Williams works with LOCAD-PTS Experiment Hardware in the US Lab during Expedition 15

NASA Image and Video Library

2007-05-05

ISS015-E-06773 (5 May 2007) --- Astronaut Sunita L. Williams, Expedition 15 flight engineer, sets up a video camera inside a flame resistant covering to film a chip during Lab-on-a-Chip Application Development-Portable Test System (LOCAD-PTS) Swab Operations in the Destiny laboratory of the International Space Station.

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

NASA Technical Reports Server (NTRS)

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

2004-01-01

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

Smartphone technology can be transformative to the deployment of lab-on-chip diagnostics.

PubMed

Erickson, David; O'Dell, Dakota; Jiang, Li; Oncescu, Vlad; Gumus, Abdurrahman; Lee, Seoho; Mancuso, Matthew; Mehta, Saurabh

2014-09-07

The rapid expansion of mobile technology is transforming the biomedical landscape. By 2016 there will be 260 M active smartphones in the US and millions of health accessories and software "apps" running off them. In parallel with this have come major technical achievements in lab-on-a-chip technology leading to incredible new biochemical sensors and molecular diagnostic devices. Despite these advancements, the uptake of lab-on-a-chip technologies at the consumer level has been somewhat limited. We believe that the widespread availability of smartphone technology and the capabilities they offer in terms of computation, communication, social networking, and imaging will be transformative to the deployment of lab-on-a-chip type technology both in the developed and developing world. In this paper we outline why we believe this is the case, the new business models that may emerge, and detail some specific application areas in which this synergy will have long term impact, namely: nutrition monitoring and disease diagnostics in limited resource settings.

Smartphone technology can be transformative to the deployment of lab-on-chip diagnostics

PubMed Central

Erickson, David; O’Dell, Dakota; Jiang, Li; Oncescu, Vlad; Gumus, Abdurrahman; Lee, Seoho; Mancuso, Matthew; Mehta, Saurabh

2014-01-01

The rapid expansion of mobile technology is transforming the biomedical landscape. By 2016 there will be 260M active smartphones in the US and millions of health accessories and software “apps” running off them. In parallel with this have come major technical achievements in lab-on-a-chip technology leading to incredible new biochemical sensors and molecular diagnostic devices. Despite these advancements, the uptake of lab-on-a-chip technologies at the consumer level has been somewhat limited. We believe that the widespread availability of smartphone technology and the capabilities they offer in terms of computation, communication, social networking, and imaging will be transformative to the deployment of lab-on-a-chip type technology both in the developed and developing world. In this paper we outline why we believe this is the case, the new business models that may emerge, and detail some specific application areas in which this synergy will have long term impact, namely: nutrition monitoring and disease diagnostics in limited resource settings. PMID:24700127

Photonics-on-a-chip: recent advances in integrated waveguides as enabling detection elements for real-world, lab-on-a-chip biosensing applications.

PubMed

Washburn, Adam L; Bailey, Ryan C

2011-01-21

By leveraging advances in semiconductor microfabrication technologies, chip-integrated optical biosensors are poised to make an impact as scalable and multiplexable bioanalytical measurement tools for lab-on-a-chip applications. In particular, waveguide-based optical sensing technology appears to be exceptionally amenable to chip integration and miniaturization, and, as a result, the recent literature is replete with examples of chip-integrated waveguide sensing platforms developed to address a wide range of contemporary analytical challenges. As an overview of the most recent advances within this dynamic field, this review highlights work from the last 2-3 years in the areas of grating-coupled, interferometric, photonic crystal, and microresonator waveguide sensors. With a focus towards device integration, particular emphasis is placed on demonstrations of biosensing using these technologies within microfluidically controlled environments. In addition, examples of multiplexed detection and sensing within complex matrices--important features for real-world applicability--are given special attention.

A Lab-on-Chip Design for Miniature Autonomous Bio-Chemoprospecting Planetary Rovers

NASA Astrophysics Data System (ADS)

Santoli, S.

The performance of the so-called ` Lab-on-Chip ' devices, featuring micrometre size components and employed at present for carrying out in a very fast and economic way the extremely high number of sequence determinations required in genomic analyses, can be largely improved as to further size reduction, decrease of power consumption and reaction efficiency through development of nanofluidics and of nano-to-micro inte- grated systems. As is shown, such new technologies would lead to robotic, fully autonomous, microwatt consumption and complete ` laboratory on a chip ' units for accurate, fast and cost-effective astrobiological and planetary exploration missions. The theory and the manufacturing technologies for the ` active chip ' of a miniature bio/chemoprospecting planetary rover working on micro- and nanofluidics are investigated. The chip would include micro- and nanoreactors, integrated MEMS (MicroElectroMechanical System) components, nanoelectronics and an intracavity nanolaser for highly accurate and fast chemical analysis as an application of such recently introduced solid state devices. Nano-reactors would be able to strongly speed up reaction kinetics as a result of increased frequency of reactive collisions. The reaction dynamics may also be altered with respect to standard macroscopic reactors. A built-in miniature telemetering unit would connect a network of other similar rovers and a central, ground-based or orbiting control unit for data collection and transmission to an Earth-based unit through a powerful antenna. The development of the ` Lab-on-Chip ' concept for space applications would affect the economy of space exploration missions, as the rover's ` Lab-on-Chip ' development would link space missions with the ever growing terrestrial market and business concerning such devices, largely employed in modern genomics and bioinformatics, so that it would allow the recoupment of space mission costs.

Space Science

NASA Image and Video Library

2003-12-01

Dr. Lisa Monaco, Marshall Space Flight Center’s (MSFC’s) project scientist for the Lab-on-a-Chip Applications Development (LOCAD) program, examines a lab on a chip. The small dots are actually ports where fluids and chemicals can be mixed or samples can be collected for testing. Tiny channels, only clearly visible under a microscope, form pathways between the ports. Many chemical and biological processes, previously conducted on large pieces of laboratory equipment, can now be performed on these small glass or plastic plates. Monaco and other researchers at MSFC in Huntsville, Alabama, are customizing the chips to be used for many space applications, such as monitoring microbes inside spacecraft and detecting life on other planets. The portable, handheld Lab-on-a Chip Application Development Portable Test System (LOCAD-PTS) made its debut flight aboard Discovery during the STS-116 mission launched December 9, 2006. The system allowed crew members to monitor their environment for problematic contaminants such as yeast, mold, and even E.coli, and salmonella. Once LOCAD-PTS reached the International Space Station (ISS), the Marshall team continued to manage the experiment, monitoring the study from a console in the Payload Operations Center at MSFC. The results of these studies will help NASA researchers refine the technology for future Moon and Mars missions. (NASA/MSFC/D.Stoffer)

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

Evolvable Smartphone-Based Platforms for Point-of-Care In-Vitro Diagnostics Applications.

PubMed

Patou, François; AlZahra'a Alatraktchi, Fatima; Kjægaard, Claus; Dimaki, Maria; Madsen, Jan; Svendsen, Winnie E

2016-09-03

The association of smart mobile devices and lab-on-chip technologies offers unprecedented opportunities for the emergence of direct-to-consumer in vitro medical diagnostics applications. Despite their clear transformative potential, obstacles remain to the large-scale disruption and long-lasting success of these systems in the consumer market. For instance, the increasing level of complexity of instrumented lab-on-chip devices, coupled to the sporadic nature of point-of-care testing, threatens the viability of a business model mainly relying on disposable/consumable lab-on-chips. We argued recently that system evolvability, defined as the design characteristic that facilitates more manageable transitions between system generations via the modification of an inherited design, can help remedy these limitations. In this paper, we discuss how platform-based design can constitute a formal entry point to the design and implementation of evolvable smart device/lab-on-chip systems. We present both a hardware/software design framework and the implementation details of a platform prototype enabling at this stage the interfacing of several lab-on-chip variants relying on current- or impedance-based biosensors. Our findings suggest that several change-enabling mechanisms implemented in the higher abstraction software layers of the system can promote evolvability, together with the design of change-absorbing hardware/software interfaces. Our platform architecture is based on a mobile software application programming interface coupled to a modular hardware accessory. It allows the specification of lab-on-chip operation and post-analytic functions at the mobile software layer. We demonstrate its potential by operating a simple lab-on-chip to carry out the detection of dopamine using various electroanalytical methods.

Evolvable Smartphone-Based Platforms for Point-of-Care In-Vitro Diagnostics Applications

PubMed Central

Patou, François; AlZahra’a Alatraktchi, Fatima; Kjægaard, Claus; Dimaki, Maria; Madsen, Jan; Svendsen, Winnie E.

2016-01-01

The association of smart mobile devices and lab-on-chip technologies offers unprecedented opportunities for the emergence of direct-to-consumer in vitro medical diagnostics applications. Despite their clear transformative potential, obstacles remain to the large-scale disruption and long-lasting success of these systems in the consumer market. For instance, the increasing level of complexity of instrumented lab-on-chip devices, coupled to the sporadic nature of point-of-care testing, threatens the viability of a business model mainly relying on disposable/consumable lab-on-chips. We argued recently that system evolvability, defined as the design characteristic that facilitates more manageable transitions between system generations via the modification of an inherited design, can help remedy these limitations. In this paper, we discuss how platform-based design can constitute a formal entry point to the design and implementation of evolvable smart device/lab-on-chip systems. We present both a hardware/software design framework and the implementation details of a platform prototype enabling at this stage the interfacing of several lab-on-chip variants relying on current- or impedance-based biosensors. Our findings suggest that several change-enabling mechanisms implemented in the higher abstraction software layers of the system can promote evolvability, together with the design of change-absorbing hardware/software interfaces. Our platform architecture is based on a mobile software application programming interface coupled to a modular hardware accessory. It allows the specification of lab-on-chip operation and post-analytic functions at the mobile software layer. We demonstrate its potential by operating a simple lab-on-chip to carry out the detection of dopamine using various electroanalytical methods. PMID:27598208

Around Marshall

NASA Image and Video Library

2004-02-01

Andy Jenkins, an engineer for the Lab on a Chip Applications Development program, helped build the Applications Development Unit (ADU-25), a one-of-a-kind facility for controlling and analyzing processes on chips with extreme accuracy. Pressure is used to cause fluids to travel through network of fluid pathways, or micro-channels, embossed on the chips through a process similar to the one used to print circuits on computer chips. To make customized chips for various applications, NASA has an agreement with the U.S. Army's Micro devices and Micro fabrication Laboratory at Redstone Arsenal in Huntsville, Alabama, where NASA's Marshall Space Flight Center (MSFC) is located. The Marshall Center team is also collaborating with scientists at other NASA centers and at universities to develop custom chip designs for many applications, such as studying how fluidic systems work in spacecraft and identifying microbes in self-contained life support systems. Chips could even be designed for use on Earth, such as for detecting deadly microbes in heating and air systems. (NASA/MSFC/D.Stoffer)

Recent lab-on-chip developments for novel drug discovery.

PubMed

Khalid, Nauman; Kobayashi, Isao; Nakajima, Mitsutoshi

2017-07-01

Microelectromechanical systems (MEMS) and micro total analysis systems (μTAS) revolutionized the biochemical and electronic industries, and this miniaturization process became a key driver for many markets. Now, it is a driving force for innovations in life sciences, diagnostics, analytical sciences, and chemistry, which are called 'lab-on-a-chip, (LOC)' devices. The use of these devices allows the development of fast, portable, and easy-to-use systems with a high level of functional integration for applications such as point-of-care diagnostics, forensics, the analysis of biomolecules, environmental or food analysis, and drug development. In this review, we report on the latest developments in fabrication methods and production methodologies to tailor LOC devices. A brief overview of scale-up strategies is also presented together with their potential applications in drug delivery and discovery. The impact of LOC devices on drug development and discovery has been extensively reviewed in the past. The current research focuses on fast and accurate detection of genomics, cell mutations and analysis, drug delivery, and discovery. The current research also differentiates the LOC devices into new terminology of microengineering, like organ-on-a-chip, stem cells-on-a-chip, human-on-a-chip, and body-on-a-chip. Key challenges will be the transfer of fabricated LOC devices from lab-scale to industrial large-scale production. Moreover, extensive toxicological studies are needed to justify the use of microfabricated drug delivery vehicles in biological systems. It will also be challenging to transfer the in vitro findings to suitable and promising in vivo models. WIREs Syst Biol Med 2017, 9:e1381. doi: 10.1002/wsbm.1381 For further resources related to this article, please visit the WIREs website. © 2017 Wiley Periodicals, Inc.

Lab-on-a-Chip Pathogen Sensors for Food Safety

PubMed Central

Yoon, Jeong-Yeol; Kim, Bumsang

2012-01-01

There have been a number of cases of foodborne illness among humans that are caused by pathogens such as Escherichia coli O157:H7, Salmonella typhimurium, etc. The current practices to detect such pathogenic agents are cell culturing, immunoassays, or polymerase chain reactions (PCRs). These methods are essentially laboratory-based methods that are not at all real-time and thus unavailable for early-monitoring of such pathogens. They are also very difficult to implement in the field. Lab-on-a-chip biosensors, however, have a strong potential to be used in the field since they can be miniaturized and automated; they are also potentially fast and very sensitive. These lab-on-a-chip biosensors can detect pathogens in farms, packaging/processing facilities, delivery/distribution systems, and at the consumer level. There are still several issues to be resolved before applying these lab-on-a-chip sensors to field applications, including the pre-treatment of a sample, proper storage of reagents, full integration into a battery-powered system, and demonstration of very high sensitivity, which are addressed in this review article. Several different types of lab-on-a-chip biosensors, including immunoassay- and PCR-based, have been developed and tested for detecting foodborne pathogens. Their assay performance, including detection limit and assay time, are also summarized. Finally, the use of optical fibers or optical waveguide is discussed as a means to improve the portability and sensitivity of lab-on-a-chip pathogen sensors. PMID:23112625

Lab-on-a-chip workshop activities for secondary school students

PubMed Central

Esfahani, Mohammad M. N.; Tarn, Mark D.; Choudhury, Tahmina A.; Hewitt, Laura C.; Mayo, Ashley J.; Rubin, Theodore A.; Waller, Mathew R.; Christensen, Martin G.; Dawson, Amy; Pamme, Nicole

2016-01-01

The ability to engage and inspire younger generations in novel areas of science is important for bringing new researchers into a burgeoning field, such as lab-on-a-chip. We recently held a lab-on-a-chip workshop for secondary school students, for which we developed a number of hands-on activities that explained various aspects of microfluidic technology, including fabrication (milling and moulding of microfluidic devices, and wax printing of microfluidic paper-based analytical devices, so-called μPADs), flow regimes (gradient formation via diffusive mixing), and applications (tissue analysis and μPADs). Questionnaires completed by the students indicated that they found the workshop both interesting and informative, with all activities proving successful, while providing feedback that could be incorporated into later iterations of the event. PMID:26865902

A Medipix3 readout system based on the National Instruments FlexRIO card and using the LabVIEW programming environment

NASA Astrophysics Data System (ADS)

Horswell, I.; Gimenez, E. N.; Marchal, J.; Tartoni, N.

2011-01-01

Hybrid silicon photon-counting detectors are becoming standard equipment for many synchrotron applications. The latest in the Medipix family of read-out chips designed as part of the Medipix Collaboration at CERN is the Medipix3, which while maintaining the same pixel size as its predecessor, offers increased functionality and operating modes. The active area of the Medipix3 chip is approx 14mm × 14mm (containing 256 × 256 pixels) which is not large enough for many detector applications, this results in the need to tile many sensors and chips. As a first step on the road to develop such a detector, it was decided to build a prototype single chip readout system to gain the necessary experience in operating a Medipix3 chip. To provide a flexible learning and development tool it was decided to build an interface based on the recently released FlexRIOTM system from National Instruments and to use the LabVIEWTM graphical programming environment. This system and the achieved performance are described in this paper.

Lab-on-a-chip technologies for genodermatoses: Recent progress and future perspectives.

PubMed

Hongzhou, Cui; Shuping, Guo; Wenju, Wang; Li, Li; Lulu, Wei; Linjun, Deng; Jingmin, Li; Xiaoli, Ren; Li, Bai

2017-02-01

In recent years, molecular biology has proven to be a great asset in our understanding of mechanisms in genodermatoses. However, bench to bedside translation research lags far behind. Advances in lab-on-a-chip technologies enabled programmable, reconfigurable, and scalable manipulation of a variety of laboratory procedures. Sample preparation, microfluidic reactions, and continuous monitoring systems can be integrated on a small chip. These advantages have attracted attention in various fields of clinical application including diagnosis of inherited skin diseases. This review lists an overview of the underlying genes and mutations and describes prospective application of lab-on-a-chip technologies as solutions to challenges for point-of-care genodematoses diagnosis. Copyright © 2016. Published by Elsevier B.V.

Lab-on-fiber technology: a new vision for chemical and biological sensing.

PubMed

Ricciardi, Armando; Crescitelli, Alessio; Vaiano, Patrizio; Quero, Giuseppe; Consales, Marco; Pisco, Marco; Esposito, Emanuela; Cusano, Andrea

2015-12-21

The integration of microfluidics and photonic biosensors has allowed achievement of several laboratory functions in a single chip, leading to the development of photonic lab-on-a-chip technology. Although a lot of progress has been made to implement such sensors in small and easy-to-use systems, many applications such as point-of-care diagnostics and in vivo biosensing still require a sensor probe able to perform measurements at precise locations that are often hard to reach. The intrinsic property of optical fibers to conduct light to a remote location makes them an ideal platform to meet this demand. The motivation to combine the good performance of photonic biosensors on chips with the unique advantages of optical fibers has thus led to the development of the so-called lab-on-fiber technology. This emerging technology envisages the integration of functionalized materials on micro- and nano-scales (i.e. the labs) with optical fibers to realize miniaturized and advanced all-in-fiber probes, especially useful for (but not limited to) label-free chemical and biological applications. This review presents a broad overview of lab-on-fiber biosensors, with particular reference to lab-on-tip platforms, where the labs are integrated on the optical fiber facet. Light-matter interaction on the fiber tip is achieved through the integration of thin layers of nanoparticles or nanostructures supporting resonant modes, both plasmonic and photonic, highly sensitive to local modifications of the surrounding environment. According to the physical principle that is exploited, different configurations - such as localized plasmon resonance probes, surface enhanced Raman scattering probes and photonic probes - are classified, while various applications are presented in context throughout. For each device, the surface chemistry and the related functionalization protocols are reviewed. Moreover, the implementation strategies and fabrication processes, either based on bottom-up or top-down approaches, are discussed. In conclusion we highlight some of the further development opportunities, including lab-in-a-needle technology, which could have a direct and disruptive impact in localized cancer treatment applications.

Justification of rapid prototyping in the development cycle of thermoplastic-based lab-on-a-chip.

PubMed

Preywisch, Regina; Ritzi-Lehnert, Marion; Drese, Klaus S; Röser, Tina

2011-11-01

During the developmental cycle of lab-on-a-chip devices, various microstructuring techniques are required. While in the designing and assay implementation phase direct structuring or so-called rapid-prototyping methods such as milling or laser ablation are applied, replication methods like hot embossing or injection moulding are favourable for large quantity manufacturing. This work investigated the applicability of rapid-prototyping techniques for thermoplastic chip development in general, and the reproducibility of performances in dependency of the structuring technique. A previously published chip for prenatal diagnosis that preconcentrates DNA via electrokinetic trapping and field-amplified-sample-stacking and afterwards separates it in CGE was chosen as a model. The impact of structuring, sealing, and the integration of membranes on the mobility of the EOF, DNA preconcentration, and DNA separation was studied. Structuring methods were found to significantly change the location where preconcentration of DNA occurs. However, effects on the mobility of the EOF and the separation quality of DNA were not observed. Exchange of the membrane has no effect on the chip performance, whereas the sealing method impairs the separation of DNA within the chip. The overall assay performance is not significantly influenced by different structuring methods; thus, the application of rapid-prototyping methods during a chip development cycle is well justified. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chip-based generation of carbon nanodots via electrochemical oxidation of screen printed carbon electrodes and the applications for efficient cell imaging and electrochemiluminescence enhancement

NASA Astrophysics Data System (ADS)

Xu, Yuanhong; Liu, Jingquan; Zhang, Jizhen; Zong, Xidan; Jia, Xiaofang; Li, Dan; Wang, Erkang

2015-05-01

A portable lab-on-a-chip methodology to generate ionic liquid-functionalized carbon nanodots (CNDs) was developed via electrochemical oxidation of screen printed carbon electrodes. The CNDs can be successfully applied for efficient cell imaging and solid-state electrochemiluminescence sensor fabrication on the paper-based chips.A portable lab-on-a-chip methodology to generate ionic liquid-functionalized carbon nanodots (CNDs) was developed via electrochemical oxidation of screen printed carbon electrodes. The CNDs can be successfully applied for efficient cell imaging and solid-state electrochemiluminescence sensor fabrication on the paper-based chips. Electronic supplementary information (ESI) available: Experimental section; Fig. S1. XPS spectra of the as-prepared CNDs after being dialyzed for 72 hours; Fig. S2. LSCM images showing time-dependent fluorescence signals of HeLa cells treated by the as-prepared CNDs; Tripropylamine analysis using the Nafion/CNDs modified ECL sensor. See DOI: 10.1039/c5nr01765c

Comment on "The promise of microfluidic artificial lungs" by J. A. Potkay, Lab Chip, 2014, 14, 4122-4138.

PubMed

Wagner, Georg; Kaesler, Andreas; Steinseifer, Ulrich; Schmitz-Rode, Thomas; Arens, Jutta

2016-04-07

This comment on an article that appeared in this journal (Potkay, Lab Chip, 2014, 14, 4122-4138) presents an alternative view on the feasibility and clinical application of current microfluidic artificial lungs.

Novel immunoassay formats for integrated microfluidic circuits: diffusion immunoassays (DIA)

NASA Astrophysics Data System (ADS)

Weigl, Bernhard H.; Hatch, Anson; Kamholz, Andrew E.; Yager, Paul

2000-03-01

Novel designs of integrated fluidic microchips allow separations, chemical reactions, and calibration-free analytical measurements to be performed directly in very small quantities of complex samples such as whole blood and contaminated environmental samples. This technology lends itself to applications such as clinical diagnostics, including tumor marker screening, and environmental sensing in remote locations. Lab-on-a-Chip based systems offer many *advantages over traditional analytical devices: They consume extremely low volumes of both samples and reagents. Each chip is inexpensive and small. The sampling-to-result time is extremely short. They perform all analytical functions, including sampling, sample pretreatment, separation, dilution, and mixing steps, chemical reactions, and detection in an integrated microfluidic circuit. Lab-on-a-Chip systems enable the design of small, portable, rugged, low-cost, easy to use, yet extremely versatile and capable diagnostic instruments. In addition, fluids flowing in microchannels exhibit unique characteristics ('microfluidics'), which allow the design of analytical devices and assay formats that would not function on a macroscale. Existing Lab-on-a-chip technologies work very well for highly predictable and homogeneous samples common in genetic testing and drug discovery processes. One of the biggest challenges for current Labs-on-a-chip, however, is to perform analysis in the presence of the complexity and heterogeneity of actual samples such as whole blood or contaminated environmental samples. Micronics has developed a variety of Lab-on-a-Chip assays that can overcome those shortcomings. We will now present various types of novel Lab- on-a-Chip-based immunoassays, including the so-called Diffusion Immunoassays (DIA) that are based on the competitive laminar diffusion of analyte molecules and tracer molecules into a region of the chip containing antibodies that target the analyte molecules. Advantages of this technique are a reduction in reagents, higher sensitivity, minimal preparation of complex samples such as blood, real-time calibration, and extremely rapid analysis.

Chemical and biological threat-agent detection using electrophoresis-based lab-on-a-chip devices.

PubMed

Borowsky, Joseph; Collins, Greg E

2007-10-01

The ability to separate complex mixtures of analytes has made capillary electrophoresis (CE) a powerful analytical tool since its modern configuration was first introduced over 25 years ago. The technique found new utility with its application to the microfluidics based lab-on-a-chip platform (i.e., microchip), which resulted in ever smaller footprints, sample volumes, and analysis times. These features, coupled with the technique's potential for portability, have prompted recent interest in the development of novel analyzers for chemical and biological threat agents. This article will comment on three main areas of microchip CE as applied to the separation and detection of threat agents: detection techniques and their corresponding limits of detection, sampling protocol and preparation time, and system portability. These three areas typify the broad utility of lab-on-a-chip for meeting critical, present-day security, in addition to illustrating areas wherein advances are necessary.

Lab-on a-Chip

NASA Technical Reports Server (NTRS)

1999-01-01

Labs on chips are manufactured in many shapes and sizes and can be used for numerous applications, from medical tests to water quality monitoring to detecting the signatures of life on other planets. The eight holes on this chip are actually ports that can be filled with fluids or chemicals. Tiny valves control the chemical processes by mixing fluids that move in the tiny channels that look like lines, connecting the ports. Scientists at NASA's Marshall Space Flight Center (MSFC) in Huntsville, Alabama designed this chip to grow biological crystals on the International Space Station (ISS). Through this research, they discovered that this technology is ideally suited for solving the challenges of the Vision for Space Exploration. For example, thousands of chips the size of dimes could be loaded on a Martian rover looking for biosignatures of past or present life. Other types of chips could be placed in handheld devices used to monitor microbes in water or to quickly conduct medical tests on astronauts. The portable, handheld Lab-on-a Chip Application Development Portable Test System (LOCAD-PTS) made its debut flight aboard Discovery during the STS-116 mission launched December 9, 2006. The system allowed crew members to monitor their environment for problematic contaminants such as yeast, mold, and even E.coli, and salmonella. Once LOCAD-PTS reached the ISS, the Marshall team continued to manage the experiment, monitoring the study from a console in the Payload Operations Center at MSFC. The results of these studies will help NASA researchers refine the technology for future Moon and Mars missions. (NASA/MSFC/D.Stoffer)

Magnetic domain wall conduits for single cell applications.

PubMed

Donolato, M; Torti, A; Kostesha, N; Deryabina, M; Sogne, E; Vavassori, P; Hansen, M F; Bertacco, R

2011-09-07

The ability to trap, manipulate and release single cells on a surface is important both for fundamental studies of cellular processes and for the development of novel lab-on-chip miniaturized tools for biological and medical applications. In this paper we demonstrate how magnetic domain walls generated in micro- and nano-structures fabricated on a chip surface can be used to handle single yeast cells labeled with magnetic beads. In detail, first we show that the proposed approach maintains the microorganism viable, as proven by monitoring the division of labeled yeast cells trapped by domain walls over 16 hours. Moreover, we demonstrate the controlled transport and release of individual yeast cells via displacement and annihilation of individual domain walls in micro- and nano-sized magnetic structures. These results pave the way to the implementation of magnetic devices based on domain walls technology in lab-on-chip systems devoted to accurate individual cell trapping and manipulation.

On-chip liquid storage and dispensing for lab-on-a-chip applications

NASA Astrophysics Data System (ADS)

Bodén, Roger; Lehto, Marcus; Margell, Joakim; Hjort, Klas; Schweitz, Jan-Åke

2008-07-01

This work presents novel components for on-chip storage and dispensing inside a lab-on-a-chip (LOC) for applications in immunoassay point-of-care testing (POCT), where incubation and washing steps are essential. It involves easy-to-use on-chip solutions for the sequential thermo-hydraulic actuation of liquids. The novel concept of combining the use of a rubber plug, both as a non-return valve cap and as a liquid injection interface of a sealed reservoir, allows simple filling of a sterilized cavity, as well as the storage and dispensing of reagent and washing buffer liquids. Segmenting the flow with air spacers enables effective rinsing and the use of small volumes of on-chip stored liquids. The chip uses low-resistance resistors as heaters in the paraffin actuator, providing the low-voltage actuation that is preferred for handheld battery driven instruments.

A portable pressure pump for microfluidic lab-on-a-chip systems using a porous polydimethylsiloxane (PDMS) sponge.

PubMed

Cha, Kyoung Je; Kim, Dong Sung

2011-10-01

In this paper, we propose a novel portable and disposable pressure pump using a porous polydimethylsiloxane (PDMS) sponge and demonstrate its application to a microfluidic lab-on-a-chip. The porous PDMS sponge was simply fabricated by a sugar leaching technique based on capillary suction of pre-cured PDMS into lumps of sugar, thereby enabling us to achieve the porous PDMS sponge composed of interconnected micropores. To indicate the characteristics of the porous PDMS sponge and pump, we measured the average porosities of them whose values were 0.64 and 0.34, respectively. A stress-strain relationship of the fabricated portable pressure pump represented a linear behavior in the compressive strain range of 0 to 20%. Within this range, a pumping volume of the pressure pump could be linearly controlled by the compressed strain. Finally, the fabricated porous PDMS pump was successfully demonstrated as a portable pressure pump for a disposable microfluidic lab-on-a-chip for efficient detection of agglutination. The proposed portable pressure pump can be potentially applicable to various disposable microfluidic lab-on-a-chip systems.

BioMEMS and Lab-on-a-Chip Course Education at West Virginia University

PubMed Central

Liu, Yuxin

2011-01-01

With the rapid growth of Biological/Biomedical MicroElectroMechanical Systems (BioMEMS) and microfluidic-based lab-on-a-chip (LOC) technology to biological and biomedical research and applications, demands for educated and trained researchers and technicians in these fields are rapidly expanding. Universities are expected to develop educational plans to address these specialized needs in BioMEMS, microfluidic and LOC science and technology. A course entitled BioMEMS and Lab-on-a-Chip was taught recently at the senior undergraduate and graduate levels in the Department of Computer Science and Electrical Engineering at West Virginia University (WVU). The course focused on the basic principles and applications of BioMEMS and LOC technology to the areas of biomedicine, biology, and biotechnology. The course was well received and the enrolled students had diverse backgrounds in electrical engineering, material science, biology, mechanical engineering, and chemistry. Student feedback and a review of the course evaluations indicated that the course was effective in achieving its objectives. Student presentations at the end of the course were a highlight and a valuable experience for all involved. The course proved successful and will continue to be offered regularly. This paper provides an overview of the course as well as some development and future improvements. PMID:25586697

Sub-micro-liter Electrochemical Single-Nucleotide-Polymorphism Detector for Lab-on-a-Chip System

NASA Astrophysics Data System (ADS)

Tanaka, Hiroyuki; Fiorini, Paolo; Peeters, Sara; Majeed, Bivragh; Sterken, Tom; de Beeck, Maaike Op; Hayashi, Miho; Yaku, Hidenobu; Yamashita, Ichiro

2012-04-01

A sub-micro-liter single-nucleotide-polymorphism (SNP) detector for lab-on-a-chip applications is developed. This detector enables a fast, sensitive, and selective SNP detection directly from human blood. The detector is fabricated on a Si substrate by a standard complementary metal oxide semiconductor/micro electro mechanical systems (CMOS/MEMS) process and Polydimethylsiloxane (PDMS) molding. Stable and reproducible measurements are obtained by implementing an on-chip Ag/AgCl electrode and encapsulating the detector. The detector senses the presence of SNPs by measuring the concentration of pyrophosphoric acid generated during selective DNA amplification. A 0.5-µL-volume detector enabled the successful performance of the typing of a SNP within the ABO gene using human blood. The measured sensitivity is 566 pA/µM.

Williams works with LOCAD-PTS in Destiny lab

NASA Image and Video Library

2007-04-01

ISS014-E-18822 (31 March 2007) --- Astronaut Sunita L. Williams, Expedition 14 flight engineer, works with the Lab-on-a-Chip Application Development-Portable Test System (LOCAD-PTS) experiment in the Destiny laboratory of the International Space Station. LOCAD-PTS is a handheld device for rapid detection of biological and chemical substances onboard the station.

Williams works with LOCAD-PTS in Destiny lab

NASA Image and Video Library

2007-04-01

ISS014-E-18818 (31 March 2007) --- Astronaut Sunita L. Williams, Expedition 14 flight engineer, works with the Lab-on-a-Chip Application Development-Portable Test System (LOCAD-PTS) experiment in the Destiny laboratory of the International Space Station. LOCAD-PTS is a handheld device for rapid detection of biological and chemical substances onboard the station.

Williams works with LOCAD-PTS in Destiny lab

NASA Image and Video Library

2007-04-01

ISS014-E-18811 (31 March 2007) --- Astronaut Sunita L. Williams, Expedition 14 flight engineer, works with the Lab-on-a-Chip Application Development-Portable Test System (LOCAD-PTS) experiment in the Destiny laboratory of the International Space Station. LOCAD-PTS is a handheld device for rapid detection of biological and chemical substances onboard the station.

On-Chip Biomedical Imaging

PubMed Central

Göröcs, Zoltán; Ozcan, Aydogan

2012-01-01

Lab-on-a-chip systems have been rapidly emerging to pave the way toward ultra-compact, efficient, mass producible and cost-effective biomedical research and diagnostic tools. Although such microfluidic and micro electromechanical systems achieved high levels of integration, and are capable of performing various important tasks on the same chip, such as cell culturing, sorting and staining, they still rely on conventional microscopes for their imaging needs. Recently several alternative on-chip optical imaging techniques have been introduced, which have the potential to substitute conventional microscopes for various lab-on-a-chip applications. Here we present a critical review of these recently emerging on-chip biomedical imaging modalities, including contact shadow imaging, lensfree holographic microscopy, fluorescent on-chip microscopy and lensfree optical tomography. PMID:23558399

Microfluidic Platform for the Long-Term On-Chip Cultivation of Mammalian Cells for Lab-On-A-Chip Applications.

PubMed

Bunge, Frank; Driesche, Sander van den; Vellekoop, Michael J

2017-07-10

Lab-on-a-Chip (LoC) applications for the long-term analysis of mammalian cells are still very rare due to the lack of convenient cell cultivation devices. The difficulties are the integration of suitable supply structures, the need of expensive equipment like an incubator and sophisticated pumps as well as the choice of material. The presented device is made out of hard, but non-cytotoxic materials (silicon and glass) and contains two vertical arranged membranes out of hydrogel. The porous membranes are used to separate the culture chamber from two supply channels for gases and nutrients. The cells are fed continuously by diffusion through the membranes without the need of an incubator and low requirements on the supply of medium to the assembly. The diffusion of oxygen is modelled in order to find the optimal dimensions of the chamber. The chip is connected via 3D-printed holders to the macroscopic world. The holders are coated with Parlyene C to ensure that only biocompatible materials are in contact with the culture medium. The experiments with MDCK-cells show the successful seeding inside the chip, culturing and passaging. Consequently, the presented platform is a step towards Lab-on-a-Chip applications that require long-term cultivation of mammalian cells.

Williams working on the LOCAD-PTS Experiment in the US Lab during Expedition 15

NASA Image and Video Library

2007-04-30

ISS015-E-05649 (30 April 2007) --- Astronaut Sunita L. Williams, Expedition 15 flight engineer, works with the Lab-on-a-Chip Application Development-Portable Test System (LOCAD-PTS) experiment in the Destiny laboratory of the International Space Station. LOCAD-PTS is a handheld device for rapid detection of biological and chemical substances onboard the station.

Williams works on the LOCAD-PTS Experiment in the US Lab during Expedition 15

NASA Image and Video Library

2007-05-05

ISS015-E-06777 (5 May 2007) --- Astronaut Sunita L. Williams, Expedition 15 flight engineer, works with the Lab-on-a-Chip Application Development-Portable Test System (LOCAD-PTS) experiment in the Destiny laboratory of the International Space Station. LOCAD-PTS is a handheld device for rapid detection of biological and chemical substances onboard the station.

Williams working on the LOCAD-PTS Experiment in the US Lab during Expedition 15

NASA Image and Video Library

2007-04-30

ISS015-E-05640 (30 April 2007) --- Astronaut Sunita L. Williams, Expedition 15 flight engineer, works with the Lab-on-a-Chip Application Development-Portable Test System (LOCAD-PTS) experiment in the Destiny laboratory of the International Space Station. LOCAD-PTS is a handheld device for rapid detection of biological and chemical substances onboard the station.

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.

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

NASA Astrophysics Data System (ADS)

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

2015-03-01

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

Nanophotonics for Lab-on-Chip Applications

NASA Astrophysics Data System (ADS)

Seitz, Peter

Optical methods are the preferred measurement techniques for biosensors and lab-on-chip applications. Their key properties are sensitivity, selectivity and robustness. To simplify the systems and their operation, it is desirable to employ label-free optical methods, requiring the functionalization of interfaces. Evanescent electromagnetic waves are probing the optical proper ties near the interfaces, a few 100 nm deep into the sample fluid. The sensitivity of these measurements can be improved with optical micro-resonators, in particular whispering gallery mode devices. Q factors as high as 2x108 have been achieved in practice. The resulting narrow-linewidth resonances and an unexpected thermo-optic effect make it possible to detect single biomolecules using a label-free biosensor principle. Future generations of biosensors and labs-on-chip for point-of-care and high-troughput screening applications will require large numbers of parallel measurement channels, necessitating optical micro-resonators in array format produced very cost-effectively.

The Extended Core Coax: A novel nanoarchitecture for lab-on-a-chip electrochemical diagnostics

NASA Astrophysics Data System (ADS)

Valera, Amy E.; D'Imperio, Luke; Burns, Michael J.; Naughton, Michael J.; Chiles, Thomas C.

We report a novel nanoarchitecture, the Extended Core Coax (ECC) that has applicability for the detection of biomarkers in lab-on-a-chip diagnostic devices. ECC is capable of providing accessible, highly sensitive, and specific disease diagnosis at point-of-care. The architecture represents a vertically oriented nanocoax comprised of a gold inner metal core that extends 200nm above a chrome outer metal shield, separated by a dielectric annulus. Each ECC chip contains 7 discrete sensing arrays, 0.49 mm2 in size, containing 35,000 nanoscale coaxes wired in parallel. Previous non-extended nanocoaxial architectures have demonstrated a limit of detection (LOD) of 2 ng/mL of cholera toxin using an off-chip setup. This sensitivity compares favorably to the standard optical ELISA used in clinical settings. The ECC matches this LOD, and additionally offers the benefit of specific and reliable biofunctionalization on the extended gold core. Thus, the ECC is an attractive candidate for development as a full lab-on-a-chip biosensor for detection of infectious disease biomarkers, such as cholera toxin, through tethering of biomarker recognition proteins, such as antibodies, directly on the device. Support from the National Institutes of Health (National Cancer Institute award No. CA137681 and National Institute of Allergy and Infectious Diseases award No. AI100216).

Optimized holographic femtosecond laser patterning method towards rapid integration of high-quality functional devices in microchannels.

PubMed

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

2016-09-13

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

Optimized holographic femtosecond laser patterning method towards rapid integration of high-quality functional devices in microchannels

NASA Astrophysics Data System (ADS)

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

2016-09-01

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

Three-dimensional femtosecond laser processing for lab-on-a-chip applications

NASA Astrophysics Data System (ADS)

Sima, Felix; Sugioka, Koji; Vázquez, Rebeca Martínez; Osellame, Roberto; Kelemen, Lóránd; Ormos, Pal

2018-02-01

The extremely high peak intensity associated with ultrashort pulse width of femtosecond laser allows us to induce nonlinear interaction such as multiphoton absorption and tunneling ionization with materials that are transparent to the laser wavelength. More importantly, focusing the femtosecond laser beam inside the transparent materials confines the nonlinear interaction only within the focal volume, enabling three-dimensional (3D) micro- and nanofabrication. This 3D capability offers three different schemes, which involve undeformative, subtractive, and additive processing. The undeformative processing preforms internal refractive index modification to construct optical microcomponents including optical waveguides. Subtractive processing can realize the direct fabrication of 3D microfluidics, micromechanics, microelectronics, and photonic microcomponents in glass. Additive processing represented by two-photon polymerization enables the fabrication of 3D polymer micro- and nanostructures for photonic and microfluidic devices. These different schemes can be integrated to realize more functional microdevices including lab-on-a-chip devices, which are miniaturized laboratories that can perform reaction, detection, analysis, separation, and synthesis of biochemical materials with high efficiency, high speed, high sensitivity, low reagent consumption, and low waste production. This review paper describes the principles and applications of femtosecond laser 3D micro- and nanofabrication for lab-on-a-chip applications. A hybrid technique that promises to enhance functionality of lab-on-a-chip devices is also introduced.

Development of a versatile lab-on-a-chip enzyme assay platform for pathogen detection in CBRNE scenarios

NASA Astrophysics Data System (ADS)

Klemm, Richard; Schattschneider, Sebastian; Jahn, Tobias; Hlawatsch, Nadine; Julich, Sandra; Becker, Holger; Gärtner, Claudia

2013-05-01

The ability to integrate complete assays on a microfluidic chip helps to greatly simplify instrument requirements and allows the use of lab-on-a-chip technology in the field. A core application for such field-portable systems is the detection of pathogens in a CBRNE scenario such as permanent monitoring of airborne pathogens, e.g. in metro stations or hospitals etc. As one assay methodology for the pathogen identification, enzymatic assays were chosen. In order evaluate different detection strategies, the realized on-chip enzyme assay module has been designed as a general platform chip. In all application cases, the assays are based on immobilized probes located in microfluidic channels. Therefore a microfluidic chip was realized containing a set of three individually addressable channels, not only for detection of the sample itself also to have a set of references for a quantitative analysis. It furthermore includes two turning valves and a waste container for clear and sealed storage of potential pathogenic liquids to avoid contamination of the environment. All liquids remain in the chip and can be disposed of in proper way subsequently to the analysis. The chip design includes four inlet ports consisting of one sample port (Luer interface) and three mini Luer interfaces for fluidic support of e.g. washing buffer, substrate and enzyme solution. The sample can be applied via a special, sealable sampling vessel with integrated female Luer interface. Thereby also pre-anaytical contamination of the environment can be provided. Other reagents that are required for analysis will be stored off chip.

MineLoC: A Rapid Production of Lab-on-a-Chip Biosensors Using 3D Printer and the Sandbox Game, Minecraft.

PubMed

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

2018-06-10

Here, MineLoC is described as a pipeline developed to generate 3D printable models of master templates for Lab-on-a-Chip (LoC) by using a popular multi-player sandbox game “Minecraft”. The user can draw a simple diagram describing the channels and chambers of the Lab-on-a-Chip devices with pre-registered color codes which indicate the height of the generated structure. MineLoC converts the diagram into large chunks of blocks (equal sized cube units composing every object in the game) in the game world. The user and co-workers can simultaneously access the game and edit, modify, or review, which is a feature not generally supported by conventional design software. Once the review is complete, the resultant structure can be exported into a stereolithography (STL) file which can be used in additive manufacturing. Then, the Lab-on-a-Chip device can be fabricated by the standard protocol to produce a Lab-on-a-Chip. The simple polydimethylsiloxane (PDMS) device for the bacterial growth measurement used in the previous research was copied by the proposed method. The error calculation by a 3D model comparison showed an accuracy of 86%. It is anticipated that this work will facilitate more use of 3D printer-based Lab-on-a-Chip fabrication, which greatly lowers the entry barrier in the field of Lab-on-a-Chip research.

Multilayer-based lab-on-a-chip systems for perfused cell-based assays

NASA Astrophysics Data System (ADS)

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

2014-12-01

A novel integrated technology chain of laser-microstructured multilayer foils for fast, flexible, and low-cost manufacturing of lab-on-a-chip devices especially for complex cell and tissue culture applications, which provides pulsatile fluid flow within physiological ranges at low media-to-cells ratio, was developed and established. Initially the microfluidic system is constructively divided into individual layers, which are formed by separate foils or plates. Based on the functional boundary conditions and the necessary properties of each layer, their corresponding foils and plates are chosen. In the third step, the foils and plates are laser microstructured and functionalized from both sides. In the fourth and last manufacturing step, the multiple plates and foils are joined using different bonding techniques like adhesive bonding, welding, etc. This multilayer technology together with pneumatically driven micropumps and valves permits the manufacturing of fluidic structures and perfusion systems, which spread out above multiple planes. Based on the established lab-on-a-chip platform for perfused cell-based assays, a multilayer microfluidic system with two parallel connected cell culture chambers was successfully implemented.

Laser subtractive-additive-welding microfabrication for Lab-On-Chip (LOC) applications

NASA Astrophysics Data System (ADS)

Jonušauskas, Linas; RekštytÄ--, Sima; Buivydas, Ričardas; Butkus, Simas; Paipulas, Domas; Gadonas, Roaldas; Juodkazis, Saulius; Malinauskas, Mangirdas

2017-02-01

An approach employing ultrafast laser hybrid microfabrication combining ablation, 3D nanolithography and welding is proposed for the realization of Lab-On-Chip (LOC) device. The same laser setup is shown to be suitable for fabricating microgrooves in glass slabs, polymerization of fine meshes inside them, and, lastly, sealing the whole chip with cover glass into one monolithic piece. The created micro fluidic device proved its particle sorting function by separating 1 μm and 10 μm polystyrene spheres from a mixture. Next, a lens adapter for a cell phone's camera was manufactured via thermal extrusion 3D printing technique which allowed to achieve sufficient magnification to clearly resolve <10 μm features. All together shows fs-laser microfabrication technology as a flexible and versatile tool for study and manufacturing of Lab-On-Chip devices.

Creating a Tiny Human Body on a Chip

ScienceCinema

Hunsberger, Maren; Soscia, Dave; Moya, Monica

2018-06-21

LLNL science communicator Maren Hunsberger takes us "Inside the Lab" to learn about the iChip (In-vitro Chip-based Human Investigational Platform) project at Lawrence Livermore National Laboratory. "One application of the iChip system would be to develop new pharmaceutical drugs," explains Dave Soscia, LLNL postdoc. "When you test in a mouse for example, it's not as close to the human system as you can get. If we can take human cells and put them on devices and actually mimic the structure and function of the organ systems in the human, we can actually replace animal testing and even make a better system for testing pharmaceutical drugs."

Real-time PCR machine system modeling and a systematic approach for the robust design of a real-time PCR-on-a-chip system.

PubMed

Lee, Da-Sheng

2010-01-01

Chip-based DNA quantification systems are widespread, and used in many point-of-care applications. However, instruments for such applications may not be maintained or calibrated regularly. Since machine reliability is a key issue for normal operation, this study presents a system model of the real-time Polymerase Chain Reaction (PCR) machine to analyze the instrument design through numerical experiments. Based on model analysis, a systematic approach was developed to lower the variation of DNA quantification and achieve a robust design for a real-time PCR-on-a-chip system. Accelerated lift testing was adopted to evaluate the reliability of the chip prototype. According to the life test plan, this proposed real-time PCR-on-a-chip system was simulated to work continuously for over three years with similar reproducibility in DNA quantification. This not only shows the robustness of the lab-on-a-chip system, but also verifies the effectiveness of our systematic method for achieving a robust design.

Optimized holographic femtosecond laser patterning method towards rapid integration of high-quality functional devices in microchannels

PubMed Central

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

2016-01-01

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

Lab-on-a-Chip: Frontier Science in the Classroom

ERIC Educational Resources Information Center

Wietsma, Jan Jaap; van der Veen, Jan T.; Buesink, Wilfred; van den Berg, Albert; Odijk, Mathieu

2018-01-01

Lab-on-a-chip technology is brought into the classroom through development of a lesson series with hands-on practicals. Students can discover the principles of microfluidics with different practicals covering laminar flow, micromixing, and droplet generation, as well as trapping and counting beads. A quite affordable novel production technique…

A versatile electrowetting-based digital microfluidic platform for quantitative homogeneous and heterogeneous bio-assays

NASA Astrophysics Data System (ADS)

Vergauwe, Nicolas; Witters, Daan; Ceyssens, Frederik; Vermeir, Steven; Verbruggen, Bert; Puers, Robert; Lammertyn, Jeroen

2011-05-01

Electrowetting-on-dielectric (EWOD) lab-on-a-chip systems have already proven their potential within a broad range of bio-assays. Nevertheless, research on the analytical performance of those systems is limited, yet crucial for a further breakthrough in the diagnostic field. Therefore, this paper presents the intrinsic possibilities of an EWOD lab-on-a-chip as a versatile platform for homogeneous and heterogeneous bio-assays with high analytical performance. Both droplet dispensing and splitting cause variations in droplet size, thereby directly influencing the assay's performance. The extent to which they influence the performance is assessed by a theoretical sensitivity analysis, which allows the definition of a basic framework for the reduction of droplet size variability. Taking advantage of the optimized droplet manipulations, both homogeneous and heterogeneous bio-assays are implemented in the EWOD lab-on-a-chip to demonstrate the analytical capabilities and versatility of the device. A fully on-chip enzymatic assay is realized with high analytical performance. It demonstrates the promising capabilities of an EWOD lab-on-a-chip in food-related and medical applications, such as nutritional and blood analyses. Further, a magnetic bio-assay for IgE detection using superparamagnetic nanoparticles is presented whereby the nanoparticles are used as solid carriers during the bio-assay. Crucial elements are the precise manipulation of the superparamagnetic nanoparticles with respect to dispensing and separation. Although the principle of using nano-carriers is demonstrated for protein detection, it can be easily extended to a broader range of bio-related applications like DNA sensing. In heterogeneous bio-assays the chip surface is actively involved during the execution of the bio-assay. Through immobilization of specific biological compounds like DNA, proteins and cells a reactive chip surface is realized, which enhances the bio-assay performance. To demonstrate this potential, on-chip adhesion islands are fabricated to immobilize MCF-7 human breast cancer cells. Viability studies are performed to assess the functionalization efficiency.

Cambridge Healthtech Institute's Third Annual Conference on Lab-on-a-Chip and Microarrays. 22-24 January 2001, Zurich, Switzerland.

PubMed

Jain, K K

2001-02-01

Cambridge Healthtech Institute's Third Annual Conference on Lab-on-a-Chip and Microarray technology covered the latest advances in this technology and applications in life sciences. Highlights of the meetings are reported briefly with emphasis on applications in genomics, drug discovery and molecular diagnostics. There was an emphasis on microfluidics because of the wide applications in laboratory and drug discovery. The lab-on-a-chip provides the facilities of a complete laboratory in a hand-held miniature device. Several microarray systems have been used for hybridisation and detection techniques. Oligonucleotide scanning arrays provide a versatile tool for the analysis of nucleic acid interactions and provide a platform for improving the array-based methods for investigation of antisense therapeutics. A method for analysing combinatorial DNA arrays using oligonucleotide-modified gold nanoparticle probes and a conventional scanner has considerable potential in molecular diagnostics. Various applications of microarray technology for high-throughput screening in drug discovery and single nucleotide polymorphisms (SNP) analysis were discussed. Protein chips have important applications in proteomics. With the considerable amount of data generated by the different technologies using microarrays, it is obvious that the reading of the information and its interpretation and management through the use of bioinformatics is essential. Various techniques for data analysis were presented. Biochip and microarray technology has an essential role to play in the evolving trends in healthcare, which integrate diagnosis with prevention/treatment and emphasise personalised medicines.

Creating a Tiny Human Body on a Chip

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

Hunsberger, Maren; Soscia, Dave; Moya, Monica

LLNL science communicator Maren Hunsberger takes us "Inside the Lab" to learn about the iChip (In-vitro Chip-based Human Investigational Platform) project at Lawrence Livermore National Laboratory. "One application of the iChip system would be to develop new pharmaceutical drugs," explains Dave Soscia, LLNL postdoc. "When you test in a mouse for example, it's not as close to the human system as you can get. If we can take human cells and put them on devices and actually mimic the structure and function of the organ systems in the human, we can actually replace animal testing and even make a bettermore » system for testing pharmaceutical drugs."« less

Recent advances in nanoplasmonic biosensors: applications and lab-on-a-chip integration

NASA Astrophysics Data System (ADS)

Lopez, Gerardo A.; Estevez, M.-Carmen; Soler, Maria; Lechuga, Laura M.

2017-01-01

Motivated by the recent progress in the nanofabrication field and the increasing demand for cost-effective, portable, and easy-to-use point-of-care platforms, localized surface plasmon resonance (LSPR) biosensors have been subjected to a great scientific interest in the last few years. The progress observed in the research of this nanoplasmonic technology is remarkable not only from a nanostructure fabrication point of view but also in the complete development and integration of operative devices and their application. The potential benefits that LSPR biosensors can offer, such as sensor miniaturization, multiplexing opportunities, and enhanced performances, have quickly positioned them as an interesting candidate in the design of lab-on-a-chip (LOC) optical biosensor platforms. This review covers specifically the most significant achievements that occurred in recent years towards the integration of this technology in compact devices, with views of obtaining LOC devices. We also discuss the most relevant examples of the use of the nanoplasmonic biosensors for real bioanalytical and clinical applications from assay development and validation to the identification of the implications, requirements, and challenges to be surpassed to achieve fully operative devices.

Lab-on-a-chip modules for detection of highly pathogenic bacteria: from sample preparation to detection

NASA Astrophysics Data System (ADS)

Julich, S.; Kopinč, R.; Hlawatsch, N.; Moche, C.; Lapanje, A.; Gärtner, C.; Tomaso, H.

2014-05-01

Lab-on-a-chip systems are innovative tools for the detection and identification of microbial pathogens in human and veterinary medicine. The major advantages are small sample volume and a compact design. Several fluidic modules have been developed to transform analytical procedures into miniaturized scale including sampling, sample preparation, target enrichment, and detection procedures. We present evaluation data for single modules that will be integrated in a chip system for the detection of pathogens. A microfluidic chip for purification of nucleic acids was established for cell lysis using magnetic beads. This assay was evaluated with spiked environmental aerosol and swab samples. Bacillus thuringiensis was used as simulant for Bacillus anthracis, which is closely related but non-pathogenic for humans. Stationary PCR and a flow-through PCR chip module were investigated for specific detection of six highly pathogenic bacteria. The conventional PCR assays could be transferred into miniaturized scale using the same temperature/time profile. We could demonstrate that the microfluidic chip modules are suitable for the respective purposes and are promising tools for the detection of bacterial pathogens. Future developments will focus on the integration of these separate modules to an entire lab-on-a-chip system.

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

NASA Astrophysics Data System (ADS)

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

2016-03-01

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

Lab-on-a-Chip Based Protein Crystallization

NASA Technical Reports Server (NTRS)

vanderWoerd, Mark J.; Brasseur, Michael M.; Spearing, Scott F.; Whitaker, Ann F. (Technical Monitor)

2001-01-01

We are developing a novel technique with which we will grow protein crystals in very small volumes, utilizing chip-based, microfluidic ("LabChip") technology. This development, which is a collaborative effort between NASA's Marshall Space Flight Center and Caliper Technologies Corporation, promises a breakthrough in the field of protein crystal growth. Our initial results obtained from two model proteins, Lysozyme and Thaumatin, show that it is feasible to dispense and adequately mix protein and precipitant solutions on a nano-liter scale. The mixtures have shown crystal growth in volumes in the range of 10 nanoliters to 5 microliters. In addition, large diffraction quality crystals were obtained by this method. X-ray data from these crystals were shown to be of excellent quality. Our future efforts will include the further development of protein crystal growth with LabChip(trademark) technology for more complex systems. We will initially address the batch growth method, followed by the vapor diffusion method and the liquid-liquid diffusion method. The culmination of these chip developments is to lead to an on orbit protein crystallization facility on the International Space Station. Structural biologists will be invited to utilize the on orbit Iterative Biological Crystallization facility to grow high quality macromolecular crystals in microgravity.

Multicore: Fallout from a Computing Evolution

ScienceCinema

Yelick, Kathy [Director, NERSC

2017-12-09

July 22, 2008 Berkeley Lab lecture: Parallel computing used to be reserved for big science and engineering projects, but in two years that's all changed. Even laptops and hand-helds use parallel processors. Unfortunately, the software hasn't kept pace. Kathy Yelick, Director of the National Energy Research Scientific Computing Center at Berkeley Lab, describes the resulting chaos and the computing community's efforts to develop exciting applications that take advantage of tens or hundreds of processors on a single chip.

Development and applications of 3-dimensional integration nanotechnologies.

PubMed

Kim, Areum; Choi, Eunmi; Son, Hyungbin; Pyo, Sung Gyu

2014-02-01

Unlike conventional two-dimensional (2D) planar structures, signal or power is supplied through through-silicon via (TSV) in three-dimensional (3D) integration technology to replace wires for binding the chip/wafer. TSVs have becomes an essential technology, as they satisfy Moore's law. This 3D integration technology enables system and sensor functions at a nanoscale via the implementation of a highly integrated nano-semiconductor as well as the fabrication of a single chip with multiple functions. Thus, this technology is considered to be a new area of development for the systemization of the nano-bio area. In this review paper, the basic technology required for such 3D integration is described and methods to measure the bonding strength in order to measure the void occurring during bonding are introduced. Currently, CMOS image sensors and memory chips associated with nanotechnology are being realized on the basis of 3D integration technology. In this paper, we intend to describe the applications of high-performance nano-biosensor technology currently under development and the direction of development of a high performance lab-on-a-chip (LOC).

Biosensor system-on-a-chip including CMOS-based signal processing circuits and 64 carbon nanotube-based sensors for the detection of a neurotransmitter.

PubMed

Lee, Byung Yang; Seo, Sung Min; Lee, Dong Joon; Lee, Minbaek; Lee, Joohyung; Cheon, Jun-Ho; Cho, Eunju; Lee, Hyunjoong; Chung, In-Young; Park, Young June; Kim, Suhwan; Hong, Seunghun

2010-04-07

We developed a carbon nanotube (CNT)-based biosensor system-on-a-chip (SoC) for the detection of a neurotransmitter. Here, 64 CNT-based sensors were integrated with silicon-based signal processing circuits in a single chip, which was made possible by combining several technological breakthroughs such as efficient signal processing, uniform CNT networks, and biocompatible functionalization of CNT-based sensors. The chip was utilized to detect glutamate, a neurotransmitter, where ammonia, a byproduct of the enzymatic reaction of glutamate and glutamate oxidase on CNT-based sensors, modulated the conductance signals to the CNT-based sensors. This is a major technological advancement in the integration of CNT-based sensors with microelectronics, and this chip can be readily integrated with larger scale lab-on-a-chip (LoC) systems for various applications such as LoC systems for neural networks.

Real-time PCR Machine System Modeling and a Systematic Approach for the Robust Design of a Real-time PCR-on-a-Chip System

PubMed Central

Lee, Da-Sheng

2010-01-01

Chip-based DNA quantification systems are widespread, and used in many point-of-care applications. However, instruments for such applications may not be maintained or calibrated regularly. Since machine reliability is a key issue for normal operation, this study presents a system model of the real-time Polymerase Chain Reaction (PCR) machine to analyze the instrument design through numerical experiments. Based on model analysis, a systematic approach was developed to lower the variation of DNA quantification and achieve a robust design for a real-time PCR-on-a-chip system. Accelerated lift testing was adopted to evaluate the reliability of the chip prototype. According to the life test plan, this proposed real-time PCR-on-a-chip system was simulated to work continuously for over three years with similar reproducibility in DNA quantification. This not only shows the robustness of the lab-on-a-chip system, but also verifies the effectiveness of our systematic method for achieving a robust design. PMID:22315563

Polymeric LabChip Real-Time PCR as a Point-of-Care-Potential Diagnostic Tool for Rapid Detection of Influenza A/H1N1 Virus in Human Clinical Specimens

PubMed Central

Song, Hyun-Ok; Kim, Je-Hyoung; Ryu, Ho-Sun; Lee, Dong-Hoon; Kim, Sun-Jin; Kim, Deog-Joong; Suh, In Bum; Choi, Du Young; In, Kwang-Ho; Kim, Sung-Woo; Park, Hyun

2012-01-01

It is clinically important to be able to detect influenza A/H1N1 virus using a fast, portable, and accurate system that has high specificity and sensitivity. To achieve this goal, it is necessary to develop a highly specific primer set that recognizes only influenza A viral genes and a rapid real-time PCR system that can detect even a single copy of the viral gene. In this study, we developed and validated a novel fluidic chip-type real-time PCR (LabChip real-time PCR) system that is sensitive and specific for the detection of influenza A/H1N1, including the pandemic influenza strain A/H1N1 of 2009. This LabChip real-time PCR system has several remarkable features: (1) It allows rapid quantitative analysis, requiring only 15 min to perform 30 cycles of real-time PCR. (2) It is portable, with a weight of only 5.5 kg. (3) The reaction cost is low, since it uses disposable plastic chips. (4) Its high efficiency is equivalent to that of commercially available tube-type real-time PCR systems. The developed disposable LabChip is an economic, heat-transferable, light-transparent, and easy-to-fabricate polymeric chip compared to conventional silicon- or glass-based labchip. In addition, our LabChip has large surface-to-volume ratios in micro channels that are required for overcoming time consumed for temperature control during real-time PCR. The efficiency of the LabChip real-time PCR system was confirmed using novel primer sets specifically targeted to the hemagglutinin (HA) gene of influenza A/H1N1 and clinical specimens. Eighty-five human clinical swab samples were tested using the LabChip real-time PCR. The results demonstrated 100% sensitivity and specificity, showing 72 positive and 13 negative cases. These results were identical to those from a tube-type real-time PCR system. This indicates that the novel LabChip real-time PCR may be an ultra-fast, quantitative, point-of-care-potential diagnostic tool for influenza A/H1N1 with a high sensitivity and specificity. PMID:23285281

The multifunctional application of microfluidic lab-on-a-chip surface enhanced Raman spectroscopy (LOC-SERS) within the field of bioanalytics

NASA Astrophysics Data System (ADS)

März, Anne; Mönch, Bettina; Walter, Angela; Bocklitz, Thomas; Schumacher, Wilm; Rösch, Petra; Kiehntopf, Michael; Popp, Jürgen

2011-07-01

This contribution will present a variety of applications of lab-on-a-chip surface enhanced Raman spectroscopy in the field of bioanalytic. Beside the quantification and online monitoring of drugs and pharmaceuticals, determination of enzyme activity and discrimination of bacteria are successfully carried out utilizing LOC-SERS. The online-monitoring of drugs using SERS in a microfluidic device is demonstrated for nicotine. The enzyme activity of thiopurine methyltransferase (TPMT) in lysed red blood cells is determined by SERS in a lab-on-a-chip device. To analyse the activity of TPMT the metabolism of 6-mercaptopurine to 6-methylmercaptopurine is investigated. The discrimination of bacteria on strain level is carried out with different E. coli strains. For the investigations, the bacteria are busted by ultra sonic to achieve a high information output. This sample preparation provides the possibility to detect SERS spectra containing information of the bacterial cell walls as well as of the cytoplasm. This contribution demonstrates the great potential of LOC-SERS in the field of bioanalytics.

On-Demand Urine Analyzer

NASA Technical Reports Server (NTRS)

Farquharson, Stuart; Inscore, Frank; Shende, Chetan

2010-01-01

A lab-on-a-chip was developed that is capable of extracting biochemical indicators from urine samples and generating their surface-enhanced Raman spectra (SERS) so that the indicators can be quantified and identified. The development was motivated by the need to monitor and assess the effects of extended weightlessness, which include space motion sickness and loss of bone and muscle mass. The results may lead to developments of effective exercise programs and drug regimes that would maintain astronaut health. The analyzer containing the lab-on-a- chip includes materials to extract 3- methylhistidine (a muscle-loss indicator) and Risedronate (a bone-loss indicator) from the urine sample and detect them at the required concentrations using a Raman analyzer. The lab-on- a-chip has both an extractive material and a SERS-active material. The analyzer could be used to monitor the onset of diseases, such as osteoporosis.

A microfluidic platform with integrated arrays for immunologic assays for biological pathogen detection

NASA Astrophysics Data System (ADS)

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

2014-05-01

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

Lab-on-a-Chip

NASA Technical Reports Server (NTRS)

2004-01-01

Labs on chips are manufactured in many shapes and sizes and can be used for numerous applications, from medical tests to water quality monitoring to detecting the signatures of life on other planets. The eight holes on this chip are actually ports that can be filled with fluids or chemicals. Tiny valves control the chemical processes by mixing fluids that move in the tiny channels that look like lines, connecting the ports. Scientists at NASA's Marshall Space Flight Center (MSFC) in Huntsville, Alabama designed this chip to grow biological crystals on the International Space Station. Through this research, they discovered that this technology is ideally suited for solving the challenges of the Vision for Space Exploration. For example, thousands of chips the size of dimes could be loaded on a Martian rover looking for biosignatures of past or present life. Other types of chips could be placed in handheld devices used to monitor microbes in water or to quickly conduct medical tests on astronauts. (NASA/MSFC/D.Stoffer)

Rapid detection of aflatoxigenic Aspergillus sp. in herbal specimens by a simple, bendable, paper-based lab-on-a-chip.

PubMed

Chaumpluk, Piyasak; Plubcharoensook, Pattra; Prasongsuk, Sehanat

2016-06-01

Postharvest herbal product contamination with mycotoxins and mycotoxin-producing fungi represents a potentially carcinogenic hazard. Aspergillus flavus is a major cause of this issue. Available mold detection methods are PCR-based and rely heavily on laboratories; thus, they are unsuitable for on-site monitoring. In this study, a bendable, paper-based lab-on-a-chip platform was developed to rapidly detect toxigenic Aspergillus spp. DNA. The 3.0-4.0 cm(2) chip is fabricated using Whatman™ filter paper, fishing line and a simple plastic lamination process and has nucleic acid amplification and signal detection components. The Aspergillus assay specifically amplifies the aflatoxin biosynthesis gene, aflR, using loop-mediated isothermal amplification (LAMP); hybridization between target DNA and probes on blue silvernanoplates (AgNPls) yields colorimetric results. Positive results are indicated by the detection pad appearing blue due to dispersed blue AgNPls; negative results are indicated by the detection pad appearing colorless or pale yellow due to probe/target DNA hybridization and AgNPls aggregation. Assay completion requires less than 40 min, has a limit of detection (LOD) of 100 aflR copies, and has high specificity (94.47%)and sensitivity (100%). Contamination was identified in 14 of 32 herbal samples tested (43.75%). This work demonstrates the fabrication of a simple, low-cost, paper-based lab-on-a-chip platform suitable for rapid-detection applications. Copyright © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

Rotational microfluidic motor for on-chip microcentrifugation

NASA Astrophysics Data System (ADS)

Shilton, Richie J.; Glass, Nick R.; Chan, Peggy; Yeo, Leslie Y.; Friend, James R.

2011-06-01

We report on the design of a surface acoustic wave (SAW) driven fluid-coupled micromotor which runs at high rotational velocities. A pair of opposing SAWs generated on a lithium niobate substrate are each obliquely passed into either side of a fluid drop to drive rotation of the fluid, and the thin circular disk set on the drop. Using water for the drop, a 5 mm diameter disk was driven with rotation speeds and start-up torques up to 2250 rpm and 60 nN m, respectively. Most importantly for lab-on-a-chip applications, radial accelerations of 172 m/s2 was obtained, presenting possibilities for microcentrifugation, flow sequencing, assays, and cell culturing in truly microscale lab-on-a-chip devices.

Transient Flow Dynamics in Optical Micro Well Involving Gas Bubbles

NASA Technical Reports Server (NTRS)

Johnson, B.; Chen, C. P.; Jenkins, A.; Spearing, S.; Monaco, L. A.; Steele, A.; Flores, G.

2006-01-01

The Lab-On-a-Chip Application Development (LOCAD) team at NASA s Marshall Space Flight Center is utilizing Lab-On-a-Chip to support technology development specifically for Space Exploration. In this paper, we investigate the transient two-phase flow patterns in an optic well configuration with an entrapped bubble through numerical simulation. Specifically, the filling processes of a liquid inside an expanded chamber that has bubbles entrapped. Due to the back flow created by channel expansion, the entrapped bubbles tend to stay stationary at the immediate downstream of the expansion. Due to the huge difference between the gas and liquid densities, mass conservation issues associated with numerical diffusion need to be specially addressed. The results are presented in terms of the movement of the bubble through the optic well. Bubble removal strategies are developed that involve only pressure gradients across the optic well. Results show that for the bubble to be moved through the well, pressure pulsations must be utilized in order to create pressure gradients across the bubble itself.

Lab-on-a-chip sensor for measuring Zn by stripping voltammetry

NASA Astrophysics Data System (ADS)

Pei, Xing; Kang, Wenjing; Yue, Wei; Bange, Adam; Wong, Hector R.; Heineman, William R.; Papautsky, Ian

2012-03-01

This work reports on continuing development of a lab-on-a-chip sensor for electrochemical detection of heavy metal zinc in blood serum. The sensor consists of a three electrode system, including an environmentally-friendly bismuth working electrode, a Ag/AgCl reference electrode, and a gold auxiliary electrode. By optimizing the electrodeposition of bismuth film, better control of fabrication steps and improving interface between the sensor and potentiostat, repeatability and sensitivity of the lab-on-a-chip sensor has been improved. Through optimization of electrolyte and stripping voltammetry parameters, limits of detection were greatly improved. The optimized sensor was able to measure zinc in in the physiological range of 65-95 μg/dL. Ultimately, with further development and integrated sample preparation sensor system will permit rapid (min) measurements of zinc from a sub-mL sample (a few drops of blood) for bedside monitoring.

CHIP, CHIP, ARRAY! THREE CHIPS FOR POST-GENOMIC RESEARCH

EPA Science Inventory

Cambridge Healthtech Institute recently held the 4th installment of their popular "Lab-on-a-Chip" series in Zurich, Switzerland. As usual, it was enthusiastically received and over 225 people attended the 2-1/2 day meeting to see and hear about some of the latest developments an...

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

PubMed Central

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

2016-01-01

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

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

PubMed

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

2016-04-14

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

Lab-on-a-chip nucleic-acid analysis towards point-of-care applications

NASA Astrophysics Data System (ADS)

Kopparthy, Varun Lingaiah

Recent infectious disease outbreaks, such as Ebola in 2013, highlight the need for fast and accurate diagnostic tools to combat the global spread of the disease. Detection and identification of the disease-causing viruses and bacteria at the genetic level is required for accurate diagnosis of the disease. Nucleic acid analysis systems have shown promise in identifying diseases such as HIV, anthrax, and Ebola in the past. Conventional nucleic acid analysis systems are still time consuming, and are not suitable for point-ofcare applications. Miniaturized nucleic acid systems has shown great promise for rapid analysis, but they have not been commercialized due to several factors such as footprint, complexity, portability, and power consumption. This dissertation presents the development of technologies and methods for a labon-a-chip nucleic acid analysis towards point-of-care applications. An oscillatory-flow PCR methodology in a thermal gradient is developed which provides real-time analysis of nucleic-acid samples. Oscillating flow PCR was performed in the microfluidic device under thermal gradient in 40 minutes. Reverse transcription PCR (RT-PCR) was achieved in the system without an additional heating element for incubation to perform reverse transcription step. A novel method is developed for the simultaneous pattering and bonding of all-glass microfluidic devices in a microwave oven. Glass microfluidic devices were fabricated in less than 4 minutes. Towards an integrated system for the detection of amplified products, a thermal sensing method is studied for the optimization of the sensor output. Calorimetric sensing method is characterized to identify design considerations and optimal parameters such as placement of the sensor, steady state response, and flow velocity for improved performance. An understanding of these developed technologies and methods will facilitate the development of lab-on-a-chip systems for point-of-care analysis.

Imaging electric field dynamics with graphene optoelectronics.

PubMed

Horng, Jason; Balch, Halleh B; McGuire, Allister F; Tsai, Hsin-Zon; Forrester, Patrick R; Crommie, Michael F; Cui, Bianxiao; Wang, Feng

2016-12-16

The use of electric fields for signalling and control in liquids is widespread, spanning bioelectric activity in cells to electrical manipulation of microstructures in lab-on-a-chip devices. However, an appropriate tool to resolve the spatio-temporal distribution of electric fields over a large dynamic range has yet to be developed. Here we present a label-free method to image local electric fields in real time and under ambient conditions. Our technique combines the unique gate-variable optical transitions of graphene with a critically coupled planar waveguide platform that enables highly sensitive detection of local electric fields with a voltage sensitivity of a few microvolts, a spatial resolution of tens of micrometres and a frequency response over tens of kilohertz. Our imaging platform enables parallel detection of electric fields over a large field of view and can be tailored to broad applications spanning lab-on-a-chip device engineering to analysis of bioelectric phenomena.

The recent development and applications of fluidic channels by 3D printing.

PubMed

Zhou, Yufeng

2017-10-18

The technology of "Lab-on-a-Chip" allows the synthesis and analysis of chemicals and biological substance within a portable or handheld device. The 3D printed structures enable precise control of various geometries. The combination of these two technologies in recent years makes a significant progress. The current approaches of 3D printing, such as stereolithography, polyjet, and fused deposition modeling, are introduced. Their manufacture specifications, such as surface roughness, resolution, replication fidelity, cost, and fabrication time, are compared with each other. Finally, novel application of 3D printed channel in biology are reviewed, including pathogenic bacteria detection using magnetic nanoparticle clusters in a helical microchannel, cell stimulation by 3D chemical gradients, perfused functional vascular channels, 3D tissue construct, organ-on-a-chip, and miniaturized fluidic "reactionware" devices for chemical syntheses. Overall, the 3D printed fluidic chip is becoming a powerful tool in the both medical and chemical industries.

An Integrated Lab-on-Chip for Rapid Identification and Simultaneous Differentiation of Tropical Pathogens

PubMed Central

Sato, Mitsuharu; Watthanaworawit, Wanitda; Ling, Clare L.; Mauduit, Marjorie; Malleret, Benoît; Grüner, Anne-Charlotte; Tan, Rosemary; Nosten, François H.; Snounou, Georges; Rénia, Laurent; Ng, Lisa F. P.

2014-01-01

Tropical pathogens often cause febrile illnesses in humans and are responsible for considerable morbidity and mortality. The similarities in clinical symptoms provoked by these pathogens make diagnosis difficult. Thus, early, rapid and accurate diagnosis will be crucial in patient management and in the control of these diseases. In this study, a microfluidic lab-on-chip integrating multiplex molecular amplification and DNA microarray hybridization was developed for simultaneous detection and species differentiation of 26 globally important tropical pathogens. The analytical performance of the lab-on-chip for each pathogen ranged from 102 to 103 DNA or RNA copies. Assay performance was further verified with human whole blood spiked with Plasmodium falciparum and Chikungunya virus that yielded a range of detection from 200 to 4×105 parasites, and from 250 to 4×107 PFU respectively. This lab-on-chip was subsequently assessed and evaluated using 170 retrospective patient specimens in Singapore and Thailand. The lab-on-chip had a detection sensitivity of 83.1% and a specificity of 100% for P. falciparum; a sensitivity of 91.3% and a specificity of 99.3% for P. vivax; a positive 90.0% agreement and a specificity of 100% for Chikungunya virus; and a positive 85.0% agreement and a specificity of 100% for Dengue virus serotype 3 with reference methods conducted on the samples. Results suggested the practicality of an amplification microarray-based approach in a field setting for high-throughput detection and identification of tropical pathogens. PMID:25078474

Lab-on-a-chip synthesis of inorganic nanomaterials and quantum dots for biomedical applications.

PubMed

Krishna, Katla Sai; Li, Yuehao; Li, Shuning; Kumar, Challa S S R

2013-11-01

The past two decades have seen a dramatic raise in the number of investigations leading to the development of Lab-on-a-Chip (LOC) devices for synthesis of nanomaterials. A majority of these investigations were focused on inorganic nanomaterials comprising of metals, metal oxides, nanocomposites and quantum dots. Herein, we provide an analysis of these findings, especially, considering the more recent developments in this new decade. We made an attempt to bring out the differences between chip-based as well as tubular continuous flow systems. We also cover, for the first time, various opportunities the tools from the field of computational fluid dynamics provide in designing LOC systems for synthesis inorganic nanomaterials. Particularly, we provide unique examples to demonstrate that there is a need for concerted effort to utilize LOC devices not only for synthesis of inorganic nanomaterials but also for carrying out superior in vitro studies thereby, paving the way for faster clinical translation. Even though LOC devices with the possibility to carry out multi-step syntheses have been designed, surprisingly, such systems have not been utilized for carrying out simultaneous synthesis and bio-functionalization of nanomaterials. While traditionally, LOC devices are primarily based on microfluidic systems, in this review article, we make a case for utilizing millifluidic systems for more efficient synthesis, bio-functionalization and in vitro studies of inorganic nanomaterials tailor-made for biomedical applications. Finally, recent advances in the field clearly point out the possibility for pushing the boundaries of current medical practices towards personalized health care with a vision to develop automated LOC-based instrumentation for carrying out simultaneous synthesis, bio-functionalization and in vitro evaluation of inorganic nanomaterials for biomedical applications. Copyright © 2013 Elsevier B.V. All rights reserved.

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.

Physical-level synthesis for digital lab-on-a-chip considering variation, contamination, and defect.

PubMed

Liao, Chen; Hu, Shiyan

2014-03-01

Microfluidic lab-on-a-chips have been widely utilized in biochemical analysis and human health studies due to high detection accuracy, high timing efficiency, and low cost. The increasing design complexity of lab-on-a-chips necessitates the computer-aided design (CAD) methodology in contrast to the classical manual design methodology. A key part in lab-on-a-chip CAD is physical-level synthesis. It includes the lab-on-a-chip placement and routing, where placement is to determine the physical location and the starting time of each operation and routing is to transport each droplet from the source to the destination. In the lab-on-a-chip design, variation, contamination, and defect need to be considered. This work designs a physical-level synthesis flow which simultaneously considers variation, contamination, and defect of the lab-on-a-chip design. It proposes a maze routing based, variation, contamination, and defect aware droplet routing technique, which is seamlessly integrated into an existing placement technique. The proposed technique improves the placement solution for routing and achieves the placement and routing co-optimization to handle variation, contamination, and defect. The simulation results demonstrate that our technique does not use any defective/contaminated grids, while the technique without considering contamination and defect uses 17.0% of the defective/contaminated grids on average. In addition, our routing variation aware technique significantly improves the average routing yield by 51.2% with only 3.5% increase in completion time compared to a routing variation unaware technique.

Magnetic particles for in vitro molecular diagnosis: From sample preparation to integration into microsystems.

PubMed

Tangchaikeeree, Tienrat; Polpanich, Duangporn; Elaissari, Abdelhamid; Jangpatarapongsa, Kulachart

2017-10-01

Colloidal magnetic particles (MPs) have been developed in association with molecular diagnosis for several decades. MPs have the great advantage of easy manipulation using a magnet. In nucleic acid detection, these particles can act as a capture support for rapid and simple biomolecule separation. The surfaces of MPs can be modified by coating with various polymer materials to provide functionalization for different applications. The use of MPs enhances the sensitivity and specificity of detection due to the specific activity on the surface of the particles. Practical applications of MPs demonstrate greater efficiency than conventional methods. Beyond traditional detection, MPs have been successfully adopted as a smart carrier in microfluidic and lab-on-a-chip biosensors. The versatility of MPs has enabled their integration into small single detection units. MPs-based biosensors can facilitate rapid and highly sensitive detection of very small amounts of a sample. In this review, the application of MPs to the detection of nucleic acids, from sample preparation to analytical readout systems, is described. State-of-the-art integrated microsystems containing microfluidic and lab-on-a-chip biosensors for the nucleic acid detection are also addressed. Copyright © 2017 Elsevier B.V. All rights reserved.

Spectral Demultiplexing in Holographic and Fluorescent On-chip Microscopy

NASA Astrophysics Data System (ADS)

Sencan, Ikbal; Coskun, Ahmet F.; Sikora, Uzair; Ozcan, Aydogan

2014-01-01

Lensfree on-chip imaging and sensing platforms provide compact and cost-effective designs for various telemedicine and lab-on-a-chip applications. In this work, we demonstrate computational solutions for some of the challenges associated with (i) the use of broadband, partially-coherent illumination sources for on-chip holographic imaging, and (ii) multicolor detection for lensfree fluorescent on-chip microscopy. Specifically, we introduce spectral demultiplexing approaches that aim to digitally narrow the spectral content of broadband illumination sources (such as wide-band light emitting diodes or even sunlight) to improve spatial resolution in holographic on-chip microscopy. We also demonstrate the application of such spectral demultiplexing approaches for wide-field imaging of multicolor fluorescent objects on a chip. These computational approaches can be used to replace e.g., thin-film interference filters, gratings or other optical components used for spectral multiplexing/demultiplexing, which can form a desirable solution for cost-effective and compact wide-field microscopy and sensing needs on a chip.

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

PubMed

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

2017-07-15

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

Controlled microfluidic interfaces for microsensors

NASA Astrophysics Data System (ADS)

Jiang, H.

2009-02-01

Lab on a chip has found many applications in biological and chemical analysis, including pathogen detections. Because these labs on chips involve handling of fluids at the microscale, surface tension profoundly affects the behavior and performance of these systems. Through careful engineering, controlled liquid-liquid or liquid-gas interfaces at the microscale can be formed and used in many interesting applications. In this talk, I will present our work on applying such interfaces to microsensing. These interfaces are created at hydrophobic-hydrophilic boundaries formed within microfluidic channels and pinned by surface tension. We have designed and fabricated a few microsensing techniques including chemical and biological sensing using dissolvable micromembranes in microchannels, chemical and biological sensing at liquid crystals interfacing either air or aqueous solutions, and collection of gaseous samples and aerosols through air-liquid microfludic interfaces. I will next introduce on-chip microlenses and microlens arrays for optical detection, including smart and adaptive liquid microlenses actuated by stimuli-responsive hydrogels, and liquid microlenses in situ formed within microfluidic channels via pneumatic control of droplets.

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.

State-of-the-art lab chip sensors for environmental water monitoring

NASA Astrophysics Data System (ADS)

Jang, Am; Zou, Zhiwei; Kug Lee, Kang; Ahn, Chong H.; Bishop, Paul L.

2011-03-01

As a result of increased water demand and water pollution, both surface water and groundwater quantity and quality are of major concern worldwide. In particular, the presence of nutrients and heavy metals in water is a serious threat to human health. The initial step for the effective management of surface waters and groundwater requires regular, continuous monitoring of water quality in terms of contaminant distribution and source identification. Because of this, there is a need for screening and monitoring measurements of these compounds at contaminated areas. However, traditional monitoring techniques are typically still based on laboratory analyses of representative field-collected samples; this necessitates considerable effort and expense, and the sample may change before analysis. Furthermore, currently available equipment is so large that it cannot usually be made portable. Alternatively, lab chip and electrochemical sensing-based portable monitoring systems appear well suited to complement standard analytical methods for a number of environmental monitoring applications. In addition, this type of portable system could save tremendous amounts of time, reagent, and sample if it is installed at contaminated sites such as Superfund sites (the USA's worst toxic waste sites) and Resource Conservation and Recovery Act (RCRA) facilities or in rivers and lakes. Accordingly, state-of-the-art monitoring equipment is necessary for accurate assessments of water quality. This article reviews details on our development of these lab-on-a-chip (LOC) sensors.

Automated Lab-on-a-Chip Technology for Fish Embryo Toxicity Tests Performed under Continuous Microperfusion (μFET).

PubMed

Zhu, Feng; Wigh, Adriana; Friedrich, Timo; Devaux, Alain; Bony, Sylvie; Nugegoda, Dayanthi; Kaslin, Jan; Wlodkowic, Donald

2015-12-15

The fish embryo toxicity (FET) biotest has gained popularity as one of the alternative approaches to acute fish toxicity tests in chemical hazard and risk assessment. Despite the importance and common acceptance of FET, it is still performed in multiwell plates and requires laborious and time-consuming manual manipulation of specimens and solutions. This work describes the design and validation of a microfluidic Lab-on-a-Chip technology for automation of the zebrafish embryo toxicity test common in aquatic ecotoxicology. The innovative device supports rapid loading and immobilization of large numbers of zebrafish embryos suspended in a continuous microfluidic perfusion as a means of toxicant delivery. Furthermore, we also present development of a customized mechatronic automation interface that includes a high-resolution USB microscope, LED cold light illumination, and miniaturized 3D printed pumping manifolds that were integrated to enable time-resolved in situ analysis of developing fish embryos. To investigate the applicability of the microfluidic FET (μFET) in toxicity testing, copper sulfate, phenol, ethanol, caffeine, nicotine, and dimethyl sulfoxide were tested as model chemical stressors. Results obtained on a chip-based system were compared with static protocols performed in microtiter plates. This work provides evidence that FET analysis performed under microperfusion opens a brand new alternative for inexpensive automation in aquatic ecotoxicology.

Biosensors-on-chip: a topical review

NASA Astrophysics Data System (ADS)

Chen, Sensen; Shamsi, Mohtashim H.

2017-08-01

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

Next Generation LOCAD-PTS Cartridge Development

NASA Technical Reports Server (NTRS)

Morris, H.; Nutter, D.; Weite, E.; Wells, M.; Maule, J.; Damon, M.; Monaco, L.; Steele, A.; Wainwright, N.

2008-01-01

Future astrobiology exploration missions will require rapid, point-of-use techniques for surface science experiments and contamination monitoring. The Lab-On-a-Chip Application Development (LOCAD) team is developing operational instruments that advance spaceflight technologies to molecular-based methods. Currently, LOCAD-Portable Test System (PTS) is quantifying levels of the bacterial molecule endotoxin onboard the Internatioal Space Station. Future research and development will focus on more sensitive molecular techniques that expand the number of compounds detected to include beta-glucan from fungal cell walls.

Lab-on-a-chip technologies for proteomic analysis from isolated cells.

PubMed

Sedgwick, H; Caron, F; Monaghan, P B; Kolch, W; Cooper, J M

2008-10-06

Lab-on-a-chip systems offer a versatile environment in which low numbers of cells and molecules can be manipulated, captured, detected and analysed. We describe here a microfluidic device that allows the isolation, electroporation and lysis of single cells. A431 human epithelial carcinoma cells, expressing a green fluorescent protein-labelled actin, were trapped by dielectrophoresis within an integrated lab-on-a-chip device containing saw-tooth microelectrodes. Using these same trapping electrodes, on-chip electroporation was performed, resulting in cell lysis. Protein release was monitored by confocal fluorescence microscopy.

Exploring plasmonic nanoantenna arrays as a platform for biosensing

NASA Astrophysics Data System (ADS)

Toussaint, Kimani C.

2017-08-01

In recent years, the PROBE Lab at the University of Illinois at Urbana-Champaign has made significant developments in plasmonic nanoantenna technology by more closely exploring the rich parameter space associated with these structures including geometry and material composition, as well as the optical excitation conditions. Indeed, plasmonic nanoantennas are attractive for a variety of potential applications in nanotechnology, biology, and photonics due to their ability to tightly confine and strongly enhance optical fields. This talk will discuss our work with arrays of Au bowtie nanoantennas (BNAs) with an emphasis on how their field enhancement properties could be harnessed for particle manipulation and sensing. We also present our work with pillar-supported BNAs (p-BNAs) and discuss their potential for sensing applications, particularly when adapted for response in the near-IR. The talk will conclude with a brief discussion of some of the future work pursued by the PROBE lab, including adapting BNAs for lab-on-a-chip applications.

Determination of pore-scale hydrate phase equilibria in sediments using lab-on-a-chip technology.

PubMed

Almenningen, Stian; Flatlandsmo, Josef; Kovscek, Anthony R; Ersland, Geir; Fernø, Martin A

2017-11-21

We present an experimental protocol for fast determination of hydrate stability in porous media for a range of pressure and temperature (P, T) conditions. Using a lab-on-a-chip approach, we gain direct optical access to dynamic pore-scale hydrate formation and dissociation events to study the hydrate phase equilibria in sediments. Optical pore-scale observations of phase behavior reproduce the theoretical hydrate stability line with methane gas and distilled water, and demonstrate the accuracy of the new method. The procedure is applicable for any kind of hydrate transitions in sediments, and may be used to map gas hydrate stability zones in nature.

Lab-on-a-chip technologies for proteomic analysis from isolated cells

PubMed Central

Sedgwick, H.; Caron, F.; Monaghan, P.B.; Kolch, W.; Cooper, J.M.

2008-01-01

Lab-on-a-chip systems offer a versatile environment in which low numbers of cells and molecules can be manipulated, captured, detected and analysed. We describe here a microfluidic device that allows the isolation, electroporation and lysis of single cells. A431 human epithelial carcinoma cells, expressing a green fluorescent protein-labelled actin, were trapped by dielectrophoresis within an integrated lab-on-a-chip device containing saw-tooth microelectrodes. Using these same trapping electrodes, on-chip electroporation was performed, resulting in cell lysis. Protein release was monitored by confocal fluorescence microscopy. PMID:18534931

Ionic electroactive polymer actuators as active microfluidic mixers

DOE PAGES

Meis, Catherine; Montazami, Reza; Hashemi, Nastaran

2015-11-06

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

Tracking Clouds with low cost GNSS chips aided by the Arduino platform

NASA Astrophysics Data System (ADS)

Hameed, Saji; Realini, Eugenio; Ishida, Shinya

2016-04-01

The Global Navigation Satellite System (GNSS) is a constellation of satellites that is used to provide geo-positioning services. Besides this application, the GNSS system is important for a wide range of scientific and civilian applications. For example, GNSS systems are routinely used in civilian applications such as surveying and scientific applications such as the study of crustal deformation. Another important scientific application of GNSS system is in meteorological research. Here it is mainly used to determine the total water vapour content of the troposphere, hereafter Precipitable Water Vapor (PWV). However, both GNSS receivers and software have prohibitively high price due to a variety of reasons. To overcome this somewhat artificial barrier we are exploring the use of low-cost GNSS receivers along with open source GNSS software for scientific research, in particular for GNSS meteorology research. To achieve this aim, we have developed a custom Arduino compatible data logging board that is able to operate together with a specific low-cost single frequency GNSS receiver chip from NVS Technologies AG. We have also developed an open-source software bundle that includes a new Arduino core for the Atmel324p chip, which is the main processor used in our custom logger. We have also developed software code that enables data collection, logging and parsing of the GNSS data stream. Additionally we have comprehensively evaluated the low power characteristics of the GNSS receiver and logger boards. Currently we are exploring the use of several openly source or free to use for research software to map GNSS delays to PWV. These include the open source goGPS (http://www.gogps-project.org/) and gLAB (http://gage.upc.edu/gLAB) and the openly available GAMIT software from Massachusetts Institute of Technology (MIT). We note that all the firmware and software developed as part of this project is available on an open source license.

Fully integrated multiplexed lab-on-a-card assay for enteric pathogens

NASA Astrophysics Data System (ADS)

Weigl, B. H.; Gerdes, J.; Tarr, P.; Yager, P.; Dillman, L.; Peck, R.; Ramachandran, S.; Lemba, M.; Kokoris, M.; Nabavi, M.; Battrell, F.; Hoekstra, D.; Klein, E. J.; Denno, D. M.

2006-01-01

Under this NIH-funded project, we are developing a lab-on-a-card platform to identify enteric bacterial pathogens in patients presenting with acute diarrhea, with special reference to infections that might be encountered in developing countries. Component functions that are integrated on this platform include on-chip immunocapture of live or whole pathogens, multiplexed nucleic acid amplification and on-chip detection, sample processing to support direct use of clinical specimens, and dry reagent storage and handling. All microfluidic functions are contained on the lab card. This new diagnostic test will be able to rapidly identify and differentiate Shigella dysenteriae serotype 1, Shigella toxin-producing Escherichia coli, E. coli 0157, Campylobacter jejuni, and Salmonella and Shigella species. This presentation will report on progress to date on sample and bacteria processing methodologies, identification and validation of capture antibodies and strategy for organism immunocapture, identification and validation of specific polymerase chain reaction (PCR) primer sequences for over 200 clinical isolates of enteric pathogens, and implementation of on-chip nucleic acid extraction for a subset of those pathogens.

Lab-on-chip systems for integrated bioanalyses

PubMed Central

Madaboosi, Narayanan; Soares, Ruben R.G.; Fernandes, João Tiago S.; Novo, Pedro; Moulas, Geraud; Chu, Virginia

2016-01-01

Biomolecular detection systems based on microfluidics are often called lab-on-chip systems. To fully benefit from the miniaturization resulting from microfluidics, one aims to develop ‘from sample-to-answer’ analytical systems, in which the input is a raw or minimally processed biological, food/feed or environmental sample and the output is a quantitative or qualitative assessment of one or more analytes of interest. In general, such systems will require the integration of several steps or operations to perform their function. This review will discuss these stages of operation, including fluidic handling, which assures that the desired fluid arrives at a specific location at the right time and under the appropriate flow conditions; molecular recognition, which allows the capture of specific analytes at precise locations on the chip; transduction of the molecular recognition event into a measurable signal; sample preparation upstream from analyte capture; and signal amplification procedures to increase sensitivity. Seamless integration of the different stages is required to achieve a point-of-care/point-of-use lab-on-chip device that allows analyte detection at the relevant sensitivity ranges, with a competitive analysis time and cost. PMID:27365042

Imaging electric field dynamics with graphene optoelectronics

DOE PAGES

Horng, Jason; Balch, Halleh B.; McGuire, Allister F.; ...

2016-12-16

The use of electric fields for signalling and control in liquids is widespread, spanning bioelectric activity in cells to electrical manipulation of microstructures in lab-on-a-chip devices. However, an appropriate tool to resolve the spatio-temporal distribution of electric fields over a large dynamic range has yet to be developed. Here we present a label-free method to image local electric fields in real time and under ambient conditions. Our technique combines the unique gate-variable optical transitions of graphene with a critically coupled planar waveguide platform that enables highly sensitive detection of local electric fields with a voltage sensitivity of a few microvolts,more » a spatial resolution of tens of micrometres and a frequency response over tens of kilohertz. Our imaging platform enables parallel detection of electric fields over a large field of view and can be tailored to broad applications spanning lab-on-a-chip device engineering to analysis of bioelectric phenomena.« less

Imaging electric field dynamics with graphene optoelectronics

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

Horng, Jason; Balch, Halleh B.; McGuire, Allister F.

The use of electric fields for signalling and control in liquids is widespread, spanning bioelectric activity in cells to electrical manipulation of microstructures in lab-on-a-chip devices. However, an appropriate tool to resolve the spatio-temporal distribution of electric fields over a large dynamic range has yet to be developed. Here we present a label-free method to image local electric fields in real time and under ambient conditions. Our technique combines the unique gate-variable optical transitions of graphene with a critically coupled planar waveguide platform that enables highly sensitive detection of local electric fields with a voltage sensitivity of a few microvolts,more » a spatial resolution of tens of micrometres and a frequency response over tens of kilohertz. Our imaging platform enables parallel detection of electric fields over a large field of view and can be tailored to broad applications spanning lab-on-a-chip device engineering to analysis of bioelectric phenomena.« less

Allergen screening bioassays: recent developments in lab-on-a-chip and lab-on-a-disc systems.

PubMed

Ho, Ho-pui; Lau, Pui-man; Kwok, Ho-chin; Wu, Shu-yuen; Gao, Minghui; Cheung, Anthony Ka-lun; Chen, Qiulan; Wang, Guanghui; Kwan, Yiu-wa; Wong, Chun-kwok; Kong, Siu-kai

2014-01-01

Allergies occur when a person's immune system mounts an abnormal response with or without IgE to a normally harmless substance called an allergen. The standard skin-prick test introduces suspected allergens into the skin with lancets in order to trigger allergic reactions. This test is annoying and sometimes life threatening. New tools such as lab-on-a-chip and lab-on-a-disc, which rely on microfabrication, are designed for allergy testing. These systems provide benefits such as short analysis times, enhanced sensitivity, simplified procedures, minimal consumption of sample and reagents and low cost. This article gives a summary of these systems. In particular, a cell-based assay detecting both the IgE- and non-IgE-type triggers through the study of degranulation in a centrifugal microfluidic system is highlighted.

Two-layer Lab-on-a-chip (LOC) with passive capillary valves for mHealth medical diagnostics.

PubMed

Balsam, Joshua; Bruck, Hugh Alan; Rasooly, Avraham

2015-01-01

There is a new potential to address needs for medical diagnostics in Point-of-Care (PoC) applications using mHealth (Mobile computing, medical sensors, and communications technologies for health care), a mHealth based lab test will require a LOC to perform clinical analysis. In this work, we describe the design of a simple Lab-on-a-chip (LOC) platform for mHealth medical diagnostics. The LOC utilizes a passive capillary valve with no moving parts for fluid control using channels with very low aspect ratios cross sections (i.e., channel width ≫ height) achieved through transitions in the channel geometry via that arrest capillary flow. Using a CO2 laser in raster engraving mode, we have designed and fabricated an eight-channel LOC for fluorescence signal detection fabricated by engraving and combining just two polymer layers. Each of the LOC channels is capable of mixing two reagents (e.g., enzyme and substrate) for various assays. For mHealth detection, we used a mobile CCD detector equipped with LED multispectral illumination in the red, green, blue, and white range. This technology enables the development of low-cost LOC platforms for mHealth whose fabrication is compatible with standard industrial plastic fabrication processes to enable mass production of mHealth diagnostic devices, which may broaden the use of LOCs in PoC applications, especially in global health settings.

Lab-on-a-Chip Instrument Development for Titan Exploration

NASA Astrophysics Data System (ADS)

Willis, P. A.; Greer, F.; Fisher, A.; Hodyss, R. P.; Grunthaner, F.; Jiao, H.; Mair, D.; Harrison, J.

2009-12-01

This contribution will describe the initial stages of a new ASTID-funded research program initiated in Fall 2009 aimed at lab-on-a-chip system development for astrobiological investigations on Titan. This technology development builds off related work at JPL and Berkeley [1-3] on the ultrasensitive compositional and chiral analysis of amino acids on Mars in order to search for signatures of past or present life. The Mars-focused instrument system utilizes a microcapillary electrophoresis (μCE) system integrated with on-chip perfluoropolyether (PFPE) membrane valves and pumps for automated liquid sample handling, on-chip derivitization of samples with fluorescent tags, dilution, and mixing with standards for data calibration. It utilizes a four-layer wafer stack design with CE channels patterned in glass, along with a PFPE membrane, a pneumatic manifold layer, and a fluidic bus layer. Three pneumatically driven on-chip diaphragm valves placed in series are used to peristaltically pump reagents, buffers, and samples to and from capillary electrophoresis electrode well positions. Electrophoretic separation occurs in the all-glass channels near the base of the structure. The Titan specific lab-on-a-chip system under development here focuses its attention on the unique organic chemistry of Titan. In order to chromatographically separate mixtures of neutral organics such as polycyclic aromatic hydrocarbons (PAHs), the Titan-specific microfluidic platform utilizes the related technique of microcapillary electrochromatography (μCEC). This technique differs from conventional μCE in that microchannels are filled with a porous stationary phase that presents surfaces upon which analyte species can adsorb/desorb. It is this additional surface interaction that enables separations of species critical to the understanding of the astrobiological potential of Titan that are not readily separated by the μCE technique. We have developed two different approaches for the integration of these stationary phases into microdevices, both by the packing of submicron-sized beads, and by the growth of porous polymer monoliths inside empty channels via a photoinitiated chemical polymerization process. References: 1. “Monolithic photolithographically patterned Fluorocur™ PFPE membrane valves and pumps for in situ planetary exploration”, P. A. Willis et al., Lab Chip 8, 1024 (2008). 2. “The Urey Instrument: An Advanced In Situ Organic and Oxidant Detector for Mars Exploration”, A. Aubrey et al., Astrobiology 8, 583 (2008). 3. “Development and evaluation of a microdevice for amino acid biomarker detection and analysis on Mars” A. M. Skelley et al., PNAS 102, 1041 (2005).

Biosensors in Health Care: The Milestones Achieved in Their Development towards Lab-on-Chip-Analysis

PubMed Central

Patel, Suprava; Nanda, Rachita; Sahoo, Sibasish; Mohapatra, Eli

2016-01-01

Immense potentiality of biosensors in medical diagnostics has driven scientists in evolution of biosensor technologies and innovating newer tools in time. The cornerstone of the popularity of biosensors in sensing wide range of biomolecules in medical diagnostics is due to their simplicity in operation, higher sensitivity, ability to perform multiplex analysis, and capability to be integrated with different function by the same chip. There remains a huge challenge to meet the demands of performance and yield to its simplicity and affordability. Ultimate goal stands for providing point-of-care testing facility to the remote areas worldwide, particularly the developing countries. It entails continuous development in technology towards multiplexing ability, fabrication, and miniaturization of biosensor devices so that they can provide lab-on-chip-analysis systems to the community. PMID:27042353

Origin and Future of Plasmonic Optical Tweezers

PubMed Central

Huang, Jer-Shing; Yang, Ya-Tang

2015-01-01

Plasmonic optical tweezers can overcome the diffraction limits of conventional optical tweezers and enable the trapping of nanoscale objects. Extension of the trapping and manipulation of nanoscale objects with nanometer position precision opens up unprecedented opportunities for applications in the fields of biology, chemistry and statistical and atomic physics. Potential applications include direct molecular manipulation, lab-on-a-chip applications for viruses and vesicles and the study of nanoscale transport. This paper reviews the recent research progress and development bottlenecks and provides an overview of possible future directions in this field. PMID:28347051

Origin and Future of Plasmonic Optical Tweezers.

PubMed

Huang, Jer-Shing; Yang, Ya-Tang

2015-06-12

Plasmonic optical tweezers can overcome the diffraction limits of conventional optical tweezers and enable the trapping of nanoscale objects. Extension of the trapping and manipulation of nanoscale objects with nanometer position precision opens up unprecedented opportunities for applications in the fields of biology, chemistry and statistical and atomic physics. Potential applications include direct molecular manipulation, lab-on-a-chip applications for viruses and vesicles and the study of nanoscale transport. This paper reviews the recent research progress and development bottlenecks and provides an overview of possible future directions in this field.

A lab-on-chip for malaria diagnosis and surveillance

PubMed Central

2014-01-01

Background Access to timely and accurate diagnostic tests has a significant impact in the management of diseases of global concern such as malaria. While molecular diagnostics satisfy this need effectively in developed countries, barriers in technology, reagent storage, cost and expertise have hampered the introduction of these methods in developing countries. In this study a simple, lab-on-chip PCR diagnostic was created for malaria that overcomes these challenges. Methods The platform consists of a disposable plastic chip and a low-cost, portable, real-time PCR machine. The chip contains a desiccated hydrogel with reagents needed for Plasmodium specific PCR. Chips can be stored at room temperature and used on demand by rehydrating the gel with unprocessed blood, avoiding the need for sample preparation. These chips were run on a custom-built instrument containing a Peltier element for thermal cycling and a laser/camera setup for amplicon detection. Results This diagnostic was capable of detecting all Plasmodium species with a limit of detection for Plasmodium falciparum of 2 parasites/μL of blood. This exceeds the sensitivity of microscopy, the current standard for diagnosis in the field, by ten to fifty-fold. In a blind panel of 188 patient samples from a hyper-endemic region of malaria transmission in Uganda, the diagnostic had high sensitivity (97.4%) and specificity (93.8%) versus conventional real-time PCR. The test also distinguished the two most prevalent malaria species in mixed infections, P. falciparum and Plasmodium vivax. A second blind panel of 38 patient samples was tested on a streamlined instrument with LED-based excitation, achieving a sensitivity of 96.7% and a specificity of 100%. Conclusions These results describe the development of a lab-on-chip PCR diagnostic from initial concept to ready-for-manufacture design. This platform will be useful in front-line malaria diagnosis, elimination programmes, and clinical trials. Furthermore, test chips can be adapted to detect other pathogens for a differential diagnosis in the field. The flexibility, reliability, and robustness of this technology hold much promise for its use as a novel molecular diagnostic platform in developing countries. PMID:24885206

Fabrication of pseudo-spin-MOSFETs using a multi-project wafer CMOS chip

NASA Astrophysics Data System (ADS)

Nakane, R.; Shuto, Y.; Sukegawa, H.; Wen, Z. C.; Yamamoto, S.; Mitani, S.; Tanaka, M.; Inomata, K.; Sugahara, S.

2014-12-01

We demonstrate monolithic integration of pseudo-spin-MOSFETs (PS-MOSFETs) using vendor-made MOSFETs fabricated in a low-cost multi-project wafer (MPW) product and lab-made magnetic tunnel junctions (MTJs) formed on the topmost passivation film of the MPW chip. The tunneling magnetoresistance (TMR) ratio of the fabricated MTJs strongly depends on the surface roughness of the passivation film. Nevertheless, after the chip surface was atomically flattened by SiO2 deposition on it and successive chemical-mechanical polish (CMP) process for the surface, the fabricated MTJs on the chip exhibits a sufficiently large TMR ratio (>140%) adaptable to the PS-MOSFET application. The implemented PS-MOSFETs show clear modulation of the output current controlled by the magnetization configuration of the MTJs, and a maximum magnetocurrent ratio of 90% is achieved. These magnetocurrent behaviour is quantitatively consistent with those predicted by HSPICE simulations. The developed integration technique using a MPW CMOS chip would also be applied to monolithic integration of CMOS devices/circuits and other various functional devices/materials, which would open the door for exploring CMOS-based new functional hybrid circuits.

Integrated chemical/biochemical sample collection, pre-concentration, and analysis on a digital microfluidic lab-on-a-chip platform

NASA Astrophysics Data System (ADS)

Fair, Richard B.; Khlystov, A.; Srinivasan, Vijay; Pamula, Vamsee K.; Weaver, Kathryn N.

2004-12-01

An ideal on-site chemical/biochemical analysis system must be inexpensive, sensitive, fully automated and integrated, reliable, and compatible with a broad range of samples. The advent of digital microfluidic lab-on-a-chip (LoC) technology offers such a detection system due to the advantages in portability, reduction of the volumes of the sample and reagents, faster analysis times, increased automation, low power consumption, compatibility with mass manufacturing, and high throughput. We describe progress towards integrating sample collection onto a digital microfluidic LoC that is a component of a cascade impactor device. The sample collection is performed by impacting airborne particles directly onto the surface of the chip. After the collection phase, the surface of the chip is washed with a micro-droplet of solvent. The droplet will be digitally directed across the impaction surface, dissolving sample constituents. Because of the very small droplet volume used for extraction of the sample from a wide colection area, the resulting solution is realatively concentrated and the analytes can be detected after a very short sampling time (1 min) due to such pre-concentration. After the washing phase, the droplet is mixed with specific reagents that produce colored reaction products. The concentration of the analyte is quantitatively determined by measuring absorption at target wavelengths using a simple light emitting diode and photodiode setup. Specific applications include automatic measurements of major inorganic ions in aerosols, such as sulfate, nitrate and ammonium, with a time resolution of 1 min and a detection limit of 30 nm/m3. We have already demonstrated the detection and quantification of nitroaromatic explosives without integrating the sample collection. Other applications being developed include airborne bioagent detection.

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

NASA Astrophysics Data System (ADS)

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

2013-03-01

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

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

PubMed

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

2014-01-01

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

Magnetically engineered smart thin films: toward lab-on-chip ultra-sensitive molecular imaging.

PubMed

Hassan, Muhammad A; Saqib, Mudassara; Shaikh, Haseeb; Ahmad, Nasir M; Elaissari, Abdelhamid

2013-03-01

Magnetically responsive engineered smart thin films of nanoferrites as contrast agent are employed to develop surface based magnetic resonance imaging to acquire simple yet fast molecular imaging. The work presented here can be of significant potential for future lab-on-chip point-of-care diagnostics from the whole blood pool on almost any substrates to reduce or even prevent clinical studies involve a living organism to enhance the non-invasive imaging to advance the '3Rs' of work in animals-replacement, refinement and reduction.

A primary battery-on-a-chip using monolayer graphene.

PubMed

Iost, Rodrigo M; Crespilho, Frank N; Kern, Klaus; Balasubramanian, Kannan

2016-06-14

We present here a bottom-up approach for realizing on-chip on-demand batteries starting out with chemical vapor deposition-grown graphene. Single graphene monolayers contacted by electrode lines on a silicon chip serve as electrodes. The anode and cathode are realized by electrodeposition of zinc and copper respectively onto graphene, leading to the realization of a miniature graphene-based Daniell cell on a chip. The electrolyte is housed partly in a gel and partly in liquid form in an on-chip enclosure molded using a 3d printer or made out of poly(dimethylsiloxane). The realized batteries provide a stable voltage (∼1.1 V) for many hours and exhibit capacities as high as 15 μAh, providing enough power to operate a pocket calculator. The realized batteries show promise for deployment as on-chip power sources for autonomous systems in lab-on-a-chip or biomedical applications.

A primary battery-on-a-chip using monolayer graphene

NASA Astrophysics Data System (ADS)

Iost, Rodrigo M.; Crespilho, Frank N.; Kern, Klaus; Balasubramanian, Kannan

2016-07-01

We present here a bottom-up approach for realizing on-chip on-demand batteries starting out with chemical vapor deposition-grown graphene. Single graphene monolayers contacted by electrode lines on a silicon chip serve as electrodes. The anode and cathode are realized by electrodeposition of zinc and copper respectively onto graphene, leading to the realization of a miniature graphene-based Daniell cell on a chip. The electrolyte is housed partly in a gel and partly in liquid form in an on-chip enclosure molded using a 3d printer or made out of poly(dimethylsiloxane). The realized batteries provide a stable voltage (∼1.1 V) for many hours and exhibit capacities as high as 15 μAh, providing enough power to operate a pocket calculator. The realized batteries show promise for deployment as on-chip power sources for autonomous systems in lab-on-a-chip or biomedical applications.

Clinically relevant advances in on-chip affinity-based electrophoresis and electrochromatography.

PubMed

Hou, Chenlu; Herr, Amy E

2008-08-01

Clinical and point-of-care disease diagnostics promise to play an important role in personalized medicine, new approaches to global health, and health monitoring. Emerging instrument platforms based on lab-on-a-chip technology can confer performance advantages successfully exploited in electrophoresis and electrochromatography to affinity-based electrokinetic separations. This review surveys lab-on-a-chip diagnostic developments in affinity-based electrokinetic separations for quantitation of proteins, integration of preparatory functions needed for subsequent analysis of diverse biological samples, and initial forays into multiplexed analyses. The technologies detailed here underpin new clinical and point-of-care diagnostic strategies. The techniques and devices promise to advance translation of until now laboratory-based sample preparation and analytical assays to near-patient settings.

Last Advances in Silicon-Based Optical Biosensors.

PubMed

Fernández Gavela, Adrián; Grajales García, Daniel; Ramirez, Jhonattan C; Lechuga, Laura M

2016-02-24

We review the most important achievements published in the last five years in the field of silicon-based optical biosensors. We focus specially on label-free optical biosensors and their implementation into lab-on-a-chip platforms, with an emphasis on developments demonstrating the capability of the devices for real bioanalytical applications. We report on novel transducers and materials, improvements of existing transducers, new and improved biofunctionalization procedures as well as the prospects for near future commercialization of these technologies.

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

NASA Astrophysics Data System (ADS)

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

2016-02-01

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

High spatial and temporal resolution cell manipulation techniques in microchannels.

PubMed

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

2016-03-21

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

Ultra-Sensitive Lab-on-a-Chip Detection of Sudan I in Food using Plasmonics-Enhanced Diatomaceous Thin Film.

PubMed

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

2017-09-01

Sudan I is a carcinogenic compound containing an azo group that has been illegally utilized as an adulterant in food products to impart a bright red color to foods. In this paper, we develop a facile lab-on-a-chip device for instant, ultra-sensitive detection of Sudan I from real food samples using plasmonics-enhanced diatomaceous thin film, which can simultaneously perform on-chip separation using thin layer chromatography (TLC) and highly specific sensing using surface-enhanced Raman scattering (SERS) spectroscopy. Diatomite is a kind of nature-created photonic crystal biosilica with periodic pores and was used both as the stationary phase of the TLC plate and photonic crystals to enhance the SERS sensitivity. The on-chip chromatography capability of the TLC plate was verified by isolating Sudan I in a mixture solution containing Rhodamine 6G, while SERS sensing was achieved by spraying gold colloidal nanoparticles into the sensing spot. Such plasmonics-enhanced diatomaceous film can effectively detect Sudan I with more than 10 times improvement of the Raman signal intensity than commercial silica gel TLC plates. We applied this lab-on-a-chip device for real food samples and successfully detected Sudan I in chili sauce and chili oil down to 1 ppm, or 0.5 ng/spot. This on-chip TLC-SERS biosensor based on diatomite biosilica can function as a cost-effective, ultra-sensitive, and reliable technology for screening Sudan I and many other illicit ingredients to enhance food safety.

Macromolecular Crystal Growth by Means of Microfluidics

NASA Technical Reports Server (NTRS)

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

2002-01-01

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

Laser vibrometry characterisation of a microfluidic lab-on-a-chip device: a preliminary investigation

NASA Astrophysics Data System (ADS)

Fury, C.; Gélat, P. N.; Jones, P. H.; Memoli, G.

2014-04-01

Since their original inception as ultrasound contrast agents, potential applications of microbubbles have evolved to encompass molecular imaging and targeted drug delivery. As these areas develop, so does the need to understand the mechanisms behind the interaction of microbubbles both with biological tissue and with other microbubbles. There is therefore a metrological requirement to develop a controlled environment in which to study these processes. Presented here is the design and characterisation of such a system, which consists of a microfluidic chip, specifically developed for manipulating microbubbles using both optical and acoustic trapping. A laser vibrometer is used to observe the coupling of acoustic energy into the chip from a piezoelectric transducer bonded to the surface. Measurement of the velocity of surface waves on the chip is investigated as a potential method for inferring the nature of the acoustic fields excited within the liquid medium of the device. Comparison of measured surface wavelengths with wave types suggests the observation of anti-symmetric Lamb or Love-Kirchhoff waves. Further visual confirmation of the acoustic fields through bubble aggregation highlights differences between the model and experimental results in predicting the position of acoustic pressure nodes in relation to excitation frequency.

Magnetic Trapping of Bacteria at Low Magnetic Fields

NASA Astrophysics Data System (ADS)

Wang, Z. M.; Wu, R. G.; Wang, Z. P.; Ramanujan, R. V.

2016-06-01

A suspension of non-magnetic entities in a ferrofluid is referred to as an inverse ferrofluid. Current research to trap non-magnetic entities in an inverse ferrofluid focuses on using large permanent magnets to generate high magnetic field gradients, which seriously limits Lab-on-a-Chip applications. On the other hand, in this work, trapping of non-magnetic entities, e.g., bacteria in a uniform external magnetic field was studied with a novel chip design. An inverse ferrofluid flows in a channel and a non-magnetic island is placed in the middle of this channel. The magnetic field was distorted by this island due to the magnetic susceptibility difference between this island and the surrounding ferrofluid, resulting in magnetic forces applied on the non-magnetic entities. Both the ferromagnetic particles and the non-magnetic entities, e.g., bacteria were attracted towards the island, and subsequently accumulate in different regions. The alignment of the ferrimagnetic particles and optical transparency of the ferrofluid was greatly enhanced by the bacteria at low applied magnetic fields. This work is applicable to lab-on-a-chip based detection and trapping of non-magnetic entities bacteria and cells.

Thermoelectricity in Heterogeneous Nanofluidic Channels.

PubMed

Li, Long; Wang, Qinggong

2018-05-01

Ionic fluids are essential to energy conversion, water desalination, drug delivery, and lab-on-a-chip devices. Ionic transport in nanoscale confinements and complex physical fields still remain elusive. Here, a nanofluidic system is developed using nanochannels of heterogeneous surface properties to investigate transport properties of ions under different temperatures. Steady ionic currents are observed under symmetric temperature gradients, which is equivalent to generating electricity using waste heat (e.g., electronic chips and solar panels). The currents increase linearly with temperature gradient and nonlinearly with channel size. Contributions to ion motion from temperatures and channel properties are evaluated for this phenomenon. The findings provide insights into the study of confined ionic fluids in multiphysical fields, and suggest applications in thermal energy conversion, temperature sensors, and chip-level thermal management. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

NASA Astrophysics Data System (ADS)

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

2015-06-01

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

A novel lab-on-chip platform with integrated solid phase PCR and Supercritical Angle Fluorescence (SAF) microlens array for highly sensitive and multiplexed pathogen detection.

PubMed

Hung, Tran Quang; Chin, Wai Hoe; Sun, Yi; Wolff, Anders; Bang, Dang Duong

2017-04-15

Solid-phase PCR (SP-PCR) has become increasingly popular for molecular diagnosis and there have been a few attempts to incorporate SP-PCR into lab-on-a-chip (LOC) devices. However, their applicability for on-line diagnosis is hindered by the lack of sensitive and portable on-chip optical detection technology. In this paper, we addressed this challenge by combining the SP-PCR with super critical angle fluorescence (SAF) microlens array embedded in a microchip. We fabricated miniaturized SAF microlens array as part of a microfluidic chamber in thermoplastic material and performed multiplexed SP-PCR directly on top of the SAF microlens array. Attribute to the high fluorescence collection efficiency of the SAF microlens array, the SP-PCR assay on the LOC platform demonstrated a high sensitivity of 1.6 copies/µL, comparable to off-chip detection using conventional laser scanner. The combination of SP-PCR and SAF microlens array allows for on-chip highly sensitive and multiplexed pathogen detection with low-cost and compact optical components. The LOC platform would be widely used as a high-throughput biosensor to analyze food, clinical and environmental samples. Copyright © 2016 Elsevier B.V. All rights reserved.

Droplet-based biosensing for lab-on-a-chip, open microfluidics platforms

USDA-ARS?s Scientific Manuscript database

Low cost, portable sensors can transform health care by bringing easily available diagnostic devices to low and middle income population, particularly in developing countries. Sample preparation, analyte handling and labeling are primary cost concerns for traditional lab-based diagnostic systems. La...

Critical stages of a biodetection platform development from sensor chip fabrication to surface chemistry and assay development

NASA Astrophysics Data System (ADS)

Uludag, Yildiz

2014-06-01

Once viewed solely as a tool to analyse biomolecular interactions, biosensors are gaining widespread interest for diagnostics, biological defense, environmental and quality assurance in agriculture/food industries. Advanced micro fabrication techniques have facilitated integration of microfluidics with sensing functionalities on the same chip making system automation more convenient1. Biosensor devices relying on lab-on-a-chip technologies and nanotechnology has attracted much of attention in recent years for biological defense research and development. However, compared with the numerous publications and patents available, the commercialization of biosensors technology has significantly lagged behind the research output. This paper reviews the reasons behind the slow commercialisation of biosensors with an insight to the critical stages of a biosensor development from the sensor chip fabrication to surface chemistry applications and nanotechnology applications in sensing with case studies. In addition, the paper includes the description of a new biodetection platform based on Real-time Electrochemical ProfilingTM (REPTM) that comprises novel electrode arrays and nanoparticle based sensing. The performance of the REPTM platform has been tested for the detection of Planktothrix agardhii, one of the toxic bloom-forming cyanobacteria, usually found in shallow fresh water sources that can be used for human consumption. The optimised REPTM assay allowed the detection of P. agardhii DNA down to 6 pM. This study, showed the potential of REPTM as a new biodetection platform for toxic bacteria and hence further studies will involve the development of a portable multi-analyte biosensor based on REPTM technology for on-site testing.

Development of a Plastic-Based Microfluidic Immunosensor Chip for Detection of H1N1 Influenza

PubMed Central

Lee, Kyoung G.; Lee, Tae Jae; Jeong, Soon Woo; Choi, Ho Woon; Heo, Nam Su; Park, Jung Youn; Park, Tae Jung; Lee, Seok Jae

2012-01-01

Lab-on-a-chip can provide convenient and accurate diagnosis tools. In this paper, a plastic-based microfluidic immunosensor chip for the diagnosis of swine flu (H1N1) was developed by immobilizing hemagglutinin antigen on a gold surface using a genetically engineered polypeptide. A fluorescent dye-labeled antibody (Ab) was used for quantifying the concentration of Ab in the immunosensor chip using a fluorescent technique. For increasing the detection efficiency and reducing the errors, three chambers and three microchannels were designed in one microfluidic chip. This protocol could be applied to the diagnosis of other infectious diseases in a microfluidic device. PMID:23112630

Technologies for autonomous integrated lab-on-chip systems for space missions

NASA Astrophysics Data System (ADS)

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

2016-11-01

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

Silicon-on-insulator sensors using integrated resonance-enhanced defect-mediated photodetectors.

PubMed

Fard, Sahba Talebi; Murray, Kyle; Caverley, Michael; Donzella, Valentina; Flueckiger, Jonas; Grist, Samantha M; Huante-Ceron, Edgar; Schmidt, Shon A; Kwok, Ezra; Jaeger, Nicolas A F; Knights, Andrew P; Chrostowski, Lukas

2014-11-17

A resonance-enhanced, defect-mediated, ring resonator photodetector has been implemented as a single unit biosensor on a silicon-on-insulator platform, providing a cost effective means of integrating ring resonator sensors with photodetectors for lab-on-chip applications. This method overcomes the challenge of integrating hybrid photodetectors on the chip. The demonstrated responsivity of the photodetector-sensor was 90 mA/W. Devices were characterized using refractive index modified solutions and showed sensitivities of 30 nm/RIU.

Micro-patterning and characterization of PHEMA-co-PAM-based optical chemical sensors for lab-on-a-chip applications.

PubMed

Zhu, Haixin; Zhou, Xianfeng; Su, Fengyu; Tian, Yanqing; Ashili, Shashanka; Holl, Mark R; Meldrum, Deirdre R

2012-10-01

We report a novel method for wafer level, high throughput optical chemical sensor patterning, with precise control of the sensor volume and capability of producing arbitrary microscale patterns. Monomeric oxygen (O(2)) and pH optical probes were polymerized with 2-hydroxyethyl methacrylate (HEMA) and acrylamide (AM) to form spin-coatable and further crosslinkable polymers. A micro-patterning method based on micro-fabrication techniques (photolithography, wet chemical process and reactive ion etch) was developed to miniaturize the sensor film onto glass substrates in arbitrary sizes and shapes. The sensitivity of fabricated micro-patterns was characterized under various oxygen concentrations and pH values. The process for spatially integration of two sensors (Oxygen and pH) on the same substrate surface was also developed, and preliminary fabrication and characterization results were presented. To the best of our knowledge, it is the first time that poly (2-hydroxylethyl methacrylate)-co-poly (acrylamide) (PHEMA-co-PAM)-based sensors had been patterned and integrated at the wafer level with micron scale precision control using microfabrication techniques. The developed methods can provide a feasible way to miniaturize and integrate the optical chemical sensor system and can be applied to any lab-on-a-chip system, especially the biological micro-systems requiring optical sensing of single or multiple analytes.

Pattern manipulation via on-chip phase modulation between orbital angular momentum beams

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

Li, Huanlu; School of Engineering, University of Glasgow, Rankine Building, Oakfield Avenue, Glasgow G12 8LP; Strain, Michael J.

2015-08-03

An integrated approach to thermal modulation of relative phase between two optical vortices with opposite chirality has been demonstrated on a silicon-on-insulator substrate. The device consists of a silicon-integrated optical vortex emitter and a phase controlled 3 dB coupler. The relative phase between two optical vortices can be actively modulated on chip by applying a voltage on the integrated heater. The phase shift is shown to be linearly proportional to applied electrical power, and the rotation angle of the interference pattern is observed to be inversely proportional to topological charge. This scheme can be used in lab-on-chip, communications and sensing applications.more » It can be intentionally implemented with other modulation elements to achieve more complicated applications.« less

Last Advances in Silicon-Based Optical Biosensors

PubMed Central

Fernández Gavela, Adrián; Grajales García, Daniel; Ramirez, Jhonattan C.; Lechuga, Laura M.

2016-01-01

We review the most important achievements published in the last five years in the field of silicon-based optical biosensors. We focus specially on label-free optical biosensors and their implementation into lab-on-a-chip platforms, with an emphasis on developments demonstrating the capability of the devices for real bioanalytical applications. We report on novel transducers and materials, improvements of existing transducers, new and improved biofunctionalization procedures as well as the prospects for near future commercialization of these technologies. PMID:26927105

Direct-referencing Two-dimensional-array Digital Microfluidics Using Multi-layer Printed Circuit Board

PubMed Central

Gong, Jian; Kim, Chang-Jin “CJ”

2008-01-01

Digital (i.e. droplet-based) microfluidics, by the electrowetting-on-dielectric (EWOD) mechanism, has shown great potential for a wide range of applications, such as lab-on-a-chip. While most reported EWOD chips use a series of electrode pads essentially in one-dimensional line pattern designed for specific tasks, the desired universal chips allowing user-reconfigurable paths would require the electrode pads in two-dimensional pattern. However, to electrically access the electrode pads independently, conductive lines need to be fabricated underneath the pads in multiple layers, raising a cost issue especially for disposable chip applications. In this article, we report the building of digital microfluidic plates based on a printed-circuit-board (PCB), in which multilayer electrical access lines were created inexpensively using mature PCB technology. However, due to its surface topography and roughness and resulting high resistance against droplet movement, as-fabricated PCB surfaces require unacceptably high (~500 V) voltages unless coated with or immersed in oil. Our goal is EWOD operations of aqueous droplets not only on oil-covered but also on dry surfaces. To meet varying levels of performances, three types of gradually complex post-PCB microfabrication processes are developed and evaluated. By introducing land-grid-array (LGA) sockets in the packaging, a scalable digital microfluidics system with reconfigurable and low-cost chip is also demonstrated. PMID:19234613

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.

Water analysis in a lab-on-a-chip system

NASA Astrophysics Data System (ADS)

Freimuth, Herbert; von Germar, Frithjof; Frese, Ines; Nahrstedt, Elzbieta; Küpper, Michael; Schenk, Rainer; Baser, Björn; Ott, Johannes; Drese, Klaus; Detemple, Peter; Doll, Theodor

2006-01-01

The development of a lab-on-chip system which allows the parallel detection of a variety of different parameters of a water sample is presented. Water analysis typically comprises the determination of around 30 physical and chemical parameters. An even larger number can arise when special contaminations of organic molecules are of interest. A demonstration system has been realised to show the feasibility and performance of an integrated device for the determination of physical quantities like electrical conductivity, light absorption and turbidity. Additionally, chemical quantities like the pH-value and the content of inorganic and organic contaminations are also determined. Two chips of credit card size contain the analytical functions and will be fabricated by injection moulding. First prototypes have been manufactured by milling or precision milling for the optical components.

Microcontact Printing of Thiol-Functionalized Ionic Liquid Microarrays for "Membrane-less" and "Spill-less" Gas Sensors.

PubMed

Gondosiswanto, Richard; Gunawan, Christian A; Hibbert, David B; Harper, Jason B; Zhao, Chuan

2016-11-16

Lab-on-a-chip systems have gained significant interest for both chemical synthesis and assays at the micro-to-nanoscale with a unique set of benefits. However, solvent volatility represents one of the major hurdles to the reliability and reproducibility of the lab-on-a-chip devices for large-scale applications. Here we demonstrate a strategy of combining nonvolatile and functionalized ionic liquids with microcontact printing for fabrication of "wall-less" microreactors and microfluidics with high reproducibility and high throughput. A range of thiol-functionalized ionic liquids have been synthesized and used as inks for microcontact printing of ionic liquid microdroplet arrays onto gold chips. The covalent bonds formed between the thiol-functionalized ionic liquids and the gold substrate offer enhanced stability of the ionic liquid microdroplets, compared to conventional nonfunctionalized ionic liquids, and these microdroplets remain stable in a range of nonpolar and polar solvents, including water. We further demonstrate the use of these open ionic liquid microarrays for fabrication of "membrane-less" and "spill-less" gas sensors with enhanced reproducibility and robustness. Ionic-liquid-based microarray and microfluidics fabricated using the described microcontact printing may provide a versatile platform for a diverse number of applications at scale.

Lab-on-a-Chip: From Astrobiology to the International Space Station

NASA Technical Reports Server (NTRS)

Maule, Jake; Wainwright, Nor; Steele, Andrew; Gunter, Dan; Monaco, Lisa A.; Wells, Mark E.; Morris, Heather C.; Boudreaux, Mark E.

2008-01-01

The continual and long-term habitation of enclosed environments, such as Antarctic stations, nuclear submarines and space stations, raises unique engineering, medical and operational challenges. There is no easy way out and no easy way to get supplies in. This situation elevates the importance of monitoring technology that can rapidly detect events within the habitat that affect crew safety such as fire, release of toxic chemicals and hazardous microorganisms. Traditional methods to monitor microorganisms on the International Space Station (ISS) have consisted of culturing samples for 3-5 days and eventual sample return to Earth. To augment these culture methods with new, rapid molecular techniques, we developed the Lab-on-a-Chip Application Development - Portable Test System (LOCAD-PTS). The system consists of a hand-held spectrophotometer, a series of interchangeable cartridges and a surface sampling/dilution kit that enables crew to collect samples and detect a range of biological molecules, all within 15 minutes. LOCAD-PTS was launched to the ISS aboard Space Shuttle Discovery in December 2006, where it was operated for the first time during March-May 2007. The surfaces of five separate sites in the US Lab and Node 1 of ISS were analyzed for endotoxin, using cartridges that employ the Limulus Amebocyte Lysate (LAL) assay; results of these tests will be presented. LOCAD-PTS will remain permanently onboard ISS with new cartridges scheduled for launch in February and October of 2008 for the detection of fungi (Beta-glucan) and Gram-positive bacteria (lipoteichoic acid), respectively.

Blister pouches for effective reagent storage and release for low cost point-of-care diagnostic applications

NASA Astrophysics Data System (ADS)

Smith, Suzanne; Sewart, Rene; Land, Kevin; Roux, Pieter; Gärtner, Claudia; Becker, Holger

2016-03-01

Lab-on-a-chip devices are often applied to point-of-care diagnostic solutions as they are low-cost, compact, disposable, and require only small sample volumes. For such devices, various reagents are required for sample preparation and analysis and, for an integrated solution to be realized, on-chip reagent storage and automated introduction are required. This work describes the implementation and characterization of effective liquid reagent storage and release mechanisms utilizing blister pouches applied to various point-of-care diagnostic device applications. The manufacturing aspects as well as performance parameters are evaluated.

Programmable lab-on-a-chip system for single cell analysis

NASA Astrophysics Data System (ADS)

Thalhammer, S.

2009-05-01

The collection, selection, amplification and detection of minimum genetic samples became a part of everyday life in medical and biological laboratories, to analyze DNA-fragments of pathogens, patient samples and traces on crime scenes. About a decade ago, a handful of researchers began discussing an intriguing idea. Could the equipment needed for everyday chemistry and biology procedures be shrunk to fit on a chip in the size of a fingernail? Miniature devices for, say, analysing DNA and proteins should be faster and cheaper than conventional versions. Lab-on-a-chip is an advanced technology that integrates a microfluidic system on a microscale chip device. The "laboratory" is created by means of channels, mixers, reservoirs, diffusion chambers, integrated electrodes, pumps, valves and more. With lab-ona- chip technology, complete laboratories on a square centimetre can be created. Here, a multifunctional programmable Lab-on-a-Chip driven by nanofluidics and controlled by surface acoustic waves (SAW) is presented. This system combines serial DNA-isolation-, amplification- and array-detection-process on a modified glass-platform. The fluid actuation is controlled via SAW by interdigital transducers implemented in the chemical modified chip surface. The chemical surface modification allows fluid handling in the sub-microliter range. Minute amount of sample material is extracted by laser-based microdissection out of e.g. histological sections at the single cell level. A few picogram of genetic material are isolated and transferred via a low-pressure transfer system (SPATS) onto the chip. Subsequently the genetic material inside single droplets, which behave like "virtual" beaker, is transported to the reaction and analysis centers on the chip surface via surface acoustic waves, mainly known as noise dumping filters in mobile phones. At these "biological reactors" the genetic material is processed, e.g. amplified via polymerase chain reaction methods, and genetically characterized.

Automated, Ultra-Sterile Solid Sample Handling and Analysis on a Chip

NASA Technical Reports Server (NTRS)

Mora, Maria F.; Stockton, Amanda M.; Willis, Peter A.

2013-01-01

There are no existing ultra-sterile lab-on-a-chip systems that can accept solid samples and perform complete chemical analyses without human intervention. The proposed solution is to demonstrate completely automated lab-on-a-chip manipulation of powdered solid samples, followed by on-chip liquid extraction and chemical analysis. This technology utilizes a newly invented glass micro-device for solid manipulation, which mates with existing lab-on-a-chip instrumentation. Devices are fabricated in a Class 10 cleanroom at the JPL MicroDevices Lab, and are plasma-cleaned before and after assembly. Solid samples enter the device through a drilled hole in the top. Existing micro-pumping technology is used to transfer milligrams of powdered sample into an extraction chamber where it is mixed with liquids to extract organic material. Subsequent chemical analysis is performed using portable microchip capillary electrophoresis systems (CE). These instruments have been used for ultra-highly sensitive (parts-per-trillion, pptr) analysis of organic compounds including amines, amino acids, aldehydes, ketones, carboxylic acids, and thiols. Fully autonomous amino acid analyses in liquids were demonstrated; however, to date there have been no reports of completely automated analysis of solid samples on chip. This approach utilizes an existing portable instrument that houses optics, high-voltage power supplies, and solenoids for fully autonomous microfluidic sample processing and CE analysis with laser-induced fluorescence (LIF) detection. Furthermore, the entire system can be sterilized and placed in a cleanroom environment for analyzing samples returned from extraterrestrial targets, if desired. This is an entirely new capability never demonstrated before. The ability to manipulate solid samples, coupled with lab-on-a-chip analysis technology, will enable ultraclean and ultrasensitive end-to-end analysis of samples that is orders of magnitude more sensitive than the ppb goal given in the Science Instruments.

A step towards on-chip biochemical energy cascade of microorganisms: carbon dioxide generation induced by ethanol fermentation in 3D printed modular lab-on-a-chip

NASA Astrophysics Data System (ADS)

Podwin, A.; Kubicki, W.; Adamski, K.; Walczak, R.; Dziuban, J. A.

2016-11-01

The concept of biochemical energy cascade of microorganisms towards oxygen generation in 3D printed lab-on-a-chip has been presented. In this work, carbon dioxide - a product of ethanol fermentation of yeasts has been utilized to enable light-initialized photosynthesis of euglenas and as a result of their metabolic transitions produce pure oxygen.

Lab-on-a-chip platforms for quantification of multicellular interactions in bone remodeling.

PubMed

George, Estee L; Truesdell, Sharon L; York, Spencer L; Saunders, Marnie M

2018-04-01

Researchers have been using lab-on-a-chip systems to isolate factors for study, simulate laboratory analysis and model cellular, tissue and organ level processes. The technology is increasing rapidly, but the bone field has been slow to keep pace. Novel models are needed that have the power and flexibility to investigate the elegant and synchronous multicellular interactions that occur in normal bone turnover and in disease states in which remodeling is implicated. By removing temporal and spatial limitations and enabling quantification of functional outcomes, the platforms should provide unique environments that are more biomimetic than single cell type systems while minimizing complex systemic effects of in vivo models. This manuscript details the development and characterization of lab-on-a-chip platforms for stimulating osteocytes and quantifying bone remodeling. Our platforms provide the foundation for a model that can be used to investigate remodeling interactions as a whole or as a standard mechanotransduction tool by which isolated activity can be quantified as a function of load. Copyright © 2018 Elsevier Inc. All rights reserved.

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.

Future lab-on-a-chip technologies for interrogating individual molecules.

PubMed

Craighead, Harold

2006-07-27

Advances in technology have allowed chemical sampling with high spatial resolution and the manipulation and measurement of individual molecules. Adaptation of these approaches to lab-on-a-chip formats is providing a new class of research tools for the investigation of biochemistry and life processes.

Multifunctional microvalves control by optical illumination on nanoheaters and its application in centrifugal microfluidic devices.

PubMed

Park, Jong-Myeon; Cho, Yoon-Kyoung; Lee, Beom-Seok; Lee, Jeong-Gun; Ko, Christopher

2007-05-01

Valving is critical in microfluidic systems. Among many innovative microvalves used in lab-on-a-chip applications, phase change based microvalves using paraffin wax are particularly attractive for disposable biochip applications because they are simple to implement, cost-effective and biocompatible. However, previously reported paraffin-based valves require embedded microheaters and therefore multi-step operation of many microvalves was a difficult problem. Besides, the operation time was relatively long, 2-10 s. In this paper, we report a unique phase change based microvalve for rapid and versatile operation of multiple microvalves using a single laser diode. The valve is made of nanocomposite materials in which 10 nm-sized iron oxide nanoparticles are dispersed in paraffin wax and used as nanoheaters when excited by laser irradiation. Laser light of relatively weak intensity was able to melt the paraffin wax with the embedded iron oxide nanoparticles, whereas even a very intense laser beam does not melt wax alone. The microvalves are leak-free up to 403.0 +/- 7.6 kPa and the response times to operate both normally closed and normally opened microvalves are less than 0.5 s. Furthermore, a sequential operation of multiple microvalves on a centrifugal microfluidic device using a single laser diode was demonstrated. It showed that the optical control of multiple microvalves is fast, robust, simple to operate, and requires minimal chip space and thus is well suited for fully integrated lab-on-a-chip applications.

Development of a magnetic lab-on-a-chip for point-of-care sepsis diagnosis

NASA Astrophysics Data System (ADS)

Schotter, Joerg; Shoshi, Astrit; Brueckl, Hubert

2009-05-01

We present design criteria, operation principles and experimental examples of magnetic marker manipulation for our magnetic lab-on-a-chip prototype. It incorporates both magnetic sample preparation and detection by embedded GMR-type magnetoresistive sensors and is optimized for the automated point-of-care detection of four different sepsis-indicative cytokines directly from about 5 μl of whole blood. The sample volume, magnetic particle size and cytokine concentration determine the microfluidic volume, sensor size and dimensioning of the magnetic gradient field generators. By optimizing these parameters to the specific diagnostic task, best performance is expected with respect to sensitivity, analysis time and reproducibility.

Multicore: Fallout From a Computing Evolution (LBNL Summer Lecture Series)

ScienceCinema

Yelick, Kathy [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). National Energy Research Scientific Computing Center (NERSC)

2018-05-07

Summer Lecture Series 2008: Parallel computing used to be reserved for big science and engineering projects, but in two years that's all changed. Even laptops and hand-helds use parallel processors. Unfortunately, the software hasn't kept pace. Kathy Yelick, Director of the National Energy Research Scientific Computing Center at Berkeley Lab, describes the resulting chaos and the computing community's efforts to develop exciting applications that take advantage of tens or hundreds of processors on a single chip.

Towards on-chip time-resolved thermal mapping with micro-/nanosensor arrays

PubMed Central

2012-01-01

In recent years, thin-film thermocouple (TFTC) array emerged as a versatile candidate in micro-/nanoscale local temperature sensing for its high resolution, passive working mode, and easy fabrication. However, some key issues need to be taken into consideration before real instrumentation and industrial applications of TFTC array. In this work, we will demonstrate that TFTC array can be highly scalable from micrometers to nanometers and that there are potential applications of TFTC array in integrated circuits, including time-resolvable two-dimensional thermal mapping and tracing the heat source of a device. Some potential problems and relevant solutions from a view of industrial applications will be discussed in terms of material selection, multiplexer reading, pattern designing, and cold-junction compensation. We show that the TFTC array is a powerful tool for research fields such as chip thermal management, lab-on-a-chip, and other novel electrical, optical, or thermal devices. PMID:22931306

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

NASA Technical Reports Server (NTRS)

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

2002-01-01

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

Numerical and experimental evaluation of microfluidic sorting devices.

PubMed

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

2008-01-01

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

Microfluidic redox battery.

PubMed

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

2013-07-07

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

Comparison of selected analytical techniques for protein sizing, quantitation and molecular weight determination.

PubMed

Goetz, H; Kuschel, M; Wulff, T; Sauber, C; Miller, C; Fisher, S; Woodward, C

2004-09-30

Protein analysis techniques are developing fast due to the growing number of proteins obtained by recombinant DNA techniques. In the present paper we compare selected techniques, which are used for protein sizing, quantitation and molecular weight determination: sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE), lab-on-a-chip or microfluidics technology (LoaC), size exclusion chromatography (SEC) and mass spectrometry (MS). We compare advantages and limitations of each technique in respect to different application areas, analysis time, protein sizing and quantitation performance.

Low loss hollow-core waveguide on a silicon substrate

NASA Astrophysics Data System (ADS)

Yang, Weijian; Ferrara, James; Grutter, Karen; Yeh, Anthony; Chase, Chris; Yue, Yang; Willner, Alan E.; Wu, Ming C.; Chang-Hasnain, Connie J.

2012-07-01

Optical-fiber-based, hollow-core waveguides (HCWs) have opened up many new applications in laser surgery, gas sensors, and non-linear optics. Chip-scale HCWs are desirable because they are compact, light-weight and can be integrated with other devices into systems-on-a-chip. However, their progress has been hindered by the lack of a low loss waveguide architecture. Here, a completely new waveguiding concept is demonstrated using two planar, parallel, silicon-on-insulator wafers with high-contrast subwavelength gratings to reflect light in-between. We report a record low optical loss of 0.37 dB/cm for a 9-μm waveguide, mode-matched to a single mode fiber. Two-dimensional light confinement is experimentally realized without sidewalls in the HCWs, which is promising for ultrafast sensing response with nearly instantaneous flow of gases or fluids. This unique waveguide geometry establishes an entirely new scheme for low-cost chip-scale sensor arrays and lab-on-a-chip applications.

Optical application of electrowetting

NASA Astrophysics Data System (ADS)

He, Mei; Peng, Runling; Chen, Jiabi

2017-02-01

Since electrowetting has been proposed, researchers began to apply eletrowetting into different fields, such as lab-on-chip systems, display technologies, printings and optics etc. This paper mainly introduced structure, theory and application of optical devices based on electrowetting. The optical devices include liquid optical prism, liquid optical lens and display. The paper introduced their principle, specific application and many advantages in optical applications. When they are applied to optical system, production and experiment, they can reduce mechanical moving parts, simplify the structure, operate easily, decrease manufacturing cost and energy consumption, improve working efficiency, and so on. We learn and research them in detail that will contribute to research and develop optical eletrowetting in the future.

Biomimetic microstructures for photonic and fluidic synergies

NASA Astrophysics Data System (ADS)

Vasileiou, Maria; Mpatzaka, Theodora; Alexandropoulos, Dimitris; Vainos, Nikolaos A.

2017-08-01

Nature-inspired micro- and nano-structures offer a unique platform for the development of novel synergetic systems combining photonic and microfluidic functionalities. In this context, we examine the paradigm of butterfly Vanessa cardui and develop artificial diffractive microstructures inspired by its natural designs. Softlithographic and nanoimprint protocols are developed to replicate surfaces of natural specimens. Further to their optical behavior, interphases tailored by such microstructures exhibit enhanced hydrophobic properties, as compared to their planar counterparts made of the same materials. Such synergies exploited by new design approaches pave the way to prospective optofluidic, lab-on-chip and sensing applications.

Micro-patterning and characterization of PHEMA-co-PAM-based optical chemical sensors for lab-on-a-chip applications

PubMed Central

Zhu, Haixin; Zhou, Xianfeng; Su, Fengyu; Tian, Yanqing; Ashili, Shashanka; Holl, Mark R.; Meldrum, Deirdre R.

2012-01-01

We report a novel method for wafer level, high throughput optical chemical sensor patterning, with precise control of the sensor volume and capability of producing arbitrary microscale patterns. Monomeric oxygen (O2) and pH optical probes were polymerized with 2-hydroxyethyl methacrylate (HEMA) and acrylamide (AM) to form spin-coatable and further crosslinkable polymers. A micro-patterning method based on micro-fabrication techniques (photolithography, wet chemical process and reactive ion etch) was developed to miniaturize the sensor film onto glass substrates in arbitrary sizes and shapes. The sensitivity of fabricated micro-patterns was characterized under various oxygen concentrations and pH values. The process for spatially integration of two sensors (Oxygen and pH) on the same substrate surface was also developed, and preliminary fabrication and characterization results were presented. To the best of our knowledge, it is the first time that poly (2-hydroxylethyl methacrylate)-co-poly (acrylamide) (PHEMA-co-PAM)-based sensors had been patterned and integrated at the wafer level with micron scale precision control using microfabrication techniques. The developed methods can provide a feasible way to miniaturize and integrate the optical chemical sensor system and can be applied to any lab-on-a-chip system, especially the biological micro-systems requiring optical sensing of single or multiple analytes. PMID:23175599

Stem cell culture and differentiation in microfluidic devices toward organ-on-a-chip.

PubMed

Zhang, Jie; Wei, Xiaofeng; Zeng, Rui; Xu, Feng; Li, XiuJun

2017-06-01

Microfluidic lab-on-a-chip provides a new platform with unique advantages to mimic complex physiological microenvironments in vivo and has been increasingly exploited to stem cell research. In this review, we highlight recent advances of microfluidic devices for stem cell culture and differentiation toward the development of organ-on-a-chip, especially with an emphasis on vital innovations within the last 2 years. Various aspects for improving on-chip stem-cell culture and differentiation, particularly toward organ-on-a-chip, are discussed, along with microenvironment control, surface modification, extracellular scaffolds, high throughput and stimuli. The combination of microfluidic technologies and stem cells hold great potential toward versatile systems of 'organ-on-a-chip' as desired. Adapted with permission from [1-8].

Wireless poly(dimethylsiloxane) quartz-crystal-microbalance biosensor chip fabricated by nanoimprint lithography for micropump integration aiming at application in lab-on-a-chip

NASA Astrophysics Data System (ADS)

Kato, Fumihito; Noguchi, Hiroyuki; Kodaka, Yukinari; Oshida, Naoya; Ogi, Hirotsugu

2018-07-01

We developed a quartz-crystal-microbalance (QCM) biosensor chip that operates wirelessly via electromagnetic waves, using poly(dimethylsiloxane) (PDMS). An AT-cut quartz oscillator (22–30 µm) is packaged in a microchannel, where it is supported by micropillars without mechanical fixing. As a result, the quartz oscillator is little affected by the thermal stress caused by the difference in the thermal expansion coefficients of the components, and the leakage of the vibration energy of the quartz oscillator is reduced. Consequently, high-frequency (∼56 MHz) measurement with a stable baseline (±∼2 ppm) is realized. We succeeded in repeatedly monitoring the binding reaction between immunoglobulin G (IgG) and Staphylococcus aureus protein A (SPA) with the quartz oscillator on which SPA molecules were immobilized nonspecifically. In addition, the affinity between SPA and IgG was calculated from the association and dissociation curves, and the usefulness of our wireless PDMS QCM biosensor was demonstrated.

Imaging live cells at high spatiotemporal resolution for lab-on-a-chip applications.

PubMed

Chin, Lip Ket; Lee, Chau-Hwang; Chen, Bi-Chang

2016-05-24

Conventional optical imaging techniques are limited by the diffraction limit and difficult-to-image biomolecular and sub-cellular processes in living specimens. Novel optical imaging techniques are constantly evolving with the desire to innovate an imaging tool that is capable of seeing sub-cellular processes in a biological system, especially in three dimensions (3D) over time, i.e. 4D imaging. For fluorescence imaging on live cells, the trade-offs among imaging depth, spatial resolution, temporal resolution and photo-damage are constrained based on the limited photons of the emitters. The fundamental solution to solve this dilemma is to enlarge the photon bank such as the development of photostable and bright fluorophores, leading to the innovation in optical imaging techniques such as super-resolution microscopy and light sheet microscopy. With the synergy of microfluidic technology that is capable of manipulating biological cells and controlling their microenvironments to mimic in vivo physiological environments, studies of sub-cellular processes in various biological systems can be simplified and investigated systematically. In this review, we provide an overview of current state-of-the-art super-resolution and 3D live cell imaging techniques and their lab-on-a-chip applications, and finally discuss future research trends in new and breakthrough research areas of live specimen 4D imaging in controlled 3D microenvironments.

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

PubMed

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

2016-08-01

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

Selective filling for patterning in microfluidic channels and integration of chromatography in "lab-on-a-chip" devices using sol-gel technology

NASA Astrophysics Data System (ADS)

Jindal, Rohit

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

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.

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

PubMed

Pandiyan, Vimal Prabhu; John, Renu

2016-01-20

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

DNA transformation via local heat shock

NASA Astrophysics Data System (ADS)

Li, Sha; Meadow Anderson, L.; Yang, Jui-Ming; Lin, Liwei; Yang, Haw

2007-07-01

This work describes transformation of foreign DNA into bacterial host cells by local heat shock using a microfluidic system with on-chip, built-in platinum heaters. Plasmid DNA encoding ampicillin resistance and a fluorescent protein can be effectively transformed into the DH5α chemically competent E. coli using this device. Results further demonstrate that only one-thousandth of volume is required to obtain transformation efficiencies as good as or better than conventional practices. As such, this work complements other lab-on-a-chip technologies for potential gene cloning/therapy and protein expression applications.

Micro Machining of Injection Mold Inserts for Fluidic Channel of Polymeric Biochips

PubMed Central

Jung, Woo-Chul; Heo, Young-Moo; Yoon, Gil-Sang; Shin, Kwang-Ho; Chang, Sung-Ho; Kim, Gun-Hee; Cho, Myeong-Woo

2007-01-01

Recently, the polymeric micro-fluidic biochip, often called LOC (lab-on-a-chip), has been focused as a cheap, rapid and simplified method to replace the existing biochemical laboratory works. It becomes possible to form miniaturized lab functionalities on a chip with the development of MEMS technologies. The micro-fluidic chips contain many micro-channels for the flow of sample and reagents, mixing, and detection tasks. Typical substrate materials for the chip are glass and polymers. Typical techniques for microfluidic chip fabrication are utilizing various micro pattern forming methods, such as wet-etching, micro-contact printing, and hot-embossing, micro injection molding, LIGA, and micro powder blasting processes, etc. In this study, to establish the basis of the micro pattern fabrication and mass production of polymeric micro-fluidic chips using injection molding process, micro machining method was applied to form micro-channels on the LOC molds. In the research, a series of machining experiments using micro end-mills were performed to determine optimum machining conditions to improve surface roughness and shape accuracy of designed simplified micro-channels. Obtained conditions were used to machine required mold inserts for micro-channels using micro end-mills. Test injection processes using machined molds and COC polymer were performed, and then the results were investigated.

Radiation hardened microprocessor for small payloads

NASA Technical Reports Server (NTRS)

Shah, Ravi

1993-01-01

The RH-3000 program is developing a rad-hard space qualified 32-bit MIPS R-3000 RISC processor under the Naval Research Lab sponsorship. In addition, under IR&D Harris is developing RHC-3000 for embedded control applications where low cost and radiation tolerance are primary concerns. The development program leverages heavily from commercial development of the MIPS R-3000. The commercial R-3000 has a large installed user base and several foundry partners are currently producing a wide variety of R-3000 derivative products. One of the MIPS derivative products, the LR33000 from LSI Logic, was used as the basis for the design of the RH-3000 chipset. The RH-3000 chipset consists of three core chips and two support chips. The core chips include the CPU, which is the R-3000 integer unit and the FPA/MD chip pair, which performs the R-3010 floating point functions. The two support whips contain all the support functions required for fault tolerance support, real-time support, memory management, timers, and other functions. The Harris development effort had first passed silicon success in June, 1992 with the first rad-hard 32-bit RH-3000 CPU chip. The CPU device is 30 kgates, has a 508 mil by 503 mil die size and is fabricated at Harris Semiconductor on the rad-hard CMOS Silicon on Sapphire (SOS) process. The CPU device successfully passed tesing against 600,000 test vectors derived directly on the LSI/MIPS test suite and has been operational as a single board computer running C code for the past year. In addition, the RH-3000 program has developed the methodology for converting commercially developed designs utilizing logic synthesis techniques based on a combination of VHDK and schematic data bases.

Plastic lab-on-a-chip for fluorescence excitation with integrated organic semiconductor lasers.

PubMed

Vannahme, Christoph; Klinkhammer, Sönke; Lemmer, Uli; Mappes, Timo

2011-04-25

Laser light excitation of fluorescent markers offers highly sensitive and specific analysis for bio-medical or chemical analysis. To profit from these advantages for applications in the field or at the point-of-care, a plastic lab-on-a-chip with integrated organic semiconductor lasers is presented here. First order distributed feedback lasers based on the organic semiconductor tris(8-hydroxyquinoline) aluminum (Alq3) doped with the laser dye 4-dicyanomethylene-2-methyl-6-(p-dimethylaminostyril)-4H-pyrane (DCM), deep ultraviolet induced waveguides, and a nanostructured microfluidic channel are integrated into a poly(methyl methacrylate) (PMMA) substrate. A simple and parallel fabrication process is used comprising thermal imprint, DUV exposure, evaporation of the laser material, and sealing by thermal bonding. The excitation of two fluorescent marker model systems including labeled antibodies with light emitted by integrated lasers is demonstrated.

Lab-on-a-Chip Design-Build Project with a Nanotechnology Component in a Freshman Engineering Course

ERIC Educational Resources Information Center

Allam, Yosef; Tomasko, David L.; Trott, Bruce; Schlosser, Phil; Yang, Yong; Wilson, Tiffany M.; Merrill, John

2008-01-01

A micromanufacturing lab-on-a-chip project with a nanotechnology component was introduced as an alternate laboratory in the required first-year engineering curriculum at The Ohio State University. Nanotechnology is introduced in related reading and laboratory tours as well as laboratory activities including a quarter-length design, build, and test…

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

NASA Astrophysics Data System (ADS)

Brecher, Christian; Baum, Christoph; Bastuck, Thomas

2015-03-01

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

Optical trapping for complex fluid microfluidics

NASA Astrophysics Data System (ADS)

Vestad, Tor; Oakey, John; Marr, David W. M.

2004-10-01

Many proposed applications of microfluidics involve the manipulation of complex fluid mixtures such as blood or bacterial suspensions. To sort and handle the constituent particles within these suspensions, we have developed a miniaturized automated cell sorter using optical traps. This microfluidic cell sorter offers the potential to perform chip-top microbiology more rapidly and with less associated hardware and preparation time than other techniques currently available. To realize the potential of this technology in practical clinical and consumer lab-on-a-chip devices however, microscale control of not only particulates but also the fluid phase must be achieved. To address this, we have developed a mechanical fluid control scheme that integrates well with our optical separations approach. We demonstrate here a combined technique, one that employs both mechanical actuation and optical trapping for the precise control of complex suspensions. This approach enables both cell and particle separations as well as the subsequent fluid control required for the completion of complex analyses.

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

NASA Astrophysics Data System (ADS)

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

2013-05-01

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

Lab-on-chip components for molecular detection

NASA Astrophysics Data System (ADS)

Adam, Tijjani; Dhahi, Th S.; Mohammed, Mohammed; Hashim, U.; Noriman, N. Z.; Dahham, Omar S.

2017-09-01

We successfully fabricated Lab on chip components and integrated for possible use in biomedical application. The sensor was fabricated by using conventional photolithography method integrated with PDMS micro channels for smooth delivery of sample to the sensing domain. The sensor was silanized and aminated with 3-Aminopropyl triethoxysilane (APTES) to functionalize the surface with biomolecules and create molecular binding chemistry. The resulting Si-O-Si- components were functionalized with oligonucleotides probe of HPV, which interacted with the single stranded HPV DNA target to create a field across on the device. The fabrication, immobilization and hybridization processes were characterized with current voltage (I-V) characterization (KEITHLEY, 6487). The sensor show selectivity for the HPV DNA target in a linear range from concentration 0.1 nM to 1 µM. This strategy presented a simple, rapid and sensitive platform for HPV detection and would become a powerful tool for pathogenic microorganisms screening in clinical diagnosis.

PhyloChip Tackles Coral Disease

ScienceCinema

Todd DeSantis

2017-12-09

Scientists at Berkeley Lab and the University of California, Merced are using an innovative DNA array developed at Berkeley Lab to catalog the microbes that live among coral in the tropical waters off the coast of Puerto Rico.

Electrical Chips for Biological Point-of-Care Detection.

PubMed

Reddy, Bobby; Salm, Eric; Bashir, Rashid

2016-07-11

As the future of health care diagnostics moves toward more portable and personalized techniques, there is immense potential to harness the power of electrical signals for biological sensing and diagnostic applications at the point of care. Electrical biochips can be used to both manipulate and sense biological entities, as they can have several inherent advantages, including on-chip sample preparation, label-free detection, reduced cost and complexity, decreased sample volumes, increased portability, and large-scale multiplexing. The advantages of fully integrated electrical biochip platforms are particularly attractive for point-of-care systems. This review summarizes these electrical lab-on-a-chip technologies and highlights opportunities to accelerate the transition from academic publications to commercial success.

3D printed microfluidics for biological applications.

PubMed

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

2015-01-01

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

Lab-on-CMOS Integration of Microfluidics and Electrochemical Sensors

PubMed Central

Huang, Yue; Mason, Andrew J.

2013-01-01

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

Lab-on-CMOS integration of microfluidics and electrochemical sensors.

PubMed

Huang, Yue; Mason, Andrew J

2013-10-07

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

Development of a portable analyzer with polymer lab-on-a-chip (LOC) for continuous sampling and monitoring of Pb(II).

PubMed

Jang, A; Zou, Z; MacKnight, E; Wu, P M; Kim, I S; Ahn, C H; Bishop, P L

2009-01-01

A new portable analyzer with polymer lab-on-a-chip (LOC) has been designed, fabricated and fully characterized for continuous sampling and monitoring of lead (Pb(II)) in this work. As the working electrodes of the sensor, bismuth (Bi (III)) which allowed the advantage of being more environmentally friendly than traditional mercury drop electrodes was used, while maintaining similar sensitivity and other desirable characteristics. The size of a portable analyzer was 30 cmx23 cmx7 cm, and the weight was around 3 kg. The small size gives the advantage of being portable for field use while not sacrificing portability for accuracy of measurement. Furthermore, the autonomous system developed in coordination with the development of new polymer LOC integrated with electrochemical sensors can provide an innovative way to monitor surface waters in an efficient, cost-effective and sustainable manner.

On-chip microlasers for biomolecular detection via highly localized deposition of a multifunctional phospholipid ink.

PubMed

Bog, Uwe; Laue, Thomas; Grossmann, Tobias; Beck, Torsten; Wienhold, Tobias; Richter, Benjamin; Hirtz, Michael; Fuchs, Harald; Kalt, Heinz; Mappes, Timo

2013-07-21

We report on a novel approach to realize on-chip microlasers, by applying highly localized and material-saving surface functionalization of passive photonic whispering gallery mode microresonators. We apply dip-pen nanolithography on a true three-dimensional structure. We coat solely the light-guiding circumference of pre-fabricated poly(methyl methacrylate) resonators with a multifunctional molecular ink. The functionalization is performed in one single fabrication step and simultaneously provides optical gain as well as molecular binding selectivity. This allows for a direct and flexible realization of on-chip microlasers, which can be utilized as biosensors in optofluidic lab-on-a-chip applications. In a proof-of-concept we show how this highly localized molecule deposition suffices for low-threshold lasing in air and water, and demonstrate the capability of the ink-lasers as biosensors in a biotin-streptavidin binding experiment.

Robust and versatile ionic liquid microarrays achieved by microcontact printing

NASA Astrophysics Data System (ADS)

Gunawan, Christian A.; Ge, Mengchen; Zhao, Chuan

2014-04-01

Lab-on-a-chip and miniaturized systems have gained significant popularity motivated by marked differences in material performance at the micro-to-nano-scale realm. However, to fully exploit micro-to-nano-scale chemistry, solvent volatility and lack of reproducibility need to be overcome. Here, we combine the non-volatile and versatile nature of ionic liquids with microcontact printing in an attempt to establish a facile protocol for high throughput fabrication of open microreactors and microfluidics. The micropatterned ionic liquid droplets have been demonstrated as electrochemical cells and reactors for microfabrication of metals and charge transfer complexes, substrates for immobilization of proteins and as membrane-free high-performance amperometric gas sensor arrays. The results suggest that miniaturized ionic liquid systems can be used to solve the problems of solvent volatility and slow mass transport in viscous ionic liquids in lab-on-a-chip devices, thus providing a versatile platform for a diverse number of applications.

Total-Internal-Reflection Platforms for Chemical and Biological Sensing Applications

NASA Astrophysics Data System (ADS)

Sapsford, Kim E.

Sensing platforms based on the principle of total internal reflection (TIR) represent a fairly mature yet still expanding and exciting field of research. Sensor development has mainly been driven by the need for rapid, stand-alone, automated devices for application in the fields of clinical diagnosis and screening, food and water safety, environmental monitoring, and chemical and biological warfare agent detection. The technologies highlighted in this chapter are continually evolving, taking advantage of emerging advances in microfabrication, lab-on-a-chip, excitation, and detection techniques. This chapter describes many of the underlying principles of TIR-based sensing platforms and additionally focusses on planar TIR fluorescence (TIRF)-based chemical and biological sensors.

A High-Resolution Minimicroscope System for Wireless Real-Time Monitoring.

PubMed

Wang, Zongjie; Boddeda, Akash; Parker, Benjamin; Samanipour, Roya; Ghosh, Sanjoy; Menard, Frederic; Kim, Keekyoung

2018-07-01

Compact, cost-effective, and high-performance microscope that enables the real-time imaging of cells and lab-on-a-chip devices is highly demanded for cell biology and biomedical engineering. This paper aims to present the design and application of an inexpensive wireless minimicroscope with resolution up to 2592 × 1944 pixels and speed up to 90 f/s. The minimicroscope system was built on a commercial embedded system (Raspberry Pi). We modified a camera module and adopted an inverse dual lens system to obtain the clear field of view and appropriate magnification for tens of micrometer objects. The system was capable of capturing time-lapse images and transferring image data wirelessly. The entire system can be operated wirelessly and cordlessly in a conventional cell culturing incubator. The developed minimicroscope was used to monitor the attachment and proliferation of NIH-3T3 and HEK 293 cells inside an incubator for 50 h. In addition, the minimicroscope was used to monitor a droplet generation process in a microfluidic device. The high-quality images captured by the minimicroscope enabled us an automated analysis of experimental parameters. The successful applications prove the great potential of the developed minimicroscope for monitoring various biological samples and microfluidic devices. This paper presents the design of a high-resolution minimicroscope system that enables the wireless real-time imaging of cells inside the incubator. This system has been verified to be a useful tool to obtain high-quality images and videos for the automated quantitative analysis of biological samples and lab-on-a-chip devices in the long term.

Low cost lab-on-a-chip prototyping with a consumer grade 3D printer.

PubMed

Comina, Germán; Suska, Anke; Filippini, Daniel

2014-08-21

Versatile prototyping of 3D printed lab-on-a-chip devices, supporting different forms of sample delivery, transport, functionalization and readout, is demonstrated with a consumer grade printer, which centralizes all critical fabrication tasks. Devices cost 0.57US$ and are demonstrated in chemical sensing and micromixing examples, which exploit established principles from reference technologies.

Random lasers for lab-on-chip applications

NASA Astrophysics Data System (ADS)

Giehl, J. M.; Butzbach, F.; Jorge, K. C.; Alvarado, M. A.; Carreño, M. N. P.; Alayo, M. I.; Wetter, N. U.

2016-04-01

Random lasers are laser sources in which the feedback is provided by scattering instead of reflection and which, for this reason, do not require surfaces with optical finish such as mirrors. The investigation of such lasing action in a large variety of disordered materials is a subject of high interest with very important applications such as threedimensional and speckle-free imaging, detection of cancer tissue and photonic coding and encryption. However, potential applications require optimization of random laser performance especially with respect to optical efficiency and directionality or brightness. This work demonstrates such an optimization procedure with the goal of achieving a random laser with sufficient efficiency and brightness in order to be used in practical applications. Two random lasers are demonstrated, one solid and on liquid, that fulfil directionality and efficiency requirements. The first one consists of a neodymium doped powder laser with a record slope efficiency of 1.6%. The second one is a liquid random laser injected into a HC-ARROW waveguide which uses a microchannel connected to a much larger reservoir in order to achieve the necessary directionality. Both devices can be produced by low cost fabricating technologies and easily integrated into next-generation, lab-on-chip devices used for in-situ determination of infectious tropical diseases, which is the main goal of this project.

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

NASA Astrophysics Data System (ADS)

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

2017-11-01

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

Interfacing Lab-on-a-Chip Embryo Technology with High-Definition Imaging Cytometry.

PubMed

Zhu, Feng; Hall, Christopher J; Crosier, Philip S; Wlodkowic, Donald

2015-08-01

To spearhead deployment of zebrafish embryo biotests in large-scale drug discovery studies, automated platforms are needed to integrate embryo in-test positioning and immobilization (suitable for high-content imaging) with fluidic modules for continuous drug and medium delivery under microperfusion to developing embryos. In this work, we present an innovative design of a high-throughput three-dimensional (3D) microfluidic chip-based device for automated immobilization and culture and time-lapse imaging of developing zebrafish embryos under continuous microperfusion. The 3D Lab-on-a-Chip array was fabricated in poly(methyl methacrylate) (PMMA) transparent thermoplastic using infrared laser micromachining, while the off-chip interfaces were fabricated using additive manufacturing processes (fused deposition modelling and stereolithography). The system's design facilitated rapid loading and immobilization of a large number of embryos in predefined clusters of traps during continuous microperfusion of drugs/toxins. It was conceptually designed to seamlessly interface with both upright and inverted fluorescent imaging systems and also to directly interface with conventional microtiter plate readers that accept 96-well plates. Compared with the conventional Petri dish assays, the chip-based bioassay was much more convenient and efficient as only small amounts of drug solutions were required for the whole perfusion system running continuously over 72 h. Embryos were spatially separated in the traps that assisted tracing single embryos, preventing interembryo contamination and improving imaging accessibility.

A Brief Review of OPT101 Sensor Application in Near-Infrared Spectroscopy Instrumentation for Intensive Care Unit Clinics

PubMed Central

Li, Ting; Zhong, Fulin; Pan, Boan; Li, Zebin; Huang, Chong; Deng, Zishan

2017-01-01

The optoelectronic sensor OPT101 have merits in advanced optoelectronic response characteristics at wavelength range for medical near-infrared spectroscopy and small-size chip design with build-in trans-impedance amplifier. Our lab is devoted to developing a series of portable near-infrared spectroscopy (NIRS) devices embedded with OPT101 for applications in intensive care unit clinics, based on NIRS principle. Here we review the characteristics and advantages of OPT101 relative to clinical NIRS instrumentation, and the most recent achievements, including early-diagnosis and therapeutic effect evaluation of thrombus, noninvasive monitoring of patients' shock severity, and fatigue evaluation. The future prospect on OPT101 improvements in noninvasive clinical applications is also discussed. PMID:28757564

Chemically Polymerized Polypyrrole for On-Chip Concentration of Volatile Breath Metabolites

PubMed Central

Strand, Nicholas; Bhushan, Abhinav; Schivo, Michael; Kenyon, Nicholas J.; Davis, Cristina E.

2009-01-01

A wide range of metabolites are measured in the gas phase of exhaled human breath, and some of these biomarkers are frequently observed to be up- or down-regulated in certain disease states. Portable breath analysis systems have the potential for a wide range of applications in health diagnostics. However, this is currently limited by the lack of concentration mechanisms to enhance trace metabolites found in the breath to levels that can be adequately recorded using miniaturized gas-phase sensors. In this study we have created chip-based polymeric pre-concentration devices capable of absorbing and desorbing breath volatiles for subsequent chemical analysis. These devices appear to concentrate chemicals from both environmental air samples as well as directly from exhaled human breath, and these devices may have applications in lab-on-a-chip-based environmental and health monitoring systems. PMID:20161533

Lab-on-a-Chip Proteomic Assays for Psychiatric Disorders.

PubMed

Peter, Harald; Wienke, Julia; Guest, Paul C; Bistolas, Nikitas; Bier, Frank F

2017-01-01

Lab-on-a-chip assays allow rapid identification of multiple parameters on an automated user-friendly platform. Here we describe a fully automated multiplex immunoassay and readout in less than 15 min using the Fraunhofer in vitro diagnostics (ivD) platform to enable inexpensive point-of-care profiling of sera or a single drop of blood from patients with various diseases such as psychiatric disorders.

Quantification of cellular penetrative forces using lab-on-a-chip technology and finite element modeling

PubMed Central

Sanati Nezhad, Amir; Naghavi, Mahsa; Packirisamy, Muthukumaran; Bhat, Rama; Geitmann, Anja

2013-01-01

Tip-growing cells have the unique property of invading living tissues and abiotic growth matrices. To do so, they exert significant penetrative forces. In plant and fungal cells, these forces are generated by the hydrostatic turgor pressure. Using the TipChip, a microfluidic lab-on-a-chip device developed for tip-growing cells, we tested the ability to exert penetrative forces generated in pollen tubes, the fastest-growing plant cells. The tubes were guided to grow through microscopic gaps made of elastic polydimethylsiloxane material. Based on the deformation of the gaps, the force exerted by the elongating tubes to permit passage was determined using finite element methods. The data revealed that increasing mechanical impedance was met by the pollen tubes through modulation of the cell wall compliance and, thus, a change in the force acting on the obstacle. Tubes that successfully passed a narrow gap frequently burst, raising questions about the sperm discharge mechanism in the flowering plants. PMID:23630253

Development of a lab-on-chip electrochemical biosensor for water quality analysis based on microalgal photosynthesis.

PubMed

Tsopela, A; Laborde, A; Salvagnac, L; Ventalon, V; Bedel-Pereira, E; Séguy, I; Temple-Boyer, P; Juneau, P; Izquierdo, R; Launay, J

2016-05-15

The present work was dedicated to the development of a lab-on-chip device for water toxicity analysis and more particularly herbicide detection in water. It consists in a portable system for on-site detection composed of three-electrode electrochemical microcells, integrated on a fluidic platform constructed on a glass substrate. The final goal is to yield a system that gives the possibility of conducting double, complementary detection: electrochemical and optical and therefore all materials used for the fabrication of the lab-on-chip platform were selected in order to obtain a device compatible with optical technology. The basic detection principle consisted in electrochemically monitoring disturbances in metabolic photosynthetic activities of algae induced by the presence of Diuron herbicide. Algal response, evaluated through oxygen (O2) monitoring through photosynthesis was different for each herbicide concentration in the examined sample. A concentration-dependent inhibition effect of the herbicide on photosynthesis was demonstrated. Herbicide detection was achieved through a range (blank - 1 µM Diuron herbicide solution) covering the limit of maximum acceptable concentration imposed by Canadian government (0.64 µM), using a halogen white light source for the stimulation of algal photosynthetic apparatus. Superior sensitivity results (limit of detection of around 0.1 µM) were obtained with an organic light emitting diode (OLED), having an emission spectrum adapted to algal absorption spectrum and assembled on the final system. Copyright © 2015 Elsevier B.V. All rights reserved.

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

NASA Astrophysics Data System (ADS)

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

2016-02-01

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

A versatile lab-on-chip test platform to characterize elementary deformation mechanisms and electromechanical couplings in nanoscopic objects

NASA Astrophysics Data System (ADS)

Pardoen, Thomas; Colla, Marie-Sthéphane; Idrissi, Hosni; Amin-Ahmadi, Behnam; Wang, Binjie; Schryvers, Dominique; Bhaskar, Umesh K.; Raskin, Jean-Pierre

2016-03-01

A nanomechanical on-chip test platform has recently been developed to deform under a variety of loading conditions freestanding thin films, ribbons and nanowires involving submicron dimensions. The lab-on-chip involves thousands of elementary test structures from which the elastic modulus, strength, strain hardening, fracture, creep properties can be extracted. The technique is amenable to in situ transmission electron microscopy (TEM) investigations to unravel the fundamental underlying deformation and fracture mechanisms that often lead to size-dependent effects in small-scale samples. The method allows addressing electrical and magnetic couplings as well in order to evaluate the impact of large mechanical stress levels on different solid-state physics phenomena. We had the chance to present this technique in details to Jacques Friedel in 2012 who, unsurprisingly, made a series of critical and very relevant suggestions. In the spirit of his legacy, the paper will address both mechanics of materials related phenomena and couplings with solids state physics issues.

A portable optical reader and wall projector towards enumeration of bio-conjugated beads or cells

PubMed Central

McArdle, Niamh A.; Kendlin, Jane L.; O’Connell, Triona M.; Ducrée, Jens

2017-01-01

Measurement of the height of a packed column of cells or beads, which can be direclty related to the number of cells or beads present in a chamber, is an important step in a number of diagnostic assays. For example, haematocrit measurements may rapidly identify anemia or polycthemia. Recently, user-friendly and cost-efficient Lab-on-a-Chip devices have been developed towards isolating and counting cell sub-populations for diagnostic purposes. In this work, we present a low-cost optical module for estimating the filling level of packed magnetic beads within a Lab-on-a-Chip device. The module is compatible with a previously introduced, disposable microfluidic chip for rapid determination of CD4+ cell counts. The device is a simple optical microscope module is manufactured by 3D printing. An objective lens directly interrogates the height of packed beads which are efficiently isolated on the finger-actuated chip. Optionally, an inexpensive, battery-powered Light Emitting Diode may project a shadow of the microfluidic chip at approximately 50-fold magnification onto a nearby surface. The reader is calibrated with the filling levels of known concentrations of paramagnetic beads within the finger actuated chip. Results in direct and projector mode are compared to measurements from a conventional, inverted white-light microscope. All three read-out methods indicate a maximum variation of 6.5% between methods. PMID:29267367

Microfluidic desalination techniques and their potential applications.

PubMed

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

2015-09-07

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

Screening applications in drug discovery based on microfluidic technology

PubMed Central

Eribol, P.; Uguz, A. K.; Ulgen, K. O.

2016-01-01

Microfluidics has been the focus of interest for the last two decades for all the advantages such as low chemical consumption, reduced analysis time, high throughput, better control of mass and heat transfer, downsizing a bench-top laboratory to a chip, i.e., lab-on-a-chip, and many others it has offered. Microfluidic technology quickly found applications in the pharmaceutical industry, which demands working with leading edge scientific and technological breakthroughs, as drug screening and commercialization are very long and expensive processes and require many tests due to unpredictable results. This review paper is on drug candidate screening methods with microfluidic technology and focuses specifically on fabrication techniques and materials for the microchip, types of flow such as continuous or discrete and their advantages, determination of kinetic parameters and their comparison with conventional systems, assessment of toxicities and cytotoxicities, concentration generations for high throughput, and the computational methods that were employed. An important conclusion of this review is that even though microfluidic technology has been in this field for around 20 years there is still room for research and development, as this cutting edge technology requires ingenuity to design and find solutions for each individual case. Recent extensions of these microsystems are microengineered organs-on-chips and organ arrays. PMID:26865904

Screening applications in drug discovery based on microfluidic technology.

PubMed

Eribol, P; Uguz, A K; Ulgen, K O

2016-01-01

Microfluidics has been the focus of interest for the last two decades for all the advantages such as low chemical consumption, reduced analysis time, high throughput, better control of mass and heat transfer, downsizing a bench-top laboratory to a chip, i.e., lab-on-a-chip, and many others it has offered. Microfluidic technology quickly found applications in the pharmaceutical industry, which demands working with leading edge scientific and technological breakthroughs, as drug screening and commercialization are very long and expensive processes and require many tests due to unpredictable results. This review paper is on drug candidate screening methods with microfluidic technology and focuses specifically on fabrication techniques and materials for the microchip, types of flow such as continuous or discrete and their advantages, determination of kinetic parameters and their comparison with conventional systems, assessment of toxicities and cytotoxicities, concentration generations for high throughput, and the computational methods that were employed. An important conclusion of this review is that even though microfluidic technology has been in this field for around 20 years there is still room for research and development, as this cutting edge technology requires ingenuity to design and find solutions for each individual case. Recent extensions of these microsystems are microengineered organs-on-chips and organ arrays.

Piezoresistive microcantilever based lab-on-a-chip system for detection of macronutrients in the soil

NASA Astrophysics Data System (ADS)

Patkar, Rajul S.; Ashwin, Mamta; Rao, V. Ramgopal

2017-12-01

Monitoring of soil nutrients is very important in precision agriculture. In this paper, we have demonstrated a micro electro mechanical system based lab-on-a-chip system for detection of various soil macronutrients which are available in ionic form K+, NO3-, and H2PO4-. These sensors are highly sensitive piezoresistive silicon microcantilevers coated with a polymer matrix containing methyltridodecylammonium nitrate ionophore/ nitrate ionophore VI for nitrate sensing, 18-crown-6 ether for potassium sensing and Tributyltin chloride for phosphate detection. A complete lab-on-a-chip system integrating a highly sensitive current excited Wheatstone's bridge based portable electronic setup along with arrays of microcantilever devices mounted on a printed circuit board with a liquid flow cell for on the site experimentation for soil test has been demonstrated.

Self-sustainable, high-power-density bio-solar cells for lab-on-a-chip applications.

PubMed

Liu, Lin; Choi, Seokheun

2017-11-07

A microfluidic lab-on-a-chip system that generates its own power is essential for stand-alone, independent, self-sustainable point-of-care diagnostic devices to work in limited-resource and remote regions. Miniaturized biological solar cells (or micro-BSCs) can be the most suitable power source for those lab-on-a-chip applications because the technique resembles the earth's natural ecosystem - living organisms work in conjunction with non-living components of their environment to create a self-assembling and self-maintaining system. Micro-BSCs can continuously generate electricity from microbial photosynthetic and respiratory activities over day-night cycles, offering a clean and renewable power source with self-sustaining potential. However, the promise of this technology has not been translated into practical applications because of its relatively low power (∼nW cm -2 ) and current short lifetimes (∼a couple of hours). In this work, we enabled high-performance, self-sustaining, long-life micro-BSCs by using fundamental breakthroughs of device architectures and electrode materials. A 3-D biocompatible, conductive, and porous anode demonstrated great microbial biofilm formation and a high rate of bacterial extracellular electron transfer, which led to greater power generation. Furthermore, our micro-BSCs promoted gas exchange to the bacteria through a gas-permeable PDMS membrane in a well-controlled, tightly enclosed micro-chamber, substantially enhancing sustainability. Through photosynthetic reactions of the cyanobacteria Synechocystis sp. PCC 6803 without additional organic fuel, the 90 μL single-chambered bio-solar cell generated a maximum power density of 43.8 μW cm -2 and sustained consistent power production of ∼18.6 μW cm -2 during the day and ∼11.4 μW cm -2 at night for 20 days, which is the highest and longest reported success of any existing micro-scale bio-solar cells.

Lab-On-a-Chip for carbon nanotubes based immunoassay detection of Staphylococcal Enterotoxin B (SEB).

PubMed

Yang, Minghui; Sun, Steven; Kostov, Yordan; Rasooly, Avraham

2010-04-21

We describe a new eight channel Lab-On-a-Chip (LOC) for a Carbon Nanotube (CNT) based immunoassay with optical detection of Staphylococcal Enterotoxin B (SEB) for food safety applications. In this work, we combined four biosensing elements: (1) CNT technology for primary antibody immobilization, (2) Enhanced Chemiluminescence (ECL) for light signal generation, (3) a cooled charge-coupled device (CCD) for detection and (4) polymer lamination technology for developing a point of care immunological assay for SEB detection. Our concept for developing versatile LOCs, which can be used for many different applications, is to use a modular design with interchangeable recognition elements (e.g. various antibodies) to determine the specificity. Polymer lamination technology was used for the fabrication of a six layer, syringe operated LOC capable of analyzing eight samples simultaneously. An anti-SEB antibody-nanotube mixture was immobilized onto a polycarbonate strip, to serve as an interchangeable ligand surface that was then bonded onto the LOC. SEB samples are loaded into the device and detected by an ELISA assay using Horse Radish Peroxidase (HRP) conjugated anti-SEB IgG as a secondary antibody and ECL, with detection by a previously described portable cooled CCD detector. Eight samples of SEB in buffer or soy milk were assayed simultaneously with a limit of detection of 0.1 ng mL(-1). CNT immobilization of the antibody increased the sensitivity of detection six fold. Use of a simple interchangeable immunological surface allows this LOC to be adapted to any immunoassay by simply replacing the ligand surface. A syringe was used to move fluids for this assay so no power is needed to operate the device. Our versatile portable point-of-care CCD detector combined with the LOC immunoassay method described here can be used to reduce the exposure of users to toxins and other biohazards when working outside the lab, as well as to simplify and increase sensitivity for many other types of immunological diagnostics and detection assays.

Guided self-assembly of magnetic beads for biomedical applications

NASA Astrophysics Data System (ADS)

Gusenbauer, Markus; Nguyen, Ha; Reichel, Franz; Exl, Lukas; Bance, Simon; Fischbacher, Johann; Özelt, Harald; Kovacs, Alexander; Brandl, Martin; Schrefl, Thomas

2014-02-01

Micromagnetic beads are widely used in biomedical applications for cell separation, drug delivery, and hyperthermia cancer treatment. Here we propose to use self-organized magnetic bead structures which accumulate on fixed magnetic seeding points to isolate circulating tumor cells. The analysis of circulating tumor cells is an emerging tool for cancer biology research and clinical cancer management including the detection, diagnosis and monitoring of cancer. Microfluidic chips for isolating circulating tumor cells use either affinity, size or density capturing methods. We combine multiphysics simulation techniques to understand the microscopic behavior of magnetic beads interacting with soft magnetic accumulation points used in lab-on-chip technologies. Our proposed chip technology offers the possibility to combine affinity and size capturing with special antibody-coated bead arrangements using a magnetic gradient field created by Neodymium Iron Boron permanent magnets. The multiscale simulation environment combines magnetic field computation, fluid dynamics and discrete particle dynamics.

Inkjet Printing of Lanthanide-Organic Frameworks for Anti-Counterfeiting Applications.

PubMed

da Luz, Leonis L; Milani, Raquel; Felix, Jorlandio F; Ribeiro, Igor R B; Talhavini, Márcio; Neto, Brenno A D; Chojnacki, Jaroslaw; Rodrigues, Marcelo O; Júnior, Severino A

2015-12-16

Photoluminescent lanthanide-organic frameworks (Ln-MOFs) were printed onto plastic and paper foils with a conventional inkjet printer. Ln-MOF inks were used to reproduce color images that can only be observed under UV light irradiation. This approach opens a new window for exploring Ln-MOF materials in technological applications, such as optical devices (e.g., lab-on-a-chip), as proof of authenticity for official documents.

Space Science

NASA Image and Video Library

2004-02-01

Labs on chips are manufactured in many shapes and sizes and can be used for numerous applications, from medical tests to water quality monitoring to detecting the signatures of life on other planets. The eight holes on this chip are actually ports that can be filled with fluids or chemicals. Tiny valves control the chemical processes by mixing fluids that move in the tiny channels that look like lines, connecting the ports. Scientists at NASA's Marshall Space Flight Center (MSFC) in Huntsville, Alabama designed this chip to grow biological crystals on the International Space Station. Through this research, they discovered that this technology is ideally suited for solving the challenges of the Vision for Space Exploration. For example, thousands of chips the size of dimes could be loaded on a Martian rover looking for biosignatures of past or present life. Other types of chips could be placed in handheld devices used to monitor microbes in water or to quickly conduct medical tests on astronauts. (NASA/MSFC/D.Stoffer)

Quantitative detection of liver-relevant biomarkers by SERS-immunolabeled gold nanoparticles

NASA Astrophysics Data System (ADS)

Payne, William Mark

Lab-on-a-chip technology has the potential to rapidly change the way experiments are conducted in a variety of fields ranging from medicine to environmental science. Specifically, sensors, detectors, and monitoring devices are increasingly being miniaturized to perform many experiments or measurements on a single chip. In this research, we develop an immunolabeled gold nanoparticle complex capable of detecting liver organoid biomarkers intended for use in a microfluidic device. Human Serum Albumin (HSA) and alpha-Glutathione S-Transferase (alpha-GST) are liver biomarkers that indicate liver health and damage respectively. Herein we demonstrate detection of the liver organoid biomarkers at nanomolar concentrations. Through plasmonic coupling induced by aggregation in the presence of analyte, the SERS signal obtained from the nanoparticles is dramatically increased. Furthermore, detection is demonstrated in a simple fluidic device to show the feasibility of implementing an optimized SERS-immunolabeled nanoparticle for translational application.

Advances in the manufacturing, types, and applications of biosensors

NASA Astrophysics Data System (ADS)

Ravindra, Nuggehalli M.; Prodan, Camelia; Fnu, Shanmugamurthy; Padronl, Ivan; Sikha, Sushil K.

2007-12-01

In recent years, there have been significant technological advancements in the manufacturing, types, and applications of biosensors. Applications include clinical and non-clinical diagnostics for home, bio-defense, bio-remediation, environment, agriculture, and the food industry. Biosensors have progressed beyond the detection of biological threats such as anthrax and are finding use in a number of non-biological applications. Emerging biosensor technologies such as lab-on-a-chip have revolutionized the integration approaches for a very flexible, innovative, and user-friendly platform. An overview of the fundamentals, types, applications, and manufacturers, as well as the market trends of biosensors is presented here. Two case studies are discussed: one focused on a characterization technique—patch clamping and dielectric spectroscopy as a biological sensor—and the other about lithium phthalocyanine, a material that is being developed for in-vivo oxymetry.

Sequential and selective localized optical heating in water via on-chip dielectric nanopatterning.

PubMed

Morsy, Ahmed M; Biswas, Roshni; Povinelli, Michelle L

2017-07-24

We study the use of nanopatterned silicon membranes to obtain optically-induced heating in water. We show that by varying the detuning between an absorptive optical resonance of the patterned membrane and an illumination laser, both the magnitude and response time of the temperature rise can be controlled. This allows for either sequential or selective heating of different patterned areas on chip. We obtain a steady-state temperature of approximately 100 °C for a 805.5nm CW laser power density of 66 µW/μm 2 and observe microbubble formation. The ability to spatially and temporally control temperature on the microscale should enable the study of heat-induced effects in a variety of chemical and biological lab-on-chip applications.

The development of lab-on-a-chip fabricated from two molds

NASA Astrophysics Data System (ADS)

Pramuanjaroenkij, A.; Bunta, J.; Thiangpadung, J.; Sansaradee, S.; Kamsopa, P.; Sodsai, S.; Vichainsan, S.; Wongpanit, K.; Maturos, T.; Lomas, T.; Tuantranont, A.; Cetin, B.; Phankhoksoong, S.; Tongkratoke, A.

2018-01-01

Development of diagnostic technique of microfluidic or lab-on-a-chip (LOCs) is currently of great interest for researchers and inventors for their many advantages. It can be used as a real laboratory was many ways to help to the diagnosis faster. This research aims to develop Polydimethylsiloxane (PDMS) lab-on-a-chip (LOCs) which were produced from different molds; the silicon wafer mold and the stainless mold to investigate the flow of the biological sample as the flow in nanochannels. In addition, this research proposes a means to leakage and the blockage of the channel flow. The experimental results were found that the LOCs casted from the silicon wafer mold sandwiched by both the plasma cleaner machine and H shaped acrylic sheets showed leakages around the electrode areas because the first new electrodes were too thick, the proper thickness of the nickel electrode was at 0.05 millimeters. The LOCs casted from the stainless mold were inserted by the nickel electrodes produced by the from the prototype shaped electroplating process; this LOCs using nickel plated electrodes 2 times to make a groove on the nickel electrode backsides when pouring the PDMS into the LOCs casted from the stainless mold. It was found that PDMS was able to flow under the nickel electrode and the PDMS sheet could stick with the glass slide smoothly. In conclusion, it was possible to develop these LOC designs and new electrode fabrications continually under helps from Micro-Electro-Mechanical system, Thailand National Electronics and Computer Technology Center, since causes of the LOC problems were found, and demonstrated the feasibility of developing the LOCs for chemical detection and disease diagnostics.

CMOS capacitive biosensors for highly sensitive biosensing applications.

PubMed

Chang, An-Yu; Lu, Michael S-C

2013-01-01

Magnetic microbeads are widely used in biotechnology and biomedical research for manipulation and detection of cells and biomolecules. Most lab-on-chip systems capable of performing manipulation and detection require external instruments to perform one of the functions, leading to increased size and cost. This work aims at developing an integrated platform to perform these two functions by implementing electromagnetic microcoils and capacitive biosensors on a CMOS (complementary metal oxide semiconductor) chip. Compared to most magnetic-type sensors, our detection method requires no externally applied magnetic fields and the associated fabrication is less complicated. In our experiment, microbeads coated with streptavidin were driven to the sensors located in the center of microcoils with functionalized anti-streptavidin antibody. Detection of a single microbead was successfully demonstrated using a capacitance-to-frequency readout. The average capacitance changes for the experimental and control groups were -5.3 fF and -0.2 fF, respectively.

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

PubMed

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

2018-06-05

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

Optimized acoustic biochip integrated with microfluidics for biomarkers detection in molecular diagnostics.

PubMed

Papadakis, G; Friedt, J M; Eck, M; Rabus, D; Jobst, G; Gizeli, E

2017-09-01

The development of integrated platforms incorporating an acoustic device as the detection element requires addressing simultaneously several challenges of technological and scientific nature. The present work was focused on the design of a microfluidic module, which, combined with a dual or array type Love wave acoustic chip could be applied to biomedical applications and molecular diagnostics. Based on a systematic study we optimized the mechanics of the flow cell attachment and the sealing material so that fluidic interfacing/encapsulation would impose minimal losses to the acoustic wave. We have also investigated combinations of operating frequencies with waveguide materials and thicknesses for maximum sensitivity during the detection of protein and DNA biomarkers. Within our investigations neutravidin was used as a model protein biomarker and unpurified PCR amplified Salmonella DNA as the model genetic target. Our results clearly indicate the need for experimental verification of the optimum engineering and analytical parameters, in order to develop commercially viable systems for integrated analysis. The good reproducibility of the signal together with the ability of the array biochip to detect multiple samples hold promise for the future use of the integrated system in a Lab-on-a-Chip platform for application to molecular diagnostics.

3D printed high density, reversible, chip-to-chip microfluidic interconnects.

PubMed

Gong, Hua; Woolley, Adam T; Nordin, Gregory P

2018-02-13

Our latest developments in miniaturizing 3D printed microfluidics [Gong et al., Lab Chip, 2016, 16, 2450; Gong et al., Lab Chip, 2017, 17, 2899] offer the opportunity to fabricate highly integrated chips that measure only a few mm on a side. For such small chips, an interconnection method is needed to provide the necessary world-to-chip reagent and pneumatic connections. In this paper, we introduce simple integrated microgaskets (SIMs) and controlled-compression integrated microgaskets (CCIMs) to connect a small device chip to a larger interface chip that implements world-to-chip connections. SIMs or CCIMs are directly 3D printed as part of the device chip, and therefore no additional materials or components are required to make the connection to the larger 3D printed interface chip. We demonstrate 121 chip-to-chip interconnections in an 11 × 11 array for both SIMs and CCIMs with an areal density of 53 interconnections per mm 2 and show that they withstand fluid pressures of 50 psi. We further demonstrate their reusability by testing the devices 100 times without seal failure. Scaling experiments show that 20 × 20 interconnection arrays are feasible and that the CCIM areal density can be increased to 88 interconnections per mm 2 . We then show the utility of spatially distributed discrete CCIMs by using an interconnection chip with 28 chip-to-world interconnects to test 45 3D printed valves in a 9 × 5 array. Each valve is only 300 μm in diameter (the smallest yet reported for 3D printed valves). Every row of 5 valves is tested to at least 10 000 actuations, with one row tested to 1 000 000 actuations. In all cases, there is no sign of valve failure, and the CCIM interconnections prove an effective means of using a single interface chip to test a series of valve array chips.

Validation and perspectives of a femtosecond laser fabricated monolithic optical stretcher

PubMed Central

Bellini, Nicola; Bragheri, Francesca; Cristiani, Ilaria; Guck, Jochen; Osellame, Roberto; Whyte, Graeme

2012-01-01

The combination of high power laser beams with microfluidic delivery of cells is at the heart of high-throughput, single-cell analysis and disease diagnosis with an optical stretcher. So far, the challenges arising from this combination have been addressed by externally aligning optical fibres with microfluidic glass capillaries, which has a limited potential for integration into lab-on-a-chip environments. Here we demonstrate the successful production and use of a monolithic glass chip for optical stretching of white blood cells, featuring microfluidic channels and optical waveguides directly written into bulk glass by femtosecond laser pulses. The performance of this novel chip is compared to the standard capillary configuration. The robustness, durability and potential for intricate flow patterns provided by this monolithic optical stretcher chip suggest its use for future diagnostic and biotechnological applications. PMID:23082304

System-on-Chip Considerations for Heterogeneous Integration of CMOS and Fluidic Bio-Interfaces.

PubMed

Datta-Chaudhuri, Timir; Smela, Elisabeth; Abshire, Pamela A

2016-12-01

CMOS chips are increasingly used for direct sensing and interfacing with fluidic and biological systems. While many biosensing systems have successfully combined CMOS chips for readout and signal processing with passive sensing arrays, systems that co-locate sensing with active circuits on a single chip offer significant advantages in size and performance but increase the complexity of multi-domain design and heterogeneous integration. This emerging class of lab-on-CMOS systems also poses distinct and vexing technical challenges that arise from the disparate requirements of biosensors and integrated circuits (ICs). Modeling these systems must address not only circuit design, but also the behavior of biological components on the surface of the IC and any physical structures. Existing tools do not support the cross-domain simulation of heterogeneous lab-on-CMOS systems, so we recommend a two-step modeling approach: using circuit simulation to inform physics-based simulation, and vice versa. We review the primary lab-on-CMOS implementation challenges and discuss practical approaches to overcome them. Issues include new versions of classical challenges in system-on-chip integration, such as thermal effects, floor-planning, and signal coupling, as well as new challenges that are specifically attributable to biological and fluidic domains, such as electrochemical effects, non-standard packaging, surface treatments, sterilization, microfabrication of surface structures, and microfluidic integration. We describe these concerns as they arise in lab-on-CMOS systems and discuss solutions that have been experimentally demonstrated.

Lithographic microfabrication of biocompatible polymers for tissue engineering and lab-on-a-chip applications

NASA Astrophysics Data System (ADS)

Balciunas, Evaldas; Jonusauskas, Linas; Valuckas, Vytautas; Baltriukiene, Daiva; Bukelskiene, Virginija; Gadonas, Roaldas; Malinauskas, Mangirdas

2012-06-01

In this work, a combination of Direct Laser Writing (DLW), PoliDiMethylSiloxane (PDMS) soft lithography and UV lithography was used to create cm- scale microstructured polymer scaolds for cell culture experiments out of dierent biocompatible materials: novel hybrid organic-inorganic SZ2080, PDMS elastomer, biodegradable PEG- DA-258 and SU-8. Rabbit muscle-derived stem cells were seeded on the fabricated dierent periodicity scaolds to evaluate if the relief surface had any eect on cell proliferation. An array of microlenses was fabricated using DLW out of SZ2080 and replicated in PDMS and PEG-DA-258, showing good potential applicability of the used techniques in many other elds like micro- and nano- uidics, photonics, and MicroElectroMechanical Systems (MEMS). The synergetic employment of three dierent fabrication techniques allowed to produce desired objects with low cost, high throughput and precision as well as use materials that are dicult to process by other means (PDMS and PEG-DA-258). DLW is a relatively slow fabrication method, since the object has to be written point-by-point. By applying PDMS soft lithography, we were enabled to replicate laser-fabricated scaolds for stem cell growth and micro-optical elements for lab-on-a-chip applications with high speed, low cost and good reproducible quality.

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.

Electroosmotic pumps for microflow analysis

PubMed Central

Wang, Xiayan; Wang, Shili; Gendhar, Brina; Cheng, Chang; Byun, Chang Kyu; Li, Guanbin; Zhao, Meiping; Liu, Shaorong

2009-01-01

With rapid development in microflow analysis, electroosmotic pumps are receiving increasing attention. Compared to other micropumps, electroosmotic pumps have several unique features. For example, they are bi-directional, can generate constant and pulse-free flows with flow rates well suited to microanalytical systems, and can be readily integrated with lab-on-chip devices. The magnitude and the direction of flow of an electroosmotic pump can be changed instantly. In addition, electroosmotic pumps have no moving parts. In this article, we discuss common features, introduce fabrication technologies and highlight applications of electroosmotic pumps. PMID:20047021

Well Monitoring System For EGS

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

Normann, Randy; Glowka, Dave; Normann, Charles

This grant is a collection of projects designed to move aircraft high temperature electronics technology into the geothermal industry. Randy Normann is the lead. He licensed the HT83SNL00 chip from Sandia National Labs. This chip enables aircraft developed electronics for work within a geothermal well logging tool. However, additional elements are needed to achieve commercially successful logging tools. These elements are offered by a strong list of industrial partners on this grant as: Electrochemical Systems Inc. for HT Rechargeable Batteries, Frequency Management Systems for 300C digital clock, Sandia National Labs for experts in high temperature solder, Honeywell Solid-State Electronics Centermore » for reprogrammable high temperature memory. During the course of this project MagiQ Technologies for high temperature fiber optics.« less

Fluid Mechanics and Homeland Security

NASA Astrophysics Data System (ADS)

Settles, Gary S.

2006-01-01

Homeland security involves many applications of fluid mechanics and offers many opportunities for research and development. This review explores a wide selection of fluids topics in counterterrorism and suggests future directions. Broad topics range from preparedness and deterrence of impending terrorist attacks to detection, response, and recovery. Specific topics include aircraft hardening, blast mitigation, sensors and sampling, explosive detection, microfluidics and labs-on-a-chip, chemical plume dispersal in urban settings, and building ventilation. Also discussed are vapor plumes and standoff detection, nonlethal weapons, airborne disease spread, personal protective equipment, and decontamination. Involvement in these applications requires fluid dynamicists to think across the traditional boundaries of the field and to work with related disciplines, especially chemistry, biology, aerosol science, and atmospheric science.

Design, Fabrication and Characterization of an In Silico Cell Physiology lab for Bio Sensing Applications

NASA Astrophysics Data System (ADS)

Haque, A. ul; Rokkam, M.; DeCarlo, A. R.; Wereley, S. T.; Wells, H. W.; McLamb, W. T.; Roux, S. J.; Irazoqui, P. P.; Porterfield, D. M.

2006-04-01

In this paper, we report the design, fabrication and characterization of an In Silico cell physiology biochip for measuring Ca2+ ion concentrations and currents around single cells. This device has been designed around specific science objectives of measuring real time multidimensional calcium flux patterns around sixteen Ceratopteris richardii fern spores in microgravity flight experiments and ground studies. The sixteen microfluidic cell holding pores are 150 by 150 µm each and have 4 Ag/AgCl electrodes leading into them. An SU-8 structural layer is used for insulation and packaging purposes. The In Silico cell physiology lab is wire bonded on to a custom PCB for easy interface with a state of the art data acquisition system. The electrodes are coated with a Ca2+ ion selective membrane based on ETH-5234 ionophore and operated against an Ag/AgCl reference electrode. Initial characterization results have shown Nernst slopes of 30mv/decade that were stable over a number of measurement cycles. While this work is focused on technology to enable basic research on the Ceratopteris richardii spores, we anticipate that this type of cell physiology lab-on-a-chip will be broadly applied in biomedical and pharmacological research by making minor modifications to the electrode material and the measurement technique. Future applications include detection of glucose, hormones such as plant auxin, as well as multiple analyte detection on the same chip.

LABONFOIL: investigations regarding microfluidic skin patches for drug detection using flexible OLEDs

NASA Astrophysics Data System (ADS)

Scholles, M.; Kroker, L.; Vogel, U.; Krüger, J.; Walczak, R.; Ruano-Lopez, J.

2010-02-01

This contribution describes first results concerning the overall and especially optical system design of microfluidic skin patches for drug detection based on fluorescence analysis of sweat samples. This work has been carried out within the European project LABONFOIL which aims to develop low-cost lab-on-chip systems for four different applications, one of them for the detection of cocaine abuse by professional drivers. To date work has focused on the integrated design of the skin patch itself including methods for sweat collection as well as studies concerning the feasibility of OLEDs for optical excitation of the fluorescence signal.

Optofluidic-Tunable Color Filters And Spectroscopy Based On Liquid-Crystal Microflows

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

Cuennet, J. G.; Vasdekis, Andreas E.; Psaltis, D.

The integration of color filters with microfluidics has attracted substantial attention in recent years, for on-chip absorption, fluorescence, or Raman analysis. We describe such tunable filters based on the micro-flow of liquid crystals. The filter operation is based on the wavelength dependent liquid crystal birefringence that can be tuned by modifying the flow velocity field in the microchannel. The latter is possible both temporally and spatially by varying the inlet pressure and the channel geometry respectively. We explored the use of these optofluidic filters for on-chip absorption spectroscopy; by integrating the distance dependent color filter with a dye-filled micro-channel, themore » absorption spectrum of a dye could be measured. Liquid crystal microflows simplify substantially the optofluidic integration, actuation and tuning of color filters for lab-on-a-chip spectroscopic applications.« less

Photonic crystal fibres in biomedical investigations

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

Skibina, Yu S; Tuchin, Valerii V; Beloglazov, V I

2011-04-30

The state of the art in the field of design and study of photonic crystal fibres for biomedical applications is considered and some original results recently obtained by the authors are presented. Optical properties of the fibres that offer prospects of their wide application as biological sensors, 'labs-on-a-chip', and facilities of electromagnetic radiation control in a wide range of wavelengths aimed at designing novel biomedical instrumentation are considered (optical technologies in biophysics and medicine)

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.

A brief review on microfluidic platforms for hormones detection.

PubMed

Ozhikandathil, Jayan; Badilescu, Simona; Packirisamy, Muthukumaran

2017-01-01

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

Helicase dependent OnChip-amplification and its use in multiplex pathogen detection.

PubMed

Andresen, Dennie; von Nickisch-Rosenegk, Markus; Bier, Frank F

2009-05-01

The need for fast, specific and sensitive multiparametric detection methods is an ever growing demand in molecular diagnostics. Here we report on a newly developed method, the helicase dependent OnChip amplification (OnChip-HDA). This approach integrates the analysis and detection in one single reaction thus leading to time and cost savings in multiparametric analysis. HDA is an isothermal amplification method that is not depending on thermocycling as known from PCR due to the helicases' ability to unwind DNA double-strands. We have combined the HDA with microarray based detection, making it suitable for multiplex detection. As an example we used the OnChip HDA in single and multiplex amplifications for the detection of the two pathogens N. gonorrhoeae and S. aureus directly on surface bound primers. We have successfully shown the OnChip-HDA and applied it for single- and duplex-detection of the pathogens N. gonorrhoeae and S. aureus. We have developed a new method, the OnChip-HDA for the multiplex detection of pathogens. Its simplicity in reaction setup and potential for miniaturization and multiparametric analysis is advantageous for the integration in miniaturized Lab on Chip systems, e.g. needed in point of care diagnostics.

Characterization of aqueous two phase systems by combining lab-on-a-chip technology with robotic liquid handling stations.

PubMed

Amrhein, Sven; Schwab, Marie-Luise; Hoffmann, Marc; Hubbuch, Jürgen

2014-11-07

Over the last decade, the use of design of experiment approaches in combination with fully automated high throughput (HTP) compatible screenings supported by robotic liquid handling stations (LHS), adequate fast analytics and data processing has been developed in the biopharmaceutical industry into a strategy of high throughput process development (HTPD) resulting in lower experimental effort, sample reduction and an overall higher degree of process optimization. Apart from HTP technologies, lab-on-a-chip technology has experienced an enormous growth in the last years and allows further reduction of sample consumption. A combination of LHS and lab-on-a-chip technology is highly desirable and realized in the present work to characterize aqueous two phase systems with respect to tie lines. In particular, a new high throughput compatible approach for the characterization of aqueous two phase systems regarding tie lines by exploiting differences in phase densities is presented. Densities were measured by a standalone micro fluidic liquid density sensor, which was integrated into a liquid handling station by means of a developed generic Tip2World interface. This combination of liquid handling stations and lab-on-a-chip technology enables fast, fully automated, and highly accurate density measurements. The presented approach was used to determine the phase diagram of ATPSs composed of potassium phosphate (pH 7) and polyethylene glycol (PEG) with a molecular weight of 300, 400, 600 and 1000 Da respectively in the presence and in the absence of 3% (w/w) sodium chloride. Considering the whole ATPS characterization process, two complete ATPSs could be characterized within 24h, including four runs per ATPS for binodal curve determination (less than 45 min/run), and tie line determination (less than 45 min/run for ATPS preparation and 8h for density determination), which can be performed fully automated over night without requiring man power. The presented methodology provides a cost, time and material effective approach for characterization of ATPS phase diagram on base on highly accurate and comprehensive data. By this means the derived data opens the door for a more detailed description of ATPS towards generating mechanistic based models, since molecular approaches such as MD simulations or molecular descriptions along the line of QSAR heavily rely on accurate and comprehensive data. Copyright © 2014 Elsevier B.V. All rights reserved.

Chip morphology as a performance predictor during high speed end milling of soda lime glass

NASA Astrophysics Data System (ADS)

Bagum, M. N.; Konneh, M.; Abdullah, K. A.; Ali, M. Y.

2018-01-01

Soda lime glass has application in DNA arrays and lab on chip manufacturing. Although investigation revealed that machining of such brittle material is possible using ductile mode under controlled cutting parameters and tool geometry, it remains a challenging task. Furthermore, ability of ductile machining is usually assed through machined surface texture examination. Soda lime glass is a strain rate and temperature sensitive material. Hence, influence on attainment of ductile surface due to adiabatic heat generated during high speed end milling using uncoated tungsten carbide tool is investigated in this research. Experimental runs were designed using central composite design (CCD), taking spindle speed, feed rate and depth of cut as input variable and tool-chip contact point temperature (Ttc) and the surface roughness (Rt) as responses. Along with machined surface texture, Rt and chip morphology was examined to assess machinability of soda lime glass. The relation between Ttc and chip morphology was examined. Investigation showed that around glass transition temperature (Tg) ductile chip produced and subsequently clean and ductile final machined surface produced.

A Conductometric Indium Oxide Semiconducting Nanoparticle Enzymatic Biosensor Array

PubMed Central

Lee, Dongjin; Ondrake, Janet; Cui, Tianhong

2011-01-01

We report a conductometric nanoparticle biosensor array to address the significant variation of electrical property in nanomaterial biosensors due to the random network nature of nanoparticle thin-film. Indium oxide and silica nanoparticles (SNP) are assembled selectively on the multi-site channel area of the resistors using layer-by-layer self-assembly. To demonstrate enzymatic biosensing capability, glucose oxidase is immobilized on the SNP layer for glucose detection. The packaged sensor chip onto a ceramic pin grid array is tested using syringe pump driven feed and multi-channel I–V measurement system. It is successfully demonstrated that glucose is detected in many different sensing sites within a chip, leading to concentration dependent currents. The sensitivity has been found to be dependent on the channel length of the resistor, 4–12 nA/mM for channel lengths of 5–20 μm, while the apparent Michaelis-Menten constant is 20 mM. By using sensor array, analytical data could be obtained with a single step of sample solution feeding. This work sheds light on the applicability of the developed nanoparticle microsensor array to multi-analyte sensors, novel bioassay platforms, and sensing components in a lab-on-a-chip. PMID:22163696

Electroosmotic pumps and their applications in microfluidic systems

PubMed Central

Wang, Xiayan; Cheng, Chang; Wang, Shili; Liu, Shaorong

2009-01-01

Electroosmotic pumping is receiving increasing attention in recent years owing to the rapid development in micro total analytical systems. Compared with other micropumps, electroosmotic pumps (EOPs) offer a number of advantages such as creation of constant pulse-free flows and elimination of moving parts. The flow rates and pumping pressures of EOPs matches well with micro analysis systems. The common materials and fabrication technologies make it readily integrateable with lab-on-a-chip devices. This paper reviews the recent progress on EOP fabrications and applications in order to promote the awareness of EOPs to researchers interested in using micro- and nano-fluidic devices. The pros and cons of EOPs are also discussed, which helps these researchers in designing and constructing their micro platforms. PMID:20126306

Nanophotonic trapping for precise manipulation of biomolecular arrays.

PubMed

Soltani, Mohammad; Lin, Jun; Forties, Robert A; Inman, James T; Saraf, Summer N; Fulbright, Robert M; Lipson, Michal; Wang, Michelle D

2014-06-01

Optical trapping is a powerful manipulation and measurement technique widely used in the biological and materials sciences. Miniaturizing optical trap instruments onto optofluidic platforms holds promise for high-throughput lab-on-a-chip applications. However, a persistent challenge with existing optofluidic devices has been achieving controlled and precise manipulation of trapped particles. Here, we report a new class of on-chip optical trapping devices. Using photonic interference functionalities, an array of stable, three-dimensional on-chip optical traps is formed at the antinodes of a standing-wave evanescent field on a nanophotonic waveguide. By employing the thermo-optic effect via integrated electric microheaters, the traps can be repositioned at high speed (∼30 kHz) with nanometre precision. We demonstrate sorting and manipulation of individual DNA molecules. In conjunction with laminar flows and fluorescence, we also show precise control of the chemical environment of a sample with simultaneous monitoring. Such a controllable trapping device has the potential to achieve high-throughput precision measurements on chip.

Fish species identification using PCR-RFLP analysis and lab-on-a-chip capillary electrophoresis: application to detect white fish species in food products and an interlaboratory study.

PubMed

Dooley, John J; Sage, Helen D; Clarke, Marie-Anne L; Brown, Helen M; Garrett, Stephen D

2005-05-04

Identification of 10 white fish species associated with U.K. food products was achieved using PCR-RFLP of the mitochondrial cytochrome b gene. Use of lab-on-a-chip capillary electrophoresis for end-point analysis enabled accurate sizing of DNA fragments and identification of fish species at a level of 5% (w/w) in a fish admixture. One restriction enzyme, DdeI, allowed discrimination of eight species. When combined with NlaIII and HaeIII, specific profiles for all 10 species were generated. The method was applied to a range of products and subjected to an interlaboratory study carried out by five U.K. food control laboratories. One hundred percent correct identification of single species samples and six of nine admixture samples was achieved by all laboratories. The results indicated that fish species identification could be carried out using a database of PCR-RFLP profiles without the need for reference materials.

Semi-contact-writing of polymer molds for prototyping PDMS chips with low surface roughness, sharp edges and locally varying channel heights

NASA Astrophysics Data System (ADS)

Gutzweiler, Ludwig; Stumpf, Fabian; Tanguy, Laurent; Roth, Guenter; Koltay, Peter; Zengerle, Roland; Riegger, Lutz

2016-04-01

Microfluidic systems fabricated in polydimethylsiloxane (PDMS) enable a broad variety of applications and are widespread in the field of Lab-on-a-Chip. Here we demonstrate semi-contact-writing, a novel method for fabrication of polymer based molds for casting microfluidic PDMS chips in a highly flexible, time and cost-efficient manner. The method is related to direct-writing of an aqueous polymer solution on a planar glass substrate and substitutes conventional, time- and cost-consuming UV-lithography. This technique facilitates on-demand prototyping in a low-cost manner and is therefore ideally suited for rapid chip layout iterations. No cleanroom facilities and less expertise are required. Fabrication time from scratch to ready-to-use PDMS-chip is less than 5 h. This polymer writing method enables structure widths down to 140 μm and controllable structure heights ranging from 5.5 μm for writing single layers up to 98 μm by stacking. As a unique property, freely selectable height variations across a substrate can be achieved by application of local stacking. Furthermore, the molds exhibit low surface roughness (R a   =  24 nm, R RMS  =  28 nm) and high fidelity edge sharpness. We validated the method by fabrication of molds to cast PDMS chips for droplet based flow-through PCR with single-cell sensitivity.

Nanophotonic Trapping for Precise Manipulation of Biomolecular Arrays

PubMed Central

Soltani, Mohammad; Lin, Jun; Forties, Robert A.; Inman, James T.; Saraf, Summer N.; Fulbright, Robert M.; Lipson, Michal; Wang, Michelle D.

2014-01-01

Optical trapping is a powerful manipulation and measurement technique widely employed in the biological and materials sciences1–8. Miniaturizing optical trap instruments onto optofluidic platforms holds promise for high throughput lab-on-chip applications9–16. However, a persistent challenge with existing optofluidic devices has been controlled and precise manipulation of trapped particles. Here we report a new class of on-chip optical trapping devices. Using photonic interference functionalities, an array of stable, three-dimensional on-chip optical traps is formed at the antinodes of a standing-wave evanescent field on a nanophotonic waveguide. By employing the thermo-optic effect via integrated electric microheaters, the traps can be repositioned at high speed (~ 30 kHz) with nanometer precision. We demonstrate sorting and manipulation of individual DNA molecules. In conjunction with laminar flows and fluorescence, we also show precise control of the chemical environment of a sample with simultaneous monitoring. Such a controllable trapping device has the potential for high-throughput precision measurements on chip. PMID:24776649

Miniaturized devices towards an integrated lab-on-a-chip platform for DNA diagnostics

NASA Astrophysics Data System (ADS)

Kaprou, G.; Papadakis, G.; Kokkoris, G.; Papadopoulos, V.; Kefala, I.; Papageorgiou, D.; Gizeli, E.; Tserepi, A.

2015-06-01

Microfluidics is an emerging technology enabling the development of Lab-on-a-chip (LOC) systems for clinical diagnostics, drug discovery and screening, food safety and environmental analysis. LOC systems integrate and scale down one or several laboratory functions on a single chip of a few mm2 to cm2 in size, and account for many advantages on biochemical analyses, such as low sample and reagent consumption, low cost, reduced analysis time, portability and point-of-need compatibility. Currently, available nucleic acid diagnostic tests take advantage of Polymerase Chain Reaction (PCR) that allows exponential amplification of portions of nucleic acid sequences that can be used as indicators for the identification of various diseases. Here, we present a comparison between static chamber and continuous flow miniaturized PCR devices, in terms of energy consumption for devices fabricated on the same material stack, with identical sample volume and channel dimensions. The comparison is implemented by a computational study coupling heat transfer in both solid and fluid, mass conservation of species, and joule heating. Based on the conclusions of this study, we develop low-cost and fast DNA amplification devices for both PCR and isothermal amplification, and we implement them in the detection of mutations related to breast cancer. The devices are fabricated by mass production amenable technologies on printed circuit board (PCB) substrates, where copper facilitates the incorporation of on-chip microheaters, defining the thermal zones necessary for PCR or isothermal amplification methods.

Thin Film Differential Photosensor for Reduction of Temperature Effects in Lab-on-Chip Applications.

PubMed

de Cesare, Giampiero; Carpentiero, Matteo; Nascetti, Augusto; Caputo, Domenico

2016-02-20

This paper presents a thin film structure suitable for low-level radiation measurements in lab-on-chip systems that are subject to thermal treatments of the analyte and/or to large temperature variations. The device is the series connection of two amorphous silicon/amorphous silicon carbide heterojunctions designed to perform differential current measurements. The two diodes experience the same temperature, while only one is exposed to the incident radiation. Under these conditions, temperature and light are the common and differential mode signals, respectively. A proper electrical connection reads the differential current of the two diodes (ideally the photocurrent) as the output signal. The experimental characterization shows the benefits of the differential structure in minimizing the temperature effects with respect to a single diode operation. In particular, when the temperature varies from 23 to 50 °C, the proposed device shows a common mode rejection ratio up to 24 dB and reduces of a factor of three the error in detecting very low-intensity light signals.

Thin Film Differential Photosensor for Reduction of Temperature Effects in Lab-on-Chip Applications

PubMed Central

de Cesare, Giampiero; Carpentiero, Matteo; Nascetti, Augusto; Caputo, Domenico

2016-01-01

This paper presents a thin film structure suitable for low-level radiation measurements in lab-on-chip systems that are subject to thermal treatments of the analyte and/or to large temperature variations. The device is the series connection of two amorphous silicon/amorphous silicon carbide heterojunctions designed to perform differential current measurements. The two diodes experience the same temperature, while only one is exposed to the incident radiation. Under these conditions, temperature and light are the common and differential mode signals, respectively. A proper electrical connection reads the differential current of the two diodes (ideally the photocurrent) as the output signal. The experimental characterization shows the benefits of the differential structure in minimizing the temperature effects with respect to a single diode operation. In particular, when the temperature varies from 23 to 50 °C, the proposed device shows a common mode rejection ratio up to 24 dB and reduces of a factor of three the error in detecting very low-intensity light signals. PMID:26907292

Detection of alprazolam with a lab on paper economical device integrated with urchin like Ag@ Pd shell nano-hybrids.

PubMed

Narang, Jagriti; Malhotra, Nitesh; Singhal, Chaitali; Mathur, Ashish; Pn, Anoop Krishna; Pundir, C S

2017-11-01

We present results of the studies relating to fabrication of a microfluidic biosensor chip based on urchin like Ag@ Pd shell nano-hybrids that is capable of sensing alprazolam through electrochemical detection. Using this chip we demonstrate, with high reliability and in a time efficient manner, the detection of alprazolam present in buffer solutions at clinically relevant concentrations. Methylene blue (MB) was also doped as redox transition substance for sensing alprazolam. Nano-hybrids modified EμPAD showed wide linear range 1-300ng/ml and low detection limit of 0.025ng/l. Low detection limit can further enhance its suitability for forensic application. Nano-hybrids modified EμPAD was also employed for determination of drug in real samples such as human urine. Reported facile lab paper approach integrated with urchin like Ag@ Pd shell nano-hybrids could be well applied for the determination of serum metabolites. Copyright © 2016 Elsevier B.V. All rights reserved.

Flexible plastic, paper and textile lab-on-a chip platforms for electrochemical biosensing.

PubMed

Economou, Anastasios; Kokkinos, Christos; Prodromidis, Mamas

2018-06-26

Flexible biosensors represent an increasingly important and rapidly developing field of research. Flexible materials offer several advantages as supports of biosensing platforms in terms of flexibility, weight, conformability, portability, cost, disposability and scope for integration. On the other hand, electrochemical detection is perfectly suited to flexible biosensing devices. The present paper reviews the field of integrated electrochemical bionsensors fabricated on flexible materials (plastic, paper and textiles) which are used as functional base substrates. The vast majority of electrochemical flexible lab-on-a-chip (LOC) biosensing devices are based on plastic supports in a single or layered configuration. Among these, wearable devices are perhaps the ones that most vividly demonstrate the utility of the concept of flexible biosensors while diagnostic cards represent the state-of-the art in terms of integration and functionality. Another important type of flexible biosensors utilize paper as a functional support material enabling the fabrication of low-cost and disposable paper-based devices operating on the lateral flow, drop-casting or folding (origami) principles. Finally, textile-based biosensors are beginning to emerge enabling real-time measurements in the working environment or in wound care applications. This review is timely due to the significant advances that have taken place over the last few years in the area of LOC biosensors and aims to direct the readers to emerging trends in this field.

Digital Microfluidics Sample Analyzer

NASA Technical Reports Server (NTRS)

Pollack, Michael G.; Srinivasan, Vijay; Eckhardt, Allen; Paik, Philip Y.; Sudarsan, Arjun; Shenderov, Alex; Hua, Zhishan; Pamula, Vamsee K.

2010-01-01

Three innovations address the needs of the medical world with regard to microfluidic manipulation and testing of physiological samples in ways that can benefit point-of-care needs for patients such as premature infants, for which drawing of blood for continuous tests can be life-threatening in their own right, and for expedited results. A chip with sample injection elements, reservoirs (and waste), droplet formation structures, fluidic pathways, mixing areas, and optical detection sites, was fabricated to test the various components of the microfluidic platform, both individually and in integrated fashion. The droplet control system permits a user to control droplet microactuator system functions, such as droplet operations and detector operations. Also, the programming system allows a user to develop software routines for controlling droplet microactuator system functions, such as droplet operations and detector operations. A chip is incorporated into the system with a controller, a detector, input and output devices, and software. A novel filler fluid formulation is used for the transport of droplets with high protein concentrations. Novel assemblies for detection of photons from an on-chip droplet are present, as well as novel systems for conducting various assays, such as immunoassays and PCR (polymerase chain reaction). The lab-on-a-chip (a.k.a., lab-on-a-printed-circuit board) processes physiological samples and comprises a system for automated, multi-analyte measurements using sub-microliter samples of human serum. The invention also relates to a diagnostic chip and system including the chip that performs many of the routine operations of a central labbased chemistry analyzer, integrating, for example, colorimetric assays (e.g., for proteins), chemiluminescence/fluorescence assays (e.g., for enzymes, electrolytes, and gases), and/or conductometric assays (e.g., for hematocrit on plasma and whole blood) on a single chip platform.

A 3D Microfluidic Chip for Electrochemical Detection of Hydrolysed Nucleic Bases by a Modified Glassy Carbon Electrode

PubMed Central

Vlachova, Jana; Tmejova, Katerina; Kopel, Pavel; Korabik, Maria; Zitka, Jan; Hynek, David; Kynicky, Jindrich; Adam, Vojtech; Kizek, Rene

2015-01-01

Modification of carbon materials, especially graphene-based materials, has wide applications in electrochemical detection such as electrochemical lab-on-chip devices. A glassy carbon electrode (GCE) modified with chemically alternated graphene oxide was used as a working electrode (glassy carbon modified by graphene oxide with sulphur containing compounds and Nafion) for detection of nucleobases in hydrolysed samples (HCl pH = 2.9, 100 °C, 1 h, neutralization by NaOH). It was found out that modification, especially with trithiocyanuric acid, increased the sensitivity of detection in comparison with pure GCE. All processes were finally implemented in a microfluidic chip formed with a 3D printer by fused deposition modelling technology. As a material for chip fabrication, acrylonitrile butadiene styrene was chosen because of its mechanical and chemical stability. The chip contained the one chamber for the hydrolysis of the nucleic acid and another for the electrochemical detection by the modified GCE. This chamber was fabricated to allow for replacement of the GCE. PMID:25621613

A 3D microfluidic chip for electrochemical detection of hydrolysed nucleic bases by a modified glassy carbon electrode.

PubMed

Vlachova, Jana; Tmejova, Katerina; Kopel, Pavel; Korabik, Maria; Zitka, Jan; Hynek, David; Kynicky, Jindrich; Adam, Vojtech; Kizek, Rene

2015-01-22

Modification of carbon materials, especially graphene-based materials, has wide applications in electrochemical detection such as electrochemical lab-on-chip devices. A glassy carbon electrode (GCE) modified with chemically alternated graphene oxide was used as a working electrode (glassy carbon modified by graphene oxide with sulphur containing compounds and Nafion) for detection of nucleobases in hydrolysed samples (HCl pH = 2.9, 100 °C, 1 h, neutralization by NaOH). It was found out that modification, especially with trithiocyanuric acid, increased the sensitivity of detection in comparison with pure GCE. All processes were finally implemented in a microfluidic chip formed with a 3D printer by fused deposition modelling technology. As a material for chip fabrication, acrylonitrile butadiene styrene was chosen because of its mechanical and chemical stability. The chip contained the one chamber for the hydrolysis of the nucleic acid and another for the electrochemical detection by the modified GCE. This chamber was fabricated to allow for replacement of the GCE.

Small-scale heat detection using catalytic microengines irradiated by laser

NASA Astrophysics Data System (ADS)

Liu, Zhaoqian; Li, Jinxing; Wang, Jiao; Huang, Gaoshan; Liu, Ran; Mei, Yongfeng

2013-01-01

We demonstrate a novel approach to modulating the motion speed of catalytic microtubular engines via laser irradiation/heating with regard to small-scale heat detection. Laser irradiation on the engines leads to a thermal heating effect and thus enhances the engine speed. During a laser on/off period, the motion behaviour of a microengine can be repeatable and reversible, demonstrating a regulation of motion speeds triggered by laser illumination. Also, the engine velocity exhibits a linear dependence on laser power in various fuel concentrations, which implies an application potential as local heat sensors. Our work may hold great promise in applications such as lab on a chip, micro/nano factories, and environmental detection.We demonstrate a novel approach to modulating the motion speed of catalytic microtubular engines via laser irradiation/heating with regard to small-scale heat detection. Laser irradiation on the engines leads to a thermal heating effect and thus enhances the engine speed. During a laser on/off period, the motion behaviour of a microengine can be repeatable and reversible, demonstrating a regulation of motion speeds triggered by laser illumination. Also, the engine velocity exhibits a linear dependence on laser power in various fuel concentrations, which implies an application potential as local heat sensors. Our work may hold great promise in applications such as lab on a chip, micro/nano factories, and environmental detection. Electronic supplementary information (ESI) available. See DOI: 10.1039/c2nr32494f

Expanding the horizons for single-cell applications on lab-on-a-chip devices.

PubMed

Kim, Soo Hyeon; Fourmy, Dominique; Fujii, Teruo

2012-01-01

Stochastic events in gene expression, protein synthesis, and metabolite synthesis or degradation lead to cellular heterogeneity essential to life. In a tissue as we see in organs, there is strong heterogeneity among the constituting cells critical to its function. Thus, there exists a strong demand to develop new micro/nanosystems that would enable us to conduct single-cell analysis. This field is rapidly growing, as exemplified below with recent emerging technologies that now reveal sensitive single-cell "omics" analysis. We describe in the review some of the most promising technologies that will certainly transform our view of biology in the near future.

Bench-Top Fabrication of an All-PDMS Microfluidic Electrochemical Cell Sensor Integrating Micro/Nanostructured Electrodes.

PubMed

Saem, Sokunthearath; Zhu, Yujie; Luu, Helen; Moran-Mirabal, Jose

2017-03-31

In recent years, efforts in the development of lab-on-a-chip (LoC) devices for point-of-care (PoC) applications have increased to bring affordable, portable, and sensitive diagnostics to the patients' bedside. To reach this goal, research has shifted from using traditional microfabrication methods to more versatile, rapid, and low-cost options. This work focuses on the benchtop fabrication of a highly sensitive, fully transparent, and flexible poly (dimethylsiloxane) (PDMS) microfluidic (μF) electrochemical cell sensor. The μF device encapsulates 3D structured gold and platinum electrodes, fabricated using a shape-memory polymer shrinking method, which are used to set up an on-chip electrochemical cell. The PDMS to PDMS-structured electrode bonding protocol to fabricate the μF chip was optimized and found to have sufficient bond strength to withstand up to 100 mL/min flow rates. The sensing capabilities of the on-chip electrochemical cell were demonstrated by using cyclic voltammetry to monitor the adhesion of murine 3T3 fibroblasts in the presence of a redox reporter. The charge transfer across the working electrode was reduced upon cell adhesion, which was used as the detection mechanism, and allowed the detection of as few as 24 cells. The effective utilization of simple and low cost bench-top fabrication methods could accelerate the prototyping and development of LoC technologies and bring PoC diagnostics and personalized medicine to the patients' bedside.

Bench-Top Fabrication of an All-PDMS Microfluidic Electrochemical Cell Sensor Integrating Micro/Nanostructured Electrodes

PubMed Central

Saem, Sokunthearath; Zhu, Yujie; Luu, Helen; Moran-Mirabal, Jose

2017-01-01

In recent years, efforts in the development of lab-on-a-chip (LoC) devices for point-of-care (PoC) applications have increased to bring affordable, portable, and sensitive diagnostics to the patients’ bedside. To reach this goal, research has shifted from using traditional microfabrication methods to more versatile, rapid, and low-cost options. This work focuses on the benchtop fabrication of a highly sensitive, fully transparent, and flexible poly (dimethylsiloxane) (PDMS) microfluidic (μF) electrochemical cell sensor. The μF device encapsulates 3D structured gold and platinum electrodes, fabricated using a shape-memory polymer shrinking method, which are used to set up an on-chip electrochemical cell. The PDMS to PDMS-structured electrode bonding protocol to fabricate the μF chip was optimized and found to have sufficient bond strength to withstand up to 100 mL/min flow rates. The sensing capabilities of the on-chip electrochemical cell were demonstrated by using cyclic voltammetry to monitor the adhesion of murine 3T3 fibroblasts in the presence of a redox reporter. The charge transfer across the working electrode was reduced upon cell adhesion, which was used as the detection mechanism, and allowed the detection of as few as 24 cells. The effective utilization of simple and low cost bench-top fabrication methods could accelerate the prototyping and development of LoC technologies and bring PoC diagnostics and personalized medicine to the patients’ bedside. PMID:28362329

Plasmonic nanoparticles-decorated diatomite biosilica: extending the horizon of on-chip chromatography and label-free biosensing.

PubMed

Kong, Xianming; Li, Erwen; Squire, Kenny; Liu, Ye; Wu, Bo; Cheng, Li-Jing; Wang, Alan X

2017-11-01

Diatomite consists of fossilized remains of ancient diatoms and is a type of naturally abundant photonic crystal biosilica with multiple unique physical and chemical functionalities. In this paper, we explored the fluidic properties of diatomite as the matrix for on-chip chromatography and, simultaneously, the photonic crystal effects to enhance the plasmonic resonances of metallic nanoparticles for surface-enhanced Raman scattering (SERS) biosensing. The plasmonic nanoparticle-decorated diatomite biosilica provides a lab-on-a-chip capability to separate and detect small molecules from mixture samples with ultra-high detection sensitivity down to 1 ppm. We demonstrate the significant potential for biomedical applications by screening toxins in real biofluid, achieving simultaneous label-free biosensing of phenethylamine and miR21cDNA in human plasma with unprecedented sensitivity and specificity. To the best of our knowledge, this is the first time demonstration to detect target molecules from real biofluids by on-chip chromatography-SERS techniques. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Dielectrophoretic lab-on-CMOS platform for trapping and manipulation of cells.

PubMed

Park, Kyoungchul; Kabiri, Shideh; Sonkusale, Sameer

2016-02-01

Trapping and manipulation of cells are essential operations in numerous studies in biology and life sciences. We discuss the realization of a Lab-on-a-Chip platform for dielectrophoretic trapping and repositioning of cells and microorganisms on a complementary metal oxide semiconductor (CMOS) technology, which we define here as Lab-on-CMOS (LoC). The LoC platform is based on dielectrophoresis (DEP) which is the force experienced by any dielectric particle including biological entities in non-uniform AC electrical field. DEP force depends on the permittivity of the cells, its size and shape and also on the permittivity of the medium and therefore it enables selective targeting of cells based on their phenotype. In this paper, we address an important matter that of electrode design for DEP for which we propose a three-dimensional (3D) octapole geometry to create highly confined electric fields for trapping and manipulation of cells. Conventional DEP-based platforms are implemented stand-alone on glass, silicon or polymers connected to external infrastructure for electronics and optics, making it bulky and expensive. In this paper, the use of CMOS as a platform provides a pathway to truly miniaturized lab-on-CMOS or LoC platform, where DEP electrodes are designed using built-in multiple metal layers of the CMOS process for effective trapping of cells, with built-in electronics for in-situ impedance monitoring of the cell position. We present electromagnetic simulation results of DEP force for this unique 3D octapole geometry on CMOS. Experimental results with yeast cells validate the design. These preliminary results indicate the promise of using CMOS technology for truly compact miniaturized lab-on-chip platform for cell biotechnology applications.

PhyloChip Tackles Coral Disease

ScienceCinema

DeSantis, Todd

2017-12-13

Scientists at Berkeley Lab and the University of California, Merced are using an innovative DNA array developed at Berkeley Lab to catalog the microbes that live among coral in the tropical waters off the coast of Puerto Rico. More info: http://newscenter.lbl.gov/feature-stories/2009/02/02/coral-reefs/

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

PubMed

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

2013-01-21

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

DNA extraction on bio-chip: history and preeminence over conventional and solid-phase extraction methods.

PubMed

Ayoib, Adilah; Hashim, Uda; Gopinath, Subash C B; Md Arshad, M K

2017-11-01

This review covers a developmental progression on early to modern taxonomy at cellular level following the advent of electron microscopy and the advancement in deoxyribonucleic acid (DNA) extraction for expatiation of biological classification at DNA level. Here, we discuss the fundamental values of conventional chemical methods of DNA extraction using liquid/liquid extraction (LLE) followed by development of solid-phase extraction (SPE) methods, as well as recent advances in microfluidics device-based system for DNA extraction on-chip. We also discuss the importance of DNA extraction as well as the advantages over conventional chemical methods, and how Lab-on-a-Chip (LOC) system plays a crucial role for the future achievements.

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

PubMed

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

2010-08-07

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

Programmable bio-nano-chip system: a flexible point-of-care platform for bioscience and clinical measurements

PubMed Central

McRae, Michael. P.; Simmons, Glennon. W.; Wong, Jorge; Shadfan, Basil; Gopalkrishnan, Sanjiv; Christodoulides, Nicolaos

2015-01-01

The development of integrated instrumentation for universal bioassay systems serves as a key goal for the lab-on-a-chip community. The programmable bio-nano-chip (p-BNC) system is a versatile multiplexed and multiclass chemical- and bio-sensing system for bioscience and clinical measurements. The system is comprised of two main components, a disposable cartridge and a portable analyzer. The customizable single-use plastic cartridges, which now can be manufactured in high volumes using injection molding, are designed for analytical performance, ease of use, reproducibility, and low cost. These labcard devices implement high surface area nano-structured biomarker capture elements that enable high performance signaling and are index matched to real-world biological specimens. This detection modality, along with the convenience of on-chip fluid storage in blisters and self-contained waste, represents a standard process to digitize biological signatures at the point-of-care. A companion portable analyzer prototype has been developed to integrate fluid motivation, optical detection, and automated data analysis, and it serves as the human interface for complete assay automation. In this report, we provide a systems-level perspective of the p-BNC universal biosensing platform with an emphasis on flow control, device integration, and automation. To demonstrate the flexibility of the p-BNC, we distinguish diseased and non-case patients across three significant disease applications: prostate cancer, ovarian cancer, and acute myocardial infarction. Progress towards developing a rapid 7 minute myoglobin assay is presented using the fully automated p-BNC system. PMID:26308851

Lab on a Chip Packing of Submicron Particles for High Performance EOF Pumping

DTIC Science & Technology

2010-08-26

and wet etching techniques, using a soda lime glass substrate coated with chromium and photoresist (Nanofilm, Westlake Village, CA). A weir structure...observed previously for these soda lime glass microchips [8]. Images of the three segments of different sized particles con- tainedwithin the packed... Silica beads High pressure Lab on a chip a b s t r a c t The packing of submicrometer sized silica beads inside a microchannel was enabled by a novel

Development of environmentally conscious cleaning process for leadless chip carrier assemblies. Final report

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

Adams, B.E.

1995-04-01

A cross-functional team of process, product, quality, material, and design lab engineers was assembled to develop an environmentally friendly cleaning process for leadless chip carrier assemblies (LCCAs). Using flush and filter testing, Auger surface analysis, GC-Mass spectrophotometry, production yield results, and electrical testing results over an extended testing period, the team developed an aqueous cleaning process for LCCAs. The aqueous process replaced the Freon vapor degreasing/ultrasonic rinse process.

A self-pumping lab-on-a-chip for rapid detection of botulinum toxin.

PubMed

Lillehoj, Peter B; Wei, Fang; Ho, Chih-Ming

2010-09-07

A robust poly(dimethylsiloxane) (PDMS) surface treatment was utilized for the development of a self-pumping lab-on-a-chip (LOC) to rapidly detect minute quantities of toxic substances. One such toxin, botulinum neurotoxin (BoNT), is an extremely lethal substance, which has the potential to cause hundreds of thousands of fatalities if as little as a few grams are released into the environment. To prevent such an outcome, a quick (<45 min) and sensitive detection format is needed. We have developed a self-pumping LOC that can sense down to 1 pg of BoNT type A (in a 1 microL sample) within 15 min in an autonomous manner. The key technologies enabling for such a device are a sensitive electrochemical sensor, an optimized fluidic network and a robust hydrophilic PDMS coating, thereby facilitating autonomous delivery of liquid samples for rapid detection. The stability, simplicity and portability of this device make possible for a storable and distributable system for monitoring bioterrorist attacks.

An integrated CMOS high voltage supply for lab-on-a-chip systems.

PubMed

Behnam, M; Kaigala, G V; Khorasani, M; Marshall, P; Backhouse, C J; Elliott, D G

2008-09-01

Electrophoresis is a mainstay of lab-on-a-chip (LOC) implementations of molecular biology procedures and is the basis of many medical diagnostics. High voltage (HV) power supplies are necessary in electrophoresis instruments and are a significant part of the overall system cost. This cost of instrumentation is a significant impediment to making LOC technologies more widely available. We believe one approach to overcoming this problem is to use microelectronic technology (complementary metal-oxide semiconductor, CMOS) to generate and control the HV. We present a CMOS-based chip (3 mm x 2.9 mm) that generates high voltages (hundreds of volts), switches HV outputs, and is powered by a 5 V input supply (total power of 28 mW) while being controlled using a standard computer serial interface. Microchip electrophoresis with laser induced fluorescence (LIF) detection is implemented using this HV CMOS chip. With the other advancements made in the LOC community (e.g. micro-fluidic and optical devices), these CMOS chips may ultimately enable 'true' LOC solutions where essentially all the microfluidics, photonics and electronics are on a single chip.

A lab-on-a-chip system with integrated sample preparation and loop-mediated isothermal amplification for rapid and quantitative detection of Salmonella spp. in food samples.

PubMed

Sun, Yi; Quyen, Than Linh; Hung, Tran Quang; Chin, Wai Hoe; Wolff, Anders; Bang, Dang Duong

2015-04-21

Foodborne disease is a major public health threat worldwide. Salmonellosis, an infectious disease caused by Salmonella spp., is one of the most common foodborne diseases. Isolation and identification of Salmonella by conventional bacterial culture or molecular-based methods are time consuming and usually take a few hours to days to complete. In response to the demand for rapid on line or on site detection of pathogens, in this study, we describe for the first time an eight-chamber lab-on-a-chip (LOC) system with integrated magnetic bead-based sample preparation and loop-mediated isothermal amplification (LAMP) for rapid and quantitative detection of Salmonella spp. in food samples. The whole diagnostic procedures including DNA isolation, isothermal amplification, and real-time detection were accomplished in a single chamber. Up to eight samples could be handled simultaneously and the system was capable to detect Salmonella at concentration of 50 cells per test within 40 min. The simple design, together with high level of integration, isothermal amplification, and quantitative analysis of multiple samples in short time, will greatly enhance the practical applicability of the LOC system for rapid on-site screening of Salmonella for applications in food safety control, environmental surveillance, and clinical diagnostics.

Frontiers of optofluidics in synthetic biology.

PubMed

Tan, Cheemeng; Lo, Shih-Jie; LeDuc, Philip R; Cheng, Chao-Min

2012-10-07

The development of optofluidic-based technology has ushered in a new era of lab-on-a-chip functionality, including miniaturization of biomedical devices, enhanced sensitivity for molecular detection, and multiplexing of optical measurements. While having great potential, optofluidic devices have only begun to be exploited in many biotechnological applications. Here, we highlight the potential of integrating optofluidic devices with synthetic biological systems, which is a field focusing on creating novel cellular systems by engineering synthetic gene and protein networks. First, we review the development of synthetic biology at different length scales, ranging from single-molecule, single-cell, to cellular population. We emphasize light-sensitive synthetic biological systems that would be relevant for the integration with optofluidic devices. Next, we propose several areas for potential applications of optofluidics in synthetic biology. The integration of optofluidics and synthetic biology would have a broad impact on point-of-care diagnostics and biotechnology.

Multiplexed capillary microfluidic immunoassay with smartphone data acquisition for parallel mycotoxin detection.

PubMed

Machado, Jessica M D; Soares, Ruben R G; Chu, Virginia; Conde, João P

2018-01-15

The field of microfluidics holds great promise for the development of simple and portable lab-on-a-chip systems. The use of capillarity as a means of fluidic manipulation in lab-on-a-chip systems can potentially reduce the complexity of the instrumentation and allow the development of user-friendly devices for point-of-need analyses. In this work, a PDMS microchannel-based, colorimetric, autonomous capillary chip provides a multiplexed and semi-quantitative immunodetection assay. Results are acquired using a standard smartphone camera and analyzed with a simple gray scale quantification procedure. The performance of this device was tested for the simultaneous detection of the mycotoxins ochratoxin A (OTA), aflatoxin B1 (AFB1) and deoxynivalenol (DON) which are strictly regulated food contaminants with severe detrimental effects on human and animal health. The multiplexed assay was performed approximately within 10min and the achieved sensitivities of<40, 0.1-0.2 and<10ng/mL for OTA, AFB1 and DON, respectively, fall within the majority of currently enforced regulatory and/or recommended limits. Furthermore, to assess the potential of the device to analyze real samples, the immunoassay was successfully validated for these 3 mycotoxins in a corn-based feed sample after a simple sample preparation procedure. Copyright © 2017 Elsevier B.V. All rights reserved.

High efficiency integration of three-dimensional functional microdevices inside a microfluidic chip by using femtosecond laser multifoci parallel microfabrication

NASA Astrophysics Data System (ADS)

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

2016-01-01

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

Parallel manipulation of individual magnetic microbeads for lab-on-a-chip applications

NASA Astrophysics Data System (ADS)

Peng, Zhengchun

Many scientists and engineers are turning to lab-on-a-chip systems for faster and cheaper analysis of chemical reactions and biomolecular interactions. A common approach that facilitates the handling of reagents and biomolecules in these systems utilizes micro/nano beads as the solid carrier. Physical manipulation, such as assembly, transport, sorting, and tweezing, of beads on a chip represents an essential step for fully utilizing their potentials in a wide spectrum of bead-based analysis. Previous work demonstrated manipulation of either an ensemble of beads without individual control, or single beads but lacks the capability for parallel operation. Parallel manipulation of individual beads is required to meet the demand for high-throughput and location-specific analysis. In this work, we introduced two methods for parallel manipulation of individual magnetic microbeads, which can serve as effective lab-on-a-chip platforms and/or efficient analytic tools. The first method employs arrays of soft ferromagnetic patterns fabricated inside a microfluidic channel and subjected to an external magnetic field. We demonstrated that the system can be used to assemble individual beads (1-3 mum) from a flow of suspended beads into a regular array on the chip, hence improving the integrated electrochemical detection of biomolecules bound to the bead surface. By rotating the external field, the assembled microbeads can be remotely controlled with synchronized, high-speed circular motion around individual soft magnets on the chip. We employed this manipulation mode for efficient sample mixing in continuous microflow. Furthermore, we discovered a simple but effective way of transporting the microbeads on the chip by varying the strength of the local bias field within a revolution of the external field. In addition, selective transport of microbeads with different size was realized, providing a platform for effective on-chip sample separation and offering the potential for multiplexing capability. The second method integrates magnetic and dielectrophoretic manipulations of the same microbeads. The device combines tapered conducting wires and fingered electrodes to generate desirable magnetic and electric fields, respectively. By externally programming the magnetic attraction and dielectrophoretic repulsion forces, out-of-plane oscillation of the microbeads across the channel height was realized. This manipulation mode can facilitate the interaction between the beads with multiple layers of sample fluid inside the channel. We further demonstrated the tweezing of microbeads in liquid with high spatial resolutions, i.e., from submicrometer to nanometer range, by fine-tuning the net force from magnetic attraction and dielectrophoretic repulsion of the beads. The highresolution control of the out-of-plane motion of the microbeads led to the invention of massively parallel biomolecular tweezers. We believe the maturation of bead-based microtweezers will revolutionize the state-of-art tools currently used for single cell and single molecule studies.

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

PubMed

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

2016-10-18

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

SAW-Based Phononic Crystal Microfluidic Sensor—Microscale Realization of Velocimetry Approaches for Integrated Analytical Platform Applications

PubMed Central

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

2017-01-01

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

SAW-Based Phononic Crystal Microfluidic Sensor-Microscale Realization of Velocimetry Approaches for Integrated Analytical Platform Applications.

PubMed

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

2017-09-23

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

3D printed disposable optics and lab-on-a-chip devices for chemical sensing with cell phones

NASA Astrophysics Data System (ADS)

Comina, G.; Suska, A.; Filippini, D.

2017-02-01

Digital manufacturing (DM) offers fast prototyping capabilities and great versatility to configure countless architectures at affordable development costs. Autonomous lab-on-a-chip (LOC) devices, conceived as only disposable accessory to interface chemical sensing to cell phones, require specific features that can be achieved using DM techniques. Here we describe stereo-lithography 3D printing (SLA) of optical components and unibody-LOC (ULOC) devices using consumer grade printers. ULOC devices integrate actuation in the form of check-valves and finger pumps, as well as the calibration range required for quantitative detection. Coupling to phone camera readout depends on the detection approach, and includes different types of optical components. Optical surfaces can be locally configured with a simple polishing-free post-processing step, and the representative costs are 0.5 US$/device, same as ULOC devices, both involving fabrication times of about 20 min.

A highly attenuating and frequency tailorable annular hole phononic crystal for surface acoustic waves.

PubMed

Ash, B J; Worsfold, S R; Vukusic, P; Nash, G R

2017-08-02

Surface acoustic wave (SAW) devices are widely used for signal processing, sensing and increasingly for lab-on-a-chip applications. Phononic crystals can control the propagation of SAW, analogous to photonic crystals, enabling components such as waveguides and cavities. Here we present an approach for the realisation of robust, tailorable SAW phononic crystals, based on annular holes patterned in a SAW substrate. Using simulations and experiments, we show that this geometry supports local resonances which create highly attenuating phononic bandgaps at frequencies with negligible coupling of SAWs into other modes, even for relatively shallow features. The enormous bandgap attenuation is up to an order-of-magnitude larger than that achieved with a pillar phononic crystal of the same size, enabling effective phononic crystals to be made up of smaller numbers of elements. This work transforms the ability to exploit phononic crystals for developing novel SAW device concepts, mirroring contemporary progress in photonic crystals.The control and manipulation of propagating sound waves on a surface has applications in on-chip signal processing and sensing. Here, Ash et al. deviate from standard designs and fabricate frequency tailorable phononic crystals with an order-of-magnitude increase in attenuation.

Modular 3D printed lab-on-a-chip bio-reactor for the biochemical energy cascade of microorganisms

NASA Astrophysics Data System (ADS)

Podwin, Agnieszka; Dziuban, Jan A.

2017-10-01

The paper presents the sandwiched polymer 3D printed lab-on-a-chip bio-reactor for the biochemical energy cascade of microorganisms. Euglenas and yeast were separately and simultaneously cultured for 10 d in the chip. As a result of the experiments, euglenas, light-initialized and nourished by CO2—a product of ethanol fermentation handled by yeast—generated oxygen, based on the photosynthesis process. The presence of oxygen in the bio-reactor was confirmed by the colorimetric method—a bicarbonate (pH) indicator. Preliminary studies towards the obtainment of an effective source of oxygen are promising and further research should be done to enable the utility of the bio-reactor in, for instance, microbial fuel cells.

Challenges and opportunities for translating medical microdevices: insights from the programmable bio-nano-chip

PubMed Central

McRae, Michael P; Simmons, Glennon; McDevitt, John T

2016-01-01

This perspective highlights the major challenges for the bioanalytical community, in particular the area of lab-on-a-chip sensors, as they relate to point-of-care diagnostics. There is a strong need for general-purpose and universal biosensing platforms that can perform multiplexed and multiclass assays on real-world clinical samples. However, the adoption of novel lab-on-a-chip/microfluidic devices has been slow as several key challenges remain for the translation of these new devices to clinical practice. A pipeline of promising medical microdevice technologies will be made possible by addressing the challenges of integration, failure to compete with cost and performance of existing technologies, requisite for new content, and regulatory approval and clinical adoption. PMID:27071710

Submicron magnetic core conducting polypyrrole polymer shell: Preparation and characterization.

PubMed

Tenório-Neto, Ernandes Taveira; Baraket, Abdoullatif; Kabbaj, Dounia; Zine, Nadia; Errachid, Abdelhamid; Fessi, Hatem; Kunita, Marcos Hiroiuqui; Elaissari, Abdelhamid

2016-04-01

Magnetic particles are of great interest in various biomedical applications, such as, sample preparation, in vitro biomedical diagnosis, and both in vivo diagnosis and therapy. For in vitro applications and especially in labs-on-a-chip, microfluidics, microsystems, or biosensors, the needed magnetic dispersion should answer various criteria, for instance, submicron size in order to avoid a rapid sedimentation rate, fast separations under an applied magnetic field, and appreciable colloidal stability (stable dispersion under shearing process). Then, the aim of this work was to prepare highly magnetic particles with a magnetic core and conducting polymer shell particles in order to be used not only as a carrier, but also for the in vitro detection step. The prepared magnetic seed dispersions were functionalized using pyrrole and pyrrole-2-carboxylic acid. The obtained core-shell particles were characterized in terms of particle size, size distribution, magnetization properties, FTIR analysis, surface morphology, chemical composition, and finally, the conducting property of those particles were evaluated by cyclic voltammetry. The obtained functional submicron highly magnetic particles are found to be conducting material bearing function carboxylic group on the surface. These promising conducting magnetic particles can be used for both transport and lab-on-a-chip detection. Copyright © 2015. Published by Elsevier B.V.

A Charge Sensitive Pre-Amplifier for Smart Point-of-Care Devices Employing Polymer Based Lab-on-a-Chip

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

Wang, Hanfeng; Britton, Charles; Quaiyum, Farhan

With increasing emphasis on implantable and portable medical devices, low-power, small-chip-area sensor readout system realized in lab-on-a-chip (LOC) platform is gaining more and more importance these days. The main building blocks of the LOC system include a front-end transducer that generates an electrical signal in response to the presence of an analyte of interest, signal processing electronics to process the signal to comply with a specific transmission protocol and a low-power transmitter, all realized in a single integrated circuit platform. Low power consumption and compactness of the components are essential requirements of the LOC system. This paper presents a novelmore » charge sensitive pre-amplifier developed in a standard 180-nm CMOS process suitable for implementing in an LOC platform. The pre-amplifier converts the charge generated by a pyroelectric transducer into a voltage signal, which provides a measurement of the temperature variation in biological fluids. The proposed design is capable of providing 0.8-mV/pC gain while consuming only 2.1 μW of power. Finally, the pre-amplifier composed of integrated components occupies an area of 0.038 mm 2.« less

A Charge Sensitive Pre-Amplifier for Smart Point-of-Care Devices Employing Polymer Based Lab-on-a-Chip

DOE PAGES

Wang, Hanfeng; Britton, Charles; Quaiyum, Farhan; ...

2018-01-01

With increasing emphasis on implantable and portable medical devices, low-power, small-chip-area sensor readout system realized in lab-on-a-chip (LOC) platform is gaining more and more importance these days. The main building blocks of the LOC system include a front-end transducer that generates an electrical signal in response to the presence of an analyte of interest, signal processing electronics to process the signal to comply with a specific transmission protocol and a low-power transmitter, all realized in a single integrated circuit platform. Low power consumption and compactness of the components are essential requirements of the LOC system. This paper presents a novelmore » charge sensitive pre-amplifier developed in a standard 180-nm CMOS process suitable for implementing in an LOC platform. The pre-amplifier converts the charge generated by a pyroelectric transducer into a voltage signal, which provides a measurement of the temperature variation in biological fluids. The proposed design is capable of providing 0.8-mV/pC gain while consuming only 2.1 μW of power. Finally, the pre-amplifier composed of integrated components occupies an area of 0.038 mm 2.« less

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

PubMed

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

2011-06-01

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

Another expert system rule inference based on DNA molecule logic gates

NASA Astrophysics Data System (ADS)

WÄ siewicz, Piotr

2013-10-01

With the help of silicon industry microfluidic processors were invented utilizing nano membrane valves, pumps and microreactors. These so called lab-on-a-chips combined together with molecular computing create molecular-systems-ona- chips. This work presents a new approach to implementation of molecular inference systems. It requires the unique representation of signals by DNA molecules. The main part of this work includes the concept of logic gates based on typical genetic engineering reactions. The presented method allows for constructing logic gates with many inputs and for executing them at the same quantity of elementary operations, regardless of a number of input signals. Every microreactor of the lab-on-a-chip performs one unique operation on input molecules and can be connected by dataflow output-input connections to other ones.

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.

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

PubMed

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

2010-07-21

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

A flexible microcontroller-based data acquisition device.

PubMed

Hercog, Darko; Gergič, Bojan

2014-06-02

This paper presents a low-cost microcontroller-based data acquisition device. The key component of the presented solution is a configurable microcontroller-based device with an integrated USB transceiver and a 12-bit analogue-to-digital converter (ADC). The presented embedded DAQ device contains a preloaded program (firmware) that enables easy acquisition and generation of analogue and digital signals and data transfer between the device and the application running on a PC via USB bus. This device has been developed as a USB human interface device (HID). This USB class is natively supported by most of the operating systems and therefore any installation of additional USB drivers is unnecessary. The input/output peripheral of the presented device is not static but rather flexible, and could be easily configured to customised needs without changing the firmware. When using the developed configuration utility, a majority of chip pins can be configured as analogue input, digital input/output, PWM output or one of the SPI lines. In addition, LabVIEW drivers have been developed for this device. When using the developed drivers, data acquisition and signal processing algorithms as well as graphical user interface (GUI), can easily be developed using a well-known, industry proven, block oriented LabVIEW programming environment.

Amperometric IFN-γ immunosensors with commercially fabricated PCB sensing electrodes.

PubMed

Moschou, Despina; Greathead, Louise; Pantelidis, Panagiotis; Kelleher, Peter; Morgan, Hywel; Prodromakis, Themistoklis

2016-12-15

Lab-on-a-Chip (LoC) technology has the potential to revolutionize medical Point-of-Care diagnostics. Currently, considerable research efforts are focused on innovative production technologies that will make commercial upscaling of lab-on-chip products financially viable. Printed circuit board (PCB) manufacturing techniques have several advantages in this field. In this paper we focus on transferring a complete IFN-γ enzyme-linked immune-sorbent assay (ELISA) onto a commercial PCB electrochemical biosensing platform, We adapted a commercially available ELISA to detect the enzyme product TMB/H2O2 using amperometry, successfully reproducing the colorimetry-obtained ELISA standard curve. The results demonstrate the potential for the integration of these components into an automated, disposable, electronic ELISA Lab-on-PCB diagnostic platform. Copyright © 2016 Elsevier B.V. All rights reserved.

Lab-On-Chip Clinorotation System for Live-Cell Microscopy Under Simulated Microgravity

NASA Technical Reports Server (NTRS)

Yew, Alvin G.; Atencia, Javier; Chinn, Ben; Hsieh, Adam H.

2013-01-01

Cells in microgravity are subject to mechanical unloading and changes to the surrounding chemical environment. How these factors jointly influence cellular function is not well understood. We can investigate their role using ground-based analogues to spaceflight, where mechanical unloading is simulated through the time-averaged nullification of gravity. The prevailing method for cellular microgravity simulation is to use fluid-filled containers called clinostats. However, conventional clinostats are not designed for temporally tracking cell response, nor are they able to establish dynamic fluid environments. To address these needs, we developed a Clinorotation Time-lapse Microscopy (CTM) system that accommodates lab-on- chip cell culture devices for visualizing time-dependent alterations to cellular behavior. For the purpose of demonstrating CTM, we present preliminary results showing time-dependent differences in cell area between human mesenchymal stem cells (hMSCs) under modeled microgravity and normal gravity.

Lab-On-Chip Clinorotation System for Live-Cell Microscopy Under Simulated Microgravity

NASA Technical Reports Server (NTRS)

Yew, Alvin G.; Atencia, Javier; Chinn, Ben; Hsieh, Adam H.

1980-01-01

Cells in microgravity are subject to mechanical unloading and changes to the surrounding chemical environment. How these factors jointly influence cellular function is not well understood. We can investigate their role using ground-based analogues to spaceflight, where mechanical unloading is simulated through the time-averaged nullification of gravity. The prevailing method for cellular microgravity simulation is to use fluid-filled containers called clinostats. However, conventional clinostats are not designed for temporally tracking cell response, nor are they able to establish dynamic fluid environments. To address these needs, we developed a Clinorotation Time-lapse Microscopy (CTM) system that accommodates lab-on- chip cell culture devices for visualizing time-dependent alterations to cellular behavior. For the purpose of demonstrating CTM, we present preliminary results showing time-dependent differences in cell area between human mesenchymal stem cells (hMSCs) under modeled microgravity and normal gravity.

High-pressure microfluidic control in lab-on-a-chip devices using mobile polymer monoliths.

PubMed

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

2002-10-01

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

Preliminary Study for Measurement of Shear Stress and Hemocompatibility Using Commercialized Lab on a Chip.

PubMed

Lee, Joshua; Kim, In Gi; Oh, Young Min; Park, Chan-Hee; Kim, Cheol Sang

2018-02-01

We have investigated the effect of flow rate on shear stress and in turn thrombus formation on a lab-on-a-chip with a microchannel that is suitable for cell culture and growth. Using a combination of Arduino UNO, Arduino Motor Shield, and a SERVO stepper motor, we created a pump system that closely mimics the in vivo conditions of the human body. With this system, we achieved continuous flow of blood and observed attached platelets at the bottom of the collagen coated microslide, confirming that with shear stress, thrombus formation increases.

Microfluidic Arrayed Lab-On-A-Chip for Electrochemical Capacitive Detection of DNA Hybridization Events.

PubMed

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

2017-01-01

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

OpenSource lab-on-a-chip physiometer for accelerated zebrafish embryo biotests.

PubMed

Akagi, Jin; Hall, Chris J; Crosier, Kathryn E; Cooper, Jonathan M; Crosier, Philip S; Wlodkowic, Donald

2014-01-02

Zebrafish (Danio rerio) embryo assays have recently come into the spotlight as convenient experimental models in both biomedicine and ecotoxicology. As a small aquatic model organism, zebrafish embryo assays allow for rapid physiological, embryo-, and genotoxic tests of drugs and environmental toxins that can be simply dissolved in water. This protocol describes prototyping and application of an innovative, miniaturized, and polymeric chip-based device capable of immobilizing a large number of living fish embryos for real-time and/or time-lapse microscopic examination. The device provides a physical address designation to each embryo during analysis, continuous perfusion of medium, and post-analysis specimen recovery. Miniaturized embryo array is a new concept of immobilization and real-time drug perfusion of multiple individual and developing zebrafish embryos inside the mesofluidic device. The OpenSource device presented in this protocol is particularly suitable to perform accelerated fish embryo biotests in ecotoxicology and phenotype-based pharmaceutical screening. Copyright © 2014 John Wiley & Sons, Inc.

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.

Subwavelength engineered fiber-to-chip silicon-on-sapphire interconnects for mid-infrared applications (Conference Presentation)

NASA Astrophysics Data System (ADS)

Alonso-Ramos, Carlos; Han, Zhaohong; Le Roux, Xavier; Lin, Hongtao; Singh, Vivek; Lin, Pao Tai; Tan, Dawn; Cassan, Eric; Marris-Morini, Delphine; Vivien, Laurent; Wada, Kazumi; Hu, Juejun; Agarwal, Anuradha; Kimerling, Lionel C.

2016-05-01

The mid-Infrared wavelength range (2-20 µm), so-called fingerprint region, contains the very sharp vibrational and rotational resonances of many chemical and biological substances. Thereby, on-chip absorption-spectrometry-based sensors operating in the mid-Infrared (mid-IR) have the potential to perform high-precision, label-free, real-time detection of multiple target molecules within a single sensor, which makes them an ideal technology for the implementation of lab-on-a-chip devices. Benefiting from the great development realized in the telecom field, silicon photonics is poised to deliver ultra-compact efficient and cost-effective devices fabricated at mass scale. In addition, Si is transparent up to 8 µm wavelength, making it an ideal material for the implementation of high-performance mid-IR photonic circuits. The silicon-on-insulator (SOI) technology, typically used in telecom applications, relies on silicon dioxide as bottom insulator. Unfortunately, silicon dioxide absorbs light beyond 3.6 µm, limiting the usability range of the SOI platform for the mid-IR. Silicon-on-sapphire (SOS) has been proposed as an alternative solution that extends the operability region up to 6 µm (sapphire absorption), while providing a high-index contrast. In this context, surface grating couplers have been proved as an efficient means of injecting and extracting light from mid-IR SOS circuits that obviate the need of cleaving sapphire. However, grating couplers typically have a reduced bandwidth, compared with facet coupling solutions such as inverse or sub-wavelength tapers. This feature limits their feasibility for absorption spectroscopy applications that may require monitoring wide wavelength ranges. Interestingly, sub-wavelength engineering can be used to substantially improve grating coupler bandwidth, as demonstrated in devices operating at telecom wavelengths. Here, we report on the development of fiber-to-chip interconnects to ZrF4 optical fibers and integrated SOS circuits with 500 nm thick Si, operating around 3.8 µm wavelength. Results on facet coupling and sub-wavelength engineered grating coupler solutions in the mid-IR regime will be compared.

A mini-microscope for in situ monitoring of cells.

PubMed

Kim, Sang Bok; Koo, Kyo-in; Bae, Hojae; Dokmeci, Mehmet R; Hamilton, Geraldine A; Bahinski, Anthony; Kim, Sun Min; Ingber, Donald E; Khademhosseini, Ali

2012-10-21

A mini-microscope was developed for in situ monitoring of cells by modifying off-the-shelf components of a commercial webcam. The mini-microscope consists of a CMOS imaging module, a small plastic lens and a white LED illumination source. The CMOS imaging module was connected to a laptop computer through a USB port for image acquisition and analysis. Due to its compact size, 8 × 10 × 9 cm, the present microscope is portable and can easily fit inside a conventional incubator, and enables real-time monitoring of cellular behaviour. Moreover, the mini-microscope can be used for imaging cells in conventional cell culture flasks, such as Petri dishes and multi-well plates. To demonstrate the operation of the mini-microscope, we monitored the cellular migration of mouse 3T3 fibroblasts in a scratch assay in medium containing three different concentrations of fetal bovine serum (5, 10, and 20%) and demonstrated differential responses depending on serum levels. In addition, we seeded embryonic stem cells inside poly(ethylene glycol) microwells and monitored the formation of stem cell aggregates in real time using the mini-microscope. Furthermore, we also combined a lab-on-a-chip microfluidic device for microdroplet generation and analysis with the mini-microscope and observed the formation of droplets under different flow conditions. Given its cost effectiveness, robust imaging and portability, the presented platform may be useful for a range of applications for real-time cellular imaging using lab-on-a-chip devices at low cost.

A mini-microscope for in situ monitoring of cells†‡

PubMed Central

Kim, Sang Bok; Koo, Kyo-in; Bae, Hojae; Dokmeci, Mehmet R.; Hamilton, Geraldine A.; Bahinski, Anthony; Kim, Sun Min; Ingber, Donald E.

2013-01-01

A mini-microscope was developed for in situ monitoring of cells by modifying off-the-shelf components of a commercial webcam. The mini-microscope consists of a CMOS imaging module, a small plastic lens and a white LED illumination source. The CMOS imaging module was connected to a laptop computer through a USB port for image acquisition and analysis. Due to its compact size, 8 × 10 × 9 cm, the present microscope is portable and can easily fit inside a conventional incubator, and enables real-time monitoring of cellular behaviour. Moreover, the mini-microscope can be used for imaging cells in conventional cell culture flasks, such as Petri dishes and multi-well plates. To demonstrate the operation of the mini-microscope, we monitored the cellular migration of mouse 3T3 fibroblasts in a scratch assay in medium containing three different concentrations of fetal bovine serum (5, 10, and 20%) and demonstrated differential responses depending on serum levels. In addition, we seeded embryonic stem cells inside poly(ethylene glycol) microwells and monitored the formation of stem cell aggregates in real time using the mini-microscope. Furthermore, we also combined a lab-on-a-chip microfluidic device for microdroplet generation and analysis with the mini-microscope and observed the formation of droplets under different flow conditions. Given its cost effectiveness, robust imaging and portability, the presented platform may be useful for a range of applications for real-time cellular imaging using lab-on-a-chip devices at low cost. PMID:22911426

A new approach for downscaling of electromembrane extraction as a lab on-a-chip device followed by sensitive Red-Green-Blue detection.

PubMed

Baharfar, Mahroo; Yamini, Yadollah; Seidi, Shahram; Arain, Muhammad Balal

2018-05-30

A new design of electromembrane extraction (EME) as a lab on-a-chip device was proposed for the extraction and determination of phenazopyridine as the model analyte. The extraction procedure was accomplished by coupling of EME and the packing of a sorbent. The analyte was extracted under the applied electrical field across a membrane sheet impregnated by nitrophenyl octylether (NPOE) into an acceptor phase. It was followed by the absorption of the analyte on strong cation exchanger as a sorbent. The designed chip contained separate spiral channels for donor and acceptor phases featuring embedded platinum electrodes to enhance extraction efficiency. The selected donor and acceptor phases were 0 mM HCl and 100 mM HCl, respectively. The on-chip electromembrane extraction was carried out under the voltage level of 70 V for 50 min. The analysis was carried out by two modes of a simple Red-Green-Blue (RGB) image analysis tool and a conventional HPLC-UV system. After the absorption of the analyte on the solid phase, its color changed and a digital picture of the sorbent was taken for the RGB analysis. The effective parameters on the performance of the chip device, comprising the EME and solid phase microextraction steps, were distinguished and optimized. The accumulation of the analyte on the solid phase showed excellent sensitivity and a limit of detection (LOD) lower than 1.0 μg L-1 achieved by an image analysis using a smartphone. This device also offered acceptable intra- and inter-assay RSD% (<10%). The calibration curves were linear within the range of 10-1000 μg L-1 and 30-1000 μg L-1 (r2 > 0.9969) for HPLC-UV and RGB analysis, respectively. To investigate the applicability of the method in complicated matrices, urine samples of patients being treated with phenazopyridine were analyzed.

Lab-on-a-Chip Device for Rapid Measurement of Vitamin D Levels.

PubMed

Peter, Harald; Bistolas, Nikitas; Schumacher, Soeren; Laurisch, Cecilia; Guest, Paul C; Höller, Ulrich; Bier, Frank F

2018-01-01

Lab-on-a-chip assays allow rapid analysis of one or more molecular analytes on an automated user-friendly platform. Here we describe a fully automated assay and readout for measurement of vitamin D levels in less than 15 min using the Fraunhofer in vitro diagnostics platform. Vitamin D (25-hydroxyvitamin D 3 [25(OH)D 3 ]) dilution series in buffer were successfully tested down to 2 ng/mL. This could be applied in the future as an inexpensive point-of-care analysis for patients suffering from a variety of conditions marked by vitamin D deficiencies.

Silk-microfluidics for advanced biotechnological applications: A progressive review.

PubMed

Konwarh, Rocktotpal; Gupta, Prerak; Mandal, Biman B

2016-01-01

Silk based biomaterials have not only carved a unique niche in the domain of regenerative medicine but new avenues are also being explored for lab-on-a-chip applications. It is pertinent to note that biospinning of silk represents nature's signature microfluidic-maneuver. Elucidation of non-Newtonian flow of silk in the glands of spiders and silkworms has inspired researchers to fabricate devices for continuous extrusion and concentration of silk. Microfluidic channel networks within porous silk scaffolds ensure optimal nutrient and oxygen supply apart from serving as precursors for vascularization in tissue engineering applications. On the other hand, unique topographical features and surface wettability of natural silk fibers have inspired development of a number of simple and cost-effective devices for applications like blood typing and chemical sensing. This review mirrors the recent progress and challenges in the domain of silk-microfluidics for prospective avant-garde applications in the realm of biotechnology. Copyright © 2016 Elsevier Inc. All rights reserved.

Self-organizing magnetic beads for biomedical applications

NASA Astrophysics Data System (ADS)

Gusenbauer, Markus; Kovacs, Alexander; Reichel, Franz; Exl, Lukas; Bance, Simon; Özelt, Harald; Schrefl, Thomas

2012-03-01

In the field of biomedicine magnetic beads are used for drug delivery and to treat hyperthermia. Here we propose to use self-organized bead structures to isolate circulating tumor cells using lab-on-chip technologies. Typically blood flows past microposts functionalized with antibodies for circulating tumor cells. Creating these microposts with interacting magnetic beads makes it possible to tune the geometry in size, position and shape. We developed a simulation tool that combines micromagnetics and discrete particle dynamics, in order to design micropost arrays made of interacting beads. The simulation takes into account the viscous drag of the blood flow, magnetostatic interactions between the magnetic beads and gradient forces from external aligned magnets. We developed a particle-particle particle-mesh method for effective computation of the magnetic force and torque acting on the particles.

Microscale Concentration Measurements Using Laser Light Scattering Methods

NASA Technical Reports Server (NTRS)

Niederhaus, Charles; Miller, Fletcher

2004-01-01

The development of lab-on-a-chip devices for microscale biochemical assays has led to the need for microscale concentration measurements of specific analyses. While fluorescence methods are the current choice, this method requires developing fluorophore-tagged conjugates for each analyte of interest. In addition, fluorescent imaging is also a volume-based method, and can be limiting as smaller detection regions are required.

Optoelectrofluidic platforms for chemistry and biology.

PubMed

Hwang, Hyundoo; Park, Je-Kyun

2011-01-07

Extraordinary advances in lab on a chip systems have been made on the basis of the development of micro/nanofluidics and its fusion with other technologies based on electrokinetics and optics. Optoelectrofluidic technology, which has been recently introduced as a new manipulation scheme, allows programmable manipulation of particles or fluids in microenvironments based on optically induced electrokinetics. Herein, the behaviour of particles or fluids can be controlled by inducing or perturbing electric fields on demand in an optical manner, which includes photochemical, photoconductive, and photothermal effects. This elegant scheme of the optoelectrofluidic platform has attracted attention in various fields of science and engineering. A lot of research on optoelectrofluidic manipulation technologies has been reported and the field has advanced rapidly, although some technical hurdles still remain. This review describes recent developments and future perspectives of optoelectrofluidic platforms for chemical and biological applications.

MOEMS optical delay line for optical coherence tomography

NASA Astrophysics Data System (ADS)

Choudhary, Om P.; Chouksey, S.; Sen, P. K.; Sen, P.; Solanki, J.; Andrews, J. T.

2014-09-01

Micro-Opto-Electro-Mechanical optical coherence tomography, a lab-on-chip for biomedical applications is designed, studied, fabricated and characterized. To fabricate the device standard PolyMUMPS processes is adopted. We report the utilization of electro-optic modulator for a fast scanning optical delay line for time domain optical coherence tomography. Design optimization are performed using Tanner EDA while simulations are performed using COMSOL. The paper summarizes various results and fabrication methodology adopted. The success of the device promises a future hand-held or endoscopic optical coherence tomography for biomedical applications.

A novel alternating current multiple array electrothermal micropump for lab-on-a-chip applications.

PubMed

Salari, A; Navi, M; Dalton, C

2015-01-01

The AC electrothermal technique is very promising for biofluid micropumping, due to its ability to pump high conductivity fluids. However, compared to electroosmotic micropumps, a lack of high fluid flow is a disadvantage. In this paper, a novel AC multiple array electrothermal (MAET) micropump, utilizing multiple microelectrode arrays placed on the side-walls of the fluidic channel of the micropump, is introduced. Asymmetric coplanar microelectrodes are placed on all sides of the microfluidic channel, and are actuated in different phases: one, two opposing, two adjacent, three, or all sides at the same time. Micropumps with different combinations of side electrodes and cross sections are numerically investigated in this paper. The effect of the governing parameters with respect to thermal, fluidic, and electrical properties are studied and discussed. To verify the simulations, the AC MAET concept was then fabricated and experimentally tested. The resulted fluid flow achieved by the experiments showed good agreement with the corresponding simulations. The number of side electrode arrays and the actuation patterns were also found to greatly influence the micropump performance. This study shows that the new multiple array electrothermal micropump design can be used in a wide range of applications such as drug delivery and lab-on-a-chip, where high flow rate and high precision micropumping devices for high conductivity fluids are needed.

Control and gating of kinesin-microtubule motility on electrically heated thermo-chips.

PubMed

Ramsey, Laurence; Schroeder, Viktor; van Zalinge, Harm; Berndt, Michael; Korten, Till; Diez, Stefan; Nicolau, Dan V

2014-06-01

First lab-on-chip devices based on active transport by biomolecular motors have been demonstrated for basic detection and sorting applications. However, to fully employ the advantages of such hybrid nanotechnology, versatile spatial and temporal control mechanisms are required. Using a thermo-responsive polymer, we demonstrated a temperature controlled gate that either allows or disallows the passing of microtubules through a topographically defined channel. The gate is addressed by a narrow gold wire, which acts as a local heating element. It is shown that the electrical current flowing through a narrow gold channel can control the local temperature and as a result the conformation of the polymer. This is the first demonstration of a spatially addressable gate for microtubule motility which is a key element of nanodevices based on biomolecular motors.

Modeling and Simulation of Lab-on-a-Chip Systems

DTIC Science & Technology

2005-08-12

complex chip geometries (including multiple turns). Variations of sample concentration profiles in laminar diffusion-based micromixers are also derived...CHAPTER 6 MODELING OF LAMINAR DIFFUSION-BASED COMPLEX ELECTROKINETIC PASSIVE MICROMIXERS ...140 6.4.4 Multi-Stream (Inter-Digital) Micromixers

Webcam camera as a detector for a simple lab-on-chip time based approach.

PubMed

Wongwilai, Wasin; Lapanantnoppakhun, Somchai; Grudpan, Supara; Grudpan, Kate

2010-05-15

A modification of a webcam camera for use as a small and low cost detector was demonstrated with a simple lab-on-chip reactor. Real time continuous monitoring of the reaction zone could be done. Acid-base neutralization with phenolphthalein indicator was used as a model reaction. The fading of pink color of the indicator when the acidic solution diffused into the basic solution zone was recorded as the change of red, blue and green colors (%RBG.) The change was related to acid concentration. A low cost portable semi-automation analysis system was achieved.

Monitoring dynamic interactions of tumor cells with tissue and immune cells in a lab-on-a-chip.

PubMed

Charwat, Verena; Rothbauer, Mario; Tedde, Sandro F; Hayden, Oliver; Bosch, Jacobus J; Muellner, Paul; Hainberger, Rainer; Ertl, Peter

2013-12-03

A complementary cell analysis method has been developed to assess the dynamic interactions of tumor cells with resident tissue and immune cells using optical light scattering and impedance sensing to shed light on tumor cell behavior. The combination of electroanalytical and optical biosensing technologies integrated in a lab-on-a-chip allows for continuous, label-free, and noninvasive probing of dynamic cell-to-cell interactions between adherent and nonadherent cocultures, thus providing real-time insights into tumor cell responses under physiologically relevant conditions. While the study of adherent cocultures is important for the understanding and suppression of metastatic invasion, the analysis of tumor cell interactions with nonadherent immune cells plays a vital role in cancer immunotherapy research. For the first time, the direct cell-to-cell interactions of tumor cells with bead-activated primary T cells were continuously assessed using an effector cell to target a cell ratio of 10:1.

Integrated luminescent chemical microsensors based on GaN LEDs for security applications using smartphones

NASA Astrophysics Data System (ADS)

Orellana, Guillermo; Muñoz, Elias; Gil-Herrera, Luz K.; Muñoz, Pablo; Lopez-Gejo, Juan; Palacio, Carlos

2012-09-01

Development of PCB-integrateable microsensors for monitoring chemical species is a goal in areas such as lab-on-a-chip analytical devices, diagnostics medicine and electronics for hand-held instruments where the device size is a major issue. Cellular phones have pervaded the world inhabitants and their usefulness has dramatically increased with the introduction of smartphones due to a combination of amazing processing power in a confined space, geolocalization and manifold telecommunication features. Therefore, a number of physical and chemical sensors that add value to the terminal for health monitoring, personal safety (at home, at work) and, eventually, national security have started to be developed, capitalizing also on the huge number of circulating cell phones. The chemical sensor-enabled "super" smartphone provides a unique (bio)sensing platform for monitoring airborne or waterborne hazardous chemicals or microorganisms for both single user and crowdsourcing security applications. Some of the latest ones are illustrated by a few examples. Moreover, we have recently achieved for the first time (covalent) functionalization of p- and n-GaN semiconductor surfaces with tuneable luminescent indicator dyes of the Ru-polypyridyl family, as a key step in the development of innovative microsensors for smartphone applications. Chemical "sensoring" of GaN-based blue LED chips with those indicators has also been achieved by plasma treatment of their surface, and the micrometer-sized devices have been tested to monitor O2 in the gas phase to show their full functionality. Novel strategies to enhance the sensor sensitivity such as changing the length and nature of the siloxane buffer layer are discussed in this paper.

[Development of molecular detection of food-borne pathogenic bacteria using miniaturized microfluidic devices].

PubMed

Iván, Kristóf; Maráz, Anna

2015-12-20

Detection and identification of food-borne pathogenic bacteria are key points for the assurance of microbiological food safety. Traditional culture-based methods are more and more replaced by or supplemented with nucleic acid based molecular techniques, targeting specific (preferably virulence) genes in the genomes. Internationally validated DNA amplification - most frequently real-time polymerase chain reaction - methods are applied by the food microbiological testing laboratories for routine analysis, which will result not only in shortening the time for results but they also improve the performance characteristics (e.g. sensitivity, specificity) of the methods. Beside numerous advantages of the polymerase chain reaction based techniques for routine microbiological analysis certain drawbacks have to be mentioned, such as the high cost of the equipment and reagents, as well as the risk of contamination of the laboratory environment by the polymerase chain reaction amplicons, which require construction of an isolated laboratory system. Lab-on-a-chip systems can integrate most of these laboratory processes within a miniaturized device that delivers the same specificity and reliability as the standard protocols. The benefits of miniaturized devices are: simple - often automated - use, small overall size, portability, sterility due to single use possibility. These miniaturized rapid diagnostic tests are being researched and developed at the best research centers around the globe implementing various sample preparation and molecular DNA amplification methods on-chip. In parallel, the aim of the authors' research is to develop microfluidic Lab-on-a-chip devices for the detection and identification of food-borne pathogenic bacteria.

Microfluidic on-chip fluorescence-activated interface control system

PubMed Central

Haiwang, Li; Nguyen, N. T.; Wong, T. N.; Ng, S. L.

2010-01-01

A microfluidic dynamic fluorescence-activated interface control system was developed for lab-on-a-chip applications. The system consists of a straight rectangular microchannel, a fluorescence excitation source, a detection sensor, a signal conversion circuit, and a high-voltage feedback system. Aqueous NaCl as conducting fluid and aqueous glycerol as nonconducting fluid were introduced to flow side by side into the straight rectangular microchannel. Fluorescent dye was added to the aqueous NaCl to work as a signal representing the interface position. Automatic control of the liquid interface was achieved by controlling the electroosmotic effect that exists only in the conducting fluid using a high-voltage feedback system. A LABVIEW program was developed to control the output of high-voltage power supply according the actual interface position, and then the interface position is modified as the output of high-voltage power supply. At last, the interface can be moved to the desired position automatically using this feedback system. The results show that the system presented in this paper can control an arbitrary interface location in real time. The effects of viscosity ratio, flow rates, and polarity of electric field were discussed. This technique can be extended to switch the sample flow and droplets automatically. PMID:21173886

Carbon nanotubes for voltage reduction and throughput enhancement of electrical cell lysis on a lab-on-a-chip.

PubMed

Shahini, Mehdi; Yeow, John T W

2011-08-12

We report on the enhancement of electrical cell lysis using carbon nanotubes (CNTs). Electrical cell lysis systems are widely utilized in microchips as they are well suited to integration into lab-on-a-chip devices. However, cell lysis based on electrical mechanisms has high voltage requirements. Here, we demonstrate that by incorporating CNTs into microfluidic electrolysis systems, the required voltage for lysis is reduced by half and the lysis throughput at low voltages is improved by ten times, compared to non-CNT microchips. In our experiment, E. coli cells are lysed while passing through an electric field in a microchannel. Based on the lightning rod effect, the electric field strengthened at the tip of the CNTs enhances cell lysis at lower voltage and higher throughput. This approach enables easy integration of cell lysis with other on-chip high-throughput sample-preparation processes.

Integrated DNA and RNA extraction and purification on an automated microfluidic cassette from bacterial and viral pathogens causing community-acquired lower respiratory tract infections.

PubMed

Van Heirstraeten, Liesbet; Spang, Peter; Schwind, Carmen; Drese, Klaus S; Ritzi-Lehnert, Marion; Nieto, Benjamin; Camps, Marta; Landgraf, Bryan; Guasch, Francesc; Corbera, Antoni Homs; Samitier, Josep; Goossens, Herman; Malhotra-Kumar, Surbhi; Roeser, Tina

2014-05-07

In this paper, we describe the development of an automated sample preparation procedure for etiological agents of community-acquired lower respiratory tract infections (CA-LRTI). The consecutive assay steps, including sample re-suspension, pre-treatment, lysis, nucleic acid purification, and concentration, were integrated into a microfluidic lab-on-a-chip (LOC) cassette that is operated hands-free by a demonstrator setup, providing fluidic and valve actuation. The performance of the assay was evaluated on viral and Gram-positive and Gram-negative bacterial broth cultures previously sampled using a nasopharyngeal swab. Sample preparation on the microfluidic cassette resulted in higher or similar concentrations of pure bacterial DNA or viral RNA compared to manual benchtop experiments. The miniaturization and integration of the complete sample preparation procedure, to extract purified nucleic acids from real samples of CA-LRTI pathogens to, and above, lab quality and efficiency, represent important steps towards its application in a point-of-care test (POCT) for rapid diagnosis of CA-LRTI.

Microcantilever-based platforms as biosensing tools.

PubMed

Alvarez, Mar; Lechuga, Laura M

2010-05-01

The fast and progressive growth of the biotechnology and pharmaceutical fields forces the development of new and powerful sensing techniques for process optimization and detection of biomolecules at very low concentrations. During the last years, the simplest MEMS structures, i.e. microcantilevers, have become an emerging and promising technology for biosensing applications, due to their small size, fast response, high sensitivity and their compatible integration into "lab-on-a-chip" devices. This article provides an overview of some of the most interesting bio-detections carried out during the last 2-3 years with the microcantilever-based platforms, which highlight the continuous expansion of this kind of sensor in the medical diagnosis field, reaching limits of detection at the single molecule level.

In-plane cost-effective magnetically actuated valve for microfluidic applications

NASA Astrophysics Data System (ADS)

Pugliese, Marco; Ferrara, Francesco; Bramanti, Alessandro Paolo; Gigli, Giuseppe; Maiorano, Vincenzo

2017-04-01

We present a new in-plane magnetically actuated microfluidic valve. Its simple design includes a circular area joining two channels lying on the same plane. The area is parted by a septum lying on and adhering to a magneto-active polymeric ‘floor’ membrane, keeping the channels normally separated (valve closed). Under the action of a magnetic field, the membrane collapses, letting the liquid flow below the septum (valve open). The valve was extensively characterized experimentally, and modeled and optimized theoretically. The growing interest in lab on chips, especially for diagnostics and precision medicine, is driving researchers towards smart, efficient and low cost solutions to the management of biological samples. In this context, the valve developed in this work represents a useful building-block for microfluidic applications requiring precise flow control, its main features being easy and rapid manufacturing, biocompatibility and low cost.

BANSAI - An optofluidic approach for biomedical analysis

NASA Astrophysics Data System (ADS)

Knoerzer, Markus; Prokop, Christoph; Rodrigues Ribeiro, Graciete M.; Mayer, Horst; Brümmer, Jens; Mitchell, Arnan; Rabus, Dominik G.; Karnutsch, Christian

2015-12-01

Lab-on-a-chip based portable blood analysis systems would allow point-of-care measurements, e.g. in an ambulance, or in remote areas with no fast access to medical care. Such a systemwould provide much faster information about the health of a patient. Here,we present a system that is based on absorption spectroscopy and uses an organic laser, which is tunable in the visible range. The feasibility of the system is shown with a table-top setup using laboratory equipment. Measurements of human albumin show linear behaviour in a range from 2.5 g/L to 60 g/L. In a consecutive setup the system is implemented on a microfluidic chip and is capable of measuring simultaneously transmitted and side scattered intensities, even with ambient light present. Air-suspended grating couplers on polymers are shown as the first element of a lab-on-a-chip implementation.

BANSAI - An optofluidic approach for biomedical analysis

NASA Astrophysics Data System (ADS)

Knoerzer, Markus; Prokop, Christoph; Rodrigues Ribeiro, Graciete M.; Mayer, Horst; Brümmer, Jens; Mitchell, Arnan; Rabus, Dominik G.; Karnutsch, Christian

2016-02-01

Lab-on-a-chip based portable blood analysis systems would allow point-of-care measurements, e.g. in an ambulance, or in remote areas with no fast access to medical care. Such a systemwould provide much faster information about the health of a patient. Here,we present a system that is based on absorption spectroscopy and uses an organic laser, which is tunable in the visible range. The feasibility of the system is shown with a table-top setup using laboratory equipment. Measurements of human albumin show linear behaviour in a range from 2.5 g/L to 60 g/L. In a consecutive setup the system is implemented on a microfluidic chip and is capable of measuring simultaneously transmitted and side scattered intensities, even with ambient light present. Air-suspended grating couplers on polymers are shown as the first element of a lab-on-a-chip implementation.

Electroosmotic mixing in microchannels.

PubMed

Glasgow, Ian; Batton, John; Aubry, Nadine

2004-12-01

Mixing is an essential, yet challenging, process step for many Lab on a Chip (LOC) applications. This paper presents a method of mixing for microfluidic devices that relies upon electroosmotic flow. In physical tests and in computer simulations, we periodically vary the electric field with time to mix two aqueous solutions. Good mixing is shown to occur when the electroosmotic flow at the two inlets pulse out of phase, the Strouhal number is on the order of 1, and the pulse volumes are on the order of the intersection volume.

Experimental investigation of evanescence-based infrared biodetection technique for micro-total-analysis systems.

PubMed

Chandrasekaran, Arvind; Packirisamy, Muthukumaran

2009-01-01

The advent of microoptoelectromechanical systems (MOEMS) and its integration with other technologies such as microfluidics, microthermal, immunoproteomics, etc. has led to the concept of an integrated micro-total-analysis systems (microTAS) or Lab-on-a-Chip for chemical and biological applications. Recently, research and development of microTAS have attained a significant growth rate over several biodetection sciences, in situ medical diagnoses, and point-of-care testing applications. However, it is essential to develop suitable biophysical label-free detection methods for the success, reliability, and ease of use of the microTAS. We proposed an infrared (IR)-based evanescence wave detection system on the silicon-on-insulator platform for biodetection with microTAS. The system operates on the principle of bio-optical interaction that occurs due to the evanescence of light from the waveguide device. The feasibility of biodetection has been experimentally investigated by the detection of horse radish peroxidase upon its reaction with hydrogen peroxide.

Numerical studies on a plasmonic temperature nanosensor based on a metal-insulator-metal ring resonator structure for optical integrated circuit applications

NASA Astrophysics Data System (ADS)

Al-mahmod, Md. Jubayer; Hyder, Rakib; Islam, Md Zahurul

2017-07-01

A nanosensor, based on a metal-insulator-metal (MIM) plasmonic ring resonator, is proposed for potential on-chip temperature sensing and its performance is evaluated numerically. The sensor components can be fabricated by using planar processes on a silicon substrate, making its manufacturing compatible to planar electronic fabrication technology. The sensor, constructed using silver as the metal rings and a thermo-optic liquid ethanol film between the metal layers, is capable of sensing temperature with outstanding optical sensitivity, as high as -0.53 nm/°C. The resonance wavelength is found to be highly sensitive to the refractive index of the liquid dielectric film. The resonance peak can be tuned according to the requirement of intended application by changing the radii of the ring resonator geometries in the design phase. The compact size, planar and silicon-based design, and very high resolutions- these characteristics are expected to make this sensor technology a preferred choice for lab-on-a-chip applications, as compared to other contemporary sensors.

Automation of daphtoxkit-F biotest using a microfluidic lab-on-a-chip technology

NASA Astrophysics Data System (ADS)

Huang, Yushi; Nugegoda, Dayanthi; Wlodkowic, Donald

2015-12-01

An increased rigor in water quality monitoring is not only a legal requirement, but is also critical to ensure timely chemical hazard emergency responses and protection of human and animal health. Bioindication is a method that applies very sensitive living organisms to detect environmental changes using their natural responses. Although bioindicators do not deliver information on an exact type or intensity of toxicants present in water samples, they do provide an overall snapshot and early-warning information about presence of harmful and dangerous parameters. Despite the advantages of biotests performed on sentinel organisms, their wider application is limited by the nonexistence of high-throughput laboratory automation systems. As a result majority of biotests used in ecotoxicology require time-consuming and laborious manual procedures. In this work, we present development of a miniaturized Lab-on-a-Chip (LOC) platform for automation and enhancement of acute ecotoxicity test based on immobilization of a freshwater crustacean Daphnia magna (Daphtoxkit-FTM). Daphnids' immobilization in response to sudden changes in environment parameters is fast, unambiguous, and easy to record optically. We also for the first time demonstrate that LOC system enables studies of sub-lethal ecotoxic effects using behavioral responses of Daphnia magna as sentinels of water pollution. The system working principle incorporated a high definition (HD) time-resolved video data analysis to dynamically assess impact of the reference toxicant on swimming behavior of D. magna. Our system design combined: (i) microfluidic device for caging of Daphnia sp.; (ii) mechatronic interface for fluidic actuation; (iii) video data acquisition; and (iv) algorithms for animal movement tracking and analysis.

Advances in Candida detection platforms for clinical and point-of-care applications

PubMed Central

Safavieh, Mohammadali; Coarsey, Chad; Esiobu, Nwadiuto; Memic, Adnan; Vyas, Jatin Mahesh; Shafiee, Hadi; Asghar, Waseem

2016-01-01

Invasive candidiasis remains one of the most serious community and healthcare-acquired infections worldwide. Conventional Candida detection methods based on blood and plate culture are time-consuming and require at least 2–4 days to identify various Candida species. Despite considerable advances for candidiasis detection, the development of simple, compact and portable point-of-care diagnostics for rapid and precise testing that automatically performs cell lysis, nucleic acid extraction, purification and detection still remains a challenge. Here, we systematically review most prominent conventional and nonconventional techniques for the detection of various Candida species, including Candida staining, blood culture, serological testing and nucleic acid-based analysis. We also discuss the most advanced lab on a chip devices for candida detection. PMID:27093473

3D Printing and Assay Development for Point-of-Care Applications

NASA Astrophysics Data System (ADS)

Jagadeesh, Shreesha

Existing centralized labs do not serve patients adequately in remote areas. To enable universal timely healthcare, there is a need to develop low cost, portable systems that can diagnose multiple disease (Point-of-Care (POC) devices). Future POC diagnostics can be more multi-functional if medical device vendors can develop interoperability standards. This thesis developed the following medical diagnostic modules: Plasma from 25 microl blood was extracted through a filter membrane to demonstrate a 3D printed sample preparation module. Sepsis biomarker, C - reactive protein, was quantified through adsorption on nylon beads to demonstrate bead-based assay suitable for 3D printed disposable cartridge module. Finally, a modular fluorescent detection kit was built using 3D printed parts to detect CD4 cells in a disposable cartridge from ChipCare Corp. Due to the modularity enabled by 3D printing technique, the developed units can be easily adapted to detect other diseases.

Towards toxicity detection using a lab-on-chip based on the integration of MOEMS and whole-cell sensors.

PubMed

Elman, Noel M; Ben-Yoav, Hadar; Sternheim, Marek; Rosen, Rachel; Krylov, Slava; Shacham-Diamand, Yosi

2008-06-15

A lab-on-chip consisting of a unique integration of whole-cell sensors, a MOEMS (Micro-Opto-Electro-Mechanical-System) modulator, and solid-state photo-detectors was implemented for the first time. Whole-cell sensors were genetically engineered to express a bioluminescent reporter (lux) as a function of the lac promoter. The MOEMS modulator was designed to overcome the inherent low frequency noise of solid-state photo-detectors by means of a previously reported modulation technique, named IHOS (Integrated Heterodyne Optical System). The bio-reporter signals were modulated prior to photo-detection, increasing the SNR of solid-state photo-detectors at least by three orders of magnitude. Experiments were performed using isopropyl-beta-d-thiogalactopyranoside (IPTG) as a preliminary step towards testing environmental toxicity. The inducer was used to trigger the expression response of the whole-cell sensors testing the sensitivity of the lab-on-chip. Low intensity bio-reporter optical signals were measured after the whole-cell sensors were exposed to IPTG concentrations of 0.1, 0.05, and 0.02mM. The experimental results reveal the potential of this technology for future implementation as an inexpensive massive method for rapid environmental toxicity detection.

Handheld analyzer with on-chip molecularly-imprinted biosensors for electrical detection of propofol in plasma samples.

PubMed

Hong, Chien-Chong; Lin, Chih-Chung; Hong, Chian-Lang; Lin, Zi-Xiang; Chung, Meng-Hua; Hsieh, Pei-Wen

2016-12-15

This paper proposes a novel handheld analyzer with disposable lab-on-a-chip technology for the electrical detection of the anesthetic propofol in human plasma samples for clinical diagnoses. The developed on-chip biosensors are based on the conduction of molecularly imprinted polymers (MIPs) that employ label-free electrical detection techniques. Propofol in total intravenous anesthesia is widely used with a target-controlled infusion system. At present, the methods employed for detecting blood propofol concentrations in hospitals comprise high-performance liquid chromatography and ion mobility spectrometry. These conventional instruments are bulky, expensive, and difficult to access. In this study, we developed a novel plastic microfluidic biochip with an on-chip anesthetic biosensor that was characterized for the rapid detection of propofol concentrations. The experimental results revealed that the response time of the developed propofol biosensors was 25s. The specific binding of an MIP to a nonimprinted polymer (NIP) reached up to 560%. Moreover, the detection limit of the biosensors was 0.1μg/mL, with a linear detection range of 0.1-30μg/mL. The proposed disposable microfluidic biochip with an on-chip anesthetic biosensor using MIPs exhibited excellent performance in the separation and sensing of propofol molecules in the human plasma samples. Compared with large-scale conventional instruments, the developed microfluidic biochips with on-chip MIP biosensors present the advantages of a compact size, high selectivity, low cost, rapid response, and single-step detection. Copyright © 2016 Elsevier B.V. All rights reserved.

Biomaterials and bioengineering tomorrow’s healthcare

PubMed Central

Bhat, Sumrita; Kumar, Ashok

2013-01-01

Biomaterials are being used for the healthcare applications from ancient times. But subsequent evolution has made them more versatile and has increased their utility. Biomaterials have revolutionized the areas like bioengineering and tissue engineering for the development of novel strategies to combat life threatening diseases. Together with biomaterials, stem cell technology is also being used to improve the existing healthcare facilities. These concepts and technologies are being used for the treatment of different diseases like cardiac failure, fractures, deep skin injuries, etc. Introduction of nanomaterials on the other hand is becoming a big hope for a better and an affordable healthcare. Technological advancements are underway for the development of continuous monitoring and regulating glucose levels by the implantation of sensor chips. Lab-on-a-chip technology is expected to modernize the diagnostics and make it more easy and regulated. Other area which can improve the tomorrow’s healthcare is drug delivery. Micro-needles have the potential to overcome the limitations of conventional needles and are being studied for the delivery of drugs at different location in human body. There is a huge advancement in the area of scaffold fabrication which has improved the potentiality of tissue engineering. Most emerging scaffolds for tissue engineering are hydrogels and cryogels. Dynamic hydrogels have huge application in tissue engineering and drug delivery. Furthermore, cryogels being supermacroporous allow the attachment and proliferation of most of the mammalian cell types and have shown application in tissue engineering and bioseparation. With further developments we expect these technologies to hit the market in near future which can immensely improve the healthcare facilities. PMID:23628868

Monitoring CO2 invasion processes at the pore scale using geological labs on chip.

PubMed

Morais, S; Liu, N; Diouf, A; Bernard, D; Lecoutre, C; Garrabos, Y; Marre, S

2016-09-21

In order to investigate at the pore scale the mechanisms involved during CO2 injection in a water saturated pore network, a series of displacement experiments is reported using high pressure micromodels (geological labs on chip - GLoCs) working under real geological conditions (25 < T (°C) < 75 and 4.5 < p (MPa) < 8). The experiments were focused on the influence of three experimental parameters: (i) the p, T conditions, (ii) the injection flow rates and (iii) the pore network characteristics. By using on-chip optical characterization and imaging approaches, the CO2 saturation curves as a function of either time or the number of pore volume injected were determined. Three main mechanisms were observed during CO2 injection, namely, invasion, percolation and drying, which are discussed in this paper. Interestingly, besides conventional mechanisms, two counterintuitive situations were observed during the invasion and drying processes.

Nanoscale Imaging Technology for THz Frequency Transmission Microscopy

DTIC Science & Technology

2014-12-16

potential assays, Lab on a Chip, (04 2012): 2719. doi : 10.1039/c2lc40086c Peter J. Burke, Nima Rouhi, Yung Yu Wang. Ultrahigh conductivity of large area...suspended few layer graphene films, Applied Physics Letters, (12 2012): 0. doi : 10.1063/1.4772797 Peter J. Burke, Yung Yu Wang. A large-area and...contamination-free graphene transistor for liquid-gated sensing applications, Applied Physics Letters, (07 2013): 0. doi : 10.1063/1.4816764

Biotechnology for Solar System Exploration

NASA Astrophysics Data System (ADS)

Steele, A.; Maule, J.; Toporski, J.; Parro-Garcia, V.; Briones, C.; Schweitzer, M.; McKay, D.

With the advent of a new era of astrobiology missions in the exploration of the solar system and the search for evidence of life elsewhere, we present a new approach to this goal, the integration of biotechnology. We have reviewed the current list of biotechnology techniques, which are applicable to miniaturization, automatization and integration into a combined flight platform. Amongst the techniques reviewed are- The uses of antibodies- Fluorescent detection strategies- Protein and DNA chip technology- Surface plasmon resonance and its relation to other techniques- Micro electronic machining (MEMS where applicable to biologicalsystems)- nanotechnology (e.g. molecular motors)- Lab-on-a-chip technology (including PCR)- Mass spectrometry (i.e. MALDI-TOF)- Fluid handling and extraction technologies- Chemical Force Microscopy (CFM)- Raman Spectroscopy We have begun to integrate this knowledge into a single flight instrument approach for the sole purpose of combining several mutually confirming tests for life, organic and/or microbial contamination, as well as prebiotic and abiotic organic chemicals. We will present several innovative designs for new instrumentation including pro- engineering design drawings of a protein chip reader for space flight and fluid handling strategies. We will also review the use of suitable extraction methodologies for use on different solar system bodies.

A Flexible Microcontroller-Based Data Acquisition Device

PubMed Central

Hercog, Darko; Gergič, Bojan

2014-01-01

This paper presents a low-cost microcontroller-based data acquisition device. The key component of the presented solution is a configurable microcontroller-based device with an integrated USB transceiver and a 12-bit analogue-to-digital converter (ADC). The presented embedded DAQ device contains a preloaded program (firmware) that enables easy acquisition and generation of analogue and digital signals and data transfer between the device and the application running on a PC via USB bus. This device has been developed as a USB human interface device (HID). This USB class is natively supported by most of the operating systems and therefore any installation of additional USB drivers is unnecessary. The input/output peripheral of the presented device is not static but rather flexible, and could be easily configured to customised needs without changing the firmware. When using the developed configuration utility, a majority of chip pins can be configured as analogue input, digital input/output, PWM output or one of the SPI lines. In addition, LabVIEW drivers have been developed for this device. When using the developed drivers, data acquisition and signal processing algorithms as well as graphical user interface (GUI), can easily be developed using a well-known, industry proven, block oriented LabVIEW programming environment. PMID:24892494

Biofunctionalized self-propelled micromotors as an alternative on-chip concentrating system.

PubMed

Restrepo-Pérez, Laura; Soler, Lluís; Martínez-Cisneros, Cynthia; Sánchez, Samuel; Schmidt, Oliver G

2014-08-21

Sample pre-concentration is crucial to achieve high sensitivity and low detection limits in lab-on-a-chip devices. Here, we present a system in which self-propelled catalytic micromotors are biofunctionalized and trapped acting as an alternative concentrating mechanism. This system requires no external energy source, which facilitates integration and miniaturization.

Complex Microfluidic Systems Architectures and Applications to Micropower Generation

DTIC Science & Technology

2010-07-07

signal. Images are recorded via an Hamamatsu Orca camera and processed with Matlab. The observed results show the ability of the micromixer to distribute...Generator was produced. References [1] F. Bottausci, C. Cardonne, C. Meinhart, and I. Mezić. An ultrashort mixing length micromixer : The shear superposition... micromixer . Lab on a Chip, 7(3):396–398, 2007. [2] F. Bottausci, I. Mezić, C.D. Meinhart, and C. Cardonne. Mixing in the shear superposition

Invited Article: Terahertz microfluidic chips sensitivity-enhanced with a few arrays of meta-atoms

NASA Astrophysics Data System (ADS)

Serita, Kazunori; Matsuda, Eiki; Okada, Kosuke; Murakami, Hironaru; Kawayama, Iwao; Tonouchi, Masayoshi

2018-05-01

We present a nonlinear optical crystal (NLOC)-based terahertz (THz) microfluidic chip with a few arrays of split ring resonators (SRRs) for ultra-trace and quantitative measurements of liquid solutions. The proposed chip operates on the basis of near-field coupling between the SRRs and a local emission of point like THz source that is generated in the process of optical rectification in NLOCs on a sub-wavelength scale. The liquid solutions flowing inside the microchannel modify the resonance frequency and peak attenuation in the THz transmission spectra. In contrast to conventional bio-sensing with far/near-field THz waves, our technique can be expected to compactify the chip design as well as realize high sensitive near-field measurement of liquid solutions without any high-power optical/THz source, near-field probes, and prisms. Using this chip, we have succeeded in observing the 31.8 fmol of ion concentration in actual amount of 318 pl water solutions from the shift of the resonance frequency. The technique opens the door to microanalysis of biological samples with THz waves and accelerates development of THz lab-on-chip devices.

Lab-on-a-brane: nanofibrous polymer membranes to recreate organ-capillary interfaces

NASA Astrophysics Data System (ADS)

Budhwani, Karim I.; Thomas, Vinoy; Sethu, Palaniappan

2016-03-01

Drug discovery is a complex and time consuming process involving significant basic research and preclinical evaluation prior to testing in patients. Preclinical studies rely extensively on animal models which often fail in human trials. Biomimetic microphysiological systems (MPS) using human cells can be a promising alternative to animal models; where critical interactions between different organ systems are recreated to provide physiologically relevant in vitro human models. Central here are blood-vessel networks, the interface controlling transport of cellular and biomolecular components between the circulating fluid and underlying tissue. Here we present a novel lab-on-a-brane (or lab-on-a-membrane) nanofluidics MPS that combines the elegance of lab-on-a-chip with the more realistic morphology of 3D fibrous tissue-engineering constructs. Our blood-vessel lab-on-a-brane effectively simulates in vivo vessel-tissue interface for evaluating transendothelial transport in various pharmacokinetic and nanomedicine applications. Attributes of our platform include (a) nanoporous barrier interface enabling transmembrane molecular transport, (b) transformation of substrate into nanofibrous 3D tissue matrix, (c) invertible-sandwich architecture, and (d) simple co-culture mechanism for endothelial and smooth muscle layers to accurately mimic arterial anatomy. Structural, mechanical, and transport characterization using scanning electron microscopy, stress/strain analysis, infrared spectroscopy, immunofluorescence, and FITC-Dextran hydraulic permeability confirm viability of this in vitro system. Thus, our lab-on-a-brane provides an effective and efficient, yet considerably inexpensive, physiologically relevant alternative for pharmacokinetic evaluation; possibly reducing animals used in preclinical testing, costs from false starts, and time-to-market. Furthermore, it can be configured in multiple simultaneous arrays for personalized and precision medicine applications and for evaluating localized and targeted therapeutic delivery.

Cell manipulation in microfluidics.

PubMed

Yun, Hoyoung; Kim, Kisoo; Lee, Won Gu

2013-06-01

Recent advances in the lab-on-a-chip field in association with nano/microfluidics have been made for new applications and functionalities to the fields of molecular biology, genetic analysis and proteomics, enabling the expansion of the cell biology field. Specifically, microfluidics has provided promising tools for enhancing cell biological research, since it has the ability to precisely control the cellular environment, to easily mimic heterogeneous cellular environment by multiplexing, and to analyze sub-cellular information by high-contents screening assays at the single-cell level. Various cell manipulation techniques in microfluidics have been developed in accordance with specific objectives and applications. In this review, we examine the latest achievements of cell manipulation techniques in microfluidics by categorizing externally applied forces for manipulation: (i) optical, (ii) magnetic, (iii) electrical, (iv) mechanical and (v) other manipulations. We furthermore focus on history where the manipulation techniques originate and also discuss future perspectives with key examples where available.

Development of a lab-on-chip electrochemical immunosensor for detection of Polycyclic Aromatic Hydrocarbons (PAH) in environmental water

NASA Astrophysics Data System (ADS)

Felemban, Shifa; Vazquez, Patricia; Dehnert, Jan; Goridko, Vadim; Tijero, Maria; Moore, Eric

2017-06-01

The work described in this manuscript focuses on how the integration of immunoassay techniques in combination with electrochemical detection can provide a portable and very accurate solution for detection of water pollutants that are detrimental for human health. In particular, we focus our work on the quantification of polycyclic aromatic hydrocarbons (PAHs) in polluted water. Our integrative approach facilitates a real-time detection of this family of organic compounds, by reducing the time of analysis to less than one hour. Additionally, the use of a lab-on-a-chip platform delivers a portable solution that could be used in situ. Optimization of a displacement assay that investigates the presence and concentration of Benzo[a]pyrene in water, allows with the miniaturization of the standard ELISA format into a highly accurate system that provides fast results. The limits of detection obtained are comparable to those of available state-of-the art tools, and achieve the values set by European Drinking Water Directive, 0.10ng/l, as the limit for PAHs in drinking water.

Gas-driven ultrafast reversible switching of super-hydrophobic adhesion on palladium-coated silicon nanowires.

PubMed

Seo, Jungmok; Lee, Soonil; Han, Heetak; Jung, Hwae Bong; Hong, Juree; Song, Giyoung; Cho, Suk Man; Park, Cheolmin; Lee, Wooyoung; Lee, Taeyoon

2013-08-14

A gas-driven ultrafast adhesion switching of water droplets on palladium-coated Si nanowire arrays is demonstrated. By regulating the gas-ambient between the atmosphere and H2 , the super-hydrophobic adhesion is repeatedly switched between water-repellent and water-adhesive. The capability of modulating the super-hydrophobic adhesion on a super-hydrophobic surface with a non-contact mode could be applicable to novel functional lab-on-a-chip platforms. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

a New Approach for Complete Mixing by Transverse and Streamwise Flow Motions in Micro-Channels

NASA Astrophysics Data System (ADS)

Wang, Muh-Rong; Dai, Chiau-Yi; Huang, Yang-Sheng

Mixing control is an important issue in micro-fluid chip applications, such as μTAS (Micro-Total Analysis System) or LOC (Lab-on-Chip) because the flow at micro-scale is highly laminar. Several flow control schemes had been developed for complete mixing in the micro-channels in the past decades. However, most of the mixing control schemes are performed by utilizing specific excitation devices, such as electrokinetic, magnetic or pressure drivers. This paper investigates a new control scheme which is composed of a series of flow manipulation by changing the pressure at the two inlets of the micromixer as the external excitation. The fluids from two inlets are introduced to a square mixing chamber, which provides a space where the streamwise and transverse flow motions take place. The results show that the micromixer can be used to produce a large recirculation zone with series of small transverse fringes under external excitations. It is found that this new flow pattern enhances mixing processes at the micro-scale. A complete mixing can be achieved under appropriate flow control with the corresponding design.

Magnetic helical micromachines.

PubMed

Peyer, Kathrin E; Tottori, Soichiro; Qiu, Famin; Zhang, Li; Nelson, Bradley J

2013-01-02

Helical microrobots have the potential to be used in a variety of application areas, such as in medical procedures, cell biology, or lab-on-a-chip. They are powered and steered wirelessly using low-strength rotating magnetic fields. The helical shape of the device allows propulsion through numerous types of materials and fluids, from tissue to different types of bodily fluids. Helical propulsion is suitable for pipe flow conditions or for 3D swimming in open fluidic environments. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

Nabeel A. Riza

The goals of the Year 2006 Continuation Phase 2 three months period (April 1 to Sept. 30) of this project were to (a) conduct a probe elements industrial environment feasibility study and (b) fabricate embedded optical phase or microstructured SiC chips for individual gas species sensing. Specifically, SiC chips for temperature and pressure probe industrial applications were batch fabricated. Next, these chips were subject to a quality test for use in the probe sensor. A batch of the best chips for probe design were selected and subject to further tests that included sensor performance based on corrosive chemical exposure, powermore » plant soot exposure, light polarization variations, and extreme temperature soaking. Experimental data were investigated in detail to analyze these mentioned industrial parameters relevant to a power plant. Probe design was provided to overcome mechanical vibrations. All these goals have been achieved and are described in detail in the report. The other main focus of the reported work is to modify the SiC chip by fabricating an embedded optical phase or microstructures within the chip to enable gas species sensing under high temperature and pressure. This has been done in the Kar UCF Lab. using a laser-based system whose design and operation is explained. Experimental data from the embedded optical phase-based chip for changing temperatures is provided and shown to be isolated from gas pressure and species. These design and experimentation results are summarized to give positive conclusions on the proposed high temperature high pressure gas species detection optical sensor technology.« less

Design and Modelling of a Microfluidic Electro-Lysis Device with Controlling Plates

NASA Technical Reports Server (NTRS)

Jenkins, A.; Chen, C. P.; Spearing, S.; Monaco, L. A.; Steele, A.; Flores, G.

2006-01-01

Many Lab-on-Chip applications require sample pre-treatment systems. Using electric fields to perform cell-lysis in bio-MEMS systems has provided a powerful tool which can be integrated into Lab-on-a-Chip platforms. The major design considerations for electro-lysis devices include optimal geometry and placement of micro-electrodes, cell concentration, flow rates, optimal electric field (e.g. pulsed DC vs. AC), etc. To avoid electrolysis of the flowing solution at the exposed electrode surfaces, magnitudes and the applied voltages and duration of the DC pulse, or the AC frequency of the AC, have to be optimized for a given configuration. Using simulation tools for calculation of electric fields has proved very useful, for exploring alternative configurations and operating conditions for achieving electro cell-lysis. To alleviate the problem associated with low electric fields within the microfluidics channel and the high voltage demand on the contact electrode strips, two "control plates" are added to the microfluidics configuration. The principle of placing the two controlling plate-electrodes is based on the electric fields generated by a combined insulator/dielectric (gladwater) media. Surface charges are established at the insulator/dielectric interface. This paper discusses the effects of this interface charge on the modification of the electric field of the flowing liquid/cell solution.

Design and Modelling of a Microfluidic Electro-Lysis Device with Controlling Plates

NASA Astrophysics Data System (ADS)

Jenkins, A.; Chen, C. P.; Spearing, S.; Monaco, L. A.; Steele, A.; Flores, G.

2006-04-01

Many Lab-on-Chip applications require sample pre-treatment systems. Using electric fields to perform cell lysis in bio-MEMS systems has provided a powerful tool which can be integrated into Lab-on-a- Chip platforms. The major design considerations for electro-lysis devices include optimal geometry and placement of micro-electrodes, cell concentration, flow rates, optimal electric field (e.g. pulsed DC vs. AC), etc. To avoid electrolysis of the flowing solution at the exposed electrode surfaces, magnitudes and the applied voltages and duration of the DC pulse, or the AC frequency of the AC, have to be optimized for a given configuration. Using simulation tools for calculation of electric fields has proved very useful, for exploring alternative configurations and operating conditions for achieving electro cell-lysis. To alleviate the problem associated with low electric fields within the microfluidics channel and the high voltage demand on the contact electrode strips, two ''control plates'' are added to the microfluidics configuration. The principle of placing the two controlling plate-electrodes is based on the electric fields generated by a combined insulator/dielectric (glass/water) media. Surface charges are established at the insulator/dielectric interface. This paper discusses the effects of this interface charge on the modification of the electric field of the flowing liquid/cell solution.

Monolithic Teflon membrane valves and pumps for harsh chemical and low-temperature use.

PubMed

Willis, Peter A; Hunt, Brian D; White, Victor E; Lee, Michael C; Ikeda, Michael; Bae, Sam; Pelletier, Michael J; Grunthaner, Frank J

2007-11-01

Microfluidic diaphragm valves and pumps capable of surviving conditions required for unmanned spaceflight applications have been developed. The Pasteur payload of the European ExoMars Rover is expected to experience temperatures ranging between -100 degrees C and +50 degrees C during its transit to Mars and on the Martian surface. As such, the Urey instrument package, which contains at its core a lab-on-a-chip capillary electrophoresis analysis system first demonstrated by Mathies et al., requires valving and pumping systems that are robust under these conditions before and after exposure to liquid samples, which are to be analyzed for chemical signatures of past or present living processes. The microfluidic system developed to meet this requirement uses membranes consisting of Teflon and Teflon AF as a deformable material in the valve seat region between etched Borofloat glass wafers. Pneumatic pressure and vacuum, delivered via off-chip solenoid valves, are used to actuate individual on-chip valves. Valve sealing properties of Teflon diaphragm valves, as well as pumping properties from collections of valves, are characterized. Secondary processing for embossing the membrane against the valve seats after fabrication is performed to optimize single valve sealing characteristics. A variety of different material solutions are found to produce robust devices. The optimal valve system utilizes a membrane of mechanically cut Teflon sandwiched between two thin spun films of Teflon AF-1600 as a composite "laminated" diaphragm. Pump rates up to 1600 nL s(-1) are achieved with pumps of this kind. These high pumping rates are possible because of the very fast response of the membranes to applied pressure, enabling extremely fast pump cycling with relatively small liquid volumes, compared to analogous diaphragm pumps. The developed technologies are robust over extremes of temperature cycling and are applicable in a wide range of chemical environments.

Miniature stick-packaging--an industrial technology for pre-storage and release of reagents in lab-on-a-chip systems.

PubMed

van Oordt, Thomas; Barb, Yannick; Smetana, Jan; Zengerle, Roland; von Stetten, Felix

2013-08-07

Stick-packaging of goods in tubular-shaped composite-foil pouches has become a popular technology for food and drug packaging. We miniaturized stick-packaging for use in lab-on-a-chip (LOAC) systems to pre-store and on-demand release the liquid and dry reagents in a volume range of 80-500 μl. An integrated frangible seal enables the pressure-controlled release of reagents and simplifies the layout of LOAC systems, thereby making the package a functional microfluidic release unit. The frangible seal is adjusted to defined burst pressures ranging from 20 to 140 kPa. The applied ultrasonic welding process allows the packaging of temperature sensitive reagents. Stick-packs have been successfully tested applying recovery tests (where 99% (STDV = 1%) of 250 μl pre-stored liquid is released), long-term storage tests (where there is loss of only <0.5% for simulated 2 years) and air transport simulation tests. The developed technology enables the storage of a combination of liquid and dry reagents. It is a scalable technology suitable for rapid prototyping and low-cost mass production.

On-chip collection of particles and cells by AC electroosmotic pumping and dielectrophoresis using asymmetric microelectrodes.

PubMed

Melvin, Elizabeth M; Moore, Brandon R; Gilchrist, Kristin H; Grego, Sonia; Velev, Orlin D

2011-09-01

The recent development of microfluidic "lab on a chip" devices requiring sample sizes <100 μL has given rise to the need to concentrate dilute samples and trap analytes, especially for surface-based detection techniques. We demonstrate a particle collection device capable of concentrating micron-sized particles in a predetermined area by combining AC electroosmosis (ACEO) and dielectrophoresis (DEP). The planar asymmetric electrode pattern uses ACEO pumping to induce equal, quadrilateral flow directed towards a stagnant region in the center of the device. A number of system parameters affecting particle collection efficiency were investigated including electrode and gap width, chamber height, applied potential and frequency, and number of repeating electrode pairs and electrode geometry. The robustness of the on-chip collection design was evaluated against varying electrolyte concentrations, particle types, and particle sizes. These devices are amenable to integration with a variety of detection techniques such as optical evanescent waveguide sensing.

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.

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

NASA Astrophysics Data System (ADS)

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

2017-03-01

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

Graphene-based microfluidics for serial crystallography.

PubMed

Sui, Shuo; Wang, Yuxi; Kolewe, Kristopher W; Srajer, Vukica; Henning, Robert; Schiffman, Jessica D; Dimitrakopoulos, Christos; Perry, Sarah L

2016-08-02

Microfluidic strategies to enable the growth and subsequent serial crystallographic analysis of micro-crystals have the potential to facilitate both structural characterization and dynamic structural studies of protein targets that have been resistant to single-crystal strategies. However, adapting microfluidic crystallization platforms for micro-crystallography requires a dramatic decrease in the overall device thickness. We report a robust strategy for the straightforward incorporation of single-layer graphene into ultra-thin microfluidic devices. This architecture allows for a total material thickness of only ∼1 μm, facilitating on-chip X-ray diffraction analysis while creating a sample environment that is stable against significant water loss over several weeks. We demonstrate excellent signal-to-noise in our X-ray diffraction measurements using a 1.5 μs polychromatic X-ray exposure, and validate our approach via on-chip structure determination using hen egg white lysozyme (HEWL) as a model system. Although this work is focused on the use of graphene for protein crystallography, we anticipate that this technology should find utility in a wide range of both X-ray and other lab on a chip applications.

Microfluidic Controlled Conformal Coating of Particles

NASA Astrophysics Data System (ADS)

Tsai, Scott; Wexler, Jason; Wan, Jiandi; Stone, Howard

2011-11-01

Coating flows are an important class of fluid mechanics problems. Typically a substrate is coated with a moving continuous film, but it is also possible to consider coating of discrete objects. In particular, in applications involving coating of particles that are useful in drug delivery, the coatings act as drug-carrying vehicles, while in cell therapy a thin polymeric coating is required to protect the cells from the host's immune system. Although many functional capabilities have been developed for lab-on-a-chip devices, a technique for coating has not been demonstrated. We present a microfluidic platform developed to coat micron-size spheres with a thin aqueous layer by magnetically pulling the particles from the aqueous phase to the non-aqueous phase in a co-flow. Coating thickness can be adjusted by the average fluid speed and the number of beads encapsulated inside a single coat is tuned by the ratio of magnetic to interfacial forces acting on the beads.

A system for characterization of DEPFET silicon pixel matrices and test beam results

NASA Astrophysics Data System (ADS)

Furletov, Sergey; DEPFET Collaboration

2011-02-01

The DEPFET pixel detector offers first stage in-pixel amplification by incorporating a field effect transistor in the high resistivity silicon substrate. In this concept, a very small input capacitance can be realized thus allowing for low noise measurements. This makes DEPFET sensors a favorable technology for tracking in particle physics. Therefore a system with a DEPFET pixel matrix was developed to test DEPFET performance for an application as a vertex detector for the Belle II experiment. The system features a current based, row-wise readout of a DEPFET pixel matrix with a designated readout chip, steering chips for matrix control, a FPGA based data acquisition board, and a dedicated software package. The system was successfully operated in both test beam and lab environment. In 2009 new DEPFET matrices have been characterized in a 120 GeV pion beam at the CERN SPS. The current status of the DEPFET system and test beam results are presented.

Microfluidic magnetic bead conveyor belt.

PubMed

van Pelt, Stijn; Frijns, Arjan; den Toonder, Jaap

2017-11-07

Magnetic beads play an important role in the miniaturization of clinical diagnostics systems. In lab-on-chip platforms, beads can be made to link to a target species and can then be used for the manipulation and detection of this species. Current bead actuation systems utilize complex on-chip coil systems that offer low field strengths and little versatility. We demonstrate a novel system based on an external rotating magnetic field and on-chip soft-magnetic structures to focus the field locally. These structures were designed and optimized using finite element simulations in order to create a number of local flux density maxima. These maxima, to which the magnetic beads are attracted, move over the chip surface in a continuous way together with the rotation of the external field, resulting in a mechanism similar to that of a conveyor belt. A prototype was fabricated using PDMS molding techniques mixed with iron powder for the magnetic structures. In the subsequent experiments, a quadrupole electromagnet was used to create the rotating external field. We observed that beads formed agglomerates that rolled over the chip surface, just above the magnetic structures. Field rotation frequencies between 0.1-50 Hz were tested resulting in magnetic bead speeds of over 1 mm s -1 for the highest frequency. With this, we have shown that our novel concept works, combining a simple design and simple operation with a powerful and versatile method for bead actuation. This makes it a promising method for further research and utilization in lab-on-chip systems.

Injection and injection-compression moulding replication capability for the production of polymer lab-on-a-chip with nano structures

NASA Astrophysics Data System (ADS)

Calaon, M.; Tosello, G.; Garnaes, J.; Hansen, H. N.

2017-10-01

The manufacturing precision and accuracy in the production of polymer lab-on-a-chip components with 100-130 nm deep nanochannels are evaluated using a metrological approach. Replication fidelity on corresponding process fingerprint test nanostructures over different substrates (nickel tool and polymer part) is quantified through traceable atomic force microscope measurements. Dimensions of injection moulded (IM) and injection-compression moulded (ICM) thermoplastic cyclic olefin copolymer nanofeatures are characterized depending on process parameters and four different features positions on a 30  ×  80 mm2 area. Replication capability of IM and ICM technologies are quantified and the products tolerance at the nanometre dimensional scale verified.

Impedance feedback control of microfluidic valves for reliable post processing combinatorial droplet injection.

PubMed

Axt, Brant; Hsieh, Yi-Fan; Nalayanda, Divya; Wang, Tza-Huei

2017-09-01

Droplet microfluidics has found use in many biological assay applications as a means of high-throughput sample processing. One of the challenges of the technology, however, is the ability to control and merge droplets on-demand as they flow through the microdevices. It is in the interest of developing lab-on-chip devices to be able to combinatorically program additive mixing steps for more complex multistep and multiplex assays. Existing technologies to merge droplets are either passive in nature or require highly predictable droplet movement for feedforward control, making them vulnerable to errors during high throughput operation. In this paper, we describe and demonstrate a microfluidic valve-based device for the purpose of combinatorial droplet injection at any stage in a multistep assay. Microfluidic valves are used to robustly control fluid flow, droplet generation, and droplet mixing in the device on-demand, while on-chip impedance measurements taken in real time are used as feedback to accurately time the droplet injections. The presented system is contrasted to attempts without feedback, and is shown to be 100% reliable over long durations. Additionally, content detection and discretionary injections are explored and successfully executed.

Portable capillary electrophoresis-system for on-site food analysis with lab-on-a-chip based contactless conductivity detection

NASA Astrophysics Data System (ADS)

Gärtner, Claudia; Sewart, René; Klemm, Richard; Becker, Holger

2014-06-01

A portable analytical system for the characterization of liquid environmental samples and beverages in food control was realized. The key element is the implementation of contactless conductivity detection on lab-on-a-chip basis ensuring the system to be operated in a label free mode. Typical target molecules such as small ionic species like Li+, Na+, K+, SO4 2- or NO3-, organic acids in wine whose concentration and ratio to each other documents the wine quality, or caffeine or phosphate in coke were detected. Results from sample matrices like various beverages as water, cola, tea, wine and milk, water from heaters, environmental samples and blood will be presented.

Localized heating on silicon field effect transistors: device fabrication and temperature measurements in fluid.

PubMed

Elibol, Oguz H; Reddy, Bobby; Nair, Pradeep R; Dorvel, Brian; Butler, Felice; Ahsan, Zahab S; Bergstrom, Donald E; Alam, Muhammad A; Bashir, Rashid

2009-10-07

We demonstrate electrically addressable localized heating in fluid at the dielectric surface of silicon-on-insulator field-effect transistors via radio-frequency Joule heating of mobile ions in the Debye layer. Measurement of fluid temperatures in close vicinity to surfaces poses a challenge due to the localized nature of the temperature profile. To address this, we developed a localized thermometry technique based on the fluorescence decay rate of covalently attached fluorophores to extract the temperature within 2 nm of any oxide surface. We demonstrate precise spatial control of voltage dependent temperature profiles on the transistor surfaces. Our results introduce a new dimension to present sensing systems by enabling dual purpose silicon transistor-heaters that serve both as field effect sensors as well as temperature controllers that could perform localized bio-chemical reactions in Lab on Chip applications.

Polydimethylsiloxane SlipChip for mammalian cell culture applications.

PubMed

Chang, Chia-Wen; Peng, Chien-Chung; Liao, Wei-Hao; Tung, Yi-Chung

2015-11-07

This paper reports a polydimethylsiloxane (PDMS) SlipChip for in vitro cell culture applications, multiple-treatment assays, cell co-cultures, and cytokine detection assays. The PDMS SlipChip is composed of two PDMS layers with microfluidic channels on each surface that are separated by a thin silicone fluid (Si-fluid) layer. The integration of Si-fluid enables the two PDMS layers to be slid to different positions; therefore, the channel patterns can be re-arranged for various applications. The SlipChip design significantly reduces the complexity of sample handling, transportation, and treatment processes. To apply the developed SlipChip for cell culture applications, human lung adenocarcinoma epithelial cells (A549) and lung fibroblasts (MRC-5) were cultured to examine the biocompatibility of the developed PDMS SlipChip. Moreover, embryonic pluripotent stem cells (ES-D3) were also cultured in the device to evaluate the retention of their stemness in the device. The experimental results show that cell morphology, viability and proliferation are not affected when the cells are cultured in the SlipChip, indicating that the device is highly compatible with mammalian cell culture. In addition, the stemness of the ES-D3 cells was highly retained after they were cultured in the device, suggesting the feasibility of using the SlipChip for stem cell research. Various cell experiments, such as simultaneous triple staining of cells and co-culture of MRC-5 with A549 cells, were also performed to demonstrate the functionalities of the PDMS SlipChip. Furthermore, we used a cytokine detection assay to evaluate the effect of endotoxin (lipopolysaccharides, LPS) treatment on the cytokine secretion of A549 cells using the SlipChip. The developed PDMS SlipChip provides a straightforward and effective platform for various on-chip in vitro cell cultures and consequent analysis, which is promising for a number of cell biology studies and biomedical applications.

Real-time label-free biosensing with integrated planar waveguide ring resonators

NASA Astrophysics Data System (ADS)

Sohlström, Hans; Gylfason, Kristinn B.; Hill, Daniel

2010-05-01

We review the use of planar integrated optical waveguide ring resonators for label free bio-sensing and present recent results from two European biosensor collaborations: SABIO and InTopSens. Planar waveguide ring resonators are attractive for label-free biosensing due to their small footprint, high Q-factors, and compatibility with on-chip optics and microfluidics. This enables integrated sensor arrays for compact labs-on-chip. One application of label-free sensor arrays is for point-of-care medical diagnostics. Bringing such powerful tools to the single medical practitioner is an important step towards personalized medicine, but requires addressing a number of issues: improving limit of detection, managing the influence of temperature, parallelization of the measurement for higher throughput and on-chip referencing, efficient light-coupling strategies to simplify alignment, and packaging of the optical chip and integration with microfluidics. From the SABIO project we report refractive index measurement and label-free biosensing in an 8-channel slotwaveguide ring resonator sensor array, within a compact cartridge with integrated microfluidics. The sensors show a volume sensing detection limit of 5 x 10-6 RIU and a surface sensing detection limit of 0.9 pg/mm2. From the InTopSens project we report early results on silicon-on-insulator racetrack resonators.

A versatile electrophoresis-based self-test platform.

PubMed

Staal, Steven; Ungerer, Mathijn; Floris, Arjan; Ten Brinke, Hans-Willem; Helmhout, Roy; Tellegen, Marian; Janssen, Kjeld; Karstens, Erik; van Arragon, Charlotte; Lenk, Stefan; Staijen, Erik; Bartholomew, Jody; Krabbe, Hans; Movig, Kris; Dubský, Pavel; van den Berg, Albert; Eijkel, Jan

2015-03-01

This paper reports on recent research creating a family of electrophoresis-based point of care devices for the determination of a wide range of ionic analytes in various sample matrices. These devices are based on a first version for the point-of-care measurement of Li(+), reported in 2010 by Floris et al. (Lab Chip 2010, 10, 1799-1806). With respect to this device, significant improvements in accuracy, precision, detection limit, and reliability have been obtained especially by the use of multiple injections of one sample on a single chip and integrated data analysis. Internal and external validation by clinical laboratories for the determination of analytes in real patients by a self-test is reported. For Li(+) in blood better precision than the standard clinical determination for Li(+) was achieved. For Na(+) in human urine the method was found to be within the clinical acceptability limits. In a veterinary application, Ca(2+) and Mg(2+) were determined in bovine blood by means of the same chip, but using a different platform. Finally, promising preliminary results are reported with the Medimate platform for the determination of creatinine in whole blood and quantification of both cations and anions through replicate measurements on the same sample with the same chip. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

'Fab-chips': a versatile, fabric-based platform for low-cost, rapid and multiplexed diagnostics.

PubMed

Bhandari, Paridhi; Narahari, Tanya; Dendukuri, Dhananjaya

2011-08-07

Low cost and scalable manufacture of lab-on-chip devices for applications such as point-of-care testing is an urgent need. Weaving is presented as a unified, scalable and low-cost platform for the manufacture of fabric chips that can be used to perform such testing. Silk yarns with different properties are first selected, treated with the appropriate reagent solutions, dried and handloom-woven in one step into an integrated fabric chip. This platform has the unique advantage of scaling up production using existing and low cost physical infrastructure. We have demonstrated the ability to create pre-defined flow paths in fabric by using wetting and non-wetting silk yarns and a Jacquard attachment in the loom. Further, we show that yarn parameters such as the yarn twist frequency and weaving coverage area may be conveniently used to tune both the wicking rate and the absorptive capacity of the fabric. Yarns optimized for their final function were used to create an integrated fabric chip containing reagent-coated yarns. Strips of this fabric were then used to perform a proof-of-concept immunoassay with sample flow taking place by capillary action and detection being performed by a visual readout. This journal is © The Royal Society of Chemistry 2011

Development of CMOS Active Pixel Image Sensors for Low Cost Commercial Applications

NASA Technical Reports Server (NTRS)

Fossum, E.; Gee, R.; Kemeny, S.; Kim, Q.; Mendis, S.; Nakamura, J.; Nixon, R.; Ortiz, M.; Pain, B.; Zhou, Z.;

Trapping of vesicles on patterned surfaces by physisorption for potential biosensing applications.

PubMed

Bera, L K; Ong, Kian Soo; Wong, Zheng Zheng; Fu, Zhikang; Nallani, Madhavan; Shea, Sean O'

2012-01-01

The pre-defined selective positioning of a controlled number of vesicles on a rigid substrate is crucial in many potential applications such as diagnostics, biosensors, lab-on-a chip, microanalyses and reaction chambers. In this paper, the vesicles made up of block copolymer using Poly [-(2-methyloxazoline) -poly- (dimethylsiloxane)-poly- (2-methyloxazoline)] (ABA) with dimensions of 100-200 nm are trapped by physisorption on hydrophilic surfaces. We discuss the protocols established for vesicle trapping. The optimum conditions obtained for physisorption is 15 minutes incubation followed by one cycle of DI water rinse. Trapping of 1-10 vesicles in lobe shape micro-wells fabricated by photo lithography using photoresist on UltraStick(™) slides was demonstrated. To overcome the issue of amalgamation of emitted light from optically sensitive photoresist and fluorescently tagged vesicles, an alternative approach of Si/SiO(2) microwell array coupled with APTES (3-AminoPropylTriEthoxySilane) treated bottom surfaces was developed.

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

NASA Astrophysics Data System (ADS)

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

2011-02-01

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

Optical devices for biochemical sensing in flame hydrolysis deposited glass

NASA Astrophysics Data System (ADS)

Ruano-Lopez, Jesus M.

Previous research in the field of Flame Hydrolysis Deposition (FHD) of glasses has focused on the production of low cost optical devices for the field of telecommunications. The originality of this doctoral research resides in the exploration of this technology in the fabrication of optical bio-chemical sensors, with integrated "Lab-on-a-chip" devices. To achieve this goal, we have combined and applied different microfabrication processes for the manufacture of sensor platforms using FHD. These structures are unique in that they take advantage of the intrinsic benefits of the microfabrication process, such as, miniaturisation and mass production, and combine them with the properties of FHD glass, namely: low loss optical transducing mechanisms, planar technologies and monolithic integration. This thesis demonstrates that FHD is a suitable technology for biosensing and Lab- on-a-Chip applications. The objective is to provide future researchers with the necessary tools to accomplish an integrated analytical system based on FHD. We have designed, fabricated, and successfully tested a FHD miniaturised sensor, which comprised optical and microfluidic circuitry, in the framework of low volume fluorescence assays. For the first time, volumes as low as 570 pL were analysed with a Cyanine-5 fluorophore with a detection limit of 20 pM, or ca. 6000 molecules (+/-3sigma) for this platform. The fabrication of the sensor generated a compilation of processes that were then utilised to produce other possible optical platforms for bio-chemical sensors in FHD, e.g. arrays and microfluidics. The "catalogue" of methods used included new recipes for reactive ion etching, glass deposition and bonding techniques that enabled the development of the microfluidic circuitry, integrated with an optical circuitry. Furthermore, we developed techniques to implement new tasks such as optical signal treatment using integrated optical structures, planar arraying of sensors, a separating element for liquid chromatography, and finally a pumping system for delivering small amounts of liquid along the microfluidic channels. This thesis comprises six chapters. In Chapter 1, an overview of the topic was presented, offering a review of the various fields addressed, as well as a description of the motivation and originality of this work. Chapter 2 describes the processes developed to fabricate an optical sensor, and Chapter 3 assesses its performance. In Chapter 4, integrated optical circuit designs and their fabrication methods, as well as developing and testing of an array of sensors, are presented. The description of a separating element involved in a liquid chromatography system, and the pumping of liquids in a FHD optical device, were addressed in Chapter 5. Finally, Chapter 6 summarised the conclusions and suggested possible future work. Last but not least, the appendix, contains techniques for hybrid integration; recipes for etching of rare earth glasses; as well as instrumentation designs. This research has taken Flame Hydrolysis Deposition technique into the world of optical bio-chemical sensors, creating a bridge between analytical assays and FHD glass. In this respect, the demonstrated flexibility of the technology will enable a variety of configurations to be created and implemented, with the prospect of using the techniques for laboratory-on-a-chip technologies. The work has been patented by the University of Glasgow, for future exploitation in analytical biotechnology and Lab-on-a-Chip.

Investigation on hemolytic effect of poly(lactic co-glycolic) acid nanoparticles synthesized using continuous flow and batch processes

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

Libi, Sumit; Calenic, Bogdan; Astete, Carlos E.

Abstract With the increasing interest in polymeric nanoparticles for biomedical applications, there is a need for continuous flow methodologies that allow for the precise control of nanoparticle synthesis. Poly(lactide-co-glycolic) acid (PLGA) nanoparticles with diameters of 220–250 nm were synthesized using a lab-on-a-chip, exploiting the precise flow control offered by a millifluidic platform. The association and the effect of PLGA nanoparticles on red blood cells (RBCs) were compared for fluorescent PLGA nanoparticles made by this novel continuous flow process using a millifluidic chip and smaller PLGA nanoparticles made by a batch method. Results indicated that all PLGA nanoparticles studied, independent ofmore » the synthesis method and size, adhered to the surface of RBCs but had no significant hemolytic effect at concentrations lower than 10 mg/ml.« less

Miniaturization of environmental chemical assays in flowing systems: the lab-on-a-valve approach vis-à-vis lab-on-a-chip microfluidic devices.

PubMed

Miró, Manuel; Hansen, Elo Harald

2007-09-26

The analytical capabilities of the microminiaturized lab-on-a-valve (LOV) module integrated into a microsequential injection (muSI) fluidic system in terms of analytical chemical performance, microfluidic handling and on-line sample processing are compared to those of the micro total analysis systems (muTAS), also termed lab-on-a-chip (LOC). This paper illustrates, via selected representative examples, the potentials of the LOV scheme vis-à-vis LOC microdevices for environmental assays. By means of user-friendly programmable flow and the exploitation of the interplay between the thermodynamics and the kinetics of the chemical reactions at will, LOV allows accommodation of reactions which, at least at the present stage, are not feasible by application of microfluidic LOC systems. Thus, in LOV one may take full advantage of kinetic discriminations schemes, where even subtle differences in reactions are utilized for analytical purposes. Furthermore, it is also feasible to handle multi-step sequential reactions of divergent kinetics; to conduct multi-parametric determinations without manifold reconfiguration by utilization of the inherent open-architecture of the micromachined unit for implementation of peripheral modules and automated handling of a variety of reagents; and most importantly, it offers itself as a versatile front end to a plethora of detection schemes. Not the least, LOV is regarded as an emerging downscaled tool to overcome the dilemma of LOC microsystems to admit real-life samples. This is nurtured via its intrinsic flexibility for accommodation of sample pre-treatment schemes aimed at the on-line manipulation of complex samples. Thus, LOV is playing a prominent role in the environmental field, whenever the monitoring of trace level concentration of pollutants is pursued, because both matrix isolation and preconcentration of target analytes is most often imperative, or in fact necessary, prior to sample presentation to the detector.

Immunoassay of paralytic shellfish toxins by moving magnetic particles in a stationary liquid-phase lab-on-a-chip.

PubMed

Kim, Myoung-Ho; Choi, Suk-Jung

2015-04-15

In this study, we devised a stationary liquid-phase lab-on-a-chip (SLP LOC), which was operated by moving solid-phase magnetic particles in the stationary liquid phase. The SLP LOC consisted of a sample chamber to which a sample and reactants were added, a detection chamber containing enzyme substrate solution, and a narrow channel connecting the two chambers and filled with buffer. As a model system, competitive immunoassays of saxitoxin (STX), a paralytic shellfish toxin, were conducted in the SLP LOC using protein G-coupled magnetic particles (G-MPs) as the solid phase. Anti-STX antibodies, STX-horseradish peroxidase conjugate, G-MPs, and a STX sample were added to the sample chamber and reacted by shaking. While liquids were in the stationary state, G-MPs were transported from the sample chamber to the detection chamber by moving a magnet below the LOC. After incubation to allow the enzymatic reaction to occur, the absorbance of the detection chamber solution was found to be reciprocally related to the STX concentration of the sample. Thus, the SLP LOC may represent a novel, simple format for point-of-care testing applications of enzyme-linked immunosorbent assays by eliminating complicated liquid handling steps. Copyright © 2014 Elsevier B.V. All rights reserved.

Ultrasensitive optofluidic-nanoplasmonic BioNEMS for life sciences and point-of-care diagnostics

NASA Astrophysics Data System (ADS)

Yanik, Ahmet Ali

2014-03-01

Recent progress on the development of optofluidic-nanoplasmonic BioNEMS is reviewed in this proceeding. Following a brief summary of the fundamental limitations in current lab-on-chip platforms, optofluidic-nanoplasmonic BioNEMS are discussed in detail and means to overcome mass transport limitations are shown. Finally, nanofluidic approach is extended to a cross fluidic scheme for efficiently isolation of rare circulating tumor cells.

Enabling rapid behavioral ecotoxicity studies using an integrated lab-on-a-chip systems

NASA Astrophysics Data System (ADS)

Huang, Yushi; Nugegoda, Dayanthi; Wlodkowic, Donald

2015-12-01

Behavioral ecotoxicity tests are gaining an increasing recognition in environmental toxicology. Behavior of sensitive bioindicator species can change rapidly in response to an acute exposure to contaminants and thus has a much higher sensitivity as compared to conventional LC50 mortality tests. Furthermore, behavioral endpoints seems to be very good candidates to develop early-warning biomonitoring systems needed for rapid chemical risk assessment. Behavioral tests are non-invasive, fast, do not harm indicator organisms (behavioural changes are very rapid) and are thus fully compatible with 3R (Replacement - Reduction - Refinement) principle encouraging alternatives to conventional animal testing. These characteristics are essential when designing improved ecotoxicity tests for chemical risk assessment. In this work, we present a pilot development of miniaturized Lab-on-a-Chip (LOC) devices for studying toxin avoidance behaviors of small aquatic crustaceans. As an investigative tool, LOCs represent a new direction that may miniaturize and revolutionize behavioral ecotoxicology. Specifically our innovative microfluidic prototype: (i) enables convening "caging" of specimens for real-time videomicroscopy; (ii) eliminates the evaporative water loss thus providing an opportunity for long-term behavioral studies; (iii) exploits laminar fluid flow under low Reynolds numbers to generate discrete domains and gradients enabling for the first time toxin avoidance studies on small aquatic crustaceans; (iv) integrates off-the-chip mechatronic interfaces and video analysis algorithms for single animal movement analysis. We provide evidence that by merging innovative bioelectronic and biomicrofluidic technologies we can deploy inexpensive and reliable systems for culture, electronic tracking and complex computational analysis of behavior of bioindicator organisms.

Microoptical device for efficient read-out of active WGM resonators

NASA Astrophysics Data System (ADS)

Wienhold, Tobias; Brammer, Marko; Grossmann, Tobias; Schneider, Marc; Kalt, Heinz; Mappes, Timo

2012-06-01

Whispering-gallery mode (WGM) resonators are known to offer outstanding properties for applications in photonics and telecommunication. Despite their promising performance, one major obstacle for the use of WGM resonators in industrial products is the need of expensive components and high-precision setups for their operation, requiring a controlled lab environment. For industrial applications technically simpler and more robust realizations are desired. Active WGM resonators utilize an optical gain medium for light amplification within the resonator and may be operated as lasers. They offer several advantages over their passive counterparts, such as cheap pump sources, free space excitation of resonator modes, and potentially narrower line widths. However, collection of the light emitted from the resonator still bears several challenges. Emission occurs in plane of the resonator and radiation is emitted isotropically along the circumference. Thus, detectors positioned in plane of the resonator may collect only a limited angular segment of the resonator's light emission. We report on a microoptical device which is integrated on the resonator chip and redirects all in-plane emission of active WGM resonators into a defined off-plane direction. Redirected light can easily be collected using a standard detector. Contrary to other approaches our microoptical device does not decrease the quality factor (Q factor) of the resonator. As light from all angular segments of the resonator is collected, the detected signal-to-noise ratio is expected to be largely improved. Our microoptical device therefore offers a promising approach towards mass-producible integration of active WGM resonators, e. g. into a Lab-on-a-Chip, for sensor applications, where smallest possible frequency shifts need to be read out by a highly sensitive detector.

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.

The application of biomedical engineering techniques to the diagnosis and management of tropical diseases: a review.

PubMed

Ibrahim, Fatimah; Thio, Tzer Hwai Gilbert; Faisal, Tarig; Neuman, Michael

2015-03-23

This paper reviews a number of biomedical engineering approaches to help aid in the detection and treatment of tropical diseases such as dengue, malaria, cholera, schistosomiasis, lymphatic filariasis, ebola, leprosy, leishmaniasis, and American trypanosomiasis (Chagas). Many different forms of non-invasive approaches such as ultrasound, echocardiography and electrocardiography, bioelectrical impedance, optical detection, simplified and rapid serological tests such as lab-on-chip and micro-/nano-fluidic platforms and medical support systems such as artificial intelligence clinical support systems are discussed. The paper also reviewed the novel clinical diagnosis and management systems using artificial intelligence and bioelectrical impedance techniques for dengue clinical applications.

Microfluidic multiplexed partitioning enables flexible and effective utilization of magnetic sensor arrays.

PubMed

Bechstein, Daniel J B; Ng, Elaine; Lee, Jung-Rok; Cone, Stephanie G; Gaster, Richard S; Osterfeld, Sebastian J; Hall, Drew A; Weaver, James A; Wilson, Robert J; Wang, Shan X

2015-11-21

We demonstrate microfluidic partitioning of a giant magnetoresistive sensor array into individually addressable compartments that enhances its effective use. Using different samples and reagents in each compartment enables measuring of cross-reactive species and wide dynamic ranges on a single chip. This compartmentalization technique motivates the employment of high density sensor arrays for highly parallelized measurements in lab-on-a-chip devices.

Dancing Around My Technology Classroom Box (My Second RET Lab)

ERIC Educational Resources Information Center

Carter, Terry

2010-01-01

The laboratory the author had been assigned for his RET (Research Experience for Teachers) at Vanderbilt University is new and different from the one he had previously experienced. This summer he was assigned to the Microfluidics and Lab-on-a-chip laboratory to help research dielectrophoresis. As this is an emerging technology, there was not a lot…

Fish swarm intelligent to optimize real time monitoring of chips drying using machine vision

NASA Astrophysics Data System (ADS)

Hendrawan, Y.; Hawa, L. C.; Damayanti, R.

2018-03-01

This study attempted to apply machine vision-based chips drying monitoring system which is able to optimise the drying process of cassava chips. The objective of this study is to propose fish swarm intelligent (FSI) optimization algorithms to find the most significant set of image features suitable for predicting water content of cassava chips during drying process using artificial neural network model (ANN). Feature selection entails choosing the feature subset that maximizes the prediction accuracy of ANN. Multi-Objective Optimization (MOO) was used in this study which consisted of prediction accuracy maximization and feature-subset size minimization. The results showed that the best feature subset i.e. grey mean, L(Lab) Mean, a(Lab) energy, red entropy, hue contrast, and grey homogeneity. The best feature subset has been tested successfully in ANN model to describe the relationship between image features and water content of cassava chips during drying process with R2 of real and predicted data was equal to 0.9.

Detection of thiopurine methyltransferase activity in lysed red blood cells by means of lab-on-a-chip surface enhanced Raman spectroscopy (LOC-SERS).

PubMed

März, Anne; Mönch, Bettina; Rösch, Petra; Kiehntopf, Michael; Henkel, Thomas; Popp, Jürgen

2011-07-01

In this contribution, the great potential of surface enhanced Raman spectroscopy (SERS) in a lab-on-a-chip (LOC) device for the detection of analyte molecules in a complex environment is demonstrated. Using LOC-SERS, the enzyme activity of thiopurine S-methyltransferase (TPMT) is analysed and identified in lysed red blood cells. The conversion of 6-mercaptopurine to 6-methylmercaptopurine catalysed by TPMT is observed as it gives evidence for the enzyme activity. Being able to determine the TPMT activity before starting a treatment using 6-mercaptopurine, an optimized dosage can be applied to each patient and serious toxicity appearing within thiopurine treatment will be prevented.

Advances in Hydrogen, Carbon Dioxide, and Hydrocarbon Gas Sensor Technology Using GaN and ZnO-Based Devices

PubMed Central

Anderson, Travis; Ren, Fan; Pearton, Stephen; Kang, Byoung Sam; Wang, Hung-Ta; Chang, Chih-Yang; Lin, Jenshan

2009-01-01

In this paper, we review our recent results in developing gas sensors for hydrogen using various device structures, including ZnO nanowires and GaN High Electron Mobility Transistors (HEMTs). ZnO nanowires are particularly interesting because they have a large surface area to volume ratio, which will improve sensitivity, and because they operate at low current levels, will have low power requirements in a sensor module. GaN-based devices offer the advantage of the HEMT structure, high temperature operation, and simple integration with existing fabrication technology and sensing systems. Improvements in sensitivity, recoverability, and reliability are presented. Also reported are demonstrations of detection of other gases, including CO2 and C2H4 using functionalized GaN HEMTs. This is critical for the development of lab-on-a-chip type systems and can provide a significant advance towards a market-ready sensor application. PMID:22408548

Magnetron sputtered diamond-like carbon microelectrodes for on-chip measurement of quantal catecholamine release from cells

PubMed Central

Gao, Yuanfang; Chen, Xiaohui; Gupta, Sanju; Gillis, Kevin D.; Gangopadhyay, Shubhra

2008-01-01

Carbon electrodes are widely used in electrochemistry due to their low cost, wide potential window, and low and stable background noise. Carbon-fiber electrodes (CFE) are commonly used to electrochemically measure “quantal” catecholamine release via exocytosis from individual cells, but it is difficult to integrate CFEs into lab-on-a-chip devices. Here we report the development of nitrogen doped diamond-like carbon (DLC:N) microelectrodes on a chip to monitor quantal release of catecholamines from cells. Advantages of DLC:N microelectrodes are that they are batch producible at low cost, and are harder and more durable than graphite films. The DLC:N microelectrodes were prepared by a magnetron sputtering process with nitrogen doping. The 30 μm by 40 μm DLC:N microelectrodes were patterned onto microscope glass slides by photolithography and lift-off technology. The properties of the DLC:N microelectrodes were characterized by AFM, Raman spectroscopy and cyclic voltammetry. Quantal catecholamine release was recorded amperometrically from bovine adrenal chromaffin cells on the DLC:N microelectrodes. Amperometric spikes due to quantal release of catecholamines were similar in amplitude and area as those recorded using CFEs and the background current and noise levels of microchip DLC:N electrodes were also comparable to CFEs. Therefore, DLC:N microelectrodes are suitable for microchip-based high-throughput measurement of quantal exocytosis with applications in basic research, drug discovery and cell-based biosensors. PMID:18493856

Towards autonomous lab-on-a-chip devices for cell phone biosensing.

PubMed

Comina, Germán; Suska, Anke; Filippini, Daniel

2016-03-15

Modern cell phones are a ubiquitous resource with a residual capacity to accommodate chemical sensing and biosensing capabilities. From the different approaches explored to capitalize on such resource, the use of autonomous disposable lab-on-a-chip (LOC) devices-conceived as only accessories to complement cell phones-underscores the possibility to entirely retain cell phones' ubiquity for distributed biosensing. The technology and principles exploited for autonomous LOC devices are here selected and reviewed focusing on their potential to serve cell phone readout configurations. Together with this requirement, the central aspects of cell phones' resources that determine their potential for analytical detection are examined. The conversion of these LOC concepts into universal architectures that are readable on unaccessorized phones is discussed within this context. Copyright © 2015 Elsevier B.V. All rights reserved.

New results on diamond pixel sensors using ATLAS frontend electronics

NASA Astrophysics Data System (ADS)

Keil, M.; Adam, W.; Berdermann, E.; Bergonzo, P.; de Boer, W.; Bogani, F.; Borchi, E.; Brambilla, A.; Bruzzi, M.; Colledani, C.; Conway, J.; D'Angelo, P.; Dabrowski, W.; Delpierre, P.; Dulinski, W.; Doroshenko, J.; Doucet, M.; van Eijk, B.; Fallou, A.; Fischer, P.; Fizzotti, F.; Kania, D.; Gan, K. K.; Grigoriev, E.; Hallewell, G.; Han, S.; Hartjes, F.; Hrubec, J.; Husson, D.; Kagan, H.; Kaplon, J.; Kass, R.; Knöpfle, K. T.; Koeth, T.; Krammer, M.; Logiudice, A.; mac Lynne, L.; Manfredotti, C.; Meier, D.; Menichelli, D.; Meuser, S.; Mishina, M.; Moroni, L.; Noomen, J.; Oh, A.; Pan, L. S.; Pernicka, M.; Perera, L.; Riester, J. L.; Roe, S.; Rudge, A.; Russ, J.; Sala, S.; Sampietro, M.; Schnetzer, S.; Sciortino, S.; Stelzer, H.; Stone, R.; Suter, B.; Trischuk, W.; Tromson, D.; Vittone, E.; Weilhammer, P.; Wermes, N.; Wetstein, M.; Zeuner, W.; Zoeller, M.

2003-03-01

Diamond is a promising sensor material for future collider experiments due to its radiation hardness. Diamond pixel sensors have been bump bonded to an ATLAS pixel readout chip using PbSn solder bumps. Single chip devices have been characterised by lab measurements and in a high-energy pion beam at CERN. Results on charge collection, spatial resolution, efficiency and the charge carrier lifetime are presented.

Separation of superparamagnetic particles through ratcheted Brownian motion and periodically switching magnetic fields.

PubMed

Liu, Fan; Jiang, Li; Tan, Huei Ming; Yadav, Ashutosh; Biswas, Preetika; van der Maarel, Johan R C; Nijhuis, Christian A; van Kan, Jeroen A

2016-11-01

Brownian ratchet based particle separation systems for application in lab on chip devices have drawn interest and are subject to ongoing theoretical and experimental investigations. We demonstrate a compact microfluidic particle separation chip, which implements an extended on-off Brownian ratchet scheme that actively separates and sorts particles using periodically switching magnetic fields, asymmetric sawtooth channel sidewalls, and Brownian motion. The microfluidic chip was made with Polydimethylsiloxane (PDMS) soft lithography of SU-8 molds, which in turn was fabricated using Proton Beam Writing. After bonding of the PDMS chip to a glass substrate through surface activation by oxygen plasma treatment, embedded electromagnets were cofabricated by the injection of InSn metal into electrode channels. This fabrication process enables rapid production of high resolution and high aspect ratio features, which results in parallel electrodes accurately aligned with respect to the separation channel. The PDMS devices were tested with mixtures of 1.51  μ m, 2.47  μ m, and 2.60  μ m superparamagnetic particles suspended in water. Experimental results show that the current device design has potential for separating particles with a size difference around 130 nm. Based on the promising results, we will be working towards extending this design for the separation of cells or biomolecules.

Separation of superparamagnetic particles through ratcheted Brownian motion and periodically switching magnetic fields

PubMed Central

Liu, Fan; Jiang, Li; Tan, Huei Ming; Yadav, Ashutosh; Biswas, Preetika; van der Maarel, Johan R. C.; Nijhuis, Christian A.; van Kan, Jeroen A.

2016-01-01

Brownian ratchet based particle separation systems for application in lab on chip devices have drawn interest and are subject to ongoing theoretical and experimental investigations. We demonstrate a compact microfluidic particle separation chip, which implements an extended on-off Brownian ratchet scheme that actively separates and sorts particles using periodically switching magnetic fields, asymmetric sawtooth channel sidewalls, and Brownian motion. The microfluidic chip was made with Polydimethylsiloxane (PDMS) soft lithography of SU-8 molds, which in turn was fabricated using Proton Beam Writing. After bonding of the PDMS chip to a glass substrate through surface activation by oxygen plasma treatment, embedded electromagnets were cofabricated by the injection of InSn metal into electrode channels. This fabrication process enables rapid production of high resolution and high aspect ratio features, which results in parallel electrodes accurately aligned with respect to the separation channel. The PDMS devices were tested with mixtures of 1.51 μm, 2.47 μm, and 2.60 μm superparamagnetic particles suspended in water. Experimental results show that the current device design has potential for separating particles with a size difference around 130 nm. Based on the promising results, we will be working towards extending this design for the separation of cells or biomolecules. PMID:27917252

Multifunctional, inexpensive, and reusable nanoparticle-printed biochip for cell manipulation and diagnosis

PubMed Central

Esfandyarpour, Rahim; DiDonato, Matthew J.; Yang, Yuxin; Durmus, Naside Gozde; Harris, James S.; Davis, Ronald W.

2017-01-01

Isolation and characterization of rare cells and molecules from a heterogeneous population is of critical importance in diagnosis of common lethal diseases such as malaria, tuberculosis, HIV, and cancer. For the developing world, point-of-care (POC) diagnostics design must account for limited funds, modest public health infrastructure, and low power availability. To address these challenges, here we integrate microfluidics, electronics, and inkjet printing to build an ultra–low-cost, rapid, and miniaturized lab-on-a-chip (LOC) platform. This platform can perform label-free and rapid single-cell capture, efficient cellular manipulation, rare-cell isolation, selective analytical separation of biological species, sorting, concentration, positioning, enumeration, and characterization. The miniaturized format allows for small sample and reagent volumes. By keeping the electronics separate from microfluidic chips, the former can be reused and device lifetime is extended. Perhaps most notably, the device manufacturing is significantly less expensive, time-consuming, and complex than traditional LOC platforms, requiring only an inkjet printer rather than skilled personnel and clean-room facilities. Production only takes 20 min (vs. up to weeks) and $0.01—an unprecedented cost in clinical diagnostics. The platform works based on intrinsic physical characteristics of biomolecules (e.g., size and polarizability). We demonstrate biomedical applications and verify cell viability in our platform, whose multiplexing and integration of numerous steps and external analyses enhance its application in the clinic, including by nonspecialists. Through its massive cost reduction and usability we anticipate that our platform will enable greater access to diagnostic facilities in developed countries as well as POC diagnostics in resource-poor and developing countries. PMID:28167769

‘Chip-olate’ and dry-film resists for efficient fabrication, singulation and sealing of microfluidic chips

NASA Astrophysics Data System (ADS)

Temiz, Yuksel; Delamarche, Emmanuel

2014-09-01

This paper describes a technique for high-throughput fabrication and efficient singulation of chips having closed microfluidic structures and takes advantage of dry-film resists (DFRs) for efficient sealing of capillary systems. The technique is illustrated using 4-inch Si/SiO2 wafers. Wafers carrying open microfluidic structures are partially diced to about half of their thickness. Treatments such as surface cleaning are done at wafer-level, then the structures are sealed using low-temperature (45 °C) lamination of a DFR that is pre-patterned using a craft cutter, and ready-to-use chips are finally separated manually like a chocolate bar by applying a small force (≤ 4 N). We further show that some DFRs have low auto-fluorescence at wavelengths typically used for common fluorescent dyes and that mechanical properties of some DFRs allow for the lamination of 200 μm wide microfluidic structures with negligible sagging (~1 μm). The hydrophilicity (advancing contact angle of ~60°) of the DFR supports autonomous capillary-driven flow without the need for additional surface treatment of the microfluidic chips. Flow rates from 1 to 5 µL min-1 are generated using different geometries of channels and capillary pumps. In addition, the ‘chip-olate’ technique is compatible with the patterning of capture antibodies on DFR for use in immunoassays. We believe this technique to be applicable to the fabrication of a wide range of microfluidic and lab-on-a-chip devices and to offer a viable alternative to many labor-intensive processes that are currently based on wafer bonding techniques or on the molding of poly(dimethylsiloxane) (PDMS) layers.

Lab-on-a-chip in vitro compartmentalization technologies for protein studies.

PubMed

Zhu, Yonggang; Power, Barbara E

2008-01-01

In vitro compartmentalization (IVC) is a powerful tool for studying protein-protein reactions, due to its high capacity and the versatility of droplet technologies. IVC bridges the gap between chemistry and biology as it enables the incorporation of unnatural amino acids with modifications into biological systems, through protein transcription and translation reactions, in a cell-like microdrop environment. The quest for the ultimate chip for protein studies using IVC is the drive for the development of various microfluidic droplet technologies to enable these unusual biochemical reactions to occur. These techniques have been shown to generate precise microdrops with a controlled size. Various chemical and physical phenomena have been utilized for on-chip manipulation to allow the droplets to be generated, fused, and split. Coupled with detection techniques, droplets can be sorted and selected. These capabilities allow directed protein evolution to be carried out on a microchip. With further technological development of the detection module, factors such as addressable storage, transport and interfacing technologies, could be integrated and thus provide platforms for protein studies with high efficiency and accuracy that conventional laboratories cannot achieve.

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

NASA Astrophysics Data System (ADS)

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

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

A high-throughput lab-on-a-chip interface for zebrafish embryo tests in drug discovery and ecotoxicology

NASA Astrophysics Data System (ADS)

Zhu, Feng; Akagi, Jin; Hall, Chris J.; Crosier, Kathryn E.; Crosier, Philip S.; Delaage, Pierre; Wlodkowic, Donald

2013-12-01

Drug discovery screenings performed on zebrafish embryos mirror with a high level of accuracy. The tests usually performed on mammalian animal models, and the fish embryo toxicity assay (FET) is one of the most promising alternative approaches to acute ecotoxicity testing with adult fish. Notwithstanding this, conventional methods utilising 96-well microtiter plates and manual dispensing of fish embryos are very time-consuming. They rely on laborious and iterative manual pipetting that is a main source of analytical errors and low throughput. In this work, we present development of a miniaturised and high-throughput Lab-on-a-Chip (LOC) platform for automation of FET assays. The 3D high-density LOC array was fabricated in poly-methyl methacrylate (PMMA) transparent thermoplastic using infrared laser micromachining while the off-chip interfaces were fabricated using additive manufacturing processes (FDM and SLA). The system's design facilitates rapid loading and immobilization of a large number of embryos in predefined clusters of traps during continuous microperfusion of drugs/toxins. It has been conceptually designed to seamlessly interface with both upright and inverted fluorescent imaging systems and also to directly interface with conventional microtiter plate readers that accept 96-well plates. We also present proof-of-concept interfacing with a high-speed imaging cytometer Plate RUNNER HD® capable of multispectral image acquisition with resolution of up to 8192 x 8192 pixels and depth of field of about 40 μm. Furthermore, we developed a miniaturized and self-contained analytical device interfaced with a miniaturized USB microscope. This system modification is capable of performing rapid imaging of multiple embryos at a low resolution for drug toxicity analysis.

Shrink-film microfluidic education modules: Complete devices within minutes

PubMed Central

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

2011-01-01

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

Plasmonic nanofocusing of light in an integrated silicon photonics platform.

PubMed

Desiatov, Boris; Goykhman, Ilya; Levy, Uriel

2011-07-04

The capability to focus electromagnetic energy at the nanoscale plays an important role in nanoscinece and nanotechnology. It allows enhancing light matter interactions at the nanoscale with applications related to nonlinear optics, light emission and light detection. It may also be used for enhancing resolution in microscopy, lithography and optical storage systems. Hereby we propose and experimentally demonstrate the nanoscale focusing of surface plasmons by constructing an integrated plasmonic/photonic on chip nanofocusing device in silicon platform. The device was tested directly by measuring the optical intensity along it using a near-field microscope. We found an order of magnitude enhancement of the intensity at the tip's apex. The spot size is estimated to be 50 nm. The demonstrated device may be used as a building block for "lab on a chip" systems and for enhancing light matter interactions at the apex of the tip.

Additive manufacturing of microfluidic glass chips

NASA Astrophysics Data System (ADS)

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

2018-02-01

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

A Review of the Application of Body-on-a-Chip for Drug Test and Its Latest Trend of Incorporating Barrier Tissue.

PubMed

Jin, Haoyi; Yu, Yanqiu

2016-10-01

High-quality preclinical bioassay models are essential for drug research and development. We reviewed the emerging body-on-a-chip technology, which serves as a promising model to overcome the limitations of traditional bioassay models, and introduced existing models of body-on-a-chip, their constitutional details, application for drug testing, and individual features of these models. We put special emphasis on the latest trend in this field of incorporating barrier tissue into body-on-a-chip and discussed several remaining challenges of current body-on-a-chip. © 2015 Society for Laboratory Automation and Screening.

Fishing on chips: up-and-coming technological advances in analysis of zebrafish and Xenopus embryos.

PubMed

Zhu, Feng; Skommer, Joanna; Huang, Yushi; Akagi, Jin; Adams, Dany; Levin, Michael; Hall, Chris J; Crosier, Philip S; Wlodkowic, Donald

2014-11-01

Biotests performed on small vertebrate model organisms provide significant investigative advantages as compared with bioassays that employ cell lines, isolated primary cells, or tissue samples. The main advantage offered by whole-organism approaches is that the effects under study occur in the context of intact physiological milieu, with all its intercellular and multisystem interactions. The gap between the high-throughput cell-based in vitro assays and low-throughput, disproportionally expensive and ethically controversial mammal in vivo tests can be closed by small model organisms such as zebrafish or Xenopus. The optical transparency of their tissues, the ease of genetic manipulation and straightforward husbandry, explain the growing popularity of these model organisms. Nevertheless, despite the potential for miniaturization, automation and subsequent increase in throughput of experimental setups, the manipulation, dispensing and analysis of living fish and frog embryos remain labor-intensive. Recently, a new generation of miniaturized chip-based devices have been developed for zebrafish and Xenopus embryo on-chip culture and experimentation. In this work, we review the critical developments in the field of Lab-on-a-Chip devices designed to alleviate the limits of traditional platforms for studies on zebrafish and clawed frog embryo and larvae. © 2014 International Society for Advancement of Cytometry. © 2014 International Society for Advancement of Cytometry.

Control of microparticles packing density in a microfluidic channel for bead based immunoassays applications

NASA Astrophysics Data System (ADS)

Caballero-Robledo, Gabriel; Guevara-Pantoja, Pablo

2014-11-01

Bead based immunoassays in microfluidic devices have shown to greatly outperform conventional methods. But if functional point-of-care devices are to be developed, precise and reproducible control over the granulate packings inside microchannels is needed. In this work we study the efficiency of a nanoparticles magnetic trap previously developed by B. Teste et al. [Lab Chip 11, 4207 (2011)] when we vary the compaction of micrometric iron beads packed against a restriction inside a microfluidic channel. The packing density of the beads is finely and reproducibly changed by applying a vibrational protocol originally developed for macroscopic, dry granular systems. We find, counterintuitively, that the most compact and stable packings are up to four times less efficient in trapping nano particles than the loosest packings. This work has been supported by Conacyt, Mexico, under Grant No. 180873.

Influence of Electric Fields and Conductivity on Pollen Tube Growth assessed via Electrical Lab-on-Chip

PubMed Central

Agudelo, Carlos; Packirisamy, Muthukumaran; Geitmann, Anja

2016-01-01

Pollen tubes are polarly growing plant cells that are able to rapidly respond to a combination of chemical, mechanical, and electrical cues. This behavioural feature allows them to invade the flower pistil and deliver the sperm cells in highly targeted manner to receptive ovules in order to accomplish fertilization. How signals are perceived and processed in the pollen tube is still poorly understood. Evidence for electrical guidance in particular is vague and highly contradictory. To generate reproducible experimental conditions for the investigation of the effect of electric fields on pollen tube growth we developed an Electrical Lab-on-Chip (ELoC). Pollen from the species Camellia displayed differential sensitivity to electric fields depending on whether the entire cell or only its growing tip was exposed. The response to DC fields was dramatically higher than that to AC fields of the same strength. However, AC fields were found to restore and even promote pollen growth. Surprisingly, the pollen tube response correlated with the conductivity of the growth medium under different AC frequencies—consistent with the notion that the effect of the field on pollen tube growth may be mediated via its effect on the motion of ions. PMID:26804186

"Student Lab"-on-a-Chip: Integrating Low-Cost Microfluidics into Undergraduate Teaching Labs to Study Multiphase Flow Phenomena in Small Vessels

ERIC Educational Resources Information Center

Young, Edmond W. K.; Simmons, Craig A.

2009-01-01

We describe a simple, low-cost laboratory session to demonstrate the Fahraeus-Lindqvist effect, a microphase flow phenomenon that occurs in small blood vessels and alters the effective rheological properties of blood. The experiments are performed by flowing cells through microchannels fabricated by soft lithography and characterization of cell…

Optofluidic plasmonic onchip nanosensor array for biodetection

NASA Astrophysics Data System (ADS)

Huang, Min

Surface plasmon resonance (SPR) sensing has been demonstrated in the past decade to be the gold standard technique for biochemical interaction analysis, and plays an important role in drug discovery and biomedical research. The technique circumvents the need of fluorescence/radioactive tagging or enzymatic detection, enables ultrasensitive remote sensing, and quantitatively monitors bio-interaction in real time. Although SPR has these attractive features that can satisfy most research/clinic requirements, there still exist problems that limit its applications. First, the reflection geometry of the prism coupling scheme adds limitations for high throughput screening application. Additionally, SPR instrumentations are bulky and not suitable for point-of-care settings. Moreover, the SPR sensor is embedded in conventional micro-fluidic cells, in which the sensor performance is limited by inefficient analyte transport. Suspended plasmonic nanohole array (PNA) offers an opportunity to overcome these limitations. A collinear excitation/collection coupling scheme combined with the small footprint of PNA provides unique platform for multiplexing and system minimization. The suspended nanohole structure also offers a unique configuration to integrate nano-photonics with nano-fluidics. This thesis focuses on developing a lab-on-a-chip PNA platform for point-of-care bio-detection. To achieve this, we first demonstrate that the figure-of-merit of our PNA sensor surpasses that of the prism coupled SPR. We also show that the ultrasensitive label-free PNA sensor is able to directly detect intact viruses from biological media at clinically relevant concentrations with little sample preparation. We then present a plasmonic microarray with over one million PNA sensors on a microscope slide for high throughput screening applications. A dual-color filter imaging method is introduced to increase the accuracy, reliability, and signal-to-noise ratio in a highly multiplexed manner. Finally, we present a nanoplasmonic-nanofluidic platform enabling active delivery of analyte to the sensor. Sensor response time is reduced by an order of magnitude compared to the conventional flow scheme. A dynamic range spanning 5 orders of magnitude from 103 to 107 particles/mL is shown on this platform corresponding to analyte concentration sufficient for clinical applications. The proposed approach opens up opportunities of a lab-on-a-chip bio-detection system for drug screening, disease diagnostic as well as clinic studies.

OpenDrop: An Integrated Do-It-Yourself Platform for Personal Use of Biochips

PubMed Central

Alistar, Mirela; Gaudenz, Urs

2017-01-01

Biochips, or digital labs-on-chip, are developed with the purpose of being used by laboratory technicians or biologists in laboratories or clinics. In this article, we expand this vision with the goal of enabling everyone, regardless of their expertise, to use biochips for their own personal purposes. We developed OpenDrop, an integrated electromicrofluidic platform that allows users to develop and program their own bio-applications. We address the main challenges that users may encounter: accessibility, bio-protocol design and interaction with microfluidics. OpenDrop consists of a do-it-yourself biochip, an automated software tool with visual interface and a detailed technique for at-home operations of microfluidics. We report on two years of use of OpenDrop, released as an open-source platform. Our platform attracted a highly diverse user base with participants originating from maker communities, academia and industry. Our findings show that 47% of attempts to replicate OpenDrop were successful, the main challenge remaining the assembly of the device. In terms of usability, the users managed to operate their platforms at home and are working on designing their own bio-applications. Our work provides a step towards a future in which everyone will be able to create microfluidic devices for their personal applications, thereby democratizing parts of health care. PMID:28952524

Localized Heating on Silicon Field Effect Transistors: Device Fabrication and Temperature Measurements in Fluid

PubMed Central

Elibol, Oguz H.; Reddy, Bobby; Nair, Pradeep R.; Dorvel, Brian; Butler, Felice; Ahsan, Zahab; Bergstrom, Donald E.; Alam, Muhammad A.; Bashir, Rashid

2010-01-01

We demonstrate electrically addressable localized heating in fluid at the dielectric surface of silicon-on-insulator field-effect transistors via radio-frequency Joule heating of mobile ions in the Debye layer. Measurement of fluid temperatures in close vicinity to surfaces poses a challenge due to the localized nature of the temperature profile. To address this, we developed a localized thermometry technique based on the fluorescence decay rate of covalently attached fluorophores to extract the temperature within 2 nm of any oxide surface. We demonstrate precise spatial control of voltage dependent temperature profiles on the transistor surfaces. Our results introduce a new dimension to present sensing systems by enabling dual purpose silicon transistor-heaters that serve both as field effect sensors as well as temperature controllers that could perform localized bio-chemical reactions in Lab on Chip applications. PMID:19967115

Rayleigh surface acoustic wave as an efficient heating system for biological reactions: investigation of microdroplet temperature uniformity.

PubMed

Roux-Marchand, Thibaut; Beyssen, Denis; Sarry, Frederic; Elmazria, Omar

2015-04-01

When a microdroplet is put on the Rayleigh surface acoustic wave path, longitudinal waves are radiated into the liquid and induce several phenomena such as the wellknown surface acoustic wave streaming. At the same time, the temperature of the microdroplet increases as it has been shown. In this paper, we study the temperature uniformity of a microdroplet heated by Rayleigh surface acoustic wave for discrete microfluidic applications such as biological reactions. To precisely ascertain the temperature uniformity and not interfere with the biological reaction, we used an infrared camera. We then tested the temperature uniformity as a function of three parameters: the microdroplet volume, the Rayleigh surface acoustic wave frequency, and the continuous applied radio frequency power. Based on these results, we propose a new device structure to develop a future lab on a chip based on reaction temperatures.

Micro-nano-biosystems: An overview of European research.

PubMed

Lymberis, Andreas

2010-06-01

New developments in science, technologies and applications are blurring the boundaries between information and communications technology (ICT), micro-nano systems and life sciences, e.g. through miniaturisation and the ability to manipulate matter at the atomic scale and to interface live and man-made systems. Interdisciplinary research towards integrated systems and their applications based on emerging convergence of information & communication technologies, micro-nano and bio technologies is expected to have a direct influence on healthcare, ageing population and well being. Micro-Nano-Bio Systems (MNBS) research and development activities under the European Union's R&D Programs, Information & Communication Technologies priority address miniaturised, smart and integrated systems for in-vitro testing e.g. lab-on-chips and systems interacting with the human e.g. autonomous implants, endoscopic capsules and robotics for minimally invasive surgery. The MNBS group involves hundreds of key public and private international organisations working on system development and validation in diverse applications such as cancer detection and therapy follow-up, minimally invasive surgery, capsular endocsopy, wearable biochemical monitoring and repairing of vital functions with active implant devices. The paper presents MNBS rationale and activities, discusses key research and innovation challenges and proposes R&D directions to achieve the expected impact on healthcare and quality of life.

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.

Summary of Medipix Technology's 3-Years in Space and Plans for Future Developments

NASA Astrophysics Data System (ADS)

Pinsky, Lawrence

2016-07-01

NASA has evaluated 7 Timepix-based radiation imaging detectors from the CERN-based Medipix2 collaboration on the International Space Station (ISS), collecting more than 3-years of data, as well on the December, 2014 EFT-1 mission testing the new Orion Multi-Purpose Crew Vehicle. These data along with data collected at ground-based accelerator facilities including the NASA Space Radiation Lab (NSRL) at Brookhaven in the US, as well as at the HIMAC facility at the National Institute for Radiological Sciences in Japan, have allowed the development of software analysis techniques sufficient to provide a stand-alone accurate assessment of the space radiation environment for dosimetric purposes. Recent comparisons of the performance of the Timepix with both n-on-p and p-on-n Si sensors will be presented. The further evolution of the Timepix technology by the Medipix3 collaboration in the form of the Timepix3 chip, which employs a continuous data-driven readout scheme, is being evaluated for possible use in future space research applications. Initial performance evaluations at accelerators will be reported. The Medipix2 Collaboration is also in the process of designing an updated version of the Timepix chip, called the Timepix2, which will continue the frame-based readout scheme of the current Timepix chip, but add simultaneous charge encoding using the Time-Over-Threshold (TOT) and first-hit Time-of-Arrival (TOA) encoding. Current plans are to replace the Timepix by the Timepix2 with minimal reconfiguration of the supporting electronics. Longer-term plans include participation in the currently forming Medipix4 collaboration. A summary of these prospects will also be included.

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

PubMed

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

2018-03-01

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

High-Pressure Open-Channel On-Chip Electroosmotic Pump for Nanoflow High Performance Liquid Chromatography

PubMed Central

2015-01-01

Here, we construct an open-channel on-chip electroosmotic pump capable of generating pressures up to ∼170 bar and flow rates up to ∼500 nL/min, adequate for high performance liquid chromatographic (HPLC) separations. A great feature of this pump is that a number of its basic pump units can be connected in series to enhance its pumping power; the output pressure is directly proportional to the number of pump units connected. This additive nature is excellent and useful, and no other pumps can work in this fashion. We demonstrate the feasibility of using this pump to perform nanoflow HPLC separations; tryptic digests of bovine serum albumin (BSA), transferrin factor (TF), and human immunoglobulins (IgG) are utilized as exemplary samples. We also compare the performance of our electroosmotic (EO)-driven HPLC with Agilent 1200 HPLC; comparable efficiencies, resolutions, and peak capacities are obtained. Since the pump is based on electroosmosis, it has no moving parts. The common material and process also allow this pump to be integrated with other microfabricated functional components. Development of this high-pressure on-chip pump will have a profound impact on the advancement of lab-on-a-chip devices. PMID:24495233

Multi-angle lensless digital holography for depth resolved imaging on a chip.

PubMed

Su, Ting-Wei; Isikman, Serhan O; Bishara, Waheb; Tseng, Derek; Erlinger, Anthony; Ozcan, Aydogan

2010-04-26

A multi-angle lensfree holographic imaging platform that can accurately characterize both the axial and lateral positions of cells located within multi-layered micro-channels is introduced. In this platform, lensfree digital holograms of the micro-objects on the chip are recorded at different illumination angles using partially coherent illumination. These digital holograms start to shift laterally on the sensor plane as the illumination angle of the source is tilted. Since the exact amount of this lateral shift of each object hologram can be calculated with an accuracy that beats the diffraction limit of light, the height of each cell from the substrate can be determined over a large field of view without the use of any lenses. We demonstrate the proof of concept of this multi-angle lensless imaging platform by using light emitting diodes to characterize various sized microparticles located on a chip with sub-micron axial and lateral localization over approximately 60 mm(2) field of view. Furthermore, we successfully apply this lensless imaging approach to simultaneously characterize blood samples located at multi-layered micro-channels in terms of the counts, individual thicknesses and the volumes of the cells at each layer. Because this platform does not require any lenses, lasers or other bulky optical/mechanical components, it provides a compact and high-throughput alternative to conventional approaches for cytometry and diagnostics applications involving lab on a chip systems.

Development of a Fully Integrated Lab-on-a-Chip Electrophoresis System for ExoMars and Future Astrobiology Missions

NASA Astrophysics Data System (ADS)

Willis, P. A.; Fisher, A.; Greer, F.; Grunthaner, F. J.; Hoppe, D.; Chiesl, T.; Mathies, R. A.; Rolland, J. P.

2009-04-01

This paper will describe current and future development efforts in lab-on-a-chip instrumentation for astrobiological investigations underway at JPL. We will begin with a discussion of the current technology status of our autonomous microfluidic capillary electrophoresis (μCE) system integrated with on-chip perfluoropolyether (PFPE) membrane valves and pumps [1], as part of the Urey Instrument. This work builds on the μCE system developed by Skelley et al. [2], but extends the system capability through the use of bio- and spaceflight-compatible PFPE-membrane valves rather than utilizing a PDMS-based approach. The ultimate goal of this μCE system is to perform ultrasensitive compositional and chiral analysis of amino acids in order to determine if Mars harbors signatures of past or present life. An autonomously functioning flight version of this instrument will examine extracts from the Martian regolith as part of the Pasteur Payload of the 2016 ExoMars astrobiology mission. The four-layer wafer stack design utilizes independent CE channels patterned in glass, along with a PFPE membrane, a pneumatic manifold layer, and a fluidic bus layer. Three pneumatically driven on-chip diaphragm valves placed in series are used to peristaltically pump reagents, buffers, and samples to and from capillary electrophoresis electrode well positions. Electrophoretic separation occurs in the all-glass channels near the base of the structure. The valve geometries and layouts in our integrated two-channel PFPE system have been optimized for valve sealing characteristics and uniform device spacing across the wafer surface. This paper will discuss current experimental development work in our research group involving further integration of functionality into an autonomous multi-channel system with no human intervention, enabling CE analysis upon a dried sample after receipt of a single pre-programmed instruction set from the user. The key structure under current development is an expanded sample handling bus, which performs on-chip derivitization of samples with fluorescent tags, serial sample dilutions, and mixing with standard samples for the purpose of data calibration. For laboratory general-purpose use, the wafer stack is mounted on a fluorescent microscope stage in a custom fixture, which interfaces the pneumatic and high voltage lines and has the capability for controlled atmosphere testing. Additionally, simulation work is also underway on a more complex six-channel system with additional functionality. A 3D SolidWorks model of this more highly integrated six-channel autonomous system capable of all expected instrument functionality is modeled using COMSOL FEMLAB multiphysics software to ensure that the integrated system will perform as desired aboard a roving Martian platform. FEMLAB simulations of μCE separations of relevant mixtures of amino acids have been performed using custom code written at JPL, which enables direct comparison of experimental and simulated data, as well as providing crucial engineering data, in particular, the electric field strengths present throughout the instrument during operation. Finally, a discussion of advanced instrument concepts under development at JPL for "next-generation" Urey-like astrobiology instrumentation will also be presented. References: 1. "Monolithic photolithographically patterned Fluorocur PFPE membrane valves and pumps for in situ planetary exploration", P. A. Willis, F. Greer, M. C. Lee, J. A. Smith, V. E. White, F. J. Grunthaner, J. J. Sprague, and J. P. Rolland, Lab Chip 8, 1024 (2008). 2. "Development and evaluation of a microdevice for amino acid biomarker detection and analysis on Mars" A. M. Skelley, J. R. Scherer, A. D. Aubrey, W. H. Grover, R. H. C. Ivester, P. Ehrenfreund, F. J. Grunthaner, J. L. Bada, R. A. Mathies, PNAS 102, 1041(2005).

Development of an anti-EPO antibody detection kit based on lab-on-a-chip and bridging antibody technologies.

PubMed

Oh, Jin-Gyo; Seong, Jihyun; Han, Sunmi; Heo, Tae-Hwe

2018-05-17

Immunogenicity is a major concern in the use of biological drugs. In particular, antibody-mediated pure red cell aplasia (PRCA) is a rare condition that is caused by administration of recombinant erythropoietin. There are numerous assay platforms for detect EPO anti-drug antibody (ADA), and most have appropriate assay sensitivity, but in need of improvement in terms of assay turnaround time and user accessibility. Here, the new method was developed based on lab-on-a-chip technology and bridging ELISA. The FREND™ Cartridge is equipped with a microfluidic lateral flow channel, enabling easy, fast and accurate immunoassays with small sample volumes. Biotinylated EPO was immobilized on the avidin-coated solid phase of the test zone in the FREND™ cartridge. Initially, ADA in the serum sample binds to the detector conjugate (EPO-HRP-anti HRP antibody-FL bead) in the conjugation zone, and it flows into the test zone prepared with capture complex (avidin-biotinylated EPO). Unbound detector complexes are captured in the reference zone. The FREND™ system detects and quantifies the fluorescence signals in each zone and then calculates the concentration of EPO ADA in the sample. The FREND™ EPO ADA kit may be useful in local clinics as a rapid method for monitoring patients administered recombinant erythropoietin. Copyright © 2018 International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.

A Computer Engineering Curriculum for the Air Force Academy: An Implementation Plan

DTIC Science & Technology

1985-04-01

engineerinq is needed as a r ul of the findings? 5. What is the impact of this study’s rocommendat ion to pursue the Electrico I Engineering deqree with onpt...stepper motor 9 S35 LAB 36 Serial 10 S37 GR #3 - 38 8251 10 chip ) 39 LAB serial 10 10 * 40 LAB " 1)41 LAB S 42 Course review - S FINAL EXAM 00 % 80 0

Remote detection of single emitters via optical waveguides

NASA Astrophysics Data System (ADS)

Then, Patrick; Razinskas, Gary; Feichtner, Thorsten; Haas, Philippe; Wild, Andreas; Bellini, Nicola; Osellame, Roberto; Cerullo, Giulio; Hecht, Bert

2014-05-01

The integration of lab-on-a-chip technologies with single-molecule detection techniques may enable new applications in analytical chemistry, biotechnology, and medicine. We describe a method based on the reciprocity theorem of electromagnetic theory to determine and optimize the detection efficiency of photons emitted by single quantum emitters through truncated dielectric waveguides of arbitrary shape positioned in their proximity. We demonstrate experimentally that detection of single quantum emitters via such waveguides is possible, confirming the predicted behavior of the detection efficiency. Our findings blaze the trail towards efficient lensless single-emitter detection compatible with large-scale optofluidic integration.

Microfabrication of three-dimensional filters for liposome extrusion

NASA Astrophysics Data System (ADS)

Baldacchini, Tommaso; Nuñez, Vicente; LaFratta, Christopher N.; Grech, Joseph S.; Vullev, Valentine I.; Zadoyan, Ruben

2015-03-01

Liposomes play a relevant role in the biomedical field of drug delivery. The ability of these lipid vesicles to encapsulate and transport a variety of bioactive molecules has fostered their use in several therapeutic applications, from cancer treatments to the administration of drugs with antiviral activities. Size and uniformity are key parameters to take into consideration when preparing liposomes; these factors greatly influence their effectiveness in both in vitro and in vivo experiments. A popular technique employed to achieve the optimal liposome dimension (around 100 nm in diameter) and uniform size distribution is repetitive extrusion through a polycarbonate filter. We investigated two femtosecond laser direct writing techniques for the fabrication of three-dimensional filters within a microfluidics chip for liposomes extrusion. The miniaturization of the extrusion process in a microfluidic system is the first step toward a complete solution for lab-on-a-chip preparation of liposomes from vesicles self-assembly to optical characterization.

Applications and theory of electrokinetic enrichment in micro-nanofluidic chips.

PubMed

Chen, Xueye; Zhang, Shuai; Zhang, Lei; Yao, Zhen; Chen, Xiaodong; Zheng, Yue; Liu, Yanlin

2017-09-01

This review reports the progress on the recent development of electrokinetic enrichment in micro-nanofluidic chips. The governing equations of electrokinetic enrichment in micro-nanofluidic chips are given. Various enrichment applications including protein analysis, DNA analysis, bacteria analysis, viruses analysis and cell analysis are illustrated and discussed. The advantages and difficulties of each enrichment method are expatiated. This paper will provide a particularly convenient and valuable reference to those who intend to research the electrokinetic enrichment based on micro-nanofluidic chips.

Single-step fabrication of polydimethylsiloxane microwell arrays with long-lasting hydrophilic inner surfaces

NASA Astrophysics Data System (ADS)

Gowa Oyama, Tomoko; Barba, Bin Jeremiah Duenas; Hosaka, Yuji; Taguchi, Mitsumasa

2018-05-01

We propose a single-step fabrication method for polydimethylsiloxane (PDMS) cell-adhesive microwell arrays with long-lasting (>10 months in aqueous medium) hydrophilic inner surfaces without the need for any chemical treatment such as development. Irradiation of a PDMS film with a low-energy electron beam (55 kV) in air generated a ˜40-μm-thick hydrophilic silica-like layer on the PDMS surface, which was the key to the prolonged hydrophilicity. Moreover, the concomitant compaction of the irradiated area produced dozens-of-micrometers-deep concave wells. The hydrophilic microwells generated on the hydrophobic non-irradiated PDMS surface easily trapped nano-/picoliter droplets and cells/single-cells. In addition, the surfaces of the microwells offered stable and favorable cell-adherent environments. The method presented here can realize stable and reliable lab-on-chips and cater to the expanding demand in biological and medical applications.

Ultra-dense magnetoresistive mass memory

NASA Technical Reports Server (NTRS)

Daughton, J. M.; Sinclair, R.; Dupuis, T.; Brown, J.

1992-01-01

This report details the progress and accomplishments of Nonvolatile Electronics (NVE), Inc., on the design of the wafer scale MRAM mass memory system during the fifth quarter of the project. NVE has made significant progress this quarter on the one megabit design in several different areas. A test chip, which will verify a working GMR bit with the dimensions required by the 1 Meg chip, has been designed, laid out, and is currently being processed in the NVE labs. This test chip will allow electrical specifications, tolerances, and processing issues to be finalized before construction of the actual chip, thus providing a greater assurance of success of the final 1 Meg design. A model has been developed to accurately simulate the parasitic effects of unselected sense lines. This model gives NVE the ability to perform accurate simulations of the array electronic and test different design concepts. Much of the circuit design for the 1 Meg chip has been completed and simulated and these designs are included. Progress has been made in the wafer scale design area to verify the reliable operation of the 16 K macrocell. This is currently being accomplished with the design and construction of two stand alone test systems which will perform life tests and gather data on reliabiliy and wearout mechanisms for analysis.

Microfluidic Exosome Analysis toward Liquid Biopsy for Cancer.

PubMed

He, Mei; Zeng, Yong

2016-08-01

Assessment of a tumor's molecular makeup using biofluid samples, known as liquid biopsy, is a prominent research topic in precision medicine for cancer, due to its noninvasive property allowing repeat sampling for monitoring molecular changes of tumors over time. Circulating exosomes recently have been recognized as promising tumor surrogates because they deliver enriched biomarkers, such as proteins, RNAs, and DNA. However, purification and characterization of these exosomes are technically challenging. Microfluidic lab-on-a-chip technology effectively addresses these challenges owing to its inherent advantages in integration and automation of multiple functional modules, enhancing sensing performance, and expediting analysis processes. In this article, we review the state-of-the-art development of microfluidic technologies for exosome isolation and molecular characterization with emphasis on their applications toward liquid biopsy-based analysis of cancer. Finally, we share our perspectives on current challenges and future directions of microfluidic exosome analysis. © 2016 Society for Laboratory Automation and Screening.

Generation of Monodisperse Liquid Droplets in a Microfluidic Chip Using a High-Speed Gaseous Microflow

NASA Astrophysics Data System (ADS)

Tirandazi, Pooyan; Hidrovo, Carlos

2015-11-01

Over the last few years, microfluidic systems known as Lab-on-a-Chip (LOC) and micro total analysis systems (μTAS) have been increasingly developed as essential components for numerous biochemical applications. Droplet microfluidics, however, provides a distinctive attribute for delivering and processing discrete as well as ultrasmall volumes of fluid, which make droplet-based systems more beneficial over their continuous-phase counterparts. Droplet generation in its conventional scheme usually incorporates the injection of a liquid (water) into a continuous immiscible liquid (oil) medium. In this study we demonstrate a novel scheme for controlled generation of monodisperse droplets in confined gas-liquid microflows. We experimentally investigate the manipulation of water droplets in flow-focusing configurations using a high inertial air stream. Different flow regimes are observed by varying the gas and liquid flow rates, among which, the ``dripping regime'' where monodisperse droplets are generated is of great importance. The controlled size and generation rate of droplets in this region provide the capability for precise and contaminant-free delivery of microliter to nanoliter volumes of fluid. Furthermore, the high speed droplets generated in this method represent the basis for a new approach based on droplet pair collisions for fast efficient micromixing which provides a significant development in modern LOC and μTAS devices. This project is currently being supported by an NSF CAREER Award grant CBET-1151091.

Integrated sample-to-detection chip for nucleic acid test assays.

PubMed

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

2016-06-01

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

Microfluidic lab-on-a-foil for nucleic acid analysis based on isothermal recombinase polymerase amplification (RPA).

PubMed

Lutz, Sascha; Weber, Patrick; Focke, Max; Faltin, Bernd; Hoffmann, Jochen; Müller, Claas; Mark, Daniel; Roth, Günter; Munday, Peter; Armes, Niall; Piepenburg, Olaf; Zengerle, Roland; von Stetten, Felix

2010-04-07

For the first time we demonstrate a self-sufficient lab-on-a-foil system for the fully automated analysis of nucleic acids which is based on the recently available isothermal recombinase polymerase amplification (RPA). The system consists of a novel, foil-based centrifugal microfluidic cartridge including prestored liquid and dry reagents, and a commercially available centrifugal analyzer for incubation at 37 degrees C and real-time fluorescence detection. The system was characterized with an assay for the detection of the antibiotic resistance gene mecA of Staphylococcus aureus. The limit of detection was <10 copies and time-to-result was <20 min. Microfluidic unit operations comprise storage and release of liquid reagents, reconstitution of lyophilized reagents, aliquoting the sample into < or = 30 independent reaction cavities, and mixing of reagents with the DNA samples. The foil-based cartridge was produced by blow-molding and sealed with a self-adhesive tape. The demonstrated system excels existing PCR based lab-on-a-chip platforms in terms of energy efficiency and time-to-result. Applications are suggested in the field of mobile point-of-care analysis, B-detection, or in combination with continuous monitoring systems.

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

The Application of Biomedical Engineering Techniques to the Diagnosis and Management of Tropical Diseases: A Review

PubMed Central

Ibrahim, Fatimah; Thio, Tzer Hwai Gilbert; Faisal, Tarig; Neuman, Michael

2015-01-01

This paper reviews a number of biomedical engineering approaches to help aid in the detection and treatment of tropical diseases such as dengue, malaria, cholera, schistosomiasis, lymphatic filariasis, ebola, leprosy, leishmaniasis, and American trypanosomiasis (Chagas). Many different forms of non-invasive approaches such as ultrasound, echocardiography and electrocardiography, bioelectrical impedance, optical detection, simplified and rapid serological tests such as lab-on-chip and micro-/nano-fluidic platforms and medical support systems such as artificial intelligence clinical support systems are discussed. The paper also reviewed the novel clinical diagnosis and management systems using artificial intelligence and bioelectrical impedance techniques for dengue clinical applications. PMID:25806872

Molecular strain typing of Brucella abortus isolates from Italy by two VNTR allele sizing technologies.

PubMed

De Santis, Riccardo; Ancora, Massimo; De Massis, Fabrizio; Ciammaruconi, Andrea; Zilli, Katiuscia; Di Giannatale, Elisabetta; Pittiglio, Valentina; Fillo, Silvia; Lista, Florigio

2013-10-01

Brucellosis, one of the most important re-emerging zoonoses in many countries, is caused by bacteria belonging to the genus Brucella. Furthermore these bacteria represent potential biological warfare agents and the identification of species and biovars of field strains may be crucial for tracing back source of infection, allowing to discriminate naturally occurring outbreaks instead of bioterrorist events. In the last years, multiple-locus variable-number tandem repeat analysis (MLVA) has been proposed as complement of the classical biotyping methods and it has been applied for genotyping large collections of Brucella spp. At present, the MLVA band profiles may be resolved by automated or manual procedures. The Lab on a chip technology represents a valid alternative to standard genotyping techniques (as agarose gel electrophoresis) and it has been previously used for Brucella genotyping. Recently, a new high-throughput genotyping analysis system based on capillary gel electrophoresis, the QIAxcel, has been described. The aim of the study was to evaluate the ability of two DNA sizing equipments, the QIAxcel System and the Lab chip GX, to correctly call alleles at the sixteen loci including one frequently used MLVA assay for Brucella genotyping. The results confirmed that these technologies represent a meaningful advancement in high-throughput Brucella genotyping. Considering the accuracy required to confidently resolve loci discrimination, QIAxcel shows a better ability to measure VNTR allele sizes compared to LabChip GX.

Autonomous capillary microfluidic system with embedded optics for improved troponin I cardiac biomarker detection.

PubMed

Mohammed, M I; Desmulliez, M P Y

2014-11-15

Cardiovascular diseases are the most prevalent medical conditions affecting the modern world, reducing the quality of life for those affected and causing an ever increasing burden on clinical resources. Cardiac biomarkers are crucial in the diagnosis and management of patient outcomes. In that respect, such proteins are desirable to be measured at the point of care, overcoming the shortcomings of current instrumentation. We present a CO2 laser engraving technique for the rapid prototyping of a polymeric autonomous capillary system with embedded on-chip planar lenses and biosensing elements, the first step towards a fully miniaturised and integrated cardiac biosensing platform. The system has been applied to the detection of cardiac Troponin I, the gold standard biomarker for the diagnosis of acute myocardial infarction. The devised lab-on-a-chip device was demonstrated to have 24 pg/ml limit of detection, which is well within the minimum threshold for clinically applicable concentrations. Assays were completed within approximately 7-9 min. Initial results suggest that, given the portability, low power consumption and high sensitivity of the device, this technology could be developed further into point of care instrumentation useful in the diagnosis of various forms of cardiovascular diseases. Copyright © 2014 Elsevier B.V. All rights reserved.

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

NASA Astrophysics Data System (ADS)

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

2017-09-01

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

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

PubMed

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

2017-11-07

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

Development of economic MeV-ion microbeam technology at Chiang Mai University

NASA Astrophysics Data System (ADS)

Singkarat, S.; Puttaraksa, N.; Unai, S.; Yu, L. D.; Singkarat, K.; Pussadee, N.; Whitlow, H. J.; Natyanum, S.; Tippawan, U.

2017-08-01

Developing high technologies but in economic manners is necessary and also feasible for developing countries. At Chiang Mai University, Thailand, we have developed MeV-ion microbeam technology based on a 1.7-MV Tandetron tandem accelerator with our limited resources in a cost-effective manner. Instead of using expensive and technically complex electrostatic or magnetic quadrupole focusing lens systems, we have developed cheap MeV-ion microbeams using programmed L-shaped blade aperture and capillary techniques for MeV ion beam lithography or writing and mapping. The programmed L-shaped blade micro-aperture system consists of a pair of L-shaped movable aperture pieces which are controlled by computer to cut off the ion beam for controlling the beam size down to the micrometer order. The capillary technique utilizes our home-fabricated tapered glass capillaries to realize microbeams. Either system can be installed inside the endstation of the MeV ion beam line of the accelerator. Both systems have been applied to MeV-ion beam lithography or writing of micro-patterns for microfluidics applications to fabricate lab-on-chip devices. The capillary technique is being developed for MeV-ion beam mapping of biological samples. The paper reports details of the techniques and introduces some applications.

Three-unit posterior zirconia-ceramic fixed dental prostheses (FDPs) veneered with layered and milled (CAD-on) veneering ceramics: 1-year follow-up of a randomized controlled clinical trial.

PubMed

Grohmann, Philipp; Bindl, Andreas; Hämmerle, Christoph; Mehl, Albert; Sailer, Irena

2015-01-01

The aim of this multicenter randomized controlled clinical trial was to test posterior zirconia-ceramic fixed dental prostheses (FDPs) veneered with a computer-aided design/computer- assisted manufacture (CAD/CAM) lithium disilicate veneering ceramic (CAD-on) and manually layered zirconia veneering ceramic with respect to survival of the FDPs, and technical and biologic outcomes. Sixty patients in need of one posterior three-unit FDP were included. The zirconia frameworks were produced with a CAD/CAM system (Cerec inLab 3D/Cerec inEOS inLab). Thirty FDPs were veneered with a CAD/CAM lithium disilicate veneering ceramic (Cad-on) (test) and 30 were veneered with a layered zirconia veneering ceramic (control). For the clinical evaluation at baseline, 6, and 12 months, the United States Public Health Service (USPHS) criteria were used. The biologic outcome was judged by comparing the plaque control record (PCR), bleeding on probing (BOP), and probing pocket depth (PPD). Data were statistically analyzed. Fifty-six patients were examined at a mean follow-up of 13.9 months. At the 1-year follow-up the survival rate was 100% in the test and in the control group. No significant differences of the technical outcomes occurred. Major chipping occurred in the control group (n = 3) and predominantly minor chipping in the test group (minor n = 2, major n = 1). No biologic problems or differences were found. Both types of zirconia-ceramic FDPs exhibited very good clinical outcomes without differences between groups. Chipping occurred in both types of FDPs at small amounts, yet the extension of the chippings differed. The test FDPs predominantly exhibited minor chipping, the control FDPs major chipping.

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.

A novel bonding method for large scale poly(methyl methacrylate) micro- and nanofluidic chip fabrication

NASA Astrophysics Data System (ADS)

Qu, Xingtian; Li, Jinlai; Yin, Zhifu

2018-04-01

Micro- and nanofluidic chips are becoming increasing significance for biological and medical applications. Future advances in micro- and nanofluidics and its utilization in commercial applications depend on the development and fabrication of low cost and high fidelity large scale plastic micro- and nanofluidic chips. However, the majority of the present fabrication methods suffer from a low bonding rate of the chip during thermal bonding process due to air trapping between the substrate and the cover plate. In the present work, a novel bonding technique based on Ar plasma and water treatment was proposed to fully bond the large scale micro- and nanofluidic chips. The influence of Ar plasma parameters on the water contact angle and the effect of bonding conditions on the bonding rate and the bonding strength of the chip were studied. The fluorescence tests demonstrate that the 5 × 5 cm2 poly(methyl methacrylate) chip with 180 nm wide and 180 nm deep nanochannels can be fabricated without any block and leakage by our newly developed method.

Nanophotonic lab-on-a-chip platforms including novel bimodal interferometers, microfluidics and grating couplers.

PubMed

Duval, Daphné; González-Guerrero, Ana Belén; Dante, Stefania; Osmond, Johann; Monge, Rosa; Fernández, Luis J; Zinoviev, Kirill E; Domínguez, Carlos; Lechuga, Laura M

2012-05-08

One of the main limitations for achieving truly lab-on-a-chip (LOC) devices for point-of-care diagnosis is the incorporation of the "on-chip" detection. Indeed, most of the state-of-the-art LOC devices usually require complex read-out instrumentation, losing the main advantages of portability and simplicity. In this context, we present our last advances towards the achievement of a portable and label-free LOC platform with highly sensitive "on-chip" detection by using nanophotonic biosensors. Bimodal waveguide interferometers fabricated by standard silicon processes have been integrated with sub-micronic grating couplers for efficient light in-coupling, showing a phase resolution of 6.6 × 10(-4)× 2π rad and a limit of detection of 3.3 × 10(-7) refractive index unit (RIU) in bulk. A 3D network of SU-8 polymer microfluidics monolithically assembled at the wafer-level was included, ensuring perfect sealing and compact packaging. To overcome some of the drawbacks inherent to interferometric read-outs, a novel all-optical wavelength modulation system has been implemented, providing a linear response and a direct read-out of the phase variation. Sensitivity, specificity and reproducibility of the wavelength modulated BiMW sensor has been demonstrated through the label-free immunodetection of the human hormone hTSH at picomolar level using a reliable biofunctionalization process.

Programmable Nano-Bio-Chip Sensors: Analytical Meets Clinical

PubMed Central

Jokerst, Jesse V.; Floriano, Pierre N.; Christodoulides, Nicolaos; McDevitt, John T.; Jacobson, James W.; Bhagwandin, Bryon D.

2010-01-01

synopsis There have been many recent advances in the nano-bio-chip (NBC) analysis methodology with implications for a number of high-morbidity diseases including HIV, cancer, and heart disease. In their Feature article, Jesse V. Jokerst of The University of Texas at Austin; Pierre N. Floriano, Nicolaos Christodoulides, and John T. McDevitt of Rice University; and James W. Jacobson and Bryon D. Bhagwandin of LabNow, Inc. discuss the construction, capabilities, and advantages of NBCs. The cover shows arrays of NBCs. Images courtesy of Glennon Simmons/McDevitt Lab and Marcha Miller of The University of Texas at Austin. PMID:20128622

High-aspect ratio magnetic nanocomposite polymer cilium

NASA Astrophysics Data System (ADS)

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

2014-03-01

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

Nitrogen removal in wood chip combined substrate baffled subsurface-flow constructed wetlands: impact of matrix arrangement and intermittent aeration.

PubMed

Li, Huai; Chi, Zifang; Yan, Baixing; Cheng, Long; Li, Jianzheng

2017-02-01

In this study, two lab-scale baffled subsurface-flow constructed wetlands (BSFCWs), including gravel-wood chips-slag and gravel-slag-wood chips, were operated at different intermittent aeration to evaluate the effect of artificial aeration and slow-released carbon source on the treatment efficiency of high-strength nitrogen wastewater. Results indicated that gravel-slag-wood chips extended aerobic/anaerobic alternating environment to gravel and slag zones and maintained anaerobic condition in the subsequent wood chip section. The order of gravel-slag-wood chip was more beneficial to pollutant removal. Sufficient carbon source supply resulted from wood-chip-framework substrate simultaneously obtained high removals of COD (97%), NH 4 + -N (95%), and TN (94%) in BSFCWs at 2 h aeration per day. The results suggest that intermittent aeration combined with wood chips could achieve high nitrogen removal in BSFCWs.

Advances in developing rapid, reliable and portable detection systems for alcohol.

PubMed

Thungon, Phurpa Dema; Kakoti, Ankana; Ngashangva, Lightson; Goswami, Pranab

2017-11-15

Development of portable, reliable, sensitive, simple, and inexpensive detection system for alcohol has been an instinctive demand not only in traditional brewing, pharmaceutical, food and clinical industries but also in rapidly growing alcohol based fuel industries. Highly sensitive, selective, and reliable alcohol detections are currently amenable typically through the sophisticated instrument based analyses confined mostly to the state-of-art analytical laboratory facilities. With the growing demand of rapid and reliable alcohol detection systems, an all-round attempt has been made over the past decade encompassing various disciplines from basic and engineering sciences. Of late, the research for developing small-scale portable alcohol detection system has been accelerated with the advent of emerging miniaturization techniques, advanced materials and sensing platforms such as lab-on-chip, lab-on-CD, lab-on-paper etc. With these new inter-disciplinary approaches along with the support from the parallel knowledge growth on rapid detection systems being pursued for various targets, the progress on translating the proof-of-concepts to commercially viable and environment friendly portable alcohol detection systems is gaining pace. Here, we summarize the progress made over the years on the alcohol detection systems, with a focus on recent advancement towards developing portable, simple and efficient alcohol sensors. Copyright © 2017 Elsevier B.V. All rights reserved.

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

PubMed

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

2016-08-16

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

[Theoretical foundations of protein chips and their possible use in medical research and diagnostics].

PubMed

Spisák, Sándor; Molnár, Béla; Galamb, Orsolya; Sipos, Ferenc; Tulassay, Zsolt

2007-08-12

The confirmation of mRNA expression studies by protein chips is of high recent interest due to the widespread application of expression arrays. In this review the advantages, technical limitations, application fields and the first results of the protein arrays is described. The bottlenecks of the increasing protein array applications are the fast decomposition of proteins, the problem with aspecific binding and the lack of amplification techniques. Today glass slide based printed, SELDI (MS) based, electrophoresis based and tissue microarray based technologies are available. The advantage of the glass slide based chips are the simplicity of their application, and relatively low cost. The SELDI based protein chip technique is applicable to minute amounts of starting material (<1 microg) but it is the most expensive one. The electrophoresis based techniques are still under intensive development. The tissue microarrays can be used for the parallel testing of the sensitivity and specificity of single antibodies on a broad range of histological specimens on a single slide. Protein chips were successfully used for serum tumor marker detection, cancer research, cell physiology studies and for the verification of mRNA expression studies. Protein chips are envisioned to be available for routine diagnostic applications if the ongoing technology development will be successful in increase in sensitivity, specificity, costs reduction and for the reduction of the necessary sample volume.

Micromotor-based lab-on-chip immunoassays.

PubMed

García, Miguel; Orozco, Jahir; Guix, Maria; Gao, Wei; Sattayasamitsathit, Sirilak; Escarpa, Alberto; Merkoçi, Arben; Wang, Joseph

2013-02-21

Here we describe the first example of using self-propelled antibody-functionalized synthetic catalytic microengines for capturing and transporting target proteins between the different reservoirs of a lab-on-a-chip (LOC) device. A new catalytic polymer/Ni/Pt microtube engine, containing carboxy moieties on its mixed poly(3,4-ethylenedioxythiophene) (PEDOT)/COOH-PEDOT polymeric outermost layer, is further functionalized with the antibody receptor to selectively recognize and capture the target protein. The new motor-based microchip immunoassay operations are carried out without any bulk fluid flow, replacing the common washing steps in antibody-based protein bioassays with the active transport of the captured protein throughout the different reservoirs, where each step of the immunoassay takes place. A first microchip format involving an 'on-the-fly' double-antibody sandwich assay (DASA) is used for demonstrating the selective capture of the target protein, in the presence of excess of non-target proteins. A secondary antibody tagged with a polymeric-sphere tracer allows the direct visualization of the binding events. In a second approach the immuno-nanomotor captures and transports the microsphere-tagged antigen through a microchannel network. An anti-protein-A modified microengine is finally used to demonstrate the selective capture, transport and convenient label-free optical detection of a Staphylococcus aureus target bacteria (containing proteinA in its cell wall) in the presence of a large excess of non-target (Saccharomyces cerevisiae) cells. The resulting nanomotor-based microchip immunoassay offers considerable potential for diverse applications in clinical diagnostics, environmental and security monitoring fields.

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

PubMed

Temiz, Yuksel; Delamarche, Emmanuel

2017-01-01

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

Efficient SNP Discovery by Combining Microarray and Lab-on-a-Chip Data for Animal Breeding and Selection

PubMed Central

Huang, Chao-Wei; Lin, Yu-Tsung; Ding, Shih-Torng; Lo, Ling-Ling; Wang, Pei-Hwa; Lin, En-Chung; Liu, Fang-Wei; Lu, Yen-Wen

2015-01-01

The genetic markers associated with economic traits have been widely explored for animal breeding. Among these markers, single-nucleotide polymorphism (SNPs) are gradually becoming a prevalent and effective evaluation tool. Since SNPs only focus on the genetic sequences of interest, it thereby reduces the evaluation time and cost. Compared to traditional approaches, SNP genotyping techniques incorporate informative genetic background, improve the breeding prediction accuracy and acquiesce breeding quality on the farm. This article therefore reviews the typical procedures of animal breeding using SNPs and the current status of related techniques. The associated SNP information and genotyping techniques, including microarray and Lab-on-a-Chip based platforms, along with their potential are highlighted. Examples in pig and poultry with different SNP loci linked to high economic trait values are given. The recommendations for utilizing SNP genotyping in nimal breeding are summarized. PMID:27600241

Integrated circuit-based instrumentation for microchip capillary electrophoresis.

PubMed

Behnam, M; Kaigala, G V; Khorasani, M; Martel, S; Elliott, D G; Backhouse, C J

2010-09-01

Although electrophoresis with laser-induced fluorescence (LIF) detection has tremendous potential in lab on chip-based point-of-care disease diagnostics, the wider use of microchip electrophoresis has been limited by the size and cost of the instrumentation. To address this challenge, the authors designed an integrated circuit (IC, i.e. a microelectronic chip, with total silicon area of <0.25 cm2, less than 5 mmx5 mm, and power consumption of 28 mW), which, with a minimal additional infrastructure, can perform microchip electrophoresis with LIF detection. The present work enables extremely compact and inexpensive portable systems consisting of one or more complementary metal-oxide-semiconductor (CMOS) chips and several other low-cost components. There are, to the authors' knowledge, no other reports of a CMOS-based LIF capillary electrophoresis instrument (i.e. high voltage generation, switching, control and interface circuit combined with LIF detection). This instrument is powered and controlled using a universal serial bus (USB) interface to a laptop computer. The authors demonstrate this IC in various configurations and can readily analyse the DNA produced by a standard medical diagnostic protocol (end-labelled polymerase chain reaction (PCR) product) with a limit of detection of approximately 1 ng/microl (approximately 1 ng of total DNA). The authors believe that this approach may ultimately enable lab-on-a-chip-based electrophoretic instruments that cost on the order of several dollars.

Lift-off process with bi-layer photoresist patterns for conformal-coated superhydrophilic pulsed plasma chemical vapor deposition-SiOx on SiCx for lab-on-a-chip applications

NASA Astrophysics Data System (ADS)

Konishi, Satoshi; Nakagami, Chise; Kobayashi, Taizo; Tonomura, Wataru; Kaizuma, Yoshihiro

2015-04-01

In this work, a lift-off process with bi-layer photoresist patterns was applied to the formation of hydrophobic/hydrophilic micropatterns on practical polymer substrates used in healthcare diagnostic commercial products. The bi-layer photoresist patterns with undercut structures made it possible to peel the conformal-coated silicon oxide (SiOx) films from substrates. SiOx and silicon carbide (SiCx) layers were deposited by pulsed plasma chemical vapor deposition (PPCVD) method which can form roughened surfaces to enhance hydrophilicity of SiOx and hydrophobicity of SiCx. Microfluidic applications using hydrophobic/hydrophilic patterns were also demonstrated on low-cost substrates such as poly(ethylene terephthalate) (PET) and paper films.

High-performance packaging for monolithic microwave and millimeter-wave integrated circuits

NASA Technical Reports Server (NTRS)

Shalkhauser, K. A.; Li, K.; Shih, Y. C.

1992-01-01

Packaging schemes were developed that provide low-loss, hermetic enclosure for advanced monolithic microwave and millimeter-wave integrated circuits (MMICs). The package designs are based on a fused quartz substrate material that offers improved radio frequency (RF) performance through 44 gigahertz (GHz). The small size and weight of the packages make them appropriate for a variety of applications, including phased array antenna systems. Packages were designed in two forms; one for housing a single MMIC chip, the second in the form of a multi-chip phased array module. The single chip array module was developed in three separate sizes, for chips of different geometry and frequency requirements. The phased array module was developed to address packaging directly for antenna applications, and includes transmission line and interconnect structures to support multi-element operation. All packages are fabricated using fused quartz substrate materials. As part of the packaging effort, a test fixture was developed to interface the single chip packages to conventional laboratory instrumentation for characterization of the packaged devices. The package and test fixture designs were both developed in a generic sense, optimizing performance for a wide range of possible applications and devices.

Application of 3D Printing Technology in Increasing the Diagnostic Performance of Enzyme-Linked Immunosorbent Assay (ELISA) for Infectious Diseases

PubMed Central

Singh, Harpal; Shimojima, Masayuki; Shiratori, Tomomi; An, Le Van; Sugamata, Masami; Yang, Ming

2015-01-01

Enzyme-linked Immunosorbent Assay (ELISA)-based diagnosis is the mainstay for measuring antibody response in infectious diseases and to support pathogen identification of potential use in infectious disease outbreaks and clinical care of individual patients. The development of laboratory diagnostics using readily available 3D printing technologies provides a timely opportunity for further expansion of this technology into immunodetection systems. Utilizing available 3D printing platforms, a ‘3D well’ was designed and developed to have an increased surface area compared to those of 96-well plates. The ease and rapidity of the development of the 3D well prototype provided an opportunity for its rapid validation through the diagnostic performance of ELISA in infectious disease without modifying current laboratory practices for ELISA. The improved sensitivity of the 3D well of up to 2.25-fold higher compared to the 96-well ELISA provides a potential for the expansion of this technology towards miniaturization and Lab-On-a-Chip platforms to reduce time, volume of reagents and samples needed for such assays in the laboratory diagnosis of infectious and other diseases including applications in other disciplines. PMID:26184194

Application of 3D Printing Technology in Increasing the Diagnostic Performance of Enzyme-Linked Immunosorbent Assay (ELISA) for Infectious Diseases.

PubMed

Singh, Harpal; Shimojima, Masayuki; Shiratori, Tomomi; An, Le Van; Sugamata, Masami; Yang, Ming

2015-07-08

Enzyme-linked Immunosorbent Assay (ELISA)-based diagnosis is the mainstay for measuring antibody response in infectious diseases and to support pathogen identification of potential use in infectious disease outbreaks and clinical care of individual patients. The development of laboratory diagnostics using readily available 3D printing technologies provides a timely opportunity for further expansion of this technology into immunodetection systems. Utilizing available 3D printing platforms, a '3D well' was designed and developed to have an increased surface area compared to those of 96-well plates. The ease and rapidity of the development of the 3D well prototype provided an opportunity for its rapid validation through the diagnostic performance of ELISA in infectious disease without modifying current laboratory practices for ELISA. The improved sensitivity of the 3D well of up to 2.25-fold higher compared to the 96-well ELISA provides a potential for the expansion of this technology towards miniaturization and Lab-On-a-Chip platforms to reduce time, volume of reagents and samples needed for such assays in the laboratory diagnosis of infectious and other diseases including applications in other disciplines.

Real-time microfluidic recombinase polymerase amplification for the toxin B gene of Clostridium difficile on a SlipChip platform.

PubMed

Tsaloglou, M-N; Watson, R J; Rushworth, C M; Zhao, Y; Niu, X; Sutton, J M; Morgan, H

2015-01-07

Clostridium difficile is one of the key bacterial pathogens that cause infectious diarrhoea both in the developed and developing world. Isothermal nucleic acid amplification methods are increasingly used for identification of toxinogenic infection by clinical labs. For this purpose, we developed a low-cost microfluidic platform based on the SlipChip concept and implemented real-time isothermal recombinase polymerase amplification (RPA). The on-chip RPA assay targets the Clostridium difficile toxin B gene (tcdB) coding for toxin B, one of the proteins responsible for bacterial toxicity. The device was fabricated in clear acrylic using rapid prototyping methods. It has six replicate 500 nL reaction wells as well as two sets of 500 nL control wells. The reaction can be monitored in real-time using exonuclease fluorescent probes with an initial sample volume of as little as 6.4 μL. We demonstrated a limit of detection of 1000 DNA copies, corresponding to 1 fg, at a time-to-result of <20 minutes. This miniaturised platform for pathogen detection has potential for use in resource-limited environments or at the point-of-care because of its ease of use and low cost, particularly if combined with preserved reagents.

NeuroSeek dual-color image processing infrared focal plane array

NASA Astrophysics Data System (ADS)

McCarley, Paul L.; Massie, Mark A.; Baxter, Christopher R.; Huynh, Buu L.

1998-09-01

Several technologies have been developed in recent years to advance the state of the art of IR sensor systems including dual color affordable focal planes, on-focal plane array biologically inspired image and signal processing techniques and spectral sensing techniques. Pacific Advanced Technology (PAT) and the Air Force Research Lab Munitions Directorate have developed a system which incorporates the best of these capabilities into a single device. The 'NeuroSeek' device integrates these technologies into an IR focal plane array (FPA) which combines multicolor Midwave IR/Longwave IR radiometric response with on-focal plane 'smart' neuromorphic analog image processing. The readout and processing integrated circuit very large scale integration chip which was developed under this effort will be hybridized to a dual color detector array to produce the NeuroSeek FPA, which will have the capability to fuse multiple pixel-based sensor inputs directly on the focal plane. Great advantages are afforded by application of massively parallel processing algorithms to image data in the analog domain; the high speed and low power consumption of this device mimic operations performed in the human retina.

ELISA-LOC: lab-on-a-chip for enzyme-linked immunodetection.

PubMed

Sun, Steven; Yang, Minghui; Kostov, Yordan; Rasooly, Avraham

2010-08-21

A miniature 96 sample ELISA-lab-on-a-chip (ELISA-LOC) was designed, fabricated, and tested for immunological detection of Staphylococcal Enterotoxin B (SEB). The chip integrates a simple microfluidics system into a miniature ninety-six sample plate, allowing the user to carry out an immunological assay without a laboratory. Assay reagents are delivered into the assay plate without the need for separate devices commonly used in immunoassays. The ELISA-LOC was constructed using Laminated Object Manufacturing (LOM) technology to assemble six layers with an acrylic (poly(methyl methacrylate) (PMMA)) core and five polycarbonate layers micromachined by a CO(2) laser. The ELISA-LOC has three main functional elements: reagent loading fluidics, assay and detection wells, and reagent removal fluidics, a simple "surface tension" valve used to control the flow. To enhance assay sensitivity and to perform the assay without a lab, ELISA-LOC detection combines several biosensing elements: (1) carbon nanotube (CNT) technology to enhance primary antibody immobilization, (2) sensitive ECL (electrochemiluminescence) detection, and (3) a charge-coupled device (CCD) detector for measuring the light signal generated by ECL. Using a sandwich ELISA assay, the system detected SEB at concentrations as low as 0.1 ng ml(-1), which is similar to the reported sensitivity of conventional ELISA. The fluidics system can be operated by a syringe and does not require power for operation. This simple point-of-care (POC) system is useful for carrying out various immunological assays and other complex medical assays without a laboratory.

The SmartBioPhone, a point of care vision under development through two European projects: OPTOLABCARD and LABONFOIL.

PubMed

Ruano-López, Jesus M; Agirregabiria, Maria; Olabarria, Garbiñe; Verdoy, Dolores; Bang, Dang D; Bu, Minqiang; Wolff, Anders; Voigt, Anja; Dziuban, Jan A; Walczak, Rafał; Berganzo, Javier

2009-06-07

This paper describes how sixteen partners from eight different countries across Europe are working together in two EU projects focused on the development of a point of care system. This system uses disposable Lab on a Chips (LOCs) that carry out the complete assay from sample preparation to result interpretation of raw samples. The LOC is either embedded in a flexible motherboard with the form of a smartcard (Labcard) or in a Skinpatch. The first project, OPTOLABCARD, extended and tested the use of a thick photoresit (SU-8) as a structural material to manufacture LOCs by lamination. This project produced several examples where SU-8 microfluidic circuitry revealed itself as a viable material for several applications, such as the integration on chip of a Polymerase Chain Reaction (PCR) that includes sample concentration, PCR amplification and optical detection of Salmonella spp. using clinical samples. The ongoing project, LABONFOIL, is using two results of OPTOLABCARD: the sample concentration method and the capability to fabricate flexible and ultra thin LOCs based on sheets instead of wafers. This rupture from the limited and expensive wafer surface heritage allows the development of a platform where LOCs are big enough to include all the sample preparation subcomponents at a low price. These LOCs will be used in four point of care applications: environment, food, cancer and drug monitoring. The user will obtain the results of the tests by connecting the Labcard/Skinpatch reader to a very popular interface (a smartphone), creating a new instrument namely "The SmartBioPhone". All standard smartphone capabilities will be at the disposal of the point of care instrument by a simple click. In order to guarantee the future mass production of these LOCs, the project will develop a large dry film equipment where LOCs will be fabricated at a low cost.

Next Generation Programmable Bio-Nano-Chip System for On-Site Detection in Oral Fluids.

PubMed

Christodoulides, Nicolaos; De La Garza, Richard; Simmons, Glennon W; McRae, Michael P; Wong, Jorge; Newton, Thomas F; Kosten, Thomas R; Haque, Ahmed; McDevitt, John T

2015-11-23

Current on-site drug of abuse detection methods involve invasive sampling of blood and urine specimens, or collection of oral fluid, followed by qualitative screening tests using immunochromatographic cartridges. Test confirmation and quantitative assessment of a presumptive positive are then provided by remote laboratories, an inefficient and costly process decoupled from the initial sampling. Recently, a new noninvasive oral fluid sampling approach that is integrated with the chip-based Programmable Bio-Nano-Chip (p-BNC) platform has been developed for the rapid (~ 10 minutes), sensitive detection (~ ng/ml) and quantitation of 12 drugs of abuse. Furthermore, the system can provide the time-course of select drug and metabolite profiles in oral fluids. For cocaine, we observed three slope components were correlated with cocaine-induced impairment using this chip-based p-BNC detection modality. Thus, this p-BNC has significant potential for roadside drug testing by law enforcement officers. Initial work reported on chip-based drug detection was completed using 'macro' or "chip in the lab" prototypes, that included metal encased "flow cells", external peristaltic pumps and a bench-top analyzer system instrumentation. We now describe the next generation miniaturized analyzer instrumentation along with customized disposables and sampling devices. These tools will offer real-time oral fluid drug monitoring capabilities, to be used for roadside drug testing as well as testing in clinical settings as a non-invasive, quantitative, accurate and sensitive tool to verify patient adherence to treatment.

Surface transport and stable trapping of particles and cells by an optical waveguide loop.

PubMed

Hellesø, Olav Gaute; Løvhaugen, Pål; Subramanian, Ananth Z; Wilkinson, James S; Ahluwalia, Balpreet Singh

2012-09-21

Waveguide trapping has emerged as a useful technique for parallel and planar transport of particles and biological cells and can be integrated with lab-on-a-chip applications. However, particles trapped on waveguides are continuously propelled forward along the surface of the waveguide. This limits the practical usability of the waveguide trapping technique with other functions (e.g. analysis, imaging) that require particles to be stationary during diagnosis. In this paper, an optical waveguide loop with an intentional gap at the centre is proposed to hold propelled particles and cells. The waveguide acts as a conveyor belt to transport and deliver the particles/cells towards the gap. At the gap, the diverging light fields hold the particles at a fixed position. The proposed waveguide design is numerically studied and experimentally implemented. The optical forces on the particle at the gap are calculated using the finite element method. Experimentally, the method is used to transport and trap micro-particles and red blood cells at the gap with varying separations. The waveguides are only 180 nm thick and thus could be integrated with other functions on the chip, e.g. microfluidics or optical detection, to make an on-chip system for single cell analysis and to study the interaction between cells.

DNA Microarray for Rapid Detection and Identification of Food and Water Borne Bacteria: From Dry to Wet Lab.

PubMed

Ranjbar, Reza; Behzadi, Payam; Najafi, Ali; Roudi, Raheleh

2017-01-01

A rapid, accurate, flexible and reliable diagnostic method may significantly decrease the costs of diagnosis and treatment. Designing an appropriate microarray chip reduces noises and probable biases in the final result. The aim of this study was to design and construct a DNA Microarray Chip for a rapid detection and identification of 10 important bacterial agents. In the present survey, 10 unique genomic regions relating to 10 pathogenic bacterial agents including Escherichia coli (E.coli), Shigella boydii, Sh.dysenteriae, Sh.flexneri, Sh.sonnei, Salmonella typhi, S.typhimurium, Brucella sp., Legionella pneumophila, and Vibrio cholera were selected for designing specific long oligo microarray probes. For this reason, the in-silico operations including utilization of the NCBI RefSeq database, Servers of PanSeq and Gview, AlleleID 7.7 and Oligo Analyzer 3.1 was done. On the other hand, the in-vitro part of the study comprised stages of robotic microarray chip probe spotting, bacterial DNAs extraction and DNA labeling, hybridization and microarray chip scanning. In wet lab section, different tools and apparatus such as Nexterion® Slide E, Qarray mini spotter, NimbleGen kit, TrayMix TM S4, and Innoscan 710 were used. A DNA microarray chip including 10 long oligo microarray probes was designed and constructed for detection and identification of 10 pathogenic bacteria. The DNA microarray chip was capable to identify all 10 bacterial agents tested simultaneously. The presence of a professional bioinformatician as a probe designer is needed to design appropriate multifunctional microarray probes to increase the accuracy of the outcomes.

An optimized resistor pattern for temperature gradient control in microfluidics

NASA Astrophysics Data System (ADS)

Selva, Bertrand; Marchalot, Julien; Jullien, Marie-Caroline

2009-06-01

In this paper, we demonstrate the possibility of generating high-temperature gradients with a linear temperature profile when heating is provided in situ. Thanks to improved optimization algorithms, the shape of resistors, which constitute the heating source, is optimized by applying the genetic algorithm NSGA-II (acronym for the non-dominated sorting genetic algorithm) (Deb et al 2002 IEEE Trans. Evol. Comput. 6 2). Experimental validation of the linear temperature profile within the cavity is carried out using a thermally sensitive fluorophore, called Rhodamine B (Ross et al 2001 Anal. Chem. 73 4117-23, Erickson et al 2003 Lab Chip 3 141-9). The high level of agreement obtained between experimental and numerical results serves to validate the accuracy of this method for generating highly controlled temperature profiles. In the field of actuation, such a device is of potential interest since it allows for controlling bubbles or droplets moving by means of thermocapillary effects (Baroud et al 2007 Phys. Rev. E 75 046302). Digital microfluidics is a critical area in the field of microfluidics (Dreyfus et al 2003 Phys. Rev. Lett. 90 14) as well as in the so-called lab-on-a-chip technology. Through an example, the large application potential of such a technique is demonstrated, which entails handling a single bubble driven along a cavity using simple and tunable embedded resistors.

Lab-on-chip platform for circulating tumor cells isolation

NASA Astrophysics Data System (ADS)

Maurya, D. K.; Fooladvand, M.; Gray, E.; Ziman, M.; Alameh, K.

2015-12-01

We design, develop and demonstrate the principle of a continuous, non-intrusive, low power microfluidics-based lab-ona- chip (LOC) structure for Circulating Tumor Cell (CTC) separation. Cell separation is achieved through 80 cascaded contraction and expansion microchannels of widths 60 μm and 300 μm, respectively, and depth 60 μm, which enable momentum-change-induced inertial forces to be exerted on the cells, thus routing them to desired destinations. The total length of the developed LOC is 72 mm. The LOC structure is simulated using the COMSOL multiphysics software, which enables the optimization of the dimensions of the various components of the LOC structure, namely the three inlets, three filters, three contraction and expansion microchannel segments and five outlets. Simulation results show that the LOC can isolate CTCs of sizes ranging from 15 to 30 μm with a recovery rate in excess of 90%. Fluorescent microparticles of two different sizes (5 μm and 15 μm), emulating blood and CTC cells, respectively, are used to demonstrate the principle of the developed LOC. A mixture of these microparticles is injected into the primary LOC inlet via an electronically-controlled syringe pump, and the large-size particles are routed to the primary LOC outlet through the contraction and expansion microchannels. Experimental results demonstrate the ability of the developed LOC to isolate particles by size exclusion with an accuracy of 80%. Ongoing research is focusing on the LOC design improvement for better separation efficiency and testing of biological samples for isolation of CTCs.

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

PubMed

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

2009-06-07

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

Organ-on-a-chip: development and clinical prospects toward toxicity assessment with an emphasis on bone marrow.

PubMed

Kim, Jeehye; Lee, Hanna; Selimović, Šeila; Gauvin, Robert; Bae, Hojae

2015-05-01

Conventional approaches for toxicity evaluation of drugs and chemicals, such as animal tests, can be impractical due to the large experimental scale and the immunological differences between species. Organ-on-a-chip models have recently been recognized as a prominent alternative to conventional toxicity tests aiming to simulate the human in vivo physiology. This review focuses on the organ-on-a-chip applications for high-throughput screening of candidate drugs against toxicity, with a particular emphasis on bone-marrow-on-a-chip. Studies in which organ-on-a-chip models have been developed and utilized to maximize the efficiency and predictability in toxicity assessment are introduced. The potential of these devices to replace tests of acute systemic toxicity in animals, and the challenges that are inherent in simulating the human immune system are also discussed. As a promising approach to overcome the limitations, we further focus on an in-depth analysis of the development of bone-marrow-on-a-chip that is capable of simulating human immune responses against external stimuli due to the key roles of marrow in immune systems with hematopoietic activities. Owing to the complex interactions between hematopoietic stem cells and marrow microenvironments, precise control of both biochemical and physical niches that are critical in maintenance of hematopoiesis remains a key challenge. Thus, recently developed bone-marrow-on-a-chip models support immunogenicity and immunotoxicity testing in long-term cultivation with repeated antigen stimulation. In this review, we provide an overview of clinical studies that have been carried out on bone marrow transplants in patients with immune-related diseases and future aspects of clinical and pharmaceutical application of bone-marrow-on-a-chip.

System-Level Biochip for Impedance Sensing and Programmable Manipulation of Bladder Cancer Cells

PubMed Central

Chuang, Cheng-Hsin; Huang, Yao-Wei; Wu, Yao-Tung

2011-01-01

This paper develops a dielectrophoretic (DEP) chip with multi-layer electrodes and a micro-cavity array for programmable manipulations of cells and impedance measurement. The DEP chip consists of an ITO top electrode, flow chamber, middle electrode on an SU-8 surface, micro-cavity arrays of SU-8 and distributed electrodes at the bottom of the micro-cavity. Impedance sensing of single cells could be performed as follows: firstly, cells were trapped in a micro-cavity array by negative DEP force provided by top and middle electrodes; then, the impedance measurement for discrimination of different stage of bladder cancer cells was accomplished by the middle and bottom electrodes. After impedance sensing, the individual releasing of trapped cells was achieved by negative DEP force using the top and bottom electrodes in order to collect the identified cells once more. Both cell manipulations and impedance measurement had been integrated within a system controlled by a PC-based LabVIEW program. In the experiments, two different stages of bladder cancer cell lines (grade III: T24 and grade II: TSGH8301) were utilized for the demonstration of programmable manipulation and impedance sensing; as the results show, the lower-grade bladder cancer cells (TSGH8301) possess higher impedance than the higher-grade ones (T24). In general, the multi-step manipulations of cells can be easily programmed by controlling the electrical signal in our design, which provides an excellent platform technology for lab-on-a-chip (LOC) or a micro-total-analysis-system (Micro TAS). PMID:22346685

Front-End Processing of Cell Lysates for Enhanced Chip-Based Detection

DTIC Science & Technology

2006-07-28

manipulation used in lab-on-a-chip devices. A small unknown sample is first mixed with the PNA surfactants (“PNAA”) to tag the DNA targets, and then the...unknown sample is first mixed with the PNA surfactants (hereafter referred to as “PNA amphiphiles” or “PNAA”) to tag the DNA targets, and then the...prolate ellipsoid, and mixed PNAA/SDS micelles form spherical micelles. On addition of complementary DNA, the PNAA/DNA duplexes do not participate in

Product assurance technology for procuring reliable, radiation-hard, custom LSI/VLSI electronics

NASA Technical Reports Server (NTRS)

Buehler, M. G.; Allen, R. A.; Blaes, B. R.; Hicks, K. A.; Jennings, G. A.; Lin, Y.-S.; Pina, C. A.; Sayah, H. R.; Zamani, N.

1989-01-01

Advanced measurement methods using microelectronic test chips are described. These chips are intended to be used in acquiring the data needed to qualify Application Specific Integrated Circuits (ASIC's) for space use. Efforts were focused on developing the technology for obtaining custom IC's from CMOS/bulk silicon foundries. A series of test chips were developed: a parametric test strip, a fault chip, a set of reliability chips, and the CRRES (Combined Release and Radiation Effects Satellite) chip, a test circuit for monitoring space radiation effects. The technical accomplishments of the effort include: (1) development of a fault chip that contains a set of test structures used to evaluate the density of various process-induced defects; (2) development of new test structures and testing techniques for measuring gate-oxide capacitance, gate-overlap capacitance, and propagation delay; (3) development of a set of reliability chips that are used to evaluate failure mechanisms in CMOS/bulk: interconnect and contact electromigration and time-dependent dielectric breakdown; (4) development of MOSFET parameter extraction procedures for evaluating subthreshold characteristics; (5) evaluation of test chips and test strips on the second CRRES wafer run; (6) two dedicated fabrication runs for the CRRES chip flight parts; and (7) publication of two papers: one on the split-cross bridge resistor and another on asymmetrical SRAM (static random access memory) cells for single-event upset analysis.

Slotted Photonic Crystal Sensors

PubMed Central

Scullion, Mark G.; Krauss, Thomas F.; Di Falco, Andrea

2013-01-01

Optical biosensors are increasingly being considered for lab-on-a-chip applications due to their benefits such as small size, biocompatibility, passive behaviour and lack of the need for fluorescent labels. The light guiding mechanisms used by many of them results in poor overlap of the optical field with the target molecules, reducing the maximum sensitivity achievable. This review article presents a new platform for optical biosensors, namely slotted photonic crystals, which provide higher sensitivities due to their ability to confine, spatially and temporally, the optical mode peak within the analyte itself. Loss measurements showed values comparable to standard photonic crystals, confirming their ability to be used in real devices. A novel resonant coupler was designed, simulated, and experimentally tested, and was found to perform better than other solutions within the literature. Combining with cavities, microfluidics and biological functionalization allowed proof-of-principle demonstrations of protein binding to be carried out. Higher sensitivities were observed in smaller structures than possible with most competing devices reported in the literature. This body of work presents slotted photonic crystals as a realistic platform for complete on-chip biosensing; addressing key design, performance and application issues, whilst also opening up exciting new ideas for future study. PMID:23503295

Multifrequency sources of quantum correlated photon pairs on-chip: a path toward integrated Quantum Frequency Combs

NASA Astrophysics Data System (ADS)

Caspani, Lucia; Reimer, Christian; Kues, Michael; Roztocki, Piotr; Clerici, Matteo; Wetzel, Benjamin; Jestin, Yoann; Ferrera, Marcello; Peccianti, Marco; Pasquazi, Alessia; Razzari, Luca; Little, Brent E.; Chu, Sai T.; Moss, David J.; Morandotti, Roberto

2016-06-01

Recent developments in quantum photonics have initiated the process of bringing photonic-quantumbased systems out-of-the-lab and into real-world applications. As an example, devices to enable the exchange of a cryptographic key secured by the laws of quantum mechanics are already commercially available. In order to further boost this process, the next step is to transfer the results achieved by means of bulky and expensive setups into miniaturized and affordable devices. Integrated quantum photonics is exactly addressing this issue. In this paper, we briefly review the most recent advancements in the generation of quantum states of light on-chip. In particular, we focus on optical microcavities, as they can offer a solution to the problem of low efficiency that is characteristic of the materials typically used in integrated platforms. In addition, we show that specifically designed microcavities can also offer further advantages, such as compatibility with telecom standards (for exploiting existing fibre networks) and quantum memories (necessary to extend the communication distance), as well as giving a longitudinal multimode character for larger information transfer and processing. This last property (i.e., the increased dimensionality of the photon quantum state) is achieved through the ability to generate multiple photon pairs on a frequency comb, corresponding to the microcavity resonances. Further achievements include the possibility of fully exploiting the polarization degree of freedom, even for integrated devices. These results pave the way for the generation of integrated quantum frequency combs that, in turn, may find important applications toward the realization of a compact quantum-computing platform.

Capacitance Variation Induced by Microfluidic Two-Phase Flow across Insulated Interdigital Electrodes in Lab-On-Chip Devices

PubMed Central

Dong, Tao; Barbosa, Cátia

2015-01-01

Microfluidic two-phase flow detection has attracted plenty of interest in various areas of biology, medicine and chemistry. This work presents a capacitive sensor using insulated interdigital electrodes (IDEs) to detect the presence of droplets in a microchannel. This droplet sensor is composed of a glass substrate, patterned gold electrodes and an insulation layer. A polydimethylsiloxane (PDMS) cover bonded to the multilayered structure forms a microchannel. Capacitance variation induced by the droplet passage was thoroughly investigated with both simulation and experimental work. Olive oil and deionized water were employed as the working fluids in the experiments to demonstrate the droplet sensor. The results show a good sensitivity of the droplet with the appropriate measurement connection. This capacitive droplet sensor is promising to be integrated into a lab-on-chip device for in situ monitoring/counting of droplets or bubbles. PMID:25629705

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.

Single molecule actuation and detection on a lab-on-a-chip magnetoresistive platform

NASA Astrophysics Data System (ADS)

Chaves, R. C.; Bensimon, D.; Freitas, P. P.

2011-03-01

On-chip magnetic tweezers based on current loops were integrated with magnetoresistive sensors. Magnetic forces up to 1.0±0.3pN are produced to actuate on DNA anchored to the surface of a flow cell and labeled with micrometer-sized magnetic beads. The levitation of the beads stretches the immobilized DNA. The relative position of the magnetic beads is monitored using spin-valve sensors. A bead vertical displacement resolution of 60nm is derived for DNA molecular motor activity in a tweezer steady current regime.

[Lab-on-a-chip systems in the point-of-care diagnostics].

PubMed

Szabó, Barnabás; Borbíró, András; Fürjes, Péter

2015-12-27

The need in modern medicine for near-patient diagnostics being able to accelerate therapeutic decisions and possibly replacing laboratory measurements is significantly growing. Reliable and cost-effective bioanalytical measurement systems are required which - acting as a micro-laboratory - contain integrated biomolecular recognition, sensing, signal processing and complex microfluidic sample preparation modules. These micro- and nanofabricated Lab-on-a-chip systems open new perspectives in the diagnostic supply chain, since they are able even for quantitative, high-precision and immediate analysis of special disease specific molecular markers or their combinations from a single drop of sample. Accordingly, crucial requirements regarding the instruments and the analytical methods are the high selectivity, extremely low detection limit, short response time and integrability into the healthcare information networks. All these features can make the hierarchical examination chain shorten, and revolutionize laboratory diagnostics, evolving a brand new situation in therapeutic intervention.

On-demand Droplet Manipulation via Triboelectrification

NASA Astrophysics Data System (ADS)

Wang, Wei; Vahabi, Hamed; Cackovic, Matthew; Jiang, Rui; Kota, Arun

2017-11-01

Controlled manipulation of liquid droplets has attracted tremendous interest across different scientific fields over the past two decades. To date, a variety of external stimuli-mediated methods such as magnetic field, electric field, and light have been developed for manipulating droplets on surfaces. However, these methods usually have drawbacks such as complex fabrication of manipulation platform, low droplet motility, expensive actuation system and lack of precise control. In this work, we demonstrate the controlled manipulation of liquid droplet with both high (e.g., water) and low (e.g., n-hexadecane) dielectric strengths on a smooth, slippery surface via triboelectric effect. Our highly simple, facile and portable methodology enables on-demand, precise manipulation of droplets using solely the electrostatic attraction or repulsion force, which is exerted on the droplet by a simple charged actuator (e.g., Teflon film). We envision that our triboelectric effect enabled droplet manipulation methodology will open a new avenue for droplet based lab-on-a-chip systems, energy harvesting devices and biomedical applications.

Optical and Electric Multifunctional CMOS Image Sensors for On-Chip Biosensing Applications.

PubMed

Tokuda, Takashi; Noda, Toshihiko; Sasagawa, Kiyotaka; Ohta, Jun

2010-12-29

In this review, the concept, design, performance, and a functional demonstration of multifunctional complementary metal-oxide-semiconductor (CMOS) image sensors dedicated to on-chip biosensing applications are described. We developed a sensor architecture that allows flexible configuration of a sensing pixel array consisting of optical and electric sensing pixels, and designed multifunctional CMOS image sensors that can sense light intensity and electric potential or apply a voltage to an on-chip measurement target. We describe the sensors' architecture on the basis of the type of electric measurement or imaging functionalities.

PBPK Modeling - A Predictive, Eco-Friendly, Bio-Waiver Tool for Drug Research.

PubMed

De, Baishakhi; Bhandari, Koushik; Mukherjee, Ranjan; Katakam, Prakash; Adiki, Shanta K; Gundamaraju, Rohit; Mitra, Analava

2017-01-01

The world has witnessed growing complexities in disease scenario influenced by the drastic changes in host-pathogen- environment triadic relation. Pharmaceutical R&Ds are in constant search of novel therapeutic entities to hasten transition of drug molecules from lab bench to patient bedside. Extensive animal studies and human pharmacokinetics are still the "gold standard" in investigational new drug research and bio-equivalency studies. Apart from cost, time and ethical issues on animal experimentation, burning questions arise relating to ecological disturbances, environmental hazards and biodiversity issues. Grave concerns arises when the adverse outcomes of continued studies on one particular disease on environment gives rise to several other pathogenic agents finally complicating the total scenario. Thus Pharma R&Ds face a challenge to develop bio-waiver protocols. Lead optimization, drug candidate selection with favorable pharmacokinetics and pharmacodynamics, toxicity assessment are vital steps in drug development. Simulation tools like Gastro Plus™, PK Sim®, SimCyp find applications for the purpose. Advanced technologies like organ-on-a chip or human-on-a chip where a 3D representation of human organs and systems can mimic the related processes and activities, thereby linking them to major features of human biology can be successfully incorporated in the drug development tool box. PBPK provides the State of Art to serve as an optional of animal experimentation. PBPK models can successfully bypass bio-equivalency studies, predict bioavailability, drug interactions and on hyphenation with in vitro-in vivo correlation can be extrapolated to humans thus serving as bio-waiver. PBPK can serve as an eco-friendly bio-waiver predictive tool in drug development. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

A multilevel Lab on chip platform for DNA analysis.

PubMed

Marasso, Simone Luigi; Giuri, Eros; Canavese, Giancarlo; Castagna, Riccardo; Quaglio, Marzia; Ferrante, Ivan; Perrone, Denis; Cocuzza, Matteo

2011-02-01

Lab-on-chips (LOCs) are critical systems that have been introduced to speed up and reduce the cost of traditional, laborious and extensive analyses in biological and biomedical fields. These ambitious and challenging issues ask for multi-disciplinary competences that range from engineering to biology. Starting from the aim to integrate microarray technology and microfluidic devices, a complex multilevel analysis platform has been designed, fabricated and tested (All rights reserved-IT Patent number TO2009A000915). This LOC successfully manages to interface microfluidic channels with standard DNA microarray glass slides, in order to implement a complete biological protocol. Typical Micro Electro Mechanical Systems (MEMS) materials and process technologies were employed. A silicon/glass microfluidic chip and a Polydimethylsiloxane (PDMS) reaction chamber were fabricated and interfaced with a standard microarray glass slide. In order to have a high disposable system all micro-elements were passive and an external apparatus provided fluidic driving and thermal control. The major microfluidic and handling problems were investigated and innovative solutions were found. Finally, an entirely automated DNA hybridization protocol was successfully tested with a significant reduction in analysis time and reagent consumption with respect to a conventional protocol.

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

PubMed Central

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

2010-01-01

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

Collapse of Non-Rectangular Channels in a Soft Elastomer

NASA Astrophysics Data System (ADS)

Tepayotl-Ramirez, Daniel; Park, Yong-Lae; Lu, Tong; Majidi, Carmel

2013-03-01

We examine the collapse of microchannels in a soft elastomer by treating the sidewalls as in- denters that penetrate the channel base. This approach leads to a closed-form algebraic mapping between applied pressure and cross-sectional deformation that are in strong agreement with ex- perimental measurements and Finite Element Analysis (FEA) simulation. Applications of this new approach to modeling soft microchannel collapse range from lab-on-a-chip microfluidics for pressure-controlled protein filtration to soft-matter pressures sensing. We demonstrate the latter by comparing theoretical predictions with experimental measurements of the pressure-controlled electrical resistance of liquid-phase Gallium alloy microchannels embedded in a soft silicone elas- tomer.

Single-cell trapping and selective treatment via co-flow within a microfluidic platform.

PubMed

Benavente-Babace, A; Gallego-Pérez, D; Hansford, D J; Arana, S; Pérez-Lorenzo, E; Mujika, M

2014-11-15

Lab on a chip (LOC) systems provide interesting and low-cost solutions for key studies and applications in the biomedical field. Along with microfluidics, these microdevices make single-cell manipulation possible with high spatial and temporal resolution. In this work we have designed, fabricated and characterized a versatile and inexpensive microfluidic platform for on-chip selective single-cell trapping and treatment using laminar co-flow. The combination of co-existing laminar flow manipulation and hydrodynamic single-cell trapping for selective treatment offers a cost-effective solution for studying the effect of novel drugs on single-cells. The operation of the whole system is experimentally simple, highly adaptable and requires no specific equipment. As a proof of concept, a cytotoxicity study of ethanol in isolated hepatocytes is presented. The developed microfluidic platform controlled by means of co-flow is an attractive and multipurpose solution for the study of new substances of high interest in cell biology research. In addition, this platform will pave the way for the study of cell behavior under dynamic and controllable fluidic conditions providing information at the individual cell level. Thus, this analysis device could also hold a great potential to easily use the trapped cells as sensing elements expanding its functionalities as a cell-based biosensor with single-cell resolution. Copyright © 2014 Elsevier B.V. All rights reserved.

An update on Lab Rover: A hospital material transporter

NASA Technical Reports Server (NTRS)

Mattaboni, Paul

1994-01-01

The development of a hospital material transporter, 'Lab Rover', is described. Conventional material transport now utilizes people power, push carts, pneumatic tubes and tracked vehicles. Hospitals are faced with enormous pressure to reduce operating costs. Cyberotics, Inc. developed an Autonomous Intelligent Vehicle (AIV). This battery operated service robot was designed specifically for health care institutions. Applications for the AIV include distribution of clinical lab samples, pharmacy drugs, administrative records, x-ray distribution, meal tray delivery, and certain emergency room applications. The first AIV was installed at Lahey Clinic in Burlington, Mass. Lab Rover was beta tested for one year and has been 'on line' for an additional 2 years.

NEW EPICS/RTEMS IOC BASED ON ALTERA SOC AT JEFFERSON LAB

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

Yan, Jianxun; Seaton, Chad; Allison, Trent L.

A new EPICS/RTEMS IOC based on the Altera System-on-Chip (SoC) FPGA is being designed at Jefferson Lab. The Altera SoC FPGA integrates a dual ARM Cortex-A9 Hard Processor System (HPS) consisting of processor, peripherals and memory interfaces tied seamlessly with the FPGA fabric using a high-bandwidth interconnect backbone. The embedded Altera SoC IOC has features of remote network boot via U-Boot from SD card or QSPI Flash, 1Gig Ethernet, 1GB DDR3 SDRAM on HPS, UART serial ports, and ISA bus interface. RTEMS for the ARM processor BSP were built with CEXP shell, which will dynamically load the EPICS applications atmore » runtime. U-Boot is the primary bootloader to remotely load the kernel image into local memory from a DHCP/TFTP server over Ethernet, and automatically run RTEMS and EPICS. The first design of the SoC IOC will be compatible with Jefferson Lab’s current PC104 IOCs, which have been running in CEBAF 10 years. The next design would be mounting in a chassis and connected to a daughter card via standard HSMC connectors. This standard SoC IOC will become the next generation of low-level IOC for the accelerator controls at Jefferson Lab.« less

Preliminary performance assessment of biotoxin detection for UWS applications using a MicroChemLab device.

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

VanderNoot, Victoria A.; Haroldsen, Brent L.; Renzi, Ronald F.

2010-03-01

In a multiyear research agreement with Tenix Investments Pty. Ltd., Sandia has been developing field deployable technologies for detection of biotoxins in water supply systems. The unattended water sensor or UWS employs microfluidic chip based gel electrophoresis for monitoring biological analytes in a small integrated sensor platform. This instrument collects, prepares, and analyzes water samples in an automated manner. Sample analysis is done using the {mu}ChemLab{trademark} analysis module. This report uses analysis results of two datasets collected using the UWS to estimate performance of the device. The first dataset is made up of samples containing ricin at varying concentrations andmore » is used for assessing instrument response and detection probability. The second dataset is comprised of analyses of water samples collected at a water utility which are used to assess the false positive probability. The analyses of the two sets are used to estimate the Receiver Operating Characteristic or ROC curves for the device at one set of operational and detection algorithm parameters. For these parameters and based on a statistical estimate, the ricin probability of detection is about 0.9 at a concentration of 5 nM for a false positive probability of 1 x 10{sup -6}.« less

Challenges and trends in magnetic sensor integration with microfluidics for biomedical applications

NASA Astrophysics Data System (ADS)

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

2017-06-01

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

A resettable in-line particle concentrator using AC electrokinetics for distributed monitoring of microalgae in source waters

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

Yuan, Quan; Purdue Univ., West Lafayette, IN; Wu, Jayne

Green algae have been studied as an important and effective biomarker to indicate water quality due to their sensitivity to toxic agents in freshwater sources. But, conventional methods to monitor algal physiology use a chlorophyll fluorometer whose use is hampered by high-cost, large footprint, and limited sensitivity for practical samples containing low algal concentration. In order to overcome these constraints, we developed a multi-level electrode platform for resettable trapping of algae via AC electro-osmosis (ACEO) and negative dielectrophoresis. Preliminary experiments were performed in freshwater with conductivity of 0.02 S/m. Algal trapping was demonstrated at a low voltage of 2 V.more » The concentration effect was experimentally verified by measuring the fluorescence intensity of algae and using hemocytometer counting chambers at the inlet and outlet of the multilevel microchannel lab-on-a-chip. An optimal frequency was found for trapping, which agrees with the frequency dependence of ACEO flow velocity. Through-flow rate and electrode dimensions were optimized as well. Trapping efficiencies within the range of 26% - 65% have been obtained. A maximum trapping rate of 182 cells/s was obtained with a flow rate of 20 l/min. Our lab-on-a-chip shows high potential for improving the limit of detection in algal monitoring and enabling the development of a portable, integrated and automated system for monitoring the quality of source drinking waters.« less

A resettable in-line particle concentrator using AC electrokinetics for distributed monitoring of microalgae in source waters

DOE PAGES

Yuan, Quan; Purdue Univ., West Lafayette, IN; Wu, Jayne; ...

2016-12-29

Green algae have been studied as an important and effective biomarker to indicate water quality due to their sensitivity to toxic agents in freshwater sources. But, conventional methods to monitor algal physiology use a chlorophyll fluorometer whose use is hampered by high-cost, large footprint, and limited sensitivity for practical samples containing low algal concentration. In order to overcome these constraints, we developed a multi-level electrode platform for resettable trapping of algae via AC electro-osmosis (ACEO) and negative dielectrophoresis. Preliminary experiments were performed in freshwater with conductivity of 0.02 S/m. Algal trapping was demonstrated at a low voltage of 2 V.more » The concentration effect was experimentally verified by measuring the fluorescence intensity of algae and using hemocytometer counting chambers at the inlet and outlet of the multilevel microchannel lab-on-a-chip. An optimal frequency was found for trapping, which agrees with the frequency dependence of ACEO flow velocity. Through-flow rate and electrode dimensions were optimized as well. Trapping efficiencies within the range of 26% - 65% have been obtained. A maximum trapping rate of 182 cells/s was obtained with a flow rate of 20 l/min. Our lab-on-a-chip shows high potential for improving the limit of detection in algal monitoring and enabling the development of a portable, integrated and automated system for monitoring the quality of source drinking waters.« less

Design of a novel magnetic platform for cell manipulation

NASA Astrophysics Data System (ADS)

Lucarini, Gioia; Iacovacci, Veronica; Gouveia, Pedro J.; Ricotti, Leonardo; Menciassi, Arianna

2018-02-01

Cell manipulation tasks, especially in lab-on-a-chip applications for personalized medicine, could greatly benefit from mobile untethered microdevices able to wirelessly navigate in fluidic environments by means of magnetic fields. In this paper, the design, fabrication and testing of a magnetic platform enabling the controlled locomotion and immersion of microrobots placed at the air/liquid interface is proposed and exploited for cell manipulation. The proposed microrobot consists of a polymeric magnetic thin film that acts as cell transporter and a specific coating strategy, devised to enhance a safe cancer cell adhesion to the magnetic film. Experimental results demonstrated an overall cell viability and a fine control of magnetic microrobot locomotion. The proposed technologies are promising in view of future cell manipulation tasks for personalized medicine applications.

Microchip assays for screening monoclonal antibody product quality.

PubMed

Chen, Xiaoyu; Tang, Kaiyan; Lee, Maximilian; Flynn, Gregory C

2008-12-01

Microchip CE-SDS was evaluated as a high-throughput alternative to conventional CE-SDS for monitoring monoclonal antibody protein quality. A commercial instrument (LabChip) 90) was used to separate dodecyl sulfate coated proteins through a sieving polymer based on the proteins' sizes. Under reducing conditions, the microchip CE-SDS separation was similar to that of conventional CE-SDS, providing reasonable resolution of the non-glycosylated and the glycosylated heavy chains. The fluorescence detection on LabChip 90 using non-covalent fluorescent labeling method was about as sensitive as the 220 nm UV detection used in a conventional CE instrument. A simple glycan typing assay was developed for the reducing microchip CE-SDS format. Antibodies, either pure or in crude cell culture media are treated with Endoglycosidase H, which specifically cleaves the hybrid and high mannose type glycans. A heavy chain migration shift on reducing CE-SDS resulting from the loss of glycan is used to measure the level of high mannose/hybrid type glycans as a percentage of the total glycans. Microchip CE-SDS, under both non-reducing and reducing conditions, can be used in a variety of antibody product screening assays. The microchip analyses provide sufficient resolution and sensitivity for this purpose but on a time scale approximately 70 times faster (41 s versus 50 min per sample) than conventional CE separation under typical operational conditions.

Current characteristics of λ-DNA molecules/polystyrene nanoparticles in TBE buffer solution through micro/nanofluidic capillaries under DC electric field

NASA Astrophysics Data System (ADS)

Duan, Yifei; Zhao, Wei; Xue, Jing; Sun, Dan; Wang, Kaige; Wang, Guiren; Li, Junjie; Bai, Jintao; Gu, Changzhi

2017-03-01

In practical applications of biochips and bio-sensors, electrokinetic mechanisms are commonly employed to manipulate single bio-molecules and analyze their characteristics. To accurately and flexibly control the movement of single-molecule within micro/nanofluidic channels which are the basic components of Lab-chips, the current signals in micro/nanocapillaries filled with solutions of DNA molecules or polystyrene (PS) nanoparticles are systematically studied. Experimental results indicate that the current response along the micro/nanocapillaries can be significantly influenced by the diameter of the capillaries and the pH value of the solutions. Specifically, when there is only a pure (TBE) solution, the electric conductance does not monotonically decrease with decreasing the diameter of the capillaries, but slightly increases with decreasing the capillary diameter. When λ-DNA molecules or PS nanoparticles are added into the TBE buffer, the size effect on the electric conductance of the solutions are quite different. Although in the former, the electric conductance behaves differently from that in the pure TBE solution and decreases with the decreasing diameter, in the latter, the change is similar to that in the pure TBE solution. Besides, an abnormal ‘falling’ of the electric conductance is observed in a capillary with diameter of 200 nm. The investigation will significantly enhance the understanding on the electric properties of the solutions of biomolecules and particles in micro/nanofluidics. This is especially helpful for designing functional Lab-chip devices.

Simple, low-cost fabrication of semi-circular channel using the surface tension of solder paste and its application to microfluidic valves.

PubMed

Yan, Sheng; Li, Yuxing; Zhu, Yuanqing; Liu, Minsu; Zhao, Qianbin; Yuan, Dan; Yun, Guolin; Zhang, Shiwu; Wen, Weijia; Tang, Shi-Yang; Li, Weihua

2018-06-01

This work presents a simple, low-cost method to fabricate semi-circular channels using solder paste, which can amalgamate the cooper surface to form a half-cylinder mold using the surface tension of Sn-Pd alloy (the main component in solder paste). This technique enables semi-circular channels to be manufactured with different dimensions. These semi-circular channels will then be integrated with a polymethylmethacrylate frame and machine screws to create miniaturized, portable microfluidic valves for sequential liquid delivery and particle synthesis. This approach avoids complicated fabrication processes and expensive facilities and thus has the potential to be a useful tool for lab-on-a-chip applications. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Organic Lasers: Recent Developments on Materials, Device Geometries, and Fabrication Techniques.

PubMed

Kuehne, Alexander J C; Gather, Malte C

2016-11-09

Organic dyes have been used as gain medium for lasers since the 1960s, long before the advent of today's organic electronic devices. Organic gain materials are highly attractive for lasing due to their chemical tunability and large stimulated emission cross section. While the traditional dye laser has been largely replaced by solid-state lasers, a number of new and miniaturized organic lasers have emerged that hold great potential for lab-on-chip applications, biointegration, low-cost sensing and related areas, which benefit from the unique properties of organic gain materials. On the fundamental level, these include high exciton binding energy, low refractive index (compared to inorganic semiconductors), and ease of spectral and chemical tuning. On a technological level, mechanical flexibility and compatibility with simple processing techniques such as printing, roll-to-roll, self-assembly, and soft-lithography are most relevant. Here, the authors provide a comprehensive review of the developments in the field over the past decade, discussing recent advances in organic gain materials, which are today often based on solid-state organic semiconductors, as well as optical feedback structures, and device fabrication. Recent efforts toward continuous wave operation and electrical pumping of solid-state organic lasers are reviewed, and new device concepts and emerging applications are summarized.

A Framework for Lab Work Management in Mass Courses. Application to Low Level Input/Output without Hardware

ERIC Educational Resources Information Center

Rodriguez, Santiago; Zamorano, Juan; Rosales, Francisco; Dopico, Antonio Garcia; Pedraza, Jose Luis

2007-01-01

This paper describes a complete lab work management framework designed and developed in the authors' department to help teachers to manage the small projects that students are expected to complete as lab assignments during their graduate-level computer engineering studies. The paper focuses on an application example of the framework to a specific…

Semi-automated lab-on-a-chip for dispensing GA-68 radiotracers

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

Weinberg, Irving

We solved a technical problem that is hindering American progress in molecular medicine, and restricting US citizens from receiving optimal diagnostic care. Specifically, the project deals with a mother/daughter generator of positron-emitting radiotracers (Ge-68/Ga-68). These generator systems are approved in Europe but cannot be used in the USA, because of safety issues related to possible breakthrough of long-lived Ge-68 (mother) atoms. Europeans have demonstrated abilities of Ga-68-labeled radiotracers to image cancer foci with high sensitivity and specificity, and to use such methods to effectively plan therapy.The USA Food and Drug Administration (FDA) and Nuclear Regulatory Commission (NRC) have taken themore » position that every patient administration of Ga-68 should be preceded by an assay demonstrated that Ge-68 breakthrough is within acceptable limits. Breakthrough of parent elements is a sensitive subject at the FDA, as evidenced by the recent recall of Rb-82 generators due to inadvertent administrations of Sr-82. Commercially, there is no acceptable rapid method for assaying breakthrough of Ge-68 prior to each human administration. The gamma emissions of daughter Ga-68 have higher energies than the parent Ge-68, so that the shielding assays typically employed for Mo-99/Tc-99m generators cannot be applied to Ga-68 generators. The half-life of Ga-68 is 68 minutes, so that the standard 10-half-life delay (used to assess breakthrough in Sr-82/Rb-82 generators) cannot be applied to Ga-68 generators. As a result of the aforementioned regulatory requirements, Ga-68 generators are sold in the USA for animal use only.The American clinical community’s inability to utilize Ga-68 generators impairs abilities to treat patients domestically, and puts the USA at a disadvantage in developing exportable products. The proposed DOE project aimed to take advantage of recent technological advances developed for lab-on-a-chip (LOC) applications. Based on our experiences constructing such devices, the proposed microfluidics-based approach could provide cost-effective validation of breakthrough compliance in minutes.« less

Optofluidic two-dimensional grating volume refractive index sensor.

PubMed

Sarkar, Anirban; Shivakiran Bhaktha, B N; Khastgir, Sugata Pratik

2016-09-10

We present an optofluidic reservoir with a two-dimensional grating for a lab-on-a-chip volume refractive index sensor. The observed diffraction pattern from the device resembles the analytically obtained fringe pattern. The change in the diffraction pattern has been monitored in the far-field for fluids with different refractive indices. Reliable measurements of refractive index variations, with an accuracy of 6×10^-3 refractive index units, for different fluids establishes the optofluidic device as a potential on-chip tool for monitoring dynamic refractive index changes.

ChIP and ChIP-Related Techniques: Expanding the Fields of Application and Improving ChIP Performance.

PubMed

Visa, Neus; Jordán-Pla, Antonio

2018-01-01

Protein-DNA interactions in vivo can be detected and quantified by chromatin immunoprecipitation (ChIP). ChIP has been instrumental for the advancement of epigenetics and has set the groundwork for the development of a number of ChIP-related techniques that have provided valuable information about the organization and function of genomes. Here, we provide an introduction to ChIP and discuss the applications of ChIP in different research areas. We also review some of the strategies that have been devised to improve ChIP performance.

Producing fluid flow using 3D carbon electrodes

NASA Astrophysics Data System (ADS)

Rouabah, H. A.; Park, B. Y.; Zaouk, R. B.; Madou, M. J.; Green, Nicolas G.

2008-12-01

Moving and manipulating bio-particles and fluids on the microscale is central to many lab-on-a-chip applications. Techniques for pumping fluids which use electric fields have shown promise using both DC and AC voltages. AC techniques, however, require the use of integrated metal electrodes which have a low resistance but can suffer from unwanted chemical reactions even at low potentials. In this paper we introduce the use of carbon MEMS technology (C-MEMS), a fabrication method which produces 3D conductive polymeric structures. Results are presented of the fabrication of an innovative design of 3D AC-electroosmotic micropump and preliminary experimental measurements which demonstrate the potential of both the technology and the design.

Optical and Electric Multifunctional CMOS Image Sensors for On-Chip Biosensing Applications

PubMed Central

Tokuda, Takashi; Noda, Toshihiko; Sasagawa, Kiyotaka; Ohta, Jun

2010-01-01

In this review, the concept, design, performance, and a functional demonstration of multifunctional complementary metal-oxide-semiconductor (CMOS) image sensors dedicated to on-chip biosensing applications are described. We developed a sensor architecture that allows flexible configuration of a sensing pixel array consisting of optical and electric sensing pixels, and designed multifunctional CMOS image sensors that can sense light intensity and electric potential or apply a voltage to an on-chip measurement target. We describe the sensors’ architecture on the basis of the type of electric measurement or imaging functionalities. PMID:28879978

On chip cryo-anesthesia of Drosophila larvae for high resolution in vivo imaging applications.

PubMed

Chaudhury, Amrita Ray; Insolera, Ryan; Hwang, Ran-Der; Fridell, Yih-Woei; Collins, Catherine; Chronis, Nikos

2017-06-27

We present a microfluidic chip for immobilizing Drosophila melanogaster larvae for high resolution in vivo imaging. The chip creates a low-temperature micro-environment that anaesthetizes and immobilizes the larva in under 3 minutes. We characterized the temperature distribution within the chip and analyzed the resulting larval body movement using high resolution fluorescence imaging. Our results indicate that the proposed method minimizes submicron movements of internal organs and tissue without affecting the larva physiology. It can be used to continuously immobilize larvae for short periods of time (minutes) or for longer periods (several hours) if used intermittently. The same chip can be used to accommodate and immobilize arvae across all developmental stages (1st instar to late 3rd instar), and loading larvae onto the chip does not require any specialized skills. To demonstrate the usability of the chip, we observed mitochondrial trafficking in neurons from the cell bodies to the axon terminals along with mitochondrial fusion and neuro-synaptic growth through time in intact larvae. Besides studying sub-cellular processes and cellular development, we envision the use of on chip cryo-anesthesia in a wide variety of biological in vivo imaging applications, including observing organ development of the salivary glands, fat bodies and body-wall muscles.

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.