Digital microfluidics for automated hanging drop cell spheroid culture.

PubMed

Aijian, Andrew P; Garrell, Robin L

2015-06-01

Cell spheroids are multicellular aggregates, grown in vitro, that mimic the three-dimensional morphology of physiological tissues. Although there are numerous benefits to using spheroids in cell-based assays, the adoption of spheroids in routine biomedical research has been limited, in part, by the tedious workflow associated with spheroid formation and analysis. Here we describe a digital microfluidic platform that has been developed to automate liquid-handling protocols for the formation, maintenance, and analysis of multicellular spheroids in hanging drop culture. We show that droplets of liquid can be added to and extracted from through-holes, or "wells," and fabricated in the bottom plate of a digital microfluidic device, enabling the formation and assaying of hanging drops. Using this digital microfluidic platform, spheroids of mouse mesenchymal stem cells were formed and maintained in situ for 72 h, exhibiting good viability (>90%) and size uniformity (% coefficient of variation <10% intraexperiment, <20% interexperiment). A proof-of-principle drug screen was performed on human colorectal adenocarcinoma spheroids to demonstrate the ability to recapitulate physiologically relevant phenomena such as insulin-induced drug resistance. With automatable and flexible liquid handling, and a wide range of in situ sample preparation and analysis capabilities, the digital microfluidic platform provides a viable tool for automating cell spheroid culture and analysis. © 2014 Society for Laboratory Automation and Screening.

Three-dimensional fit-to-flow microfluidic assembly.

PubMed

Chen, Arnold; Pan, Tingrui

2011-12-01

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

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.

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.

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.

Droplet-based pyrosequencing using digital microfluidics.

PubMed

Boles, Deborah J; Benton, Jonathan L; Siew, Germaine J; Levy, Miriam H; Thwar, Prasanna K; Sandahl, Melissa A; Rouse, Jeremy L; Perkins, Lisa C; Sudarsan, Arjun P; Jalili, Roxana; Pamula, Vamsee K; Srinivasan, Vijay; Fair, Richard B; Griffin, Peter B; Eckhardt, Allen E; Pollack, Michael G

2011-11-15

The feasibility of implementing pyrosequencing chemistry within droplets using electrowetting-based digital microfluidics is reported. An array of electrodes patterned on a printed-circuit board was used to control the formation, transportation, merging, mixing, and splitting of submicroliter-sized droplets contained within an oil-filled chamber. A three-enzyme pyrosequencing protocol was implemented in which individual droplets contained enzymes, deoxyribonucleotide triphosphates (dNTPs), and DNA templates. The DNA templates were anchored to magnetic beads which enabled them to be thoroughly washed between nucleotide additions. Reagents and protocols were optimized to maximize signal over background, linearity of response, cycle efficiency, and wash efficiency. As an initial demonstration of feasibility, a portion of a 229 bp Candida parapsilosis template was sequenced using both a de novo protocol and a resequencing protocol. The resequencing protocol generated over 60 bp of sequence with 100% sequence accuracy based on raw pyrogram levels. Excellent linearity was observed for all of the homopolymers (two, three, or four nucleotides) contained in the C. parapsilosis sequence. With improvements in microfluidic design it is expected that longer reads, higher throughput, and improved process integration (i.e., "sample-to-sequence" capability) could eventually be achieved using this low-cost platform.

Droplet-Based Pyrosequencing Using Digital Microfluidics

PubMed Central

Boles, Deborah J.; Benton, Jonathan L.; Siew, Germaine J.; Levy, Miriam H.; Thwar, Prasanna K.; Sandahl, Melissa A.; Rouse, Jeremy L.; Perkins, Lisa C.; Sudarsan, Arjun P.; Jalili, Roxana; Pamula, Vamsee K.; Srinivasan, Vijay; Fair, Richard B.; Griffin, Peter B.; Eckhardt, Allen E.; Pollack, Michael G.

2013-01-01

The feasibility of implementing pyrosequencing chemistry within droplets using electrowetting-based digital microfluidics is reported. An array of electrodes patterned on a printed-circuit board was used to control the formation, transportation, merging, mixing, and splitting of submicroliter-sized droplets contained within an oil-filled chamber. A three-enzyme pyrosequencing protocol was implemented in which individual droplets contained enzymes, deoxyribonucleotide triphosphates (dNTPs), and DNA templates. The DNA templates were anchored to magnetic beads which enabled them to be thoroughly washed between nucleotide additions. Reagents and protocols were optimized to maximize signal over background, linearity of response, cycle efficiency, and wash efficiency. As an initial demonstration of feasibility, a portion of a 229 bp Candida parapsilosis template was sequenced using both a de novo protocol and a resequencing protocol. The resequencing protocol generated over 60 bp of sequence with 100% sequence accuracy based on raw pyrogram levels. Excellent linearity was observed for all of the homopolymers (two, three, or four nucleotides) contained in the C. parapsilosis sequence. With improvements in microfluidic design it is expected that longer reads, higher throughput, and improved process integration (i.e., “sample-to-sequence” capability) could eventually be achieved using this low-cost platform. PMID:21932784

Passive microfluidic array card and reader

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

Dugan, Lawrence Christopher; Coleman, Matthew A

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

Self-digitization microfluidic chip for absolute quantification of mRNA in single cells.

PubMed

Thompson, Alison M; Gansen, Alexander; Paguirigan, Amy L; Kreutz, Jason E; Radich, Jerald P; Chiu, Daniel T

2014-12-16

Quantification of mRNA in single cells provides direct insight into how intercellular heterogeneity plays a role in disease progression and outcomes. Quantitative polymerase chain reaction (qPCR), the current gold standard for evaluating gene expression, is insufficient for providing absolute measurement of single-cell mRNA transcript abundance. Challenges include difficulties in handling small sample volumes and the high variability in measurements. Microfluidic digital PCR provides far better sensitivity for minute quantities of genetic material, but the typical format of this assay does not allow for counting of the absolute number of mRNA transcripts samples taken from single cells. Furthermore, a large fraction of the sample is often lost during sample handling in microfluidic digital PCR. Here, we report the absolute quantification of single-cell mRNA transcripts by digital, one-step reverse transcription PCR in a simple microfluidic array device called the self-digitization (SD) chip. By performing the reverse transcription step in digitized volumes, we find that the assay exhibits a linear signal across a wide range of total RNA concentrations and agrees well with standard curve qPCR. The SD chip is found to digitize a high percentage (86.7%) of the sample for single-cell experiments. Moreover, quantification of transferrin receptor mRNA in single cells agrees well with single-molecule fluorescence in situ hybridization experiments. The SD platform for absolute quantification of single-cell mRNA can be optimized for other genes and may be useful as an independent control method for the validation of mRNA quantification techniques.

Hydrophilic strips for preventing air bubble formation in a microfluidic chamber.

PubMed

Choi, Munseok; Na, Yang; Kim, Sung-Jin

2015-12-01

In a microfluidic chamber, unwanted formation of air bubbles is a critical problem. Here, we present a hydrophilic strip array that prevents air bubble formation in a microfluidic chamber. The array is located on the top surface of the chamber, which has a large variation in width, and consists of a repeated arrangement of super- and moderately hydrophilic strips. This repeated arrangement allows a flat meniscus (i.e. liquid front) to form when various solutions consisting of a single stream or two parallel streams with different hydrophilicities move through the chamber. The flat meniscus produced by the array completely prevents the formation of bubbles. Without the array in the chamber, the meniscus shape is highly convex, and bubbles frequently form in the chamber. This hydrophilic strip array will facilitate the use of a microfluidic chamber with a large variation in width for various microfluidic applications. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

PubMed

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

2016-02-21

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

In-line digital holography with phase-shifting Greek-ladder sieves

NASA Astrophysics Data System (ADS)

Xie, Jing; Zhang, Junyong; Zhang, Yanli; Zhou, Shenlei; Zhu, Jianqiang

2018-04-01

Phase shifting is the key technique in in-line digital holography, but traditional phase shifters have their own limitations in short wavelength regions. Here, phase-shifting Greek-ladder sieves with amplitude-only modulation are introduced into in-line digital holography, which are essentially a kind of diffraction lens with three-dimensional array diffraction-limited foci. In the in-line digital holographic experiment, we design two kinds of sieves by lithography and verify the validity of their phase-shifting function by measuring a 1951 U.S. Air Force resolution test target and three-dimensional array foci. With advantages of high resolving power, low cost, and no limitations at shorter wavelengths, phase-shifting Greek-ladder sieves have great potential in X-ray holography or biochemical microscopy for the next generation of synchrotron light sources.

Digital microfluidics: A promising technique for biochemical applications

NASA Astrophysics Data System (ADS)

Wang, He; Chen, Liguo; Sun, Lining

2017-12-01

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

Three-dimensional micro-electrode array for recording dissociated neuronal cultures.

PubMed

Musick, Katherine; Khatami, David; Wheeler, Bruce C

2009-07-21

This work demonstrates the design, fabrication, packaging, characterization, and functionality of an electrically and fluidically active three-dimensional micro-electrode array (3D MEA) for use with neuronal cell cultures. The successful function of the device implies that this basic concept-construction of a 3D array with a layered approach-can be utilized as the basis for a new family of neural electrode arrays. The 3D MEA prototype consists of a stack of individually patterned thin films that form a cell chamber conducive to maintaining and recording the electrical activity of a long-term three-dimensional network of rat cortical neurons. Silicon electrode layers contain a polymer grid for neural branching, growth, and network formation. Along the walls of these electrode layers lie exposed gold electrodes which permit recording and stimulation of the neuronal electrical activity. Silicone elastomer micro-fluidic layers provide a means for loading dissociated neurons into the structure and serve as the artificial vasculature for nutrient supply and aeration. The fluidic layers also serve as insulation for the micro-electrodes. Cells have been shown to survive in the 3D MEA for up to 28 days, with spontaneous and evoked electrical recordings performed in that time. The micro-fluidic capability was demonstrated by flowing in the drug tetrotodoxin to influence the activity of the culture.

Stochastic Model of Clogging in a Microfluidic Cell Sorter

NASA Astrophysics Data System (ADS)

Fai, Thomas; Rycroft, Chris

2016-11-01

Microfluidic devices for sorting cells by deformability show promise for various medical purposes, e.g. detecting sickle cell anemia and circulating tumor cells. One class of such devices consists of a two-dimensional array of narrow channels, each column containing several identical channels in parallel. Cells are driven through the device by an applied pressure or flow rate. Such devices allows for many cells to be sorted simultaneously, but cells eventually clog individual channels and change the device properties in an unpredictable manner. In this talk, we propose a stochastic model for the failure of such microfluidic devices by clogging and present preliminary theoretical and computational results. The model can be recast as an ODE that exhibits finite time blow-up under certain conditions. The failure time distribution is investigated analytically in certain limiting cases, and more realistic versions of the model are solved by computer simulation.

Digital microfluidics-enabled single-molecule detection by printing and sealing single magnetic beads in femtoliter droplets.

PubMed

Witters, Daan; Knez, Karel; Ceyssens, Frederik; Puers, Robert; Lammertyn, Jeroen

2013-06-07

Digital microfluidics is introduced as a novel platform with unique advantages for performing single-molecule detection. We demonstrate how superparamagnetic beads, used for capturing single protein molecules, can be printed with unprecedentedly high loading efficiency and single bead resolution on an electrowetting-on-dielectric-based digital microfluidic chip by micropatterning the Teflon-AF surface of the device. By transporting droplets containing suspended superparamagnetic beads over a hydrophilic-in-hydrophobic micropatterned Teflon-AF surface, single beads are trapped inside the hydrophilic microwells due to their selective wettability and tailored dimensions. Digital microfluidics presents the following advantages for printing and sealing magnetic beads for single-molecule detection: (i) droplets containing suspended beads can be transported back and forth over the array of hydrophilic microwells to obtain high loading efficiencies of microwells with single beads, (ii) the use of hydrophilic-in-hydrophobic patterns permits the use of a magnet to speed up the bead transfer process to the wells, while the receding droplet meniscus removes excess beads off the chip surface and thereby shortens the bead patterning time, and (iii) reagents can be transported over the printed beads multiple times, while capillary forces and a magnet hold the printed beads in place. High loading efficiencies (98% with a CV of 0.9%) of single beads in microwells were obtained by transporting droplets of suspended beads over the array 10 times in less than 1 min, which is much higher than previously reported methods (40-60%), while the total surface area needed for performing single-molecule detection can be decreased. The performance of the device was demonstrated by fluorescent detection of the presence of the biotinylated enzyme β-galactosidase on streptavidin-coated beads with a linear dynamic range of 4 orders of magnitude ranging from 10 aM to 90 fM.

3D nanofabrication inside rapid prototyped microfluidic channels showcased by wet-spinning of single micrometre fibres.

PubMed

Lölsberg, Jonas; Linkhorst, John; Cinar, Arne; Jans, Alexander; Kuehne, Alexander J C; Wessling, Matthias

2018-05-01

Microfluidics is an established multidisciplinary research domain with widespread applications in the fields of medicine, biotechnology and engineering. Conventional production methods of microfluidic chips have been limited to planar structures, preventing the exploitation of truly three-dimensional architectures for applications such as multi-phase droplet preparation or wet-phase fibre spinning. Here the challenge of nanofabrication inside a microfluidic chip is tackled for the showcase of a spider-inspired spinneret. Multiphoton lithography, an additive manufacturing method, was used to produce free-form microfluidic masters, subsequently replicated by soft lithography. Into the resulting microfluidic device, a three-dimensional spider-inspired spinneret was directly fabricated in-chip via multiphoton lithography. Applying this unprecedented fabrication strategy, the to date smallest printed spinneret nozzle is produced. This spinneret resides tightly sealed, connecting it to the macroscopic world. Its functionality is demonstrated by wet-spinning of single-digit micron fibres through a polyacrylonitrile coagulation process induced by a water sheath layer. The methodology developed here demonstrates fabrication strategies to interface complex architectures into classical microfluidic platforms. Using multiphoton lithography for in-chip fabrication adopts a high spatial resolution technology for improving geometry and thus flow control inside microfluidic chips. The showcased fabrication methodology is generic and will be applicable to multiple challenges in fluid control and beyond.

Machine vision for digital microfluidics

NASA Astrophysics Data System (ADS)

Shin, Yong-Jun; Lee, Jeong-Bong

2010-01-01

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

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

PubMed

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

2012-11-21

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

Digital biology and chemistry.

PubMed

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

2014-09-07

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

Quantum Cascade Laser Tuning by Digital Micromirror Array-controlled External Cavity

DTIC Science & Technology

2014-01-01

P. Vujkovic-Cvijin, B. Gregor, A. C. Samuels, E. S. Roese, Quantum cascade laser tuning by digital micromirror array-controlled external cavity...REPORT TYPE 3. DATES COVERED 00-00-2014 to 00-00-2014 4. TITLE AND SUBTITLE Quantum cascade laser tuning by digital micromirror array-controlled...dimensional digital micromirror array (DMA) is described. The laser is tuned by modulating the reflectivity of DMA micromirror pixels under computer

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

PubMed

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

2009-03-01

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

Three-dimensional cross point readout detector design for including depth information

NASA Astrophysics Data System (ADS)

Lee, Seung-Jae; Baek, Cheol-Ha

2018-04-01

We designed a depth-encoding positron emission tomography (PET) detector using a cross point readout method with wavelength-shifting (WLS) fibers. To evaluate the characteristics of the novel detector module and the PET system, we used the DETECT2000 to perform optical photon transport in the crystal array. The GATE was also used. The detector module is made up of four layers of scintillator arrays, the five layers of WLS fiber arrays, and two sensor arrays. The WLS fiber arrays in each layer cross each other to transport light to each sensor array. The two sensor arrays are coupled to the forward and left sides of the WLS fiber array, respectively. The identification of three-dimensional pixels was determined using a digital positioning algorithm. All pixels were well decoded, with the system resolution ranging from 2.11 mm to 2.29 mm at full width at half maximum (FWHM).

Microfluidic vascular channels in gels using commercial 3D printers

NASA Astrophysics Data System (ADS)

Selvaganapathy, P. Ravi; Attalla, Rana

2016-03-01

This paper details the development of a three dimensional (3D) printing system with a modified microfluidic printhead used for the generation of complex vascular tissue scaffolds. The print-head features an integrated coaxial nozzle that allows the fabrication of hollow, calcium-polymerized alginate tubes that can easily be patterned using 3Dbioprinting techniques. This microfluidic design allows the incorporation of a wide range of scaffold materials as well as biological constituents such as cells, growth factors, and ECM material. With this setup, gel constructs with embedded arrays of hollow channels can be created and used as a potential substitute for blood vessel networks.

Noncoherent parallel optical processor for discrete two-dimensional linear transformations.

PubMed

Glaser, I

1980-10-01

We describe a parallel optical processor, based on a lenslet array, that provides general linear two-dimensional transformations using noncoherent light. Such a processor could become useful in image- and signal-processing applications in which the throughput requirements cannot be adequately satisfied by state-of-the-art digital processors. Experimental results that illustrate the feasibility of the processor by demonstrating its use in parallel optical computation of the two-dimensional Walsh-Hadamard transformation are presented.

Programmable diagnostic devices made from paper and tape.

PubMed

Martinez, Andres W; Phillips, Scott T; Nie, Zhihong; Cheng, Chao-Min; Carrilho, Emanuel; Wiley, Benjamin J; Whitesides, George M

2010-10-07

This paper describes three-dimensional microfluidic paper-based analytical devices (3-D microPADs) that can be programmed (postfabrication) by the user to generate multiple patterns of flow through them. These devices are programmed by pressing single-use 'on' buttons, using a stylus or a ballpoint pen. Pressing a button closes a small space (gap) between two vertically aligned microfluidic channels, and allows fluids to wick from one channel to the other. These devices are simple to fabricate, and are made entirely out of paper and double-sided adhesive tape. Programmable devices expand the capabilities of microPADs and provide a simple method for controlling the movement of fluids in paper-based channels. They are the conceptual equivalent of field-programmable gate arrays (FPGAs) widely used in electronics.

Generation of digitized microfluidic filling flow by vent control.

PubMed

Yoon, Junghyo; Lee, Eundoo; Kim, Jaehoon; Han, Sewoon; Chung, Seok

2017-06-15

Quantitative microfluidic point-of-care testing has been translated into clinical applications to support a prompt decision on patient treatment. A nanointerstice-driven filling technique has been developed to realize the fast and robust filling of microfluidic channels with liquid samples, but it has failed to provide a consistent filling time owing to the wide variation in liquid viscosity, resulting in an increase in quantification errors. There is a strong demand for simple and quick flow control to ensure accurate quantification, without a serious increase in system complexity. A new control mechanism employing two-beam refraction and one solenoid valve was developed and found to successfully generate digitized filling flow, completely free from errors due to changes in viscosity. The validity of digitized filling flow was evaluated by the immunoassay, using liquids with a wide range of viscosity. This digitized microfluidic filling flow is a novel approach that could be applied in conventional microfluidic point-of-care testing. Copyright © 2016 Elsevier B.V. All rights reserved.

Controlled droplet microfluidic systems for multistep chemical and biological assays.

PubMed

Kaminski, T S; Garstecki, P

2017-10-16

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

Two-dimensional optoelectronic interconnect-processor and its operational bit error rate

NASA Astrophysics Data System (ADS)

Liu, J. Jiang; Gollsneider, Brian; Chang, Wayne H.; Carhart, Gary W.; Vorontsov, Mikhail A.; Simonis, George J.; Shoop, Barry L.

2004-10-01

Two-dimensional (2-D) multi-channel 8x8 optical interconnect and processor system were designed and developed using complementary metal-oxide-semiconductor (CMOS) driven 850-nm vertical-cavity surface-emitting laser (VCSEL) arrays and the photodetector (PD) arrays with corresponding wavelengths. We performed operation and bit-error-rate (BER) analysis on this free-space integrated 8x8 VCSEL optical interconnects driven by silicon-on-sapphire (SOS) circuits. Pseudo-random bit stream (PRBS) data sequence was used in operation of the interconnects. Eye diagrams were measured from individual channels and analyzed using a digital oscilloscope at data rates from 155 Mb/s to 1.5 Gb/s. Using a statistical model of Gaussian distribution for the random noise in the transmission, we developed a method to compute the BER instantaneously with the digital eye-diagrams. Direct measurements on this interconnects were also taken on a standard BER tester for verification. We found that the results of two methods were in the same order and within 50% accuracy. The integrated interconnects were investigated in an optoelectronic processing architecture of digital halftoning image processor. Error diffusion networks implemented by the inherently parallel nature of photonics promise to provide high quality digital halftoned images.

Single-exposure two-dimensional superresolution in digital holography using a vertical cavity surface-emitting laser source array.

PubMed

Granero, Luis; Zalevsky, Zeev; Micó, Vicente

2011-04-01

We present a new implementation capable of producing two-dimensional (2D) superresolution (SR) imaging in a single exposure by aperture synthesis in digital lensless Fourier holography when using angular multiplexing provided by a vertical cavity surface-emitting laser source array. The system performs the recording in a single CCD snapshot of a multiplexed hologram coming from the incoherent addition of multiple subholograms, where each contains information about a different 2D spatial frequency band of the object's spectrum. Thus, a set of nonoverlapping bandpass images of the input object can be recovered by Fourier transformation (FT) of the multiplexed hologram. The SR is obtained by coherent addition of the information contained in each bandpass image while generating an enlarged synthetic aperture. Experimental results demonstrate improvement in resolution and image quality.

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

PubMed

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

2014-08-01

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

DESIGN OF A PATTERN RECOGNITION DIGITAL COMPUTER WITH APPLICATION TO THE AUTOMATIC SCANNING OF BUBBLE CHAMBER NEGATIVES

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

McCormick, B.H.; Narasimhan, R.

1963-01-01

The overall computer system contains three main parts: an input device, a pattern recognition unit (PRU), and a control computer. The bubble chamber picture is divided into a grid of st run. Concent 1-mm squares on the film. It is then processed in parallel in a two-dimensional array of 1024 identical processing modules (stalactites) of the PRU. The array can function as a two- dimensional shift register in which results of successive shifting operations can be accumulated. The pattern recognition process is generally controlled by a conventional arithmetic computer. (A.G.W.)

Digital microfluidic three-dimensional cell culture and chemical screening platform using alginate hydrogels

PubMed Central

2015-01-01

Electro wetting-on-dielectric (EWOD) digital microfluidics (DMF) can be used to develop improved chemical screening platforms using 3-dimensional (3D) cell culture. Alginate hydrogels are one common method by which a 3D cell culture environment is created. This paper presents a study of alginate gelation on EWOD DMF and investigates designs to obtain uniform alginate hydrogels that can be repeatedly addressed by any desired liquids. A design which allows for gels to be retained in place during liquid delivery and removal without using any physical barriers or hydrophilic patterning of substrates is presented. A proof of concept screening platform is demonstrated by examining the effects of different concentrations of a test chemical on 3D cells in alginate hydrogels. In addition, the temporal effects of the various chemical concentrations on different hydrogel posts are demonstrated, thereby establishing the benefits of an EWOD DMF 3D cell culture and chemical screening platform using alginate hydrogels. PMID:25945142

Development of a digital microfluidic platform for point of care testing

PubMed Central

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

2009-01-01

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

Resolution improvement of 3D stereo-lithography through the direct laser trajectory programming: Application to microfluidic deterministic lateral displacement device.

PubMed

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

2018-02-13

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

Adaptation of a Simple Microfluidic Platform for High-Dimensional Quantitative Morphological Analysis of Human Mesenchymal Stromal Cells on Polystyrene-Based Substrates.

PubMed

Lam, Johnny; Marklein, Ross A; Jimenez-Torres, Jose A; Beebe, David J; Bauer, Steven R; Sung, Kyung E

2017-12-01

Multipotent stromal cells (MSCs, often called mesenchymal stem cells) have garnered significant attention within the field of regenerative medicine because of their purported ability to differentiate down musculoskeletal lineages. Given the inherent heterogeneity of MSC populations, recent studies have suggested that cell morphology may be indicative of MSC differentiation potential. Toward improving current methods and developing simple yet effective approaches for the morphological evaluation of MSCs, we combined passive pumping microfluidic technology with high-dimensional morphological characterization to produce robust tools for standardized high-throughput analysis. Using ultraviolet (UV) light as a modality for reproducible polystyrene substrate modification, we show that MSCs seeded on microfluidic straight channel devices incorporating UV-exposed substrates exhibited morphological changes that responded accordingly to the degree of substrate modification. Substrate modification also effected greater morphological changes in MSCs seeded at a lower rather than higher density within microfluidic channels. Despite largely comparable trends in morphology, MSCs seeded in microscale as opposed to traditional macroscale platforms displayed much higher sensitivity to changes in substrate properties. In summary, we adapted and qualified microfluidic cell culture platforms comprising simple straight channel arrays as a viable and robust tool for high-throughput quantitative morphological analysis to study cell-material interactions.

A robotics platform for automated batch fabrication of high density, microfluidics-based DNA microarrays, with applications to single cell, multiplex assays of secreted proteins

NASA Astrophysics Data System (ADS)

Ahmad, Habib; Sutherland, Alex; Shin, Young Shik; Hwang, Kiwook; Qin, Lidong; Krom, Russell-John; Heath, James R.

2011-09-01

Microfluidics flow-patterning has been utilized for the construction of chip-scale miniaturized DNA and protein barcode arrays. Such arrays have been used for specific clinical and fundamental investigations in which many proteins are assayed from single cells or other small sample sizes. However, flow-patterned arrays are hand-prepared, and so are impractical for broad applications. We describe an integrated robotics/microfluidics platform for the automated preparation of such arrays, and we apply it to the batch fabrication of up to eighteen chips of flow-patterned DNA barcodes. The resulting substrates are comparable in quality with hand-made arrays and exhibit excellent substrate-to-substrate consistency. We demonstrate the utility and reproducibility of robotics-patterned barcodes by utilizing two flow-patterned chips for highly parallel assays of a panel of secreted proteins from single macrophage cells.

A robotics platform for automated batch fabrication of high density, microfluidics-based DNA microarrays, with applications to single cell, multiplex assays of secreted proteins

PubMed Central

Ahmad, Habib; Sutherland, Alex; Shin, Young Shik; Hwang, Kiwook; Qin, Lidong; Krom, Russell-John; Heath, James R.

2011-01-01

Microfluidics flow-patterning has been utilized for the construction of chip-scale miniaturized DNA and protein barcode arrays. Such arrays have been used for specific clinical and fundamental investigations in which many proteins are assayed from single cells or other small sample sizes. However, flow-patterned arrays are hand-prepared, and so are impractical for broad applications. We describe an integrated robotics/microfluidics platform for the automated preparation of such arrays, and we apply it to the batch fabrication of up to eighteen chips of flow-patterned DNA barcodes. The resulting substrates are comparable in quality with hand-made arrays and exhibit excellent substrate-to-substrate consistency. We demonstrate the utility and reproducibility of robotics-patterned barcodes by utilizing two flow-patterned chips for highly parallel assays of a panel of secreted proteins from single macrophage cells. PMID:21974603

A robotics platform for automated batch fabrication of high density, microfluidics-based DNA microarrays, with applications to single cell, multiplex assays of secreted proteins.

PubMed

Ahmad, Habib; Sutherland, Alex; Shin, Young Shik; Hwang, Kiwook; Qin, Lidong; Krom, Russell-John; Heath, James R

2011-09-01

Microfluidics flow-patterning has been utilized for the construction of chip-scale miniaturized DNA and protein barcode arrays. Such arrays have been used for specific clinical and fundamental investigations in which many proteins are assayed from single cells or other small sample sizes. However, flow-patterned arrays are hand-prepared, and so are impractical for broad applications. We describe an integrated robotics/microfluidics platform for the automated preparation of such arrays, and we apply it to the batch fabrication of up to eighteen chips of flow-patterned DNA barcodes. The resulting substrates are comparable in quality with hand-made arrays and exhibit excellent substrate-to-substrate consistency. We demonstrate the utility and reproducibility of robotics-patterned barcodes by utilizing two flow-patterned chips for highly parallel assays of a panel of secreted proteins from single macrophage cells. © 2011 American Institute of Physics

The dynamics and stability of lubricating oil films during droplet transport by electrowetting in microfluidic devices.

PubMed

Kleinert, Jairus; Srinivasan, Vijay; Rival, Arnaud; Delattre, Cyril; Velev, Orlin D; Pamula, Vamsee K

2015-05-01

The operation of digital microfluidic devices with water droplets manipulated by electrowetting is critically dependent on the static and dynamic stability and lubrication properties of the oil films that separate the droplets from the solid surfaces. The factors determining the stability of the films and preventing surface fouling in such systems are not yet thoroughly understood and were experimentally investigated in this study. The experiments were performed using a standard digital microfluidic cartridge in which water droplets enclosed in a thin, oil-filled gap were transported over an array of electrodes. Stable, continuous oil films separated the droplets from the surfaces when the droplets were stationary. During droplet transport, capillary waves formed in the films on the electrode surfaces as the oil menisci receded. The waves evolved into dome-shaped oil lenses. Droplet deformation and oil displacement caused the films at the surface opposite the electrode array to transform into dimples of oil trapped over the centers of the droplets. Lower actuation voltages were associated with slower film thinning and formation of fewer, but larger, oil lenses. Lower ac frequencies induced oscillations in the droplets that caused the films to rupture. Films were also destabilized by addition of surfactants to the oil or droplet phases. Such a comprehensive understanding of the oil film behavior will enable more robust electrowetting-actuated lab-on-a-chip devices through prevention of loss of species from droplets and contamination of surfaces at points where films may break.

The dynamics and stability of lubricating oil films during droplet transport by electrowetting in microfluidic devices

PubMed Central

Kleinert, Jairus; Srinivasan, Vijay; Rival, Arnaud; Delattre, Cyril; Velev, Orlin D.; Pamula, Vamsee K.

2015-01-01

The operation of digital microfluidic devices with water droplets manipulated by electrowetting is critically dependent on the static and dynamic stability and lubrication properties of the oil films that separate the droplets from the solid surfaces. The factors determining the stability of the films and preventing surface fouling in such systems are not yet thoroughly understood and were experimentally investigated in this study. The experiments were performed using a standard digital microfluidic cartridge in which water droplets enclosed in a thin, oil-filled gap were transported over an array of electrodes. Stable, continuous oil films separated the droplets from the surfaces when the droplets were stationary. During droplet transport, capillary waves formed in the films on the electrode surfaces as the oil menisci receded. The waves evolved into dome-shaped oil lenses. Droplet deformation and oil displacement caused the films at the surface opposite the electrode array to transform into dimples of oil trapped over the centers of the droplets. Lower actuation voltages were associated with slower film thinning and formation of fewer, but larger, oil lenses. Lower ac frequencies induced oscillations in the droplets that caused the films to rupture. Films were also destabilized by addition of surfactants to the oil or droplet phases. Such a comprehensive understanding of the oil film behavior will enable more robust electrowetting-actuated lab-on-a-chip devices through prevention of loss of species from droplets and contamination of surfaces at points where films may break. PMID:26045729

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

PubMed

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

2016-04-26

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

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

PubMed

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

2014-05-07

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

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

PubMed Central

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

2015-01-01

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

Mosquitoes meet microfluidics: High-throughput microfluidic tools for insect-parasite ecology in field conditions

NASA Astrophysics Data System (ADS)

Prakash, Manu; Mukundarajan, Haripriya

2013-11-01

A simple bite from an insect is the transmission mechanism for many deadly diseases worldwide--including malaria, yellow fever, west nile and dengue. Very little is known about how populations of numerous insect species and disease-causing parasites interact in their natural habitats due to a lack of measurement techniques. At present, vector surveillance techniques involve manual capture by using humans as live bait, which is hard to justify on ethical grounds. Individual mosquitoes are manually dissected to isolate salivary glands to detect sporozites. With typical vector infection rates being very low even in endemic areas, it is almost impossible to get an accurate picture of disease distribution, in both space and time. Here we present novel high-throughput microfluidic tools for vector surveillance, specifically mosquitoes. A two-dimensional high density array with baits provide an integrated platform for multiplex PCR for detection of both vector and parasite species. Combining techniques from engineering and field ecology, methods and tools developed here will enable high-throughput measurement of infection rates for a number of diseases in mosquito populations in field conditions. Pew Foundation.

An Interactive Program on Digitizing Historical Seismograms

NASA Astrophysics Data System (ADS)

Xu, Y.; Xu, T.

2013-12-01

Retrieving information from historical seismograms is of great importance since they are considered the unique sources that provide quantitative information of historical earthquakes. Modern techniques of seismology require digital forms of seismograms that are essentially a sequence of time-amplitude pairs. However, the historical seismograms, after scanned into computers, are two dimensional arrays. Each element of the arrays contains the grayscale value or RGB value of the corresponding pixel. The problem of digitizing historical seismograms, referred to as converting historical seismograms to digital seismograms, can be formulated as an inverse problem that generating sequences of time-amplitude pairs from a two dimension arrays. This problem has infinite solutions. The algorithm for automatic digitization of historical seismogram presented considers several features of seismograms, including continuity, smoothness of the seismic traces as the prior information, and assumes that the amplitude is a single-valued function of time. An interactive program based on the algorithm is also presented. The program is developed using Matlab GUI and has both automatic and manual modality digitization. Users can easily switch between them, and try different combinations to get the optimal results. Several examples are given to illustrate the results of digitizing seismograms using the program, including a photographic record and a wide-angle reflection/refraction seismogram. Digitized result of the program (redrawn using Golden Software Surfer for high resolution image). (a) shows the result of automatic digitization, and (b) is the result after manual correction.

Electronic drop sensing in microfluidic devices: automated operation of a nanoliter viscometer

PubMed Central

Srivastava, Nimisha; Burns, Mark A.

2007-01-01

We describe three droplet sensing techniques: a digital electrode, an analog electrode, and a thermal method. All three techniques use a single layer of metal lines that is easy to microfabricate and an electronic signal can be produced using low DC voltages. While the electrode methods utilize changes in electrical conductivity when the air/liquid interface of the droplet passes over a pair of electrodes, the thermal method is based on convective heat loss from a locally heated region. For the electrode method, the analog technique is able to detect 25 nL droplets while the digital technique is capable of detecting droplets as small as 100 pL. For thermal sensing, temperature profiles in the range of 36 °C and higher were used. Finally, we have used the digital electrode method and an array of electrodes located at preset distances to automate the operation of a previously described microfluidic viscometer. The viscometer is completely controlled by a laptop computer, and the total time for operation including setup, calibration, sample addition and viscosity calculation is approximately 4 minutes. PMID:16738725

Fast reconstruction of off-axis digital holograms based on digital spatial multiplexing.

PubMed

Sha, Bei; Liu, Xuan; Ge, Xiao-Lu; Guo, Cheng-Shan

2014-09-22

A method for fast reconstruction of off-axis digital holograms based on digital multiplexing algorithm is proposed. Instead of the existed angular multiplexing (AM), the new method utilizes a spatial multiplexing (SM) algorithm, in which four off-axis holograms recorded in sequence are synthesized into one SM function through multiplying each hologram with a tilted plane wave and then adding them up. In comparison with the conventional methods, the SM algorithm simplifies two-dimensional (2-D) Fourier transforms (FTs) of four N*N arrays into a 1.25-D FTs of one N*N arrays. Experimental results demonstrate that, using the SM algorithm, the computational efficiency can be improved and the reconstructed wavefronts keep the same quality as those retrieved based on the existed AM method. This algorithm may be useful in design of a fast preview system of dynamic wavefront imaging in digital holography.

Operating scheme for the light-emitting diode array of a volumetric display that exhibits multiple full-color dynamic images

NASA Astrophysics Data System (ADS)

Hirayama, Ryuji; Shiraki, Atsushi; Nakayama, Hirotaka; Kakue, Takashi; Shimobaba, Tomoyoshi; Ito, Tomoyoshi

2017-07-01

We designed and developed a control circuit for a three-dimensional (3-D) light-emitting diode (LED) array to be used in volumetric displays exhibiting full-color dynamic 3-D images. The circuit was implemented on a field-programmable gate array; therefore, pulse-width modulation, which requires high-speed processing, could be operated in real time. We experimentally evaluated the developed system by measuring the luminance of an LED with varying input and confirmed that the system works appropriately. In addition, we demonstrated that the volumetric display exhibits different full-color dynamic two-dimensional images in two orthogonal directions. Each of the exhibited images could be obtained only from the prescribed viewpoint. Such directional characteristics of the system are beneficial for applications, including digital signage, security systems, art, and amusement.

All-electronic droplet generation on-chip with real-time feedback control for EWOD digital microfluidics.

PubMed

Gong, Jian; Kim, Chang-Jin C J

2008-06-01

Electrowetting-on-dielectric (EWOD) actuation enables digital (or droplet) microfluidics where small packets of liquids are manipulated on a two-dimensional surface. Due to its mechanical simplicity and low energy consumption, EWOD holds particular promise for portable systems. To improve volume precision of the droplets, which is desired for quantitative applications such as biochemical assays, existing practices would require near-perfect device fabrication and operation conditions unless the droplets are generated under feedback control by an extra pump setup off of the chip. In this paper, we develop an all-electronic (i.e., no ancillary pumping) real-time feedback control of on-chip droplet generation. A fast voltage modulation, capacitance sensing, and discrete-time PID feedback controller are integrated on the operating electronic board. A significant improvement is obtained in the droplet volume uniformity, compared with an open loop control as well as the previous feedback control employing an external pump. Furthermore, this new capability empowers users to prescribe the droplet volume even below the previously considered minimum, allowing, for example, 1 : x (x < 1) mixing, in comparison to the previously considered n : m mixing (i.e., n and m unit droplets).

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

PubMed

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

2014-08-21

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

Note: Toward multiple addressable optical trapping

PubMed Central

Faustov, Alexei R.; Webb, Michael R.; Walt, David R.

2010-01-01

We describe a setup for addressable optical trapping in which a laser source is focused on a digital micromirror device and generates an optical trap in a microfluidic cell. In this paper, we report a proof-of-principle single beam∕single micromirror∕single three-dimensional trap arrangement that should serve as the basis for a multiple-trap instrument. PMID:20192526

Rectangular Array Of Digital Processors For Planning Paths

NASA Technical Reports Server (NTRS)

Kemeny, Sabrina E.; Fossum, Eric R.; Nixon, Robert H.

1993-01-01

Prototype 24 x 25 rectangular array of asynchronous parallel digital processors rapidly finds best path across two-dimensional field, which could be patch of terrain traversed by robotic or military vehicle. Implemented as single-chip very-large-scale integrated circuit. Excepting processors on edges, each processor communicates with four nearest neighbors along paths representing travel to north, south, east, and west. Each processor contains delay generator in form of 8-bit ripple counter, preset to 1 of 256 possible values. Operation begins with choice of processor representing starting point. Transmits signals to nearest neighbor processors, which retransmits to other neighboring processors, and process repeats until signals propagated across entire field.

NASA Tech Briefs, May 2009

NASA Technical Reports Server (NTRS)

2009-01-01

Topics covered include: Valve-"Health"-Monitoring System; Microstrip Antenna for Remote Sensing of Soil Moisture and Sea Surface Salinity; Biomedical Wireless Ambulatory Crew Monitor; Wireless Avionics Packet to Support Fault Tolerance for Flight Applications; Aerobot Autonomy Architecture; Submillimeter Confocal Imaging Active Module; Traveling-Wave Maser for 32 GHz; System Synchronizes Recordings from Separated Video Cameras; Piecewise-Planar Parabolic Reflectarray Antenna; Reducing Interference in ATC Voice Communication; EOS MLS Level 1B Data Processing, Version 2.2; Auto-Generated Semantic Processing Services; Geospatial Authentication; Maneuver Automation Software; Event Driven Messaging with Role-Based Subscriptions; Estimating Relative Positions of Outer-Space Structures; Fabricating PFPE Membranes for Capillary Electrophoresis; Linear Actuator Has Long Stroke and High Resolution; Installing a Test Tap on a Metal Battery Case; Fabricating PFPE Membranes for Microfluidic Valves and Pumps; Room-Temperature-Cured Copolymers for Lithium Battery Gel Electrolytes; Catalysts for Efficient Production of Carbon Nanotubes; Amorphous Silk Fibroin Membranes for Separation of CO2; "Zero-Mass" Noninvasive Pressure Transducers; Radial-Electric-Field Piezoelectric Diaphragm Pumps; Ejector-Enhanced, Pulsed, Pressure-Gain Combustor; Suppressing Ghost Diffraction in E-Beam-Written Gratings; Target-Tracking Camera for a Metrology System; Polarimetric Imaging using Two Photoelastic Modulators; Miniature Wide-Angle Lens for Small-Pixel Electronic Camera; Modal Filters for Infrared Interferometry; Mo(3)Sb(7-x)Te(x) for Thermoelectric Power Generation; Two-Dimensional Quantum Model of a Nanotransistor; Scanning Miniature Microscopes without Lenses; Manipulating Neutral Atoms in Chip-Based Magnetic Traps; Expansion Compression Contacts for Thermoelectric Legs; Processing Electromyographic Signals to Recognize Words; Physical Principle for Generation of Randomness; DSN Beowulf Cluster-Based VLBI Correlator; Hybrid NN/SVM Computational System for Optimizing Designs; Criteria for Modeling in LES of Multicomponent Fuel Flow; Computerized Machine for Cutting Space Shuttle Thermal Tiles; Orbiting Depot and Reusable Lander for Lunar Transportation; FPGA-Based Networked Phasemeter for a Heterodyne Interferometer; Aquarius Digital Processing Unit; Three-Dimensional Optical Coherence Tomography; Benchtop Antigen Detection Technique using Nanofiltration and Fluorescent Dyes; Isolation of Precursor Cells from Waste Solid Fat Tissue; Identification of Bacteria and Determination of Biological Indicators; Further Development of Scaffolds for Regeneration of Nerves; Chemically Assisted Photocatalytic Oxidation System; Use of Atomic Oxygen for Increased Water Contact Angles of Various Polymers for Biomedical Applications; Crashworthy Seats Would Afford Superior Protection; Open-Access, Low-Magnetic-Field MRI System for Lung Research; Microfluidic Mixing Technology for a Universal Health Sensor; Microfluidic Extraction of Biomarkers using Water as Solvent; Microwell Arrays for Studying Many Individual Cells; Droplet-Based Production of Liposomes; and Identifying and Inactivating Bacterial Spores

3D cardiac μ tissues within a microfluidic device with real-time contractile stress readout

PubMed Central

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

2015-01-01

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

A development of two-dimensional birefringence distribution measurement system with a sampling rate of 1.3 MHz

NASA Astrophysics Data System (ADS)

Onuma, Takashi; Otani, Yukitoshi

2014-03-01

A two-dimensional birefringence distribution measurement system with a sampling rate of 1.3 MHz is proposed. A polarization image sensor is developed as core device of the system. It is composed of a pixelated polarizer array made from photonic crystal and a parallel read out circuit with a multi-channel analog to digital converter specialized for two-dimensional polarization detection. By applying phase shifting algorism with circularly-polarized incident light, birefringence phase difference and azimuthal angle can be measured. The performance of the system is demonstrated experimentally by measuring actual birefringence distribution and polarization device such as Babinet-Soleil compensator.

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

PubMed

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

2016-01-21

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

Suspended microfluidics.

PubMed

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

2013-06-18

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

Suspended microfluidics

PubMed Central

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

2013-01-01

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

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

PubMed

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

2017-10-15

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

Metal-coated microfluidic channels: An approach to eliminate streaming potential effects in nano biosensors.

PubMed

Lee, Jieun; Wipf, Mathias; Mu, Luye; Adams, Chris; Hannant, Jennifer; Reed, Mark A

2017-01-15

We report a method to suppress streaming potential using an Ag-coated microfluidic channel on a p-type silicon nanowire (SiNW) array measured by a multiplexed electrical readout. The metal layer sets a constant electrical potential along the microfluidic channel for a given reference electrode voltage regardless of the flow velocity. Without the Ag layer, the magnitude and sign of the surface potential change on the SiNW depends on the flow velocity, width of the microfluidic channel and the device's location inside the microfluidic channel with respect to the reference electrode. Noise analysis of the SiNW array with and without the Ag coating in the fluidic channel shows that noise frequency peaks, resulting from the operation of a piezoelectric micropump, are eliminated using the Ag layer with two reference electrodes located at inlet and outlet. This strategy presents a simple platform to eliminate the streaming potential and can become a powerful tool for nanoscale potentiometric biosensors. Copyright © 2016 Elsevier B.V. All rights reserved.

Monolithic phononic crystals with a surface acoustic band gap from surface phonon-polariton coupling.

PubMed

Yudistira, D; Boes, A; Djafari-Rouhani, B; Pennec, Y; Yeo, L Y; Mitchell, A; Friend, J R

2014-11-21

We theoretically and experimentally demonstrate the existence of complete surface acoustic wave band gaps in surface phonon-polariton phononic crystals, in a completely monolithic structure formed from a two-dimensional honeycomb array of hexagonal shape domain-inverted inclusions in single crystal piezoelectric Z-cut lithium niobate. The band gaps appear at a frequency of about twice the Bragg band gap at the center of the Brillouin zone, formed through phonon-polariton coupling. The structure is mechanically, electromagnetically, and topographically homogeneous, without any physical alteration of the surface, offering an ideal platform for many acoustic wave applications for photonics, phononics, and microfluidics.

Laser tweezer actuated microphotonic array devices for high resolution imaging and analysis in chip-based biosystems

NASA Astrophysics Data System (ADS)

Birkbeck, Aaron L.

A new technology is developed that functionally integrates arrays of lasers and micro-optics into microfluidic systems for the purpose of imaging, analyzing, and manipulating objects and biological cells. In general, the devices and technologies emerging from this area either lack functionality through the reliance on mechanical systems or provide a serial-based, time consuming approach. As compared to the current state of art, our all-optical design methodology has several distinguishing features, such as parallelism, high efficiency, low power, auto-alignment, and high yield fabrication methods, which all contribute to minimizing the cost of the integration process. The potential use of vertical cavity surface emitting lasers (VCSELs) for the creation of two-dimensional arrays of laser optical tweezers that perform independently controlled, parallel capture, and transport of large numbers of individual objects and biological cells is investigated. One of the primary biological applications for which VCSEL array sourced laser optical tweezers are considered is the formation of engineered tissues through the manipulation and spatial arrangement of different types of cells in a co-culture. Creating devices that combine laser optical tweezers with select micro-optical components permits optical imaging and analysis functions to take place inside the microfluidic channel. One such device is a micro-optical spatial filter whose motion and alignment is controlled using a laser optical tweezer. Unlike conventional spatial filter systems, our device utilizes a refractive optical element that is directly incorporated onto the lithographically patterned spatial filter. This allows the micro-optical spatial filter to automatically align itself in three-dimensions to the focal point of the microscope objective, where it then filters out the higher frequency additive noise components present in the laser beam. As a means of performing high resolution imaging in the microfluidic channel, we developed a novel technique that integrates the capacity of a laser tweezer to optically trap and manipulate objects in three-dimensions with the resolution-enhanced imaging capabilities of a solid immersion lens (SIL). In our design, the SIL is a free-floating device whose imaging beam, motion control and alignment is provided by a laser optical tweezer, which allows the microfluidic SIL to image in areas that are inaccessible to traditional solid immersion microscopes.

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

PubMed

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

2017-09-20

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

A dimensional comparison between embedded 3D-printed and silicon microchannels

NASA Astrophysics Data System (ADS)

O'Connor, J.; Punch, J.; Jeffers, N.; Stafford, J.

2014-07-01

The subject of this paper is the dimensional characterization of embedded microchannel arrays created using contemporary 3D-printing fabrication techniques. Conventional microchannel arrays, fabricated using deep reactive ion etching techniques (DRIE) and wet-etching (KOH), are used as a benchmark for comparison. Rectangular and trapezoidal cross-sectional shapes were investigated. The channel arrays were 3D-printed in vertical and horizontal directions, to examine the influence of print orientation on channel characteristics. The 3D-printed channels were benchmarked against Silicon channels in terms of the following dimensional characteristics: cross-sectional area (CSA), perimeter, and surface profiles. The 3D-printed microchannel arrays demonstrated variances in CSA of 6.6-20% with the vertical printing approach yielding greater dimensional conformity than the horizontal approach. The measured CSA and perimeter of the vertical channels were smaller than the nominal dimensions, while the horizontal channels were larger in both CSA and perimeter due to additional side-wall roughness present throughout the channel length. This side-wall roughness caused significant shape distortion. Surface profile measurements revealed that the base wall roughness was approximately the resolution of current 3D-printers. A spatial periodicity was found along the channel length which appeared at different frequencies for each channel array. This paper concludes that vertical 3D-printing is superior to the horizontal printing approach, in terms of both dimensional fidelity and shape conformity and can be applied in microfluidic device applications.

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

NASA Astrophysics Data System (ADS)

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

2009-06-01

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

2D biological representations with reduced speckle obtained from two perpendicular ultrasonic arrays.

PubMed

Rodriguez-Hernandez, Miguel A; Gomez-Sacristan, Angel; Sempere-Payá, Víctor M

2016-04-29

Ultrasound diagnosis is a widely used medical tool. Among the various ultrasound techniques, ultrasonic imaging is particularly relevant. This paper presents an improvement to a two-dimensional (2D) ultrasonic system using measurements taken from perpendicular planes, where digital signal processing techniques are used to combine one-dimensional (1D) A-scans were acquired by individual transducers in arrays located in perpendicular planes. An algorithm used to combine measurements is improved based on the wavelet transform, which includes a denoising step during the 2D representation generation process. The inclusion of this new denoising stage generates higher quality 2D representations with a reduced level of speckling. The paper includes different 2D representations obtained from noisy A-scans and compares the improvements obtained by including the denoising stage.

Mastering multi-depth bio-chip patterns with DVD LBRs

NASA Astrophysics Data System (ADS)

Carson, Doug

2017-08-01

Bio chip and bio disc are rapidly growing technologies used in medical, health and other industries. While there are numerous unique designs and features, these products all rely on precise three-dimensional micro-fluidic channels or arrays to move, separate and combine samples under test. These bio chip and bio disc consumables are typically manufactured by molding these parts to a precise three-dimensional pattern on a negative metal stamper, or they can be made in smaller quantities using an appropriate curable resin and a negative mold/stamper. Stampers required for bio chips have been traditionally made using either micro machining or XY stepping lithography. Both of these technologies have their advantages as well as limitations when it comes to creating micro-fluidic patterns. Significant breakthroughs in continuous maskless lithography have enabled accurate and efficient manufacturing of micro-fluidic masters using LBRs (Laser Beam Recorders) and DRIE (Deep Reactive Ion Etching). The important advantages of LBR continuous lithography vs. XY stepping lithography and micro machining are speed and cost. LBR based continuous lithography is >100x faster than XY stepping lithography and more accurate than micro machining. Several innovations were required in order to create multi-depth patterns with sub micron accuracy. By combining proven industrial LBRs with DCA's G3-VIA pattern generator and DRIE, three-dimensional bio chip masters and stampers are being manufactured efficiently and accurately.

Inventions Utilizing Microfluidics and Colloidal Particles

NASA Technical Reports Server (NTRS)

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

2009-01-01

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

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

PubMed Central

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

2014-01-01

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

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

PubMed

Silva, Ryan; Bhatia, Swapnil; Densmore, Douglas

2016-07-05

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

Fabrication of cross-shaped Cu-nanowire resistive memory devices using a rapid, scalable, and designable inorganic-nanowire-digital-alignment technique (Conference Presentation)

NASA Astrophysics Data System (ADS)

Xu, Wentao; Lee, Yeongjun; Min, Sung-Yong; Park, Cheolmin; Lee, Tae-Woo

2016-09-01

Resistive random-access memory (RRAM) is a candidate next generation nonvolatile memory due to its high access speed, high density and ease of fabrication. Especially, cross-point-access allows cross-bar arrays that lead to high-density cells in a two-dimensional planar structure. Use of such designs could be compatible with the aggressive scaling down of memory devices, but existing methods such as optical or e-beam lithographic approaches are too complicated. One-dimensional inorganic nanowires (i-NWs) are regarded as ideal components of nanoelectronics to circumvent the limitations of conventional lithographic approaches. However, post-growth alignment of these i-NWs precisely on a large area with individual control is still a difficult challenge. Here, we report a simple, inexpensive, and rapid method to fabricate two-dimensional arrays of perpendicularly-aligned, individually-conductive Cu-NWs with a nanometer-scale CuxO layer sandwiched at each cross point, by using an inorganic-nanowire-digital-alignment technique (INDAT) and a one-step reduction process. In this approach, the oxide layer is self-formed and patterned, so conventional deposition and lithography are not necessary. INDAT eliminates the difficulties of alignment and scalable fabrication that are encountered when using currently-available techniques that use inorganic nanowires. This simple process facilitates fabrication of cross-point nonvolatile memristor arrays. Fabricated arrays had reproducible resistive switching behavior, high on/off current ratio (Ion/Ioff) 10 6 and extensive cycling endurance. This is the first report of memristors with the resistive switching oxide layer self-formed, self-patterned and self-positioned; we envision that the new features of the technique will provide great opportunities for future nano-electronic circuits.

Microfluidic cell trap array for controlled positioning of single cells on adhesive micropatterns.

PubMed

Lin, Laiyi; Chu, Yeh-Shiu; Thiery, Jean Paul; Lim, Chwee Teck; Rodriguez, Isabel

2013-02-21

Adhesive micropattern arrays permit the continuous monitoring and systematic study of the behavior of spatially confined cells of well-defined shape and size in ordered configurations. This technique has contributed to defining mechanisms that control cell polarity and cell functions, including proliferation, apoptosis, differentiation and migration in two-dimensional cell culture systems. These micropattern studies often involve isolating a single cell on one adhesive protein micropattern using random seeding methods. Random seeding has been successful for isolated and, to a lesser degree, paired patterns, where two patterns are placed in close proximity. Using this method, we found that the probability of obtaining one cell per pattern decreases significantly as the number of micropatterns in a cluster increases, from 16% for paired micropatterns to 0.3% for clusters of 6 micropatterns. This work presents a simple yet effective platform based on a microfludic sieve-like trap array to exert precise control over the positioning of single cells on micropatterns. We observed a 4-fold improvement over random seeding in the efficiency of placing a pair of single cells on paired micropattern and a 40-fold improvement for 6-pattern clusters. The controlled nature of this platform can also allow the juxtaposition of two different cell populations through a simple modification in the trap arrangement. With excellent control of the identity, number and position of neighbouring cells, this cell-positioning platform provides a unique opportunity for the extension of two-dimensional micropattern studies beyond paired micropatterns to organizations containing many cells or different cell types.

Microfluidic sorting and multimodal typing of cancer cells in self-assembled magnetic arrays.

PubMed

Saliba, Antoine-Emmanuel; Saias, Laure; Psychari, Eleni; Minc, Nicolas; Simon, Damien; Bidard, François-Clément; Mathiot, Claire; Pierga, Jean-Yves; Fraisier, Vincent; Salamero, Jean; Saada, Véronique; Farace, Françoise; Vielh, Philippe; Malaquin, Laurent; Viovy, Jean-Louis

2010-08-17

We propose a unique method for cell sorting, "Ephesia," using columns of biofunctionalized superparamagnetic beads self-assembled in a microfluidic channel onto an array of magnetic traps prepared by microcontact printing. It combines the advantages of microfluidic cell sorting, notably the application of a well controlled, flow-activated interaction between cells and beads, and those of immunomagnetic sorting, notably the use of batch-prepared, well characterized antibody-bearing beads. On cell lines mixtures, we demonstrated a capture yield better than 94%, and the possibility to cultivate in situ the captured cells. A second series of experiments involved clinical samples--blood, pleural effusion, and fine needle aspirates--issued from healthy donors and patients with B-cell hematological malignant tumors (leukemia and lymphoma). The immunophenotype and morphology of B-lymphocytes were analyzed directly in the microfluidic chamber, and compared with conventional flow cytometry and visual cytology data, in a blind test. Immunophenotyping results using Ephesia were fully consistent with those obtained by flow cytometry. We obtained in situ high resolution confocal three-dimensional images of the cell nuclei, showing intranuclear details consistent with conventional cytological staining. Ephesia thus provides a powerful approach to cell capture and typing allowing fully automated high resolution and quantitative immunophenotyping and morphological analysis. It requires at least 10 times smaller sample volume and cell numbers than cytometry, potentially increasing the range of indications and the success rate of microbiopsy-based diagnosis, and reducing analysis time and cost.

Microfluidic sorting and multimodal typing of cancer cells in self-assembled magnetic arrays

PubMed Central

Saliba, Antoine-Emmanuel; Saias, Laure; Psychari, Eleni; Minc, Nicolas; Simon, Damien; Bidard, François-Clément; Mathiot, Claire; Pierga, Jean-Yves; Fraisier, Vincent; Salamero, Jean; Saada, Véronique; Farace, Françoise; Vielh, Philippe; Malaquin, Laurent; Viovy, Jean-Louis

2010-01-01

We propose a unique method for cell sorting, “Ephesia,” using columns of biofunctionalized superparamagnetic beads self-assembled in a microfluidic channel onto an array of magnetic traps prepared by microcontact printing. It combines the advantages of microfluidic cell sorting, notably the application of a well controlled, flow-activated interaction between cells and beads, and those of immunomagnetic sorting, notably the use of batch-prepared, well characterized antibody-bearing beads. On cell lines mixtures, we demonstrated a capture yield better than 94%, and the possibility to cultivate in situ the captured cells. A second series of experiments involved clinical samples—blood, pleural effusion, and fine needle aspirates— issued from healthy donors and patients with B-cell hematological malignant tumors (leukemia and lymphoma). The immunophenotype and morphology of B-lymphocytes were analyzed directly in the microfluidic chamber, and compared with conventional flow cytometry and visual cytology data, in a blind test. Immunophenotyping results using Ephesia were fully consistent with those obtained by flow cytometry. We obtained in situ high resolution confocal three-dimensional images of the cell nuclei, showing intranuclear details consistent with conventional cytological staining. Ephesia thus provides a powerful approach to cell capture and typing allowing fully automated high resolution and quantitative immunophenotyping and morphological analysis. It requires at least 10 times smaller sample volume and cell numbers than cytometry, potentially increasing the range of indications and the success rate of microbiopsy-based diagnosis, and reducing analysis time and cost. PMID:20679245

A switchable digital microfluidic droplet dye-laser.

PubMed

Kuehne, Alexander J C; Gather, Malte C; Eydelnant, Irwin A; Yun, Seok-Hyun; Weitz, David A; Wheeler, Aaron R

2011-11-07

Digital microfluidic devices allow the manipulation of droplets between two parallel electrodes. These electrodes can act as mirrors generating a micro-cavity, which can be exploited for a droplet dye-laser. Three representative laser-dyes with emission wavelengths spanning the whole visible spectrum are chosen to show the applicability of this concept. Sub-microlitre droplets of laser-dye solution are moved in and out of a lasing site on-chip to down-convert the UV-excitation light into blue, green and red laser-pulses. This journal is © The Royal Society of Chemistry 2011

High-resolution mapping of bifurcations in nonlinear biochemical circuits

NASA Astrophysics Data System (ADS)

Genot, A. J.; Baccouche, A.; Sieskind, R.; Aubert-Kato, N.; Bredeche, N.; Bartolo, J. F.; Taly, V.; Fujii, T.; Rondelez, Y.

2016-08-01

Analog molecular circuits can exploit the nonlinear nature of biochemical reaction networks to compute low-precision outputs with fewer resources than digital circuits. This analog computation is similar to that employed by gene-regulation networks. Although digital systems have a tractable link between structure and function, the nonlinear and continuous nature of analog circuits yields an intricate functional landscape, which makes their design counter-intuitive, their characterization laborious and their analysis delicate. Here, using droplet-based microfluidics, we map with high resolution and dimensionality the bifurcation diagrams of two synthetic, out-of-equilibrium and nonlinear programs: a bistable DNA switch and a predator-prey DNA oscillator. The diagrams delineate where function is optimal, dynamics bifurcates and models fail. Inverse problem solving on these large-scale data sets indicates interference from enzymatic coupling. Additionally, data mining exposes the presence of rare, stochastically bursting oscillators near deterministic bifurcations.

Appendix C: Automated Vitrification of Mammalian Embryos on a Digital Microfluidic Device.

PubMed

Liu, Jun; Pyne, Derek G; Abdelgawad, Mohamed; Sun, Yu

2017-01-01

This chapter introduces a digital microfluidic device that automates sample preparation for mammalian embryo vitrification. Individual microdroplets manipulated on the microfluidic device were used as microvessels to transport a single mouse embryo through a complete vitrification procedure. Advantages of this approach, compared to manual operation and channel-based microfluidic vitrification, include automated operation, cryoprotectant concentration gradient generation, and feasibility of loading and retrieval of embryos.

Rapid fabrication of three-dimensional structures for dielectrophoretic sorting of lipid-containing organisms

NASA Astrophysics Data System (ADS)

Schor, Alisha R.; Buie, Cullen R.

2016-10-01

In this work, we demonstrate a microfluidic particle sorter consisting of three-dimensional, conducting microposts. Our sorter uses dielectrophoresis (DEP) to sort high- and low-lipid phenotypes of the yeast Yarrowia lipolytica. Y. lipolytica is one of the many microorganisms being explored as a hydrocarbon source for biodiesel, Omega-3 additives, and other products derived from fatty acids. A rapid, non-destructive, lipid-based sorting tool would accelerate the commercialization of these products. Our device consists of an array of 105, 25 μm wide gold microposts that span the height of a 15 μm channel. This array generates an electric field in a microfluidic device that is uniform through the channel height, but has a custom-shaped non-uniformity in the horizontal directions. This is crucial in order to achieve continuous sorting using DEP, as it ensures all cells are exposed to the same conditions throughout the channel height. By using very low currents (100 μA), we are able to electroplate these post arrays in fewer than 15 min. This is an order of magnitude improvement over previous reports of electroplated microstructures. With an applied signal of 250 MHz, 2.6 V pp in our device, we separate a heterogeneous population with a purity of 97.8% in the low-lipid stream and 71.4% in the high-lipid stream. The high-lipid stream purity can be improved by adjusting the spacing of the array. This unique protocol for the rapid fabrication of 3D microstructures has enabled the creation of a non-invasive sorting tool for genetically engineered, lipid-producing organisms. The ability to screen organisms based on lipid content will alleviate one of the major bottlenecks in commercialization of microbial biofuels.

Three-dimensional virtual surgery models for percutaneous coronary intervention (PCI) optimization strategies

NASA Astrophysics Data System (ADS)

Wang, Hujun; Liu, Jinghua; Zheng, Xu; Rong, Xiaohui; Zheng, Xuwei; Peng, Hongyu; Silber-Li, Zhanghua; Li, Mujun; Liu, Liyu

2015-06-01

Percutaneous coronary intervention (PCI), especially coronary stent implantation, has been shown to be an effective treatment for coronary artery disease. However, in-stent restenosis is one of the longstanding unsolvable problems following PCI. Although stents implanted inside narrowed vessels recover normal flux of blood flows, they instantaneously change the wall shear stress (WSS) distribution on the vessel surface. Improper stent implantation positions bring high possibilities of restenosis as it enlarges the low WSS regions and subsequently stimulates more epithelial cell outgrowth on vessel walls. To optimize the stent position for lowering the risk of restenosis, we successfully established a digital three-dimensional (3-D) model based on a real clinical coronary artery and analysed the optimal stenting strategies by computational simulation. Via microfabrication and 3-D printing technology, the digital model was also converted into in vitro microfluidic models with 3-D micro channels. Simultaneously, physicians placed real stents inside them; i.e., they performed “virtual surgeries”. The hydrodynamic experimental results showed that the microfluidic models highly inosculated the simulations. Therefore, our study not only demonstrated that the half-cross stenting strategy could maximally reduce restenosis risks but also indicated that 3-D printing combined with clinical image reconstruction is a promising method for future angiocardiopathy research.

Numerical studies of bacterial-carpet microflows

NASA Astrophysics Data System (ADS)

Huber, Greg; Tillberg, Dan; Powers, Thomas R.

2004-03-01

Bacterial carpets are arrays of motile bacteria attached to two-dimensional surfaces. Improved understanding of carpet flows is important in the design of microfluidic devices and transport systems powered by bacterial flagellar motion. In recent experiments by the group of Howard Berg, cells of swarming S. marcescens are stuck to the surface, with most of their flagella free to rotate in the fluid. These studies show modified transport and greatly enhanced diffusion near the active carpet surface. We present theoretical models of the flagella-driven flow, bridging the nano- to the macro-scale, simulate the diffusion and advection of passive tracers, and compare the numerical results with the tracking data of Berg et al.

Polymer-based microfluidic chips for isothermal amplification of nucleic acids

NASA Astrophysics Data System (ADS)

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

2017-11-01

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

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

PubMed

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

2014-09-21

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

Reconstruction of electrocardiogram using ionic current models for heart muscles.

PubMed

Yamanaka, A; Okazaki, K; Urushibara, S; Kawato, M; Suzuki, R

1986-11-01

A digital computer model is presented for the simulation of the electrocardiogram during ventricular activation and repolarization (QRS-T waves). The part of the ventricular septum and the left ventricular free wall of the heart are represented by a two dimensional array of 730 homogeneous functional units. Ionic currents models are used to determine the spatial distribution of the electrical activities of these units at each instant of time during simulated cardiac cycle. In order to reconstruct the electrocardiogram, the model is expanded three-dimensionally with equipotential assumption along the third axis and then the surface potentials are calculated using solid angle method. Our digital computer model can be used to improve the understanding of the relationship between body surface potentials and intracellular electrical events.

Hydrodynamic and thermal modeling of two-dimensional microdroplet arrays for digitized heat transfer

NASA Astrophysics Data System (ADS)

Baird, Eric S.

This document describes hydrodynamic and thermal modeling of two-dimensional microdroplet arrays for use in digitized heat transfer (DHT), a novel active thermal management technique for high power density electronics and integrated microsystems. In DHT, thermal energy is transported by a discrete array of electrostatically activated microdroplets of liquid metals, alloys or aqueous solutions with the potential of supporting significantly higher heat transfer rates than classical air-cooled heat sinks. Actuation methods for dispensing and transporting individual fluid slugs with a high degree of precision and programmability are described, with simple approximate formulae for net forces for steady state and transient velocities in terms of known parameters. A modified cavity flow solver is developed to provide details on the internal flow properties of a translating microdroplet and used to detail the effects of droplet curvature, internal mixing, Peclet number and other parameters on the heat transfer capabilities of a discretized liquid flow. The concept of Nusselt number is generalized to an individual fluid slug and shown to oscillate with a period equal to the droplet's mixing rate. In whole, DHT is demonstrated to be a viable new alternative for achieving the most important objectives of electronic cooling (i.e., minimization of the maximum substrate temperature, reduction of the substrate temperature gradient and removal of substrate hot spots) and a sound fundamental description of the method's electro-, hydro- and thermodynamics is provided.

High-performance single cell genetic analysis using microfluidic emulsion generator arrays.

PubMed

Zeng, Yong; Novak, Richard; Shuga, Joe; Smith, Martyn T; Mathies, Richard A

2010-04-15

High-throughput genetic and phenotypic analysis at the single cell level is critical to advance our understanding of the molecular mechanisms underlying cellular function and dysfunction. Here we describe a high-performance single cell genetic analysis (SCGA) technique that combines high-throughput microfluidic emulsion generation with single cell multiplex polymerase chain reaction (PCR). Microfabricated emulsion generator array (MEGA) devices containing 4, 32, and 96 channels are developed to confer a flexible capability of generating up to 3.4 x 10(6) nanoliter-volume droplets per hour. Hybrid glass-polydimethylsiloxane diaphragm micropumps integrated into the MEGA chips afford uniform droplet formation, controlled generation frequency, and effective transportation and encapsulation of primer functionalized microbeads and cells. A multiplex single cell PCR method is developed to detect and quantify both wild type and mutant/pathogenic cells. In this method, microbeads functionalized with multiple forward primers targeting specific genes from different cell types are used for solid-phase PCR in droplets. Following PCR, the droplets are lysed and the beads are pooled and rapidly analyzed by multicolor flow cytometry. Using Escherichia coli bacterial cells as a model, we show that this technique enables digital detection of pathogenic E. coli O157 cells in a high background of normal K12 cells, with a detection limit on the order of 1/10(5). This result demonstrates that multiplex SCGA is a promising tool for high-throughput quantitative digital analysis of genetic variation in complex populations.

High-Performance Single Cell Genetic Analysis Using Microfluidic Emulsion Generator Arrays

PubMed Central

Zeng, Yong; Novak, Richard; Shuga, Joe; Smith, Martyn T.; Mathies, Richard A.

2010-01-01

High-throughput genetic and phenotypic analysis at the single cell level is critical to advance our understanding of the molecular mechanisms underlying cellular function and dysfunction. Here we describe a high-performance single cell genetic analysis (SCGA) technique that combines high-throughput microfluidic emulsion generation with single cell multiplex PCR. Microfabricated emulsion generator array (MEGA) devices containing 4, 32 and 96 channels are developed to confer a flexible capability of generating up to 3.4 × 106 nanoliter-volume droplets per hour. Hybrid glass-polydimethylsiloxane diaphragm micropumps integrated into the MEGA chips afford uniform droplet formation, controlled generation frequency, and effective transportation and encapsulation of primer functionalized microbeads and cells. A multiplex single cell PCR method is developed to detect and quantify both wild type and mutant/pathogenic cells. In this method, microbeads functionalized with multiple forward primers targeting specific genes from different cell types are used for solid-phase PCR in droplets. Following PCR, the droplets are lysed, the beads are pooled and rapidly analyzed by multi-color flow cytometry. Using E. coli bacterial cells as a model, we show that this technique enables digital detection of pathogenic E. coli O157 cells in a high background of normal K12 cells, with a detection limit on the order of 1:105. This result demonstrates that multiplex SCGA is a promising tool for high-throughput quantitative digital analysis of genetic variation in complex populations. PMID:20192178

Double emulsions from a capillary array injection microfluidic device.

PubMed

Shang, Luoran; Cheng, Yao; Wang, Jie; Ding, Haibo; Rong, Fei; Zhao, Yuanjin; Gu, Zhongze

2014-09-21

A facile microfluidic device was developed by inserting an annular capillary array into a collection channel for single-step emulsification of double emulsions. By inserting multiple inner-phase solutions into the capillary array, multicomponent double emulsions or microcapsules with inner droplets of different content could also be obtained from the device.

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.

Compressive sensing for single-shot two-dimensional coherent spectroscopy

NASA Astrophysics Data System (ADS)

Harel, E.; Spencer, A.; Spokoyny, B.

2017-02-01

In this work, we explore the use of compressive sensing for the rapid acquisition of two-dimensional optical spectra that encodes the electronic structure and ultrafast dynamics of condensed-phase molecular species. Specifically, we have developed a means to combine multiplexed single-element detection and single-shot and phase-resolved two-dimensional coherent spectroscopy. The method described, which we call Single Point Array Reconstruction by Spatial Encoding (SPARSE) eliminates the need for costly array detectors while speeding up acquisition by several orders of magnitude compared to scanning methods. Physical implementation of SPARSE is facilitated by combining spatiotemporal encoding of the nonlinear optical response and signal modulation by a high-speed digital micromirror device. We demonstrate the approach by investigating a well-characterized cyanine molecule and a photosynthetic pigment-protein complex. Hadamard and compressive sensing algorithms are demonstrated, with the latter achieving compression factors as high as ten. Both show good agreement with directly detected spectra. We envision a myriad of applications in nonlinear spectroscopy using SPARSE with broadband femtosecond light sources in so-far unexplored regions of the electromagnetic spectrum.

Investigating bacteria-surface interactions with microfluidics and Digital Holographic Microscopy

NASA Astrophysics Data System (ADS)

Agarwal, Harsh; Barry, Michael; Stocker, Roman; Sheng, Jian

2009-11-01

Quantitative data of swimming characteristics of bacteria in the shear flow adjacent to a surface are crucial for understanding cell attachment and detachment, and thus biofilm formation. We combined microfluidics and holography to expose Escherichia coli AW405 to a carefully controlled flow environment and visualize their movement in three dimensions. We investigated wall shear rates up to 200 (1/s) and recorded holograms at 40X magnification and 15fps for several minutes. Three-dimensional locations and orientations of bacteria were extracted from numerically reconstructed images. We obtained thousands of 3D trajectories over a sample volume of 380x380x200 μm, with a resolution of 0.2 μm in the two in-plane directions and 1 μm in the out-of-plane direction. Preliminary results revealed a range of behaviors, including circular trajectories near surfaces and migration normal to the wall. We expect that ongoing analysis will provide robust statistics of wall effects on bacterial motility. Sponsored by NIH (1-R21-EB008844-01) and NSF (CBET-0844647, DBI-0852875)

An optical/digital processor - Hardware and applications

NASA Technical Reports Server (NTRS)

Casasent, D.; Sterling, W. M.

1975-01-01

A real-time two-dimensional hybrid processor consisting of a coherent optical system, an optical/digital interface, and a PDP-11/15 control minicomputer is described. The input electrical-to-optical transducer is an electron-beam addressed potassium dideuterium phosphate (KD2PO4) light valve. The requirements and hardware for the output optical-to-digital interface, which is constructed from modular computer building blocks, are presented. Initial experimental results demonstrating the operation of this hybrid processor in phased-array radar data processing, synthetic-aperture image correlation, and text correlation are included. The applications chosen emphasize the role of the interface in the analysis of data from an optical processor and possible extensions to the digital feedback control of an optical processor.

Development of a microfluidic device for simultaneous mixing and pumping

NASA Astrophysics Data System (ADS)

Kim, Byoung Jae; Yoon, Sang Youl; Lee, Kyung Heon; Sung, Hyung Jin

2009-01-01

We conducted experimental and numerical studies aimed at developing a microfluidic device capable of simultaneous mixing while pumping. The proposed multifunctional device makes use of alternating current electroosmotic flow and adopts an array of planar asymmetric microelectrodes with a diagonal or herringbone shape. The pumping performance was assessed in terms of the fluid velocity at the center of the microchannel, obtained by micro PIV. To assess the mixing, flow visualizations were carried out over the electrodes to verify the lateral flows. The mixing degree was quantified in terms of a mixing efficiency obtained by three-dimensional numerical simulations. The results showed that simultaneous mixing and pumping was achieved in the channels with diagonal or herringbone electrode configurations. A herringbone electrode configuration showed better pumping compared with a reference, as well as enhanced mixing.

Digital holographic characterization of liquid microlenses array fabricated in electrode-less configuration

NASA Astrophysics Data System (ADS)

Miccio, L.; Vespini, V.; Grilli, S.; Paturzo, M.; Finizio, A.; De Nicola, S.; Ferraro, P.

2009-06-01

We show how thin liquid film on polar dielectric substrate can form an array of liquid micro-lenses. The effect is driven by the pyroelectric effect leading to a new concept in electro-wetting (EW). EW is a viable method for actuation of liquids in microfluidic systems and requires the design and fabrication of complex electrodes for suitable actuation of liquids. When compared to conventional electrowetting devices, the pyroelectric effect allowed to have an electrode-less and circuitless configuration. In our case the surface electric charge induced by the thermal stimulus is able to pattern selectively the surface wettability according to geometry of the ferroelectric domains micro-engineered into the lithium niobate crystal. We show that different geometries of liquid microlenses can be obtained showing also a tuneability of the focal lenses down to 1.6 mm. Thousand of liquid microlenses, each with 100 μm diameter, can be formed and actuated. Also different geometries such as hemi-cylindrical and toroidal liquid structures can be easily obtained. By means of a digital holography method, an accurate characterization of the micro-lenses curvature is performed and presented. The preliminary results concerning the imaging capability of the micro-lens array are also reported. Microlens array can find application in medical stereo-endoscopy, imaging, telecommunication and optical data storage too.

Novel application of digital microfluidics for the detection of biotinidase deficiency in newborns.

PubMed

Graham, Carrie; Sista, Ramakrishna S; Kleinert, Jairus; Wu, Ning; Eckhardt, Allen; Bali, Deeksha; Millington, David S; Pamula, Vamsee K

2013-12-01

Newborn screening for biotinidase deficiency can be performed using a fluorometric enzyme assay on dried blood spot specimens. As a pre-requisite to the consolidation of different enzymatic assays onto a single platform, we describe here a novel analytical method for detecting biotinidase deficiency using the same digital microfluidic cartridge that has already been demonstrated to screen for five lysosomal storage diseases (Pompe, Fabry, Gaucher, Hurler and Hunter) in a multiplex format. A novel assay to quantify biotinidase concentration in dried blood spots (DBS) was developed and optimized on the digital microfluidic platform using proficiency testing samples from the Centers for Disease Control and Prevention. The enzymatic assay uses 4-methylumbelliferyl biotin as the fluorogenic substrate. Biotinidase deficiency assays were performed on normal (n=200) and deficient (n=7) newborn DBS specimens. Enzymatic activity analysis of biotinidase deficiency revealed distinct separation between normal and affected DBS specimens using digital microfluidics and these results matched the expected activity. This study has demonstrated performance of biotinidase deficiency assays by measurement of 4-methylumbelliferyl product on a digital microfluidic platform. Due to the inherent ease in multiplexing on such a platform, consolidation of other fluorometric assays onto a single cartridge may be realized. © 2013.

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

PubMed

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

2008-03-01

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

Microfluidic quadrupole and floating concentration gradient.

PubMed

Qasaimeh, Mohammad A; Gervais, Thomas; Juncker, David

2011-09-06

The concept of fluidic multipoles, in analogy to electrostatics, has long been known as a particular class of solutions of the Navier-Stokes equation in potential flows; however, experimental observations of fluidic multipoles and of their characteristics have not been reported yet. Here we present a two-dimensional microfluidic quadrupole and a theoretical analysis consistent with the experimental observations. The microfluidic quadrupole was formed by simultaneously injecting and aspirating fluids from two pairs of opposing apertures in a narrow gap formed between a microfluidic probe and a substrate. A stagnation point was formed at the centre of the microfluidic quadrupole, and its position could be rapidly adjusted hydrodynamically. Following the injection of a solute through one of the poles, a stationary, tunable, and movable-that is, 'floating'-concentration gradient was formed at the stagnation point. Our results lay the foundation for future combined experimental and theoretical exploration of microfluidic planar multipoles including convective-diffusive phenomena.

Image Decoding of Photonic Crystal Beads Array in the Microfluidic Chip for Multiplex Assays

PubMed Central

Yuan, Junjie; Zhao, Xiangwei; Wang, Xiaoxia; Gu, Zhongze

2014-01-01

Along with the miniaturization and intellectualization of biomedical instruments, the increasing demand of health monitoring at anywhere and anytime elevates the need for the development of point of care testing (POCT). Photonic crystal beads (PCBs) as one kind of good encoded microcarriers can be integrated with microfluidic chips in order to realize cost-effective and high sensitive multiplex bioassays. However, there are difficulties in analyzing them towards automated analysis due to the characters of the PCBs and the unique detection manner. In this paper, we propose a strategy to take advantage of automated image processing for the color decoding of the PCBs array in the microfluidic chip for multiplex assays. By processing and alignment of two modal images of epi-fluorescence and epi-white light, every intact bead in the image is accurately extracted and decoded by PC colors, which stand for the target species. This method, which shows high robustness and accuracy under various configurations, eliminates the high hardware requirement of spectroscopy analysis and user-interaction software, and provides adequate supports for the general automated analysis of POCT based on PCBs array. PMID:25341876

Planar digital nanoliter dispensing system based on thermocapillary actuation.

PubMed

Darhuber, Anton A; Valentino, Joseph P; Troian, Sandra M

2010-04-21

We provide guidelines for the design and operation of a planar digital nanodispensing system based on thermocapillary actuation. Thin metallic microheaters embedded within a chemically patterned glass substrate are electronically activated to generate and control 2D surface temperature distributions which either arrest or trigger liquid flow and droplet formation on demand. This flow control is a consequence of the variation of a liquid's surface tension with temperature, which is used to draw liquid toward cooler regions of the supporting substrate. A liquid sample consisting of several microliters is placed on a flat rectangular supply cell defined by chemical patterning. Thermocapillary switches are then activated to extract a slender fluid filament from the cell and to divide the filament into an array of droplets whose position and volume are digitally controlled. Experimental results for the power required to extract a filament and to divide it into two or more droplets as a function of geometric and operating parameters are in excellent agreement with hydrodynamic simulations. The capability to dispense ultralow volumes onto a 2D substrate extends the functionality of microfluidic devices based on thermocapillary actuation previously shown effective in routing and mixing nanoliter liquid samples on glass or silicon substrates.

A digital rat atlas of sectional anatomy

NASA Astrophysics Data System (ADS)

Yu, Li; Liu, Qian; Bai, Xueling; Liao, Yinping; Luo, Qingming; Gong, Hui

2006-09-01

This paper describes a digital rat alias of sectional anatomy made by milling. Two healthy Sprague-Dawley (SD) rat weighing 160-180 g were used for the generation of this atlas. The rats were depilated completely, then euthanized by Co II. One was via vascular perfusion, the other was directly frozen at -85 °C over 24 hour. After that, the frozen specimens were transferred into iron molds for embedding. A 3% gelatin solution colored blue was used to fill the molds and then frozen at -85 °C for one or two days. The frozen specimen-blocks were subsequently sectioned on the cryosection-milling machine in a plane oriented approximately transverse to the long axis of the body. The surface of specimen-blocks were imaged by a scanner and digitalized into 4,600 x2,580 x 24 bit array through a computer. Finally 9,475 sectional images (arterial vessel were not perfused) and 1,646 sectional images (arterial vessel were perfused) were captured, which made the volume of the digital atlas up to 369.35 Gbyte. This digital rat atlas is aimed at the whole rat and the rat arterial vessels are also presented. We have reconstructed this atlas. The information from the two-dimensional (2-D) images of serial sections and three-dimensional (3-D) surface model all shows that the digital rat atlas we constructed is high quality. This work lays the foundation for a deeper study of digital rat.

A simple method of fabricating mask-free microfluidic devices for biological analysis

PubMed Central

Yi, Xin; Kodzius, Rimantas; Gong, Xiuqing; Xiao, Kang; Wen, Weijia

2010-01-01

We report a simple, low-cost, rapid, and mask-free method to fabricate two-dimensional (2D) and three-dimensional (3D) microfluidic chip for biological analysis researches. In this fabrication process, a laser system is used to cut through paper to form intricate patterns and differently configured channels for specific purposes. Bonded with cyanoacrylate-based resin, the prepared paper sheet is sandwiched between glass slides (hydrophilic) or polymer-based plates (hydrophobic) to obtain a multilayer structure. In order to examine the chip’s biocompatibility and applicability, protein concentration was measured while DNA capillary electrophoresis was carried out, and both of them show positive results. With the utilization of direct laser cutting and one-step gas-sacrificing techniques, the whole fabrication processes for complicated 2D and 3D microfluidic devices are shorten into several minutes which make it a good alternative of poly(dimethylsiloxane) microfluidic chips used in biological analysis researches. PMID:20890452

Activation and control of microlens liquid arrays on functionalized polar electric crystal substrates by electro-wetting effect and temperature

NASA Astrophysics Data System (ADS)

Ferraro, Pietro; Grilli, Simonetta; Miccio, Lisa; Vespini, Veronica; Finizio, Sergio DeNicola Andrea

2008-11-01

In recent years a variety of liquid bases optical elements have been conceived, designed and fabricated even for commercial products like digital cameras o cellular phone cameras. The impressive development of microfluidic systems in conjunction with optics has led to the creation of a completely new Science field of investigation named optofludics. Optofludics, among others topics, deals with investigation and methods for realizing liquid micro-lenses. A variety of liquid micro-lenses have been designed and realized by using different configurations. We demonstrate that a lensing effect can be obtained in an open microfluidic system by using a thin layer of liquid on a polar electric crystal such as Lithium Niobate (LiNbO3). Electrowetting patterning on LiNbO3 surface is obtained by pyroelectric effect consisting in a simple but reliable electrodes-less and circuit-less configuration. The electrodes are intrinsically embedded into the substrate. The material is functionalised by means of a micro-engineering electric filed poling process. Lens array with variable focus has been demonstrated with a large number of lens elements (10x10) on micrometric scale (aperture of single lens 100 microns).

Matrix decompositions of two-dimensional nuclear magnetic resonance spectra.

PubMed

Havel, T F; Najfeld, I; Yang, J X

1994-08-16

Two-dimensional NMR spectra are rectangular arrays of real numbers, which are commonly regarded as digitized images to be analyzed visually. If one treats them instead as mathematical matrices, linear algebra techniques can also be used to extract valuable information from them. This matrix approach is greatly facilitated by means of a physically significant decomposition of these spectra into a product of matrices--namely, S = PAPT. Here, P denotes a matrix whose columns contain the digitized contours of each individual peak or multiple in the one-dimensional spectrum, PT is its transpose, and A is an interaction matrix specific to the experiment in question. The practical applications of this decomposition are considered in detail for two important types of two-dimensional NMR spectra, double quantum-filtered correlated spectroscopy and nuclear Overhauser effect spectroscopy, both in the weak-coupling approximation. The elements of A are the signed intensities of the cross-peaks in a double quantum-filtered correlated spectrum, or the integrated cross-peak intensities in the case of a nuclear Overhauser effect spectrum. This decomposition not only permits these spectra to be efficiently simulated but also permits the corresponding inverse problems to be given an elegant mathematical formulation to which standard numerical methods are applicable. Finally, the extension of this decomposition to the case of strong coupling is given.

Matrix decompositions of two-dimensional nuclear magnetic resonance spectra.

PubMed Central

Havel, T F; Najfeld, I; Yang, J X

1994-01-01

Two-dimensional NMR spectra are rectangular arrays of real numbers, which are commonly regarded as digitized images to be analyzed visually. If one treats them instead as mathematical matrices, linear algebra techniques can also be used to extract valuable information from them. This matrix approach is greatly facilitated by means of a physically significant decomposition of these spectra into a product of matrices--namely, S = PAPT. Here, P denotes a matrix whose columns contain the digitized contours of each individual peak or multiple in the one-dimensional spectrum, PT is its transpose, and A is an interaction matrix specific to the experiment in question. The practical applications of this decomposition are considered in detail for two important types of two-dimensional NMR spectra, double quantum-filtered correlated spectroscopy and nuclear Overhauser effect spectroscopy, both in the weak-coupling approximation. The elements of A are the signed intensities of the cross-peaks in a double quantum-filtered correlated spectrum, or the integrated cross-peak intensities in the case of a nuclear Overhauser effect spectrum. This decomposition not only permits these spectra to be efficiently simulated but also permits the corresponding inverse problems to be given an elegant mathematical formulation to which standard numerical methods are applicable. Finally, the extension of this decomposition to the case of strong coupling is given. PMID:8058742

Light-addressable measurements of cellular oxygen consumption rates in microwell arrays based on phase-based phosphorescence lifetime detection

PubMed Central

Huang, Shih-Hao; Hsu, Yu-Hsuan; Wu, Chih-Wei; Wu, Chang-Jer

2012-01-01

A digital light modulation system that utilizes a modified commercial digital micromirror device (DMD) projector, which is equipped with a UV light-emitting diode as a light modulation source, has been developed to spatially direct excited light toward a microwell array device to detect the oxygen consumption rate (OCR) of single cells via phase-based phosphorescence lifetime detection. The microwell array device is composed of a combination of two components: an array of glass microwells containing Pt(II) octaethylporphine (PtOEP) as the oxygen-sensitive luminescent layer and a microfluidic module with pneumatically actuated glass lids set above the microwells to controllably seal the microwells of interest. By controlling the illumination pattern on the DMD, the modulated excitation light can be spatially projected to only excite the sealed microwell for cellular OCR measurements. The OCR of baby hamster kidney-21 fibroblast cells cultivated on the PtOEP layer within a sealed microwell has been successfully measured at 104 ± 2.96 amol s−1 cell−1. Repeatable and consistent measurements indicate that the oxygen measurements did not adversely affect the physiological state of the measured cells. The OCR of the cells exhibited a good linear relationship with the diameter of the microwells, ranging from 400 to 1000 μm and containing approximately 480 to 1200 cells within a microwell. In addition, the OCR variation of single cells in situ infected by Dengue virus with a different multiplicity of infection was also successfully measured in real-time. This proposed platform provides the potential for a wide range of biological applications in cell-based biosensing, toxicology, and drug discovery. PMID:24348889

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

PubMed

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

2012-07-01

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

Feasibility study, software design, layout and simulation of a two-dimensional Fast Fourier Transform machine for use in optical array interferometry

NASA Technical Reports Server (NTRS)

Boriakoff, Valentin

1994-01-01

The goal of this project was the feasibility study of a particular architecture of a digital signal processing machine operating in real time which could do in a pipeline fashion the computation of the fast Fourier transform (FFT) of a time-domain sampled complex digital data stream. The particular architecture makes use of simple identical processors (called inner product processors) in a linear organization called a systolic array. Through computer simulation the new architecture to compute the FFT with systolic arrays was proved to be viable, and computed the FFT correctly and with the predicted particulars of operation. Integrated circuits to compute the operations expected of the vital node of the systolic architecture were proven feasible, and even with a 2 micron VLSI technology can execute the required operations in the required time. Actual construction of the integrated circuits was successful in one variant (fixed point) and unsuccessful in the other (floating point).

Security Assessment of Cyberphysical Digital Microfluidic Biochips.

PubMed

Ali, Sk Subidh; Ibrahim, Mohamed; Sinanoglu, Ozgur; Chakrabarty, Krishnendu; Karri, Ramesh

2016-01-01

A digital microfluidic biochip (DMFB) is an emerging technology that enables miniaturized analysis systems for point-of-care clinical diagnostics, DNA sequencing, and environmental monitoring. A DMFB reduces the rate of sample and reagent consumption, and automates the analysis of assays. In this paper, we provide the first assessment of the security vulnerabilities of DMFBs. We identify result-manipulation attacks on a DMFB that maliciously alter the assay outcomes. Two practical result-manipulation attacks are shown on a DMFB platform performing enzymatic glucose assay on serum. In the first attack, the attacker adjusts the concentration of the glucose sample and thereby modifies the final result. In the second attack, the attacker tampers with the calibration curve of the assay operation. We then identify denial-of-service attacks, where the attacker can disrupt the assay operation by tampering either with the droplet-routing algorithm or with the actuation sequence. We demonstrate these attacks using a digital microfluidic synthesis simulator. The results show that the attacks are easy to implement and hard to detect. Therefore, this work highlights the need for effective protections against malicious modifications in DMFBs.

Control and automation of multilayered integrated microfluidic device fabrication.

PubMed

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

2017-01-31

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

Digital quantum simulators in a scalable architecture of hybrid spin-photon qubits

PubMed Central

Chiesa, Alessandro; Santini, Paolo; Gerace, Dario; Raftery, James; Houck, Andrew A.; Carretta, Stefano

2015-01-01

Resolving quantum many-body problems represents one of the greatest challenges in physics and physical chemistry, due to the prohibitively large computational resources that would be required by using classical computers. A solution has been foreseen by directly simulating the time evolution through sequences of quantum gates applied to arrays of qubits, i.e. by implementing a digital quantum simulator. Superconducting circuits and resonators are emerging as an extremely promising platform for quantum computation architectures, but a digital quantum simulator proposal that is straightforwardly scalable, universal, and realizable with state-of-the-art technology is presently lacking. Here we propose a viable scheme to implement a universal quantum simulator with hybrid spin-photon qubits in an array of superconducting resonators, which is intrinsically scalable and allows for local control. As representative examples we consider the transverse-field Ising model, a spin-1 Hamiltonian, and the two-dimensional Hubbard model and we numerically simulate the scheme by including the main sources of decoherence. PMID:26563516

Integrated microelectrode array and microfluidics for temperature clamp of sensory neurons in culture.

PubMed

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

2005-01-01

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

Disposable world-to-chip interface for digital microfluidics

DOEpatents

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

2017-05-16

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

Microfluidic device having an immobilized pH gradient and PAGE gels for protein separation and analysis

DOEpatents

Sommer, Gregory J.; Hatch, Anson V.; Singh, Anup K.; Wang, Ying-Chih

2012-12-11

Disclosed is a novel microfluidic device enabling on-chip implementation of a two-dimensional separation methodology. Previously disclosed microscale immobilized pH gradients (IPG) are combined with perpendicular polyacrylamide gel electrophoresis (PAGE) microchannels to achieve orthogonal separations of biological samples. Device modifications enable inclusion of sodium dodecyl sulfate (SDS) in the second dimension. The device can be fabricated to use either continuous IPG gels, or the microscale isoelectric fractionation membranes we have also previously disclosed, for the first dimension. The invention represents the first all-gel two-dimensional separation microdevice, with significantly higher resolution power over existing devices.

Microfluidic device having an immobilized pH gradient and page gels for protein separation and analysis

DOEpatents

Sommer, Gregory J; Hatch, Anson V; Singh, Anup K; Wang, Ying-Chih

2014-05-20

Disclosed is a novel microfluidic device enabling on-chip implementation of a two-dimensional separation methodology. Previously disclosed microscale immobilized pH gradients (IPG) are combined with perpendicular polyacrylamide gel electrophoresis (PAGE) microchannels to achieve orthogonal separations of biological samples. Device modifications enable inclusion of sodium dodecyl sulfate (SDS) in the second dimension. The device can be fabricated to use either continuous IPG gels, or the microscale isoelectric fractionation membranes we have also previously disclosed, for the first dimension. The invention represents the first all-gel two-dimensional separation microdevice, with significantly higher resolution power over existing devices.

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

PubMed

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

2014-04-07

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

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.

Mechanistic evaluation of the pros and cons of digital RT-LAMP for HIV-1 viral load quantification on a microfluidic device and improved efficiency via a two-step digital protocol.

PubMed

Sun, Bing; Shen, Feng; McCalla, Stephanie E; Kreutz, Jason E; Karymov, Mikhail A; Ismagilov, Rustem F

2013-02-05

Here we used a SlipChip microfluidic device to evaluate the performance of digital reverse transcription-loop-mediated isothermal amplification (dRT-LAMP) for quantification of HIV viral RNA. Tests are needed for monitoring HIV viral load to control the emergence of drug resistance and to diagnose acute HIV infections. In resource-limited settings, in vitro measurement of HIV viral load in a simple format is especially needed, and single-molecule counting using a digital format could provide a potential solution. We showed here that when one-step dRT-LAMP is used for quantification of HIV RNA, the digital count is lower than expected and is limited by the yield of desired cDNA. We were able to overcome the limitations by developing a microfluidic protocol to manipulate many single molecules in parallel through a two-step digital process. In the first step we compartmentalize the individual RNA molecules (based on Poisson statistics) and perform reverse transcription on each RNA molecule independently to produce DNA. In the second step, we perform the LAMP amplification on all individual DNA molecules in parallel. Using this new protocol, we increased the absolute efficiency (the ratio between the concentration calculated from the actual count and the expected concentration) of dRT-LAMP 10-fold, from ∼2% to ∼23%, by (i) using a more efficient reverse transcriptase, (ii) introducing RNase H to break up the DNA:RNA hybrid, and (iii) adding only the BIP primer during the RT step. We also used this two-step method to quantify HIV RNA purified from four patient samples and found that in some cases, the quantification results were highly sensitive to the sequence of the patient's HIV RNA. We learned the following three lessons from this work: (i) digital amplification technologies, including dLAMP and dPCR, may give adequate dilution curves and yet have low efficiency, thereby providing quantification values that underestimate the true concentration. Careful validation is essential before a method is considered to provide absolute quantification; (ii) the sensitivity of dLAMP to the sequence of the target nucleic acid necessitates additional validation with patient samples carrying the full spectrum of mutations; (iii) for multistep digital amplification chemistries, such as a combination of reverse transcription with amplification, microfluidic devices may be used to decouple these steps from one another and to perform them under different, individually optimized conditions for improved efficiency.

High resolution projection micro stereolithography system and method

DOEpatents

Spadaccini, Christopher M.; Farquar, George; Weisgraber, Todd; Gemberling, Steven; Fang, Nicholas; Xu, Jun; Alonso, Matthew; Lee, Howon

2016-11-15

A high-resolution P.mu.SL system and method incorporating one or more of the following features with a standard P.mu.SL system using a SLM projected digital image to form components in a stereolithographic bath: a far-field superlens for producing sub-diffraction-limited features, multiple spatial light modulators (SLM) to generate spatially-controlled three-dimensional interference holograms with nanoscale features, and the integration of microfluidic components into the resin bath of a P.mu.SL system to fabricate microstructures of different materials.

Microelectrofluidic lens for variable curvature

NASA Astrophysics Data System (ADS)

Chang, Jong-hyeon; Lee, Eunsung; Jung, Kyu-Dong; Lee, Seungwan; Choi, Minseog; Kim, Woonbae

2012-10-01

This paper presents a tunable liquid lens based on microelectrofluidic technology which integrates electrowetting and microfluidics. In the novel microelectrofluidic lens (MEFL), electrowetting in the hydrophobic surface channel induces the Laplace pressure difference between two fluidic interfaces on the lens aperture and the surface channel. Then, the pressure difference makes the lens curvature tunable. The previous electrowetting lens in which the contact angle changes at the side wall has a certain limitation of the curvature variation because of the contact angle saturation. Although the contact angle saturation also appears in the surface channel of the MEFL, the low surface channel increases the Laplace pressure and it makes the MEFL to have full variation of the optical power possible. The magnitude of the applied voltage determines the lens curvature in the analog mode MEFL as well as the electrowetting lens. Digital operation is also possible when the control electrodes of the MEFL are patterned to have an array. It is expected that the proposed MEFL is able to be widely used because of its full variation of the optical power without the use of oil and digital operation with fast response.

Point-of-Care Quantitative Measure of Glucose-6-Phosphate Dehydrogenase Enzyme Deficiency.

PubMed

Bhutani, Vinod K; Kaplan, Michael; Glader, Bertil; Cotten, Michael; Kleinert, Jairus; Pamula, Vamsee

2015-11-01

Widespread newborn screening on a point-of-care basis could prevent bilirubin neurotoxicity in newborns with glucose-6-phosphate dehydrogenase (G6PD) deficiency. We evaluated a quantitative G6PD assay on a digital microfluidic platform by comparing its performance with standard clinical methods. G6PD activity was measured quantitatively by using digital microfluidic fluorescence and the gold standard fluorescence biochemical test on a convenience sample of 98 discarded blood samples. Twenty-four samples were designated as G6PD deficient. Mean ± SD G6PD activity for normal samples using the digital microfluidic method and the standard method, respectively, was 9.7 ± 2.8 and 11.1 ± 3.0 U/g hemoglobin (Hb), respectively; for G6PD-deficient samples, it was 0.8 ± 0.7 and 1.4 ± 0.9 U/g Hb. Bland-Altman analysis determined a mean difference of -0.96 ± 1.8 U/g Hb between the digital microfluidic fluorescence results and the standard biochemical test results. The lower and upper limits for the digital microfluidic platform were 4.5 to 19.5 U/g Hb for normal samples and 0.2 to 3.7 U/g Hb for G6PD-deficient samples. The lower and upper limits for the Stanford method were 5.5 to 20.7 U/g Hb for normal samples and 0.1 to 2.8 U/g Hb for G6PD-deficient samples. The measured activity discriminated between G6PD-deficient samples and normal samples with no overlap. Pending further validation, a digital microfluidics platform could be an accurate point-of-care screening tool for rapid newborn G6PD screening. Copyright © 2015 by the American Academy of Pediatrics.

Microfluidic array platform for simultaneous lipid bilayer membrane formation.

PubMed

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

2009-01-01

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

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

PubMed

Zhang, He; Hu, Xinjiang; Fu, Xin

2014-07-15

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

Architecture and data processing alternatives for Tse computer. Volume 1: Tse logic design concepts and the development of image processing machine architectures

NASA Technical Reports Server (NTRS)

Rickard, D. A.; Bodenheimer, R. E.

1976-01-01

Digital computer components which perform two dimensional array logic operations (Tse logic) on binary data arrays are described. The properties of Golay transforms which make them useful in image processing are reviewed, and several architectures for Golay transform processors are presented with emphasis on the skeletonizing algorithm. Conventional logic control units developed for the Golay transform processors are described. One is a unique microprogrammable control unit that uses a microprocessor to control the Tse computer. The remaining control units are based on programmable logic arrays. Performance criteria are established and utilized to compare the various Golay transform machines developed. A critique of Tse logic is presented, and recommendations for additional research are included.

High Voltage Dielectrophoretic and Magnetophoretic Hybrid Integrated Circuit / Microfluidic Chip

PubMed Central

Issadore, David; Franke, Thomas; Brown, Keith A.; Hunt, Thomas P.; Westervelt, Robert M.

2010-01-01

A hybrid integrated circuit (IC) / microfluidic chip is presented that independently and simultaneously traps and moves microscopic objects suspended in fluid using both electric and magnetic fields. This hybrid chip controls the location of dielectric objects, such as living cells and drops of fluid, on a 60 × 61 array of pixels that are 30 × 38 μm2 in size, each of which can be individually addressed with a 50 V peak-to-peak, DC to 10 MHz radio frequency voltage. These high voltage pixels produce electric fields above the chip’s surface with a magnitude , resulting in strong dielectrophoresis (DEP) forces . Underneath the array of DEP pixels there is a magnetic matrix that consists of two perpendicular sets of 60 metal wires running across the chip. Each wire can be sourced with 120 mA to trap and move magnetically susceptible objects using magnetophoresis (MP). The DEP pixel array and magnetic matrix can be used simultaneously to apply forces to microscopic objects, such as living cells or lipid vesicles, that are tagged with magnetic nanoparticles. The capabilities of the hybrid IC / microfluidic chip demonstrated in this paper provide important building blocks for a platform for biological and chemical applications. PMID:20625468

High Voltage Dielectrophoretic and Magnetophoretic Hybrid Integrated Circuit / Microfluidic Chip.

PubMed

Issadore, David; Franke, Thomas; Brown, Keith A; Hunt, Thomas P; Westervelt, Robert M

2009-12-01

A hybrid integrated circuit (IC) / microfluidic chip is presented that independently and simultaneously traps and moves microscopic objects suspended in fluid using both electric and magnetic fields. This hybrid chip controls the location of dielectric objects, such as living cells and drops of fluid, on a 60 × 61 array of pixels that are 30 × 38 μm(2) in size, each of which can be individually addressed with a 50 V peak-to-peak, DC to 10 MHz radio frequency voltage. These high voltage pixels produce electric fields above the chip's surface with a magnitude , resulting in strong dielectrophoresis (DEP) forces . Underneath the array of DEP pixels there is a magnetic matrix that consists of two perpendicular sets of 60 metal wires running across the chip. Each wire can be sourced with 120 mA to trap and move magnetically susceptible objects using magnetophoresis (MP). The DEP pixel array and magnetic matrix can be used simultaneously to apply forces to microscopic objects, such as living cells or lipid vesicles, that are tagged with magnetic nanoparticles. The capabilities of the hybrid IC / microfluidic chip demonstrated in this paper provide important building blocks for a platform for biological and chemical applications.

Microfluidic Chips Controlled with Elastomeric Microvalve Arrays

PubMed Central

Li, Nianzhen; Sip, Chris; Folch, Albert

2007-01-01

Miniaturized microfluidic systems provide simple and effective solutions for low-cost point-of-care diagnostics and high-throughput biomedical assays. Robust flow control and precise fluidic volumes are two critical requirements for these applications. We have developed microfluidic chips featuring elastomeric polydimethylsiloxane (PDMS) microvalve arrays that: 1) need no extra energy source to close the fluidic path, hence the loaded device is highly portable; and 2) allow for microfabricating deep (up to 1 mm) channels with vertical sidewalls and resulting in very precise features. The PDMS microvalves-based devices consist of three layers: a fluidic layer containing fluidic paths and microchambers of various sizes, a control layer containing the microchannels necessary to actuate the fluidic path with microvalves, and a middle thin PDMS membrane that is bound to the control layer. Fluidic layer and control layers are made by replica molding of PDMS from SU-8 photoresist masters, and the thin PDMS membrane is made by spinning PDMS at specified heights. The control layer is bonded to the thin PDMS membrane after oxygen activation of both, and then assembled with the fluidic layer. The microvalves are closed at rest and can be opened by applying negative pressure (e.g., house vacuum). Microvalve closure and opening are automated via solenoid valves controlled by computer software. Here, we demonstrate two microvalve-based microfluidic chips for two different applications. The first chip allows for storing and mixing precise sub-nanoliter volumes of aqueous solutions at various mixing ratios. The second chip allows for computer-controlled perfusion of microfluidic cell cultures. The devices are easy to fabricate and simple to control. Due to the biocompatibility of PDMS, these microchips could have broad applications in miniaturized diagnostic assays as well as basic cell biology studies. PMID:18989408

Digital microfluidics: Droplet based logic gates

NASA Astrophysics Data System (ADS)

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

2007-01-01

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

Digital microfluidic platform for multiplexing enzyme assays: implications for lysosomal storage disease screening in newborns.

PubMed

Sista, Ramakrishna S; Eckhardt, Allen E; Wang, Tong; Graham, Carrie; Rouse, Jeremy L; Norton, Scott M; Srinivasan, Vijay; Pollack, Michael G; Tolun, Adviye A; Bali, Deeksha; Millington, David S; Pamula, Vamsee K

2011-10-01

Newborn screening for lysosomal storage diseases (LSDs) has been gaining considerable interest owing to the availability of enzyme replacement therapies. We present a digital microfluidic platform to perform rapid, multiplexed enzymatic analysis of acid α-glucosidase (GAA) and acid α-galactosidase to screen for Pompe and Fabry disorders. The results were compared with those obtained using standard fluorometric methods. We performed bench-based, fluorometric enzymatic analysis on 60 deidentified newborn dried blood spots (DBSs), plus 10 Pompe-affected and 11 Fabry-affected samples, at Duke Biochemical Genetics Laboratory using a 3-mm punch for each assay and an incubation time of 20 h. We used a digital microfluidic platform to automate fluorometric enzymatic assays at Advanced Liquid Logic Inc. using extract from a single punch for both assays, with an incubation time of 6 h. Assays were also performed with an incubation time of 1 h. Assay results were generally comparable, although mean enzymatic activity for GAA using microfluidics was approximately 3 times higher than that obtained using bench-based methods, which could be attributed to higher substrate concentration. Clear separation was observed between the normal and affected samples at both 6- and 1-h incubation times using digital microfluidics. A digital microfluidic platform compared favorably with a clinical reference laboratory to perform enzymatic analysis in DBSs for Pompe and Fabry disorders. This platform presents a new technology for a newborn screening laboratory to screen LSDs by fully automating all the liquid-handling operations in an inexpensive system, providing rapid results.

Interdroplet bilayer arrays in millifluidic droplet traps from 3D-printed moulds.

PubMed

King, Philip H; Jones, Gareth; Morgan, Hywel; de Planque, Maurits R R; Zauner, Klaus-Peter

2014-02-21

In droplet microfluidics, aqueous droplets are typically separated by an oil phase to ensure containment of molecules in individual droplets of nano-to-picoliter volume. An interesting variation of this method involves bringing two phospholipid-coated droplets into contact to form a lipid bilayer in-between the droplets. These interdroplet bilayers, created by manual pipetting of microliter droplets, have proved advantageous for the study of membrane transport phenomena, including ion channel electrophysiology. In this study, we adapted the droplet microfluidics methodology to achieve automated formation of interdroplet lipid bilayer arrays. We developed a 'millifluidic' chip for microliter droplet generation and droplet packing, which is cast from a 3D-printed mould. Droplets of 0.7-6.0 μL volume were packed as homogeneous or heterogeneous linear arrays of 2-9 droplets that were stable for at least six hours. The interdroplet bilayers had an area of up to 0.56 mm(2), or an equivalent diameter of up to 850 μm, as determined from capacitance measurements. We observed osmotic water transfer over the bilayers as well as sequential bilayer lysis by the pore-forming toxin melittin. These millifluidic interdroplet bilayer arrays combine the ease of electrical and optical access of manually pipetted microdroplets with the automation and reproducibility of microfluidic technologies. Moreover, the 3D-printing based fabrication strategy enables the rapid implementation of alternative channel geometries, e.g. branched arrays, with a design-to-device time of just 24-48 hours.

Disposable microfluidic sensor arrays for discrimination of antioxidants.

PubMed

Park, Seong H; Maruniak, Autumn; Kim, Jisun; Yi, Gi-Ra; Lim, Sung H

2016-06-01

A microfluidic colorimetric sensor array was developed for detection and identification of various antioxidants. The sensor was fabricated by a photolithographic method, and consists of an array of printed cross-responsive indicators. The microfluidic design also incorporates pre-activation spots to allow printing of chemically incompatible components separately. Separately printed oxidizer allowed an oxidation of adjacent redox indicators only when aqueous sample was added to the sensor cartridge. Antioxidants were primarily detected by measuring the extent of inhibition of this oxidation reaction. Using this flow-based technique, a clear differentiation of 8 different antioxidants and 4 different teas has been demonstrated with 98.5% sensitivity. Copyright © 2016 Elsevier B.V. All rights reserved.

Three-dimensional image acquisition and reconstruction system on a mobile device based on computer-generated integral imaging.

PubMed

Erdenebat, Munkh-Uchral; Kim, Byeong-Jun; Piao, Yan-Ling; Park, Seo-Yeon; Kwon, Ki-Chul; Piao, Mei-Lan; Yoo, Kwan-Hee; Kim, Nam

2017-10-01

A mobile three-dimensional image acquisition and reconstruction system using a computer-generated integral imaging technique is proposed. A depth camera connected to the mobile device acquires the color and depth data of a real object simultaneously, and an elemental image array is generated based on the original three-dimensional information for the object, with lens array specifications input into the mobile device. The three-dimensional visualization of the real object is reconstructed on the mobile display through optical or digital reconstruction methods. The proposed system is implemented successfully and the experimental results certify that the system is an effective and interesting method of displaying real three-dimensional content on a mobile device.

A novel concept of dielectrophoretic engine oil filter

NASA Astrophysics Data System (ADS)

Khusid, Boris; Shen, Yueyang; Elele, Ezinwa

2011-11-01

A novel concept of an alternating current (AC) dielectrophoretic filter with a three-dimensional electrode array is presented. A filter is constructed by winding into layers around the core tube two sheets of woven metal wire-mesh with several sheets of woven insulating wire-mesh sandwiched in between. Contrary to conventional dielectrophoretic devices, the proposed design of electrodes generates a high-gradient field over a large working volume by applying several hundred volts at a standard frequency of 60 Hz. The operating principle of filtration is based on our recently developed method of AC dielectrophoretic gating for microfluidics. The filtration efficiency is expressed in terms of two non-dimensional parameters which describe the combined influence of the particle polarizability and size, the oil viscosity and flow rate, and the field gradient on the particle captivity. The proof-of-concept is tested by measuring the single-pass performance of two filters on positively polarized particles dispersed in engine oil: spherical glass beads, fused aluminum oxide powder, and silicon metal powder, all smaller than the mesh opening. The results obtained provide critical design guidelines for the development of a filter based on the retention capability of challenge particles. The work was supported in part by ONR and NSF.

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

NASA Astrophysics Data System (ADS)

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

2007-02-01

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

Desktop aligner for fabrication of multilayer microfluidic devices.

PubMed

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

2015-07-01

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

Desktop aligner for fabrication of multilayer microfluidic devices

PubMed Central

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

2015-01-01

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

ALL-ELECTRONIC DROPLET GENERATION ON-CHIP WITH REAL-TIME FEEDBACK CONTROL FOR EWOD DIGITIAL MICROFLUIDICS

PubMed Central

Gong, Jian; Kim, Chang-Jin “CJ”

2009-01-01

Electrowetting-on-dielectric (EWOD) actuation enables digital (or droplet) microfluidics where small packets of liquids are manipulated on a two-dimensional surface. Due to its mechanical simplicity and low energy consumption, EWOD holds particular promise for portable systems. To improve volume precision of the droplets, which is desired for quantitative applications such as biochemical assays, existing practices would require near-perfect device fabricaion and operation conditions unless the droplets are generated under feedback control by an extra pump setup off of the chip. In this paper, we develop an all-electronic (i.e., no ancillary pumping) real-time feedback control of on-chip droplet generation. A fast voltage modulation, capacitance sensing, and discrete-time PID feedback controller are integrated on the operating electronic board. A significant improvement is obtained in the droplet volume uniformity, compared with an open loop control as well as the previous feedback control employing an external pump. Furthermore, this new capability empowers users to prescribe the droplet volume even below the previously considered minimum, allowing, for example, 1:x (x < 1) mixing, in comparison to the previously considered n:m mixing (i.e., n and m unit droplets). PMID:18497909

Magnetic nanohole superlattices

DOEpatents

Liu, Feng

2013-05-14

A magnetic material is disclosed including a two-dimensional array of carbon atoms and a two-dimensional array of nanoholes patterned in the two-dimensional array of carbon atoms. The magnetic material has long-range magnetic ordering at a temperature below a critical temperature Tc.

A two-dimensional intensified photodiode array for imaging spectroscopy

NASA Technical Reports Server (NTRS)

Tennyson, P. D.; Dymond, K.; Moos, H. W.; Feldman, P. D.; Mackey, E. F.

1986-01-01

The Johns Hopkins University is currently developing an instrument to fly aboard NASA's Space Shuttle as a Spartan payload in the late 1980s. This Spartan free flyer will obtain spatially resolved spectra of faint extended emission line objects in the wavelength range 750-1150 A at about 2-A resolution. The use of two-dimensional photon counting detectors will give simultaneous coverage of the 400 A spectral range and the 9 arc-minute spatial resolution along the spectrometer slit. The progress towards the flight detector is reported here with preliminary results from a laboratory breadboard detector, and a comparison with the one-dimensional detector developed for the Hopkins Ultraviolet Telescope. A hardware digital centroiding algorithm has been successfully implemented. The system is ultimately capable of 15-micron resolution in two dimensions at the image plane and can handle continuous counting rates of up to 8000 counts/s.

Buckling of Dielectric Elastomeric Plates for Electrically Active Microfludic Pumps

NASA Astrophysics Data System (ADS)

Holmes, Douglas; Tavakol, Behrouz; Bozlar, Michael; Froehlicher, Guillaume; Stone, Howard; Aksay, Ilhan

2013-11-01

Fluid flow can be directed and controlled by a variety of mechanisms within industrial and biological environments. Advances in microfluidic technology have required innovative ways to control fluid flow on a small scale, and the ability to actively control fluid flow within microfluidic devices is crucial for advancements in nanofluidics, biomedical fluidic devices, and digital microfluidics. In this work, we present a means for microfluidic control via the electrical actuation of thin, flexible valves within microfluidic channels. These structures consist of a dielectric elastomer confined between two compliant electrodes that can be actively and reversibly buckle out of plane to pump fluids from an applied voltage. The out-of-plane deformation can be quantified using two parameters: net change in surface area and the shape of deformation. Change in surface area depends on the voltage, while the deformation shape, which significantly affects the flow rate, is a function of voltage, and the pressure and volume of the chambers on each side of the thin plate. The use of solid electrodes enables a robust and reversible pumping mechanism that will have will enable advancements in rapid microfluidic diagnostics, adaptive materials, and artificial muscles.

Poly(ethylene glycol) hydrogel microstructures encapsulating living cells

NASA Technical Reports Server (NTRS)

Koh, Won-Gun; Revzin, Alexander; Pishko, Michael V.

2002-01-01

We present an easy and effective method for the encapsulation of cells inside PEG-based hydrogel microstructures fabricated using photolithography. High-density arrays of three-dimensional microstructures were created on substrates using this method. Mammalian cells were encapsulated in cylindrical hydrogel microstructures of 600 and 50 micrometers in diameter or in cubic hydrogel structures in microfluidic channels. Reducing lateral dimension of the individual hydrogel microstructure to 50 micrometers allowed us to isolate 1-3 cells per microstructure. Viability assays demonstrated that cells remained viable inside these hydrogels after encapsulation for up to 7 days.

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

PubMed

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

2012-11-21

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

Interferometric characterization of pyroelectrically activated micro-arrays of liquid lenses in lithium niobate crystals

NASA Astrophysics Data System (ADS)

Grilli, S.; Miccio, L.; Vespini, V.; Ferraro, P.

2008-08-01

In recent years a wide variety of liquid based optical elements have been conceived, designed and fabricated even for commercial products like digital cameras. The impressive development of microfluidic systems in conjunction with optics has led to the creation of a completely new field of investigation named optofludics. Among other things, the optofluidic area deals with the investigation and the realization of liquid micro-lenses. Different methods and configurations have been proposed in literature to achieve liquid variable micro-lenses. This paper reports about the possibility to achieve lensing effect by a relatively easy to accomplish technique based on an open microfluidic system consisting of a tiny amount of appropriate liquid manipulated by the pyroelectric effect onto a periodically poled LiNbO3 substrate. Basically, an electrowetting process is performed to actuate the liquid film by using the surface charges generated pyroelectrically under temperature variation. The configuration is electrode-less compared to standard electrowetting systems, thus improving the device flexibility and easiness of fabrication. The curvature of the liquid lenses has been characterized by interferometric techniques based on the evaluation of the phase map through digital holography. The results showing the evolution of the lens curvature with the temperature variation will be presented and discussed.

Microfluidic CODES: a scalable multiplexed electronic sensor for orthogonal detection of particles in microfluidic channels.

PubMed

Liu, Ruxiu; Wang, Ningquan; Kamili, Farhan; Sarioglu, A Fatih

2016-04-21

Numerous biophysical and biochemical assays rely on spatial manipulation of particles/cells as they are processed on lab-on-a-chip devices. Analysis of spatially distributed particles on these devices typically requires microscopy negating the cost and size advantages of microfluidic assays. In this paper, we introduce a scalable electronic sensor technology, called microfluidic CODES, that utilizes resistive pulse sensing to orthogonally detect particles in multiple microfluidic channels from a single electrical output. Combining the techniques from telecommunications and microfluidics, we route three coplanar electrodes on a glass substrate to create multiple Coulter counters producing distinct orthogonal digital codes when they detect particles. We specifically design a digital code set using the mathematical principles of Code Division Multiple Access (CDMA) telecommunication networks and can decode signals from different microfluidic channels with >90% accuracy through computation even if these signals overlap. As a proof of principle, we use this technology to detect human ovarian cancer cells in four different microfluidic channels fabricated using soft lithography. Microfluidic CODES offers a simple, all-electronic interface that is well suited to create integrated, low-cost lab-on-a-chip devices for cell- or particle-based assays in resource-limited settings.

Efficient processing of two-dimensional arrays with C or C++

USGS Publications Warehouse

Donato, David I.

2017-07-20

Because fast and efficient serial processing of raster-graphic images and other two-dimensional arrays is a requirement in land-change modeling and other applications, the effects of 10 factors on the runtimes for processing two-dimensional arrays with C and C++ are evaluated in a comparative factorial study. This study’s factors include the choice among three C or C++ source-code techniques for array processing; the choice of Microsoft Windows 7 or a Linux operating system; the choice of 4-byte or 8-byte array elements and indexes; and the choice of 32-bit or 64-bit memory addressing. This study demonstrates how programmer choices can reduce runtimes by 75 percent or more, even after compiler optimizations. Ten points of practical advice for faster processing of two-dimensional arrays are offered to C and C++ programmers. Further study and the development of a C and C++ software test suite are recommended.Key words: array processing, C, C++, compiler, computational speed, land-change modeling, raster-graphic image, two-dimensional array, software efficiency

NASA Tech Briefs, March 2008

NASA Technical Reports Server (NTRS)

2008-01-01

Topics covered include: WRATS Integrated Data Acquisition System; Breadboard Signal Processor for Arraying DSN Antennas; Digital Receiver Phase Meter; Split-Block Waveguide Polarization Twist for 220 to 325 GHz; Nano-Multiplication-Region Avalanche Photodiodes and Arrays; Tailored Asymmetry for Enhanced Coupling to WGM Resonators; Disabling CNT Electronic Devices by Use of Electron Beams; Conical Bearingless Motor/Generators; Integrated Force Method for Indeterminate Structures; Carbon-Nanotube-Based Electrodes for Biomedical Applications; Compact Directional Microwave Antenna for Localized Heating; Using Hyperspectral Imagery to Identify Turfgrass Stresses; Shaping Diffraction-Grating Grooves to Optimize Efficiency; Low-Light-Shift Cesium Fountain without Mechanical Shutters; Magnetic Compensation for Second-Order Doppler Shift in LITS; Nanostructures Exploit Hybrid-Polariton Resonances; Microfluidics, Chromatography, and Atomic-Force Microscopy; Model of Image Artifacts from Dust Particles; Pattern-Recognition System for Approaching a Known Target; Orchestrator Telemetry Processing Pipeline; Scheme for Quantum Computing Immune to Decoherence; Spin-Stabilized Microsatellites with Solar Concentrators; Phase Calibration of Antenna Arrays Aimed at Spacecraft; Ring Bus Architecture for a Solid-State Recorder; and Image Compression Algorithm Altered to Improve Stereo Ranging.

Advanced one-dimensional optical strain measurement system, phase 4

NASA Technical Reports Server (NTRS)

Lant, Christian T.

1992-01-01

An improved version of the speckle-shift strain measurement system was developed. The system uses a two-dimensional sensor array to maintain speckle correlation in the presence of large off-axis rigid body motions. A digital signal processor (DSP) is used to calculate strains at a rate near the RS-170 camera frame rate. Strain measurements were demonstrated on small diameter wires and fibers used in composite materials research. Accurate values of Young's modulus were measured on tungsten wires, and silicon carbide and sapphire fibers. This optical technique has measured surface strains at specimen temperatures above 750 C and has shown the potential for measurements at much higher temperatures.

Multispectral high-resolution hologram generation using orthographic projection images

NASA Astrophysics Data System (ADS)

Muniraj, I.; Guo, C.; Sheridan, J. T.

2016-08-01

We present a new method of synthesizing a digital hologram of three-dimensional (3D) real-world objects from multiple orthographic projection images (OPI). A high-resolution multiple perspectives of 3D objects (i.e., two dimensional elemental image array) are captured under incoherent white light using synthetic aperture integral imaging (SAII) technique and their OPIs are obtained respectively. The reference beam is then multiplied with the corresponding OPI and integrated to form a Fourier hologram. Eventually, a modified phase retrieval algorithm (GS/HIO) is applied to reconstruct the hologram. The principle is validated experimentally and the results support the feasibility of the proposed method.

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

PubMed

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

2016-06-20

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

A “dry and wet hybrid” lithography technique for multilevel replication templates: Applications to microfluidic neuron culture and two-phase global mixing

PubMed Central

Paul, Debjani; Saias, Laure; Pedinotti, Jean-Cedric; Chabert, Max; Magnifico, Sebastien; Pallandre, Antoine; De Lambert, Bertrand; Houdayer, Claude; Brugg, Bernard; Peyrin, Jean-Michel; Viovy, Jean-Louis

2011-01-01

A broad range of microfluidic applications, ranging from cell culture to protein crystallization, requires multilevel devices with different heights and feature sizes (from micrometers to millimeters). While state-of-the-art direct-writing techniques have been developed for creating complex three-dimensional shapes, replication molding from a multilevel template is still the preferred method for fast prototyping of microfluidic devices in the laboratory. Here, we report on a “dry and wet hybrid” technique to fabricate multilevel replication molds by combining SU-8 lithography with a dry film resist (Ordyl). We show that the two lithography protocols are chemically compatible with each other. Finally, we demonstrate the hybrid technique in two different microfluidic applications: (1) a neuron culture device with compartmentalization of different elements of a neuron and (2) a two-phase (gas-liquid) global micromixer for fast mixing of a small amount of a viscous liquid into a larger volume of a less viscous liquid. PMID:21559239

Composite x-ray image assembly for large-field digital mammography with one- and two-dimensional positioning of a focal plane array

NASA Technical Reports Server (NTRS)

Halama, G.; McAdoo, J.; Liu, H.

1998-01-01

To demonstrate the feasibility of a novel large-field digital mammography technique, a 1024 x 1024 pixel Loral charge-coupled device (CCD) focal plane array (FPA) was positioned in a mammographic field with one- and two-dimensional scan sequences to obtain 950 x 1800 pixel and 3600 x 3600 pixel composite images, respectively. These experiments verify that precise positioning of FPAs produced seamless composites and that the CCD mosaic concept has potential for high-resolution, large-field imaging. The proposed CCD mosaic concept resembles a checkerboard pattern with spacing left between the CCDs for the driver and readout electronics. To obtain a complete x-ray image, the mosaic must be repositioned four times, with an x-ray exposure at each position. To reduce the patient dose, a lead shield with appropriately patterned holes is placed between the x-ray source and the patient. The high-precision motorized translation stages and the fiber-coupled-scintillating-screen-CCD sensor assembly were placed in the position usually occupied by the film cassette. Because of the high mechanical precision, seamless composites were constructed from the subimages. This paper discusses the positioning, image alignment procedure, and composite image results. The paper only addresses the formation of a seamless composite image from subimages and will not consider the effects of the lead shield, multiple CCDs, or the speed of motion.

Pneumatic oscillator circuits for timing and control of integrated microfluidics.

PubMed

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

2013-11-05

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

Monodisperse alginate microgel formation in a three-dimensional microfluidic droplet generator.

PubMed

Lian, Meng; Collier, C Patrick; Doktycz, Mitchel J; Retterer, Scott T

2012-01-01

Droplet based microfluidic systems provide an ideal platform for partitioning and manipulating aqueous samples for analysis. Identifying stable operating conditions under which droplets are generated is challenging yet crucial for real-world applications. A novel three-dimensional microfluidic platform that facilitates the consistent generation and gelation of alginate-calcium hydrogel microbeads for microbial encapsulation, over a broad range of input pressures, in the absence of surfactants is described. The unique three-dimensional design of the fluidic network utilizes a height difference at the junction between the aqueous sample injection and organic carrier channels to induce droplet formation via a surface tension enhanced self-shearing mechanism. Combined within a flow-focusing geometry, under constant pressure control, this arrangement facilitates predictable generation of droplets over a much broader range of operating conditions than that of conventional two-dimensional systems. The impact of operating pressures and geometry on droplet gelation, aqueous and organic material flow rates, microbead size, and bead generation frequency are described. The system presented provides a robust platform for encapsulating single microbes in complex mixtures into individual hydrogel beads, and provides the foundation for the development of a complete system for sorting and analyzing microbes at the single cell level.

Monodisperse alginate microgel formation in a three-dimensional microfluidic droplet generator

PubMed Central

Lian, Meng; Collier, C. Patrick; Doktycz, Mitchel J.; Retterer, Scott T.

2012-01-01

Droplet based microfluidic systems provide an ideal platform for partitioning and manipulating aqueous samples for analysis. Identifying stable operating conditions under which droplets are generated is challenging yet crucial for real-world applications. A novel three-dimensional microfluidic platform that facilitates the consistent generation and gelation of alginate-calcium hydrogel microbeads for microbial encapsulation, over a broad range of input pressures, in the absence of surfactants is described. The unique three-dimensional design of the fluidic network utilizes a height difference at the junction between the aqueous sample injection and organic carrier channels to induce droplet formation via a surface tension enhanced self-shearing mechanism. Combined within a flow-focusing geometry, under constant pressure control, this arrangement facilitates predictable generation of droplets over a much broader range of operating conditions than that of conventional two-dimensional systems. The impact of operating pressures and geometry on droplet gelation, aqueous and organic material flow rates, microbead size, and bead generation frequency are described. The system presented provides a robust platform for encapsulating single microbes in complex mixtures into individual hydrogel beads, and provides the foundation for the development of a complete system for sorting and analyzing microbes at the single cell level. PMID:24198865

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.

Digital hydraulic drive for microfluidics and miniaturized cell culture devices based on shape memory alloy actuators

NASA Astrophysics Data System (ADS)

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

2018-08-01

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

Design and fabrication of chemically robust three-dimensional microfluidic valves.

PubMed

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

2007-09-01

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

Theoretical prediction of fast 3D AC electro-osmotic pumps.

PubMed

Bazant, Martin Z; Ben, Yuxing

2006-11-01

AC electro-osmotic (ACEO) pumps in microfluidics currently involve planar electrode arrays, but recent work on the underlying phenomenon of induced-charge electro-osmosis (ICEO) suggests that three-dimensional (3D) geometries may be exploited to achieve faster flows. In this paper, we present some new design principles for periodic 3D ACEO pumps, such as the "fluid conveyor belt" of ICEO flow over a stepped electrode array. Numerical simulations of these designs (using the standard low-voltage model) predict flow rates almost twenty times faster than existing planar ACEO pumps, for the same applied voltage and minimum feature size. These pumps may enable new portable or implantable lab-on-a-chip devices, since rather fast (mm s(-1)), tuneable flows should be attainable with battery voltages (<10 V).

Microfluidic systems for stem cell-based neural tissue engineering.

PubMed

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

2016-07-05

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

Mechanically activated artificial cell by using microfluidics

NASA Astrophysics Data System (ADS)

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

2016-09-01

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

Microfluidic converging/diverging channels optimised for homogeneous extensional deformation.

PubMed

Zografos, K; Pimenta, F; Alves, M A; Oliveira, M S N

2016-07-01

In this work, we optimise microfluidic converging/diverging geometries in order to produce constant strain-rates along the centreline of the flow, for performing studies under homogeneous extension. The design is examined for both two-dimensional and three-dimensional flows where the effects of aspect ratio and dimensionless contraction length are investigated. Initially, pressure driven flows of Newtonian fluids under creeping flow conditions are considered, which is a reasonable approximation in microfluidics, and the limits of the applicability of the design in terms of Reynolds numbers are investigated. The optimised geometry is then used for studying the flow of viscoelastic fluids and the practical limitations in terms of Weissenberg number are reported. Furthermore, the optimisation strategy is also applied for electro-osmotic driven flows, where the development of a plug-like velocity profile allows for a wider region of homogeneous extensional deformation in the flow field.

Microfluidic converging/diverging channels optimised for homogeneous extensional deformation

PubMed Central

Zografos, K.; Oliveira, M. S. N.

2016-01-01

In this work, we optimise microfluidic converging/diverging geometries in order to produce constant strain-rates along the centreline of the flow, for performing studies under homogeneous extension. The design is examined for both two-dimensional and three-dimensional flows where the effects of aspect ratio and dimensionless contraction length are investigated. Initially, pressure driven flows of Newtonian fluids under creeping flow conditions are considered, which is a reasonable approximation in microfluidics, and the limits of the applicability of the design in terms of Reynolds numbers are investigated. The optimised geometry is then used for studying the flow of viscoelastic fluids and the practical limitations in terms of Weissenberg number are reported. Furthermore, the optimisation strategy is also applied for electro-osmotic driven flows, where the development of a plug-like velocity profile allows for a wider region of homogeneous extensional deformation in the flow field. PMID:27478523

Floating Droplet Array: An Ultrahigh-Throughput Device for Droplet Trapping, Real-time Analysis and Recovery

PubMed Central

Labanieh, Louai; Nguyen, Thi N.; Zhao, Weian; Kang, Dong-Ku

2016-01-01

We describe the design, fabrication and use of a dual-layered microfluidic device for ultrahigh-throughput droplet trapping, analysis, and recovery using droplet buoyancy. To demonstrate the utility of this device for digital quantification of analytes, we quantify the number of droplets, which contain a β-galactosidase-conjugated bead among more than 100,000 immobilized droplets. In addition, we demonstrate that this device can be used for droplet clustering and real-time analysis by clustering several droplets together into microwells and monitoring diffusion of fluorescein, a product of the enzymatic reaction of β-galactosidase and its fluorogenic substrate FDG, between droplets. PMID:27134760

Vertical viewing angle enhancement for the 360  degree integral-floating display using an anamorphic optic system.

PubMed

Erdenebat, Munkh-Uchral; Kwon, Ki-Chul; Yoo, Kwan-Hee; Baasantseren, Ganbat; Park, Jae-Hyeung; Kim, Eun-Soo; Kim, Nam

2014-04-15

We propose a 360 degree integral-floating display with an enhanced vertical viewing angle. The system projects two-dimensional elemental image arrays via a high-speed digital micromirror device projector and reconstructs them into 3D perspectives with a lens array. Double floating lenses relate initial 3D perspectives to the center of a vertically curved convex mirror. The anamorphic optic system tailors the initial 3D perspectives horizontally and vertically disperse light rays more widely. By the proposed method, the entire 3D image provides both monocular and binocular depth cues, a full-parallax demonstration with high-angular ray density and an enhanced vertical viewing angle.

Tomographic and analog 3-D simulations using NORA. [Non-Overlapping Redundant Image Array formed by multiple pinholes

NASA Technical Reports Server (NTRS)

Yin, L. I.; Trombka, J. I.; Bielefeld, M. J.; Seltzer, S. M.

1984-01-01

The results of two computer simulations demonstrate the feasibility of using the nonoverlapping redundant array (NORA) to form three-dimensional images of objects with X-rays. Pinholes admit the X-rays to nonoverlapping points on a detector. The object is reconstructed in the analog mode by optical correlation and in the digital mode by tomographic computations. Trials were run with a stick-figure pyramid and extended objects with out-of-focus backgrounds. Substitution of spherical optical lenses for the pinholes increased the light transmission sufficiently that objects could be easily viewed in a dark room. Out-of-focus aberrations in tomographic reconstruction could be eliminated using Chang's (1976) algorithm.

Automated electrotransformation of Escherichia coli on a digital microfluidic platform using bioactivated magnetic beads.

PubMed

Moore, J A; Nemat-Gorgani, M; Madison, A C; Sandahl, M A; Punnamaraju, S; Eckhardt, A E; Pollack, M G; Vigneault, F; Church, G M; Fair, R B; Horowitz, M A; Griffin, P B

2017-01-01

This paper reports on the use of a digital microfluidic platform to perform multiplex automated genetic engineering (MAGE) cycles on droplets containing Escherichia coli cells. Bioactivated magnetic beads were employed for cell binding, washing, and media exchange in the preparation of electrocompetent cells in the electrowetting-on-dieletric (EWoD) platform. On-cartridge electroporation was used to deliver oligonucleotides into the cells. In addition to the optimization of a magnetic bead-based benchtop protocol for generating and transforming electrocompetent E. coli cells, we report on the implementation of this protocol in a fully automated digital microfluidic platform. Bead-based media exchange and electroporation pulse conditions were optimized on benchtop for transformation frequency to provide initial parameters for microfluidic device trials. Benchtop experiments comparing electrotransformation of free and bead-bound cells are presented. Our results suggest that dielectric shielding intrinsic to bead-bound cells significantly reduces electroporation field exposure efficiency. However, high transformation frequency can be maintained in the presence of magnetic beads through the application of more intense electroporation pulses. As a proof of concept, MAGE cycles were successfully performed on a commercial EWoD cartridge using variations of the optimal magnetic bead-based preparation procedure and pulse conditions determined by the benchtop results. Transformation frequencies up to 22% were achieved on benchtop; this frequency was matched within 1% (21%) by MAGE cycles on the microfluidic device. However, typical frequencies on the device remain lower, averaging 9% with a standard deviation of 9%. The presented results demonstrate the potential of digital microfluidics to perform complex and automated genetic engineering protocols.

Automated electrotransformation of Escherichia coli on a digital microfluidic platform using bioactivated magnetic beads

PubMed Central

Moore, J. A.; Nemat-Gorgani, M.; Madison, A. C.; Punnamaraju, S.; Eckhardt, A. E.; Pollack, M. G.; Church, G. M.; Fair, R. B.; Horowitz, M. A.; Griffin, P. B.

2017-01-01

This paper reports on the use of a digital microfluidic platform to perform multiplex automated genetic engineering (MAGE) cycles on droplets containing Escherichia coli cells. Bioactivated magnetic beads were employed for cell binding, washing, and media exchange in the preparation of electrocompetent cells in the electrowetting-on-dieletric (EWoD) platform. On-cartridge electroporation was used to deliver oligonucleotides into the cells. In addition to the optimization of a magnetic bead-based benchtop protocol for generating and transforming electrocompetent E. coli cells, we report on the implementation of this protocol in a fully automated digital microfluidic platform. Bead-based media exchange and electroporation pulse conditions were optimized on benchtop for transformation frequency to provide initial parameters for microfluidic device trials. Benchtop experiments comparing electrotransformation of free and bead-bound cells are presented. Our results suggest that dielectric shielding intrinsic to bead-bound cells significantly reduces electroporation field exposure efficiency. However, high transformation frequency can be maintained in the presence of magnetic beads through the application of more intense electroporation pulses. As a proof of concept, MAGE cycles were successfully performed on a commercial EWoD cartridge using variations of the optimal magnetic bead-based preparation procedure and pulse conditions determined by the benchtop results. Transformation frequencies up to 22% were achieved on benchtop; this frequency was matched within 1% (21%) by MAGE cycles on the microfluidic device. However, typical frequencies on the device remain lower, averaging 9% with a standard deviation of 9%. The presented results demonstrate the potential of digital microfluidics to perform complex and automated genetic engineering protocols. PMID:28191268

Volumetric Stress-Strain Analysis of Optohydrodynamically Suspended Biological Cells

PubMed Central

Liang, Yu; Saha, Asit K.

2011-01-01

Ongoing investigations are exploring the biomechanical properties of isolated and suspended biological cells in pursuit of understanding single-cell mechanobiology. An optical tweezer with minimal applied laser power has positioned biologic cells at the geometric center of a microfluidic cross-junction, creating a novel optohydrodynamic trap. The resulting fluid flow environment facilitates unique multiaxial loading of single cells with site-specific normal and shear stresses resulting in a physical albeit extensional state. A recent two-dimensional analysis has explored the cytoskeletal strain response due to these fluid-induced stresses [Wilson and Kohles, 2010, “Two-Dimensional Modeling of Nanomechanical Stresses-Strains in Healthy and Diseased Single-Cells During Microfluidic Manipulation,” J Nanotechnol Eng Med, 1(2), p. 021005]. Results described a microfluidic environment having controlled nanometer and piconewton resolution. In this present study, computational fluid dynamics combined with multiphysics modeling has further characterized the applied fluid stress environment and the solid cellular strain response in three dimensions to accompany experimental cell stimulation. A volumetric stress-strain analysis was applied to representative living cell biomechanical data. The presented normal and shear stress surface maps will guide future microfluidic experiments as well as provide a framework for characterizing cytoskeletal structure influencing the stress to strain response. PMID:21186894

Microalga propels along vorticity direction in a shear flow

NASA Astrophysics Data System (ADS)

Chengala, Anwar; Hondzo, Miki; Sheng, Jian

2013-05-01

Using high-speed digital holographic microscopy and microfluidics, we discover that, when encountering fluid flow shear above a threshold, unicellular green alga Dunaliella primolecta migrates unambiguously in the cross-stream direction that is normal to the plane of shear and coincides with the local fluid flow vorticity. The flow shear drives motile microalgae to collectively migrate in a thin two-dimensional horizontal plane and consequently alters the spatial distribution of microalgal cells within a given suspension. This shear-induced algal migration differs substantially from periodic rotational motion of passive ellipsoids, known as Jeffery orbits, as well as gyrotaxis by bottom-heavy swimming microalgae in a shear flow due to the subtle interplay between torques generated by gravity and viscous shear. Our findings could facilitate mechanistic solutions for modeling planktonic thin layers and sustainable cultivation of microalgae for human nutrition and bioenergy feedstock.

Design, fabrication and characterization of an arrayable all-polymer microfluidic valve employing highly magnetic rare-earth composite polymer

NASA Astrophysics Data System (ADS)

Rahbar, Mona; Shannon, Lesley; Gray, Bonnie L.

2016-05-01

We present a new magnetically actuated microfluidic valve that employs a highly magnetic composite polymer (M-CP) containing rare-earth hard-magnetic powder for its actuating element and for its valve seat. The M-CP offers much higher magnetization compared to the soft-magnetic, ferrite-based composite polymers typically used in microfluidic applications. Each valve consists of a permanently magnetized M-CP flap and valve seat mounted on a microfluidic channel system fabricated in poly(dimethylsiloxane) (PDMS). Each valve is actuated under a relatively small external magnetic field of 80 mT provided by a small permanent magnet mounted on a miniature linear actuator. The performance of the valve with different flap thicknesses is characterized. In addition, the effect of the magnetic valve seat on the valve’s performance is also characterized. It is experimentally shown that a valve with a 2.3 mm flap thickness, actuated under an 80 mT magnetic field, is capable of completely blocking liquid flow at a flow rate of 1 ml min-1 for pressures up to 9.65 kPa in microfluidic channels 200 μm wide and 200 μm deep. The valve can also be fabricated into an array for flow switching between multiple microfluidic channels under continuous flow conditions. The performance of arrays of valves for flow routing is demonstrated for flow rates up to 5 ml min-1 with larger microfluidic channels of up to 1 mm wide and 500 μm deep. The design of the valves is compatible with other commonly used polymeric microfluidic components, as well as other components that use the same novel permanently magnetic composite polymer, such as our previously reported cilia-based mixing devices.

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

PubMed

Shin, Sungchul; Hyun, Jinho

2017-08-09

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

Stretchable Complementary Split Ring Resonator (CSRR)-Based Radio Frequency (RF) Sensor for Strain Direction and Level Detection

PubMed Central

Eom, Seunghyun; Lim, Sungjoon

2016-01-01

In this paper, we proposed a stretchable radio frequency (RF) sensor to detect strain direction and level. The stretchable sensor is composed of two complementary split ring resonators (CSRR) with microfluidic channels. In order to achieve stretchability, liquid metal (eutectic gallium-indium, EGaIn) and Ecoflex substrate are used. Microfluidic channels are built by Ecoflex elastomer and microfluidic channel frames. A three-dimensional (3D) printer is used for fabrication of microfluidic channel frames. Two CSRR resonators are designed to resonate 2.03 GHz and 3.68 GHz. When the proposed sensor is stretched from 0 to 8 mm along the +x direction, the resonant frequency is shifted from 3.68 GHz to 3.13 GHz. When the proposed sensor is stretched from 0 to 8 mm along the −x direction, the resonant frequency is shifted from 2.03 GHz to 1.78 GHz. Therefore, we can detect stretched length and direction from independent variation of two resonant frequencies. PMID:27727173

Ultrahigh density alignment of carbon nanotube arrays by dielectrophoresis.

PubMed

Shekhar, Shashank; Stokes, Paul; Khondaker, Saiful I

2011-03-22

We report ultrahigh density assembly of aligned single-walled carbon nanotube (SWNT) two-dimensional arrays via AC dielectrophoresis using high-quality surfactant-free and stable SWNT solutions. After optimization of frequency and trapping time, we can reproducibly control the linear density of the SWNT between prefabricated electrodes from 0.5 SWNT/μm to more than 30 SWNT/μm by tuning the concentration of the nanotubes in the solution. Our maximum density of 30 SWNT/μm is the highest for aligned arrays via any solution processing technique reported so far. Further increase of SWNT concentration results in a dense array with multiple layers. We discuss how the orientation and density of the nanotubes vary with concentrations and channel lengths. Electrical measurement data show that the densely packed aligned arrays have low sheet resistances. Selective removal of metallic SWNTs via controlled electrical breakdown produced field-effect transistors with high current on-off ratio. Ultrahigh density alignment reported here will have important implications in fabricating high-quality devices for digital and analog electronics.

Collective oscillations and coupled modes in confined microfluidic droplet arrays

NASA Astrophysics Data System (ADS)

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

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

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

PubMed Central

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

2011-01-01

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

Universal lab on a smartphone: a research of TiOPc thin film as a light dependence electrode

NASA Astrophysics Data System (ADS)

Lin, PoHan; Hsu, Y. H.; Lee, C. K.

2014-02-01

In this paper, we study the photoconductivity of a polymer-based TiOPc (Titanium Oxide Phthalocyanine) thin-film for the development of a multi-opto-piezoelectric-valve-array. Using a polymer-based TiOPc thin film to serve as the electrode and a structural layer of a piezoelectric polymer, P(VDF-TrFE) poly[(vinylidenefluoride-co-trifluoroethylene], an optical control valve-array could be developed for manipulating multiple microdroplets for the application of digital microfluidic. In this ongoing project, the dependency of the light intensity, thickness, and composition of spin-coated polymer-based TiOPc thin-film was studied. The experimental finding suggested that a 14 to 55 times resistivity change could be achieved by controlling the film thickness to be between 0.9 μm and 1.5 μm with TiOPc concentration of 20% and 30% w/w compositions.

A microfluidic chip containing multiple 3D nanofibrous scaffolds for culturing human pluripotent stem cells

NASA Astrophysics Data System (ADS)

Wertheim, Lior; Shapira, Assaf; Amir, Roey J.; Dvir, Tal

2018-04-01

In microfluidics-based lab-on-a-chip systems, which are used for investigating the effect of drugs and growth factors on cells, the latter are usually cultured within the device’s channels in two-dimensional, and not in their optimal three-dimensional (3D) microenvironment. Herein, we address this shortfall by designing a microfluidic system, comprised of two layers. The upper layer of the system consists of multiple channels generating a gradient of soluble factors. The lower layer is comprised of multiple wells, each deposited with 3D, nanofibrous scaffold. We first used a mathematical model to characterize the fluid flow within the system. We then show that induced pluripotent stem cells can be seeded within the 3D scaffolds and be exposed to a well-mixed gradient of soluble factors. We believe that utilizing such system may enable in the future to identify new differentiation factors, investigate drug toxicity, and eventually allow to perform analyses on patient-specific tissues, in order to fit the appropriate combination and concentration of drugs.

Additive manufacturing of three-dimensional (3D) microfluidic-based microelectromechanical systems (MEMS) for acoustofluidic applications.

PubMed

Cesewski, Ellen; Haring, Alexander P; Tong, Yuxin; Singh, Manjot; Thakur, Rajan; Laheri, Sahil; Read, Kaitlin A; Powell, Michael D; Oestreich, Kenneth J; Johnson, Blake N

2018-06-13

Three-dimensional (3D) printing now enables the fabrication of 3D structural electronics and microfluidics. Further, conventional subtractive manufacturing processes for microelectromechanical systems (MEMS) relatively limit device structure to two dimensions and require post-processing steps for interface with microfluidics. Thus, the objective of this work is to create an additive manufacturing approach for fabrication of 3D microfluidic-based MEMS devices that enables 3D configurations of electromechanical systems and simultaneous integration of microfluidics. Here, we demonstrate the ability to fabricate microfluidic-based acoustofluidic devices that contain orthogonal out-of-plane piezoelectric sensors and actuators using additive manufacturing. The devices were fabricated using a microextrusion 3D printing system that contained integrated pick-and-place functionality. Additively assembled materials and components included 3D printed epoxy, polydimethylsiloxane (PDMS), silver nanoparticles, and eutectic gallium-indium as well as robotically embedded piezoelectric chips (lead zirconate titanate (PZT)). Electrical impedance spectroscopy and finite element modeling studies showed the embedded PZT chips exhibited multiple resonant modes of varying mode shape over the 0-20 MHz frequency range. Flow visualization studies using neutrally buoyant particles (diameter = 0.8-70 μm) confirmed the 3D printed devices generated bulk acoustic waves (BAWs) capable of size-selective manipulation, trapping, and separation of suspended particles in droplets and microchannels. Flow visualization studies in a continuous flow format showed suspended particles could be moved toward or away from the walls of microfluidic channels based on selective actuation of in-plane or out-of-plane PZT chips. This work suggests additive manufacturing potentially provides new opportunities for the design and fabrication of acoustofluidic and microfluidic devices.

Digitized molecular diagnostics: reading disk-based bioassays with standard computer drives.

PubMed

Li, Yunchao; Ou, Lily M L; Yu, Hua-Zhong

2008-11-01

We report herein a digital signal readout protocol for screening disk-based bioassays with standard optical drives of ordinary desktop/notebook computers. Three different types of biochemical recognition reactions (biotin-streptavidin binding, DNA hybridization, and protein-protein interaction) were performed directly on a compact disk in a line array format with the help of microfluidic channel plates. Being well-correlated with the optical darkness of the binding sites (after signal enhancement by gold nanoparticle-promoted autometallography), the reading error levels of prerecorded audio files can serve as a quantitative measure of biochemical interaction. This novel readout protocol is about 1 order of magnitude more sensitive than fluorescence labeling/scanning and has the capability of examining multiplex microassays on the same disk. Because no modification to either hardware or software is needed, it promises a platform technology for rapid, low-cost, and high-throughput point-of-care biomedical diagnostics.

Isothermal circular-strand-displacement polymerization of DNA and microRNA in digital microfluidic devices.

PubMed

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

2015-02-01

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

A poly(dimethylsiloxane) microfluidic sheet reversibly adhered on a glass plate for creation of emulsion droplets for droplet digital PCR.

PubMed

Nakashoji, Yuta; Tanaka, Hironari; Tsukagoshi, Kazuhiko; Hashimoto, Masahiko

2017-01-01

A PDMS microfluidic chip with T-junction channel geometry, two inlet reservoirs, and one outlet reservoir was reversibly adhered on a glass plate through the viscoelastic properties of PDMS. This formed a detachable microfluidic device for creation of water-in-oil emulsion droplets that were used as discrete reaction compartments for the droplet digital PCR. The PDMS/glass device could continuously produce monodisperse droplets without leakage of fluids using a vacuum-driven autonomous micropumping method. This droplet preparation technique only required evacuation of air dissolved in the PDMS before loading of oil and aqueous phases into separate inlet reservoirs. Degassing of the PDMS chip at approximately 300 Pa for 1.5 h in a vacuum desiccator gave 40 000 droplets in 80 min, which corresponded to a generation frequency of up to nine droplets per second. Over multiple runs the droplet creation was very reproducible, and the size reproducibility of generated droplets (polydispersity of up to 4.1%) was comparable to that acquired using other microfluidic droplet preparation techniques. Because the PDMS chip can be peeled off the glass plate, blocked channels can easily be fixed when they arise, and this extends the lifetime of the chip. Single DNA molecules partitioned into the droplets were successfully amplified by PCR. In addition, the droplet digital PCR platform allowed absolute quantification of low copy numbers of target DNA, and was robust against instrumental variance. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Dehydration induced phase transitions in a microfluidic droplet array for the separation of biomolecules

NASA Astrophysics Data System (ADS)

Nelson, Chris; Anna, Shelley

2013-11-01

Droplet-based strategies for fluid manipulation have seen significant application in microfluidics due to their ability to compartmentalize solutions and facilitate highly parallelized reactions. Functioning as micro-scale reaction vessels, droplets have been used to study protein crystallization, enzyme kinetics, and to encapsulate whole cells. Recently, the mass transport out of droplets has been used to concentrate solutions and induce phase transitions. Here, we show that droplets trapped in a microfluidic array will spontaneously dehydrate over the course of several hours. By loading these devices with an initially dilute aqueous polymer solution, we use this slow dehydration to observe phase transitions and the evolution of droplet morphology in hundreds of droplets simultaneously. As an example, we trap and dehydrate droplets of a model aqueous two-phase system consisting of polyethylene glycol and dextran. Initially the drops are homogenous, then after some time the polymer concentration reaches a critical point and two phases form. As water continues to leave the system, the drops transition from a microemulsion of DEX in PEG to a core-shell configuration. Eventually, changes in interfacial tension, driven by dehydration, cause the DEX core to completely de-wet from the PEG shell. Since aqueous two phase systems are able to selectively separate a variety of biomolecules, this core shedding behavior has the potential to provide selective, on-chip separation and concentration.

Theory and design of compact hybrid microphone arrays on two-dimensional planes for three-dimensional soundfield analysis.

PubMed

Chen, Hanchi; Abhayapala, Thushara D; Zhang, Wen

2015-11-01

Soundfield analysis based on spherical harmonic decomposition has been widely used in various applications; however, a drawback is the three-dimensional geometry of the microphone arrays. In this paper, a method to design two-dimensional planar microphone arrays that are capable of capturing three-dimensional (3D) spatial soundfields is proposed. Through the utilization of both omni-directional and first order microphones, the proposed microphone array is capable of measuring soundfield components that are undetectable to conventional planar omni-directional microphone arrays, thus providing the same functionality as 3D arrays designed for the same purpose. Simulations show that the accuracy of the planar microphone array is comparable to traditional spherical microphone arrays. Due to its compact shape, the proposed microphone array greatly increases the feasibility of 3D soundfield analysis techniques in real-world applications.

Microfluidic perfusion culture.

PubMed

Hattori, Koji; Sugiura, Shinji; Kanamori, Toshiyuki

2014-01-01

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

Microfluidic device for the assembly and transport of microparticles

DOEpatents

James, Conrad D [Albuquerque, NM; Kumar, Anil [Framingham, MA; Khusid, Boris [New Providence, NJ; Acrivos, Andreas [Stanford, CA

2010-06-29

A microfluidic device comprising independently addressable arrays of interdigitated electrodes can be used to assembly and transport large-scale microparticle structures. The device and method uses collective phenomena in a negatively polarized suspension exposed to a high-gradient strong ac electric field to assemble the particles into predetermined locations and then transport them collectively to a work area for final assembly by sequentially energizing the electrode arrays.

DNA assembly with error correction on a droplet digital microfluidics platform.

PubMed

Khilko, Yuliya; Weyman, Philip D; Glass, John I; Adams, Mark D; McNeil, Melanie A; Griffin, Peter B

2018-06-01

Custom synthesized DNA is in high demand for synthetic biology applications. However, current technologies to produce these sequences using assembly from DNA oligonucleotides are costly and labor-intensive. The automation and reduced sample volumes afforded by microfluidic technologies could significantly decrease materials and labor costs associated with DNA synthesis. The purpose of this study was to develop a gene assembly protocol utilizing a digital microfluidic device. Toward this goal, we adapted bench-scale oligonucleotide assembly methods followed by enzymatic error correction to the Mondrian™ digital microfluidic platform. We optimized Gibson assembly, polymerase chain reaction (PCR), and enzymatic error correction reactions in a single protocol to assemble 12 oligonucleotides into a 339-bp double- stranded DNA sequence encoding part of the human influenza virus hemagglutinin (HA) gene. The reactions were scaled down to 0.6-1.2 μL. Initial microfluidic assembly methods were successful and had an error frequency of approximately 4 errors/kb with errors originating from the original oligonucleotide synthesis. Relative to conventional benchtop procedures, PCR optimization required additional amounts of MgCl 2 , Phusion polymerase, and PEG 8000 to achieve amplification of the assembly and error correction products. After one round of error correction, error frequency was reduced to an average of 1.8 errors kb - 1 . We demonstrated that DNA assembly from oligonucleotides and error correction could be completely automated on a digital microfluidic (DMF) platform. The results demonstrate that enzymatic reactions in droplets show a strong dependence on surface interactions, and successful on-chip implementation required supplementation with surfactants, molecular crowding agents, and an excess of enzyme. Enzymatic error correction of assembled fragments improved sequence fidelity by 2-fold, which was a significant improvement but somewhat lower than expected compared to bench-top assays, suggesting an additional capacity for optimization.

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

PubMed

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

2016-02-01

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

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

PubMed

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

2013-12-21

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

Volumetric display containing multiple two-dimensional color motion pictures

NASA Astrophysics Data System (ADS)

Hirayama, R.; Shiraki, A.; Nakayama, H.; Kakue, T.; Shimobaba, T.; Ito, T.

2014-06-01

We have developed an algorithm which can record multiple two-dimensional (2-D) gradated projection patterns in a single three-dimensional (3-D) object. Each recorded pattern has the individual projected direction and can only be seen from the direction. The proposed algorithm has two important features: the number of recorded patterns is theoretically infinite and no meaningful pattern can be seen outside of the projected directions. In this paper, we expanded the algorithm to record multiple 2-D projection patterns in color. There are two popular ways of color mixing: additive one and subtractive one. Additive color mixing used to mix light is based on RGB colors and subtractive color mixing used to mix inks is based on CMY colors. We made two coloring methods based on the additive mixing and subtractive mixing. We performed numerical simulations of the coloring methods, and confirmed their effectiveness. We also fabricated two types of volumetric display and applied the proposed algorithm to them. One is a cubic displays constructed by light-emitting diodes (LEDs) in 8×8×8 array. Lighting patterns of LEDs are controlled by a microcomputer board. The other one is made of 7×7 array of threads. Each thread is illuminated by a projector connected with PC. As a result of the implementation, we succeeded in recording multiple 2-D color motion pictures in the volumetric displays. Our algorithm can be applied to digital signage, media art and so forth.

Rapid Protein Separations in Microfluidic Devices

NASA Technical Reports Server (NTRS)

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

2004-01-01

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

Method for Enhancing a Three Dimensional Image from a Plurality of Frames of Flash LIDAR Data

NASA Technical Reports Server (NTRS)

Bulyshev, Alexander (Inventor); Vanek, Michael D. (Inventor); Amzajerdian, Farzin (Inventor)

2013-01-01

A method for enhancing a three dimensional image from frames of flash LIDAR data includes generating a first distance R(sub i) from a first detector i to a first point on a surface S(sub i). After defining a map with a mesh theta having cells k, a first array S(k), a second array M(k), and a third array D(k) are initialized. The first array corresponds to the surface, the second array corresponds to the elevation map, and the third array D(k) receives an output for the DEM. The surface is projected onto the mesh theta, so that a second distance R(sub k) from a second point on the mesh theta to the detector can be found. From this, a height may be calculated, which permits the generation of a digital elevation map. Also, using sequential frames of flash LIDAR data, vehicle control is possible using an offset between successive frames.

Coaxial microreactor for particle synthesis

DOEpatents

Bartsch, Michael; Kanouff, Michael P; Ferko, Scott M; Crocker, Robert W; Wally, Karl

2013-10-22

A coaxial fluid flow microreactor system disposed on a microfluidic chip utilizing laminar flow for synthesizing particles from solution. Flow geometries produced by the mixing system make use of hydrodynamic focusing to confine a core flow to a small axially-symmetric, centrally positioned and spatially well-defined portion of a flow channel cross-section to provide highly uniform diffusional mixing between a reactant core and sheath flow streams. The microreactor is fabricated in such a way that a substantially planar two-dimensional arrangement of microfluidic channels will produce a three-dimensional core/sheath flow geometry. The microreactor system can comprise one or more coaxial mixing stages that can be arranged singly, in series, in parallel or nested concentrically in parallel.

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.

Deformable cells in confined geometries: From hemolysis to hydrodynamic interactions

NASA Astrophysics Data System (ADS)

Abkarian, Manouk; Faivre, Magalie; Stone, Howard A.

2004-11-01

Recent developments in microfluidics allow a wide range of possibilities for studying cellular-scale hydrodynamics. Here we use microfluidic technology to address several open questions in the blood flow literature where cell deformation and hydrodynamic interactions are significant. In particular, we investigate the pressure-driven flow of a dilute suspension in a channel and characterize the transition from steady axisymmetric cell shapes (for which numerical calculations exist) to asymmetric, highly extended shapes, which are precursors to hemolysis (i.e. destruction of the cell). In addition, we examine the influence of geometry on hydrodynamic interactions of deformable cells by contrasting one-dimensional motion of a train of particles in a channel with two-dimensional motions in a Hele-Shaw cell. This study can help to understand flow of cells in microcirculation from the unidirectional flow in capillaries to the two-dimensional flow in the lung alveoli and provides the basic steps to understand certain aspects of microcirculatory deseases like sickle cell anemia for example.

A microfluidic platform for 3-dimensional cell culture and cell-based assays.

PubMed

Kim, Minseok S; Yeon, Ju Hun; Park, Je-Kyun

2007-02-01

This paper reports a novel microfluidic platform introducing peptide hydrogel to make biocompatible microenvironment as well as realizing in situ cell-based assays. Collagen composite, OPLA and Puramatrix scaffolds are compared to select good environment for human hepatocellular carcinoma cells (HepG2) by albumin measurement. The selected biocompatible self-assembling peptide hydrogel, Puramatrix, is hydrodynamically focused in the middle of main channel of a microfluidic device, and at the same time the cells are 3-dimensionally immobilized and encapsulated without any additional surface treatment. HepG2 cells have been 3-dimensionally cultured in a poly(dimethylsiloxane) (PDMS) microfluidic device for 4 days. The cells cultured in micro peptide scaffold are compared with those cultured by conventional petri dish in morphology and the rate of albumin secretion. By injection of different reagents into either side of the peptide scaffold, the microfluidic device also forms a linear concentration gradient profile across the peptide scaffold due to molecular diffusion. Based on this characteristic, toxicity tests are performed by Triton X-100. As the higher toxicant concentration gradient forms, the wider dead zone of cells in the peptide scaffold represents. This microfluidic platform facilitates in vivo-like 3-dimensional microenvironment, and have a potential for the applications of reliable cell-based screening and assays including cytotoxicity test, real-time cell viability monitoring, and continuous dose-response assay.

On-chip clearing of arrays of 3-D cell cultures and micro-tissues.

PubMed

Grist, S M; Nasseri, S S; Poon, T; Roskelley, C; Cheung, K C

2016-07-01

Three-dimensional (3-D) cell cultures are beneficial models for mimicking the complexities of in vivo tissues, especially in tumour studies where transport limitations can complicate response to cancer drugs. 3-D optical microscopy techniques are less involved than traditional embedding and sectioning, but are impeded by optical scattering properties of the tissues. Confocal and even two-photon microscopy limit sample imaging to approximately 100-200 μm depth, which is insufficient to image hypoxic spheroid cores. Optical clearing methods have permitted high-depth imaging of tissues without physical sectioning, but they are difficult to implement for smaller 3-D cultures due to sample loss in solution exchange. In this work, we demonstrate a microfluidic platform for high-throughput on-chip optical clearing of breast cancer spheroids using the SeeDB, Clear(T2), and ScaleSQ clearing methods. Although all three methods are able to effectively clear the spheroids, we find that SeeDB and ScaleSQ more effectively clear the sample than Clear(T2); however, SeeDB induces green autofluorescence while ScaleS causes sample expansion. Our unique on-chip implementation permits clearing arrays of 3-D cultures using perfusion while monitoring the 3-D cultures throughout the process, enabling visualization of the clearing endpoint as well as monitoring of transient changes that could induce image artefacts. Our microfluidic device is compatible with on-chip 3-D cell culture, permitting the use of on-chip clearing at the endpoint after monitoring the same spheroids during their culture. This on-chip method has the potential to improve readout from 3-D cultures, facilitating their use in cell-based assays for high-content drug screening and other applications.

Wavelet compression techniques for hyperspectral data

NASA Technical Reports Server (NTRS)

Evans, Bruce; Ringer, Brian; Yeates, Mathew

1994-01-01

Hyperspectral sensors are electro-optic sensors which typically operate in visible and near infrared bands. Their characteristic property is the ability to resolve a relatively large number (i.e., tens to hundreds) of contiguous spectral bands to produce a detailed profile of the electromagnetic spectrum. In contrast, multispectral sensors measure relatively few non-contiguous spectral bands. Like multispectral sensors, hyperspectral sensors are often also imaging sensors, measuring spectra over an array of spatial resolution cells. The data produced may thus be viewed as a three dimensional array of samples in which two dimensions correspond to spatial position and the third to wavelength. Because they multiply the already large storage/transmission bandwidth requirements of conventional digital images, hyperspectral sensors generate formidable torrents of data. Their fine spectral resolution typically results in high redundancy in the spectral dimension, so that hyperspectral data sets are excellent candidates for compression. Although there have been a number of studies of compression algorithms for multispectral data, we are not aware of any published results for hyperspectral data. Three algorithms for hyperspectral data compression are compared. They were selected as representatives of three major approaches for extending conventional lossy image compression techniques to hyperspectral data. The simplest approach treats the data as an ensemble of images and compresses each image independently, ignoring the correlation between spectral bands. The second approach transforms the data to decorrelate the spectral bands, and then compresses the transformed data as a set of independent images. The third approach directly generalizes two-dimensional transform coding by applying a three-dimensional transform as part of the usual transform-quantize-entropy code procedure. The algorithms studied all use the discrete wavelet transform. In the first two cases, a wavelet transform coder was used for the two-dimensional compression. The third case used a three dimensional extension of this same algorithm.

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

NASA Astrophysics Data System (ADS)

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

2014-09-01

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

Production of arrays of chemically distinct nanolitre plugs via repeated splitting in microfluidic devices.

PubMed

Adamson, David N; Mustafi, Debarshi; Zhang, John X J; Zheng, Bo; Ismagilov, Rustem F

2006-09-01

This paper reports a method for the production of arrays of nanolitre plugs with distinct chemical compositions. One of the primary constraints on the use of plug-based microfluidics for large scale biological screening is the difficulty of fabricating arrays of chemically distinct plugs on the nanolitre scale. Here, using microfluidic devices with several T-junctions linked in series, a single input array of large (approximately 320 nL) plugs was split to produce 16 output arrays of smaller (approximately 20 nL) plugs; the composition and configuration of these arrays were identical to that of the input. This paper shows how the passive break-up of plugs in T-junction microchannel geometries can be used to produce a set of smaller-volume output arrays useful for chemical screening from a single large-volume array. A simple theoretical description is presented to describe splitting as a function of the Capillary number, the capillary pressure, the total pressure difference across the channel, and the geometric fluidic resistance. By accounting for these considerations, plug coalescence and plug-plug contamination can be eliminated from the splitting process and the symmetry of splitting can be preserved. Furthermore, single-outlet splitting devices were implemented with both valve- and volume-based methods for coordinating the release of output arrays. Arrays of plugs containing commercial sparse matrix screens were obtained from the presented splitting method and these arrays were used in protein crystallization trials. The techniques presented in this paper may facilitate the implementation of high-throughput chemical and biological screening.

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

ERIC Educational Resources Information Center

King, Travis L.

2009-01-01

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

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

PubMed

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

2018-05-08

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

Multiplex newborn screening for Pompe, Fabry, Hunter, Gaucher, and Hurler diseases using a digital microfluidic platform.

PubMed

Sista, Ramakrishna S; Wang, Tong; Wu, Ning; Graham, Carrie; Eckhardt, Allen; Winger, Theodore; Srinivasan, Vijay; Bali, Deeksha; Millington, David S; Pamula, Vamsee K

2013-09-23

New therapies for lysosomal storage diseases (LSDs) have generated interest in screening newborns for these conditions. We present performance validation data on a digital microfluidic platform that performs multiplex enzymatic assays for Pompe, Fabry, Hunter, Gaucher, and Hurler diseases. We developed an investigational disposable digital microfluidic cartridge that uses a single dried blood spot (DBS) punch for performing a 5-plex fluorometric enzymatic assay on up to 44 DBS samples. Precision and linearity of the assays were determined by analyzing quality control DBS samples; clinical performance was determined by analyzing 600 presumed normal and known affected samples (12 for Pompe, 7 for Fabry and 10 each for Hunter, Gaucher and Hurler). Overall coefficient of variation (CV) values between cartridges, days, instruments, and operators ranged from 2 to 21%; linearity correlation coefficients were ≥0.98 for all assays. The multiplex enzymatic assay performed from a single DBS punch was able to discriminate presumed normal from known affected samples for 5 LSDs. Digital microfluidic technology shows potential for rapid, high-throughput screening for 5 LSDs in a newborn screening laboratory environment. Sample preparation to enzymatic activity on each cartridge is less than 3h. Copyright © 2013 Elsevier B.V. All rights reserved.

3D-printed microfluidic automation.

PubMed

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

2015-04-21

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

Design and integration of an all-in-one biomicrofluidic chip

PubMed Central

Liu, Liyu; Cao, Wenbin; Wu, Jingbo; Wen, Weijia; Chang, Donald Choy; Sheng, Ping

2008-01-01

We demonstrate a highly integrated microfluidic chip with the function of DNA amplification. The integrated chip combines giant electrorheological-fluid actuated micromixer and micropump with a microheater array, all formed using soft lithography. Internal functional components are based on polydimethylsiloxane (PDMS) and silver∕carbon black-PDMS composites. The system has the advantages of small size with a high degree of integration, high polymerase chain reaction efficiency, digital control and simple fabrication at low cost. This integration approach shows promise for a broad range of applications in chemical synthesis and biological sensing∕analysis, as different components can be combined to target desired functionalities, with flexible designs of different microchips easily realizable through soft lithography. PMID:19693370

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

PubMed

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

2013-01-01

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

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

PubMed

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

2015-01-01

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

Structural Determination of Biomolecules in Microfluidic Systems

NASA Astrophysics Data System (ADS)

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

2004-03-01

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

Emerging Technologies for Cancer Research: towards Personalized Medicine with Microfluidic Platforms and 3D Tumor Models.

PubMed

Turetta, Matteo; Ben, Fabio Del; Brisotto, Giulia; Biscontin, Eva; Bulfoni, Michela; Cesselli, Daniela; Colombatti, Alfonso; Scoles, Giacinto; Gigli, Giuseppe; Del Mercato, Loretta L

2018-06-05

In the present review, we describe three hot topics in cancer research such as circulating tumor cells, exosomes, and 3D environment models. The first section is dedicated to microfluidic platforms for detecting circulating tumor cells, including both affinity-based methods that take advantage of antibodies and aptamers, and "label-free" approaches, exploiting cancer cells physical features and, more recently, abnormal cancer metabolism. In the second section, we briefly describe biology of exosomes and their role in cancer, as well as conventional techniques for their isolation and innovative microfluidic platforms. In the third section, the importance of tumor microenvironment is highlighted, along with techniques for modeling it in vitro. Finally, we discuss limitations of two-dimensional monolayer methods and describe advantages and disadvantages of different three-dimensional tumor systems for cell-cell interaction analysis and their potential applications in cancer management. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Understanding cell passage through constricted microfluidic channels

NASA Astrophysics Data System (ADS)

Cartas-Ayala, Marco A.; Karnik, Rohit

2012-11-01

Recently, several microfluidic platforms have been proposed to characterize cells based on their behaviour during cell passage through constricted channels. Variables like transit time have been analyzed in disease states like sickle cell anemia, malaria and sepsis. Nevertheless, it is hard to make direct comparisons between different platforms and cell types. We present experimental results of the relationship between solid deformable particle properties, i.e. stiffness and relative particle size, and flow properties, i.e. particle's velocity. We measured the hydrodynamic variables during the flow of HL-60 cells, a white myeloid cell type, in narrow microfluidic square channels using a microfluidic differential manometer. We measured the flow force required to move cells of different sizes through microchannels and quantified friction forces opposing cell passage. We determined the non-dimensional parameters that influence the flow of cells and we used them to obtain a non dimensional expression that can be used to predict the forces needed to drive cells through microchannels. We found that the friction force needed to flow HL-60 through a microfluidic channel is the sum of two parts. The first part is a static friction force that is proportional to the force needed to keep the force compressed. The second part is a factor that is proportional to the cell velocity, hence a dynamic term, and slightly sensitive to the compressive force. We thank CONACYT (Mexican Science and Technology Council) for supporting this project, grant 205899.

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.

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

PubMed

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

2018-01-15

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

Manning’s equation and two-dimensional flow analogs

NASA Astrophysics Data System (ADS)

Hromadka, T. V., II; Whitley, R. J.; Jordan, N.; Meyer, T.

2010-07-01

SummaryTwo-dimensional (2D) flow models based on the well-known governing 2D flow equations are applied to floodplain analysis purposes. These 2D models numerically solve the governing flow equations simultaneously or explicitly on a discretization of the floodplain using grid tiles or similar tile cell geometry, called "elements". By use of automated information systems such as digital terrain modeling, digital elevation models, and GIS, large-scale topographic floodplain maps can be readily discretized into thousands of elements that densely cover the floodplain in an edge-to-edge form. However, the assumed principal flow directions of the flow model analog, as applied across an array of elements, typically do not align with the floodplain flow streamlines. This paper examines the mathematical underpinnings of a four-direction flow analog using an array of square elements with respect to floodplain flow streamlines that are not in alignment with the analog's principal flow directions. It is determined that application of Manning's equation to estimate the friction slope terms of the governing flow equations, in directions that are not coincident with the flow streamlines, may introduce a bias in modeling results, in the form of slight underestimation of flow depths. It is also determined that the maximum theoretical bias, occurs when a single square element is rotated by about 13°, and not 45° as would be intuitively thought. The bias as a function of rotation angle for an array of square elements follows approximately the bias for a single square element. For both the theoretical single square element and an array of square elements, the bias as a function of alignment angle follows a relatively constant value from about 5° to about 85°, centered at about 45°. This bias was first noted about a decade prior to the present paper, and the magnitude of this bias was estimated then to be about 20% at about 10° misalignment. An adjustment of Manning's n is investigated based on a considered steady state uniform flow problem, but the magnitude of the adjustment (about 20%) is on the order of the magnitude of the accepted ranges of friction factors. For usual cases where random streamline trajectory variability within the floodplain flow is greater than a few degrees from perfect alignment, the apparent bias appears to be implicitly included in the Manning's n values. It can be concluded that the array of square elements may be applied over the digital terrain model without respect to topographic flow directions.

Microfluidic platforms for gallium-based liquid metal alloy

NASA Astrophysics Data System (ADS)

Kim, Daeyoung

As an alternative to toxic mercury, non-toxic gallium-based liquid metal alloy has been gaining popularity due to its higher thermal and electrical conductivities, and low toxicity along with liquid property. However, it is difficult to handle as the alloy becomes readily oxidized in atmospheric air environment. This instant oxidation causes the gallium-based liquid metal alloy to wet almost any solid surface. Therefore, it has been primarily limited to applications which rely only on its deformability, not on its mobility. In this research, various approaches to mobilize gallium-based liquid metal alloy were investigated. Multi-scale surface patterned with polydimethylsiloxane (PDMS) micro pillar array showed super-lyophobic property against gallium-based liquid metal alloy by minimizing the contact area between the solid surface and the liquid metal, and it was expanded to a three-dimensional tunnel shaped microfluidic channel. Vertically-aligned carbon nanotube forest leads to another promising super-lyophobic surface due to its hierarchical micro/nano scale combined structures and chemical inertness. When the carbon nanotubes were transferred onto flexible PDMS by imprinting, the super-lyophobic property was still maintained even under the mechanical deformation such as stretching and bending. Alternatively, the gallium-based liquid metal can be manipulated by modifying the surface of liquid metal itself. With chemical reaction with HCl 'vapor', the oxidized surface (mainly Ga2O3/Ga2O) of gallium-based liquid metal was converted to GaCl3/InCl 3 resulting in the recovery of non-wetting characteristics. Paper which is intrinsically porous is attractive as a super-lyophobic surface and it was found that hydrochloric acid (HCl) impregnation enhanced the anti-wetting property by the chemical reaction. As another alternative method, by coating the viscoelastic oxidized surface of liquid metal with ferromagnetic materials (CoNiMnP or Fe), it showed non-wetting property and became moveable by applying a magnetic field. Finally, using its metallic and liquid properties, microfluidic-based applications of gallium-based liquid metal alloy such as inkjet printing and reconfigurable photomask were investigated. A clog-free and oxide-free inkjet printing technique was developed by incorporating HCl-impregnated paper as orifice. Inkjet-printed liquid metal line can be used as a metallic interconnect even with significant deformation of the flexible substrate. Additionally, based on its ultraviolet light blocking property, a reconfigurable photolithography using gallium-based liquid metal alloy was demonstrated in a PDMS-based 7-segments microfluidic channel by showing single digit numbers ('0'˜'9') with attainable minimum feature size of 10 microm.

Design and integration of a generic disposable array-compatible sensor housing into an integrated disposable indirect microfluidic flow injection analysis system.

PubMed

Rapp, Bastian E; Schickling, Benjamin; Prokop, Jürgen; Piotter, Volker; Rapp, Michael; Länge, Kerstin

2011-10-01

We describe an integration strategy for arbitrary sensors intended to be used as biosensors in biomedical or bioanalytical applications. For such devices ease of handling (by a potential end user) as well as strict disposable usage are of importance. Firstly we describe a generic array compatible polymer sensor housing with an effective sample volume of 1.55 μl. This housing leaves the sensitive surface of the sensor accessible for the application of biosensing layers even after the embedding. In a second step we show how this sensor housing can be used in combination with a passive disposable microfluidic chip to set up arbitrary 8-fold sensor arrays and how such a system can be complemented with an indirect microfluidic flow injection analysis (FIA) system. This system is designed in a way that it strictly separates between disposable and reusable components- by introducing tetradecane as an intermediate liquid. This results in a sensor system compatible with the demands of most biomedical applications. Comparative measurements between a classical macroscopic FIA system and this integrated indirect microfluidic system are presented. We use a surface acoustic wave (SAW) sensor as an exemplary detector in this work.

Multiphoton writing of three-dimensional fluidic channels within a porous matrix.

PubMed

Lee, Jyh-Tsung; George, Matthew C; Moore, Jeffrey S; Braun, Paul V

2009-08-19

We demonstrate a facile method for fabricating novel 3D microfluidic channels by using two-photon-activated chemistry to locally switch the interior surface of a porous host from a hydrophobic state to a hydrophilic state. The 3D structures can be infilled selectively with water and/or hydrophobic oil with a minimum feature size of only a few micrometers. We envision that this approach may enable the fabrication of complex microfluidic structures that cannot be easily formed via current technologies.

Laser Direct Writing of Tree-Shaped Hierarchical Cones on a Superhydrophobic Film for High-Efficiency Water Collection.

PubMed

Wang, Meng; Liu, Qian; Zhang, Haoran; Wang, Chuang; Wang, Lei; Xiang, Bingxi; Fan, Yongtao; Guo, Chuan Fei; Ruan, Shuangchen

2017-08-30

Directional water collection has stimulated a great deal of interest because of its potential applications in the field of microfluidics, liquid transportation, fog harvesting, and so forth. There have been some bio or bioinspired structures for directional water collection, from one-dimensional spider silk to two-dimensional star-like patterns to three-dimensional Nepenthes alata. Here we present a simple way for the accurate design and highly controllable driving of tiny droplets: by laser direct writing of hierarchical patterns with modified wettability and desired geometry on a superhydrophobic film, the patterned film can precisely and directionally drive tiny water droplets and dramatically improve the efficiency of water collection with a factor of ∼36 compared with the original superhydrophobic film. Such a patterned film might be an ideal platform for water collection from humid air and for planar microfluidics without tunnels.

Three-dimensional microfluidic channel with arbitrary length and configuration fabricated inside glass by femtosecond laser direct writing.

PubMed

Liao, Yang; Ju, Yongfeng; Zhang, Long; He, Fei; Zhang, Qiang; Shen, Yinglong; Chen, Danping; Cheng, Ya; Xu, Zhizhan; Sugioka, Koji; Midorikawa, Katsumi

2010-10-01

We demonstrate, for the first time to the best of our knowledge, fabrication of three-dimensional microfluidic channels with arbitrary lengths and configurations inside glass by femtosecond laser direct writing. The main fabrication process includes two steps: (1) direct formation of hollow microchannels in a porous glass substrate immersed in water by femtosecond laser ablation and (2) postannealing of the glass substrate at ∼1150°C by which the porous glass can be consolidated. We show that a square-wavelike channel with a total length of ∼1.4 cm and a diameter of ∼64 μm can be easily produced ∼250 μm beneath the glass surface.

3D-Printed Microfluidic Automation

PubMed Central

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

2015-01-01

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

Apparent Softening of Wet Graphene Membranes on a Microfluidic Platform.

PubMed

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

2018-05-22

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

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

NASA Astrophysics Data System (ADS)

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

2014-06-01

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

Monolithic Integration of Two-Dimensional Liquid Chromatography-Capillary Electrophoresis and Electrospray Ionization on a Microfluidic Device

PubMed Central

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

2011-01-01

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

An integrated centrifugo-opto-microfluidic platform for arraying, analysis, identification and manipulation of individual cells.

PubMed

Burger, R; Kurzbuch, D; Gorkin, R; Kijanka, G; Glynn, M; McDonagh, C; Ducrée, J

2015-01-21

In this work we present a centrifugal microfluidic system enabling highly efficient collective trapping and alignment of particles such as microbeads and cells, their multi-colour fluorescent detection and subsequent manipulation by optical tweezers. We demonstrate array-based capture and imaging followed by "cherry-picking" of individual particles, first for fluorescently labelled polystyrene (PS) beads and then for cells. Different cell lines are discriminated based on intracellular as well as surface-based markers.

Visible light induced electropolymerization of suspended hydrogel bioscaffolds in a microfluidic chip.

PubMed

Li, Pan; Yu, Haibo; Liu, Na; Wang, Feifei; Lee, Gwo-Bin; Wang, Yuechao; Liu, Lianqing; Li, Wen Jung

2018-05-23

The development of microengineered hydrogels co-cultured with cells in vitro could advance in vivo bio-systems in both structural complexity and functional hierarchy, which holds great promise for applications in regenerative tissues or organs, drug discovery and screening, and bio-sensors or bio-actuators. Traditional hydrogel microfabrication technologies such as ultraviolet (UV) laser or multiphoton laser stereolithography and three-dimensional (3D) printing systems have advanced the development of 3D hydrogel micro-structures but need either expensive and complex equipment, or harsh material selection with limited photoinitiators. Herein, we propose a simple and flexible hydrogel microfabrication method based on a ubiquitous visible-light projection system combined with a custom-designed photosensitive microfluidic chip, to rapidly (typically several to tens of seconds) fabricate various two-dimensional (2D) hydrogel patterns and 3D hydrogel constructs. A theoretical layer-by-layer model that involves continuous polymerizing-delaminating-polymerizing cycles is presented to explain the polymerization and structural formation mechanism of hydrogels. A large area of hydrogel patterns was efficiently fabricated without the usage of costly laser systems or photoinitiators, i.e., a stereoscopic mesh-like hydrogel network with intersecting hydrogel micro-belts was fabricated via a series of dynamic-changing digital light projections. The pores and gaps of the hydrogel network are tunable, which facilitates the supply of nutrients and discharge of waste in the construction of 3D thick bio-models. Cell co-culture experiments showed the effective regulation of cell spreading by hydrogel scaffolds fabricated by the new method presented here. This visible light enabled hydrogel microfabrication method may provide new prospects for designing cell-based units for advanced biomedical studies, e.g., for 3D bio-models or bio-actuators in the future.

Red blood cell (RBC) suspensions in confined microflows: Pressure-flow relationship.

PubMed

Stauber, Hagit; Waisman, Dan; Korin, Netanel; Sznitman, Josué

2017-10-01

Microfluidic-based assays have become increasingly popular to explore microcirculation in vitro. In these experiments, blood is resuspended to a desired haematocrit level in a buffer solution, where frequent choices for preparing RBC suspensions comprise notably Dextran and physiological buffer. Yet, the rational for selecting one buffer versus another is often ill-defined and lacks detailed quantification, including ensuing changes in RBC flow characteristics. Here, we revisit RBC suspensions in microflows and attempt to quantify systematically some of the differences emanating between buffers. We measure bulk flow rate (Q) of RBC suspensions, using PBS- and Dextran-40, as a function of the applied pressure drop (ΔP) for two hematocrits (∼0% and 23%). Two distinct microfluidic designs of varying dimensions are employed: a straight channel larger than and a network array similar to the size of individual RBCs. Using the resulting pressure-flow curves, we extract the equivalent hydrodynamic resistances and estimate the relative viscosities. These efforts are a first step in rigorously quantifying the influence of the 'background' buffer on RBC flows within microfluidic devices and thereby underline the importance of purposefully selecting buffer suspensions for microfluidic in vitro assays. Copyright © 2017. Published by Elsevier Ltd.

Three-Dimensional Phenomena in Microbubble Acoustic Streaming

NASA Astrophysics Data System (ADS)

Marin, Alvaro; Rossi, Massimiliano; Rallabandi, Bhargav; Wang, Cheng; Hilgenfeldt, Sascha; Kähler, Christian J.

2015-04-01

Ultrasound-driven oscillating microbubbles are used as active actuators in microfluidic devices to perform manifold tasks such as mixing, sorting, and manipulation of microparticles. A common configuration consists of side bubbles created by trapping air pockets in blind channels perpendicular to the main channel direction. This configuration consists of acoustically excited bubbles with a semicylindrical shape that generate significant streaming flow. Because of the geometry of the channels, such flows are generally considered as quasi-two-dimensional. Similar assumptions are often made in many other microfluidic systems based on flat microchannels. However, in this Letter we show that microparticle trajectories actually present a much richer behavior, with particularly strong out-of-plane dynamics in regions close to the microbubble interface. Using astigmatism particle-tracking velocimetry, we reveal that the apparent planar streamlines are actually projections of a stream surface with a pseudotoroidal shape. We, therefore, show that acoustic streaming cannot generally be assumed as a two-dimensional phenomenon in confined systems. The results have crucial consequences for most of the applications involving acoustic streaming such as particle trapping, sorting, and mixing.

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

NASA Astrophysics Data System (ADS)

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

2014-03-01

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

Single-molecule detection of epidermal growth factor receptor mutations in plasma by microfluidics digital PCR in non-small cell lung cancer patients.

PubMed

Yung, Tony K F; Chan, K C Allen; Mok, Tony S K; Tong, Joanna; To, Ka-Fai; Lo, Y M Dennis

2009-03-15

We aim to develop a digital PCR-based method for the quantitative detection of the two common epidermal growth factor receptor (EGFR) mutations (in-frame deletion at exon 19 and L858R at exon 21) in the plasma and tumor tissues of patients suffering from non-small cell lung cancers. These two mutations account for >85% of clinically important EGFR mutations associated with responsiveness to tyrosine kinase inhibitors. DNA samples were analyzed using a microfluidics system that simultaneously performed 9,180 PCRs at nanoliter scale. A single-mutant DNA molecule in a clinical specimen could be detected and the quantities of mutant and wild-type sequences were precisely determined. Exon 19 deletion and L858R mutation were detectable in 6 (17%) and 9 (26%) of 35 pretreatment plasma samples, respectively. When compared with the sequencing results of the tumor samples, the sensitivity and specificity of plasma EGFR mutation analysis were 92% and 100%, respectively. The plasma concentration of the mutant sequences correlated well with the clinical response. Decreased concentration was observed in all patients with partial or complete clinical remission, whereas persistence of mutation was observed in a patient with cancer progression. In one patient, tyrosine kinase inhibitor was stopped after an initial response and the tumor-associated EGFR mutation reemerged 4 weeks after stopping treatment. The sensitive detection and accurate quantification of low abundance EGFR mutations in tumor tissues and plasma by microfluidics digital PCR would be useful for predicting treatment response, monitoring disease progression and early detection of treatment failure associated with acquired drug resistance.

Microfabrication and Test of a Three-Dimensional Polymer Hydro-focusing Unit for Flow Cytometry Applications

NASA Technical Reports Server (NTRS)

Yang, Ren; Feeback, Daniel L.; Wang, Wan-Jun

2005-01-01

This paper details a novel three-dimensional (3D) hydro-focusing micro cell sorter for micro flow cytometry applications. The unit was microfabricated by means of SU-8 3D lithography. The 3D microstructure for coaxial sheathing was designed, microfabricated, and tested. Three-dimensional hydrofocusing capability was demonstrated with an experiment to sort labeled tanned sheep erythrocytes (red blood cells). This polymer hydro-focusing microstructure is easily microfabricated and integrated with other polymer microfluidic structures. Keywords: SU-8, three-dimensional hydro-focusing, microfluidic, microchannel, cytometer

Microfluidic engineering of neural stem cell niches for fate determination

PubMed Central

Ma, Jingyun; Li, Na; Wang, Liang; Shen, Liming; Sun, Yu; Wang, Yajun; Zhao, Jingyuan; Wei, Wenjuan; Ren, Yan; Liu, Jing

2017-01-01

Neural stem cell (NSC) transplantation has great therapeutic potential for neurodegenerative diseases and central nervous system injuries. Successful NSC replacement therapy requires precise control over the cellular behaviors. However, the regulation of NSC fate is largely unclear, which severely restricts the potential clinical applications. To develop an effective model, we designed an assembled microfluidic system to engineer NSC niches and assessed the effects of various culture conditions on NSC fate determination. Five types of NSC microenvironments, including two-dimensional (2D) cellular monolayer culture, 2D cellular monolayer culture on the extracellular matrix (ECM), dispersed cells in the ECM, three-dimensional (3D) spheroid aggregates, and 3D spheroids cultured in the ECM, were constructed within an integrated microfluidic chip simultaneously. In addition, we evaluated the influence of static and perfusion culture on NSCs. The efficiency of this approach was evaluated comprehensively by characterization of NSC viability, self-renewal, proliferation, and differentiation into neurons, astrocytes, or oligodendrocytes. Differences in the status and fate of NSCs governed by the culture modes and micro-niches were analyzed. NSCs in the microfluidic device demonstrated good viability, the 3D culture in the ECM facilitated NSC self-renewal and proliferation, and 2D culture in the static state and spheroid culture under perfusion conditions benefited NSC differentiation. Regulation of NSC self-renewal and differentiation on this microfluidic device could provide NSC-based medicinal products and references for distinct nerve disease therapy. PMID:28798841

Two-dimensional confocal laser scanning microscopy image correlation for nanoparticle flow velocimetry

NASA Astrophysics Data System (ADS)

Jun, Brian; Giarra, Matthew; Golz, Brian; Main, Russell; Vlachos, Pavlos

2016-11-01

We present a methodology to mitigate the major sources of error associated with two-dimensional confocal laser scanning microscopy (CLSM) images of nanoparticles flowing through a microfluidic channel. The correlation-based velocity measurements from CLSM images are subject to random error due to the Brownian motion of nanometer-sized tracer particles, and a bias error due to the formation of images by raster scanning. Here, we develop a novel ensemble phase correlation with dynamic optimal filter that maximizes the correlation strength, which diminishes the random error. In addition, we introduce an analytical model of CLSM measurement bias error correction due to two-dimensional image scanning of tracer particles. We tested our technique using both synthetic and experimental images of nanoparticles flowing through a microfluidic channel. We observed that our technique reduced the error by up to a factor of ten compared to ensemble standard cross correlation (SCC) for the images tested in the present work. Subsequently, we will assess our framework further, by interrogating nanoscale flow in the cell culture environment (transport within the lacunar-canalicular system) to demonstrate our ability to accurately resolve flow measurements in a biological system.

Reconfigurable Microfluidic Magnetic Valve Arrays: Towards a Radiotherapy-Compatible Spheroid Culture Platform for the Combinatorial Screening of Cancer Therapies

PubMed Central

Labelle, Frédérique; Wong, Philip

2017-01-01

We introduce here a microfluidic cell culture platform or spheroid culture chamber array (SCCA) that can synthesize, culture, and enable fluorescence imaging of 3D cell aggregates (typically spheroids) directly on-chip while specifying the flow of reagents in each chamber via the use of an array of passive magnetic valves. The SCCA valves demonstrated sufficient resistance to burst (above 100 mBar), including after receiving radiotherapy (RT) doses of up to 8 Gy combined with standard 37 °C incubation for up to 7 days, enabling the simultaneous synthesis of multiple spheroids from different cell lines on the same array. Our results suggest that SCCA would be an asset in drug discovery processes, seeking to identify combinatorial treatments. PMID:28976942

Spatial mapping and statistical reproducibility of an array of 256 one-dimensional quantum wires

NASA Astrophysics Data System (ADS)

Al-Taie, H.; Smith, L. W.; Lesage, A. A. J.; See, P.; Griffiths, J. P.; Beere, H. E.; Jones, G. A. C.; Ritchie, D. A.; Kelly, M. J.; Smith, C. G.

2015-08-01

We utilize a multiplexing architecture to measure the conductance properties of an array of 256 split gates. We investigate the reproducibility of the pinch off and one-dimensional definition voltage as a function of spatial location on two different cooldowns, and after illuminating the device. The reproducibility of both these properties on the two cooldowns is high, the result of the density of the two-dimensional electron gas returning to a similar state after thermal cycling. The spatial variation of the pinch-off voltage reduces after illumination; however, the variation of the one-dimensional definition voltage increases due to an anomalous feature in the center of the array. A technique which quantifies the homogeneity of split-gate properties across the array is developed which captures the experimentally observed trends. In addition, the one-dimensional definition voltage is used to probe the density of the wafer at each split gate in the array on a micron scale using a capacitive model.

A Microfluidic Route to Breaking Chiral Symmetry: Theory and Experiment

NASA Astrophysics Data System (ADS)

Ocko, Samuel; Adams, Laura

A robust route for the biased production of single handed chiral structures has been found in generating non-spherical, multi-component double emulsions using glass microfluidic devices. The specific type of handedness is determined by the final packing geometry of four different inner drops inside an ultra-thin sheath of oil. Before the three dimensional chiral structures are formed, the quasi-one dimensional chain of four inner drops re-arranges in two dimensions into either checkerboard or stripe patterns. We derive an analytical model predicting which pattern is more likely and assembles in the least amount of time. Moreover, our model accurately predicts our experimental results and is based on local bending dynamics, rather than global surface energy minimization. We gratefully acknowledge Professors D. Weitz and L. Mahadevan's support.

Simultaneous Identification and Antimicrobial Susceptibility Testing of Multiple Uropathogens on a Microfluidic Chip with Paper-Supported Cell Culture Arrays.

PubMed

Xu, Banglao; Du, Yan; Lin, Jinqiong; Qi, Mingyue; Shu, Bowen; Wen, Xiaoxia; Liang, Guangtie; Chen, Bin; Liu, Dayu

2016-12-06

A microfluidic chip was developed for one-step identification and antimicrobial susceptibility testing (AST) of multiple uropathogens. The polydimethylsiloxane (PDMS) microchip used had features of cell culture chamber arrays connected through a sample introduction channel. At the bottom of each chamber, a paper substrate preloaded with chromogenic media and antimicrobial agents was embedded. By integrating a hydrophobic membrane valve on the microchip, the urine sample can be equally distributed into and confined in individual chambers. The identification and AST assays on multiple uropathogens were performed by combining the spatial resolution of the cell culture arrays and the color resolution from the chromogenic reaction. The composite microbial testing assay was based on dynamic changes in color in a serial of chambers. The bacterial antimicrobial susceptibility was determined by the lowest concentration of an antimicrobial agent that is capable of inhibiting the chromogenic reaction. Using three common uropathogenic bacteria as test models, the developed microfluidic approach was demonstrated to be able to complete the multiple colorimetric assays in 15 h. The accuracy of the microchip method, in comparison with that of the conventional approach, showed a coincidence of 94.1%. Our data suggest this microfluidic approach will be a promising tool for simple and fast uropathogen testing in resource-limited settings.

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

PubMed Central

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

2017-01-01

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

Microwell Arrays for Studying Many Individual Cells

NASA Technical Reports Server (NTRS)

Folch, Albert; Kosar, Turgut Fettah

2009-01-01

"Laboratory-on-a-chip" devices that enable the simultaneous culturing and interrogation of many individual living cells have been invented. Each such device includes a silicon nitride-coated silicon chip containing an array of micromachined wells sized so that each well can contain one cell in contact or proximity with a patch clamp or other suitable single-cell-interrogating device. At the bottom of each well is a hole, typically 0.5 m wide, that connects the well with one of many channels in a microfluidic network formed in a layer of poly(dimethylsiloxane) on the underside of the chip. The microfluidic network makes it possible to address wells (and, thus, cells) individually to supply them with selected biochemicals. The microfluidic channels also provide electrical contact to the bottoms of the wells.

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

PubMed

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

2017-08-15

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

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

NASA Astrophysics Data System (ADS)

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

2017-08-01

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

Two-dimensional ultrahigh-density X-ray optical memory.

PubMed

Bezirganyan, Hakob P; Bezirganyan, Siranush E; Bezirganyan, Hayk H; Bezirganyan, Petros H

2007-01-01

Most important aspect of nanotechnology applications in the information ultrahigh storage is the miniaturization of data carrier elements of the storage media with emphasis on the long-term stability. Proposed two-dimensional ultrahigh-density X-ray optical memory, named X-ROM, with long-term stability is an information carrier basically destined for digital data archiving. X-ROM is a semiconductor wafer, in which the high-reflectivity nanosized X-ray mirrors are embedded. Data are encoded due to certain positions of the mirrors. Ultrahigh-density data recording procedure can e.g., be performed via mask-less zone-plate-array lithography (ZPAL), spatial-phase-locked electron-beam lithography (SPLEBL), or focused ion-beam lithography (FIB). X-ROM manufactured by nanolithography technique is a write-once memory useful for terabit-scale memory applications, if the surface area of the smallest recording pits is less than 100 nm2. In this case the X-ROM surface-storage capacity of a square centimetre becomes by two orders of magnitude higher than the volumetric data density really achieved for three-dimensional optical data storage medium. Digital data read-out procedure from proposed X-ROM can e.g., be performed via glancing-angle incident X-ray micro beam (GIX) using the well-developed X-ray reflectometry technique. In presented theoretical paper the crystal-analyser operating like an image magnifier is added to the set-up of X-ROM data handling system for the purpose analogous to case of application the higher numerical aperture objective in optical data read-out system. We also propose the set-up of the X-ROM readout system based on more the one incident X-ray micro beam. Presented scheme of two-beam data handling system, which operates on two mutually perpendicular well-collimated monochromatic incident X-ray micro beams, essentially increases the reliability of the digital information read-out procedure. According the graphs of characteristic functions presented in paper, one may choose optimally the incident radiation wavelength, as well as the angle of incidence of X-ray micro beams, appropriate for proposed digital data read-out procedure.

High-resolution liquid patterns via three-dimensional droplet shape control.

PubMed

Raj, Rishi; Adera, Solomon; Enright, Ryan; Wang, Evelyn N

2014-09-25

Understanding liquid dynamics on surfaces can provide insight into nature's design and enable fine manipulation capability in biological, manufacturing, microfluidic and thermal management applications. Of particular interest is the ability to control the shape of the droplet contact area on the surface, which is typically circular on a smooth homogeneous surface. Here, we show the ability to tailor various droplet contact area shapes ranging from squares, rectangles, hexagons, octagons, to dodecagons via the design of the structure or chemical heterogeneity on the surface. We simultaneously obtain the necessary physical insights to develop a universal model for the three-dimensional droplet shape by characterizing the droplet side and top profiles. Furthermore, arrays of droplets with controlled shapes and high spatial resolution can be achieved using this approach. This liquid-based patterning strategy promises low-cost fabrication of integrated circuits, conductive patterns and bio-microarrays for high-density information storage and miniaturized biochips and biosensors, among others.

Discrete microfluidics: Reorganizing droplet arrays at a bend

NASA Astrophysics Data System (ADS)

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

2009-10-01

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

Tablet PC interaction with digital micromirror device (DMD)

NASA Astrophysics Data System (ADS)

Refai, Hakki H.; Dahshan, Mostafa H.; Sluss, James J., Jr.

2007-02-01

Digital light processing (DLP) is an innovative display technology that uses an optical switch array, known as a digital micromirror device (DMD), which allows digital control of light. To date, DMDs have been used primarily as high-speed spatial light modulators for projector applications. A tablet PC is a notebook or slate-shaped mobile PC. Its touch screen or digitizing tablet technology allows the user to operate the notebook with a stylus or digital pen instead of using a keyboard or mouse. In this paper, we describe an interface solution that translates any sketch on the tablet PC screen to an identical mirror-copy over the cross-section of the DMD micromirrors such that the image of the sketch can be projected onto a special screen. An algorithm has been created to control each single micromirror of the hundreds of thousands of micromirrors that cover the DMD surface. We demonstrate the successful application of a DMD to a high-speed two-dimensional (2D) scanning environment, acquiring the data from the tablet screen and launching its contents to the projection screen; with very high accuracy up to 13.68 μm x 13.68 μm of mirror pitch.

Activity-induced instability of phonons in 1D microfluidic crystals.

PubMed

Tsang, Alan Cheng Hou; Shelley, Michael J; Kanso, Eva

2018-02-14

One-dimensional crystals of passively-driven particles in microfluidic channels exhibit collective vibrational modes reminiscent of acoustic 'phonons'. These phonons are induced by the long-range hydrodynamic interactions among the particles and are neutrally stable at the linear level. Here, we analyze the effect of particle activity - self-propulsion - on the emergence and stability of these phonons. We show that the direction of wave propagation in active crystals is sensitive to the intensity of the background flow. We also show that activity couples, at the linear level, transverse waves to the particles' rotational motion, inducing a new mode of instability that persists in the limit of large background flow, or, equivalently, vanishingly small activity. We then report a new phenomenon of phonons switching back and forth between two adjacent crystals in both passively-driven and active systems, similar in nature to the wave switching observed in quantum mechanics, optical communication, and density stratified fluids. These findings could have implications for the design of commercial microfluidic systems and the self-assembly of passive and active micro-particles into one-dimensional structures.

Assembly of multiple cell gradients directed by three-dimensional microfluidic channels.

PubMed

Li, Yiwei; Feng, Xiaojun; Wang, Yachao; Du, Wei; Chen, Peng; Liu, Chao; Liu, Bi-Feng

2015-08-07

Active control over the cell gradient is essential for understanding biological systems and the reconstitution of the functionality of many types of tissues, particularly for organ-on-a-chip. Here, we propose a three-dimensional (3D) microfluidic strategy for generating controllable cell gradients. In this approach, a homogeneous cell suspension is loaded into a 3D stair-shaped PDMS microchannel to generate a cell gradient within 10 min by sedimentation. We demonstrate that cell gradients of various profiles (exponential and piecewise linear) can be achieved by precisely controlling the height of each layer during the fabrication. With sequential seeding, we further demonstrate the generation of two overlapping cell gradients on the same glass substrate with pre-defined designs. The cell gradient-based QD cytotoxicity assay also demonstrated that cell behaviors and resistances were regulated by the changes in cell density. These results reveal that the proposed 3D microfluidic strategy provides a simple and versatile means for establishing controllable gradients in cell density, opening up a new avenue for reconstructing functional tissues.

Symmetry-breaking bifurcations and enhanced mixing in microfluidic cross-slots

NASA Astrophysics Data System (ADS)

Poole, Rob; Haward, Simon; Oliveira, Paulo; Alves, Manuel

2014-11-01

We investigate, both experimentally and numerically, a new subcritical bifurcation phenomenon for a Newtonian fluid flowing through three-dimensional cross-slot geometries. At low Reynolds numbers the flow remains steady and symmetric. For the case of square inlets and outlets, at a critical Reynolds number of approximately 40 (based on average velocity) a pitchfork bifurcation is observed beyond which the unstable symmetrical solution is replaced by a pair of steady asymmetric solutions. Sensitivity of this critical Reynolds number to the initial conditions of the simulation, resulting in a small degree of hysteresis, suggests a subcritical instability. At higher flowrates the flow becomes unsteady. The effects of channel aspect ratio are investigated on the critical conditions and excellent agreement is found between three-dimensional finite volume simulations and flow visualisation experiments in microfluidic channels. Finally we suggest this new flow bifurcation could be an effective method of enhancing mixing in microfluidic channels as significant increases in mixing quality are observed beyond the bifurcation. This enhancement occurs at flowrates more than a factor of two smaller than those observed in the well-known T-channel micromixer.

Integrated Microfluidic Devices for Automated Microarray-Based Gene Expression and Genotyping Analysis

NASA Astrophysics Data System (ADS)

Liu, Robin H.; Lodes, Mike; Fuji, H. Sho; Danley, David; McShea, Andrew

Microarray assays typically involve multistage sample processing and fluidic handling, which are generally labor-intensive and time-consuming. Automation of these processes would improve robustness, reduce run-to-run and operator-to-operator variation, and reduce costs. In this chapter, a fully integrated and self-contained microfluidic biochip device that has been developed to automate the fluidic handling steps for microarray-based gene expression or genotyping analysis is presented. The device consists of a semiconductor-based CustomArray® chip with 12,000 features and a microfluidic cartridge. The CustomArray was manufactured using a semiconductor-based in situ synthesis technology. The micro-fluidic cartridge consists of microfluidic pumps, mixers, valves, fluid channels, and reagent storage chambers. Microarray hybridization and subsequent fluidic handling and reactions (including a number of washing and labeling steps) were performed in this fully automated and miniature device before fluorescent image scanning of the microarray chip. Electrochemical micropumps were integrated in the cartridge to provide pumping of liquid solutions. A micromixing technique based on gas bubbling generated by electrochemical micropumps was developed. Low-cost check valves were implemented in the cartridge to prevent cross-talk of the stored reagents. Gene expression study of the human leukemia cell line (K562) and genotyping detection and sequencing of influenza A subtypes have been demonstrated using this integrated biochip platform. For gene expression assays, the microfluidic CustomArray device detected sample RNAs with a concentration as low as 0.375 pM. Detection was quantitative over more than three orders of magnitude. Experiment also showed that chip-to-chip variability was low indicating that the integrated microfluidic devices eliminate manual fluidic handling steps that can be a significant source of variability in genomic analysis. The genotyping results showed that the device identified influenza A hemagglutinin and neuraminidase subtypes and sequenced portions of both genes, demonstrating the potential of integrated microfluidic and microarray technology for multiple virus detection. The device provides a cost-effective solution to eliminate labor-intensive and time-consuming fluidic handling steps and allows microarray-based DNA analysis in a rapid and automated fashion.

Microfluidics-Based PCR for Fusion Transcript Detection.

PubMed

Chen, Hui

2016-01-01

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

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

PubMed

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

2016-01-01

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

Picoliter DNA Sequencing Chemistry on an Electrowetting-based Digital Microfluidic Platform

PubMed Central

Ferguson Welch, Erin R.; Lin, Yan-You; Madison, Andrew; Fair, R.B.

2011-01-01

The results of investigations into performing DNA sequencing chemistry on a picoliter-scale electrowetting digital microfluidic platform are reported. Pyrosequencing utilizes pyrophosphate produced during nucleotide base addition to initiate a process ending with detection through a chemiluminescence reaction using firefly luciferase. The intensity of light produced during the reaction can be quantified to determine the number of bases added to the DNA strand. The logic-based control and discrete fluid droplets of a digital microfluidic device lend themselves well to the pyrosequencing process. Bead-bound DNA is magnetically held in a single location, and wash or reagent droplets added or split from it to circumvent product dilution. Here we discuss the dispensing, control, and magnetic manipulation of the paramagnetic beads used to hold target DNA. We also demonstrate and characterize the picoliter-scale reaction of luciferase with adenosine triphosphate to represent the detection steps of pyrosequencing and all necessary alterations for working on this scale. PMID:21298802

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

PubMed

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

2013-11-07

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

Acoustic Wave Guiding by Reconfigurable Tessellated Arrays

NASA Astrophysics Data System (ADS)

Zou, Chengzhe; Lynd, Danielle T.; Harne, Ryan L.

2018-01-01

The reconfiguration of origami tessellations is a prime vehicle to harness for adapting system properties governed by a structural form. While the knowledge of mechanical property changes associated with origami tessellation folding has been extensively built up, the opportunities to integrate other physics into a framework of tessellated, adaptive structures remain to be fully exploited. Acoustics appears to be a prime domain to marry with origami science. Specifically, deep technical analogies are revealed between wave-guiding properties achieved via digital methods that virtually reposition array elements and the actual repositioning of facets by folding origami-inspired tessellations. Here we capitalize on this analogy to investigate acoustic arrays established upon facet layouts of origami-inspired tessellations. We show that a concept of reconfigurable tessellated arrays may guide waves more effectively than traditional digitally phased arrays using fewer transducer elements. Moreover, we show that the refinement of tessellated arrays trends to the ideal case of classical wave radiators or receivers grounded in principles of geometrical acoustics. By linear wave physics shared among myriad scientific disciplines and across orders of magnitude in length scale, these discoveries may cultivate numerous opportunities for wave-guiding adaptive structures inspired by low-dimensional origami tessellations.

Inertial focusing in a straight channel with asymmetrical expansion-contraction cavity arrays using two secondary flows

NASA Astrophysics Data System (ADS)

Zhang, J.; Li, M.; Li, W. H.; Alici, G.

2013-08-01

The focusing of particles has a variety of applications in industry and biomedicine, including wastewater purification, fermentation filtration, and pathogen detection in flow cytometry, etc. In this paper a novel inertial microfluidic device using two secondary flows to focus particles is presented. The geometry of the proposed microfluidic channel is a simple straight channel with asymmetrically patterned triangular expansion-contraction cavity arrays. Three different focusing patterns were observed under different flow conditions: (1) a single focusing streak on the cavity side; (2) double focusing streaks on both sides; (3) half of the particles were focused on the opposite side of the cavity, while the other particles were trapped by a horizontal vortex in the cavity. The focusing performance was studied comprehensively up to flow rates of 700 µl min-1. The focusing mechanism was investigated by analysing the balance of forces between the inertial lift forces and secondary flow drag in the cross section. The influence of particle size and cavity geometry on the focusing performance was also studied. The experimental results showed that more precise focusing could be obtained with large particles, some of which even showed a single-particle focusing streak in the horizontal plane. Meanwhile, the focusing patterns and their working conditions could be adjusted by the geometry of the cavity. This novel inertial microfluidic device could offer a continuous, sheathless, and high-throughput performance, which can be potentially applied to high-speed flow cytometry or the extraction of blood cells.

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

PubMed Central

Xing, Yanlong; Dittrich, Petra S.

2018-01-01

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

Digital Microfluidics for Manipulation and Analysis of a Single Cell.

PubMed

He, Jie-Long; Chen, An-Te; Lee, Jyong-Huei; Fan, Shih-Kang

2015-09-15

The basic structural and functional unit of a living organism is a single cell. To understand the variability and to improve the biomedical requirement of a single cell, its analysis has become a key technique in biological and biomedical research. With a physical boundary of microchannels and microstructures, single cells are efficiently captured and analyzed, whereas electric forces sort and position single cells. Various microfluidic techniques have been exploited to manipulate single cells through hydrodynamic and electric forces. Digital microfluidics (DMF), the manipulation of individual droplets holding minute reagents and cells of interest by electric forces, has received more attention recently. Because of ease of fabrication, compactness and prospective automation, DMF has become a powerful approach for biological application. We review recent developments of various microfluidic chips for analysis of a single cell and for efficient genetic screening. In addition, perspectives to develop analysis of single cells based on DMF and emerging functionality with high throughput are discussed.

Digital Microfluidics for Manipulation and Analysis of a Single Cell

PubMed Central

He, Jie-Long; Chen, An-Te; Lee, Jyong-Huei; Fan, Shih-Kang

2015-01-01

The basic structural and functional unit of a living organism is a single cell. To understand the variability and to improve the biomedical requirement of a single cell, its analysis has become a key technique in biological and biomedical research. With a physical boundary of microchannels and microstructures, single cells are efficiently captured and analyzed, whereas electric forces sort and position single cells. Various microfluidic techniques have been exploited to manipulate single cells through hydrodynamic and electric forces. Digital microfluidics (DMF), the manipulation of individual droplets holding minute reagents and cells of interest by electric forces, has received more attention recently. Because of ease of fabrication, compactness and prospective automation, DMF has become a powerful approach for biological application. We review recent developments of various microfluidic chips for analysis of a single cell and for efficient genetic screening. In addition, perspectives to develop analysis of single cells based on DMF and emerging functionality with high throughput are discussed. PMID:26389890

Ultra-high aggregate bandwidth two-dimensional multiple-wavelength diode laser arrays

NASA Astrophysics Data System (ADS)

Chang-Hasnain, Connie

1994-04-01

Two-dimensional (2D) multi-wavelength vertical cavity surface emitting laser (VCSEL) arrays is promising for ultrahigh aggregate capacity optical networks. A 2D VCSEL array emitting 140 distinct wavelengths was reported by implementing a spatially graded layer in the VCSEL structure, which in turn creates a wavelength spread. In this program, we concentrated on novel epitaxial growth techniques to make reproducible and repeatable multi-wavelength VCSEL arrays.

Molecular ping-pong Game of Life on a two-dimensional DNA origami array.

PubMed

Jonoska, N; Seeman, N C

2015-07-28

We propose a design for programmed molecular interactions that continuously change molecular arrangements in a predesigned manner. We introduce a model where environmental control through laser illumination allows platform attachment/detachment oscillations between two floating molecular species. The platform is a two-dimensional DNA origami array of tiles decorated with strands that provide both, the floating molecular tiles to attach and to pass communicating signals to neighbouring array tiles. In particular, we show how algorithmic molecular interactions can control cyclic molecular arrangements by exhibiting a system that can simulate the dynamics similar to two-dimensional cellular automata on a DNA origami array platform. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

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

PubMed Central

Rhee, Minsoung

2010-01-01

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

Design and evaluation of a microfluidic system for inhibition studies of yeast cell signaling

NASA Astrophysics Data System (ADS)

Hamngren, Charlotte; Dinér, Peter; Grøtli, Morten; Goksör, Mattias; Adiels, Caroline B.

2012-10-01

In cell signaling, different perturbations lead to different responses and using traditional biological techniques that result in averaged data may obscure important cell-to-cell variations. The aim of this study was to develop and evaluate a four-inlet microfluidic system that enables single-cell analysis by investigating the effect on Hog1 localization post a selective Hog1 inhibitor treatment during osmotic stress. Optical tweezers was used to position yeast cells in an array of desired size and density inside the microfluidic system. By changing the flow rates through the inlet channels, controlled and rapid introduction of two different perturbations over the cell array was enabled. The placement of the cells was determined by diffusion rates flow simulations. The system was evaluated by monitoring the subcellular localization of a fluorescently tagged kinase of the yeast "High Osmolarity Glycerol" (HOG) pathway, Hog1-GFP. By sequential treatment of the yeast cells with a selective Hog1 kinase inhibitor and sorbitol, the subcellular localization of Hog1-GFP was analysed on a single-cell level. The results showed impaired Hog1-GFP nuclear localization, providing evidence of a congenial design. The setup made it possible to remove and add an agent within 2 seconds, which is valuable for investigating the dynamic signal transduction pathways and cannot be done using traditional methods. We are confident that the features of the four-inlet microfluidic system will be a valuable tool and hence contribute significantly to unravel the mechanisms of the HOG pathway and similar dynamic signal transduction pathways.

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

PubMed

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

2010-11-01

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

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

NASA Astrophysics Data System (ADS)

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

2010-11-01

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

Fully inkjet-printed microfluidics: a solution to low-cost rapid three-dimensional microfluidics fabrication with numerous electrical and sensing applications

PubMed Central

Su, Wenjing; Cook, Benjamin S.; Fang, Yunnan; Tentzeris, Manos M.

2016-01-01

As the needs for low-cost rapidly-produced microfluidics are growing with the trend of Lab-on-a-Chip and distributed healthcare, the fully inkjet-printing of microfluidics can be a solution to it with numerous potential electrical and sensing applications. Inkjet-printing is an additive manufacturing technique featuring no material waste and a low equipment cost. Moreover, similar to other additive manufacturing techniques, inkjet-printing is easy to learn and has a high fabrication speed, while it offers generally a great planar resolution down to below 20 µm and enables flexible designs due to its inherent thin film deposition capabilities. Due to the thin film feature, the printed objects also usually obtain a high vertical resolution (such as 4.6 µm). This paper introduces a low-cost rapid three-dimensional fabrication process of microfluidics, that relies entirely on an inkjet-printer based single platform and can be implemented directly on top of virtually any substrates. PMID:27713545

Fully inkjet-printed microfluidics: a solution to low-cost rapid three-dimensional microfluidics fabrication with numerous electrical and sensing applications

NASA Astrophysics Data System (ADS)

Su, Wenjing; Cook, Benjamin S.; Fang, Yunnan; Tentzeris, Manos M.

2016-10-01

As the needs for low-cost rapidly-produced microfluidics are growing with the trend of Lab-on-a-Chip and distributed healthcare, the fully inkjet-printing of microfluidics can be a solution to it with numerous potential electrical and sensing applications. Inkjet-printing is an additive manufacturing technique featuring no material waste and a low equipment cost. Moreover, similar to other additive manufacturing techniques, inkjet-printing is easy to learn and has a high fabrication speed, while it offers generally a great planar resolution down to below 20 µm and enables flexible designs due to its inherent thin film deposition capabilities. Due to the thin film feature, the printed objects also usually obtain a high vertical resolution (such as 4.6 µm). This paper introduces a low-cost rapid three-dimensional fabrication process of microfluidics, that relies entirely on an inkjet-printer based single platform and can be implemented directly on top of virtually any substrates.

Microfluidic System Simulation Including the Electro-Viscous Effect

NASA Technical Reports Server (NTRS)

Rojas, Eileen; Chen, C. P.; Majumdar, Alok

2007-01-01

This paper describes a practical approach using a general purpose lumped-parameter computer program, GFSSP (Generalized Fluid System Simulation Program) for calculating flow distribution in a network of micro-channels including electro-viscous effects due to the existence of electrical double layer (EDL). In this study, an empirical formulation for calculating an effective viscosity of ionic solutions based on dimensional analysis is described to account for surface charge and bulk fluid conductivity, which give rise to electro-viscous effect in microfluidics network. Two dimensional slit micro flow data was used to determine the model coefficients. Geometry effect is then included through a Poiseuille number correlation in GFSSP. The bi-power model was used to calculate flow distribution of isotropically etched straight channel and T-junction microflows involving ionic solutions. Performance of the proposed model is assessed against experimental test data.

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 hardware implementation of the discrete Pascal transform for image processing

NASA Astrophysics Data System (ADS)

Goodman, Thomas J.; Aburdene, Maurice F.

2006-02-01

The discrete Pascal transform is a polynomial transform with applications in pattern recognition, digital filtering, and digital image processing. It already has been shown that the Pascal transform matrix can be decomposed into a product of binary matrices. Such a factorization leads to a fast and efficient hardware implementation without the use of multipliers, which consume large amounts of hardware. We recently developed a field-programmable gate array (FPGA) implementation to compute the Pascal transform. Our goal was to demonstrate the computational efficiency of the transform while keeping hardware requirements at a minimum. Images are uploaded into memory from a remote computer prior to processing, and the transform coefficients can be offloaded from the FPGA board for analysis. Design techniques like as-soon-as-possible scheduling and adder sharing allowed us to develop a fast and efficient system. An eight-point, one-dimensional transform completes in 13 clock cycles and requires only four adders. An 8x8 two-dimensional transform completes in 240 cycles and requires only a top-level controller in addition to the one-dimensional transform hardware. Finally, through minor modifications to the controller, the transform operations can be pipelined to achieve 100% utilization of the four adders, allowing one eight-point transform to complete every seven clock cycles.

Standard Transistor Array (STAR). Volume 1: Placement technique

NASA Technical Reports Server (NTRS)

Cox, G. W.; Caroll, B. D.

1979-01-01

A large scale integration (LSI) technology, the standard transistor array uses a prefabricated understructure of transistors and a comprehensive library of digital logic cells to allow efficient fabrication of semicustom digital LSI circuits. The cell placement technique for this technology involves formation of a one dimensional cell layout and "folding" of the one dimensional placement onto the chip. It was found that, by use of various folding methods, high quality chip layouts can be achieved. Methods developed to measure of the "goodness" of the generated placements include efficient means for estimating channel usage requirements and for via counting. The placement and rating techniques were incorporated into a placement program (CAPSTAR). By means of repetitive use of the folding methods and simple placement improvement strategies, this program provides near optimum placements in a reasonable amount of time. The program was tested on several typical LSI circuits to provide performance comparisons both with respect to input parameters and with respect to the performance of other placement techniques. The results of this testing indicate that near optimum placements can be achieved by use of the procedures incurring severe time penalties.

Three-dimensional continuous particle focusing in a microfluidic channel via standing surface acoustic waves (SSAW).

PubMed

Shi, Jinjie; Yazdi, Shahrzad; Lin, Sz-Chin Steven; Ding, Xiaoyun; Chiang, I-Kao; Sharp, Kendra; Huang, Tony Jun

2011-07-21

Three-dimensional (3D) continuous microparticle focusing has been achieved in a single-layer polydimethylsiloxane (PDMS) microfluidic channel using a standing surface acoustic wave (SSAW). The SSAW was generated by the interference of two identical surface acoustic waves (SAWs) created by two parallel interdigital transducers (IDTs) on a piezoelectric substrate with a microchannel precisely bonded between them. To understand the working principle of the SSAW-based 3D focusing and investigate the position of the focal point, we computed longitudinal waves, generated by the SAWs and radiated into the fluid media from opposite sides of the microchannel, and the resultant pressure and velocity fields due to the interference and reflection of the longitudinal waves. Simulation results predict the existence of a focusing point which is in good agreement with our experimental observations. Compared with other 3D focusing techniques, this method is non-invasive, robust, energy-efficient, easy to implement, and applicable to nearly all types of microparticles.

Open-source, community-driven microfluidics with Metafluidics.

PubMed

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

2017-06-07

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

Deviation of a Jet at a T junction at low Reynolds number

NASA Astrophysics Data System (ADS)

Panizza, Pascal; Engl, Wilfried; Ohata, Kouske; Colin, Annie

2006-03-01

We study the hydrodynamic behaviour of a laminar jet flowing through a channel when it reaches a junction. We observe the existence of two possible flow regimes, namely the splitting and deviation of a jet in the most simple microfluidic configuration, namely a T junction. The transition between the two regimes is not monitored by the shape of the T junction nor by capillary effects, but can be easily anticipated in terms of the hydrodynamic properties of the flow. We present a simple hydrodynamic model which is in very good agreement with observed experimental jet behaviour. The transition between both regime acts as a flow or viscosity comparator. We show how this effect can be used for the design of digital and integrated microfluidic devices

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

PubMed Central

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

2015-01-01

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

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

PubMed Central

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

2015-01-01

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

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

PubMed

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

2015-01-01

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

Real-time Full-spectral Imaging and Affinity Measurements from 50 Microfluidic Channels using Nanohole Surface Plasmon Resonance†

PubMed Central

Lee, Si Hoon; Lindquist, Nathan C.; Wittenberg, Nathan J.; Jordan, Luke R.; Oh, Sang-Hyun

2012-01-01

With recent advances in high-throughput proteomics and systems biology, there is a growing demand for new instruments that can precisely quantify a wide range of receptor-ligand binding kinetics in a high-throughput fashion. Here we demonstrate a surface plasmon resonance (SPR) imaging spectroscopy instrument capable of extracting binding kinetics and affinities from 50 parallel microfluidic channels simultaneously. The instrument utilizes large-area (~cm2) metallic nanohole arrays as SPR sensing substrates and combines a broadband light source, a high-resolution imaging spectrometer and a low-noise CCD camera to extract spectral information from every channel in real time with a refractive index resolution of 7.7 × 10−6. To demonstrate the utility of our instrument for quantifying a wide range of biomolecular interactions, each parallel microfluidic channel is coated with a biomimetic supported lipid membrane containing ganglioside (GM1) receptors. The binding kinetics of cholera toxin b (CTX-b) to GM1 are then measured in a single experiment from 50 channels. By combining the highly parallel microfluidic device with large-area periodic nanohole array chips, our SPR imaging spectrometer system enables high-throughput, label-free, real-time SPR biosensing, and its full-spectral imaging capability combined with nanohole arrays could enable integration of SPR imaging with concurrent surface-enhanced Raman spectroscopy. PMID:22895607

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

DOE PAGES

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

2016-08-02

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

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

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

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

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

Microsensor Technologies for Plant Growth System Monitoring

NASA Technical Reports Server (NTRS)

Kim, Chang-Soo

2004-01-01

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

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.

A microfluidic separation platform using an array of slanted ramps

NASA Astrophysics Data System (ADS)

Risbud, Sumedh; Bernate, Jorge; Drazer, German

2013-03-01

The separation of the different components of a sample is a crucial step in many micro- and nano-fluidic applications, including the detection of infections, the capture of circulating tumor cells, the isolation of proteins, RNA and DNA, to mention but a few. Vector chromatography, in which different species migrate in different directions in a planar microfluidic device thus achieving spatial as well as temporal resolution, offers the promise of high selectivity along with high throughput. In this work, we present a microfluidic vector chromatography platform consisting of slanted ramps in a microfluidic channel for the separation of suspended particles. We construct these ramps using inclined UV lithography, such that the inclined portion of the ramps is upstream. We show that particles of different size displace laterally to a different extent when driven by a flow field over a slanted ramp. The flow close to the ramp reorients along the ramp, causing the size-dependent deflection of the particles. The cumulative effect of an array of these ramps would cause particles of different size to migrate in different directions, thus allowing their passive and continuous separation.

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.

Non-Hermitian engineering of single mode two dimensional laser arrays

PubMed Central

Teimourpour, Mohammad H.; Ge, Li; Christodoulides, Demetrios N.; El-Ganainy, Ramy

2016-01-01

A new scheme for building two dimensional laser arrays that operate in the single supermode regime is proposed. This is done by introducing an optical coupling between the laser array and lossy pseudo-isospectral chains of photonic resonators. The spectrum of this discrete reservoir is tailored to suppress all the supermodes of the main array except the fundamental one. This spectral engineering is facilitated by employing the Householder transformation in conjunction with discrete supersymmetry. The proposed scheme is general and can in principle be used in different platforms such as VCSEL arrays and photonic crystal laser arrays. PMID:27698355

A computational approach to real-time image processing for serial time-encoded amplified microscopy

NASA Astrophysics Data System (ADS)

Oikawa, Minoru; Hiyama, Daisuke; Hirayama, Ryuji; Hasegawa, Satoki; Endo, Yutaka; Sugie, Takahisa; Tsumura, Norimichi; Kuroshima, Mai; Maki, Masanori; Okada, Genki; Lei, Cheng; Ozeki, Yasuyuki; Goda, Keisuke; Shimobaba, Tomoyoshi

2016-03-01

High-speed imaging is an indispensable technique, particularly for identifying or analyzing fast-moving objects. The serial time-encoded amplified microscopy (STEAM) technique was proposed to enable us to capture images with a frame rate 1,000 times faster than using conventional methods such as CCD (charge-coupled device) cameras. The application of this high-speed STEAM imaging technique to a real-time system, such as flow cytometry for a cell-sorting system, requires successively processing a large number of captured images with high throughput in real time. We are now developing a high-speed flow cytometer system including a STEAM camera. In this paper, we describe our approach to processing these large amounts of image data in real time. We use an analog-to-digital converter that has up to 7.0G samples/s and 8-bit resolution for capturing the output voltage signal that involves grayscale images from the STEAM camera. Therefore the direct data output from the STEAM camera generates 7.0G byte/s continuously. We provided a field-programmable gate array (FPGA) device as a digital signal pre-processor for image reconstruction and finding objects in a microfluidic channel with high data rates in real time. We also utilized graphics processing unit (GPU) devices for accelerating the calculation speed of identification of the reconstructed images. We built our prototype system, which including a STEAM camera, a FPGA device and a GPU device, and evaluated its performance in real-time identification of small particles (beads), as virtual biological cells, owing through a microfluidic channel.

High-throughput microfluidic single-cell digital polymerase chain reaction.

PubMed

White, A K; Heyries, K A; Doolin, C; Vaninsberghe, M; Hansen, C L

2013-08-06

Here we present an integrated microfluidic device for the high-throughput digital polymerase chain reaction (dPCR) analysis of single cells. This device allows for the parallel processing of single cells and executes all steps of analysis, including cell capture, washing, lysis, reverse transcription, and dPCR analysis. The cDNA from each single cell is distributed into a dedicated dPCR array consisting of 1020 chambers, each having a volume of 25 pL, using surface-tension-based sample partitioning. The high density of this dPCR format (118,900 chambers/cm(2)) allows the analysis of 200 single cells per run, for a total of 204,000 PCR reactions using a device footprint of 10 cm(2). Experiments using RNA dilutions show this device achieves shot-noise-limited performance in quantifying single molecules, with a dynamic range of 10(4). We performed over 1200 single-cell measurements, demonstrating the use of this platform in the absolute quantification of both high- and low-abundance mRNA transcripts, as well as micro-RNAs that are not easily measured using alternative hybridization methods. We further apply the specificity and sensitivity of single-cell dPCR to performing measurements of RNA editing events in single cells. High-throughput dPCR provides a new tool in the arsenal of single-cell analysis methods, with a unique combination of speed, precision, sensitivity, and specificity. We anticipate this approach will enable new studies where high-performance single-cell measurements are essential, including the analysis of transcriptional noise, allelic imbalance, and RNA processing.

Microfluidic droplet trapping array as nanoliter reactors for gas-liquid chemical reaction.

PubMed

Zhang, Qingquan; Zeng, Shaojiang; Qin, Jianhua; Lin, Bingcheng

2009-09-01

This article presents a simple method for trapping arrays of droplets relying on the designed microstructures of the microfluidic device, and this has been successfully used for parallel gas-liquid chemical reaction. In this approach, the trapping structure is composed of main channel, lateral channel and trapping region. Under a negative pressure, array droplets can be generated and trapped in the microstructure simultaneously, without the use of surfactant and the precise control of the flow velocity. By using a multi-layer microdevice containing the microstructures, single (pH gradient) and multiple gas-liquid reactions (metal ion-NH3 complex reaction) can be performed in array droplets through the transmembrane diffusion of the gas. The droplets with quantitative concentration gradient can be formed by only replacing the specific membrane. The established method is simple, robust and easy to operate, demonstrating the potential of this device for droplet-based high-throughput screening.

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.

Label-free cancer cell separation from human whole blood using inertial microfluidics at low shear stress.

PubMed

Lee, Myung Gwon; Shin, Joong Ho; Bae, Chae Yun; Choi, Sungyoung; Park, Je-Kyun

2013-07-02

We report a contraction-expansion array (CEA) microchannel device that performs label-free high-throughput separation of cancer cells from whole blood at low Reynolds number (Re). The CEA microfluidic device utilizes hydrodynamic field effect for cancer cell separation, two kinds of inertial effects: (1) inertial lift force and (2) Dean flow, which results in label-free size-based separation with high throughput. To avoid cell damages potentially caused by high shear stress in conventional inertial separation techniques, the CEA microfluidic device isolates the cells with low operational Re, maintaining high-throughput separation, using nondiluted whole blood samples (hematocrit ~45%). We characterized inertial particle migration and investigated the migration of blood cells and various cancer cells (MCF-7, SK-BR-3, and HCC70) in the CEA microchannel. The separation of cancer cells from whole blood was demonstrated with a cancer cell recovery rate of 99.1%, a blood cell rejection ratio of 88.9%, and a throughput of 1.1 × 10(8) cells/min. In addition, the blood cell rejection ratio was further improved to 97.3% by a two-step filtration process with two devices connected in series.

Diffraction-Based Optical Switching with MEMS

DOE PAGES

Blanche, Pierre-Alexandre; LaComb, Lloyd; Wang, Youmin; ...

2017-04-19

In this article, we are presenting an overview of MEMS-based (Micro-Electro-Mechanical System) optical switch technology starting from the reflective two-dimensional (2D) and three-dimensional (3D) MEMS implementations. To further increase the speed of the MEMS from these devices, the mirror size needs to be reduced. Small mirror size prevents efficient reflection but favors a diffraction-based approach. Two implementations have been demonstrated, one using the Texas Instruments DLP (Digital Light Processing), and the other an LCoS-based (Liquid Crystal on Silicon) SLM (Spatial Light Modulator). These switches demonstrated the benefit of diffraction, by independently achieving high speed, efficiency, and high number of ports.more » We also demonstrated for the first time that PSK (Phase Shift Keying) modulation format can be used with diffraction-based devices. To be truly effective in diffraction mode, the MEMS pixels should modulate the phase of the incident light. We are presenting our past and current efforts to manufacture a new type of MEMS where the pixels are moving in the vertical direction. The original structure is a 32 x 32 phase modulator array with high contrast grating pixels, and we are introducing a new sub-wavelength linear array capable of a 310 kHz modulation rate« less

Diffraction-Based Optical Switching with MEMS

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

Blanche, Pierre-Alexandre; LaComb, Lloyd; Wang, Youmin

In this article, we are presenting an overview of MEMS-based (Micro-Electro-Mechanical System) optical switch technology starting from the reflective two-dimensional (2D) and three-dimensional (3D) MEMS implementations. To further increase the speed of the MEMS from these devices, the mirror size needs to be reduced. Small mirror size prevents efficient reflection but favors a diffraction-based approach. Two implementations have been demonstrated, one using the Texas Instruments DLP (Digital Light Processing), and the other an LCoS-based (Liquid Crystal on Silicon) SLM (Spatial Light Modulator). These switches demonstrated the benefit of diffraction, by independently achieving high speed, efficiency, and high number of ports.more » We also demonstrated for the first time that PSK (Phase Shift Keying) modulation format can be used with diffraction-based devices. To be truly effective in diffraction mode, the MEMS pixels should modulate the phase of the incident light. We are presenting our past and current efforts to manufacture a new type of MEMS where the pixels are moving in the vertical direction. The original structure is a 32 x 32 phase modulator array with high contrast grating pixels, and we are introducing a new sub-wavelength linear array capable of a 310 kHz modulation rate« less

GFZ Wireless Seismic Array (GFZ-WISE), a Wireless Mesh Network of Seismic Sensors: New Perspectives for Seismic Noise Array Investigations and Site Monitoring

PubMed Central

Picozzi, Matteo; Milkereit, Claus; Parolai, Stefano; Jaeckel, Karl-Heinz; Veit, Ingo; Fischer, Joachim; Zschau, Jochen

2010-01-01

Over the last few years, the analysis of seismic noise recorded by two dimensional arrays has been confirmed to be capable of deriving the subsoil shear-wave velocity structure down to several hundred meters depth. In fact, using just a few minutes of seismic noise recordings and combining this with the well known horizontal-to-vertical method, it has also been shown that it is possible to investigate the average one dimensional velocity structure below an array of stations in urban areas with a sufficient resolution to depths that would be prohibitive with active source array surveys, while in addition reducing the number of boreholes required to be drilled for site-effect analysis. However, the high cost of standard seismological instrumentation limits the number of sensors generally available for two-dimensional array measurements (i.e., of the order of 10), limiting the resolution in the estimated shear-wave velocity profiles. Therefore, new themes in site-effect estimation research by two-dimensional arrays involve the development and application of low-cost instrumentation, which potentially allows the performance of dense-array measurements, and the development of dedicated signal-analysis procedures for rapid and robust estimation of shear-wave velocity profiles. In this work, we present novel low-cost wireless instrumentation for dense two-dimensional ambient seismic noise array measurements that allows the real–time analysis of the surface-wavefield and the rapid estimation of the local shear-wave velocity structure for site response studies. We first introduce the general philosophy of the new system, as well as the hardware and software that forms the novel instrument, which we have tested in laboratory and field studies. PMID:22319298

Development of micropump-actuated negative pressure pinched injection for parallel electrophoresis on array microfluidic chip.

PubMed

Li, Bowei; Jiang, Lei; Xie, Hua; Gao, Yan; Qin, Jianhua; Lin, Bingcheng

2009-09-01

A micropump-actuated negative pressure pinched injection method is developed for parallel electrophoresis on a multi-channel LIF detection system. The system has a home-made device that could individually control 16-port solenoid valves and a high-voltage power supply. The laser beam is excitated and distributes to the array separation channels for detection. The hybrid Glass-PDMS microfluidic chip comprises two common reservoirs, four separation channels coupled to their respective pneumatic micropumps and two reference channels. Due to use of pressure as a driving force, the proposed method has no sample bias effect for separation. There is only one high-voltage supply needed for separation without relying on the number of channels, which is significant for high-throughput analysis, and the time for sample loading is shortened to 1 s. In addition, the integrated micropumps can provide the versatile interface for coupling with other function units to satisfy the complicated demands. The performance is verified by separation of DNA marker and Hepatitis B virus DNA samples. And this method is also expected to show the potential throughput for the DNA analysis in the field of disease diagnosis.

Development of digital sideband separating down-conversion for Yuan-Tseh Lee Array

NASA Astrophysics Data System (ADS)

Li, Chao-Te; Kubo, Derek; Cheng, Jen-Chieh; Kuroda, John; Srinivasan, Ranjani; Ho, Solomon; Guzzino, Kim; Chen, Ming-Tang

2016-07-01

This report presents a down-conversion method involving digital sideband separation for the Yuan-Tseh Lee Array (YTLA) to double the processing bandwidth. The receiver consists of a MMIC HEMT LNA front end operating at a wavelength of 3 mm, and sub-harmonic mixers that output signals at intermediate frequencies (IFs) of 2-18 GHz. The sideband separation scheme involves an analog 90° hybrid followed by two mixers that provide down-conversion of the IF signal to a pair of in-phase (I) and quadrature (Q) signals in baseband. The I and Q baseband signals are digitized using 5 Giga sample per second (Gsps) analog-to-digital converters (ADCs). A second hybrid is digitally implemented using field-programmable gate arrays (FPGAs) to produce two sidebands, each with a bandwidth of 1.6 GHz. The 2 x 1.6 GHz band can be tuned to cover any 3.6 GHz window within the aforementioned IF range of the array. Sideband rejection ratios (SRRs) above 20 dB can be obtained across the 3.6 GHz bandwidth by equalizing the power and delay between the I and Q baseband signals. Furthermore, SRRs above 30 dB can be achieved when calibration is applied.

Two-Dimensional Array Beam Scanning Via Externally and Mutually Injection Locked Coupled Oscillators

NASA Technical Reports Server (NTRS)

Pogorzelski, Ronald J.

2000-01-01

Some years ago, Stephan proposed an approach to one dimensional (linear) phased array beam steering which requires only a single phase shifter. This involves the use of a linear array of voltage-controlled electronic oscillators coupled to nearest neighbors. The oscillators are mutually injection locked by controlling their coupling and tuning appropriately. Stephan's approach consists of deriving two signals from a master oscillator, one signal phase shifted with respect to the other by means of a single phase shifter. These two signals are injected into the end oscillators of the array. The result is a linear phase progression across the oscillator array. Thus, if radiating elements are connected to each oscillator and spaced uniformly along a line, they will radiate a beam at an angle to that line determined by the phase gradient which is, in turn, determined by the phase difference between the injection signals.The beam direction is therefore controlled by adjusting this phase difference. Recently, Pogorzelski and York presented a formulation which facilitates theoretical analysis of the above beam steering technique. This was subsequently applied by Pogorzelski in analysis of two dimensional beam steering using perimeter detuning of a coupled oscillator array. The formulation is based on a continuum model in which the oscillator phases are represented by a continuous function satisfying a partial differential equation of diffusion type. This equation can be solved via the Laplace transform and the resulting solution exhibits the dynamic behavior of the array as the beam is steered. Stephan's beam steering technique can be similarly generalized to two-dimensional arrays in which the beam control signals are applied to the oscillators on the perimeter of the array. In this paper the continuum model for this two-dimensional case is developed and the dynamic solution for the corresponding aperture phase function is obtained. The corresponding behavior of the resulting far-zone radiation pattern is displayed as well.

Depth-enhanced three-dimensional-two-dimensional convertible display based on modified integral imaging.

PubMed

Park, Jae-Hyeung; Kim, Hak-Rin; Kim, Yunhee; Kim, Joohwan; Hong, Jisoo; Lee, Sin-Doo; Lee, Byoungho

2004-12-01

A depth-enhanced three-dimensional-two-dimensional convertible display that uses a polymer-dispersed liquid crystal based on the principle of integral imaging is proposed. In the proposed method, a lens array is located behind a transmission-type display panel to form an array of point-light sources, and a polymer-dispersed liquid crystal is electrically controlled to pass or to scatter light coming from these point-light sources. Therefore, three-dimensional-two-dimensional conversion is accomplished electrically without any mechanical movement. Moreover, the nonimaging structure of the proposed method increases the expressible depth range considerably. We explain the method of operation and present experimental results.

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

PubMed Central

Lazar, Iulia M.; Kabulski, Jarod L.

2013-01-01

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

Capture and X-ray diffraction studies of protein microcrystals in a microfluidic trap array

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

Lyubimov, Artem Y.; Stanford University, Stanford, CA 94305; Stanford University, Stanford, CA 94305

A microfluidic platform has been developed for the capture and X-ray analysis of protein microcrystals, affording a means to improve the efficiency of XFEL and synchrotron experiments. X-ray free-electron lasers (XFELs) promise to enable the collection of interpretable diffraction data from samples that are refractory to data collection at synchrotron sources. At present, however, more efficient sample-delivery methods that minimize the consumption of microcrystalline material are needed to allow the application of XFEL sources to a wide range of challenging structural targets of biological importance. Here, a microfluidic chip is presented in which microcrystals can be captured at fixed, addressablemore » points in a trap array from a small volume (<10 µl) of a pre-existing slurry grown off-chip. The device can be mounted on a standard goniostat for conducting diffraction experiments at room temperature without the need for flash-cooling. Proof-of-principle tests with a model system (hen egg-white lysozyme) demonstrated the high efficiency of the microfluidic approach for crystal harvesting, permitting the collection of sufficient data from only 265 single-crystal still images to permit determination and refinement of the structure of the protein. This work shows that microfluidic capture devices can be readily used to facilitate data collection from protein microcrystals grown in traditional laboratory formats, enabling analysis when cryopreservation is problematic or when only small numbers of crystals are available. Such microfluidic capture devices may also be useful for data collection at synchrotron sources.« less

Plasmonic Nanoholes in a Multi-Channel Microarray Format for Parallel Kinetic Assays and Differential Sensing

PubMed Central

Im, Hyungsoon; Lesuffleur, Antoine; Lindquist, Nathan C.; Oh, Sang-Hyun

2009-01-01

We present nanohole arrays in a gold film integrated with a 6-channel microfluidic chip for parallel measurements of molecular binding kinetics. Surface plasmon resonance effects in the nanohole arrays enable real-time label-free measurements of molecular binding events in each channel, while adjacent negative reference channels can record measurement artifacts such as bulk solution index changes, temperature variations, or changing light absorption in the liquid. Using this platform, streptavidin-biotin specific binding kinetics are measured at various concentrations with negative controls. A high-density microarray of 252 biosensing pixels is also demonstrated with a packing density of 106 sensing elements/cm2, which can potentially be coupled with a massively parallel array of microfluidic channels for protein microarray applications. PMID:19284776

Controlling the trajectories of bubble trains at a microfluidic junction

NASA Astrophysics Data System (ADS)

Parthiban, Pravien; Khan, Saif

2011-11-01

The increasing number of applications facilitated by digital microfluidic flows has resulted in a sustained interest in not only understanding the diverse, interesting and often complex dynamics associated with such flows in microchannel networks but also in developing facile strategies to control them. We find that there are readily accessible flow speeds wherein resistance to flow in microchannels decreases with an increase in the number of confined bubbles present, and exploit this intriguing phenomenon to sort all bubble of a train exclusively into one of the arms of a nominally symmetric microfluidic loop. We also demonstrate how the arm into which the train filters into can be chosen by applying a temporary external stimulus by means of an additional flow of the continuous liquid into one the arms of the loop. Furthermore, we show how by tuning the magnitude and period of this temporary stimulus we can switch controllably, the traffic of bubbles between both arms of the loop even when the loop is asymmetric. The results of this work should aid in developing viable methods to regulate traffic of digital flows in microfluidic networks.

Rapid three-dimensional microfluidic mixer for high viscosity solutions to unravel earlier folding kinetics of G-quadruplex under molecular crowding conditions.

PubMed

Liu, Chao; Li, Ying; Li, Yiwei; Chen, Peng; Feng, Xiaojun; Du, Wei; Liu, Bi-Feng

2016-01-01

Rapid mixing of highly viscous solutions is a great challenge, which helps to analyze the reaction kinetics in viscous liquid phase, particularly to discover the folding kinetics of macromolecules under molecular crowding conditions mimicking the conditions inside cells. Here, we demonstrated a novel microfluidic mixer based on Dean flows with three-dimensional (3D) microchannel configuration for fast mixing of high-viscosity fluids. The main structure contained three consecutive subunits, each consisting of a "U"-type channel followed by a chamber with different width and height. Thus, the two solutions injected from the two inlets would undergo a mixing in the first "U"-type channel due to the Dean flow effect, and simultaneous vortices expansions in both horizontal and vertical directions in the following chamber. Numerical simulations and experimental characterizations confirmed that the micromixer could achieve a mixing time of 122.4μs for solutions with viscosities about 33.6 times that of pure water. It was the fastest micromixer for high viscosity solutions compared with previous reports. With this highly efficient 3D microfluidic mixer, we further characterized the early folding kinetics of human telomere G-quadruplex under molecular crowding conditions, and unravelled a new folding process within 550μs. Copyright © 2015 Elsevier B.V. All rights reserved.

Enhancing depth of focus in tilted microfluidics channels by digital holography.

PubMed

Matrecano, Marcella; Paturzo, Melania; Finizio, Andrea; Ferraro, Pietro

2013-03-15

In this Letter we propose a method to enhance the limited depth of field (DOF) in optical imaging systems, through digital holography. The proposed approach is based on the introduction of a cubic phase plate into the diffraction integral, analogous to what occurs in white-light imaging systems. By this approach we show that it is possible to improve the DOF and to recover the extended focus image of a tilted object in a single reconstruction step. Moreover, we demonstrate the possibility of obtaining well-focused biological cells flowing into a tilted microfluidic channel.

Partially filled electrodes for digital microfluidic devices

NASA Astrophysics Data System (ADS)

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

2013-07-01

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

High-volume production of single and compound emulsions in a microfluidic parallelization arrangement coupled with coaxial annular world-to-chip interfaces.

PubMed

Nisisako, Takasi; Ando, Takuya; Hatsuzawa, Takeshi

2012-09-21

This study describes a microfluidic platform with coaxial annular world-to-chip interfaces for high-throughput production of single and compound emulsion droplets, having controlled sizes and internal compositions. The production module consists of two distinct elements: a planar square chip on which many copies of a microfluidic droplet generator (MFDG) are arranged circularly, and a cubic supporting module with coaxial annular channels for supplying fluids evenly to the inlets of the mounted chip, assembled from blocks with cylinders and holes. Three-dimensional flow was simulated to evaluate the distribution of flow velocity in the coaxial multiple annular channels. By coupling a 1.5 cm × 1.5 cm microfluidic chip with parallelized 144 MFDGs and a supporting module with two annular channels, for example, we could produce simple oil-in-water (O/W) emulsion droplets having a mean diameter of 90.7 μm and a coefficient of variation (CV) of 2.2% at a throughput of 180.0 mL h(-1). Furthermore, we successfully demonstrated high-throughput production of Janus droplets, double emulsions and triple emulsions, by coupling 1.5 cm × 1.5 cm - 4.5 cm × 4.5 cm microfluidic chips with parallelized 32-128 MFDGs of various geometries and supporting modules with 3-4 annular channels.

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.

A computer controlled television detector for light, X-rays and particles

NASA Technical Reports Server (NTRS)

Kalata, K.

1981-01-01

A versatile, high resolution, software configurable, two-dimensional intensified vidicon quantum detector system has been developed for multiple research applications. A thin phosphor convertor allows the detection of X-rays below 20 keV and non-relativistic particles in addition to visible light, and a thicker scintillator can be used to detect X-rays up to 100 keV and relativistic particles. Faceplates may be changed to allow any active area from 1 to 40 mm square, and active areas up to 200 mm square are possible. The image is integrated in a digital memory on any software specified array size up to 4000 x 4000. The array size is selected to match the spatial resolution, which ranges from 10 to 100 microns depending on the operating mode, the active area, and the photon or particle energy. All scan and data acquisition parameters are under software control to allow optimal data collection for each application.

Boundary-layer transition and global skin friction measurement with an oil-fringe imaging technique

NASA Technical Reports Server (NTRS)

Monson, Daryl J.; Mateer, George G.; Menter, Florian R.

1993-01-01

A new oil-fringe imaging system skin friction (FISF) technique to measure skin friction on wind tunnel models is presented. In the method used to demonstrate the technique, lines of oil are applied on surfaces that connect the intended sets of measurement points, and then a wind tunnel is run so that the oil thins and forms interference fringes that are spaced in proportion to local skin friction. After a run the fringe spacings are imaged with a CCD-array digital camera and measured on a computer. Skin friction and transition measurements on a two-dimensional wing are presented and compared with computational predictions.

Scalable loading of a two-dimensional trapped-ion array

PubMed Central

Bruzewicz, Colin D.; McConnell, Robert; Chiaverini, John; Sage, Jeremy M.

2016-01-01

Two-dimensional arrays of trapped-ion qubits are attractive platforms for scalable quantum information processing. Sufficiently rapid reloading capable of sustaining a large array, however, remains a significant challenge. Here with the use of a continuous flux of pre-cooled neutral atoms from a remotely located source, we achieve fast loading of a single ion per site while maintaining long trap lifetimes and without disturbing the coherence of an ion quantum bit in an adjacent site. This demonstration satisfies all major criteria necessary for loading and reloading extensive two-dimensional arrays, as will be required for large-scale quantum information processing. Moreover, the already high loading rate can be increased by loading ions in parallel with only a concomitant increase in photo-ionization laser power and no need for additional atomic flux. PMID:27677357

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

DTIC Science & Technology

2005-10-15

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

A rapid, straightforward, and print house compatible mass fabrication method for integrating 3D paper-based microfluidics.

PubMed

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

2013-11-01

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

Development of a microfluidic perfusion 3D cell culture system

NASA Astrophysics Data System (ADS)

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

2018-04-01

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

Three-axis digital holographic microscopy for high speed volumetric imaging.

PubMed

Saglimbeni, F; Bianchi, S; Lepore, A; Di Leonardo, R

2014-06-02

Digital Holographic Microscopy allows to numerically retrieve three dimensional information encoded in a single 2D snapshot of the coherent superposition of a reference and a scattered beam. Since no mechanical scans are involved, holographic techniques have a superior performance in terms of achievable frame rates. Unfortunately, numerical reconstructions of scattered field by back-propagation leads to a poor axial resolution. Here we show that overlapping the three numerical reconstructions obtained by tilted red, green and blue beams results in a great improvement over the axial resolution and sectioning capabilities of holographic microscopy. A strong reduction in the coherent background noise is also observed when combining the volumetric reconstructions of the light fields at the three different wavelengths. We discuss the performance of our technique with two test objects: an array of four glass beads that are stacked along the optical axis and a freely diffusing rod shaped E.coli bacterium.

A microfluidic platform for controlled biochemical stimulation of twin neuronal networks.

PubMed

Biffi, Emilia; Piraino, Francesco; Pedrocchi, Alessandra; Fiore, Gianfranco B; Ferrigno, Giancarlo; Redaelli, Alberto; Menegon, Andrea; Rasponi, Marco

2012-06-01

Spatially and temporally resolved delivery of soluble factors is a key feature for pharmacological applications. In this framework, microfluidics coupled to multisite electrophysiology offers great advantages in neuropharmacology and toxicology. In this work, a microfluidic device for biochemical stimulation of neuronal networks was developed. A micro-chamber for cell culturing, previously developed and tested for long term neuronal growth by our group, was provided with a thin wall, which partially divided the cell culture region in two sub-compartments. The device was reversibly coupled to a flat micro electrode array and used to culture primary neurons in the same microenvironment. We demonstrated that the two fluidically connected compartments were able to originate two parallel neuronal networks with similar electrophysiological activity but functionally independent. Furthermore, the device allowed to connect the outlet port to a syringe pump and to transform the static culture chamber in a perfused one. At 14 days invitro, sub-networks were independently stimulated with a test molecule, tetrodotoxin, a neurotoxin known to block action potentials, by means of continuous delivery. Electrical activity recordings proved the ability of the device configuration to selectively stimulate each neuronal network individually. The proposed microfluidic approach represents an innovative methodology to perform biological, pharmacological, and electrophysiological experiments on neuronal networks. Indeed, it allows for controlled delivery of substances to cells, and it overcomes the limitations due to standard drug stimulation techniques. Finally, the twin network configuration reduces biological variability, which has important outcomes on pharmacological and drug screening.

Packings of monodisperse emulsions in flat microfluidic channels

NASA Astrophysics Data System (ADS)

Claussen, Ohle; Herminghaus, Stephan; Brinkmann, Martin

2012-06-01

In the lateral confinement of a flat microfluidic channel, monodisperse emulsion droplets spontaneously self-organize in a variety of topologically different packings. The explicit construction of mechanically equilibrated arrangements of effectively two-dimensional congruent droplet shapes reveals the existence of multiple mechanical equilibria depending on channel width W, droplet area Ad, and volume fraction φ of the dispersed phase. The corresponding boundaries of local or global stability are summarized in a packing diagram for congruent droplet shapes in terms of the dimensionless channel width w=W/Ad and φ. In agreement with experimental results, an increasingly strong hysteresis of the transition between single-row and two-row packings is observed during changes of w above a threshold volume fraction of φ*≃0.813.

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

PubMed Central

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

2016-01-01

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

Self-leveling 2D DPN probe arrays

NASA Astrophysics Data System (ADS)

Haaheim, Jason R.; Val, Vadim; Solheim, Ed; Bussan, John; Fragala, J.; Nelson, Mike

2010-02-01

Dip Pen Nanolithography® (DPN®) is a direct write scanning probe-based technique which operates under ambient conditions, making it suitable to deposit a wide range of biological and inorganic materials. Precision nanoscale deposition is a fundamental requirement to advance nanoscale technology in commercial applications, and tailoring chemical composition and surface structure on the sub-100 nm scale benefits researchers in areas ranging from cell adhesion to cell-signaling and biomimetic membranes. These capabilities naturally suggest a "Desktop Nanofab" concept - a turnkey system that allows a non-expert user to rapidly create high resolution, scalable nanostructures drawing upon well-characterized ink and substrate pairings. In turn, this system is fundamentally supported by a portfolio of MEMS devices tailored for microfluidic ink delivery, directed placement of nanoscale materials, and cm2 tip arrays for high-throughput nanofabrication. Massively parallel two-dimensional nanopatterning is now commercially available via NanoInk's 2D nano PrintArray™, making DPN a high-throughput (>3×107 μm2 per hour), flexible and versatile method for precision nanoscale pattern formation. However, cm2 arrays of nanoscopic tips introduce the nontrivial problem of getting them all evenly touching the surface to ensure homogeneous deposition; this requires extremely precise leveling of the array. Herein, we describe how we have made the process simple by way of a selfleveling gimbal attachment, coupled with semi-automated software leveling routines which bring the cm^2 chip to within 0.002 degrees of co-planarity. This excellent co-planarity yields highly homogeneous features across a square centimeter, with <6% feature size standard deviation. We have engineered the devices to be easy to use, wire-free, and fully integrated with both of our patterning tools: the DPN 5000, and the NLP 2000.

Silver nanostructures synthesis via optically induced electrochemical deposition

NASA Astrophysics Data System (ADS)

Li, Pan; Liu, Na; Yu, Haibo; Wang, Feifei; Liu, Lianqing; Lee, Gwo-Bin; Wang, Yuechao; Li, Wen Jung

2016-06-01

We present a new digitally controlled, optically induced electrochemical deposition (OED) method for fabricating silver nanostructures. Projected light patterns were used to induce an electrochemical reaction in a specialized sandwich-like microfluidic device composed of one indium tin oxide (ITO) glass electrode and an optically sensitive-layer-covered ITO electrode. Silver polyhedral nanoparticles, triangular and hexagonal nanoplates, and nanobelts were controllably synthesized in specific positions at which projected light was illuminated. The silver nanobelts had rectangular cross-sections with an average width of 300 nm and an average thickness of 100 nm. By controlling the applied voltage, frequency, and time, different silver nanostructure morphologies were obtained. Based on the classic electric double-layer theory, a dynamic process of reduction and crystallization can be described in terms of three phases. Because it is template- and surfactant-free, the digitally controlled OED method facilitates the easy, low cost, efficient, and flexible synthesis of functional silver nanostructures, especially quasi-one-dimensional nanobelts.

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.

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

PubMed

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

2011-10-15

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

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

PubMed

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

2014-03-15

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

Discrete elliptic solitons in two-dimensional waveguide arrays

NASA Astrophysics Data System (ADS)

Ye, Fangwei; Dong, Liangwei; Wang, Jiandong; Cai, Tian; Li, Yong-Ping

2005-04-01

The fundamental properties of discrete elliptic solitons (DESs) in the two-dimensional waveguide arrays were studied. The DESs show nontrivial spatial structures in their parameters space due to the introduction of the new freedom of ellipticity, and their stability is closely linked to their propagation directions in the transverse plane.

Eliminating Bias In Acousto-Optical Spectrum Analysis

NASA Technical Reports Server (NTRS)

Ansari, Homayoon; Lesh, James R.

1992-01-01

Scheme for digital processing of video signals in acousto-optical spectrum analyzer provides real-time correction for signal-dependent spectral bias. Spectrum analyzer described in "Two-Dimensional Acousto-Optical Spectrum Analyzer" (NPO-18092), related apparatus described in "Three-Dimensional Acousto-Optical Spectrum Analyzer" (NPO-18122). Essence of correction is to average over digitized outputs of pixels in each CCD row and to subtract this from the digitized output of each pixel in row. Signal processed electro-optically with reference-function signals to form two-dimensional spectral image in CCD camera.

A 45 ps time digitizer with a two-phase clock and dual-edge two-stage interpolation in a field programmable gate array device

NASA Astrophysics Data System (ADS)

Szplet, R.; Kalisz, J.; Jachna, Z.

2009-02-01

We present a time digitizer having 45 ps resolution, integrated in a field programmable gate array (FPGA) device. The time interval measurement is based on the two-stage interpolation method. A dual-edge two-phase interpolator is driven by the on-chip synthesized 250 MHz clock with precise phase adjustment. An improved dual-edge double synchronizer was developed to control the main counter. The nonlinearity of the digitizer's transfer characteristic is identified and utilized by the dedicated hardware code processor for the on-the-fly correction of the output data. Application of presented ideas has resulted in the measurement uncertainty of the digitizer below 70 ps RMS over the time interval ranging from 0 to 1 s. The use of the two-stage interpolation and a fast FIFO memory has allowed us to obtain the maximum measurement rate of five million measurements per second.

Sensitive and inexpensive digital DNA analysis by microfluidic enrichment of rolling circle amplified single-molecules

PubMed Central

Kühnemund, Malte; Hernández-Neuta, Iván; Sharif, Mohd Istiaq; Cornaglia, Matteo; Gijs, Martin A.M.

2017-01-01

Abstract Single molecule quantification assays provide the ultimate sensitivity and precision for molecular analysis. However, most digital analysis techniques, i.e. droplet PCR, require sophisticated and expensive instrumentation for molecule compartmentalization, amplification and analysis. Rolling circle amplification (RCA) provides a simpler means for digital analysis. Nevertheless, the sensitivity of RCA assays has until now been limited by inefficient detection methods. We have developed a simple microfluidic strategy for enrichment of RCA products into a single field of view of a low magnification fluorescent sensor, enabling ultra-sensitive digital quantification of nucleic acids over a dynamic range from 1.2 aM to 190 fM. We prove the broad applicability of our analysis platform by demonstrating 5-plex detection of as little as ∼1 pg (∼300 genome copies) of pathogenic DNA with simultaneous antibiotic resistance marker detection, and the analysis of rare oncogene mutations. Our method is simpler, more cost-effective and faster than other digital analysis techniques and provides the means to implement digital analysis in any laboratory equipped with a standard fluorescent microscope. PMID:28077562

High gradient magnetic field microstructures for magnetophoretic cell separation.

PubMed

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

2016-08-01

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

Low-Cost Rapid Prototyping of Whole-Glass Microfluidic Devices

ERIC Educational Resources Information Center

Yuen, Po Ki; Goral, Vasiliy N.

2012-01-01

A low-cost, straightforward, rapid prototyping of whole-glass microfluidic devices is presented using glass-etching cream that can be easily purchased in local stores. A self-adhered vinyl stencil cut out by a desktop digital craft cutter was used as an etching mask for patterning microstructures in glass using the glass-etching cream. A specific…

A droplet-to-digital (D2D) microfluidic device for single cell assays.

PubMed

Shih, Steve C C; Gach, Philip C; Sustarich, Jess; Simmons, Blake A; Adams, Paul D; Singh, Seema; Singh, Anup K

2015-01-07

We have developed a new hybrid droplet-to-digital microfluidic platform (D2D) that integrates droplet-in-channel microfluidics with digital microfluidics (DMF) for performing multi-step assays. This D2D platform combines the strengths of the two formats-droplets-in-channel for facile generation of droplets containing single cells, and DMF for on-demand manipulation of droplets including control of different droplet volumes (pL-μL), creation of a dilution series of ionic liquid (IL), and parallel single cell culturing and analysis for IL toxicity screening. This D2D device also allows for automated analysis that includes a feedback-controlled system for merging and splitting of droplets to add reagents, an integrated Peltier element for parallel cell culture at optimum temperature, and an impedance sensing mechanism to control the flow rate for droplet generation and preventing droplet evaporation. Droplet-in-channel is well-suited for encapsulation of single cells as it allows the careful manipulation of flow rates of aqueous phase containing cells and oil to optimize encapsulation. Once single cell containing droplets are generated, they are transferred to a DMF chip via a capillary where they are merged with droplets containing IL and cultured at 30 °C. The DMF chip, in addition to permitting cell culture and reagent (ionic liquid/salt) addition, also allows recovery of individual droplets for off-chip analysis such as further culturing and measurement of ethanol production. The D2D chip was used to evaluate the effect of IL/salt type (four types: NaOAc, NaCl, [C2mim] [OAc], [C2mim] [Cl]) and concentration (four concentrations: 0, 37.5, 75, 150 mM) on the growth kinetics and ethanol production of yeast and as expected, increasing IL concentration led to lower biomass and ethanol production. Specifically, [C2mim] [OAc] had inhibitory effects on yeast growth at concentrations 75 and 150 mM and significantly reduced their ethanol production compared to cells grown in other ILs/salts. The growth curve trends obtained by D2D matched conventional yeast culturing in microtiter wells, validating the D2D platform. We believe that our approach represents a generic platform for multi-step biochemical assays such as drug screening, digital PCR, enzyme assays, immunoassays and cell-based assays.

IF digitization receiver of wideband digital array radar test-bed

NASA Astrophysics Data System (ADS)

Li, Weixing; Zhang, Yue; Lin, Jianzhi; Chen, Zengping

2014-10-01

In this paper, an X-band, 8-element wideband digital array radar (DAR) test-bed is presented, which makes use of a novel digital backend coupled with highly-integrated, multi-channel intermediate frequency (IF) digital receiver. Radar returns are received by the broadband antenna and then down-converted to the IF of 0.6GHz-3.0GHz. Four band-pass filters are applied in the front-end to divide the IF returns into four frequency bands with the instantaneous bandwidth of 500MHz. Every four array elements utilize a digital receiver, which is focused in this paper. The digital receivers are designed in a compact and flexible manner to meet the demands of DAR system. Each receiver consists of a fourchannel ADC, a high-performance FPGA, four DDR3 chips and two optical transceivers. With the sampling rate of up to 1.2GHz each channel, the ADC is capable of directly sampling the IF returns of four array elements at 10bits. In addition to serving as FIFO and controller, the onboard FPGA is also utilized for the implementation of various real-time algorithms such as DDC and channel calibration. Data is converted to bit stream and transferred through two low overhead, high data rate and multi-channel optical transceivers. Key technologies such as channel calibration and wideband DOA are studied with the measured data which is obtained in the experiments to illustrate the functionality of the system.

Capture and X-ray diffraction studies of protein microcrystals in a microfluidic trap array

DOE PAGES

Lyubimov, Artem Y.; Murray, Thomas D.; Koehl, Antoine; ...

2015-03-27

X-ray free-electron lasers (XFELs) promise to enable the collection of interpretable diffraction data from samples that are refractory to data collection at synchrotron sources. At present, however, more efficient sample-delivery methods that minimize the consumption of microcrystalline material are needed to allow the application of XFEL sources to a wide range of challenging structural targets of biological importance. Here, a microfluidic chip is presented in which microcrystals can be captured at fixed, addressable points in a trap array from a small volume (<10 µl) of a pre-existing slurry grown off-chip. The device can be mounted on a standard goniostat formore » conducting diffraction experiments at room temperature without the need for flash-cooling. Proof-of-principle tests with a model system (hen egg-white lysozyme) demonstrated the high efficiency of the microfluidic approach for crystal harvesting, permitting the collection of sufficient data from only 265 single-crystal still images to permit determination and refinement of the structure of the protein. This work shows that microfluidic capture devices can be readily used to facilitate data collection from protein microcrystals grown in traditional laboratory formats, enabling analysis when cryopreservation is problematic or when only small numbers of crystals are available. Such microfluidic capture devices may also be useful for data collection at synchrotron sources.« less

Capture and X-ray diffraction studies of protein microcrystals in a microfluidic trap array

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

Lyubimov, Artem Y.; Murray, Thomas D.; Koehl, Antoine

X-ray free-electron lasers (XFELs) promise to enable the collection of interpretable diffraction data from samples that are refractory to data collection at synchrotron sources. At present, however, more efficient sample-delivery methods that minimize the consumption of microcrystalline material are needed to allow the application of XFEL sources to a wide range of challenging structural targets of biological importance. Here, a microfluidic chip is presented in which microcrystals can be captured at fixed, addressable points in a trap array from a small volume (<10 µl) of a pre-existing slurry grown off-chip. The device can be mounted on a standard goniostat formore » conducting diffraction experiments at room temperature without the need for flash-cooling. Proof-of-principle tests with a model system (hen egg-white lysozyme) demonstrated the high efficiency of the microfluidic approach for crystal harvesting, permitting the collection of sufficient data from only 265 single-crystal still images to permit determination and refinement of the structure of the protein. This work shows that microfluidic capture devices can be readily used to facilitate data collection from protein microcrystals grown in traditional laboratory formats, enabling analysis when cryopreservation is problematic or when only small numbers of crystals are available. Such microfluidic capture devices may also be useful for data collection at synchrotron sources.« less

Plenoptic camera image simulation for reconstruction algorithm verification

NASA Astrophysics Data System (ADS)

Schwiegerling, Jim

2014-09-01

Plenoptic cameras have emerged in recent years as a technology for capturing light field data in a single snapshot. A conventional digital camera can be modified with the addition of a lenslet array to create a plenoptic camera. Two distinct camera forms have been proposed in the literature. The first has the camera image focused onto the lenslet array. The lenslet array is placed over the camera sensor such that each lenslet forms an image of the exit pupil onto the sensor. The second plenoptic form has the lenslet array relaying the image formed by the camera lens to the sensor. We have developed a raytracing package that can simulate images formed by a generalized version of the plenoptic camera. Several rays from each sensor pixel are traced backwards through the system to define a cone of rays emanating from the entrance pupil of the camera lens. Objects that lie within this cone are integrated to lead to a color and exposure level for that pixel. To speed processing three-dimensional objects are approximated as a series of planes at different depths. Repeating this process for each pixel in the sensor leads to a simulated plenoptic image on which different reconstruction algorithms can be tested.

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

NASA Astrophysics Data System (ADS)

Yeo, Leslie; Rezk, Amgad

2017-11-01

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

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.

Hierarchical self-assembly of actin in micro-confinements using microfluidics

PubMed Central

Deshpande, Siddharth; Pfohl, Thomas

2012-01-01

We present a straightforward microfluidics system to achieve step-by-step reaction sequences in a diffusion-controlled manner in quasi two-dimensional micro-confinements. We demonstrate the hierarchical self-organization of actin (actin monomers—entangled networks of filaments—networks of bundles) in a reversible fashion by tuning the Mg2+ ion concentration in the system. We show that actin can form networks of bundles in the presence of Mg2+ without any cross-linking proteins. The properties of these networks are influenced by the confinement geometry. In square microchambers we predominantly find rectangular networks, whereas triangular meshes are predominantly found in circular chambers. PMID:24032070

Flexible microfluidic devices with three-dimensional interconnected microporous walls for gas and liquid applications.

PubMed

Yuen, Po Ki; DeRosa, Michael E

2011-10-07

This article presents a simple, low-cost method of fabrication and the applications of flexible polystyrene microfluidic devices with three-dimensional (3D) interconnected microporous walls based on treatment using a solvent/non-solvent mixture at room temperature. The complete fabrication process from device design concept to working device can be completed in less than an hour in a regular laboratory setting, without the need for expensive equipment. Microfluidic devices were used to demonstrate gas generation and absorption reactions by acidifying water with carbon dioxide (CO(2)) gas. By selectively treating the microporous structures with oxygen plasma, acidification of water by acetic acid (distilled white vinegar) perfusion was also demonstrated with the same device design.

Patterning two-dimensional chalcogenide crystals of Bi2Se3 and In2Se3 and efficient photodetectors

PubMed Central

Zheng, Wenshan; Xie, Tian; Zhou, Yu; Chen, Y.L.; Jiang, Wei; Zhao, Shuli; Wu, Jinxiong; Jing, Yumei; Wu, Yue; Chen, Guanchu; Guo, Yunfan; Yin, Jianbo; Huang, Shaoyun; Xu, H.Q.; Liu, Zhongfan; Peng, Hailin

2015-01-01

Patterning of high-quality two-dimensional chalcogenide crystals with unique planar structures and various fascinating electronic properties offers great potential for batch fabrication and integration of electronic and optoelectronic devices. However, it remains a challenge that requires accurate control of the crystallization, thickness, position, orientation and layout. Here we develop a method that combines microintaglio printing with van der Waals epitaxy to efficiently pattern various single-crystal two-dimensional chalcogenides onto transparent insulating mica substrates. Using this approach, we have patterned large-area arrays of two-dimensional single-crystal Bi2Se3 topological insulator with a record high Hall mobility of ∼1,750 cm2 V−1 s−1 at room temperature. Furthermore, our patterned two-dimensional In2Se3 crystal arrays have been integrated and packaged to flexible photodetectors, yielding an ultrahigh external photoresponsivity of ∼1,650 A W−1 at 633 nm. The facile patterning, integration and packaging of high-quality two-dimensional chalcogenide crystals hold promise for innovations of next-generation photodetector arrays, wearable electronics and integrated optoelectronic circuits. PMID:25898022

Study of one- and two-dimensional filtering and deconvolution algorithms for a streaming array computer

NASA Technical Reports Server (NTRS)

Ioup, G. E.

1985-01-01

Appendix 5 of the Study of One- and Two-Dimensional Filtering and Deconvolution Algorithms for a Streaming Array Computer includes a resume of the professional background of the Principal Investigator on the project, lists of this publications and research papers, graduate thesis supervised, and grants received.

Fabrication of robust tooling for mass production of polymeric microfluidic devices

NASA Astrophysics Data System (ADS)

Fu, G.; Tor, S. B.; Loh, N. H.; Hardt, D. E.

2010-08-01

Polymer microfluidic devices are gaining popularity for bio-applications. In both commonly used methods for the fabrication of polymer microfluidic devices, i.e. injection molding and hot-embossing, the quality of a mold insert is of high importance. Micro powder injection molding (μPIM) provides a suitable option for metal mold insert fabrication. In this paper, two mold inserts with micro-features of different patterns and sizes were produced using 316L stainless steel powder and an in-house binder system. The mold inserts were successfully used to produce cyclic olefin copolymer (COC, trade name TOPAS) micromixer plates with micro-channels of widths 100 µm and 50 µm. Compared with CNC-machined hot work steel mold inserts, the quality of the micro-channels is better as far as geometrical quality and dimensional tolerance are concerned. However, surface finish and flatness of the μPIM mold inserts are inferior to those of CNC-machined mold inserts.

Three-Dimensional Printing Based Hybrid Manufacturing of Microfluidic Devices.

PubMed

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

2015-05-01

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

Three-Dimensional Printing Based Hybrid Manufacturing of Microfluidic Devices

PubMed Central

Shen, Richang; Gurkan, Umut A.

2016-01-01

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

High frame rate imaging system for limited diffraction array beam imaging with square-wave aperture weightings.

PubMed

Lu, Jian-Yu; Cheng, Jiqi; Wang, Jing

2006-10-01

A general-purpose high frame rate (HFR) medical imaging system has been developed. This system has 128 independent linear transmitters, each of which is capable of producing an arbitrary broadband (about 0.05-10 MHz) waveform of up to +/- 144 V peak voltage on a 75-ohm resistive load using a 12-bit/40-MHz digital-to-analog converter. The system also has 128 independent, broadband (about 0.25-10 MHz), and time-variable-gain receiver channels, each of which has a 12-bit/40-MHz analog-to-digital converter and up to 512 MB of memory. The system is controlled by a personal computer (PC), and radio frequency echo data of each channel are transferred to the same PC via a standard USB 2.0 port for image reconstructions. Using the HFR imaging system, we have developed a new limited-diffraction array beam imaging method with square-wave aperture voltage weightings. With this method, in principle, only one or two transmitters are required to excite a fully populated two-dimensional (2-D) array transducer to achieve an equivalent dynamic focusing in both transmission and reception to reconstruct a high-quality three-dimensional image without the need of the time delays of traditional beam focusing and steering, potentially simplifying the transmitter subsystem of an imager. To validate the method, for simplicity, 2-D imaging experiments were performed using the system. In the in vitro experiment, a custom-made, 128-element, 0.32-mm pitch, 3.5-MHz center frequency linear array transducer with about 50% fractional bandwidth was used to reconstruct images of an ATS 539 tissue-mimicking phantom at an axial distance of 130 mm with a field of view of more than 90 degrees. In the in vivo experiment of a human heart, images with a field of view of more than 90 degrees at 120-mm axial distance were obtained with a 128-element, 2.5-MHz center frequency, 0.15-mm pitch Acuson V2 phased array. To ensure that the system was operated under the limits set by the U.S. Food and Drug Administration, the mechanical index, thermal index, and acoustic output were measured. Results show that higher-quality images can be reconstructed with the square-wave aperture weighting method due to an increased penetration depth as compared to the exact weighting method developed previously, and a frame rate of 486 per second was achieved at a pulse repetition frequency of about 5348 Hz for the human heart.

The research of differential reference electrode arrayed flexible IGZO glucose biosensor based on microfluidic framework

NASA Astrophysics Data System (ADS)

Chen, Jian-Syun; Chou, Jung-Chuan; Liao, Yi-Hung; Chen, Ruei-Ting; Huang, Min-Siang; Wu, Tong-Yu

2017-03-01

This study used a fast, simple, and low-cost method to fabricate arrayed flexible glucose biosensor, and the glucose biosensor was integrated with microfluidic framework for investigating sensing characteristics of glucose biosensor at the dynamic conditions. The indium gallium zinc oxide (IGZO) was adopted as sensing membrane and it was deposited on aluminum electrodes / polyethylene terephthalate (PET) substrate by the radio frequency sputtering system. Then, we utilized screen-printed technology to accomplish miniaturization of glucose biosensor. Finally, the glucose sensing membrane was composed of glucose oxidase (GOx) and nafion, which was dropped on IGZO sensing membrane to complete glucose biosensor. According to the experimental results, we found that optimal sensing characteristics of arrayed flexible IGZO glucose biosensor at the dynamic conditions were better than at the static conditions. The optimal average sensitivity and linearity of the arrayed flexible IGZO glucose biosensor were 7.255 mV/mM and 0.994 at 20 µL/min flow rate, respectively.

Microfluidic channel flow cell for simultaneous cryoelectrochemical electron spin resonance.

PubMed

Wain, Andrew J; Compton, Richard G; Le Roux, Rudolph; Matthews, Sinead; Fisher, Adrian C

2007-03-01

A novel microfluidic electrochemical channel flow cell has been constructed for in situ operation in a cylindrical TE011 resonant ESR cavity under variable temperature conditions. The cell has a U-tube configuration, consisting of an inlet and outlet channel which run parallel and contain evaporated gold film working, pseudo-reference, and counter electrodes. This geometry was employed to permit use in conjunction with variable temperature apparatus which does not allow a flow-through approach. The cell is characterized qualitatively and quantitatively using the one-electron reduction of p-bromonitrobenzene in acetonitrile at room temperature as a model system, and the ESR signal-flow rate response is validated by use of three-dimensional digital simulation of the concentration profile for a stable electrogenerated radical species under hydrodynamic conditions. The cell is then used to obtain ESR spectra for a number of radical species in acetonitrile at 233 K, including the radical anions of m- and p-iodonitrobenzene, o-bromonitrobenzene, and m-nitrobenzyl chloride, the latter three being unstable at room temperature. Spectra are also presented for the radical anion of 2-chloranthraquinone and the crystal violet radical, which display improved resolution at low temperatures.

Frequency-Switchable Microfluidic CSRR-Loaded QMSIW Band-Pass Filter Using a Liquid Metal Alloy

PubMed Central

Eom, Seunghyun; Memon, Muhammad Usman; Lim, Sungjoon

2017-01-01

In this paper, we have proposed a frequency-switchable complementary split-ring resonator (CSRR)-loaded quarter-mode substrate-integrated-waveguide (QMSIW) band-pass filter. For frequency switching, a microfluidic channel and liquid metal are used. The liquid metal used is eutectic gallium-indium (EGaIn), consisting of 24.5% indium and 75.5% gallium. The microfluidic channels are built using the elastomer polydimethylsiloxane (PDMS) and three-dimensional-printed microfluidic channel frames. The CSRR-loaded QMSIW band-pass filter is designed to have two states. Before the injection of the liquid metal, the measured center frequency and fractional bandwidths are 2.205 GHz and 6.80%, respectively. After injection, the center frequency shifts from 2.205 GHz to 2.56 GHz. Although the coupling coefficient is practically unchanged, the fractional bandwidth changes from 6.8% to 9.38%, as the CSRR shape changes and the external quality factor decreases. After the removal of the liquid metal, the measured values are similar to the values recorded before the liquid metal was injected. The repeatability of the frequency-switchable mechanism is, therefore, verified. PMID:28350355

Microfluidic Synthesis of Composite Cross-Gradient Materials for Investigating Cell–Biomaterial Interactions

PubMed Central

He, Jiankang; Du, Yanan; Guo, Yuqi; Hancock, Matthew J.; Wang, Ben; Shin, Hyeongho; Wu, Jinhui; Li, Dichen; Khademhosseini, Ali

2010-01-01

Combinatorial material synthesis is a powerful approach for creating composite material libraries for the high-throughput screening of cell–material interactions. Although current combinatorial screening platforms have been tremendously successful in identifying target (termed “hit”) materials from composite material libraries, new material synthesis approaches are needed to further optimize the concentrations and blending ratios of the component materials. Here we employed a microfluidic platform to rapidly synthesize composite materials containing cross-gradients of gelatin and chitosan for investigating cell–biomaterial interactions. The microfluidic synthesis of the cross-gradient was optimized experimentally and theoretically to produce quantitatively controllable variations in the concentrations and blending ratios of the two components. The anisotropic chemical compositions of the gelatin/chitosan cross-gradients were characterized by Fourier transform infrared spectrometry and X-ray photoelectron spectrometry. The three-dimensional (3D) porous gelatin/chitosan cross-gradient materials were shown to regulate the cellular morphology and proliferation of smooth muscle cells (SMCs) in a gradient-dependent manner. We envision that our microfluidic cross-gradient platform may accelerate the material development processes involved in a wide range of biomedical applications. PMID:20721897

Continuous inertial microparticle and blood cell separation in straight channels with local microstructures.

PubMed

Wu, Zhenlong; Chen, Yu; Wang, Moran; Chung, Aram J

2016-02-07

Fluid inertia which has conventionally been neglected in microfluidics has been gaining much attention for particle and cell manipulation because inertia-based methods inherently provide simple, passive, precise and high-throughput characteristics. Particularly, the inertial approach has been applied to blood separation for various biomedical research studies mainly using spiral microchannels. For higher throughput, parallelization is essential; however, it is difficult to realize using spiral channels because of their large two dimensional layouts. In this work, we present a novel inertial platform for continuous sheathless particle and blood cell separation in straight microchannels containing microstructures. Microstructures within straight channels exert secondary flows to manipulate particle positions similar to Dean flow in curved channels but with higher controllability. Through a balance between inertial lift force and microstructure-induced secondary flow, we deterministically position microspheres and cells based on their sizes to be separated downstream. Using our inertial platform, we successfully sorted microparticles and fractionized blood cells with high separation efficiencies, high purities and high throughputs. The inertial separation platform developed here can be operated to process diluted blood with a throughput of 10.8 mL min(-1)via radially arrayed single channels with one inlet and two rings of outlets.

Simple telemedicine for developing regions: camera phones and paper-based microfluidic devices for real-time, off-site diagnosis.

PubMed

Martinez, Andres W; Phillips, Scott T; Carrilho, Emanuel; Thomas, Samuel W; Sindi, Hayat; Whitesides, George M

2008-05-15

This article describes a prototype system for quantifying bioassays and for exchanging the results of the assays digitally with physicians located off-site. The system uses paper-based microfluidic devices for running multiple assays simultaneously, camera phones or portable scanners for digitizing the intensity of color associated with each colorimetric assay, and established communications infrastructure for transferring the digital information from the assay site to an off-site laboratory for analysis by a trained medical professional; the diagnosis then can be returned directly to the healthcare provider in the field. The microfluidic devices were fabricated in paper using photolithography and were functionalized with reagents for colorimetric assays. The results of the assays were quantified by comparing the intensities of the color developed in each assay with those of calibration curves. An example of this system quantified clinically relevant concentrations of glucose and protein in artificial urine. The combination of patterned paper, a portable method for obtaining digital images, and a method for exchanging results of the assays with off-site diagnosticians offers new opportunities for inexpensive monitoring of health, especially in situations that require physicians to travel to patients (e.g., in the developing world, in emergency management, and during field operations by the military) to obtain diagnostic information that might be obtained more effectively by less valuable personnel.

Localization and separation of acoustic sources by using a 2.5-dimensional circular microphone array.

PubMed

Bai, Mingsian R; Lai, Chang-Sheng; Wu, Po-Chen

2017-07-01

Circular microphone arrays (CMAs) are sufficient in many immersive audio applications because azimuthal angles of sources are considered more important than the elevation angles in those occasions. However, the fact that CMAs do not resolve the elevation angle well can be a limitation for some applications which involves three-dimensional sound images. This paper proposes a 2.5-dimensional (2.5-D) CMA comprised of a CMA and a vertical logarithmic-spacing linear array (LLA) on the top. In the localization stage, two delay-and-sum beamformers are applied to the CMA and the LLA, respectively. The direction of arrival (DOA) is estimated from the product of two array output signals. In the separation stage, Tikhonov regularization and convex optimization are employed to extract the source amplitudes on the basis of the estimated DOA. The extracted signals from two arrays are further processed by the normalized least-mean-square algorithm with the internal iteration to yield the source signal with improved quality. To validate the 2.5-D CMA experimentally, a three-dimensionally printed circular array comprised of a 24-element CMA and an eight-element LLA is constructed. Objective perceptual evaluation of speech quality test and a subjective listening test are also undertaken.

A lab-on-chip for biothreat detection using single-molecule DNA mapping.

PubMed

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

2011-03-07

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

Tunable two-dimensional liquid gradient refractive index (L-GRIN) lens for variable light focusing.

PubMed

Huang, Hua; Mao, Xiaole; Lin, Sz-Chin Steven; Kiraly, Brian; Huang, Yiping; Huang, Tony Jun

2010-09-21

We report a two-dimensional (2D) tunable liquid gradient refractive index (L-GRIN) lens for variable focusing of light in the out-of-plane direction. This lens focuses a light beam through a liquid medium with a 2D hyperbolic secant (HS) refractive index gradient. The refractive index gradient is established in a microfluidic chamber through the diffusion between two fluids with different refractive indices, i.e. CaCl(2) solution and deionized (DI) water. The 2D HS refractive index profile and subsequently the focal length of the L-GRIN lens can be tuned by changing the ratio of the flow rates of the CaCl(2) solution and DI water. The focusing effect is experimentally characterized through side-view and top-view image analysis, and the experimental data match well with the results from ray-tracing optical simulations. Advantages of the 2D L-GRIN lens include simple device fabrication procedure, low fluid consumption rate, convenient lens-tuning mechanism, and compatibility with existing microfluidic devices. We expect that with further optimizations, this 2D L-GRIN lens can be used in many optics-based lab-on-a-chip applications.

Drug testing and flow cytometry analysis on a large number of uniform sized tumor spheroids using a microfluidic device

NASA Astrophysics Data System (ADS)

Patra, Bishnubrata; Peng, Chien-Chung; Liao, Wei-Hao; Lee, Chau-Hwang; Tung, Yi-Chung

2016-02-01

Three-dimensional (3D) tumor spheroid possesses great potential as an in vitro model to improve predictive capacity for pre-clinical drug testing. In this paper, we combine advantages of flow cytometry and microfluidics to perform drug testing and analysis on a large number (5000) of uniform sized tumor spheroids. The spheroids are formed, cultured, and treated with drugs inside a microfluidic device. The spheroids can then be harvested from the device without tedious operation. Due to the ample cell numbers, the spheroids can be dissociated into single cells for flow cytometry analysis. Flow cytometry provides statistical information in single cell resolution that makes it feasible to better investigate drug functions on the cells in more in vivo-like 3D formation. In the experiments, human hepatocellular carcinoma cells (HepG2) are exploited to form tumor spheroids within the microfluidic device, and three anti-cancer drugs: Cisplatin, Resveratrol, and Tirapazamine (TPZ), and their combinations are tested on the tumor spheroids with two different sizes. The experimental results suggest the cell culture format (2D monolayer vs. 3D spheroid) and spheroid size play critical roles in drug responses, and also demonstrate the advantages of bridging the two techniques in pharmaceutical drug screening applications.

A review of digital microfluidics as portable platforms for lab-on a-chip applications.

PubMed

Samiei, Ehsan; Tabrizian, Maryam; Hoorfar, Mina

2016-07-07

Following the development of microfluidic systems, there has been a high tendency towards developing lab-on-a-chip devices for biochemical applications. A great deal of effort has been devoted to improve and advance these devices with the goal of performing complete sets of biochemical assays on the device and possibly developing portable platforms for point of care applications. Among the different microfluidic systems used for such a purpose, digital microfluidics (DMF) shows high flexibility and capability of performing multiplex and parallel biochemical operations, and hence, has been considered as a suitable candidate for lab-on-a-chip applications. In this review, we discuss the most recent advances in the DMF platforms, and evaluate the feasibility of developing multifunctional packages for performing complete sets of processes of biochemical assays, particularly for point-of-care applications. The progress in the development of DMF systems is reviewed from eight different aspects, including device fabrication, basic fluidic operations, automation, manipulation of biological samples, advanced operations, detection, biological applications, and finally, packaging and portability of the DMF devices. Success in developing the lab-on-a-chip DMF devices will be concluded based on the advances achieved in each of these aspects.

Method and apparatus for enhanced sensitivity filmless medical x-ray imaging, including three-dimensional imaging

DOEpatents

Parker, S.

1995-10-24

A filmless X-ray imaging system includes at least one X-ray source, upper and lower collimators, and a solid-state detector array, and can provide three-dimensional imaging capability. The X-ray source plane is distance z{sub 1} above upper collimator plane, distance z{sub 2} above the lower collimator plane, and distance z{sub 3} above the plane of the detector array. The object to be X-rayed is located between the upper and lower collimator planes. The upper and lower collimators and the detector array are moved horizontally with scanning velocities v{sub 1}, v{sub 2}, v{sub 3} proportional to z{sub 1}, z{sub 2} and z{sub 3}, respectively. The pattern and size of openings in the collimators, and between detector positions is proportional such that similar triangles are always defined relative to the location of the X-ray source. X-rays that pass through openings in the upper collimator will always pass through corresponding and similar openings in the lower collimator, and thence to a corresponding detector in the underlying detector array. Substantially 100% of the X-rays irradiating the object (and neither absorbed nor scattered) pass through the lower collimator openings and are detected, which promotes enhanced sensitivity. A computer system coordinates repositioning of the collimators and detector array, and X-ray source locations. The computer system can store detector array output, and can associate a known X-ray source location with detector array output data, to provide three-dimensional imaging. Detector output may be viewed instantly, stored digitally, and/or transmitted electronically for image viewing at a remote site. 5 figs.

Method and apparatus for enhanced sensitivity filmless medical x-ray imaging, including three-dimensional imaging

DOEpatents

Parker, Sherwood

1995-01-01

A filmless X-ray imaging system includes at least one X-ray source, upper and lower collimators, and a solid-state detector array, and can provide three-dimensional imaging capability. The X-ray source plane is distance z.sub.1 above upper collimator plane, distance z.sub.2 above the lower collimator plane, and distance z.sub.3 above the plane of the detector array. The object to be X-rayed is located between the upper and lower collimator planes. The upper and lower collimators and the detector array are moved horizontally with scanning velocities v.sub.1, v.sub.2, v.sub.3 proportional to z.sub.1, z.sub.2 and z.sub.3, respectively. The pattern and size of openings in the collimators, and between detector positions is proportional such that similar triangles are always defined relative to the location of the X-ray source. X-rays that pass through openings in the upper collimator will always pass through corresponding and similar openings in the lower collimator, and thence to a corresponding detector in the underlying detector array. Substantially 100% of the X-rays irradiating the object (and neither absorbed nor scattered) pass through the lower collimator openings and are detected, which promotes enhanced sensitivity. A computer system coordinates repositioning of the collimators and detector array, and X-ray source locations. The computer system can store detector array output, and can associate a known X-ray source location with detector array output data, to provide three-dimensional imaging. Detector output may be viewed instantly, stored digitally, and/or transmitted electronically for image viewing at a remote site.

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

PubMed Central

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

2016-01-01

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

Identification and validation of biomarkers of IgV(H) mutation status in chronic lymphocytic leukemia using microfluidics quantitative real-time polymerase chain reaction technology.

PubMed

Abruzzo, Lynne V; Barron, Lynn L; Anderson, Keith; Newman, Rachel J; Wierda, William G; O'brien, Susan; Ferrajoli, Alessandra; Luthra, Madan; Talwalkar, Sameer; Luthra, Rajyalakshmi; Jones, Dan; Keating, Michael J; Coombes, Kevin R

2007-09-01

To develop a model incorporating relevant prognostic biomarkers for untreated chronic lymphocytic leukemia patients, we re-analyzed the raw data from four published gene expression profiling studies. We selected 88 candidate biomarkers linked to immunoglobulin heavy-chain variable region gene (IgV(H)) mutation status and produced a reliable and reproducible microfluidics quantitative real-time polymerase chain reaction array. We applied this array to a training set of 29 purified samples from previously untreated patients. In an unsupervised analysis, the samples clustered into two groups. Using a cutoff point of 2% homology to the germline IgV(H) sequence, one group contained all 14 IgV(H)-unmutated samples; the other contained all 15 mutated samples. We confirmed the differential expression of 37 of the candidate biomarkers using two-sample t-tests. Next, we constructed 16 different models to predict IgV(H) mutation status and evaluated their performance on an independent test set of 20 new samples. Nine models correctly classified 11 of 11 IgV(H)-mutated cases and eight of nine IgV(H)-unmutated cases, with some models using three to seven genes. Thus, we can classify cases with 95% accuracy based on the expression of as few as three genes.

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

PubMed

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

2018-03-16

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

Single-Cell Electric Lysis on an Electroosmotic-Driven Microfluidic Chip with Arrays of Microwells

PubMed Central

Jen, Chun-Ping; Amstislavskaya, Tamara G.; Liu, Ya-Hui; Hsiao, Ju-Hsiu; Chen, Yu-Hung

2012-01-01

Accurate analysis at the single-cell level has become a highly attractive tool for investigating cellular content. An electroosmotic-driven microfluidic chip with arrays of 30-μm-diameter microwells was developed for single-cell electric lysis in the present study. The cellular occupancy in the microwells when the applied voltage was 5 V (82.4%) was slightly higher than that at an applied voltage of 10 V (81.8%). When the applied voltage was increased to 15 V, the cellular occupancy in the microwells dropped to 64.3%. More than 50% of the occupied microwells contain individual cells. The results of electric lysis experiments at the single-cell level indicate that the cells were gradually lysed as the DC voltage of 30 V was applied; the cell was fully lysed after 25 s. Single-cell electric lysis was demonstrated in the proposed microfluidic chip, which is suitable for high-throughput cell lysis. PMID:22969331

Compartmentalized microchannel array for high-throughput analysis of single cell polarized growth and dynamics

DOE PAGES

Geng, Tao; Bredeweg, Erin L.; Szymanski, Craig J.; ...

2015-11-04

Here, interrogating polarized growth is technologically challenging due to extensive cellular branching and uncontrollable environmental conditions in conventional assays. Here we present a robust and high-performance microfluidic system that enables observations of polarized growth with enhanced temporal and spatial control over prolonged periods. The system has built-in tunability and versatility to accommodate a variety of science applications requiring precisely controlled environments. Using the model filamentous fungus, Neurospora crassa, this microfluidic system enabled direct visualization and analysis of cellular heterogeneity in a clonal fungal cell population, nuclear distribution and dynamics at the subhyphal level, and quantitative dynamics of gene expression withmore » single hyphal compartment resolution in response to carbon source starvation and exchange experiments. Although the microfluidic device is demonstrated on filamentous fungi, our technology is immediately extensible to a wide array of other biosystems that exhibit similar polarized cell growth with applications ranging from bioenergy production to human health.« less

Fabricating PFPE Membranes for Microfluidic Valves and Pumps

NASA Technical Reports Server (NTRS)

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

2009-01-01

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

Microfluidic device for acoustic cell lysis

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

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

2015-08-04

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

Techniques of noninvasive optical tomographic imaging

NASA Astrophysics Data System (ADS)

Rosen, Joseph; Abookasis, David; Gokhler, Mark

2006-01-01

Recently invented methods of optical tomographic imaging through scattering and absorbing media are presented. In one method, the three-dimensional structure of an object hidden between two biological tissues is recovered from many noisy speckle pictures obtained on the output of a multi-channeled optical imaging system. Objects are recovered from many speckled images observed by a digital camera through two stereoscopic microlens arrays. Each microlens in each array generates a speckle image of the object buried between the layers. In the computer each image is Fourier transformed jointly with an image of the speckled point-like source captured under the same conditions. A set of the squared magnitudes of the Fourier-transformed pictures is accumulated to form a single average picture. This final picture is again Fourier transformed, resulting in the three-dimensional reconstruction of the hidden object. In the other method, the effect of spatial longitudinal coherence is used for imaging through an absorbing layer with different thickness, or different index of refraction, along the layer. The technique is based on synthesis of multiple peak spatial degree of coherence. This degree of coherence enables us to scan simultaneously different sample points on different altitudes, and thus decreases the acquisition time. The same multi peak degree of coherence is also used for imaging through the absorbing layer. Our entire experiments are performed with a quasi-monochromatic light source. Therefore problems of dispersion and inhomogeneous absorption are avoided.

Manufacturing of three-dimensionally microstructured nanocomposites through microfluidic infiltration.

PubMed

Dermanaki-Farahani, Rouhollah; Lebel, Louis Laberge; Therriault, Daniel

2014-03-12

Microstructured composite beams reinforced with complex three-dimensionally (3D) patterned nanocomposite microfilaments are fabricated via nanocomposite infiltration of 3D interconnected microfluidic networks. The manufacturing of the reinforced beams begins with the fabrication of microfluidic networks, which involves layer-by-layer deposition of fugitive ink filaments using a dispensing robot, filling the empty space between filaments using a low viscosity resin, curing the resin and finally removing the ink. Self-supported 3D structures with other geometries and many layers (e.g. a few hundreds layers) could be built using this method. The resulting tubular microfluidic networks are then infiltrated with thermosetting nanocomposite suspensions containing nanofillers (e.g. single-walled carbon nanotubes), and subsequently cured. The infiltration is done by applying a pressure gradient between two ends of the empty network (either by applying a vacuum or vacuum-assisted microinjection). Prior to the infiltration, the nanocomposite suspensions are prepared by dispersing nanofillers into polymer matrices using ultrasonication and three-roll mixing methods. The nanocomposites (i.e. materials infiltrated) are then solidified under UV exposure/heat cure, resulting in a 3D-reinforced composite structure. The technique presented here enables the design of functional nanocomposite macroscopic products for microengineering applications such as actuators and sensors.

An Incompressible, Depth-Averaged Lattice Boltzmann Method for Liquid Flow in Microfluidic Devices with Variable Aperture

DOE PAGES

Laleian, Artin; Valocchi, Albert J.; Werth, Charles J.

2015-11-24

Two-dimensional (2D) pore-scale models have successfully simulated microfluidic experiments of aqueous-phase flow with mixing-controlled reactions in devices with small aperture. A standard 2D model is not generally appropriate when the presence of mineral precipitate or biomass creates complex and irregular three-dimensional (3D) pore geometries. We modify the 2D lattice Boltzmann method (LBM) to incorporate viscous drag from the top and bottom microfluidic device (micromodel) surfaces, typically excluded in a 2D model. Viscous drag from these surfaces can be approximated by uniformly scaling a steady-state 2D velocity field at low Reynolds number. We demonstrate increased accuracy by approximating the viscous dragmore » with an analytically-derived body force which assumes a local parabolic velocity profile across the micromodel depth. Accuracy of the generated 2D velocity field and simulation permeability have not been evaluated in geometries with variable aperture. We obtain permeabilities within approximately 10% error and accurate streamlines from the proposed 2D method relative to results obtained from 3D simulations. Additionally, the proposed method requires a CPU run time approximately 40 times less than a standard 3D method, representing a significant computational benefit for permeability calculations.« less

Manufacturing of Three-dimensionally Microstructured Nanocomposites through Microfluidic Infiltration

PubMed Central

Dermanaki-Farahani, Rouhollah; Lebel, Louis Laberge; Therriault, Daniel

2014-01-01

Microstructured composite beams reinforced with complex three-dimensionally (3D) patterned nanocomposite microfilaments are fabricated via nanocomposite infiltration of 3D interconnected microfluidic networks. The manufacturing of the reinforced beams begins with the fabrication of microfluidic networks, which involves layer-by-layer deposition of fugitive ink filaments using a dispensing robot, filling the empty space between filaments using a low viscosity resin, curing the resin and finally removing the ink. Self-supported 3D structures with other geometries and many layers (e.g. a few hundreds layers) could be built using this method. The resulting tubular microfluidic networks are then infiltrated with thermosetting nanocomposite suspensions containing nanofillers (e.g. single-walled carbon nanotubes), and subsequently cured. The infiltration is done by applying a pressure gradient between two ends of the empty network (either by applying a vacuum or vacuum-assisted microinjection). Prior to the infiltration, the nanocomposite suspensions are prepared by dispersing nanofillers into polymer matrices using ultrasonication and three-roll mixing methods. The nanocomposites (i.e. materials infiltrated) are then solidified under UV exposure/heat cure, resulting in a 3D-reinforced composite structure. The technique presented here enables the design of functional nanocomposite macroscopic products for microengineering applications such as actuators and sensors. PMID:24686754

A study of EWOD-driven droplets by PIV investigation.

PubMed

Lu, Hsiang-Wei; Bottausci, Frederic; Fowler, Jesse D; Bertozzi, Andrea L; Meinhart, Carl; Kim, Chang-Jin C J

2008-03-01

Despite the recent interest in droplet-based microfluidics using electrowetting-on-dielectric (EWOD), fundamental understanding of the fluid dynamics remains limited to two-dimensional (2D) reduction of the Navier-Stokes equation. Experimental data are in dire need to verify the predictions and advance the field. We report an investigation of the flow inside droplets actuated by EWOD in air using micro particle image velocimetry (micro-PIV). Using the continuity equation, we reconstruct the 3D velocity field from the 2D PIV experimental data. We present some fundamental findings and build valuable insights that will help design sophisticated EWOD microfluidic devices. For example, the results confirm that efficient mixing in a droplet may be achieved by moving the droplet along an irreversible pattern that breaks the symmetry of the two circulating inner flows.

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

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

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

2013-11-21

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

Stimulation and inhibition of bacterial growth by caffeine dependent on chloramphenicol and a phenolic uncoupler--a ternary toxicity study using microfluid segment technique.

PubMed

Cao, Jialan; Kürsten, Dana; Schneider, Steffen; Köhler, J Michael

2012-10-01

A droplet-based microfluidic technique for the fast generation of three dimensional concentration spaces within nanoliter segments was introduced. The technique was applied for the evaluation of the effect of two selected antibiotic substances on the toxicity and activation of bacterial growth by caffeine. Therefore a three-dimensional concentration space was completely addressed by generating large sequences with about 1150 well separated microdroplets containing 216 different combinations of concentrations. To evaluate the toxicity of the ternary mixtures a time-resolved miniaturized optical double endpoint detection unit using a microflow-through fluorimeter and a two channel microflow-through photometer was used for the simultaneous analysis of changes on the endogenous cellular fluorescence signal and on the cell density of E. coli cultivated inside 500 nL microfluid segments. Both endpoints supplied similar results for the dose related cellular response. Strong non-linear combination effects, concentration dependent stimulation and the formation of activity summits on bolographic maps were determined. The results reflect a complex response of growing bacterial cultures in dependence on the combined effectors. A strong caffeine induced enhancement of bacterial growth was found at sublethal chloramphenicol and sublethal 2,4-dinitrophenol concentrations. The reliability of the method was proved by a high redundancy of fluidic experiments. The results indicate the importance of multi-parameter investigations for toxicological studies and prove the potential of the microsegmented flow technique for such requirements.

Transport and collision dynamics in periodic asymmetric obstacle arrays: Rational design of microfluidic rare-cell immunocapture devices

NASA Astrophysics Data System (ADS)

Gleghorn, Jason P.; Smith, James P.; Kirby, Brian J.

2013-09-01

Microfluidic obstacle arrays have been used in numerous applications, and their ability to sort particles or capture rare cells from complex samples has broad and impactful applications in biology and medicine. We have investigated the transport and collision dynamics of particles in periodic obstacle arrays to guide the design of convective, rather than diffusive, transport-based immunocapture microdevices. Ballistic and full computational fluid dynamics simulations are used to understand the collision modes that evolve in cylindrical obstacle arrays with various geometries. We identify previously unrecognized collision mode structures and differential size-based collision frequencies that emerge from these arrays. Previous descriptions of transverse displacements that assume unidirectional flow in these obstacle arrays cannot capture mode transitions properly as these descriptions fail to capture the dependence of the mode transitions on column spacing and the attendant change in the flow field. Using these analytical and computational simulations, we elucidate design parameters that induce high collision rates for all particles larger than a threshold size or selectively increase collision frequencies for a narrow range of particle sizes within a polydisperse population. Furthermore, we investigate how the particle Péclet number affects collision dynamics and mode transitions and demonstrate that experimental observations from various obstacle array geometries are well described by our computational model.

Flow distribution in parallel microfluidic networks and its effect on concentration gradient

PubMed Central

Guermonprez, Cyprien; Michelin, Sébastien; Baroud, Charles N.

2015-01-01

The architecture of microfluidic networks can significantly impact the flow distribution within its different branches and thereby influence tracer transport within the network. In this paper, we study the flow rate distribution within a network of parallel microfluidic channels with a single input and single output, using a combination of theoretical modeling and microfluidic experiments. Within the ladder network, the flow rate distribution follows a U-shaped profile, with the highest flow rate occurring in the initial and final branches. The contrast with the central branches is controlled by a single dimensionless parameter, namely, the ratio of hydrodynamic resistance between the distribution channel and the side branches. This contrast in flow rates decreases when the resistance of the side branches increases relative to the resistance of the distribution channel. When the inlet flow is composed of two parallel streams, one of which transporting a diffusing species, a concentration variation is produced within the side branches of the network. The shape of this concentration gradient is fully determined by two dimensionless parameters: the ratio of resistances, which determines the flow rate distribution, and the Péclet number, which characterizes the relative speed of diffusion and advection. Depending on the values of these two control parameters, different distribution profiles can be obtained ranging from a flat profile to a step distribution of solute, with well-distributed gradients between these two limits. Our experimental results are in agreement with our numerical model predictions, based on a simplified 2D advection-diffusion problem. Finally, two possible applications of this work are presented: the first one combines the present design with self-digitization principle to encapsulate the controlled concentration in nanoliter chambers, while the second one extends the present design to create a continuous concentration gradient within an open flow chamber. PMID:26487905

Design and production of the digital optical module of the KM3NeT project

NASA Astrophysics Data System (ADS)

Leonora, Emanuele; Giordano, Valentina

2017-03-01

The KM3NeT collaboration is building the ARCA and ORCA neutrino telescopes in the depths of the Mediterranean Sea. They will consist of 3-dimensional arrays of photodetectors, called digital optical modules, suspended in the sea by means of vertical string structures, called detection units. The optical modules are composed of a pressure-resistant 17-inch spherical glass vessel, which contains 31 small photomultiplier tubes and all the associated electronics. The multi- photomultiplier solution represents an innovative design with respect to optical modules of all currently operated neutrino telescopes comprising a single large photomultipliers.

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

PubMed

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

2013-01-01

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

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

NASA Astrophysics Data System (ADS)

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

2014-03-01

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

Thermopile Detector Arrays for Space Science Applications

NASA Technical Reports Server (NTRS)

Foote, M. C.; Kenyon, M.; Krueger, T. R.; McCann, T. A.; Chacon, R.; Jones, E. W.; Dickie, M. R.; Schofield, J. T.; McCleese, D. J.; Gaalema, S.

2004-01-01

Thermopile detectors are widely used in uncooled applications where small numbers of detectors are required, particularly in low-cost commercial applications or applications requiring accurate radiometry. Arrays of thermopile detectors, however, have not been developed to the extent of uncooled bolometer and pyroelectric/ferroelectric arrays. Efforts at JPL seek to remedy this deficiency by developing high performance thin-film thermopile detectors in both linear and two-dimensional formats. The linear thermopile arrays are produced by bulk micromachining and wire bonded to separate CMOS readout electronic chips. Such arrays are currently being fabricated for the Mars Climate Sounder instrument, scheduled for launch in 2005. Progress is also described towards realizing a two-dimensional thermopile array built over CMOS readout circuitry in the substrate.

Effectiveness of Three-Dimensional Digital Animation in Teaching Human Anatomy in an Authentic Classroom Context

ERIC Educational Resources Information Center

Hoyek, Nady; Collet, Christian; Di Rienzo, Franck; De Almeida, Mickael; Guillot, Aymeric

2014-01-01

Three-dimensional (3D) digital animations were used to teach the human musculoskeletal system to first year kinesiology students. The purpose of this study was to assess the effectiveness of this method by comparing two groups from two different academic years during two of their official required anatomy examinations (trunk and upper limb…

On the current drive capability of low dimensional semiconductors: 1D versus 2D

DOE PAGES

Zhu, Y.; Appenzeller, J.

2015-10-29

Low-dimensional electronic systems are at the heart of many scaling approaches currently pursuit for electronic applications. Here, we present a comparative study between an array of one-dimensional (1D) channels and its two-dimensional (2D) counterpart in terms of current drive capability. Lastly, our findings from analytical expressions derived in this article reveal that under certain conditions an array of 1D channels can outperform a 2D field-effect transistor because of the added degree of freedom to adjust the threshold voltage in an array of 1D devices.

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

NASA Astrophysics Data System (ADS)

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

2014-02-01

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

Simulation of electrokinetic flow in microfluidic channels

NASA Astrophysics Data System (ADS)

Sabur, Romena; Matin, M.

2005-08-01

Electrokinetic phenomena become an increasingly efficient fluid transport mechanism in micro- and nano-fluidic fields. These phenomena have also been applied successfully in microfluidic devices to achieve particle separation, pre-concentration and mixing. Electrokinetic is the flow produced by the action of an electric field on a fluid with a net charge, where the charged ions of fluid are able to drag the whole solution through the channels in the microfluidic device from one analyzing point to the other. We will present the simulation results of electrokinetic transports of fluid in various typical micro-channel geometries such as T-channel, Y-channel, cross channel and straight channel. In practice, high-speed micro-PIV technique is used to measure transient fluidic phenomena in a microfluidic channel. Particle Image Velocimetry (PIV) systems provide two- or three-dimensional velocity maps in flows using whole field techniques based on imaging the light scattered by small particles in the flow illuminated by a laser light sheet. The system generally consists of an epifluorescent microscope, CW laser and a high-speed CMOS of CCD camera. The flow of a liquid, (water for example), containing fluorescent particle is then analyzed in a counter microchannel by the highly accurate PIV method. One can then compare the simulated and experimental microfluidic flow due to electroosmotic effect.

Autonomous Agent-Based Systems and Their Applications in Fluid Dynamics, Particle Separation, and Co-evolving Networks

NASA Astrophysics Data System (ADS)

Graeser, Oliver

This thesis comprises three parts, reporting research results in Fluid Dynamics (Part I), Particle Separation (Part II) and Co-evolving Networks (Part III). Part I deals with the simulation of fluid dynamics using the lattice-Boltzmann method. Microfluidic devices often feature two-dimensional, repetitive arrays. Flows through such devices are pressure-driven and confined by solid walls. We have defined new adaptive generalised periodic boundary conditions to represent the effects of outer solid walls, and are thus able to exploit the periodicity of the array by simulating the flow through one unit cell in lieu of the entire device. The so-calculated fully developed flow describes the flow through the entire array accurately, but with computational requirements that are reduced according to the dimensions of the array. Part II discusses the problem of separating macromolecules like proteins or DNA coils. The reliable separation of such molecules is a crucial task in molecular biology. The use of Brownian ratchets as mechanisms for the separation of such particles has been proposed and discussed during the last decade. Pressure-driven flows have so far been dismissed as possible driving forces for Brownian ratchets, as they do not generate ratchet asymmetry. We propose a microfluidic design that uses pressure-driven flows to create asymmetry and hence allows particle separation. The dependence of the asymmetry on various factors of the microfluidic geometry is discussed. We further exemplify the feasibility of our approach using Brownian dynamics simulations of particles of different sizes in such a device. The results show that ratchet-based particle separation using flows as the driving force is possible. Simulation results and ratchet theory predictions are in excellent agreement. Part III deals with the co-evolution of networks and dynamic models. A group of agents occupies the nodes of a network, which defines the relationship between these agents. The evolution of the agents is defined by the rules of the dynamic model and depends on the relationship between agents, i.e., the state of the network. In return, the evolution of the network depends on the state of the dynamic model. The concept is introduced through the adaptive SIS model. We show that the previously used criterion determining the critical infected fraction, i.e., the number of infected agents required to sustain the epidemic, is inappropriate for this model. We introduce a different criterion and show that the critical infected fraction so determined is in good agreement with results obtained by numerical simulations. We further discuss the concept of co-evolving dynamics using the Snowdrift Game as a model paradigm. Co-evolution occurs through agents cutting dissatisfied links and rewiring to other agents at random. The effect of co-evolution on the emergence of cooperation is discussed using a mean-field theory and numerical simulations. A transition between a connected and a disconnected, highly cooperative state of the system is observed, and explained using the mean-field model. Quantitative deviations regarding the level of cooperation in the disconnected regime can be fully resolved through an improved mean-field theory that includes the effect of random fluctuations into its model.

MOSAIC: Software for creating mosaics from collections of images

NASA Technical Reports Server (NTRS)

Varosi, F.; Gezari, D. Y.

1992-01-01

We have developed a powerful, versatile image processing and analysis software package called MOSAIC, designed specifically for the manipulation of digital astronomical image data obtained with (but not limited to) two-dimensional array detectors. The software package is implemented using the Interactive Data Language (IDL), and incorporates new methods for processing, calibration, analysis, and visualization of astronomical image data, stressing effective methods for the creation of mosaic images from collections of individual exposures, while at the same time preserving the photometric integrity of the original data. Since IDL is available on many computers, the MOSAIC software runs on most UNIX and VAX workstations with the X-Windows or Sun View graphics interface.

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

NASA Astrophysics Data System (ADS)

Yang, Shaohua; Long, Wei; Chen, Yajun

2018-03-01

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

Design and testing of a 750MHz CW-EPR digital console for small animal imaging.

PubMed

Sato-Akaba, Hideo; Emoto, Miho C; Hirata, Hiroshi; Fujii, Hirotada G

2017-11-01

This paper describes the development of a digital console for three-dimensional (3D) continuous wave electron paramagnetic resonance (CW-EPR) imaging of a small animal to improve the signal-to-noise ratio and lower the cost of the EPR imaging system. A RF generation board, an RF acquisition board and a digital signal processing (DSP) & control board were built for the digital EPR detection. Direct sampling of the reflected RF signal from a resonator (approximately 750MHz), which contains the EPR signal, was carried out using a band-pass subsampling method. A direct automatic control system to reduce the reflection from the resonator was proposed and implemented in the digital EPR detection scheme. All DSP tasks were carried out in field programmable gate array ICs. In vivo 3D imaging of nitroxyl radicals in a mouse's head was successfully performed. Copyright © 2017 Elsevier Inc. All rights reserved.

Design and testing of a 750 MHz CW-EPR digital console for small animal imaging

NASA Astrophysics Data System (ADS)

Sato-Akaba, Hideo; Emoto, Miho C.; Hirata, Hiroshi; Fujii, Hirotada G.

2017-11-01

This paper describes the development of a digital console for three-dimensional (3D) continuous wave electron paramagnetic resonance (CW-EPR) imaging of a small animal to improve the signal-to-noise ratio and lower the cost of the EPR imaging system. A RF generation board, an RF acquisition board and a digital signal processing (DSP) & control board were built for the digital EPR detection. Direct sampling of the reflected RF signal from a resonator (approximately 750 MHz), which contains the EPR signal, was carried out using a band-pass subsampling method. A direct automatic control system to reduce the reflection from the resonator was proposed and implemented in the digital EPR detection scheme. All DSP tasks were carried out in field programmable gate array ICs. In vivo 3D imaging of nitroxyl radicals in a mouse's head was successfully performed.

Droplet-based microfluidic flow injection system with large-scale concentration gradient by a single nanoliter-scale injection for enzyme inhibition assay.

PubMed

Cai, Long-Fei; Zhu, Ying; Du, Guan-Sheng; Fang, Qun

2012-01-03

We described a microfluidic chip-based system capable of generating droplet array with a large scale concentration gradient by coupling flow injection gradient technique with droplet-based microfluidics. Multiple modules including sample injection, sample dispersion, gradient generation, droplet formation, mixing of sample and reagents, and online reaction within the droplets were integrated into the microchip. In the system, nanoliter-scale sample solution was automatically injected into the chip under valveless flow injection analysis mode. The sample zone was first dispersed in the microchannel to form a concentration gradient along the axial direction of the microchannel and then segmented into a linear array of droplets by immiscible oil phase. With the segmentation and protection of the oil phase, the concentration gradient profile of the sample was preserved in the droplet array with high fidelity. With a single injection of 16 nL of sample solution, an array of droplets with concentration gradient spanning 3-4 orders of magnitude could be generated. The present system was applied in the enzyme inhibition assay of β-galactosidase to preliminarily demonstrate its potential in high throughput drug screening. With a single injection of 16 nL of inhibitor solution, more than 240 in-droplet enzyme inhibition reactions with different inhibitor concentrations could be performed with an analysis time of 2.5 min. Compared with multiwell plate-based screening systems, the inhibitor consumption was reduced 1000-fold. © 2011 American Chemical Society

Sensitive and inexpensive digital DNA analysis by microfluidic enrichment of rolling circle amplified single-molecules.

PubMed

Kühnemund, Malte; Hernández-Neuta, Iván; Sharif, Mohd Istiaq; Cornaglia, Matteo; Gijs, Martin A M; Nilsson, Mats

2017-05-05

Single molecule quantification assays provide the ultimate sensitivity and precision for molecular analysis. However, most digital analysis techniques, i.e. droplet PCR, require sophisticated and expensive instrumentation for molecule compartmentalization, amplification and analysis. Rolling circle amplification (RCA) provides a simpler means for digital analysis. Nevertheless, the sensitivity of RCA assays has until now been limited by inefficient detection methods. We have developed a simple microfluidic strategy for enrichment of RCA products into a single field of view of a low magnification fluorescent sensor, enabling ultra-sensitive digital quantification of nucleic acids over a dynamic range from 1.2 aM to 190 fM. We prove the broad applicability of our analysis platform by demonstrating 5-plex detection of as little as ∼1 pg (∼300 genome copies) of pathogenic DNA with simultaneous antibiotic resistance marker detection, and the analysis of rare oncogene mutations. Our method is simpler, more cost-effective and faster than other digital analysis techniques and provides the means to implement digital analysis in any laboratory equipped with a standard fluorescent microscope. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Optical demodulation system for digitally encoded suspension array in fluoroimmunoassay

NASA Astrophysics Data System (ADS)

He, Qinghua; Li, Dongmei; He, Yonghong; Guan, Tian; Zhang, Yilong; Shen, Zhiyuan; Chen, Xuejing; Liu, Siyu; Lu, Bangrong; Ji, Yanhong

2017-09-01

A laser-induced breakdown spectroscopy and fluorescence spectroscopy-coupled optical system is reported to demodulate digitally encoded suspension array in fluoroimmunoassay. It takes advantage of the plasma emissions of assembled elemental materials to digitally decode the suspension array, providing a more stable and accurate recognition to target biomolecules. By separating the decoding procedure of suspension array and adsorption quantity calculation of biomolecules into two independent channels, the cross talk between decoding and label signals in traditional methods had been successfully avoided, which promoted the accuracy of both processes and realized more sensitive quantitative detection of target biomolecules. We carried a multiplexed detection of several types of anti-IgG to verify the quantitative analysis performance of the system. A limit of detection of 1.48×10-10 M was achieved, demonstrating the detection sensitivity of the optical demodulation system.

Bio-microfluidics: biomaterials and biomimetic designs.

PubMed

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

2010-01-12

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

Cooperative single-photon subradiant states in a three-dimensional atomic array

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

Jen, H.H., E-mail: sappyjen@gmail.com

2016-11-15

We propose a complete superradiant and subradiant states that can be manipulated and prepared in a three-dimensional atomic array. These subradiant states can be realized by absorbing a single photon and imprinting the spatially-dependent phases on the atomic system. We find that the collective decay rates and associated cooperative Lamb shifts are highly dependent on the phases we manage to imprint, and the subradiant state of long lifetime can be found for various lattice spacings and atom numbers. We also investigate both optically thin and thick atomic arrays, which can serve for systematic studies of super- and sub-radiance. Our proposal offers an alternative schememore » for quantum memory of light in a three-dimensional array of two-level atoms, which is applicable and potentially advantageous in quantum information processing. - Highlights: • Cooperative single-photon subradiant states in a three-dimensional atomic array. • Subradiant state manipulation via spatially-increasing phase imprinting. • Quantum storage of light in the subradiant state in two-level atoms.« less

Microfluidic immunomagnetic cell separation from whole blood.

PubMed

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

2016-02-01

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

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

PubMed

Baigl, Damien

2012-10-07

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

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

PubMed Central

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

2008-01-01

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

Direct etch method for microfludic channel and nanoheight post-fabrication by picoliter droplets

NASA Astrophysics Data System (ADS)

Demirci, Utkan; Toner, Mehmet

2006-01-01

Photolithography is an expensive and significant step in microfabrication. Approaches that could change lithography would create an impact on semiconductor industry and microelectromechanical systems technologies. We demonstrate a direct etching method by ejecting etchant droplets at desired locations by using microdroplet ejector arrays. This method could be used for easy fabrication of poly(dimethylsiloxane) microfluidic channels and nanometer height postlike structures in microfluidic channels.

Generation of atmospheric wavefronts using binary micromirror arrays.

PubMed

Anzuola, Esdras; Belmonte, Aniceto

2016-04-10

To simulate in the laboratory the influence that a turbulent atmosphere has on light beams, we introduce a practical method for generating atmospheric wavefront distortions that considers digital holographic reconstruction using a programmable binary micromirror array. We analyze the efficiency of the approach for different configurations of the micromirror array and experimentally demonstrate the benchtop technique. Though the mirrors on the digital array can only be positioned in one of two states, we show that the holographic technique can be used to devise a wide variety of atmospheric wavefront aberrations in a controllable and predictable way for a fraction of the cost of phase-only spatial light modulators.

Localized, stepwise template growth of functional nanowires from an amino acid-supported framework in a microfluidic chip.

PubMed

Puigmartí-Luis, Josep; Rubio-Martínez, Marta; Imaz, Inhar; Cvetković, Benjamin Z; Abad, Llibertat; Pérez Del Pino, Angel; Maspoch, Daniel; Amabilino, David B

2014-01-28

A spatially controlled synthesis of nanowire bundles of the functional crystalline coordination polymer (CP) Ag(I)TCNQ (tetracyanoquinodimethane) from previously fabricated and trapped monovalent silver CP (Ag(I)Cys (cysteine)) using a room-temperature microfluidic-assisted templated growth method is demonstrated. The incorporation of microengineered pneumatic clamps in a two-layer polydimethylsiloxane-based (PDMS) microfluidic platform was used. Apart from guiding the formation of the Ag(I)Cys coordination polymer, this microfluidic approach enables a local trapping of the in situ synthesized structures with a simple pneumatic clamp actuation. This method not only enables continuous and multiple chemical events to be conducted upon the trapped structures, but the excellent fluid handling ensures a precise chemical activation of the amino acid-supported framework in a position controlled by interface and clamp location that leads to a site-specific growth of Ag(I)TCNQ nanowire bundles. The synthesis is conducted stepwise starting with Ag(I)Cys CPs, going through silver metal, and back to a functional CP (Ag(I)TCNQ); that is, a novel microfluidic controlled ligand exchange (CP → NP → CP) is presented. Additionally, the pneumatic clamps can be employed further to integrate the conductive Ag(I)TCNQ nanowire bundles onto electrode arrays located on a surface, hence facilitating the construction of the final functional interfaced systems from solution specifically with no need for postassembly manipulation. This localized self-supported growth of functional matter from an amino acid-based CP shows how sequential localized chemistry in a fluid cell can be used to integrate molecular systems onto device platforms using a chip incorporating microengineered pneumatic tools. The control of clamp pressure and in parallel the variation of relative flow rates of source solutions permit deposition of materials at different locations on a chip that could be useful for device array preparation. The in situ reaction and washing procedures make this approach a powerful one for the fabrication of multicomponent complex nanomaterials using a soft bottom-up approach.

Single-Cell RT-PCR in Microfluidic Droplets with Integrated Chemical Lysis.

PubMed

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

2018-01-16

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

Self-assembly of ordered graphene nanodot arrays

DOE PAGES

Camilli, Luca; Jørgensen, Jakob H.; Tersoff, Jerry; ...

2017-06-29

Our ability to fabricate nanoscale domains of uniform size in two-dimensional materials could potentially enable new applications in nanoelectronics and the development of innovative metamaterials. But, achieving even minimal control over the growth of two-dimensional lateral heterostructures at such extreme dimensions has proven exceptionally challenging. Here we show the spontaneous formation of ordered arrays of graphene nano-domains (dots), epitaxially embedded in a two-dimensional boron–carbon–nitrogen alloy. These dots exhibit a strikingly uniform size of 1.6 ± 0.2 nm and strong ordering, and the array periodicity can be tuned by adjusting the growth conditions. Furthemore, we explain this behaviour with a modelmore » incorporating dot-boundary energy, a moiré-modulated substrate interaction and a long-range repulsion between dots. This new two-dimensional material, which theory predicts to be an ordered composite of uniform-size semiconducting graphene quantum dots laterally integrated within a larger-bandgap matrix, holds promise for novel electronic and optoelectronic properties, with a variety of potential device applications.« less

Patterned arrays of lateral heterojunctions within monolayer two-dimensional semiconductors

PubMed Central

Mahjouri-Samani, Masoud; Lin, Ming-Wei; Wang, Kai; Lupini, Andrew R.; Lee, Jaekwang; Basile, Leonardo; Boulesbaa, Abdelaziz; Rouleau, Christopher M.; Puretzky, Alexander A.; Ivanov, Ilia N.; Xiao, Kai; Yoon, Mina; Geohegan, David B.

2015-01-01

The formation of semiconductor heterojunctions and their high-density integration are foundations of modern electronics and optoelectronics. To enable two-dimensional crystalline semiconductors as building blocks in next-generation electronics, developing methods to deterministically form lateral heterojunctions is crucial. Here we demonstrate an approach for the formation of lithographically patterned arrays of lateral semiconducting heterojunctions within a single two-dimensional crystal. Electron beam lithography is used to pattern MoSe2 monolayer crystals with SiO2, and the exposed locations are selectively and totally converted to MoS2 using pulsed laser vaporization of sulfur to form MoSe2/MoS2 heterojunctions in predefined patterns. The junctions and conversion process are studied by Raman and photoluminescence spectroscopy, atomically resolved scanning transmission electron microscopy and device characterization. This demonstration of lateral heterojunction arrays within a monolayer crystal is an essential step for the integration of two-dimensional semiconductor building blocks with different electronic and optoelectronic properties for high-density, ultrathin devices. PMID:26198727

Method of pedestal and common-mode noise correction for switched-capacitor analog memories

DOEpatents

Britton, Charles L.

1997-01-01

A method and apparatus for correcting common-mode noise and pedestal noise in a multichannel array of switched-capacitor analog memories wherein each analog memory is connected to an associated analog-to-digital converter. The apparatus comprises a single differential element in two different embodiments. In a first embodiment, the differential element is a reference analog memory connected to a buffer. In the second embodiment, the differential dement is a reference analog memory connected to a reference analog-to-digital connected to an array of digital summing circuits.

Method of pedestal and common-mode noise correction for switched-capacitor analog memories

DOEpatents

Britton, Charles L.

1996-01-01

A method and apparatus for correcting common-mode noise and pedestal noise in a multichannel array of switched-capacitor analog memories wherein each analog memory is connected to an associated analog-to-digital converter. The apparatus comprises a single differential element in two different embodiments. In a first embodiment, the differential element is a reference analog memory connected to a buffer. In the second embodiment, the differential element is a reference analog memory connected to a reference analog-to-digital connected to an array of digital summing circuits.

Application of dot-matrix illumination of liquid crystal phase space light modulator in 3D imaging of APD array

NASA Astrophysics Data System (ADS)

Wang, Shuai; Sun, Huayan; Guo, Huichao

2018-01-01

Aiming at the problem of beam scanning in low-resolution APD array in three-dimensional imaging, a method of beam scanning with liquid crystal phase-space optical modulator is proposed to realize high-resolution imaging by low-resolution APD array. First, a liquid crystal phase spatial light modulator is used to generate a beam array and then a beam array is scanned. Since the sub-beam divergence angle in the beam array is smaller than the field angle of a single pixel in the APD array, the APD's pixels respond only to the three-dimensional information of the beam illumination position. Through the scanning of the beam array, a single pixel is used to collect the target three-dimensional information multiple times, thereby improving the resolution of the APD detector. Finally, MATLAB is used to simulate the algorithm in this paper by using two-dimensional scalar diffraction theory, which realizes the splitting and scanning with a resolution of 5 x 5. The feasibility is verified theoretically.

High-throughput on-chip in vivo neural regeneration studies using femtosecond laser nano-surgery and microfluidics

NASA Astrophysics Data System (ADS)

Rohde, Christopher B.; Zeng, Fei; Gilleland, Cody; Samara, Chrysanthi; Yanik, Mehmet F.

2009-02-01

In recent years, the advantages of using small invertebrate animals as model systems for human disease have become increasingly apparent and have resulted in three Nobel Prizes in medicine or chemistry during the last six years for studies conducted on the nematode Caenorhabditis elegans (C. elegans). The availability of a wide array of species-specific genetic techniques, along with the transparency of the worm and its ability to grow in minute volumes make C. elegans an extremely powerful model organism. We present a suite of technologies for complex high-throughput whole-animal genetic and drug screens. We demonstrate a high-speed microfluidic sorter that can isolate and immobilize C. elegans in a well-defined geometry, an integrated chip containing individually addressable screening chambers for incubation and exposure of individual animals to biochemical compounds, and a device for delivery of compound libraries in standard multiwell plates to microfluidic devices. The immobilization stability obtained by these devices is comparable to that of chemical anesthesia and the immobilization process does not affect lifespan, progeny production, or other aspects of animal health. The high-stability enables the use of a variety of key optical techniques. We use this to demonstrate femtosecond-laser nanosurgery and three-dimensional multiphoton microscopy. Used alone or in various combinations these devices facilitate a variety of high-throughput assays using whole animals, including mutagenesis and RNAi and drug screens at subcellular resolution, as well as high-throughput high-precision manipulations such as femtosecond-laser nanosurgery for large-scale in vivo neural degeneration and regeneration studies.

Integrated microfluidic platforms for investigating neuronal networks

NASA Astrophysics Data System (ADS)

Kim, Hyung Joon

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

Three-dimensional extracellular matrix scaffolds by microfluidic fabrication for long-term spontaneously contracted cardiomyocyte culture.

PubMed

Mei, Jeng-Chun; Wu, Aden Yuan Kun; Wu, Po-Chen; Cheng, Nai-Chen; Tsai, Wei-Bor; Yu, Jiashing

2014-11-01

To repair damaged cardiac tissue, the important principle of in vitro cell culture is to mimic the in vivo cell growth environment. Thus, micro-sized cells are more suitably cultured in three-dimensional (3D) than in two-dimensional (2D) microenvironments (ex: culture dish). With the matching dimensions of works produced by microfluidic technology, chemical engineering and biochemistry applications have used this technology extensively in cellular works. The 3D scaffolds produced in our investigation has essential properties, such has high mass transfer efficiency, and variable pore sizes, to adapt to various needs of different cell types. In addition to the malleability of these innovative scaffolds, fabrication procedure was effortless and fast. Primary neonatal mice cardiomyocytes were successfully harvested and cultured in 3D scaffolds made of gelatin and collagen. Gelatin and gelatin-collagen scaffold were produced by the formation of microbubbles through a microfluidic device, and the mechanical properties of gelatin scaffold and gelatin-collagen scaffold were measured. Cellular properties in the microbubbles were also monitored. Fluorescence staining results assured that cardiomyocytes could maintain in vivo morphology in 3D gelatin scaffold. In addition, it was found that 3D scaffold could prolong the contraction behavior of cardiomyocytes compared with a conventional 2D culture dish. Spontaneously contracted behavior was maintained for the longest (about 1 month) in the 3D gelatin scaffold, about 19 days in the 3D gelatin-collagen scaffold. To sum up, this 3D platform for cell culture has promising potential for myocardial tissue engineering.

Automated 3D-Printed Unibody Immunoarray for Chemiluminescence Detection of Cancer Biomarker Proteins

PubMed Central

Tang, C. K.; Vaze, A.; Rusling, J. F.

2017-01-01

A low cost three-dimensional (3D) printed clear plastic microfluidic device was fabricated for fast, low cost automated protein detection. The unibody device features three reagent reservoirs, an efficient 3D network for passive mixing, and an optically transparent detection chamber housing a glass capture antibody array for measuring chemiluminescence output with a CCD camera. Sandwich type assays were built onto the glass arrays using a multi-labeled detection antibody-polyHRP (HRP = horseradish peroxidase). Total assay time was ~30 min in a complete automated assay employing a programmable syringe pump so that the protocol required minimal operator intervention. The device was used for multiplexed detection of prostate cancer biomarker proteins prostate specific antigen (PSA) and platelet factor 4 (PF-4). Detection limits of 0.5 pg mL−1 were achieved for these proteins in diluted serum with log dynamic ranges of four orders of magnitude. Good accuracy vs ELISA was validated by analyzing human serum samples. This prototype device holds good promise for further development as a point-of-care cancer diagnostics tool. PMID:28067370

Computer-assisted techniques to evaluate fringe patterns

NASA Astrophysics Data System (ADS)

Sciammarella, Cesar A.; Bhat, Gopalakrishna K.

1992-01-01

Strain measurement using interferometry requires an efficient way to extract the desired information from interferometric fringes. Availability of digital image processing systems makes it possible to use digital techniques for the analysis of fringes. In the past, there have been several developments in the area of one dimensional and two dimensional fringe analysis techniques, including the carrier fringe method (spatial heterodyning) and the phase stepping (quasi-heterodyning) technique. This paper presents some new developments in the area of two dimensional fringe analysis, including a phase stepping technique supplemented by the carrier fringe method and a two dimensional Fourier transform method to obtain the strain directly from the discontinuous phase contour map.

Maskless lithography

DOEpatents

Sweatt, William C.; Stulen, Richard H.

1999-01-01

The present invention provides a method for maskless lithography. A plurality of individually addressable and rotatable micromirrors together comprise a two-dimensional array of micromirrors. Each micromirror in the two-dimensional array can be envisioned as an individually addressable element in the picture that comprises the circuit pattern desired. As each micromirror is addressed it rotates so as to reflect light from a light source onto a portion of the photoresist coated wafer thereby forming a pixel within the circuit pattern. By electronically addressing a two-dimensional array of these micromirrors in the proper sequence a circuit pattern that is comprised of these individual pixels can be constructed on a microchip. The reflecting surface of the micromirror is configured in such a way as to overcome coherence and diffraction effects in order to produce circuit elements having straight sides.

Maskless lithography

DOEpatents

Sweatt, W.C.; Stulen, R.H.

1999-02-09

The present invention provides a method for maskless lithography. A plurality of individually addressable and rotatable micromirrors together comprise a two-dimensional array of micromirrors. Each micromirror in the two-dimensional array can be envisioned as an individually addressable element in the picture that comprises the circuit pattern desired. As each micromirror is addressed it rotates so as to reflect light from a light source onto a portion of the photoresist coated wafer thereby forming a pixel within the circuit pattern. By electronically addressing a two-dimensional array of these micromirrors in the proper sequence a circuit pattern that is comprised of these individual pixels can be constructed on a microchip. The reflecting surface of the micromirror is configured in such a way as to overcome coherence and diffraction effects in order to produce circuit elements having straight sides. 12 figs.

Method for maskless lithography

DOEpatents

Sweatt, William C.; Stulen, Richard H.

2000-01-01

The present invention provides a method for maskless lithography. A plurality of individually addressable and rotatable micromirrors together comprise a two-dimensional array of micromirrors. Each micromirror in the two-dimensional array can be envisioned as an individually addressable element in the picture that comprises the circuit pattern desired. As each micromirror is addressed it rotates so as to reflect light from a light source onto a portion of the photoresist coated wafer thereby forming a pixel within the circuit pattern. By electronically addressing a two-dimensional array of these micromirrors in the proper sequence a circuit pattern that is comprised of these individual pixels can be constructed on a microchip. The reflecting surface of the micromirror is configured in such a way as to overcome coherence and diffraction effects in order to produce circuit elements having straight sides.

Fabrication of micromechanical and microoptical systems by two-photon polymerization

NASA Astrophysics Data System (ADS)

Reinhardt, Carsten; Ovsianikov, A.; Passinger, Sven; Chichkov, Boris N.

2007-01-01

The recently developed two-photon polymerisation technique is used for the fabrication of two- and three-dimensional structures in photosensitive inorganic-organic hybrid material (ORMOCER), in SU8 , and in positive tone resist with resolutions down to 100nm. In this contribution we present applications of this powerful technology for the realization of micromechanical systems and microoptical components. We will demonstrate results on the fabrication of complex movable three-dimensional micromechanical systems and microfluidic components which cannot be realized by other technologies. This approach of structuring photosensitive materials also provides unique possibilities for the fabrication of different microoptical components such as arbitrary shaped microlenses, microprisms, and 3D-photonic crystals with high optical quality.

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

PubMed

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

2015-08-01

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

Targeted cell adhesion on selectively micropatterned polymer arrays on a poly(dimethylsiloxane) surface.

PubMed

Tang, Linzhi; Min, Junhong; Lee, Eun-Cheol; Kim, Jong Sung; Lee, Nae Yoon

2010-02-01

Herein, we introduce the fabrication of polymer micropattern arrays on a chemically inert poly(dimethylsiloxane) (PDMS) surface and employ them for the selective adhesion of cells. To fabricate the micropattern arrays, a mercapto-ester-based photocurable adhesive was coated onto a mercaptosilane-coated PDMS surface and photopolymerized using a photomask to obtain patterned arrays at the microscale level. Robust polymer patterns, 380 microm in diameter, were successfully fabricated onto a PDMS surface, and cells were selectively targeted toward the patterned regions. Next, the performance of the cell adhesion was observed by anchoring cell adhesive linker, an RGD oligopeptide, on the surface of the mercapto-ester-based adhesive-cured layer. The successful anchoring of the RGD linker was confirmed through various surface characterizations such as water contact angle measurement, XPS analysis, FT-IR analysis, and AFM measurement. The micropatterning of a photocurable adhesive onto a PDMS surface can provide high structural rigidity, a highly-adhesive surface, and a physical pathway for selective cell adhesion, while the incorporated polymer micropattern arrays inside a PDMS microfluidic device can serve as a microfluidic platform for disease diagnoses and high-throughput drug screening.

Surface-Micromachined Planar Arrays of Thermopiles

NASA Technical Reports Server (NTRS)

Foote, Marc C.

2003-01-01

Planar two-dimensional arrays of thermopiles intended for use as thermal-imaging detectors are to be fabricated by a process that includes surface micromachining. These thermopile arrays are designed to perform better than do prior two-dimensional thermopile arrays. The lower performance of prior two-dimensional thermopile arrays is attributed to the following causes: The thermopiles are made from low-performance thermoelectric materials. The devices contain dielectric supporting structures, the thermal conductances of which give rise to parasitic losses of heat from detectors to substrates. The bulk-micromachining processes sometimes used to remove substrate material under the pixels, making it difficult to incorporate low-noise readout electronic circuitry. The thermoelectric lines are on the same level as the infrared absorbers, thereby reducing fill factor. The improved pixel design of a thermopile array of the type under development is expected to afford enhanced performance by virtue of the following combination of features: Surface-micromachined detectors are thermally isolated through suspension above readout circuitry. The thermopiles are made of such high-performance thermoelectric materials as Bi-Te and Bi-Sb-Te alloys. Pixel structures are supported only by the thermoelectric materials: there are no supporting dielectric structures that could leak heat by conduction to the substrate.

Repulsion of polarized particles from two-dimensional materials

NASA Astrophysics Data System (ADS)

Rodríguez-Fortuño, Francisco J.; Picardi, Michela F.; Zayats, Anatoly V.

2018-05-01

Repulsion of nanoparticles, molecules, and atoms from surfaces can have important applications in nanomechanical devices, microfluidics, optical manipulation, and atom optics. Here, through the solution of a classical scattering problem, we show that a dipole source oscillating at a frequency ω can experience a robust and strong repulsive force when its near-field interacts with a two-dimensional material. As an example, the case of graphene is considered, showing that a broad bandwidth of repulsion can be obtained at frequencies for which propagation of plasmon modes is allowed 0 <ℏ ω <(5 /3 ) μc , where μc is the chemical potential tunable electrically or by chemical doping.

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

DOEpatents

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

2010-07-13

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

Methods and devices for protein assays

DOEpatents

Chhabra, Swapnil [San Jose, CA; Cintron, Jose M [Indianapolis, IN; Shediac, Renee [Oakland, CA

2009-11-03

Methods and devices for protein assays based on Edman degradation in microfluidic channels are disclosed herein. As disclosed, the cleaved amino acid residues may be immobilized in an array format and identified by detectable labels, such as antibodies, which specifically bind given amino acid residues. Alternatively, the antibodies are immobilized in an array format and the cleaved amino acids are labeled identified by being bound by the antibodies in the array.

Heterogeneous immunoassays using magnetic beads on a digital microfluidic platform.

PubMed

Sista, Ramakrishna S; Eckhardt, Allen E; Srinivasan, Vijay; Pollack, Michael G; Palanki, Srinivas; Pamula, Vamsee K

2008-12-01

A digital microfluidic platform for performing heterogeneous sandwich immunoassays based on efficient handling of magnetic beads is presented in this paper. This approach is based on manipulation of discrete droplets of samples and reagents using electrowetting without the need for channels where the droplets are free to move laterally. Droplet-based manipulation of magnetic beads therefore does not suffer from clogging of channels. Immunoassays on a digital microfluidic platform require the following basic operations: bead attraction, bead washing, bead retention, and bead resuspension. Several parameters such as magnetic field strength, pull force, position, and buffer composition were studied for effective bead operations. Dilution-based washing of magnetic beads was demonstrated by immobilizing the magnetic beads using a permanent magnet and splitting the excess supernatant using electrowetting. Almost 100% bead retention was achieved after 7776-fold dilution-based washing of the supernatant. Efficient resuspension of magnetic beads was achieved by transporting a droplet with magnetic beads across five electrodes on the platform and exploiting the flow patterns within the droplet to resuspend the beads. All the magnetic-bead droplet operations were integrated together to generate standard curves for sandwich heterogeneous immunoassays on human insulin and interleukin-6 (IL-6) with a total time to result of 7 min for each assay.

Heterogeneous Immunoassays Using Magnetic beads On a Digital Microfluidic Platform

PubMed Central

Sista, Ramakrishna S.; Eckhardt, Allen E.; Srinivasan, Vijay; Pollack, Michael G.; Palanki, Srinivas; Pamula, Vamsee K.

2009-01-01

A digital microfluidic platform for performing heterogeneous sandwich immunoassays based on efficient handling of magnetic beads is presented in this paper. This approach is based on manipulation of discrete droplets of samples and reagents using electrowetting without the need for channels where the droplets are free to move laterally. Droplet-based manipulation of magnetic beads therefore does not suffer from clogging of channels. Immunoassays on a digital microfluidic platform require the following basic operations: bead attraction, bead washing, bead retention, and bead resuspension. Several parameters such as magnetic field strength, pull force, position, and buffer composition were studied for effective bead operations. Dilution-based washing of magnetic beads was demonstrated by immobilizing the magnetic beads using a permanent magnet and splitting the excess supernatant using electrowetting. Almost 100% bead retention was achieved after 7776 fold dilution-based washing of the supernatant. Efficient resuspension of magnetic beads was achieved by transporting a droplet with magnetic beads across five electrodes on the platform and exploiting the flow patterns within the droplet to resuspend the beads. All the magnetic-bead droplet operations were integrated together to generate standard curves for sandwich heterogeneous immunoassays on Human Insulin and Interleukin-6 (IL-6) with a total time to result of seven minutes for each assay. PMID:19023486

Fringe pattern demodulation with a two-dimensional digital phase-locked loop algorithm.

PubMed

Gdeisat, Munther A; Burton, David R; Lalor, Michael J

2002-09-10

A novel technique called a two-dimensional digital phase-locked loop (DPLL) for fringe pattern demodulation is presented. This algorithm is more suitable for demodulation of fringe patterns with varying phase in two directions than the existing DPLL techniques that assume that the phase of the fringe patterns varies only in one direction. The two-dimensional DPLL technique assumes that the phase of a fringe pattern is continuous in both directions and takes advantage of the phase continuity; consequently, the algorithm has better noise performance than the existing DPLL schemes. The two-dimensional DPLL algorithm is also suitable for demodulation of fringe patterns with low sampling rates, and it outperforms the Fourier fringe analysis technique in this aspect.

Terahertz artificial material based on integrated metal-rod-array for phase sensitive fluid detection.

PubMed

You, Borwen; Chen, Ching-Yu; Yu, Chin-Ping; Liu, Tze-An; Hattori, Toshiaki; Lu, Ja-Yu

2017-04-17

A terahertz artificial material composed of metal rod array is experimentally investigated on its transmission spectral property and successfully incorporated into microfluidics as a miniaturized terahertz waveguide with an extended optical-path-length for label-free fluidic sensing. Theoretical and experimental characterizations of terahertz transmission spectra show that the wave guidance along the metal rod array originates from the resonance of transverse-electric-polarized waves within the metal rod slits. The extended optical path length along three layers of metal-rod-array enables terahertz waves sufficiently overlapping the fluid molecules embedded among the rods, leading to strongly enhanced phase change by approximately one order of magnitude compared with the blank metal-parallel-plate waveguide. Based on the enhanced phase sensitivity, three kinds of colorless liquid analytes, namely, acetone, methanol, and ethanol, with different dipole moments are identified in situ using the metal-rod-array-based microfluidic sensor. The detection limit in molecular amounts of a liquid analyte is experimentally demonstrated to be less than 0.1 mmol, corresponding to 2.7 μmol/mm². The phase sensitive terahertz metal-rod-array-based sensor potentially has good adaptability in lab-chip technology for various practical applications, such as industrial toxic fluid detection and medical breath inspection.

Glasses-free large size high-resolution three-dimensional display based on the projector array

NASA Astrophysics Data System (ADS)

Sang, Xinzhu; Wang, Peng; Yu, Xunbo; Zhao, Tianqi; Gao, Xing; Xing, Shujun; Yu, Chongxiu; Xu, Daxiong

2014-11-01

Normally, it requires a huge amount of spatial information to increase the number of views and to provide smooth motion parallax for natural three-dimensional (3D) display similar to real life. To realize natural 3D video display without eye-wears, a huge amount of 3D spatial information is normal required. However, minimum 3D information for eyes should be used to reduce the requirements for display devices and processing time. For the 3D display with smooth motion parallax similar to the holographic stereogram, the size the virtual viewing slit should be smaller than the pupil size of eye at the largest viewing distance. To increase the resolution, two glass-free 3D display systems rear and front projection are presented based on the space multiplexing with the micro-projector array and the special designed 3D diffuse screens with the size above 1.8 m× 1.2 m. The displayed clear depths are larger 1.5m. The flexibility in terms of digitized recording and reconstructed based on the 3D diffuse screen relieves the limitations of conventional 3D display technologies, which can realize fully continuous, natural 3-D display. In the display system, the aberration is well suppressed and the low crosstalk is achieved.

Finger-triggered portable PDMS suction cup for equipment-free microfluidic pumping

NASA Astrophysics Data System (ADS)

Lee, Sanghyun; Kim, Hojin; Lee, Wonhyung; Kim, Joonwon

2018-12-01

This study presents a finger-triggered portable polydimethylsiloxane suction cup that enables equipment-free microfluidic pumping. The key feature of this method is that its operation only involves a "pressing-and-releasing" action for the cup placed at the outlet of a microfluidic device, which transports the fluid at the inlet toward the outlet through a microchannel. This method is simple, but effective and powerful. The cup is portable and can easily be fabricated from a three-dimensional printed mold, used without any pre-treatment, reversibly bonded to microfluidic devices without leakage, and applied to various material-based microfluidic devices. The effect of the suction cup geometry and fabrication conditions on the pumping performance was investigated. Furthermore, we demonstrated the practical applications of the suction cup by conducting an equipment-free pumping of thermoplastic-based microfluidic devices and water-in-oil droplet generation.

Fabrication of Microfluidic Valves Using a Hydrogel Molding Method

NASA Astrophysics Data System (ADS)

Sugiura, Yusuke; Hirama, Hirotada; Torii, Toru

2015-08-01

In this paper, a method for fabricating a microfluidic valve made of polydimethylsiloxane (PDMS) using a rapid prototyping method for microchannels through hydrogel cast molding is discussed. Currently, the valves in microchannels play an important role in various microfluidic devices. The technology to prototype microfluidic valves rapidly is actively being developed. For the rapid prototyping of PDMS microchannels, a method that uses a hydrogel as the casting mold has been recently developed. This technique can be used to prepare a three-dimensional structure through simple and uncomplicated methods. In this study, we were able to fabricate microfluidic valves easily using this rapid prototyping method that utilizes hydrogel cast molding. In addition, we confirmed that the valve displacement could be predicted within a range of constant pressures. Moreover, because microfluidic valves fabricated using this method can be directly observed from a cross-sectional direction, we anticipate that this technology will significantly contribute to clarifying fluid behavior and other phenomena in microchannels and microfluidic valves with complex structures.

Fabrication of Microfluidic Valves Using a Hydrogel Molding Method.

PubMed

Sugiura, Yusuke; Hirama, Hirotada; Torii, Toru

2015-08-24

In this paper, a method for fabricating a microfluidic valve made of polydimethylsiloxane (PDMS) using a rapid prototyping method for microchannels through hydrogel cast molding is discussed. Currently, the valves in microchannels play an important role in various microfluidic devices. The technology to prototype microfluidic valves rapidly is actively being developed. For the rapid prototyping of PDMS microchannels, a method that uses a hydrogel as the casting mold has been recently developed. This technique can be used to prepare a three-dimensional structure through simple and uncomplicated methods. In this study, we were able to fabricate microfluidic valves easily using this rapid prototyping method that utilizes hydrogel cast molding. In addition, we confirmed that the valve displacement could be predicted within a range of constant pressures. Moreover, because microfluidic valves fabricated using this method can be directly observed from a cross-sectional direction, we anticipate that this technology will significantly contribute to clarifying fluid behavior and other phenomena in microchannels and microfluidic valves with complex structures.

A 90GHz Bolometer Camera Detector System for the Green Bank Telescope

NASA Technical Reports Server (NTRS)

Benford, Dominic J.; Allen, Christine A.; Buchanan, Ernest D.; Chen, Tina C.; Chervenak, James A.; Devlin, Mark J.; Dicker, Simon R.; Forgione, Joshua B.

2004-01-01

We describe a close-packed, two-dimensional imaging detector system for operation at 90GHz (3.3mm) for the 100 m Green Bank Telescope (GBT) This system will provide high sensitivity (<1mjy in 1s rapid imaging (15'x15' to 250 microJy in 1 hr) at the world's largest steerable aperture. The heart of this camera is an 8x8 close packed, Nyquist-sampled array of superconducting transition edge sensor bolometers. We have designed and are producing a functional superconducting bolometer array system using a monolithic planar architecture and high-speed multiplexed readout electronics. With an NEP of approx. 2.10(exp 17) W/square root Hz, the TES bolometers will provide fast linear sensitive response for high performance imaging. The detectors are read out by and 8x8 time domain SQUID multiplexer. A digital/analog electronics system has been designed to enable read out by SQUID multiplexers. First light for this instrument on the GBT is expected within a year.

A 90GHz Bolometer Camera Detector System for the Green

NASA Technical Reports Server (NTRS)

Benford, Dominic J.; Allen, Christine A.; Buchanan, Ernest; Chen, Tina C.; Chervenak, James A.; Devlin, Mark J.; Dicker, Simon R.; Forgione, Joshua B.

2004-01-01

We describe a close-packed, two-dimensional imaging detector system for operation at 90GHz (3.3 mm) for the 100m Green Bank Telescope (GBT). This system will provide high sensitivity (less than 1mJy in 1s) rapid imaging (15'x15' to 150 micron Jy in 1 hr) at the world's largest steerable aperture. The heart of this camera is an 8x8 close-packed, Nyquist-sampled array of superconducting transition edge sensor (TES) bolometers. We have designed and are producing a functional superconducting bolometer array system using a monolithic planar architecture and high-speed multiplexed readout electronics. With an NEP of approximately 2 x 10(exp -17) W/square root of Hz, the TES bolometers will provide fast, linear, sensitive response for high performance imaging. The detectors are read out by an 8x8 time domain SQUID multiplexer. A digital/analog electronics system has been designed to enable read out by SQUID multiplexers. First light for this instrument on the GBT is expected within a year.

A Microfluidic System for the Investigation of Tumor Cell Extravasation.

PubMed

Kühlbach, Claudia; da Luz, Sabrina; Baganz, Frank; Hass, Volker C; Mueller, Margareta M

2018-05-23

Metastatic dissemination of cancer cells is a very complex process. It includes the intravasation of cells into the metastatic pathways, their passive distribution within the blood or lymph flow, and their extravasation into the surrounding tissue. Crucial steps during extravasation are the adhesion of the tumor cells to the endothelium and their transendothelial migration. However, the molecular mechanisms that are underlying this process are still not fully understood. Novel three dimensional (3D) models for research on the metastatic cascade include the use of microfluidic devices. Different from two dimensional (2D) models, these devices take cell⁻cell, structural, and mechanical interactions into account. Here we introduce a new microfluidic device in order to study tumor extravasation. The device consists of three different parts, containing two microfluidic channels and a porous membrane sandwiched in between them. A smaller channel together with the membrane represents the vessel equivalent and is seeded separately with primary endothelial cells (EC) that are isolated from the lung artery. The second channel acts as reservoir to collect the migrated tumor cells. In contrast to many other systems, this device does not need an additional coating to allow EC growth, as the primary EC that is used produces their own basement membrane. VE-Cadherin, an endothelial adherence junction protein, was expressed in regular localization, which indicates a tight barrier function and cell⁻cell connections of the endothelium. The EC in the device showed in vivo-like behavior under flow conditions. The GFP-transfected tumor cells that were introduced were of epithelial or mesenchymal origin and could be observed by live cell imaging, which indicates tightly adherent tumor cells to the endothelial lining under different flow conditions. These results suggest that the new device can be used for research on molecular requirements, conditions, and mechanism of extravasation and its inhibition.

Two-dimensional free-space beam steering with an optical phased array on silicon-on-insulator.

PubMed

Doylend, J K; Heck, M J R; Bovington, J T; Peters, J D; Coldren, L A; Bowers, J E

2011-10-24

We demonstrate a 16-channel, independently tuned waveguide surface grating optical phased array in silicon for two dimensional beam steering with a total field of view of 20° x 14°, beam width of 0.6° x 1.6°, and full-window background peak suppression of 10 dB. © 2011 Optical Society of America

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

PubMed

Wardrip, Nathaniel C; Arnusch, Christopher J

2016-02-13

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

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

PubMed Central

Wardrip, Nathaniel C.; Arnusch, Christopher J.

2016-01-01

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

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

PubMed

Liu, Changchun; Cui, Dafu; Li, Hui

2010-09-15

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

A survey of current solid state star tracker technology

NASA Astrophysics Data System (ADS)

Armstrong, R. W.; Staley, D. A.

1985-12-01

This paper is a survey of the current state of the art in design of star trackers for spacecraft attitude determination systems. Specific areas discussed are sensor technology, including the current state-of-the-art solid state sensors and techniques of mounting and cooling the sensor, analog image preprocessing electronics performance, and digital processing hardware and software. Three examples of area array solid state star tracker development are presented - ASTROS, developed by the Jet Propulsion Laboratory, the Retroreflector Field Tracker (RFT) by Ball Aerospace, and TRW's MADAN. Finally, a discussion of solid state line arrays explores the possibilities for one-dimensional imagers which offer simplified scan control electronics.

A Photometric Technique for Determining Fluid Concentration using Consumer-Grade Hardware

NASA Technical Reports Server (NTRS)

Leslie, F.; Ramachandran, N.

1999-01-01

In support of a separate study to produce an exponential concentration gradient in a magnetic fluid, a noninvasive technique for determining, species concentration from off-the-shelf hardware has been developed. The approach uses a backlighted fluid test cell photographed with a commercial digital camcorder. Because the light extinction coefficient is wavelength dependent, tests were conducted to determine the best filter color to use, although some guidance was also provided using an absorption spectrophotometer. With the appropriate filter in place, the provide attenuation of the light passing, through the test cell was captured by the camcorder. The digital image was analyzed for intensity using, software from Scion Image Corp. downloaded from the Internet. The analysis provides a two-dimensional array of concentration with an average error of 0.0095 ml/ml. This technique is superior to invasive techniques, which require extraction of a sample that disturbs the concentration distribution in the test cell. Refinements of this technique using a true monochromatic laser light Source are also discussed.

Direct 3D-printing of cell-laden constructs in microfluidic architectures.

PubMed

Liu, Justin; Hwang, Henry H; Wang, Pengrui; Whang, Grace; Chen, Shaochen

2016-04-21

Microfluidic platforms have greatly benefited the biological and medical fields, however standard practices require a high cost of entry in terms of time and energy. The utilization of three-dimensional (3D) printing technologies has greatly enhanced the ability to iterate and build functional devices with unique functions. However, their inability to fabricate within microfluidic devices greatly increases the cost of producing several different devices to examine different scientific questions. In this work, a variable height micromixer (VHM) is fabricated using projection 3D-printing combined with soft lithography. Theoretical and flow experiments demonstrate that altering the local z-heights of VHM improved mixing at lower flow rates than simple geometries. Mixing of two fluids occurs as low as 320 μL min(-1) in VHM whereas the planar zigzag region requires a flow rate of 2.4 mL min(-1) before full mixing occurred. Following device printing, to further demonstrate the ability of this projection-based method, complex, user-defined cell-laden scaffolds are directly printed inside the VHM. The utilization of this unique ability to produce 3D tissue models within a microfluidic system could offer a unique platform for medical diagnostics and disease modeling.

Three-dimensional investigations of the threading regime in a microfluidic flow-focusing channel

NASA Astrophysics Data System (ADS)

Gowda, Krishne; Brouzet, Christophe; Lefranc, Thibault; Soderberg, L. Daniel; Lundell, Fredrik

2017-11-01

We study the flow dynamics of the threading regime in a microfluidic flow-focusing channel through 3D numerical simulations and experiments. Making strong filaments from cellulose nano-fibrils (CNF) could potentially steer to new high-performance bio-based composites competing with conventional glass fibre composites. CNF filaments can be obtained through hydrodynamic alignment of dispersed CNF by using the concept of flow-focusing. The aligned structure is locked by diffusion of ions resulting in a dispersion-gel transition. Flow-focusing typically refers to a microfluidic channel system where the core fluid is focused by the two sheath fluids, thereby creating an extensional flow at the intersection. In this study, threading regime corresponds to an extensional flow field generated by the water sheath fluid stretching the dispersed CNF core fluid and leading to formation of long threads. The experimental measurements are performed using optical coherence tomography (OCT) and 3D numerical simulations with OpenFOAM. The prime focus is laid on the 3D characteristics of thread formation such as wetting length of core fluid, shape, aspect ratio of the thread and velocity flow-field in the microfluidic channel.

Microengineering methods for cell-based microarrays and high-throughput drug-screening applications.

PubMed

Xu, Feng; Wu, JinHui; Wang, ShuQi; Durmus, Naside Gozde; Gurkan, Umut Atakan; Demirci, Utkan

2011-09-01

Screening for effective therapeutic agents from millions of drug candidates is costly, time consuming, and often faces concerns due to the extensive use of animals. To improve cost effectiveness, and to minimize animal testing in pharmaceutical research, in vitro monolayer cell microarrays with multiwell plate assays have been developed. Integration of cell microarrays with microfluidic systems has facilitated automated and controlled component loading, significantly reducing the consumption of the candidate compounds and the target cells. Even though these methods significantly increased the throughput compared to conventional in vitro testing systems and in vivo animal models, the cost associated with these platforms remains prohibitively high. Besides, there is a need for three-dimensional (3D) cell-based drug-screening models which can mimic the in vivo microenvironment and the functionality of the native tissues. Here, we present the state-of-the-art microengineering approaches that can be used to develop 3D cell-based drug-screening assays. We highlight the 3D in vitro cell culture systems with live cell-based arrays, microfluidic cell culture systems, and their application to high-throughput drug screening. We conclude that among the emerging microengineering approaches, bioprinting holds great potential to provide repeatable 3D cell-based constructs with high temporal, spatial control and versatility.

Microengineering Methods for Cell Based Microarrays and High-Throughput Drug Screening Applications

PubMed Central

Xu, Feng; Wu, JinHui; Wang, ShuQi; Durmus, Naside Gozde; Gurkan, Umut Atakan; Demirci, Utkan

2011-01-01

Screening for effective therapeutic agents from millions of drug candidates is costly, time-consuming and often face ethical concerns due to extensive use of animals. To improve cost-effectiveness, and to minimize animal testing in pharmaceutical research, in vitro monolayer cell microarrays with multiwell plate assays have been developed. Integration of cell microarrays with microfluidic systems have facilitated automated and controlled component loading, significantly reducing the consumption of the candidate compounds and the target cells. Even though these methods significantly increased the throughput compared to conventional in vitro testing systems and in vivo animal models, the cost associated with these platforms remains prohibitively high. Besides, there is a need for three-dimensional (3D) cell based drug-screening models, which can mimic the in vivo microenvironment and the functionality of the native tissues. Here, we present the state-of-the-art microengineering approaches that can be used to develop 3D cell based drug screening assays. We highlight the 3D in vitro cell culture systems with live cell-based arrays, microfluidic cell culture systems, and their application to high-throughput drug screening. We conclude that among the emerging microengineering approaches, bioprinting holds a great potential to provide repeatable 3D cell based constructs with high temporal, spatial control and versatility. PMID:21725152

Fabrication of Three-dimensional Paper-based Microfluidic Devices for Immunoassays.

PubMed

Fernandes, Syrena C; Wilson, Daniel J; Mace, Charles R

2017-03-09

Paper wicks fluids autonomously due to capillary action. By patterning paper with hydrophobic barriers, the transport of fluids can be controlled and directed within a layer of paper. Moreover, stacking multiple layers of patterned paper creates sophisticated three-dimensional microfluidic networks that can support the development of analytical and bioanalytical assays. Paper-based microfluidic devices are inexpensive, portable, easy to use, and require no external equipment to operate. As a result, they hold great promise as a platform for point-of-care diagnostics. In order to properly evaluate the utility and analytical performance of paper-based devices, suitable methods must be developed to ensure their manufacture is reproducible and at a scale that is appropriate for laboratory settings. In this manuscript, a method to fabricate a general device architecture that can be used for paper-based immunoassays is described. We use a form of additive manufacturing (multi-layer lamination) to prepare devices that comprise multiple layers of patterned paper and patterned adhesive. In addition to demonstrating the proper use of these three-dimensional paper-based microfluidic devices with an immunoassay for human chorionic gonadotropin (hCG), errors in the manufacturing process that may result in device failures are discussed. We expect this approach to manufacturing paper-based devices will find broad utility in the development of analytical applications designed specifically for limited-resource settings.

Digital and optical shape representation and pattern recognition; Proceedings of the Meeting, Orlando, FL, Apr. 4-6, 1988

NASA Technical Reports Server (NTRS)

Juday, Richard D. (Editor)

1988-01-01

The present conference discusses topics in pattern-recognition correlator architectures, digital stereo systems, geometric image transformations and their applications, topics in pattern recognition, filter algorithms, object detection and classification, shape representation techniques, and model-based object recognition methods. Attention is given to edge-enhancement preprocessing using liquid crystal TVs, massively-parallel optical data base management, three-dimensional sensing with polar exponential sensor arrays, the optical processing of imaging spectrometer data, hybrid associative memories and metric data models, the representation of shape primitives in neural networks, and the Monte Carlo estimation of moment invariants for pattern recognition.

Compressive self-interference Fresnel digital holography with faithful reconstruction

NASA Astrophysics Data System (ADS)

Wan, Yuhong; Man, Tianlong; Han, Ying; Zhou, Hongqiang; Wang, Dayong

2017-05-01

We developed compressive self-interference digital holographic approach that allows retrieving three-dimensional information of the spatially incoherent objects from single-shot captured hologram. The Fresnel incoherent correlation holography is combined with parallel phase-shifting technique to instantaneously obtain spatial-multiplexed phase-shifting holograms. The recording scheme is regarded as compressive forward sensing model, thus the compressive-sensing-based reconstruction algorithm is implemented to reconstruct the original object from the under sampled demultiplexed sub-holograms. The concept was verified by simulations and experiments with simulating use of the polarizer array. The proposed technique has great potential to be applied in 3D tracking of spatially incoherent samples.

Nonlinear stability of Taylor's vortex array

NASA Technical Reports Server (NTRS)

Lin, S. P.; Tobak, M.

1987-01-01

It is proved that the two-dimensional Taylor vortex array, which is an exact unsteady solution of the Navier-Stokes equation, is globally and asymptotically stable in the mean with respect to three-dimensional periodic disturbances. A time-dependent bound on the decay rate of the kinetic energy of disturbances is obtained.

Two-Dimensional Planar Lightwave Circuit Integrated Spatial Filter Array and Method of Use Thereof

NASA Technical Reports Server (NTRS)

Dimov, Fedor (Inventor); Ai, Jun (Inventor)

2015-01-01

A large coherent two-dimensional (2D) spatial filter array (SFA), 30 by 30 or larger, is produced by coupling a 2D planar lightwave circuit (PLC) array with a pair of lenslet arrays at the input and output side. The 2D PLC array is produced by stacking a plurality of chips, each chip with a plural number of straight PLC waveguides. A pupil array is coated onto the focal plane of the lenslet array. The PLC waveguides are produced by deposition of a plural number of silica layers on the silicon wafer, followed by photolithography and reactive ion etching (RIE) processes. A plural number of mode filters are included in the silica-on-silicon waveguide such that the PLC waveguide is transparent to the fundamental mode but higher order modes are attenuated by 40 dB or more.

Spatiotemporal periodicity of dislocation dynamics in a two-dimensional microfluidic crystal flowing in a tapered channel

DOE PAGES

Gai, Ya; Min Leong, Chia; Cai, Wei; ...

2016-10-10

When a many-body system is driven away from equilibrium, order can spontaneously emerge in places where disorder might be expected. Here we report an unexpected order in the flow of a concentrated emulsion in a tapered microfluidic channel. The velocity profiles of individual drops in the emulsion show periodic patterns in both space and time. Such periodic patterns appear surprising from both a fluid and a solid mechanics point of view. In particular, when the emulsion is considered as a soft crystal under extrusion, a disordered scenario might be expected based on the stochastic nature of dislocation dynamics in microscopicmore » crystals. However, an orchestrated sequence of dislocation nucleation and migration is observed to give rise to a highly ordered deformation mode. This discovery suggests that nanocrystals can be made to deform more controllably than previously thought. It can also lead to novel flow control and mixing strategies in droplet microfluidics.« less

Lensless high-resolution on-chip optofluidic microscopes for Caenorhabditis elegans and cell imaging

PubMed Central

Cui, Xiquan; Lee, Lap Man; Heng, Xin; Zhong, Weiwei; Sternberg, Paul W.; Psaltis, Demetri; Yang, Changhuei

2008-01-01

Low-cost and high-resolution on-chip microscopes are vital for reducing cost and improving efficiency for modern biomedicine and bioscience. Despite the needs, the conventional microscope design has proven difficult to miniaturize. Here, we report the implementation and application of two high-resolution (≈0.9 μm for the first and ≈0.8 μm for the second), lensless, and fully on-chip microscopes based on the optofluidic microscopy (OFM) method. These systems abandon the conventional microscope design, which requires expensive lenses and large space to magnify images, and instead utilizes microfluidic flow to deliver specimens across array(s) of micrometer-size apertures defined on a metal-coated CMOS sensor to generate direct projection images. The first system utilizes a gravity-driven microfluidic flow for sample scanning and is suited for imaging elongate objects, such as Caenorhabditis elegans; and the second system employs an electrokinetic drive for flow control and is suited for imaging cells and other spherical/ellipsoidal objects. As a demonstration of the OFM for bioscience research, we show that the prototypes can be used to perform automated phenotype characterization of different Caenorhabditis elegans mutant strains, and to image spores and single cellular entities. The optofluidic microscope design, readily fabricable with existing semiconductor and microfluidic technologies, offers low-cost and highly compact imaging solutions. More functionalities, such as on-chip phase and fluorescence imaging, can also be readily adapted into OFM systems. We anticipate that the OFM can significantly address a range of biomedical and bioscience needs, and engender new microscope applications. PMID:18663227

A dynamic bead-based microarray for parallel DNA detection

NASA Astrophysics Data System (ADS)

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

2011-05-01

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

Method and apparatus for coherent imaging of infrared energy

DOEpatents

Hutchinson, Donald P.

1998-01-01

A coherent camera system performs ranging, spectroscopy, and thermal imaging. Local oscillator radiation is combined with target scene radiation to enable heterodyne detection by the coherent camera's two-dimensional photodetector array. Versatility enables deployment of the system in either a passive mode (where no laser energy is actively transmitted toward the target scene) or an active mode (where a transmitting laser is used to actively illuminate the target scene). The two-dimensional photodetector array eliminates the need to mechanically scan the detector. Each element of the photodetector array produces an intermediate frequency signal that is amplified, filtered, and rectified by the coherent camera's integrated circuitry. By spectroscopic examination of the frequency components of each pixel of the detector array, a high-resolution, three-dimensional or holographic image of the target scene is produced for applications such as air pollution studies, atmospheric disturbance monitoring, and military weapons targeting.

Method and apparatus for coherent imaging of infrared energy

DOEpatents

Hutchinson, D.P.

1998-05-12

A coherent camera system performs ranging, spectroscopy, and thermal imaging. Local oscillator radiation is combined with target scene radiation to enable heterodyne detection by the coherent camera`s two-dimensional photodetector array. Versatility enables deployment of the system in either a passive mode (where no laser energy is actively transmitted toward the target scene) or an active mode (where a transmitting laser is used to actively illuminate the target scene). The two-dimensional photodetector array eliminates the need to mechanically scan the detector. Each element of the photodetector array produces an intermediate frequency signal that is amplified, filtered, and rectified by the coherent camera`s integrated circuitry. By spectroscopic examination of the frequency components of each pixel of the detector array, a high-resolution, three-dimensional or holographic image of the target scene is produced for applications such as air pollution studies, atmospheric disturbance monitoring, and military weapons targeting. 8 figs.

Retention in porous layer pillar array planar separation platforms

DOE PAGES

Lincoln, Danielle R.; Lavrik, Nickolay V.; Kravchenko, Ivan I.; ...

2016-08-11

Here, this work presents the retention capabilities and surface area enhancement of highly ordered, high-aspect-ratio, open-platform, two-dimensional (2D) pillar arrays when coated with a thin layer of porous silicon oxide (PSO). Photolithographically prepared pillar arrays were coated with 50–250 nm of PSO via plasma-enhanced chemical vapor deposition and then functionalized with either octadecyltrichlorosilane or n-butyldimethylchlorosilane. Theoretical calculations indicate that a 50 nm layer of PSO increases the surface area of a pillar nearly 120-fold. Retention capabilities were tested by observing capillary-action-driven development under various conditions, as well as by running one-dimensional separations on varying thicknesses of PSO. Increasing the thicknessmore » of PSO on an array clearly resulted in greater retention of the analyte(s) in question in both experiments. In culmination, a two-dimensional separation of fluorescently derivatized amines was performed to further demonstrate the capabilities of these fabricated platforms.« less

Retention in porous layer pillar array planar separation platforms

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

Lincoln, Danielle R.; Lavrik, Nickolay V.; Kravchenko, Ivan I.

Here, this work presents the retention capabilities and surface area enhancement of highly ordered, high-aspect-ratio, open-platform, two-dimensional (2D) pillar arrays when coated with a thin layer of porous silicon oxide (PSO). Photolithographically prepared pillar arrays were coated with 50–250 nm of PSO via plasma-enhanced chemical vapor deposition and then functionalized with either octadecyltrichlorosilane or n-butyldimethylchlorosilane. Theoretical calculations indicate that a 50 nm layer of PSO increases the surface area of a pillar nearly 120-fold. Retention capabilities were tested by observing capillary-action-driven development under various conditions, as well as by running one-dimensional separations on varying thicknesses of PSO. Increasing the thicknessmore » of PSO on an array clearly resulted in greater retention of the analyte(s) in question in both experiments. In culmination, a two-dimensional separation of fluorescently derivatized amines was performed to further demonstrate the capabilities of these fabricated platforms.« less

Method for maskless lithography

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

NONE

The present invention provides a method for maskless lithography. A plurality of individually addressable and rotatable micromirrors together comprise a two-dimensional array of micromirrors. Each micromirror in the two-dimensional array can be envisioned as an individually addressable element in the picture that comprises the circuit pattern desired. As each micromirror is addressed it rotates so as to reflect light from a light source onto a portion of the photoresist coated wafer thereby forming a pixel within the circuit pattern. By electronically addressing a two-dimensional array of these micromirrors in the proper sequence a circuit pattern that is comprised of thesemore » individual pixels can be constructed on a microchip. The reflecting surface of the micromirror is configured in such a way as to overcome coherence and diffraction effects in order to produce circuit elements having straight sides.« less

Maskless lithography

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

Sweatt, W.C.; Stulen, R.H.

The present invention provides a method for maskless lithography. A plurality of individually addressable and rotatable micromirrors together comprise a two-dimensional array of micromirrors. Each micromirror in the two-dimensional array can be envisioned as an individually addressable element in the picture that comprises the circuit pattern desired. As each micromirror is addressed it rotates so as to reflect light from a light source onto a portion of the photoresist coated wafer thereby forming a pixel within the circuit pattern. By electronically addressing a two-dimensional array of these micromirrors in the proper sequence a circuit pattern that is comprised of thesemore » individual pixels can be constructed on a microchip. The reflecting surface of the micromirror is configured in such a way as to overcome coherence and diffraction effects in order to produce circuit elements having straight sides. 12 figs.« less

Microfluidic Devices for Forensic DNA Analysis: A Review.

PubMed

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

2016-08-05

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

Demonstration of a quantum error detection code using a square lattice of four superconducting qubits

PubMed Central

Córcoles, A.D.; Magesan, Easwar; Srinivasan, Srikanth J.; Cross, Andrew W.; Steffen, M.; Gambetta, Jay M.; Chow, Jerry M.

2015-01-01

The ability to detect and deal with errors when manipulating quantum systems is a fundamental requirement for fault-tolerant quantum computing. Unlike classical bits that are subject to only digital bit-flip errors, quantum bits are susceptible to a much larger spectrum of errors, for which any complete quantum error-correcting code must account. Whilst classical bit-flip detection can be realized via a linear array of qubits, a general fault-tolerant quantum error-correcting code requires extending into a higher-dimensional lattice. Here we present a quantum error detection protocol on a two-by-two planar lattice of superconducting qubits. The protocol detects an arbitrary quantum error on an encoded two-qubit entangled state via quantum non-demolition parity measurements on another pair of error syndrome qubits. This result represents a building block towards larger lattices amenable to fault-tolerant quantum error correction architectures such as the surface code. PMID:25923200

Demonstration of a quantum error detection code using a square lattice of four superconducting qubits.

PubMed

Córcoles, A D; Magesan, Easwar; Srinivasan, Srikanth J; Cross, Andrew W; Steffen, M; Gambetta, Jay M; Chow, Jerry M

2015-04-29

The ability to detect and deal with errors when manipulating quantum systems is a fundamental requirement for fault-tolerant quantum computing. Unlike classical bits that are subject to only digital bit-flip errors, quantum bits are susceptible to a much larger spectrum of errors, for which any complete quantum error-correcting code must account. Whilst classical bit-flip detection can be realized via a linear array of qubits, a general fault-tolerant quantum error-correcting code requires extending into a higher-dimensional lattice. Here we present a quantum error detection protocol on a two-by-two planar lattice of superconducting qubits. The protocol detects an arbitrary quantum error on an encoded two-qubit entangled state via quantum non-demolition parity measurements on another pair of error syndrome qubits. This result represents a building block towards larger lattices amenable to fault-tolerant quantum error correction architectures such as the surface code.

High-resolution laser-projection display system using a grating electromechanical system (GEMS)

NASA Astrophysics Data System (ADS)

Brazas, John C.; Kowarz, Marek W.

2004-01-01

Eastman Kodak Company has developed a diffractive-MEMS spatial-light modulator for use in printing and display applications, the grating electromechanical system (GEMS). This modulator contains a linear array of pixels capable of high-speed digital operation, high optical contrast, and good efficiency. The device operation is based on deflection of electromechanical ribbons suspended above a silicon substrate by a series of intermediate supports. When electrostatically actuated, the ribbons conform to the supporting substructure to produce a surface-relief phase grating over a wide active region. The device is designed to be binary, switching between a reflective mirror state having suspended ribbons and a diffractive grating state having ribbons in contact with substrate features. Switching times of less than 50 nanoseconds with sub-nanosecond jitter are made possible by reliable contact-mode operation. The GEMS device can be used as a high-speed digital-optical modulator for a laser-projection display system by collecting the diffracted orders and taking advantage of the low jitter. A color channel is created using a linear array of individually addressable GEMS pixels. A two-dimensional image is produced by sweeping the line image of the array, created by the projection optics, across the display screen. Gray levels in the image are formed using pulse-width modulation (PWM). A high-resolution projection display was developed using three 1080-pixel devices illuminated by red, green, and blue laser-color primaries. The result is an HDTV-format display capable of producing stunning still and motion images with very wide color gamut.

Tooth-size discrepancy: A comparison between manual and digital methods

PubMed Central

Correia, Gabriele Dória Cabral; Habib, Fernando Antonio Lima; Vogel, Carlos Jorge

2014-01-01

Introduction Technological advances in Dentistry have emerged primarily in the area of diagnostic tools. One example is the 3D scanner, which can transform plaster models into three-dimensional digital models. Objective This study aimed to assess the reliability of tooth size-arch length discrepancy analysis measurements performed on three-dimensional digital models, and compare these measurements with those obtained from plaster models. Material and Methods To this end, plaster models of lower dental arches and their corresponding three-dimensional digital models acquired with a 3Shape R700T scanner were used. All of them had lower permanent dentition. Four different tooth size-arch length discrepancy calculations were performed on each model, two of which by manual methods using calipers and brass wire, and two by digital methods using linear measurements and parabolas. Results Data were statistically assessed using Friedman test and no statistically significant differences were found between the two methods (P > 0.05), except for values found by the linear digital method which revealed a slight, non-significant statistical difference. Conclusions Based on the results, it is reasonable to assert that any of these resources used by orthodontists to clinically assess tooth size-arch length discrepancy can be considered reliable. PMID:25279529

Coordinate axes, location of origin, and redundancy for the one and two-dimensional discrete Fourier transform

NASA Technical Reports Server (NTRS)

Ioup, G. E.; Ioup, J. W.

1985-01-01

Appendix 4 of the Study of One- and Two-Dimensional Filtering and Deconvolution Algorithms for a Streaming Array Computer discusses coordinate axes, location of origin, and redundancy for the one- and two-dimensional Fourier transform for complex and real data.

Method of pedestal and common-mode noise correction for switched-capacitor analog memories

DOEpatents

Britton, C.L.

1997-09-23

A method and apparatus are disclosed for correcting common-mode noise and pedestal noise in a multichannel array of switched-capacitor analog memories wherein each analog memory is connected to an associated analog-to-digital converter. The apparatus comprises a single differential element in two different embodiments. In a first embodiment, the differential element is a reference analog memory connected to a buffer. In the second embodiment, the differential dement is a reference analog memory connected to a reference analog-to-digital connected to an array of digital summing circuits. 4 figs.

Method of pedestal and common-mode noise correction for switched-capacitor analog memories

DOEpatents

Britton, C.L.

1996-12-31

A method and apparatus are disclosed for correcting common-mode noise and pedestal noise in a multichannel array of switched-capacitor analog memories wherein each analog memory is connected to an associated analog-to-digital converter. The apparatus comprises a single differential element in two different embodiments. In a first embodiment, the differential element is a reference analog memory connected to a buffer. In the second embodiment, the differential element is a reference analog memory connected to a reference analog-to-digital connected to an array of digital summing circuits. 4 figs.

Surface modification of poly(dimethylsiloxane) for microfluidic assay applications

NASA Astrophysics Data System (ADS)

Séguin, Christine; McLachlan, Jessica M.; Norton, Peter R.; Lagugné-Labarthet, François

2010-02-01

The surface of a poly(dimethylsiloxane) (PDMS) film was imparted with patterned functionalities at the micron-scale level. Arrays of circles with diameters of 180 and 230 μm were functionalized using plasma oxidation coupled with aluminum deposition, followed by silanization with solutions of 3-aminopropyltrimethoxy silane (3-APTMS) and 3-mercaptopropyltrimethoxy silane (3-MPTMS), to obtain patterned amine and thiol functionalities, respectively. The modification of the samples was confirmed using X-ray photoelectron spectroscopy (XPS), gold nanoparticle adhesion coupled with optical microscopy, as well as by derivatization with fluorescent dyes. To further exploit the novel surface chemistry of the modified PDMS, samples with surface amine functionalities were used to develop a protein assay as well as an array capable of cellular capture and patterning. The modified substrate was shown to successfully selectively immobilize fluorescently labeled immunoglobulin G (IgG) by tethering Protein A to the surface, and, for the cellular arrays, C2C12 rat endothelial cells were captured. Finally, this novel method of patterning chemical functionalities onto PDMS has been incorporated into microfluidic channels. Finally, we demonstrate the in situ chemical modification of the protected PDMS oxidized surface within a microfluidic device. This emphasizes the potential of our method for applications involving micron-scale assays since the aluminum protective layer permits to functionalize the oxidized PDMS surface several weeks after plasma treatment simply after etching away the metallic thin film.

Microfluidic separation of magnetic nanoparticles on an ordered array of magnetized micropillars

NASA Astrophysics Data System (ADS)

Orlandi, G.; Kuzhir, P.; Izmaylov, Y.; Alves Marins, J.; Ezzaier, H.; Robert, L.; Doutre, F.; Noblin, X.; Lomenech, C.; Bossis, G.; Meunier, A.; Sandoz, G.; Zubarev, A.

2016-06-01

Microfluidic separation of magnetic particles is based on their capture by magnetized microcollectors while the suspending fluid flows past the microcollectors inside a microchannel. Separation of nanoparticles is often challenging because of strong Brownian motion. Low capture efficiency of nanoparticles limits their applications in bioanalysis. However, at some conditions, magnetic nanoparticles may undergo field-induced aggregation that amplifies the magnetic attractive force proportionally to the aggregate volume and considerably increases nanoparticle capture efficiency. In this paper, we have demonstrated the role of such aggregation on an efficient capture of magnetic nanoparticles (about 80 nm in diameter) in a microfluidic channel equipped with a nickel micropillar array. This array was magnetized by an external uniform magnetic field, of intensity as low as 6-10 kA/m, and experiments were carried out at flow rates ranging between 0.3 and 30 μ L /min . Nanoparticle capture is shown to be mostly governed by the Mason number Ma, while the dipolar coupling parameter α does not exhibit a clear effect in the studied range, 1.4 < α < 4.5. The capture efficiency Λ shows a strongly decreasing Mason number behavior, Λ ∝M a-1.78 within the range 32 ≤ Ma ≤ 3250. We have proposed a simple theoretical model which considers destructible nanoparticle chains and gives the scaling behavior, Λ ∝M a-1.7 , close to the experimental findings.

Miniature enzyme-based electrodes for detection of hydrogen peroxide release from alcohol-injured hepatocytes.

PubMed

Matharu, Zimple; Enomoto, James; Revzin, Alexander

2013-01-15

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

Simultaneous isolation and detection of circulating tumor cells with a microfluidic silicon-nanowire-array integrated with magnetic upconversion nanoprobes.

PubMed

Wang, Chao; Ye, Min; Cheng, Liang; Li, Rui; Zhu, Wenwen; Shi, Zhen; Fan, Chunhai; He, Jinkang; Liu, Jian; Liu, Zhuang

2015-06-01

The development of sensitive and convenient methods for detection, enrichment, and analysis of circulating tumor cells (CTCs), which serve as an importance diagnostic indicator for metastatic progression of cancer, has received tremendous attention in recent years. In this work, a new approach characteristic of simultaneous CTC capture and detection is developed by integrating a microfluidic silicon nanowire (SiNW) array with multifunctional magnetic upconversion nanoparticles (MUNPs). The MUNPs were conjugated with anti-EpCAM antibody, thus capable to specifically recognize tumor cells in the blood samples and pull them down under an external magnetic field. The capture efficiency of CTCs was further improved by the integration with a microfluidic SiNW array. Due to the autofluorescence free nature in upconversion luminescence (UCL) imaging, our approach allows for highly sensitive detection of small numbers of tumor cells, which afterward could be collected for further analysis and re-culturing. We have further demonstrated that this approach can be applied to detect CTCs in clinical blood samples from lung cancer patients, and obtained consistent results by analyzing the UCL signals and the clinical outcomes of lung cancer metastasis. Therefore our approach represents a promising platform in CTC capture and detection with potential clinical utilization in cancer diagnosis and prognosis. Copyright © 2015 Elsevier Ltd. All rights reserved.

Differentially photo-crosslinked polymers enable self-assembling microfluidics

PubMed Central

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

2012-01-01

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

Development of multitissue microfluidic dynamic array for assessing changes in gene expression associated with channel catfish appetite, growth, metabolism, and intestinal health

USDA-ARS?s Scientific Manuscript database

Large-scale, gene expression methods allow for high throughput analysis of physiological pathways at a fraction of the cost of individual gene expression analysis. Systems, such as the Fluidigm quantitative PCR array described here, can provide powerful assessments of the effects of diet, environme...

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

NASA Astrophysics Data System (ADS)

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

2014-09-01

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

OPTICAL PROCESSING OF INFORMATION: Multistage optoelectronic two-dimensional image switches

NASA Astrophysics Data System (ADS)

Fedorov, V. B.

1994-06-01

The implementation principles and the feasibility of construction of high-throughput multistage optoelectronic switches, capable of transmitting data in the form of two-dimensional images along interconnected pairs of optical channels, are considered. Different ways of realising compact switches are proposed. They are based on the use of polarisation-sensitive elements, arrays of modulators of the plane of polarisation of light, arrays of objectives, and free-space optics. Optical systems of such switches can theoretically ensure that the resolution and optical losses in two-dimensional image transmission are limited only by diffraction. Estimates are obtained of the main maximum-performance parameters of the proposed optoelectronic image switches.

Microfluidic device for unidirectional axon growth

NASA Astrophysics Data System (ADS)

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

2015-11-01

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

Advances in three-dimensional rapid prototyping of microfluidic devices for biological applications

PubMed Central

O'Neill, P. F.; Ben Azouz, A.; Vázquez, M.; Liu, J.; Marczak, S.; Slouka, Z.; Chang, H. C.; Diamond, D.; Brabazon, D.

2014-01-01

The capability of 3D printing technologies for direct production of complex 3D structures in a single step has recently attracted an ever increasing interest within the field of microfluidics. Recently, ultrafast lasers have also allowed developing new methods for production of internal microfluidic channels within the bulk of glass and polymer materials by direct internal 3D laser writing. This review critically summarizes the latest advances in the production of microfluidic 3D structures by using 3D printing technologies and direct internal 3D laser writing fabrication methods. Current applications of these rapid prototyped microfluidic platforms in biology will be also discussed. These include imaging of cells and living organisms, electrochemical detection of viruses and neurotransmitters, and studies in drug transport and induced-release of adenosine triphosphate from erythrocytes. PMID:25538804

A mixed-signal implementation of a polychronous spiking neural network with delay adaptation

PubMed Central

Wang, Runchun M.; Hamilton, Tara J.; Tapson, Jonathan C.; van Schaik, André

2014-01-01

We present a mixed-signal implementation of a re-configurable polychronous spiking neural network capable of storing and recalling spatio-temporal patterns. The proposed neural network contains one neuron array and one axon array. Spike Timing Dependent Delay Plasticity is used to fine-tune delays and add dynamics to the network. In our mixed-signal implementation, the neurons and axons have been implemented as both analog and digital circuits. The system thus consists of one FPGA, containing the digital neuron array and the digital axon array, and one analog IC containing the analog neuron array and the analog axon array. The system can be easily configured to use different combinations of each. We present and discuss the experimental results of all combinations of the analog and digital axon arrays and the analog and digital neuron arrays. The test results show that the proposed neural network is capable of successfully recalling more than 85% of stored patterns using both analog and digital circuits. PMID:24672422

A mixed-signal implementation of a polychronous spiking neural network with delay adaptation.

PubMed

Wang, Runchun M; Hamilton, Tara J; Tapson, Jonathan C; van Schaik, André

2014-01-01

We present a mixed-signal implementation of a re-configurable polychronous spiking neural network capable of storing and recalling spatio-temporal patterns. The proposed neural network contains one neuron array and one axon array. Spike Timing Dependent Delay Plasticity is used to fine-tune delays and add dynamics to the network. In our mixed-signal implementation, the neurons and axons have been implemented as both analog and digital circuits. The system thus consists of one FPGA, containing the digital neuron array and the digital axon array, and one analog IC containing the analog neuron array and the analog axon array. The system can be easily configured to use different combinations of each. We present and discuss the experimental results of all combinations of the analog and digital axon arrays and the analog and digital neuron arrays. The test results show that the proposed neural network is capable of successfully recalling more than 85% of stored patterns using both analog and digital circuits.

From Three-Dimensional Cell Culture to Organs-on-Chips

PubMed Central

Huh, Dongeun; Hamilton, Geraldine A.; Ingber, Donald E.

2014-01-01

Three-dimensional (3D) cell culture models have recently garnered great attention because they often promote levels of cell differentiation and tissue organization not possible in conventional two-dimensional (2D) culture systems. Here, we review new advances in 3D culture that leverage microfabrication technologies from the microchip industry and microfluidics approaches to create cell culture microenvironments that both support tissue differentiation and recapitulate the tissue-tissue interfaces, spatiotemporal chemical gradients, and mechanical microenvironments of living organs. These ‘organs-on-chips’ permit study of human physiology in an organ-specific context, enable development of novel in vitro disease models, and could potentially serve as replacements for animals used in drug development and toxin testing. PMID:22033488

Size dependence in tunneling spectra of PbSe quantum-dot arrays.

PubMed

Ou, Y C; Cheng, S F; Jian, W B

2009-07-15

Interdot Coulomb interactions and collective Coulomb blockade were theoretically argued to be a newly important topic, and experimentally identified in semiconductor quantum dots, formed in the gate confined two-dimensional electron gas system. Developments of cluster science and colloidal synthesis accelerated the studies of electron transport in colloidal nanocrystal or quantum-dot solids. To study the interdot coupling, various sizes of two-dimensional arrays of colloidal PbSe quantum dots are self-assembled on flat gold surfaces for scanning tunneling microscopy and scanning tunneling spectroscopy measurements at both room and liquid-nitrogen temperatures. The tip-to-array, array-to-substrate, and interdot capacitances are evaluated and the tunneling spectra of quantum-dot arrays are analyzed by the theory of collective Coulomb blockade. The current-voltage of PbSe quantum-dot arrays conforms properly to a scaling power law function. In this study, the dependence of tunneling spectra on the sizes (numbers of quantum dots) of arrays is reported and the capacitive coupling between quantum dots in the arrays is explored.

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

PubMed

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

2015-04-07

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

Self-powered integrated microfluidic point-of-care low-cost enabling (SIMPLE) chip

PubMed Central

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

2017-01-01

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

Integrating Multimedia Instructional Design Principles with Complex Physiological Concepts in Reproductive Science

ERIC Educational Resources Information Center

Oki, Angela Christine

2011-01-01

This dissertation examines the effect of digital multimedia presentations as a method to teach complex concepts in reproductive physiology. The digital presentations developed for this research consisted of two-dimensional (2-D) and three-dimensional (3-D) animations, scriptmessaging and narration. The topics were "Mammalian Ovarian…

Imaging RF Phased Array Receivers using Optically-Coherent Up-conversion for High Beam-Bandwidth Processing

DTIC Science & Technology

2017-03-01

It does so by using an optical lens to perform an inverse spatial Fourier Transform on the up-converted RF signals, thereby rendering a real-time... simultaneous beams or other engineered beam patterns. There are two general approaches to array-based beam forming: digital and analog. In digital beam...of significantly limiting the number of beams that can be formed simultaneously and narrowing the operational bandwidth. An alternate approach that

Two dimensional thermo-optic beam steering using a silicon photonic optical phased array

NASA Astrophysics Data System (ADS)

Mahon, Rita; Preussner, Marcel W.; Rabinovich, William S.; Goetz, Peter G.; Kozak, Dmitry A.; Ferraro, Mike S.; Murphy, James L.

2016-03-01

Components for free space optical communication terminals such as lasers, amplifiers, and receivers have all seen substantial reduction in both size and power consumption over the past several decades. However, pointing systems, such as fast steering mirrors and gimbals, have remained large, slow and power-hungry. Optical phased arrays provide a possible solution for non-mechanical beam steering devices that can be compact and lower in power. Silicon photonics is a promising technology for phased arrays because it has the potential to scale to many elements and may be compatible with CMOS technology thereby enabling batch fabrication. For most free space optical communication applications, two-dimensional beam steering is needed. To date, silicon photonic phased arrays have achieved two-dimensional steering by combining thermo-optic steering, in-plane, with wavelength tuning by means of an output grating to give angular tuning, out-of-plane. While this architecture might work for certain static communication links, it would be difficult to implement for moving platforms. Other approaches have required N2 controls for an NxN element phased array, which leads to complexity. Hence, in this work we demonstrate steering using the thermo-optic effect for both dimensions with a simplified steering mechanism requiring only two control signals, one for each steering dimension.

Two-dimensional fluid droplet arrays generated using a single nozzle

DOEpatents

Lee, Eric R.; Perl, Martin L.

1999-11-02

Amplitudes of drive pulses received by a horizontally-placed dropper determine the horizontal displacements of droplets relative to an ejection aperture of the dropper. The drive pulses are varied such that the dropper generates a two-dimensional array of vertically-falling droplets. Vertical and horizontal interdroplet spacings may be varied in real time. Applications include droplet analysis experiments such as Millikan fractional charge searches and aerosol characterization, as well as material deposition applications.

Microfluidic Device with Tunable Post Arrays and Integrated Electrodes for Studying Cellular Release

PubMed Central

Selimovic, Asmira; Erkal, Jayda L.; Spence, Dana M.; Martin, R. Scott

2015-01-01

In this paper, we describe the development of a planar, pillar array device that can be used to image either side of a tunable membrane, as well as sample and detect small molecules in a cell-free region of the microchip. The pores are created by sealing two parallel PDMS microchannels (a cell channel and a collector channel) over a gold pillar array (5 or 10 µm in height), with the device being characterized and optimized for small molecule cross-over while excluding a flowing cell line (here, red blood cells, RBCs). The device was characterized in terms of the flow rate dependence of cross-over of analyte and cell exclusion as well as the ability to perform amperometric detection of catechol and nitric oxide (NO) as they cross-over into the collector channel. Using catechol as the test analyte, the limits of detection (LOD) of the cross-over for the 10 µm and 5 µm pillar array heights were shown to be 50 nM and 106 nM, respectively. Detection of NO was made possible with a glassy carbon detection electrode (housed in the collector channel) modified with Pt-black and Nafion, to enhance sensitivity and selectivity, respectively. Reproducible cross-over of NO as a function of concentration resulted in a linear correlation (r2 = 0.995, 7.6 µM - 190 µM), with an LOD for NO of 230 nM on the glassy carbon-Pt-black-0.05% Nafion electrode. The applicability of the device was demonstrated by measuring the NO released from hypoxic RBCs, with the device allowing the released NO to cross-over into a cell free channel where it was detected in close to real-time. This type of device is an attractive alternative to the use of 3-dimensional devices with polycarbonate membranes, as either side of the membrane can be imaged and facile integration of electrochemical detection is possible. PMID:25105251

Integrated digital inverters based on two-dimensional anisotropic ReS₂ field-effect transistors

DOE PAGES

Liu, Erfu; Fu, Yajun; Wang, Yaojia; ...

2015-05-07

Semiconducting two-dimensional transition metal dichalcogenides are emerging as top candidates for post-silicon electronics. While most of them exhibit isotropic behaviour, lowering the lattice symmetry could induce anisotropic properties, which are both scientifically interesting and potentially useful. Here we present atomically thin rhenium disulfide (ReS₂) flakes with unique distorted 1T structure, which exhibit in-plane anisotropic properties. We fabricated monolayer and few-layer ReS₂ field-effect transistors, which exhibit competitive performance with large current on/off ratios (~10⁷) and low subthreshold swings (100 mV per decade). The observed anisotropic ratio along two principle axes reaches 3.1, which is the highest among all known two-dimensional semiconductingmore » materials. Furthermore, we successfully demonstrated an integrated digital inverter with good performance by utilizing two ReS₂ anisotropic field-effect transistors, suggesting the promising implementation of large-scale two-dimensional logic circuits. Our results underscore the unique properties of two-dimensional semiconducting materials with low crystal symmetry for future electronic applications.« less

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.

Cooperative suction by vertical capillary array pump for controlling flow profiles of microfluidic sensor chips.

PubMed

Horiuchi, Tsutomu; Hayashi, Katsuyoshi; Seyama, Michiko; Inoue, Suzuyo; Tamechika, Emi

2012-10-18

A passive pump consisting of integrated vertical capillaries has been developed for a microfluidic chip as an useful component with an excellent flow volume and flow rate. A fluidic chip built into a passive pump was used by connecting the bottoms of all the capillaries to a top surface consisting of a thin layer channel in the microfluidic chip where the thin layer channel depth was smaller than the capillary radius. As a result the vertical capillaries drew fluid cooperatively rather than independently, thus exerting the maximum suction efficiency at every instance. This meant that a flow rate was realized that exhibited little variation and without any external power or operation. A microfluidic chip built into this passive pump had the ability to achieve a quasi-steady rather than a rapidly decreasing flow rate, which is a universal flow characteristic in an ordinary capillary.

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

PubMed

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

2018-03-01

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