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Protein Crystal Growth With the Aid of Microfluidics

Protein crystallography is one of three well-known methods to obtain the structure of proteins. A major rate limiting step in protein crystallography is protein crystal nucleation and growth, which is still largely a process conducted by trial-and-error methods. Many attempts have been made to improve protein crystal growth by performing growth in microgravity. Although the use of microgravity appears to improve crystal quality in some attempts, this method has been inefficient because several reasons: we lack a fundamental understanding of macromolecular crystal growth in general and of the influence of microgravity in particular, we have to start with crystal growth conditions in microgravity based on conditions on the ground and finally the hardware does not allow for experimental iteration without reloading samples on the ground. To partially accommodate the disadvantages of the current hardware, we have used microfluidic technology (Lab-on-a-Chip devices) to design the concept of a more efficient crystallization device, suitable for use on the International Space Station and in high-throughput applications on the ground. The concept and properties of microfluidics, the application design process, and the advances in protein crystal growth hardware will be discussed in this presentation. Some examples of proteins crystallized in the new hardware will be discussed, including the differences between conventional crystallization versus crystallization in microfluidics.

vanderWoerd, Mark

Real-time processor for staring receivers

The design, fabrication, and testing of a state-of-the-art, high-throughput on-focal plane IR-image signal processor is described. The processing functions performed are frame differencing and thresholding. The final focal plane array will consist of a 128 x 128-pixel platinum-silicide detector bump-mounted to an on-chip CCD multiplexer. The processor is in a 128-channel parallel-pipeline format. Each channel consists of a pixel regenerator (charge differencer), 128-pixel frame store CCD memory, pixel differencer, second pixel regenerator, thresholder (analog comparator), and digital latch. Four parallel analog outputs and four parallel digital outputs are included. The digital outputs provide a bit map of the image. All analog clock signals (128 KHz, 256 KHz, and 5 MHz) are generated by on-chip TTL-input clock drivers. TTL clock driver inputs are generated off-chip. The technology is low-temperature surface and buried channel CCD/CMOS/indium bump. The design goal was 8-bit resolution at 77 K and 1000 frames/s. Applications include point- or extended-target motion detection with thresholding. Design trade-offs and enhancements (such as on-chip detector gain compensation and a simple window processor) are discussed.

Hanzal, Brian

Remotely Controlled Mixers for Light Microscopy Module (LMM) Colloid Samples

Developed by NASA Glenn Research Center, the LMM aboard the International Space Station (ISS) is enabling multiple biomedical science experiments. Techshot, Inc., has developed a series of colloid specialty cell systems (C-SPECS) for use in the colloid science experiment module on the LMM. These low-volume mixing devices will enable uniform particle density and remotely controlled repetition of LMM colloid experiments. By automating the experiment process, C-SPECS allow colloid samples to be processed more quickly. In addition, C-SPECS will minimize the time the crew will need to spend on colloid experiments as well as eliminate the need for multiple and costly colloid samples, which are expended after a single examination. This high-throughput capability will lead to more efficient and productive use of the LMM. As commercial launch vehicles begin routine visits to the ISS, C-SPECS could become a significant means to process larger quantities of high-value materials for commercial customers.

Kurk, Michael A. (Andy)

A low-power, high-throughput maximum-likelihood convolutional decoder chip for NASA's 30/20 GHz program

It is pointed out that the NASA 30/20 GHz program will place in geosynchronous orbit a technically advanced communication satellite which can process time-division multiple access (TDMA) information bursts with a data throughput in excess of 4 GBPS. To guarantee acceptable data quality during periods of signal attenuation it will be necessary to provide a significant forward error correction (FEC) capability. Convolutional decoding (utilizing the maximum-likelihood techniques) was identified as the most attractive FEC strategy. Design trade-offs regarding a maximum-likelihood convolutional decoder (MCD) in a single-chip CMOS implementation are discussed.

Mccallister, R. D.

Fault tolerant onboard packet switch architecture for communication satellites: Shared memory per beam approach

The NASA Lewis Research Center is developing a multichannel communication signal processing satellite (MCSPS) system which will provide low data rate, direct to user, commercial communications services. The focus of current space segment developments is a flexible, high-throughput, fault tolerant onboard information switching processor. This information switching processor (ISP) is a destination-directed packet switch which performs both space and time switching to route user information among numerous user ground terminals. Through both industry study contracts and in-house investigations, several packet switching architectures were examined. A contention-free approach, the shared memory per beam architecture, was selected for implementation. The shared memory per beam architecture, fault tolerance insertion, implementation, and demonstration plans are described.

Shalkhauser, Mary JO

Achieving High Throughput for Data Transfer over ATM Networks

File-transfer rates for ftp are often reported to be relatively slow, compared to the raw bandwidth available in emerging gigabit networks. While a major bottleneck is disk I/O, protocol issues impact performance as well. Ftp was developed and optimized for use over the TCP/IP protocol stack of the Internet. However, TCP has been shown to run inefficiently over ATM. In an effort to maximize network throughput, data-transfer protocols can be developed to run over UDP or directly over IP, rather than over TCP. If error-free transmission is required, techniques for achieving reliable transmission can be included as part of the transfer protocol. However, selected image-processing applications can tolerate a low level of errors in images that are transmitted over a network. In this paper we report on experimental work to develop a high-throughput protocol for unreliable data transfer over ATM networks. We attempt to maximize throughput by keeping the communications pipe full, but still keep packet loss under five percent. We use the Bay Area Gigabit Network Testbed as our experimental platform.

Johnson, Marjory J.

Genelab: Scientific Partnerships and an Open-Access Database to Maximize Usage of Omics Data from Space Biology Experiments

NASA's mission includes expanding our understanding of biological systems to improve life on Earth and to enable long-duration human exploration of space. The GeneLab Data System (GLDS) is NASA's premier open-access omics data platform for biological experiments. GLDS houses standards-compliant, high-throughput sequencing and other omics data from spaceflight-relevant experiments. The GeneLab project at NASA-Ames Research Center is developing the database, and also partnering with spaceflight projects through sharing or augmentation of experiment samples to expand omics analyses on precious spaceflight samples. The partnerships ensure that the maximum amount of data is garnered from spaceflight experiments and made publically available as rapidly as possible via the GLDS. GLDS Version 1.0, went online in April 2015. Software updates and new data releases occur at least quarterly. As of October 2016, the GLDS contains 80 datasets and has search and download capabilities. Version 2.0 is slated for release in September of 2017 and will have expanded, integrated search capabilities leveraging other public omics databases (NCBI GEO, PRIDE, MG-RAST). Future versions in this multi-phase project will provide a collaborative platform for omics data analysis. Data from experiments that explore the biological effects of the spaceflight environment on a wide variety of model organisms are housed in the GLDS including data from rodents, invertebrates, plants and microbes. Human datasets are currently limited to those with anonymized data (e.g., from cultured cell lines). GeneLab ensures prompt release and open access to high-throughput genomics, transcriptomics, proteomics, and metabolomics data from spaceflight and ground-based simulations of microgravity, radiation or other space environment factors. The data are meticulously curated to assure that accurate experimental and sample processing metadata are included with each data set. GLDS download volumes indicate strong interest of the scientific community in these data. To date GeneLab has partnered with multiple experiments including two plant (Arabidopsis thaliana) experiments, two mice experiments, and several microbe experiments. GeneLab optimized protocols in the rodent partnerships for maximum yield of RNA, DNA and protein from tissues harvested and preserved during the SpaceX-4 mission, as well as from tissues from mice that were frozen intact during spaceflight and later dissected on the ground. Analysis of GeneLab data will contribute fundamental knowledge of how the space environment affects biological systems, and as well as yield terrestrial benefits resulting from mitigation strategies to prevent effects observed during exposure to space environments.

bioinformatics

GeneLab: Scientific Partnerships and an Open-Access Database to Maximize Usage of Omics Data from Space Biology Experiments

NASA's mission includes expanding our understanding of biological systems to improve life on Earth and to enable long-duration human exploration of space. The GeneLab Data System (GLDS) is NASAs premier open-access omics data platform for biological experiments. GLDS houses standards-compliant, high-throughput sequencing and other omics data from spaceflight-relevant experiments. The GeneLab project at NASA-Ames Research Center is developing the database, and also partnering with spaceflight projects through sharing or augmentation of experiment samples to expand omics analyses on precious spaceflight samples. The partnerships ensure that the maximum amount of data is garnered from spaceflight experiments and made publically available as rapidly as possible via the GLDS. GLDS Version 1.0, went online in April 2015. Software updates and new data releases occur at least quarterly. As of October 2016, the GLDS contains 80 datasets and has search and download capabilities. Version 2.0 is slated for release in September of 2017 and will have expanded, integrated search capabilities leveraging other public omics databases (NCBI GEO, PRIDE, MG-RAST). Future versions in this multi-phase project will provide a collaborative platform for omics data analysis. Data from experiments that explore the biological effects of the spaceflight environment on a wide variety of model organisms are housed in the GLDS including data from rodents, invertebrates, plants and microbes. Human datasets are currently limited to those with anonymized data (e.g., from cultured cell lines). GeneLab ensures prompt release and open access to high-throughput genomics, transcriptomics, proteomics, and metabolomics data from spaceflight and ground-based simulations of microgravity, radiation or other space environment factors. The data are meticulously curated to assure that accurate experimental and sample processing metadata are included with each data set. GLDS download volumes indicate strong interest of the scientific community in these data. To date GeneLab has partnered with multiple experiments including two plant (Arabidopsis thaliana) experiments, two mice experiments, and several microbe experiments. GeneLab optimized protocols in the rodent partnerships for maximum yield of RNA, DNA and protein from tissues harvested and preserved during the SpaceX-4 mission, as well as from tissues from mice that were frozen intact during spaceflight and later dissected on the ground. Analysis of GeneLab data will contribute fundamental knowledge of how the space environment affects biological systems, and as well as yield terrestrial benefits resulting from mitigation strategies to prevent effects observed during exposure to space environments.

spaceflight

Emulation of Core Flight System Applications for Flight Software Development and Validation

The Mars Sample Return (MSR) campaign is an unprecedented attempt in the return of Martian samples back to Earth. The ascent from the surface will be performed by the Mars Ascent Vehicle (MAV), a critical element in the mission that National Aeronautics and Space Administration (NASA) Marshall Space Flight Center (MSFC) is developing. To this end, innovations in flight software development, verification, and validation are occurring. The MAV flight computer will run Core Flight System (cFS), an open-source software environment developed by NASA Goddard Space Flight Center (GSFC). NASA Marshall’s MAV Mission and Fault Management (M&FM) Team has implemented an emulation of two applications of this architecture: Limit Checker and Stored Command. Using an emulation of the functionalities of these applications allows for rapid prototyping of table-based algorithms. Further, M&FM is leveraging an in-house, low-fidelity but high-throughput State Analysis Model (SAM), an integrated MATLAB Stateflow Plant and Software model. This model is run in parallel with the cFS emulation for full flyout testing of the M&FM algorithms, verification of intent of these algorithms, and for future auto-generation of application-ingestible M&FM tables. The tables can then be delivered to the MAV Flight Software (FSW) team in a seamless process, reducing the cost of traditional FSW development and the risk of starting M&FM FSW development at later points in the NASA program life cycle.

Cody Wheeler

Emulation of Core Flight System Applications for Flight Software Development and Validation

The Mars Sample Return (MSR) campaign is an unprecedented attempt in the return of Martian samples back to Earth. The ascent from the surface will be performed by the Mars Ascent Vehicle (MAV), a critical element in the mission that National Aeronautics and Space Administration (NASA) Marshall Space Flight Center (MSFC) is developing. To this end, innovations in flight software development, verification, and validation are occurring. The MAV flight computer will run Core Flight System (cFS), an open-source software environment developed by NASA Goddard Space Flight Center (GSFC). NASA Marshall’s MAV Mission and Fault Management (M&FM) Team has implemented an emulation of two applications of this architecture: Limit Checker and Stored Command. Using an emulation of the functionalities of these applications allows for rapid prototyping of table-based algorithms. Further, M&FM is leveraging an in-house, low-fidelity but high-throughput State Analysis Model (SAM), an integrated MATLAB Stateflow Plant and Software model. This model is run in parallel with the cFS emulation for full flyout testing of the M&FM algorithms, verification of intent of these algorithms, and for future auto-generation of application-ingestible M&FM tables. The tables can then be delivered to the MAV Flight Software (FSW) team in a seamless process, reducing the cost of traditional FSW development and the risk of starting M&FM FSW development at later points in the NASA program life cycle.

Cody Wheeler

High-Throughput, Adaptive FFT Architecture for FPGA-Based Spaceborne Data Processors

Exponential growth in microelectronics technology such as field-programmable gate arrays (FPGAs) has enabled high-performance spaceborne instruments with increasing onboard data processing capabilities. As a commonly used digital signal processing (DSP) building block, fast Fourier transform (FFT) has been of great interest in onboard data processing applications, which needs to strike a reasonable balance between high-performance (throughput, block size, etc.) and low resource usage (power, silicon footprint, etc.). It is also desirable to be designed so that a single design can be reused and adapted into instruments with different requirements. The Multi-Pass Wide Kernel FFT (MPWK-FFT) architecture was developed, in which the high-throughput benefits of the parallel FFT structure and the low resource usage of Singleton s single butterfly method is exploited. The result is a wide-kernel, multipass, adaptive FFT architecture. The 32K-point MPWK-FFT architecture includes 32 radix-2 butterflies, 64 FIFOs to store the real inputs, 64 FIFOs to store the imaginary inputs, complex twiddle factor storage, and FIFO logic to route the outputs to the correct FIFO. The inputs are stored in sequential fashion into the FIFOs, and the outputs of each butterfly are sequentially written first into the even FIFO, then the odd FIFO. Because of the order of the outputs written into the FIFOs, the depth of the even FIFOs, which are 768 each, are 1.5 times larger than the odd FIFOs, which are 512 each. The total memory needed for data storage, assuming that each sample is 36 bits, is 2.95 Mbits. The twiddle factors are stored in internal ROM inside the FPGA for fast access time. The total memory size to store the twiddle factors is 589.9Kbits. This FFT structure combines the benefits of high throughput from the parallel FFT kernels and low resource usage from the multi-pass FFT kernels with desired adaptability. Space instrument missions that need onboard FFT capabilities such as the proposed DESDynl, SWOT (Surface Water Ocean Topography), and Europa sounding radar missions would greatly benefit from this technology with significant reductions in non-recurring cost and risk.

NguyenKobayashi, Kayla

Automated Miniaturized Instrument for Space Biology Applications and the Monitoring of the Astronauts Health Onboard the ISS

Human space travelers experience a unique environment that affects homeostasis and physiologic adaptation. The spacecraft environment subjects the traveler to noise, chemical and microbiological contaminants, increased radiation, and variable gravity forces. As humans prepare for long-duration missions to the International Space Station (ISS) and beyond, effective measures must be developed, verified and implemented to ensure mission success. Limited biomedical quantitative capabilities are currently available onboard the ISS. Therefore, the development of versatile instruments to perform space biological analysis and to monitor astronauts' health is needed. We are developing a fully automated, miniaturized system for measuring gene expression on small spacecraft in order to better understand the influence of the space environment on biological systems. This low-cost, low-power, multi-purpose instrument represents a major scientific and technological advancement by providing data on cellular metabolism and regulation. The current system will support growth of microorganisms, extract and purify the RNA, hybridize it to the array, read the expression levels of a large number of genes by microarray analysis, and transmit the measurements to Earth. The system will help discover how bacteria develop resistance to antibiotics and how pathogenic bacteria sometimes increase their virulence in space, facilitating the development of adequate countermeasures to decrease risks associated with human spaceflight. The current stand-alone technology could be used as an integrated platform onboard the ISS to perform similar genetic analyses on any biological systems from the tree of life. Additionally, with some modification the system could be implemented to perform real-time in-situ microbial monitoring of the ISS environment (air, surface and water samples) and the astronaut's microbiome using 16SrRNA microarray technology. Furthermore, the current system can be enhanced substantially by combining it with other technologies for automated, miniaturized, high-throughput biological measurements, such as fast sequencing, protein identification (proteomics) and metabolite profiling (metabolomics). Thus, the system can be integrated with other biomedical instruments in order to support and enhance telemedicine capability onboard ISS. NASA's mission includes sustained investment in critical research leading to effective countermeasures to minimize the risks associated with human spaceflight, and the use of appropriate technology to sustain space exploration at reasonable cost. Our integrated microarray technology is expected to fulfill these two critical requirements and to enable the scientific community to better understand and monitor the effects of the space environment on microorganisms and on the astronaut, in the process leveraging current capabilities and overcoming present limitations.

Human space travelers

Fabrication of Feedhorn-Coupled Transition Edge Sensor Arrays for Measurement of the Cosmic Microwave Background Polarization

Characterization of the minute cosmic microwave background polarization signature requires multi-frequency high-throughput precision instrument systems. We have previously described the detector fabrication of a 40 GHz focal plane and now describe the fabrication of the detector modules for measurement of the CMB at 90GHz. The 74-TES based bolometers in each module are coupled to a niobium based planar orthomode transducer with integrated band defining filters implemented in microstrip transmission line. A single crystal silicon dielectric substrate serves as microstrip dielectric and as a thermal link between the membrane isolated MoAu TES operating at 150mK and the heat bath. A short silicon leg between the heat bath and the TES bolometer is designed for ballistic phonon transport and provides improved process control and uniformity of thermal conductance in the presence of phonon scattering on roughened surfaces. Micro-machined structures are used to realize the orthomode transducer backshort, provide out of band signal rejection, and a silicon photonic choke for feedhorn coupling are described. The backshort, choke wafer, and detector wafer are indium bump bonded to create a single 37-element dual-polarization detector module. Fourteen such hexagonally shaped modules each 90 mm in size comprise two focal planes. These, along with the recently delivered 40GHz focal plane, will survey a large fraction of the sky as part of the Johns Hopkins University led ground based CLASS (Cosmology Large Angular Scale Surveyor) telescope.

Characterization

Fabrication of Feedhorn-Coupled Transition Edge Sensor Arrays for Measurement of the Cosmic Microwave Background Polarization

Characterization of the minute cosmic microwave background (CMB) polarization signature requires multi-frequency high-throughput precision instrument systems. We have previously described the detector fabrication of a 40 gigahertz focal plane and now describe the fabrication of a 37-element dual-polarization detector module for measurement of the CMB at 90 gigahertz. The 72-TES (Transition Edge Sensor)-based bolometers in each module are coupled to a niobium-based planar orthomode transducer with integrated band defining filters implemented in microstrip transmission line. A single crystal silicon dielectric substrate serves as microstrip dielectric and as a thermal link between the membrane isolated MoAu TES operating at 150 millikelvins and the heat bath. A short silicon leg between the heat bath and the TES bolometer is designed for ballistic phonon transport and provides improved process control and uniformity of thermal conductance in the presence of phonon scattering on roughened surfaces. Micro-machined structures are used to realize the orthomode transducer backshort, provide out of band signal rejection, and a silicon photonic choke for feedhorn coupling are described. The backshort, choke wafer, and detector wafer are indium bump-bonded to create a single 37-element dual-polarization detector module. Fourteen such hexagonally shaped modules each 80 millimeters in size comprise two focal planes. These, along with the recently delivered 40 gigahertz focal plane, will survey a large fraction of the sky as part of the Johns Hopkins University-led ground-based CLASS (Cosmology Large Angular Scale Surveyor) telescope.

Detectors

Studying Host-Pathogen Interactions In 3-D: Organotypic Models For Infectious Disease And Drug Development

Representative, reproducible and high-throughput models of human cells and tissues are critical for a meaningful evaluation of host-pathogen interactions and are an essential component of the research developmental pipeline. The most informative infection models - animals, organ explants and human trials - are not suited for extensive evaluation of pathogenesis mechanisms and screening of candidate drugs. At the other extreme, more cost effective and accessible infection models such as conventional cell culture and static co-culture may not capture physiological and three-dimensional aspects of tissue biology that are important in assessing pathogenesis, and effectiveness and cytotoxicity of therapeutics. Our lab has used innovative bioengineering technology to establish biologically meaningful 3-D models of human tissues that recapitulate many aspects of the differentiated structure and function of the parental tissue in vivo, and we have applied these models to study infectious disease. We have established a variety of different 3-D models that are currently being used in infection studies - including small intestine, colon, lung, placenta, bladder, periodontal ligament, and neuronal models. Published work from our lab has shown that our 3-D models respond to infection with bacterial and viral pathogens in ways that reflect the infection process in vivo. By virtue of their physiological relevance, 3-D cell cultures may also hold significant potential as models to provide insight into the neuropathogenesis of HIV infection. Furthermore, the experimental flexibility, reproducibility, cost-efficiency, and high throughput platform afforded by these 3-D models may have important implications for the design and development of drugs with which to effectively treat neurological complications of HIV infection.

Nickerson, Cheryl A.

Modular, Fast, Two-Dimensional Cyclic Convolver

Proposed high-throughput, real-time synthetic-aperture-radar (SAR) processor built using new, modular, two-dimensional cyclic convolver architecture based on polynomial factorization and designed for very-large-scale integrated (VLSI) circuitry. New architecture reduces cost, size, and power dissipation of SAR processor in comparison to high-speed array-processor approach. Processor also used for other image-and data-processing applications involving two-dimensional Fourier transforms.

Liu, K. Y.

Science with Constellation-X

NASA's upcoming Constellation-X mission, one of two flagship missions in the Beyond Einstein program, will have more than 100 times the collecting area of any previous spectroscopic mission operating in the 0.25-40 keV bandpass and will enable high-throughput, high spectral resolution studies of sources ranging from the most luminous accreting supermassive black holes in the Universe to the disks around young stars where planets form. This booklet, which was assembled during early 2005 using the contributions of a large team of Astrophysicists, outlines the important scientific questions for the decade following this one and describes the areas where Constellation-X is going to have a major impact. These areas include the exploration of the space-time geometry of black holes spanning nine orders of magnitude in mass and the nature of the dark energy and dark matter which govern the expansion and ultimate fate of the Universe. Constellation-X will also explore processes referred to as "cosmic feedback" whereby mechanical energy, radiation, and chemical elements from star formation and black holes are returned to interstellar and intergalactic medium, profoundly affecting the development of structure in the Universe, and will also probe all the important life cycles of matter, from stellar and planetary birth to stellar death via supernova to stellar endpoints in the form of accreting binaries and supernova remnants.

Hornschemeier, Ann

Life Science Research in Outer Space: New Platform Technologies for Low-Cost, Autonomous Small Satellite Missions

We develop integrated instruments and platforms suitable for economical, frequent space access for autonomous life science experiments and processes in outer space. The technologies represented by three of our recent free-flyer small-satellite missions are the basis of a rapidly growing toolbox of miniaturized biologically/biochemically-oriented instrumentation now enabling a new generation of in-situ space experiments. Autonomous small satellites (~ 1 50 kg) are less expensive to develop and build than fullsize spacecraft and not subject to the comparatively high costs and scheduling challenges of human-tended experimentation on the International Space Station, Space Shuttle, and comparable platforms. A growing number of commercial, government, military, and civilian space launches now carry small secondary science payloads at far lower cost than dedicated missions; the number of opportunities is particularly large for so-called cube-sat and multicube satellites in the 1 10 kg range. The recent explosion in nano-, micro-, and miniature technologies, spanning fields from telecommunications to materials to bio/chemical analysis, enables development of remarkably capable autonomous miniaturized instruments to accomplish remote biological experimentation. High-throughput drug discovery, point-of-care medical diagnostics, and genetic analysis are applications driving rapid progress in autonomous bioanalytical technology. Three of our recent missions exemplify the development of miniaturized analytical payload instrumentation: GeneSat-1 (launched: December 2006), PharmaSat (launched: May 2009), and O/OREOS (organism/organics exposure to orbital stresses; scheduled launch: May 2010). We will highlight the overall architecture and integration of fluidic, optical, sensor, thermal, and electronic technologies and subsystems to support and monitor the growth of microorganisms in culture in these small autonomous space satellites, including real-time tracking of their culture density, gene expression, and metabolic activity while in the space environment. Flight data and results will be presented from GeneSat-1, which tracked gene expression levels of GFP-labeled E. coli and from PharmaSat, which monitored the dose dependency of an antifungal agent against S. cerevisiae. The O/OREOS SESLO instrument, which will study the effects of radiation and microgravity upon the viability and growth characteristics of B. subtilis and the halophile Halorubrum chaoviatoris for periods of 0 - 6 months in space, will be described as well. The ongoing expansion of the small satellite toolbox of biological technologies will be summarized.

Ricco, Antonio J.