microfluidic platforms. PMID:24069169

Microfluidic integrated acoustic waving for manipulation of cells and molecules.

PubMed

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

2016-11-15

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

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

PubMed

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

2018-01-01

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

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

PubMed Central

Alvankarian, Jafar; Majlis, Burhanuddin Yeop

2015-01-01

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

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

NASA Astrophysics Data System (ADS)

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

2018-03-01

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

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

PubMed Central

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

2017-01-01

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

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

PubMed

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

2017-06-01

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

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

PubMed Central

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

2011-01-01

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

A simple and cost-effective molecular diagnostic system and DNA probes synthesized by light emitting diode photolithography

NASA Astrophysics Data System (ADS)

Oleksandrov, Sergiy; Kwon, Jung Ho; Lee, Ki-chang; Sujin-Ku; Paek, Mun Cheol

2014-09-01

This work introduces a novel chip to be used in the future as a simple and cost-effective method for creating DNA arrays using light emission diode (LED) photolithography. The DNA chip platform contains 24 independent reaction sites, which allows for the testing of a corresponding amount of patients' samples in hospital. An array of commercial UV LEDs and lens systems was combined with a microfluidic flow system to provide patterning of 24 individual reaction sites, each with 64 independent probes. Using the LED array instead of conventional laser exposure systems or micro-mirror systems significantly reduces the cost of equipment. The microfluidic system together with microfluidic flow cells drastically reduces the amount of used reagents, which is important due to the high cost of commercial reagents. The DNA synthesis efficiency was verified by fluorescence labeling and conventional hybridization.

An organic self-regulating microfluidic system.

PubMed

Eddington, D T; Liu, R H; Moore, J S; Beebe, D J

2001-12-01

In this paper we present an organic feedback scheme that merges microfluidics and responsive materials to address several limitations of current microfluidic systems. By using in situ fabrication and by taking advantage of microscale phenomena (e.g., laminar flow, short diffusion times), we have demonstrated feedback control of the output pH in a completely organic system. The system autonomously regulates an output stream at pH 7 under a range of input flow conditions. A single responsive hydrogel component performs the functionality of traditional feedback system components. Vertically stacked laminar flow is used to improve the time response of the hydrogel actuator. A star shaped orifice is utilized to improve the flow characteristics of the membrane/orifice valve. By changing the chemistry of the hydrogel component, the system can be altered to regulate flow based on hydrogels sensitive to temperature, light, biological/molecular, and others.

Verification of the Seismic Performance of a Rigidly Connected Modular System Depending on the Shape and Size of the Ceiling Bracket

PubMed Central

Lee, Seungjae; Park, Jaeseong; Kwak, Euishin; Shon, Sudeok; Kang, Changhoon; Choi, Hosoon

2017-01-01

Modular systems have been mostly researched in relatively low-rise structures but, lately, their applications to mid- to high-rise structures began to be reviewed, and research interest in new modularization subjects has increased. The application of modular systems to mid- to high-rise structures requires the structural stability of the frame and connections that consist of units, and the evaluation of the stiffness of structures that are combined in units. However, the combination of general units causes loss of the cross-section of columns or beams, resulting in low seismic performance and hindering installation works in the field. In addition, the evaluation of a frame considering such a cross-sectional loss is not easy. Therefore, it is necessary to develop a joint that is stable and easy to install. In the study, a rigidly connected modular system was proposed as a moment-resisting frame for a unit modular system, and their joints were developed and their performances were compared. The proposed system changed the ceiling beam into a bracket type to fasten bolts. It can be merged with other seismic force-resisting systems. To verify the seismic performance of the proposed system, a cyclic loading test was conducted, and the rigidly connected joint performance and integrated behavior at the joint of modular units were investigated. From the experimental results, the maximum resisting force of the proposed connection exceeded the theoretical parameters, indicating that a rigid joint structural performance could be secured. PMID:28772622

Modular Training Systems and Strategies: An International Meeting (Washington, D.C., May 11-12, 1992).

ERIC Educational Resources Information Center

American Society for Training and Development, Alexandria, VA.

This publication contains materials from a conference to discuss modular approaches to curriculum design. The materials from the United States and five other countries address both national skills standards and modular systems of training delivery. An introduction provides brief summaries of the conference materials and the agenda. "National…

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.

Laser ablated micropillar energy directors for ultrasonic welding of microfluidic systems

NASA Astrophysics Data System (ADS)

Esben Poulsen, Carl; Kistrup, Kasper; Korsgaard Andersen, Nis; Taboryski, Rafael; Fougt Hansen, Mikkel; Wolff, Anders

2016-06-01

We present a new type of energy director (ED) for ultrasonic welding of microfluidic systems. These micropillar EDs are based on the replication of cone like protrusion structures introduced using a pico-second laser and may therefore be added to any mould surface accessible to a pico-second laser beam. The technology is demonstrated on an injection moulded microfluidic device featuring high-aspect ratio (h  ×  w  =  2000 μm  ×  550 μm) and free-standing channel walls, where bonding is achieved with no detectable channel deformation. The bonding strength is similar to conventional EDs and the fabricated system can withstand pressures of over 9.5 bar.

A modular approach to addressing model design, scale, and parameter estimation issues in distributed hydrological modelling

USGS Publications Warehouse

Leavesley, G.H.; Markstrom, S.L.; Restrepo, Pedro J.; Viger, R.J.

2002-01-01

A modular approach to model design and construction provides a flexible framework in which to focus the multidisciplinary research and operational efforts needed to facilitate the development, selection, and application of the most robust distributed modelling methods. A variety of modular approaches have been developed, but with little consideration for compatibility among systems and concepts. Several systems are proprietary, limiting any user interaction. The US Geological Survey modular modelling system (MMS) is a modular modelling framework that uses an open source software approach to enable all members of the scientific community to address collaboratively the many complex issues associated with the design, development, and application of distributed hydrological and environmental models. Implementation of a common modular concept is not a trivial task. However, it brings the resources of a larger community to bear on the problems of distributed modelling, provides a framework in which to compare alternative modelling approaches objectively, and provides a means of sharing the latest modelling advances. The concepts and components of the MMS are described and an example application of the MMS, in a decision-support system context, is presented to demonstrate current system capabilities. Copyright ?? 2002 John Wiley and Sons, Ltd.

Rapid Protein Separations in Microfluidic Devices

NASA Technical Reports Server (NTRS)

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

2004-01-01

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

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.

Binary centrifugal microfluidics enabling novel, digital addressable functions for valving and routing.

PubMed

Wang, Guanghui; Tan, Jie; Tang, Minghui; Zhang, Changbin; Zhang, Dongying; Ji, Wenbin; Chen, Junhao; Ho, Ho-Pui; Zhang, Xuping

2018-03-16

Centrifugal microfluidics or lab-on-a-disc (LOAD) is a promising branch of lab-on-a-chip or microfluidics. Besides effective fluid transportation and inherently available density-based sample separation in centrifugal microfluidics, uniform actuation of flow on the disc makes the platform compact and scalable. However, the natural radially outward centrifugal force in a LOAD system limits its capacity to perform complex fluid manipulation steps. In order to increase the fluid manipulation freedom and integration capacity of the LOAD system, we propose a binary centrifugal microfluidics platform. With the help of Euler force, our platform allows free switching of both left and right states based on a rather simple mechanical structure. The periodical switching of state would provide a "clock" signal for a sequence of droplet binary logic operations. With the binary state platform and the "clock" signal, we can accurately handle the droplet separately in each time step with a maximum main frequency of about 10 S s-1 (switching per second). Apart from droplet manipulations such as droplet generation and metering, we also demonstrate a series of droplet logic operations, such as binary valving, droplet routing and digital addressable droplet storage. Furthermore, complex bioassays such as the Bradford assay and DNA purification assay are demonstrated on a binary platform, which is totally impossible for a traditional LOAD system. Our binary platform largely improves the capability for logic operation on the LOAD platform, and it is a simple and promising approach for microfluidic lab-on-a-disc large-scale integration.

Reconfigurable virtual electrowetting channels.

PubMed

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

2012-02-21

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

Imaging label-free biosensor with microfluidic system

NASA Astrophysics Data System (ADS)

Jahns, S.; Glorius, P.; Hansen, M.; Nazirizadeh, Y.; Gerken, M.

2015-06-01

We present a microfluidic system suitable for parallel label-free detection of several biomarkers utilizing a compact imaging measurement system. The microfluidic system contains a filter unit to separate the plasma from human blood and a functionalized, photonic crystal slab sensor chip. The nanostructure of the photonic crystal slab sensor chip is fabricated by nanoimprint lithography of a period grating surface into a photoresist and subsequent deposition of a TiO2 layer. Photonic crystal slabs are slab waveguides supporting quasi-guided modes coupling to far-field radiation, which are sensitive to refractive index changes due to biomarker binding on the functionalized surface. In our imaging read-out system the resulting resonance shift of the quasi-guided mode in the transmission spectrum is converted into an intensity change detectable with a simple camera. By continuously taking photographs of the sensor surface local intensity changes are observed revealing the binding kinetics of the biomarker to its specific target. Data from two distinct measurement fields are used for evaluation. For testing the sensor chip, 1 μM biotin as well as 1 μM recombinant human CD40 ligand were immobilized in spotsvia amin coupling to the sensor surface. Each binding experiment was performed with 250 nM streptavidin and 90 nM CD40 ligand antibody dissolved in phosphate buffered saline. In the next test series, a functionalized sensor chip was bonded onto a 15 mm x 15 mm opening of the 75 mm x 25 mm x 2 mm microfluidic system. We demonstrate the functionality of the microfluidic system for filtering human blood such that only blood plasma was transported to the sensor chip. The results of first binding experiments in buffer with this test chip will be presented.

In vitro microfluidic models of tumor microenvironment to screen transport of drugs and nanoparticles.

PubMed

Ozcelikkale, Altug; Moon, Hye-Ran; Linnes, Michael; Han, Bumsoo

2017-09-01

Advances in nanotechnology have enabled numerous types of nanoparticles (NPs) to improve drug delivery to tumors. While many NP systems have been proposed, their clinical translation has been less than anticipated primarily due to failure of current preclinical evaluation techniques to adequately model the complex interactions between the NP and physiological barriers of tumor microenvironment. This review focuses on microfluidic tumor models for characterization of delivery efficacy and toxicity of cancer nanomedicine. Microfluidics offer significant advantages over traditional macroscale cell cultures by enabling recapitulation of tumor microenvironment through precise control of physiological cues such as hydrostatic pressure, shear stress, oxygen, and nutrient gradients. Microfluidic systems have recently started to be adapted for screening of drugs and NPs under physiologically relevant settings. So far the two primary application areas of microfluidics in this area have been high-throughput screening using traditional culture settings such as single cells or multicellular tumor spheroids, and mimicry of tumor microenvironment for study of cancer-related cell-cell and cell-matrix interactions. These microfluidic technologies are also useful in modeling specific steps in NP delivery to tumor and characterize NP transport properties and outcomes by systematic variation of physiological conditions. Ultimately, it will be possible to design drug-screening platforms uniquely tailored for individual patient physiology using microfluidics. These in vitro models can contribute to development of precision medicine by enabling rapid and patient-specific evaluation of cancer nanomedicine. WIREs Nanomed Nanobiotechnol 2017, 9:e1460. doi: 10.1002/wnan.1460 For further resources related to this article, please visit the WIREs website. © 2017 Wiley Periodicals, Inc.

Compressed-air flow control system.

PubMed

Bong, Ki Wan; Chapin, Stephen C; Pregibon, Daniel C; Baah, David; Floyd-Smith, Tamara M; Doyle, Patrick S

2011-02-21

We present the construction and operation of a compressed-air driven flow system that can be used for a variety of microfluidic applications that require rapid dynamic response and precise control of multiple inlet streams. With the use of inexpensive and readily available parts, we describe how to assemble this versatile control system and further explore its utility in continuous- and pulsed-flow microfluidic procedures for the synthesis and analysis of microparticles.

Application of optically-induced-dielectrophoresis in microfluidic system for purification of circulating tumour cells for gene expression analysis- Cancer cell line model

NASA Astrophysics Data System (ADS)

Chiu, Tzu-Keng; Chou, Wen-Pin; Huang, Song-Bin; Wang, Hung-Ming; Lin, Yung-Chang; Hsieh, Chia-Hsun; Wu, Min-Hsien

2016-09-01

Circulating tumour cells (CTCs) in a blood circulation system are associated with cancer metastasis. The analysis of the drug-resistance gene expression of cancer patients’ CTCs holds promise for selecting a more effective therapeutic regimen for an individual patient. However, the current CTC isolation schemes might not be able to harvest CTCs with sufficiently high purity for such applications. To address this issue, this study proposed to integrate the techniques of optically induced dielectrophoretic (ODEP) force-based cell manipulation and fluorescent microscopic imaging in a microfluidic system to further purify CTCs after the conventional CTC isolation methods. In this study, the microfluidic system was developed, and its optimal operating conditions and performance for CTC isolation were evaluated. The results revealed that the presented system was able to isolate CTCs with cell purity as high as 100%, beyond what is possible using the previously existing techniques. In the analysis of CTC gene expression, therefore, this method could exclude the interference of leukocytes in a cell sample and accordingly contribute to higher analytical sensitivity, as demonstrated in this study. Overall, this study has presented an ODEP-based microfluidic system capable of simply and effectively isolating a specific cell species from a cell mixture.

Application of optically-induced-dielectrophoresis in microfluidic system for purification of circulating tumour cells for gene expression analysis- Cancer cell line model.

PubMed

Chiu, Tzu-Keng; Chou, Wen-Pin; Huang, Song-Bin; Wang, Hung-Ming; Lin, Yung-Chang; Hsieh, Chia-Hsun; Wu, Min-Hsien

2016-09-09

Circulating tumour cells (CTCs) in a blood circulation system are associated with cancer metastasis. The analysis of the drug-resistance gene expression of cancer patients' CTCs holds promise for selecting a more effective therapeutic regimen for an individual patient. However, the current CTC isolation schemes might not be able to harvest CTCs with sufficiently high purity for such applications. To address this issue, this study proposed to integrate the techniques of optically induced dielectrophoretic (ODEP) force-based cell manipulation and fluorescent microscopic imaging in a microfluidic system to further purify CTCs after the conventional CTC isolation methods. In this study, the microfluidic system was developed, and its optimal operating conditions and performance for CTC isolation were evaluated. The results revealed that the presented system was able to isolate CTCs with cell purity as high as 100%, beyond what is possible using the previously existing techniques. In the analysis of CTC gene expression, therefore, this method could exclude the interference of leukocytes in a cell sample and accordingly contribute to higher analytical sensitivity, as demonstrated in this study. Overall, this study has presented an ODEP-based microfluidic system capable of simply and effectively isolating a specific cell species from a cell mixture.

Application of optically-induced-dielectrophoresis in microfluidic system for purification of circulating tumour cells for gene expression analysis- Cancer cell line model

PubMed Central

Chiu, Tzu-Keng; Chou, Wen-Pin; Huang, Song-Bin; Wang, Hung-Ming; Lin, Yung-Chang; Hsieh, Chia-Hsun; Wu, Min-Hsien

2016-01-01

Circulating tumour cells (CTCs) in a blood circulation system are associated with cancer metastasis. The analysis of the drug-resistance gene expression of cancer patients’ CTCs holds promise for selecting a more effective therapeutic regimen for an individual patient. However, the current CTC isolation schemes might not be able to harvest CTCs with sufficiently high purity for such applications. To address this issue, this study proposed to integrate the techniques of optically induced dielectrophoretic (ODEP) force-based cell manipulation and fluorescent microscopic imaging in a microfluidic system to further purify CTCs after the conventional CTC isolation methods. In this study, the microfluidic system was developed, and its optimal operating conditions and performance for CTC isolation were evaluated. The results revealed that the presented system was able to isolate CTCs with cell purity as high as 100%, beyond what is possible using the previously existing techniques. In the analysis of CTC gene expression, therefore, this method could exclude the interference of leukocytes in a cell sample and accordingly contribute to higher analytical sensitivity, as demonstrated in this study. Overall, this study has presented an ODEP-based microfluidic system capable of simply and effectively isolating a specific cell species from a cell mixture. PMID:27609546

The role of intracochlear drug delivery devices in the management of inner ear disease.

PubMed

Ayoob, Andrew M; Borenstein, Jeffrey T

2015-03-01

Diseases of the inner ear include those of the auditory and vestibular systems, and frequently result in disabling hearing loss or vertigo. Despite a rapidly expanding pipeline of potential cochlear therapeutics, the inner ear remains a challenging organ for targeted drug delivery, and new technologies are required to deliver these therapies in a safe and efficacious manner. In addition to traditional approaches for direct inner ear drug delivery, novel microfluidics-based systems are under development, promising improved control over pharmacokinetics over longer periods of delivery, ultimately with application towards hair cell regeneration in humans. Advances in the development of intracochlear drug delivery systems are reviewed, including passive systems, active microfluidic technologies and cochlear prosthesis-mediated delivery. This article provides a description of novel delivery systems and their potential future clinical applications in treating inner ear disease. Recent progresses in microfluidics and miniaturization technologies are enabling the development of wearable and ultimately implantable drug delivery microsystems. Progress in this field is being spurred by the convergence of advances in molecular biology, microfluidic flow control systems and models for drug transport in the inner ear. These advances will herald a new generation of devices, with near-term applications in preclinical models, and ultimately with human clinical use for a range of diseases of the inner ear.

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

PubMed

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

2016-06-20

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

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.

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

PubMed

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

2013-02-18

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

Successes and future outlook for microfluidics-based cardiovascular drug discovery.

PubMed

Skommer, Joanna; Wlodkowic, Donald

2015-03-01

The greatest advantage of using microfluidics as a platform for the assessment of cardiovascular drug action is its ability to finely regulate fluid flow conditions, including flow rate, shear stress and pulsatile flow. At the same time, microfluidics provide means for modifying the vessel geometry (bifurcations, stenoses, complex networks), the type of surface of the vessel walls, and for patterning cells in 3D tissue-like architecture, including generation of lumen walls lined with cells and heart-on-a-chip structures for mimicking ventricular cardiomyocyte physiology. In addition, owing to the small volume of required specimens, microfluidics is ideally suited to clinical situations whereby monitoring of drug dosing or efficacy needs to be coupled with minimal phlebotomy-related drug loss. In this review, the authors highlight potential applications for the currently existing and emerging technologies and offer several suggestions on how to close the development cycle of microfluidic devices for cardiovascular drug discovery. The ultimate goal in microfluidics research for drug discovery is to develop 'human-on-a-chip' systems, whereby several organ cultures, including the vasculature and the heart, can mimic complex interactions between the organs and body systems. This would provide in vivo-like pharmacokinetics and pharmacodynamics for drug ADMET assessment. At present, however, the great variety of available designs does not go hand in hand with their use by the pharmaceutical community.

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

Microfluidics-Based in Vivo Mimetic Systems for the Study of Cellular Biology

PubMed Central

2015-01-01

Conspectus The human body is a complex network of molecules, organelles, cells, tissues, and organs: an uncountable number of interactions and transformations interconnect all the system’s components. In addition to these biochemical components, biophysical components, such as pressure, flow, and morphology, and the location of all of these interactions play an important role in the human body. Technical difficulties have frequently limited researchers from observing cellular biology as it occurs within the human body, but some state-of-the-art analytical techniques have revealed distinct cellular behaviors that occur only in the context of the interactions. These types of findings have inspired bioanalytical chemists to provide new tools to better understand these cellular behaviors and interactions. What blocks us from understanding critical biological interactions in the human body? Conventional approaches are often too naïve to provide realistic data and in vivo whole animal studies give complex results that may or may not be relevant for humans. Microfluidics offers an opportunity to bridge these two extremes: while these studies will not model the complexity of the in vivo human system, they can control the complexity so researchers can examine critical factors of interest carefully and quantitatively. In addition, the use of human cells, such as cells isolated from donated blood, captures human-relevant data and limits the use of animals in research. In addition, researchers can adapt these systems easily and cost-effectively to a variety of high-end signal transduction mechanisms, facilitating high-throughput studies that are also spatially, temporally, or chemically resolved. These strengths should allow microfluidic platforms to reveal critical parameters in the human body and provide insights that will help with the translation of pharmacological advances to clinical trials. In this Account, we describe selected microfluidic innovations within the last 5 years that focus on modeling both biophysical and biochemical interactions in cellular communication, such as flow and cell–cell networks. We also describe more advanced systems that mimic higher level biological networks, such as organ on-a-chip and animal on-a-chip models. Since the first papers in the early 1990s, interest in the bioanalytical use of microfluidics has grown significantly. Advances in micro-/nanofabrication technology have allowed researchers to produce miniaturized, biocompatible assay platforms suitable for microfluidic studies in biochemistry and chemical biology. Well-designed microfluidic platforms can achieve quick, in vitro analyses on pico- and femtoliter volume samples that are temporally, spatially, and chemically resolved. In addition, controlled cell culture techniques using a microfluidic platform have produced biomimetic systems that allow researchers to replicate and monitor physiological interactions. Pioneering work has successfully created cell–fluid, cell–cell, cell–tissue, tissue–tissue, even organ-like level interfaces. Researchers have monitored cellular behaviors in these biomimetic microfluidic environments, producing validated model systems to understand human pathophysiology and to support the development of new therapeutics. PMID:24555566

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.

Micro-Raman Technology to Interrogate Two-Phase Extraction on a Microfluidic Device.

PubMed

Nelson, Gilbert L; Asmussen, Susan E; Lines, Amanda M; Casella, Amanda J; Bottenus, Danny R; Clark, Sue B; Bryan, Samuel A

2018-05-21

Microfluidic devices provide ideal environments to study solvent extraction. When droplets form and generate plug flow down the microfluidic channel, the device acts as a microreactor in which the kinetics of chemical reactions and interfacial transfer can be examined. Here, we present a methodology that combines chemometric analysis with online micro-Raman spectroscopy to monitor biphasic extractions within a microfluidic device. Among the many benefits of microreactors is the ability to maintain small sample volumes, which is especially important when studying solvent extraction in harsh environments, such as in separations related to the nuclear fuel cycle. In solvent extraction, the efficiency of the process depends on complex formation and rates of transfer in biphasic systems. Thus, it is important to understand the kinetic parameters in an extraction system to maintain a high efficiency and effectivity of the process. This monitoring provided concentration measurements in both organic and aqueous plugs as they were pumped through the microfluidic channel. The biphasic system studied was comprised of HNO 3 as the aqueous phase and 30% (v/v) tributyl phosphate in n-dodecane comprised the organic phase, which simulated the plutonium uranium reduction extraction (PUREX) process. Using pre-equilibrated solutions (post extraction), the validity of the technique and methodology is illustrated. Following this validation, solutions that were not equilibrated were examined and the kinetics of interfacial mass transfer within the biphasic system were established. Kinetic results of extraction were compared to kinetics already determined on a macro scale to prove the efficacy of the technique.

A microfluidic paper-based analytical device for the assay of albumin-corrected fructosamine values from whole blood samples.

PubMed

Boonyasit, Yuwadee; Laiwattanapaisal, Wanida

2015-01-01

A method for acquiring albumin-corrected fructosamine values from whole blood using a microfluidic paper-based analytical system that offers substantial improvement over previous methods is proposed. The time required to quantify both serum albumin and fructosamine is shortened to 10 min with detection limits of 0.50 g dl(-1) and 0.58 mM, respectively (S/N = 3). The proposed system also exhibited good within-run and run-to-run reproducibility. The results of the interference study revealed that the acceptable recoveries ranged from 95.1 to 106.2%. The system was compared with currently used large-scale methods (n = 15), and the results demonstrated good agreement among the techniques. The microfluidic paper-based system has the potential to continuously monitor glycemic levels in low resource settings.

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

NASA Astrophysics Data System (ADS)

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

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

Microwave frequency sensor for detection of biological cells in microfluidic channels.

PubMed

Nikolic-Jaric, M; Romanuik, S F; Ferrier, G A; Bridges, G E; Butler, M; Sunley, K; Thomson, D J; Freeman, M R

2009-08-12

We present details of an apparatus for capacitive detection of biomaterials in microfluidic channels operating at microwave frequencies where dielectric effects due to interfacial polarization are minimal. A circuit model is presented, which can be used to adapt this detection system for use in other microfluidic applications and to identify ones where it would not be suitable. The detection system is based on a microwave coupled transmission line resonator integrated into an interferometer. At 1.5 GHz the system is capable of detecting changes in capacitance of 650 zF with a 50 Hz bandwidth. This system is well suited to the detection of biomaterials in a variety of suspending fluids, including phosphate-buffered saline. Applications involving both model particles (polystyrene microspheres) and living cells-baker's yeast (Saccharomyces cerevisiae) and Chinese hamster ovary cells-are presented.

Directional selection can drive the evolution of modularity in complex traits

PubMed Central

Melo, Diogo; Marroig, Gabriel

2015-01-01

Modularity is a central concept in modern biology, providing a powerful framework for the study of living organisms on many organizational levels. Two central and related questions can be posed in regard to modularity: How does modularity appear in the first place, and what forces are responsible for keeping and/or changing modular patterns? We approached these questions using a quantitative genetics simulation framework, building on previous results obtained with bivariate systems and extending them to multivariate systems. We developed an individual-based model capable of simulating many traits controlled by many loci with variable pleiotropic relations between them, expressed in populations subject to mutation, recombination, drift, and selection. We used this model to study the problem of the emergence of modularity, and hereby show that drift and stabilizing selection are inefficient at creating modular variational structures. We also demonstrate that directional selection can have marked effects on the modular structure between traits, actively promoting a restructuring of genetic variation in the selected population and potentially facilitating the response to selection. Furthermore, we give examples of complex covariation created by simple regimes of combined directional and stabilizing selection and show that stabilizing selection is important in the maintenance of established covariation patterns. Our results are in full agreement with previous results for two-trait systems and further extend them to include scenarios of greater complexity. Finally, we discuss the evolutionary consequences of modular patterns being molded by directional selection. PMID:25548154

Directional selection can drive the evolution of modularity in complex traits.

PubMed

Melo, Diogo; Marroig, Gabriel

2015-01-13

Modularity is a central concept in modern biology, providing a powerful framework for the study of living organisms on many organizational levels. Two central and related questions can be posed in regard to modularity: How does modularity appear in the first place, and what forces are responsible for keeping and/or changing modular patterns? We approached these questions using a quantitative genetics simulation framework, building on previous results obtained with bivariate systems and extending them to multivariate systems. We developed an individual-based model capable of simulating many traits controlled by many loci with variable pleiotropic relations between them, expressed in populations subject to mutation, recombination, drift, and selection. We used this model to study the problem of the emergence of modularity, and hereby show that drift and stabilizing selection are inefficient at creating modular variational structures. We also demonstrate that directional selection can have marked effects on the modular structure between traits, actively promoting a restructuring of genetic variation in the selected population and potentially facilitating the response to selection. Furthermore, we give examples of complex covariation created by simple regimes of combined directional and stabilizing selection and show that stabilizing selection is important in the maintenance of established covariation patterns. Our results are in full agreement with previous results for two-trait systems and further extend them to include scenarios of greater complexity. Finally, we discuss the evolutionary consequences of modular patterns being molded by directional selection.

Bead-based microfluidic immunoassay for diagnosis of Johne's disease

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

Wadhwa, Ashutosh; Foote, Robert; Shaw, Robert W

2012-01-01

Microfluidics technology offers a platform for development of point-of-care diagnostic devices for various infectious diseases. In this study, we examined whether serodiagnosis of Johne s disease (JD) can be conducted in a bead-based microfluidic assay system. Magnetic micro-beads were coated with antigens of the causative agent of JD, Mycobacterium avium subsp. paratuberculosis. The antigen-coated beads were incubated with serum samples of JD-positive or negative serum samples and then with a fluorescently-labeled secondary antibody (SAB). To confirm binding of serum antibodies to the antigen, the beads were subjected to flow cytometric analysis. Different conditions (dilutions of serum and SAB, types ofmore » SAB, and types of magnetic beads) were optimized for a great degree of differentiation between the JD-negative and JD-positive samples. Using the optimized conditions, we tested a well-classified set of 155 serum samples from JD negative and JD-positive cattle by using the bead-based flow cytometric assay. Of 105 JD-positive samples, 63 samples (60%) showed higher antibody binding levels than a cut-off value determined by using antibody binding levels of JD-negative samples. In contrast, only 43-49 JD-positive samples showed higher antibody binding levels than the cut-off value when the samples were tested by commercially-available immunoassays. Microfluidic assays were performed by magnetically immobilizing a number of beads within a microchannel of a glass microchip and detecting antibody on the collected beads by laser-induced fluorescence. Antigen-coated magnetic beads treated with bovine serum sample and fluorescently-labeled SAB were loaded into a microchannel to measure the fluorescence (reflecting level of antibody binding) on the beads in the microfluidic system. When the results of five bovine serum samples obtained with the system were compared to those obtained with the flow cytometer, a high level of correlation (linear regression, r2 = 0.994) was observed. In a further experiment, we magnetically immobilized antigen-coated beads in a microchannel, reacted the beads with serum and SAB in the channel, and detected antibody binding to the beads in the microfluidic system. A strong antibody binding in JD-positive serum was detected, whereas there was only negligible binding in negative control experiments. Our data suggest that the bead-based microfluidic system may form a basis for development of an on-site serodiagnosis of JD. Key Words: Mycobacterium avium ssp. paratuberculosis, Johne s disease, microfluidics, lab-on-a-chip.« less

Real-Time Microfluidic Blood-Counting System for PET and SPECT Preclinical Pharmacokinetic Studies.

PubMed

Convert, Laurence; Lebel, Réjean; Gascon, Suzanne; Fontaine, Réjean; Pratte, Jean-François; Charette, Paul; Aimez, Vincent; Lecomte, Roger

2016-09-01

Small-animal nuclear imaging modalities have become essential tools in the development process of new drugs, diagnostic procedures, and therapies. Quantification of metabolic or physiologic parameters is based on pharmacokinetic modeling of radiotracer biodistribution, which requires the blood input function in addition to tissue images. Such measurements are challenging in small animals because of their small blood volume. In this work, we propose a microfluidic counting system to monitor rodent blood radioactivity in real time, with high efficiency and small detection volume (∼1 μL). A microfluidic channel is built directly above unpackaged p-i-n photodiodes to detect β-particles with maximum efficiency. The device is embedded in a compact system comprising dedicated electronics, shielding, and pumping unit controlled by custom firmware to enable measurements next to small-animal scanners. Data corrections required to use the input function in pharmacokinetic models were established using calibrated solutions of the most common PET and SPECT radiotracers. Sensitivity, dead time, propagation delay, dispersion, background sensitivity, and the effect of sample temperature were characterized. The system was tested for pharmacokinetic studies in mice by quantifying myocardial perfusion and oxygen consumption with (11)C-acetate (PET) and by measuring the arterial input function using (99m)TcO4 (-) (SPECT). Sensitivity for PET isotopes reached 20%-47%, a 2- to 10-fold improvement relative to conventional catheter-based geometries. Furthermore, the system detected (99m)Tc-based SPECT tracers with an efficiency of 4%, an outcome not possible through a catheter. Correction for dead time was found to be unnecessary for small-animal experiments, whereas propagation delay and dispersion within the microfluidic channel were accurately corrected. Background activity and sample temperature were shown to have no influence on measurements. Finally, the system was successfully used in animal studies. A fully operational microfluidic blood-counting system for preclinical pharmacokinetic studies was developed. Microfluidics enabled reliable and high-efficiency measurement of the blood concentration of most common PET and SPECT radiotracers with high temporal resolution in small blood volume. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Advanced Nanostructures for Two-Phase Fluid and Thermal Transport

DTIC Science & Technology

2014-08-07

commercial applications. Pumped phase-change based microfluidic systems promise compact solutions with high heat removal capability. However...materials for liquid transport in microfluidics , cell manipulation in biological systems, and light tuning in optical applications via their...and 3c) with precise control for real- time fluid and optical manipulation. Inspired by hair and motile cilia on animal skin and plant leaves for

Development of a flexible microfluidic system integrating magnetic micro-actuators for trapping biological species

NASA Astrophysics Data System (ADS)

Fulcrand, R.; Jugieu, D.; Escriba, C.; Bancaud, A.; Bourrier, D.; Boukabache, A.; Gué, A. M.

2009-10-01

A flexible microfluidic system embedding microelectromagnets has been designed, modeled and fabricated by using a photosensitive resin as structural material. The fabrication process involves the integration of micro-coils in a multilayer SU-8 microfluidic system by combining standard electroplating and dry films lamination. This technique offers numerous advantages in terms of integration, biocompatibility and chemical resistance. Various designs of micro-coils, including spiral, square or serpentine wires, have been simulated and experimentally tested. It has been established that thermal dissipation in micro-coils depends strongly on the number of turns and current density but remains compatible with biological applications. Real-time experimentations show that these micro-actuators are efficient in trapping magnetic micro-beads without any external field source or a permanent magnet and highlight that the size of microfluidic channels has been adequately designed for optimal trapping. Moreover, we trap magnetic beads in less than 2 s and release them instantaneously into the micro-channel. The actuation solely relies on electric fields, which are easier to control than standard magneto-fluidic modules.

Binary particle separation in droplet microfluidics using acoustophoresis

NASA Astrophysics Data System (ADS)

Fornell, Anna; Cushing, Kevin; Nilsson, Johan; Tenje, Maria

2018-02-01

We show a method for separation of two particle species with different acoustic contrasts originally encapsulated in the same droplet in a continuous two-phase system. This was realized by using bulk acoustic standing waves in a 380 μm wide silicon-glass microfluidic channel. Polystyrene particles (positive acoustic contrast particles) and in-house synthesized polydimethylsiloxane (PDMS) particles (negative acoustic contrast particles) were encapsulated inside water-in-oil droplets either individually or in a mixture. At acoustic actuation of the system at the fundamental resonance frequency, the polystyrene particles were moved to the center of the droplet (pressure node), while the PDMS particles were moved to the sides of the droplet (pressure anti-nodes). The acoustic particle manipulation step was combined in series with a trifurcation droplet splitter, and as the original droplet passed through the splitter and was divided into three daughter droplets, the polystyrene particles were directed into the center daughter droplet, while the PDMS particles were directed into the two side daughter droplets. The presented method expands the droplet microfluidics tool-box and offers new possibilities to perform binary particle separation in droplet microfluidic systems.

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.

A Label-Free Microfluidic Biosensor for Activity Detection of Single Microalgae Cells Based on Chlorophyll Fluorescence

PubMed Central

Wang, Junsheng; Sun, Jinyang; Song, Yongxin; Xu, Yongyi; Pan, Xinxiang; Sun, Yeqing; Li, Dongqing

2013-01-01

Detection of living microalgae cells is very important for ballast water treatment and analysis. Chlorophyll fluorescence is an indicator of photosynthetic activity and hence the living status of plant cells. In this paper, we developed a novel microfluidic biosensor system that can quickly and accurately detect the viability of single microalgae cells based on chlorophyll fluorescence. The system is composed of a laser diode as an excitation light source, a photodiode detector, a signal analysis circuit, and a microfluidic chip as a microalgae cell transportation platform. To demonstrate the utility of this system, six different living and dead algae samples (Karenia mikimotoi Hansen, Chlorella vulgaris, Nitzschia closterium, Platymonas subcordiformis, Pyramidomonas delicatula and Dunaliella salina) were tested. The developed biosensor can distinguish clearly between the living microalgae cells and the dead microalgae cells. The smallest microalgae cells that can be detected by using this biosensor are 3 μm ones. Even smaller microalgae cells could be detected by increasing the excitation light power. The developed microfluidic biosensor has great potential for in situ ballast water analysis. PMID:24287532

Droplet-based microfluidics for dose-response assay of enzyme inhibitors by electrochemical method.

PubMed

Gu, Shuqing; Lu, Youlan; Ding, Yaping; Li, Li; Zhang, Fenfen; Wu, Qingsheng

2013-09-24

A simple but robust droplet-based microfluidic system was developed for dose-response enzyme inhibition assay by combining concentration gradient generation method with electrochemical detection method. A slotted-vials array and a tapered tip capillary were used for reagents introduction and concentration gradient generation, and a polydimethylsiloxane (PDMS) microfluidic chip integrated with microelectrodes was used for droplet generation and electrochemical detection. Effects of oil flow rate and surfactant on electrochemical sensing were investigated. This system was validated by measuring dose-response curves of three types of acetylcholinesterase (AChE) inhibitors, including carbamate pesticide, organophosphorus pesticide, and therapeutic drugs regulating Alzheimer's disease. Carbaryl, chlorpyrifos, and tacrine were used as model analytes, respectively, and their IC50 (half maximal inhibitory concentration) values were determined. A whole enzyme inhibition assay was completed in 6 min, and the total consumption of reagents was less than 5 μL. This microfluidic system is applicable to many biochemical reactions, such as drug screening and kinetic studies, as long as one of the reactants or products is electrochemically active. Copyright © 2013 Elsevier B.V. All rights reserved.

Systems and methods for improved telepresence

DOEpatents

Anderson, Matthew O.; Willis, W. David; Kinoshita, Robert A.

2005-10-25

The present invention provides a modular, flexible system for deploying multiple video perception technologies. The telepresence system of the present invention is capable of allowing an operator to control multiple mono and stereo video inputs in a hands-free manner. The raw data generated by the input devices is processed into a common zone structure that corresponds to the commands of the user, and the commands represented by the zone structure are transmitted to the appropriate device. This modularized approach permits input devices to be easily interfaced with various telepresence devices. Additionally, new input devices and telepresence devices are easily added to the system and are frequently interchangeable. The present invention also provides a modular configuration component that allows an operator to define a plurality of views each of which defines the telepresence devices to be controlled by a particular input device. The present invention provides a modular flexible system for providing telepresence for a wide range of applications. The modularization of the software components combined with the generalized zone concept allows the systems and methods of the present invention to be easily expanded to encompass new devices and new uses.

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.

From sample-to-answer: integrated genotyping and immunological analysis microfluidic platforms for the diagnostic and treatment of coeliac disease

NASA Astrophysics Data System (ADS)

Jung, M.; Höth, J.; Erwes, J.; Latta, D.; Strobach, X.; Hansen-Hagge, T.; Klemm, R.; Gärtner, C.; Demiris, T. M.; O'Sullivan, C.; Ritzi-Lehnert, M.; Drese, K. S.

2011-02-01

Taking advantage of microfluidics technology, a Lab-on-Chip system was developed offering the possibility of performing HLA (Human Leukocyte Antigen) typing to test genetic predisposition to coeliac disease and measure the level of immunodeficiency at the point-of-care. These analysis procedures are implemented on two different microfluidic cartridges, both having identical interfacial connections to the identical automated instrument. In order to assess the concentration of the targeted analytes in human blood, finger prick samples are processed to either extract genomic DNA carrying the coeliac disease gene or blood plasma containing the disease specific antibodies. We present here the different microfluidic modules integrated in a common platform, capable of automated sample preparation and analyte detection. In summary, this new microfluidic approach will dramatically reduce the costs of materials (polymer for the disposable chips and minute amount of bio-reagents) and minimize the time for analysis down to less than 20 minutes. In comparison to the state of the art detection of coeliac disease this work represents a tremendous improvement for the patient's quality of live and will significantly reduce the cost burden on the health care system.

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.

Framework for Defining and Assessing Benefits of a Modular Assembly Design Approach for Exploration Systems

NASA Technical Reports Server (NTRS)

Dorsey, John T.; Collins, Timothy J.; Moe, Rud V.; Doggett,. William R.

2006-01-01

A comprehensive modular assembly system model has been proposed that extends the art from modular hardware, to include in-space assembly, servicing and repair and it s critical components of infrastructure, agents and assembly operations. Benefits of modular assembly have been identified and a set of metrics defined that extends the art beyond the traditional measures of performance, with emphasis on criteria that allow life-cycle mission costs to be used as a figure of merit (and include all substantive terms that have an impact on the evaluation). The modular assembly approach was used as a basis for developing a Solar Electric Transfer Vehicle (SETV) concept and three modular assembly scenarios were developed. The modular assembly approach also allows the SETV to be entered into service much earlier than competing conventional configurations and results in a great deal of versatility in accommodating different launch vehicle payload capabilities, allowing for modules to be pre-assembled before launch or assembled on orbit, without changing the space vehicle design.

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

NASA Astrophysics Data System (ADS)

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

2016-02-01

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

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

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

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

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

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

Microfluidic chip-based technologies: emerging platforms for cancer diagnosis

PubMed Central

2013-01-01

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

A self-triggered picoinjector in microfluidics

NASA Astrophysics Data System (ADS)

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

2016-12-01

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

The modular socket system in a rural setting in Indonesia.

PubMed

Giesberts, Bob; Ennion, Liezel; Hjelmstrom, Olle; Karma, Agusni; Lechler, Knut; Hekman, Edsko; Bergsma, Arjen

2018-06-01

Prosthetic services are inaccessible to people living in rural areas. Systems like the modular socket system have the potential to be fabricated outside of the prosthetic workshop. This study aimed to evaluate the patient's performance and satisfaction with the use of the modular socket system, and the technical feasibility of its implementation in a rural setting. A quantitative longitudinal descriptive study design was followed. A total of 15 persons with a lower limb amputation were fitted with the modular socket system and followed over 4-6 months. Performance was measured using a 2-min walk test, 10-m walk test and mobility and function questionnaire. Satisfaction was measured by the Socket Fit Comfort Score, Prosthesis Evaluation Questionnaire and EuroQoL 5 Dimensions 5 Levels. Notes on technical feasibility were taken at the moment of fitting ( t 0 ), at 1-3 months post fitting ( t 1 ) and at the end evaluation at 4-6 months post fitting ( t 2 ). Performance did not change between t 0 and t 2 . The comfort of the socket fit reduced between t 0 and t 2 . Satisfaction with prosthesis and general health status stayed constant over time. The average fitting-time for the modular socket system was 6.4 h. The modular socket system can be considered a useful alternative for use in rural settings. Clinical relevance The use of the modular socket system is feasible and can improve accessibility to prosthetic technology in rural areas. Experienced prosthetic users were satisfied with the performance and the device. The shorter manufacturing time and use of only hand-held tools makes it an ideal alternative for use in remote and rural settings.

Modular, Reconfigurable, and Rapid Response Space Systems: The Remote Sensing Advanced Technology Microsatellite

NASA Technical Reports Server (NTRS)

Esper, Jaime; Andary, Jim; Oberright, John; So, Maria; Wegner, Peter; Hauser, Joe

2004-01-01

Modular, Reconfigurable, and Rapid-response (MR(sup 2)) space systems represent a paradigm shift in the way space assets of all sizes are designed, manufactured, integrated, tested, and flown. This paper will describe the MR(sup 2) paradigm in detail, and will include guidelines for its implementation. The Remote Sensing Advanced Technology microsatellite (RSAT) is a proposed flight system test-bed used for developing and implementing principles and best practices for MR(sup 2) spacecraft, and their supporting infrastructure. The initial goal of this test-bed application is to produce a lightweight (approx. 100 kg), production-minded, cost-effective, and scalable remote sensing micro-satellite capable of high performance and broad applicability. Such applications range from future distributed space systems, to sensor-webs, and rapid-response satellite systems. Architectures will be explored that strike a balance between modularity and integration while preserving the MR(sup 2) paradigm. Modularity versus integration has always been a point of contention when approaching a design: whereas one-of-a-kind missions may require close integration resulting in performance optimization, multiple and flexible application spacecraft benefit &om modularity, resulting in maximum flexibility. The process of building spacecraft rapidly (< 7 days), requires a concerted and methodical look at system integration and test processes and pitfalls. Although the concept of modularity is not new and was first developed in the 1970s by NASA's Goddard Space Flight Center (Multi-Mission Modular Spacecraft), it was never modernized and was eventually abandoned. Such concepts as the Rapid Spacecraft Development Office (RSDO) became the preferred method for acquiring satellites. Notwithstanding, over the past 30 years technology has advanced considerably, and the time is ripe to reconsider modularity in its own right, as enabler of R(sup 2), and as a key element of transformational systems. The MR2 architecture provides a competitive advantage over the old modular approach in its rapid response to market needs that are difficult to predict both from the perspectives of evolving technology, as well as mission and application requirements.

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

PubMed Central

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

2007-01-01

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

The upcoming 3D-printing revolution in microfluidics

PubMed Central

Bhattacharjee, Nirveek; Urrios, Arturo; Kang, Shawn; Folch, Albert

2016-01-01

In the last two decades, the vast majority of microfluidic systems have been built in poly(dimethylsiloxane) (PDMS) by soft lithography, a technique based on PDMS micromolding. A long list of key PDMS properties have contributed to the success of soft lithography: PDMS is biocompatible, elastomeric, transparent, gas-permeable, water-impermeable, fairly inexpensive, copyright-free, and rapidly prototyped with high precision using simple procedures. However, the fabrication process typically involves substantial human labor, which tends to make PDMS devices difficult to disseminate outside of research labs, and the layered molding limits the 3D complexity of the devices that can be produced. 3D-printing has recently attracted attention as a way to fabricate microfluidic systems due to its automated, assembly-free 3D fabrication, rapidly decreasing costs, and fast-improving resolution and throughput. Resins with properties approaching those of PDMS are being developed. Here we review past and recent efforts in 3D-printing of microfluidic systems. We compare the salient features of PDMS molding with those of 3D-printing and we give an overview of the critical barriers that have prevented the adoption of 3D-printing by microfluidic developers, namely resolution, throughput, and resin biocompatibility. We also evaluate the various forces that are persuading researchers to abandon PDMS molding in favor of 3D-printing in growing numbers. PMID:27101171

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

PubMed

Saha, Arindam; Jana, Nikhil R

2015-01-14

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

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

Compact and controlled microfluidic mixing and biological particle capture

NASA Astrophysics Data System (ADS)

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

2016-11-01

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

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

PubMed

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

2013-01-01

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

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

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.

DEPSCOR06: A Dispersed Monopropellant Microslug Approach for Discrete Satellite Micropropulsion

DTIC Science & Technology

2010-08-01

microfluidics , a controlled slug formation process represents a virtual ’self- valving ’ mechanism which affords finer resolution than a micro- valve for a... microfluidic flow system to study the effects of geometry and material properties on the microslug formation phenomena. The inspiration for this work is derived...the-shelf microfluidic chip, manufactured by Micralyne, Inc. was used as shown in Figure A-1.1. Figure 1.A.1: Geometry of the Micralyne 50 µm x 20 µm

Modular anode assemblies and methods of using the same for electrochemical reduction

DOEpatents

Wiedmeyer, Stanley G; Barnes, Laurel A; Williamson, Mark A; Willit, James L

2015-02-17

Modular anode assemblies are used in electrolytic oxide reduction systems for scalable reduced metal production via electrolysis. Assemblies include a channel frame connected to several anode rods extending into an electrolyte. An electrical system powers the rods while being insulated from the channel frame. A cooling system removes heat from anode rods and the electrical system. An anode guard attaches to the channel frame to prevent accidental electrocution or damage during handling or repositioning. Each anode rod may be divided into upper and lower sections to permit easy repair and swapping out of lower sections. The modular assemblies may have standardized components to permit placement at multiple points within a reducing system. Example methods may operate an electrolytic oxide reduction system by positioning the modular anode assemblies in the reduction system and applying electrical power to the plurality of anode assemblies.

Standardized Modular Power Interfaces for Future Space Explorations Missions

NASA Technical Reports Server (NTRS)

Oeftering, Richard

2015-01-01

Earlier studies show that future human explorations missions are composed of multi-vehicle assemblies with interconnected electric power systems. Some vehicles are often intended to serve as flexible multi-purpose or multi-mission platforms. This drives the need for power architectures that can be reconfigured to support this level of flexibility. Power system developmental costs can be reduced, program wide, by utilizing a common set of modular building blocks. Further, there are mission operational and logistics cost benefits of using a common set of modular spares. These benefits are the goals of the Advanced Exploration Systems (AES) Modular Power System (AMPS) project. A common set of modular blocks requires a substantial level of standardization in terms of the Electrical, Data System, and Mechanical interfaces. The AMPS project is developing a set of proposed interface standards that will provide useful guidance for modular hardware developers but not needlessly constrain technology options, or limit future growth in capability. In 2015 the AMPS project focused on standardizing the interfaces between the elements of spacecraft power distribution and energy storage. The development of the modular power standard starts with establishing mission assumptions and ground rules to define design application space. The standards are defined in terms of AMPS objectives including Commonality, Reliability-Availability, Flexibility-Configurability and Supportability-Reusability. The proposed standards are aimed at assembly and sub-assembly level building blocks. AMPS plans to adopt existing standards for spacecraft command and data, software, network interfaces, and electrical power interfaces where applicable. Other standards including structural encapsulation, heat transfer, and fluid transfer, are governed by launch and spacecraft environments and bound by practical limitations of weight and volume. Developing these mechanical interface standards is more difficult but an essential part of defining physical building blocks of modular power. This presentation describes the AMPS projects progress towards standardized modular power interfaces.

Engineering Bony Hybrid Organs In Vitro

DTIC Science & Technology

2006-11-01

microfluidic cell culture system using elastomeric channels and Braille displays (Gu et al., 2004; Futai et al., 2004). We have now further developed this...Takayama S, 2004: Computerized microfluidic cell culture using elastomeric channels and braille displays. Proc. Natl. Acad. Sci. USA 101, 15861-15866

Structural Determination of Biomolecules in Microfluidic Systems

NASA Astrophysics Data System (ADS)

Butler, John C.; Menard, Etienne; Rogers, John A.; Wong, Gerard C. L.

2004-03-01

Supramolecular biological complexes are often too large to be crystallized for structural studies. Here, we explore the use of microfluidic arrays to order a model self-assembled cytoskeletal system. Filamentous actin (F-actin) is a negatively charged protein rod and is a key structural component in the eukaryotic cytoskeleton. In this context, F-actin can self-assemble with actin binding proteins (ABP) in a highly regulated manner to dynamically form structures for a wide range of biomechanical functions. In this work, we will systematically study the action of 3 types of actin binding proteins (a-actinin, fimbrin, cofilin) on the self-assembled structures of F-actin that have been aligned in microfluidic arrays.

Microfluidic hubs, systems, and methods for interface fluidic modules

DOEpatents

Bartsch, Michael S; Claudnic, Mark R; Kim, Hanyoup; Patel, Kamlesh D; Renzi, Ronald F; Van De Vreugde, James L

2015-01-27

Embodiments of microfluidic hubs and systems are described that may be used to connect fluidic modules. A space between surfaces may be set by fixtures described herein. In some examples a fixture may set substrate-to-substrate spacing based on a distance between registration surfaces on which the respective substrates rest. Fluidic interfaces are described, including examples where fluid conduits (e.g. capillaries) extend into the fixture to the space between surfaces. Droplets of fluid may be introduced to and/or removed from microfluidic hubs described herein, and fluid actuators may be used to move droplets within the space between surfaces. Continuous flow modules may be integrated with the hubs in some examples.

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.

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.

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.

Hardware and circuit design of a vibrational cleaner

NASA Astrophysics Data System (ADS)

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

2016-11-01

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

Enabling Technologies for Microfluidic Flow Control and Detection

NASA Astrophysics Data System (ADS)

Leslie, Daniel Christopher

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

Decentralized Modular Systems Versus Centralized Systems.

ERIC Educational Resources Information Center

Crossey, R. E.

Building design, planning, and construction programing for modular decentralized mechanical building systems are outlined in terms of costs, performance, expansion and flexibility. Design strategy, approach, and guidelines for implementing such systems for buildings are suggested, with emphasis on mechanical equipment and building element…

Molecular solid-state inverter-converter system

NASA Technical Reports Server (NTRS)

Birchenough, A. G.

1973-01-01

A modular approach for aerospace electrical systems has been developed, using lightweight high efficiency pulse width modulation techniques. With the modular approach, a required system is obtained by paralleling modules. The modular system includes the inverters and converters, a paralleling system, and an automatic control and fault-sensing protection system with a visual annunciator. The output is 150 V dc, or a low distortion three phase sine wave at 120 V, 400 Hz. Input power is unregulated 56 V dc. Each module is rated 2.5 kW or 3.6 kVA at 0.7 power factor.

The rotary zone thermal cycler: A low-power system enabling automated rapid PCR

DOE PAGES

Bartsch, Michael S.; Edwards, Harrison S.; Gas Transmission Systems, Walnut Creek, CA; ...

2015-03-31

In this study, advances in molecular biology, microfluidics, and laboratory automation continue to expand the accessibility and applicability of these methods beyond the confines of conventional, centralized laboratory facilities and into point of use roles in clinical, military, forensic, portable, and field-deployed applications. As a result, there is a growing need to adapt the unit operations of molecular biology such as aliquoting, centrifuging, mixing, and thermal cycling to compact, portable, low-power, and automation-ready formats. Here we present one such adaptation, the rotary zone thermal cycler (RZTC), a novel wheel-based device capable of cycling up to four different fixed-temperature blocks intomore » contact with a stationary 4-microliter capillary-bound sample to realize 1-3 second transitions with steady state heater power of less than 10 W. We further demonstrate the utility of the RZTC for DNA amplification as part of a highly integrated rotary zone PCR (rzPCR) system using low-volume valves and syringe-based fluid handling to automate sample loading and unloading, thermal cycling, and between run cleaning functionalities in a compact, modular form factor. In addition to characterizing the performance of the RZTC and the efficacy of different online cleaning protocols, preliminary results are presented for rapid single-plex PCR, multiplex short tandem repeat (STR) amplification, and second strand cDNA synthesis.« less

The rotary zone thermal cycler: A low-power system enabling automated rapid PCR

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

Bartsch, Michael S.; Edwards, Harrison S.; Gas Transmission Systems, Walnut Creek, CA

In this study, advances in molecular biology, microfluidics, and laboratory automation continue to expand the accessibility and applicability of these methods beyond the confines of conventional, centralized laboratory facilities and into point of use roles in clinical, military, forensic, portable, and field-deployed applications. As a result, there is a growing need to adapt the unit operations of molecular biology such as aliquoting, centrifuging, mixing, and thermal cycling to compact, portable, low-power, and automation-ready formats. Here we present one such adaptation, the rotary zone thermal cycler (RZTC), a novel wheel-based device capable of cycling up to four different fixed-temperature blocks intomore » contact with a stationary 4-microliter capillary-bound sample to realize 1-3 second transitions with steady state heater power of less than 10 W. We further demonstrate the utility of the RZTC for DNA amplification as part of a highly integrated rotary zone PCR (rzPCR) system using low-volume valves and syringe-based fluid handling to automate sample loading and unloading, thermal cycling, and between run cleaning functionalities in a compact, modular form factor. In addition to characterizing the performance of the RZTC and the efficacy of different online cleaning protocols, preliminary results are presented for rapid single-plex PCR, multiplex short tandem repeat (STR) amplification, and second strand cDNA synthesis.« less

Preparation of Nucleic Acid Libraries for Personalized Sequencing Systems Using an Integrated Microfluidic Hub Technology (Seventh Annual Sequencing, Finishing, Analysis in the Future (SFAF) Meeting 2012)

ScienceCinema

Patel, Kamlesh D.

2018-01-22

Kamlesh (Ken) Patel from Sandia National Laboratories (Livermore, California) presents "Preparation of Nucleic Acid Libraries for Personalized Sequencing Systems Using an Integrated Microfluidic Hub Technology " at the 7th Annual Sequencing, Finishing, Analysis in the Future (SFAF) Meeting held in June, 2012 in Santa Fe, NM.

Fluid delivery manifolds and microfluidic systems

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

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

2017-02-28

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

Preparation of Nucleic Acid Libraries for Personalized Sequencing Systems Using an Integrated Microfluidic Hub Technology (Seventh Annual Sequencing, Finishing, Analysis in the Future (SFAF) Meeting 2012)

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

Patel, Kamlesh D.

2012-06-01

Kamlesh (Ken) Patel from Sandia National Laboratories (Livermore, California) presents "Preparation of Nucleic Acid Libraries for Personalized Sequencing Systems Using an Integrated Microfluidic Hub Technology " at the 7th Annual Sequencing, Finishing, Analysis in the Future (SFAF) Meeting held in June, 2012 in Santa Fe, NM.

Component Control System for a Vehicle

NASA Technical Reports Server (NTRS)

Lee, Chunhao J. (Inventor); Fraser-Chanpong, Nathan (Inventor); Vitale, Robert L. (Inventor); Akinyode, Akinjide Akinniyi (Inventor); Dawson, Andrew D. (Inventor); Guo, Raymond (Inventor); Waligora, Thomas M. (Inventor); Spain, Ivan (Inventor); Bluethmann, William J. (Inventor); Reed, Ryan M. (Inventor)

2016-01-01

A vehicle includes a chassis, a modular component, and a central operating system. The modular component is supported by the chassis. The central operating system includes a component control system, a primary master controller, and a secondary master controller. The component control system is configured for controlling the modular component. The primary and secondary master controllers are in operative communication with the component control system. The primary and secondary master controllers are configured to simultaneously transmit commands to the component control system. The component control system is configured to accept commands from the secondary master controller only when a fault occurs in the primary master controller.

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

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

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.

Label-free cell separation and sorting in microfluidic systems

PubMed Central

Gossett, Daniel R.; Weaver, Westbrook M.; Mach, Albert J.; Hur, Soojung Claire; Tse, Henry Tat Kwong; Lee, Wonhee; Amini, Hamed

2010-01-01

Cell separation and sorting are essential steps in cell biology research and in many diagnostic and therapeutic methods. Recently, there has been interest in methods which avoid the use of biochemical labels; numerous intrinsic biomarkers have been explored to identify cells including size, electrical polarizability, and hydrodynamic properties. This review highlights microfluidic techniques used for label-free discrimination and fractionation of cell populations. Microfluidic systems have been adopted to precisely handle single cells and interface with other tools for biochemical analysis. We analyzed many of these techniques, detailing their mode of separation, while concentrating on recent developments and evaluating their prospects for application. Furthermore, this was done from a perspective where inertial effects are considered important and general performance metrics were proposed which would ease comparison of reported technologies. Lastly, we assess the current state of these technologies and suggest directions which may make them more accessible. Figure A wide range of microfluidic technologies have been developed to separate and sort cells by taking advantage of differences in their intrinsic biophysical properties PMID:20419490

Windowless microfluidic platform based on capillary burst valves for high intensity x-ray measurements.

PubMed

Vig, Asger Laurberg; Haldrup, Kristoffer; Enevoldsen, Nikolaj; Thilsted, Anil Haraksingh; Eriksen, Johan; Kristensen, Anders; Feidenhans'l, Robert; Nielsen, Martin Meedom

2009-11-01

We propose and describe a microfluidic system for high intensity x-ray measurements. The required open access to a microfluidic channel is provided by an out-of-plane capillary burst valve (CBV). The functionality of the out-of-plane CBV is characterized with respect to the diameter of the windowless access hole, ranging from 10 to 130 microm. Maximum driving pressures from 22 to 280 mbar corresponding to refresh rates of the exposed sample from 300 Hz to 54 kHz is demonstrated. The microfluidic system is tested at beamline ID09b at the ESRF synchrotron radiation facility in Grenoble, and x-ray scattering measurements are shown to be feasible and to require only very limited amounts of sample, <1 ml/h of measurements without recapturing of sample. With small adjustments of the present chip design, scattering angles up to 30 degrees can be achieved without shadowing effects and integration on-chip mixing and spectroscopy appears straightforward.

Windowless microfluidic platform based on capillary burst valves for high intensity x-ray measurements

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

Vig, Asger Laurberg; Enevoldsen, Nikolaj; Thilsted, Anil Haraksingh

2009-11-15

We propose and describe a microfluidic system for high intensity x-ray measurements. The required open access to a microfluidic channel is provided by an out-of-plane capillary burst valve (CBV). The functionality of the out-of-plane CBV is characterized with respect to the diameter of the windowless access hole, ranging from 10 to 130 {mu}m. Maximum driving pressures from 22 to 280 mbar corresponding to refresh rates of the exposed sample from 300 Hz to 54 kHz is demonstrated. The microfluidic system is tested at beamline ID09b at the ESRF synchrotron radiation facility in Grenoble, and x-ray scattering measurements are shown tomore » be feasible and to require only very limited amounts of sample, <1 ml/h of measurements without recapturing of sample. With small adjustments of the present chip design, scattering angles up to 30 deg. can be achieved without shadowing effects and integration on-chip mixing and spectroscopy appears straightforward.« less

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

PubMed

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

2017-01-01

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

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

PubMed Central

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

2016-01-01

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

Novel localized heating technique on centrifugal microfluidic disc with wireless temperature monitoring system.

PubMed

Joseph, Karunan; Ibrahim, Fatimah; Cho, Jongman

2015-01-01

Recent advances in the field of centrifugal microfluidic disc suggest the need for electrical interface in the disc to perform active biomedical assays. In this paper, we have demonstrated an active application powered by the energy harvested from the rotation of the centrifugal microfluidic disc. A novel integration of power harvester disc onto centrifugal microfluidic disc to perform localized heating technique is the main idea of our paper. The power harvester disc utilizing electromagnetic induction mechanism generates electrical energy from the rotation of the disc. This contributes to the heat generation by the embedded heater on the localized heating disc. The main characteristic observed in our experiment is the heating pattern in relative to the rotation of the disc. The heating pattern is monitored wirelessly with a digital temperature sensing system also embedded on the disc. Maximum temperature achieved is 82 °C at rotational speed of 2000 RPM. The technique proves to be effective for continuous heating without the need to stop the centrifugal motion of the disc.

The Case for Modular Redundancy in Large-Scale High Performance Computing Systems

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

Engelmann, Christian; Ong, Hong Hoe; Scott, Stephen L

2009-01-01

Recent investigations into resilience of large-scale high-performance computing (HPC) systems showed a continuous trend of decreasing reliability and availability. Newly installed systems have a lower mean-time to failure (MTTF) and a higher mean-time to recover (MTTR) than their predecessors. Modular redundancy is being used in many mission critical systems today to provide for resilience, such as for aerospace and command \\& control systems. The primary argument against modular redundancy for resilience in HPC has always been that the capability of a HPC system, and respective return on investment, would be significantly reduced. We argue that modular redundancy can significantly increasemore » compute node availability as it removes the impact of scale from single compute node MTTR. We further argue that single compute nodes can be much less reliable, and therefore less expensive, and still be highly available, if their MTTR/MTTF ratio is maintained.« less

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

PubMed

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

2016-07-07

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

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.

Modular biowaste monitoring system conceptual design

NASA Technical Reports Server (NTRS)

Fogal, G. L.

1974-01-01

The objective of the study was to define requirements and generate a conceptual design for a Modular Biowaste Monitoring System for specifically supporting shuttle life science experimental and diagnostic programs.

Unmanned Aerial Vehicle Non Line of Sight Chemical Detection Final Report

DTIC Science & Technology

2016-12-01

aircraft system that is used to perform point detection of chemical warfare agents and collection of vapor, liquid, and solid samples. A modular payload...Standoff Quadcopter Unmanned aircraft system Modular payload 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF...Manufacturing Division, modular payloads are being developed to perform point detection and CBRNE sampling. The available UAS is a quadcopter capable of

Advanced, Adaptive, Modular, Distributed, Generic Universal FADEC Framework for Intelligent Propulsion Control Systems (Preprint)

DTIC Science & Technology

2007-09-01

AFRL-RZ-WP-TP-2008-2044 ADVANCED, ADAPTIVE, MODULAR, DISTRIBUTED, GENERIC UNIVERSAL FADEC FRAMEWORK FOR INTELLIGENT PROPULSION CONTROL...GRANT NUMBER 4. TITLE AND SUBTITLE ADVANCED, ADAPTIVE, MODULAR, DISTRIBUTED, GENERIC UNIVERSAL FADEC FRAMEWORK FOR INTELLIGENT PROPULSION... FADEC is unique and expensive to develop, produce, maintain, and upgrade for its particular application. Each FADEC is a centralized system, with a

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

Chemical and Biological Dynamics Using Droplet-Based Microfluidics.

PubMed

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

2017-06-12

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

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.

A sample-to-result system for blood coagulation tests on a microfluidic disk analyzer

PubMed Central

Lin, Chia-Hui; Liu, Cheng-Yuan; Shih, Chih-Hsin; Lu, Chien-Hsing

2014-01-01

In this report, we describe in detail a microfluidic analyzer, which is able to conduct blood coagulation tests using whole blood samples. Sample preparation steps, such as whole blood aliquoting and metering, plasma separation, decanting, and mixing with reagents were performed in sequence through microfluidic functions integrated on a disk. Both prothrombin time (PT) and activated partial thromboplastin time (aPTT) were carried out on the same platform and the test results can be reported in 5 min. Fifty clinical samples were tested for both PT and aPTT utilizing the microfluidic disk analyzer and the instrument used in hospitals. The test results showed good correlation and agreement between the two instruments. PMID:25332733

Chip in a lab: Microfluidics for next generation life science research

PubMed Central

Streets, Aaron M.; Huang, Yanyi

2013-01-01

Microfluidic circuits are characterized by fluidic channels and chambers with a linear dimension on the order of tens to hundreds of micrometers. Components of this size enable lab-on-a-chip technology that has much promise, for example, in the development of point-of-care diagnostics. Micro-scale fluidic circuits also yield practical, physical, and technological advantages for studying biological systems, enhancing the ability of researchers to make more precise quantitative measurements. Microfluidic technology has thus become a powerful tool in the life science research laboratory over the past decade. Here we focus on chip-in-a-lab applications of microfluidics and survey some examples of how small fluidic components have provided researchers with new tools for life science research. PMID:23460772

Microfluidic technologies for synthetic biology.

PubMed

Vinuselvi, Parisutham; Park, Seongyong; Kim, Minseok; Park, Jung Min; Kim, Taesung; Lee, Sung Kuk

2011-01-01

Microfluidic technologies have shown powerful abilities for reducing cost, time, and labor, and at the same time, for increasing accuracy, throughput, and performance in the analysis of biological and biochemical samples compared with the conventional, macroscale instruments. Synthetic biology is an emerging field of biology and has drawn much attraction due to its potential to create novel, functional biological parts and systems for special purposes. Since it is believed that the development of synthetic biology can be accelerated through the use of microfluidic technology, in this review work we focus our discussion on the latest microfluidic technologies that can provide unprecedented means in synthetic biology for dynamic profiling of gene expression/regulation with high resolution, highly sensitive on-chip and off-chip detection of metabolites, and whole-cell analysis.

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

New insight on the formation of whey protein microbeads by a microfluidic system

NASA Astrophysics Data System (ADS)

Andoyo, Robi; Guyomarc'h, Fanny; Tabuteau, Hervé; Famelart, Marie-Hélène

2018-02-01

The current paper describes the formation of whey protein microbeads (WPM) having a spherical shape and a monodispersed size distribution. A microfluidic flow-focusing geometry was used to control the production of whey protein microdroplets in a hydrophobic phase. The microfluidic system consists of two inlet channels where the WPI solution and the lipophilic phase were separately injected towards the flow-focusing (FF) junction where they eventually meet, then co-flow. A whey protein isolate (WPI) solution of 150 g/kg protein and two types of hydrophobic phases, i.e. sunflower oil and n-dodecane, were tested as the continuous phase. The formation of WPM was observed microscopically. The aim of the present study was to describe the production of stable monodisperse WPM in suspension in milk ultrafiltrate using a microfluidic system. Hints to perform the control of the running parameters, i.e. choice of the hydrophobic phase or fluids flowrates, are provided. The results showed that in the sunflower oil, microdroplets had a large polydisperse size distribution, while in n-dodecane, microdroplets with narrow size distribution were obtained. Stabilization of the whey protein microdroplets through heat-gelation at 75 °C for 20 min in n-dodecane produced WPM and no change in shape nor size is observed. Meanwhile replacing the n-dodecane by MUF using centrifugation and washing caused the swelling of the WPM, but dispersity remained low. From this study, microfluidic system seemed to be a suitable method to be used for producing small quantities of monodisperse WPM.

Modular biowaste monitoring system

NASA Technical Reports Server (NTRS)

Fogal, G. L.

1975-01-01

The objective of the Modular Biowaste Monitoring System Program was to generate and evaluate hardware for supporting shuttle life science experimental and diagnostic programs. An initial conceptual design effort established requirements and defined an overall modular system for the collection, measurement, sampling and storage of urine and feces biowastes. This conceptual design effort was followed by the design, fabrication and performance evaluation of a flight prototype model urine collection, volume measurement and sampling capability. No operational or performance deficiencies were uncovered as a result of the performance evaluation tests.

Modular disposable can (MODCAN) crash cushion: A concept investigation

NASA Technical Reports Server (NTRS)

Knoell, A.; Wilson, A.

1976-01-01

A conceptual design investigation of an improved highway crash cushion system is presented. The system is referred to as a modular disposable can (MODCAN) crash system. It is composed of a modular arrangement of disposable metal beverage cans configured to serve as an effective highway impact attenuation system. Experimental data, design considerations, and engineering calculations supporting the design development are presented. Design performance is compared to that of a conventional steel drum system. It is shown that the MODCAN concepts offers the potential for smoother and safer occupant deceleration for a larger class of vehicle impact weights than the steel drum device.

Rapidly Deployed Modular Telemetry System

NASA Technical Reports Server (NTRS)

Varnavas, Kosta A. (Inventor); Sims, William Herbert, III (Inventor)

2013-01-01

The present invention is a telemetry system, and more specifically is a rapidly deployed modular telemetry apparatus which utilizes of SDR technology and the FPGA programming capability to reduce the number of hardware components and programming required to deploy a telemetry system.

Individual differences and time-varying features of modular brain architecture.

PubMed

Liao, Xuhong; Cao, Miao; Xia, Mingrui; He, Yong

2017-05-15

Recent studies have suggested that human brain functional networks are topologically organized into functionally specialized but inter-connected modules to facilitate efficient information processing and highly flexible cognitive function. However, these studies have mainly focused on group-level network modularity analyses using "static" functional connectivity approaches. How these extraordinary modular brain structures vary across individuals and spontaneously reconfigure over time remain largely unknown. Here, we employed multiband resting-state functional MRI data (N=105) from the Human Connectome Project and a graph-based modularity analysis to systematically investigate individual variability and dynamic properties in modular brain networks. We showed that the modular structures of brain networks dramatically vary across individuals, with higher modular variability primarily in the association cortex (e.g., fronto-parietal and attention systems) and lower variability in the primary systems. Moreover, brain regions spontaneously changed their module affiliations on a temporal scale of seconds, which cannot be simply attributable to head motion and sampling error. Interestingly, the spatial pattern of intra-subject dynamic modular variability largely overlapped with that of inter-subject modular variability, both of which were highly reproducible across repeated scanning sessions. Finally, the regions with remarkable individual/temporal modular variability were closely associated with network connectors and the number of cognitive components, suggesting a potential contribution to information integration and flexible cognitive function. Collectively, our findings highlight individual modular variability and the notable dynamic characteristics in large-scale brain networks, which enhance our understanding of the neural substrates underlying individual differences in a variety of cognition and behaviors. Copyright © 2017 Elsevier Inc. All rights reserved.

Maintenance of head and neck tumor on-chip: gateway to personalized treatment?

PubMed Central

Bower, Ruth; Green, Victoria L; Kuvshinova, Elena; Kuvshinov, Dmitriy; Karsai, Laszlo; Crank, Stephen T; Stafford, Nicholas D; Greenman, John

2017-01-01

Aim: Head and neck squamous cell carcinomas (HNSCC) are solid tumors with low overall survival (40–60%). In a move toward personalized medicine, maintenance of tumor biopsies in microfluidic tissue culture devices is being developed. Methodology/results: HNSCC (n = 15) was dissected (5–10 mg) and either analyzed immediately or cultured in a microfluidic device (37°C) for 48 h. No difference was observed in morphology between pre- and postculture specimens. Dissociated samples were analyzed using trypan blue exclusion (viability), propidium iodide flow cytometry (death) and MTS assay (proliferation) with no significant difference observed highlighting tissue maintenance. Computational fluid dynamics showed laminar flow within the system. Conclusion: The microfluidic culture system successfully maintained HNSCC for 48 h, the culture system will allow testing of different treatment modalities with response monitoring. PMID:28670466

Electrostatic actuators for portable microfluidic systems

NASA Astrophysics Data System (ADS)

Tice, Joshua

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

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

Modular space station phase B extension preliminary performance specification. Volume 1: Initial station systems

NASA Technical Reports Server (NTRS)

1971-01-01

The general, operational, design/construction, and subsystem design requirements are presented for a solar powered modular space station system. While these requirements apply only to the initial station system, the system is readily adaptable to a growth configuration.

Highly-Efficient and Modular Medium-Voltage Converters

DTIC Science & Technology

2015-09-28

HVDC modular multilevel converter in decoupled double synchronous reference frame for voltage oscillation reduction," IEEE Trans. Ind...Electron., vol. 29, pp. 77-88, Jan 2014. [10] M. Guan and Z. Xu, "Modeling and control of a modular multilevel converter -based HVDC system under...34 Modular multilevel converter design for VSC HVDC applications," IEEE Journal of Emerging and Selected Topics in Power Electronics, vol. 3, pp.

Dynamics of modularity of neural activity in the brain during development

NASA Astrophysics Data System (ADS)

Deem, Michael; Chen, Man

2014-03-01

Theory suggests that more modular systems can have better response functions at short times. This theory suggests that greater cognitive performance may be achieved for more modular neural activity, and that modularity of neural activity may, therefore, likely increase with development in children. We study the relationship between age and modularity of brain neural activity in developing children. The value of modularity calculated from fMRI data is observed to increase during childhood development and peak in young adulthood. We interpret these results as evidence of selection for plasticity in the cognitive function of the human brain. We present a model to illustrate how modularity can provide greater cognitive performance at short times and enhance fast, low-level, automatic cognitive processes. Conversely, high-level, effortful, conscious cognitive processes may not benefit from modularity. We use quasispecies theory to predict how the average modularity evolves with age, given a fitness function extracted from the model. We suggest further experiments exploring the effect of modularity on cognitive performance and suggest that modularity may be a potential biomarker for injury, rehabilitation, or disease.

Simulation of electrokinetic flow in microfluidic channels

NASA Astrophysics Data System (ADS)

Sabur, Romena; Matin, M.

2005-08-01

Electrokinetic phenomena become an increasingly efficient fluid transport mechanism in micro- and nano-fluidic fields. These phenomena have also been applied successfully in microfluidic devices to achieve particle separation, pre-concentration and mixing. Electrokinetic is the flow produced by the action of an electric field on a fluid with a net charge, where the charged ions of fluid are able to drag the whole solution through the channels in the microfluidic device from one analyzing point to the other. We will present the simulation results of electrokinetic transports of fluid in various typical micro-channel geometries such as T-channel, Y-channel, cross channel and straight channel. In practice, high-speed micro-PIV technique is used to measure transient fluidic phenomena in a microfluidic channel. Particle Image Velocimetry (PIV) systems provide two- or three-dimensional velocity maps in flows using whole field techniques based on imaging the light scattered by small particles in the flow illuminated by a laser light sheet. The system generally consists of an epifluorescent microscope, CW laser and a high-speed CMOS of CCD camera. The flow of a liquid, (water for example), containing fluorescent particle is then analyzed in a counter microchannel by the highly accurate PIV method. One can then compare the simulated and experimental microfluidic flow due to electroosmotic effect.

Digitally controlled droplet microfluidic system based on electrophoretic actuation

NASA Astrophysics Data System (ADS)

Im, Do Jin; Yoo, Byeong Sun; Ahn, Myung Mo; Moon, Dustin; Kang, In Seok

2012-11-01

Most researches on direct charging and the subsequent manipulation of a charged droplet were focused on an on-demand sorting in microchannel where carrier fluid transports droplets. Only recently, an individual actuation of a droplet without microchannel and carrier fluid was tried. However, in the previous work, the system size was too large and the actuation voltage was too high (1.5 kV), which limits the applicability of the technology to mobile use. Therefore, in the current research, we have developed a miniaturized digital microfluidic system based on the electrophoresis of a charged droplet (ECD). By using a pin header socket for an array of electrodes, much smaller microfluidic system can be made from simple fabrication process with low cost. A full two dimensional manipulation (0.4 cm/s) of a droplet (300 nL) suspended in silicone oil (6 cSt) and multiple droplet actuation have been performed with reasonable actuation voltage (300 V). By multiple droplet actuation and coalescence, a practical biochemical application also has been demonstrated. We hope the current droplet manipulation method (ECD) can be a good alternative or complimentary technology to the conventional ones and therefore contributes to the development of droplet microfluidics. This work has been supported by BK21 program of the Ministry of Education, Science and Technology (MEST) of Korea.

Hybrid macro-micro fluidics system for a chip-based biosensor

NASA Astrophysics Data System (ADS)

Tamanaha, C. R.; Whitman, L. J.; Colton, R. J.

2002-03-01

We describe the engineering of a hybrid fluidics platform for a chip-based biosensor system that combines high-performance microfluidics components with powerful, yet compact, millimeter-scale pump and valve actuators. The microfluidics system includes channels, valveless diffuser-based pumps, and pinch-valves that are cast into a poly(dimethylsiloxane) (PDMS) membrane and packaged along with the sensor chip into a palm-sized plastic cartridge. The microfluidics are driven by pump and valve actuators contained in an external unit (with a volume ~30 cm3) that interfaces kinematically with the PDMS microelements on the cartridge. The pump actuator is a simple-lever, flexure-hinge displacement amplifier that increases the motion of a piezoelectric stack. The valve actuators are an array of cantilevers operated by shape memory alloy wires. All components can be fabricated without the need for complex lithography or micromachining, and can be used with fluids containing micron-sized particulates. Prototypes have been modeled and tested to ensure the delivery of microliter volumes of fluid and the even dispersion of reagents over the chip sensing elements. With this hybrid approach to the fluidics system, the biochemical assay benefits from the many advantages of microfluidics yet we avoid the complexity and unknown reliability of immature microactuator technologies.

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

PubMed

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

2009-09-22

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

Modular Software for Spacecraft Navigation Using the Global Positioning System (GPS)

NASA Technical Reports Server (NTRS)

Truong, S. H.; Hartman, K. R.; Weidow, D. A.; Berry, D. L.; Oza, D. H.; Long, A. C.; Joyce, E.; Steger, W. L.

1996-01-01

The Goddard Space Flight Center Flight Dynamics and Mission Operations Divisions have jointly investigated the feasibility of engineering modular Global Positioning SYSTEM (GPS) navigation software to support both real time flight and ground postprocessing configurations. The goals of this effort are to define standard GPS data interfaces and to engineer standard, reusable navigation software components that can be used to build a broad range of GPS navigation support applications. The paper discusses the GPS modular software (GMOD) system and operations concepts, major requirements, candidate software architecture, feasibility assessment and recommended software interface standards. In additon, ongoing efforts to broaden the scope of the initial study and to develop modular software to support autonomous navigation using GPS are addressed,

Electropermanent magnet actuation for droplet ferromicrofluidics

PubMed Central

Padovani, José I.; Jeffrey, Stefanie S.; Howe, Roger T.

2016-01-01

Droplet actuation is an essential mechanism for droplet-based microfluidic systems. On-demand electromagnetic actuation is used in a ferrofluid-based microfluidic system for water droplet displacement. Electropermanent magnets (EPMs) are used to induce 50 mT magnetic fields in a ferrofluid filled microchannel with gradients up to 6.4 × 104 kA/m2. Short 50 µs current pulses activate the electropermanent magnets and generate negative magnetophoretic forces that range from 10 to 70 nN on 40 to 80 µm water-in-ferrofluid droplets. Maximum droplet displacement velocities of up to 300 µm/s are obtained under flow and no-flow conditions. Electropermanent magnet-activated droplet sorting under continuous flow is demonstrated using a split-junction microfluidic design. PMID:27583301

Microfluidic approach for encapsulation via double emulsions.

PubMed

Wang, Wei; Zhang, Mao-Jie; Chu, Liang-Yin

2014-10-01

Double emulsions, with inner drops well protected by the outer shells, show great potential as compartmentalized systems to encapsulate multiple components for protecting actives, masking flavor, and targetedly delivering and controllably releasing drugs. Precise control of the encapsulation characteristics of each component is critical to achieve an optimal therapeutic efficacy for pharmaceutical applications. Such controllable encapsulation can be realized by using microfluidic approaches for producing monodisperse double emulsions with versatile and controllable structures as the encapsulation system. The size, number and composition of the emulsion drops can be accurately manipulated for optimizing the encapsulation of each component for pharmaceutical applications. In this review, we highlight the outstanding advantages of controllable microfluidic double emulsions for highly efficient and precisely controllable encapsulation. Copyright © 2014 Elsevier Ltd. All rights reserved.

Revisiting lab-on-a-chip technology for drug discovery.

PubMed

Neuži, Pavel; Giselbrecht, Stefan; Länge, Kerstin; Huang, Tony Jun; Manz, Andreas

2012-08-01

The field of microfluidics or lab-on-a-chip technology aims to improve and extend the possibilities of bioassays, cell biology and biomedical research based on the idea of miniaturization. Microfluidic systems allow more accurate modelling of physiological situations for both fundamental research and drug development, and enable systematic high-volume testing for various aspects of drug discovery. Microfluidic systems are in development that not only model biological environments but also physically mimic biological tissues and organs; such 'organs on a chip' could have an important role in expediting early stages of drug discovery and help reduce reliance on animal testing. This Review highlights the latest lab-on-a-chip technologies for drug discovery and discusses the potential for future developments in this field.

Coding/decoding and reversibility of droplet trains in microfluidic networks.

PubMed

Fuerstman, Michael J; Garstecki, Piotr; Whitesides, George M

2007-02-09

Droplets of one liquid suspended in a second, immiscible liquid move through a microfluidic device in which a channel splits into two branches that reconnect downstream. The droplets choose a path based on the number of droplets that occupy each branch. The interaction among droplets in the channels results in complex sequences of path selection. The linearity of the flow through the microchannels, however, ensures that the behavior of the system can be reversed. This reversibility makes it possible to encrypt and decrypt signals coded in the intervals between droplets. The encoding/decoding device is a functional microfluidic system that requires droplets to navigate a network in a precise manner without the use of valves, switches, or other means of external control.

Modular chassis simplifies packaging and interconnecting of circuit boards

NASA Technical Reports Server (NTRS)

Arens, W. E.; Boline, K. G.

1964-01-01

A system of modular chassis structures has simplified the design for mounting a number of printed circuit boards. This design is structurally adaptable to computer and industrial control system applications.

Liquid-in-gas droplet microfluidics; experimental characterization of droplet morphology, generation frequency, and monodispersity in a flow-focusing microfluidic device

NASA Astrophysics Data System (ADS)

Tirandazi, Pooyan; Hidrovo, Carlos H.

2017-07-01

Microfluidic techniques for production of uniform droplets usually rely on the use of two immiscible liquids (e.g. water-in-oil emulsions). It has been shown recently that a continuous gas flow instead of a second liquid carrier can be used as an alternative approach in droplet microfluidics. In this work we experimentally investigate the generation of liquid water droplets within air in flow-focusing configurations. Over a wide range of flow conditions we identify six distinct flow regimes inside the microchannel: Co-flowing, Threading, Plugging, Dripping, Multi-Satellite Formation, and Jetting. Flow regimes and their transitions are plotted and characterized based on the Weber number (We) of the system. We further investigate the impact of liquid microchannel size on the flow maps. Generation frequency, morphology, and monodispersity of the droplets are characterized in more detail in the Dripping regime. Generation frequency can be related to the product of the liquid and gas flow rates. However, droplet morphology (length and width) is more dependent on the gas flow rate. We demonstrate the production of monodisperse droplets (d < 100 µm and σ/d < 5 %) up to kHz formation rates in liquid-gas microfluidic systems for the first time. The results of this work provide practical and useful guidelines for precise, oil-free delivery of ultra-small volumes of fluid which can be integrated in lab-on-a-chip systems for a variety of applications in biochemical research and material synthesis.