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At least 19 records

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

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

Yew, Alvin G.↗

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

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

Yew, Alvin G.↗

A user-friendly plug-and-play cyclic olefin copolymer-based microfluidic chip for room-temperature, fixed-target serial crystallography

Over the past two decades, serial X-ray crystallography has enabled the structure determination of a wide range of proteins. With the advent of X-ray free-electron lasers (XFELs), ever-smaller crystals have yielded high-resolution diffraction and structure determination. A crucial need to continue advancement is the efficient delivery of fragile and micrometre-sized crystals to the X-ray beam intersection. This paper presents an improved design of an all-polymer microfluidic `chip' for room-temperature fixed-target serial crystallography that can be tailored to broadly meet the needs of users at either synchrotron or XFEL light sources. The chips are designed to be customized around different types of crystals and offer users a friendly, quick, convenient, ultra-low-cost and robust sample-delivery platform. Compared with the previous iteration of the chip [Gilbile et al. (2021), Lab Chip , 21 , 4831–4845], the new design eliminates cleanroom fabrication. It has a larger imaging area to volume, while maintaining crystal hydration stability for both in situ crystallization or direct crystal slurry loading. Crystals of two model proteins, lysozyme and thaumatin, were used to validate the effectiveness of the design at both synchrotron (lysozyme and thaumatin) and XFEL (lysozyme only) facilities, yielding complete data sets with resolutions of 1.42, 1.48 and 1.70 Å, respectively. Overall, the improved chip design, ease of fabrication and high modifiability create a powerful, all-around sample-delivery tool that structural biologists can quickly adopt, especially in cases of limited sample volume and small, fragile crystals.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

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

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

Monaco, Lisa↗

Experiences with Lab-on-a-chip Technology in Support of NASA Supported Research

Under the auspices of the Microgravity Sciences and Application Department at Marshall Space Flight Center, we have custom designed and fabricated a lab-on-a-chip (LOC) device, along with Caliper Technologies, for macromolecular crystal growth. The chip has been designed to deliver specified proportions of up-to five various constituents to one of two growth wells (on-chip) for crystal growth. To date, we have grown crystals of thaumatin, glucose isomerase and appoferitin on the chip. The LOC approach offered many advantages that rendered it highly suitable for space based hardware to perform crystal growth on the International Space Station. The same hardware that was utilized for the crystal growth investigations, has also been used by researchers at Glenn Research Center to investigate aspects of microfluidic phenomenon associated with two-phase flow. Additionally, our LOCAD (Lab-on-a-chip Application Development) team has lent its support to Johnson Space Center s Modular Assay for Solar System Exploration project. At present, the LOCAD team is working on the design and build of a unique lab-on-a-chip breadboard control unit whose function is not commercially available. The breadboard can be used as a test bed for the development of chip size labs for environmental monitoring, crew health monitoring assays, extended flight pharmacological preparations, and many more areas. This unique control unit will be configured for local use and/or remote operation, via the Internet, by other NASA centers. The lab-on-a-chip control unit is being developed with the primary goal of meeting Agency level strategic goals.

Monaco, Lisa↗

Lab on a Chip Application Development for Exploration

At Marshall Space Flight Center a new capability has been established to aid the advancement of microfluidics for space flight monitoring systems. Lab-On-a-Chip Application Development (LOCAD) team has created a program for advancing Technology Readiness Levels (TRL) of 1 & 2 to TRL 6 and 7, quickly and economically for Lab-On-a-Chip (LOC) applications. Scientists and engineers can utilize LOCAD's process to efficiently learn about microfluidics and determine if microfluidics is applicable to their needs. Once the applicability has been determined, LOCAD can then perform tests to develop the new fluidic protocols which are different from macro-scale chemical reaction protocols. With this information new micro-devices can be created such as the development of a microfluidic system to aid in the search for life, past and present, on Mars. Particular indicators in the Martian soil can contain the direct evidence of life. But to extract the information from the soil and present it to the proper detectors requires multiple fluidic/chemical operations. This is where LOCAD is providing its unique abilities.

Monaco, Lisa↗

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

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

Spearing, Scott F.↗

Lab on a chip for a low-carbon future

Transitioning our society to a sustainable future, with low or net-zero carbon emissions to the atmosphere, will require a wide-spread transformation of energy and environmental technologies. In this perspective article, we describe how lab-on-a-chip (LoC) systems can help address this challenge by providing insight into the fundamental physical and geochemical processes underlying new technologies critical to this transition, and developing the new processes and materials required. We focus on six areas: (I) subsurface carbon sequestration, (II) subsurface hydrogen storage, (III) geothermal energy extraction, (IV) bioenergy, (V) recovering critical materials, and (VI) water filtration and remediation. Here, we hope to engage the LoC community in the many opportunities within the transition ahead, and highlight the potential of LoC approaches to the broader community of researchers, industry experts, and policy makers working toward a low-carbon future.

42 ENGINEERING↗

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

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

Maule, Jake↗

Lab-on-a-Chip Based Protein Crystallization

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

vanderWoerd, Mark J.↗

Automated Lab-on-a-Chip Electrophoresis System

Capillary electrophoresis is an analytical technique that can be used to detect and quantify extremely small amounts of various biological molecules. In the search for biochemical traces of life on other planets, part of this search involves an examination of amino acids, which are the building blocks of life on Earth. The most sensitive method for detecting amino acids is the use of laser induced fluorescence. However, since amino acids do not, in general, fluoresce, they first must be reacted with a fluorescent dye label prior to analysis. After this process is completed, the liquid sample then must be transported into the electrophoresis system. If the system is to be reused multiple times, samples must be added and removed each time. In typical laboratories, this process is performed manually by skilled human operators using standard laboratory equipment. This level of human intervention is not possible if this technology is to be implemented on extraterrestrial targets. Microchip capillary electrophoresis (CE) combined with laser induced fluorescence detection (LIF) was selected as an extremely sensitive method to detect amino acids and other compounds that can be tagged with a fluorescent dye. It is highly desirable to package this technology into an integrated, autonomous, in situ instrument capable of performing CE-LIF on the surface of an extraterrestrial body. However, to be fully autonomous, the CE device must be able to perform a large number of sample preparation and analysis operations without the direct intervention of a human.

Willis, Peter A.↗

The promise of macromolecular crystallization in microfluidic chips

Microfluidics, or lab-on-a-chip technology, is proving to be a powerful, rapid, and efficient approach to a wide variety of bioanalytical and microscale biopreparative needs. The low materials consumption, combined with the potential for packing a large number of experiments in a few cubic centimeters, makes it an attractive technique for both initial screening and subsequent optimization of macromolecular crystallization conditions. Screening operations, which require a macromolecule solution with a standard set of premixed solutions, are relatively straightforward and have been successfully demonstrated in a microfluidics platform. Optimization methods, in which crystallization solutions are independently formulated from a range of stock solutions, are considerably more complex and have yet to be demonstrated. To be competitive with either approach, a microfluidics system must offer ease of operation, be able to maintain a sealed environment over several weeks to months, and give ready access for the observation and harvesting of crystals as they are grown.

Review↗

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

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

Mora, Maria F.↗

The Promise of Macromolecular Crystallization in Micro-fluidic Chips

Micro-fluidics, or lab on a chip technology, is proving to be a powerful, rapid, and efficient approach to a wide variety of bio-analytical and microscale bio-preparative needs. The low materials consumption, combined with the potential for packing a large number of experiments in a few cubic centimeters, makes it an attractive technique for both initial screening and subsequent optimization of macromolecular crystallization conditions. Screening operations, which require equilibrating macromolecule solution with a standard set of premixed solutions, are relatively straightforward and have been successfully demonstrated in a micro-fluidics platform. More complex optimization methods, where crystallization solutions are independently formulated from a range of stock solutions, are considerably more complex and have yet to be demonstrated. To be competitive with either approach, a micro-fluidics system must offer ease of operation, be able to maintain a sealed environment over several weeks to months, and give ready access for the observation of crystals as they are grown.

vanderWoerd, Mark↗

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

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

Jenkins, A.↗

Transport Powder and Liquid Samples by Surface Acoustic Waves

Sample transport is an important requirement for In-situ analysis of samples in NASA planetary exploration missions. Tests have shown that powders or liquid drops on a surface can be transported by surface acoustic waves (SAW) that are generated on the surface using interdigital transducers. The phenomena were investigated experimentally and to generate SAWs interdigital electrodes were deposited on wafers of 128 deg rotated Y-cut LiNbO?. Transporting capability of the SAW device was tested using particles of various sizes and drops of various viscosities liquids. Because of different interaction mechanisms with the SAWs, the powders and the liquid drops were observed to move in opposite directions. In the preliminary tests, a speed of 180 mm/s was achieved for powder transportation. The detailed experimental setup and results are presented in this paper. The transporting mechanism can potentially be applied to miniaturize sample analysis system or " lab-on-chip" devices.

Sample handling↗

Perspectives of active Si photonics devices for data communication and optical sensing

Si photonics has made rapid progress in research and commercialization in the past two decades. While it started with electronic–photonic integration on Si to overcome the interconnect bottleneck in data communications, Si photonics has now greatly expanded into optical sensing, light detection and ranging (LiDAR), optical computing, and microwave/RF photonics applications. From an applied physics point of view, this perspective discusses novel materials and integration schemes of active Si photonics devices for a broad range of applications in data communications, spectrally extended complementary metal–oxide–semiconductor (CMOS) image sensing, as well as 3D imaging for LiDAR systems. We also present a brief outlook of future synergy between Si photonic integrated circuits and Si CMOS image sensors toward ultrahigh capacity optical I/O, ultrafast imaging systems, and ultrahigh sensitivity lab-on-chip molecular biosensing.

electronic band structure↗