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NASA NTRS1984

Marketing the use of the space environment for the processing of biological and pharmaceutical materials

The perceptions of U.S. biotechnology and pharmaceutical companies concerning the potential use of the space environment for the processing of biological substances was examined. Physical phenomena that may be important in space-base processing of biological materials are identified and discussed in the context of past and current experiment programs. The capabilities of NASA to support future research and development, and to engage in cooperative risk sharing programs with industry are discussed. Meetings were held with several biotechnology and pharmaceutical companies to provide data for an analysis of the attitudes and perceptions of these industries toward the use of the space environment. Recommendations are made for actions that might be taken by NASA to facilitate the marketing of the use of the space environment, and in particular the Space Shuttle, to the biotechnology and pharmaceutical industries.

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NASA NTRS1992

Materials dispersion and biodynamics project research

The Materials Dispersion and Biodynamics Project (MDBP) focuses on dispersion and mixing of various biological materials and the dynamics of cell-to-cell communication and intracellular molecular trafficking in microgravity. Research activities encompass biomedical applications, basic cell biology, biotechnology (products from cells), protein crystal development, ecological life support systems (involving algae and bacteria), drug delivery (microencapsulation), biofilm deposition by living organisms, and hardware development to support living cells on Space Station Freedom (SSF). Project goals are to expand the existing microgravity science database through experiments on sounding rockets, the Shuttle, and COMET program orbiters and to evolve,through current database acquisition and feasibility testing, to more mature and larger-scale commercial operations on SSF. Maximized utilization of SSF for these science applications will mean that service companies will have a role in providing equipment for use by a number of different customers. An example of a potential forerunner of such a service for SSF is the Materials Dispersion Apparatus (MDA) 'mini lab' of Instrumentation Technology Associates, Inc. (ITA) in use on the Shuttle for the Commercial MDAITA Experiments (CMIX) Project. The MDA wells provide the capability for a number of investigators to perform mixing and bioprocessing experiments in space. In the area of human adaptation to microgravity, a significant database has been obtained over the past three decades. Some low-g effects are similar to Earth-based disorders (anemia, osteoporosis, neuromuscular diseases, and immune system disorders). As new information targets potential profit-making processes, services and products from microgravity, commercial space ventures are expected to expand accordingly. Cooperative CCDS research in the above mentioned areas is essential for maturing SSF biotechnology and to ensure U.S. leadership in space technology. Currently, the MDBP conducts collaborative research with investigators at the Rockefeller University, National Cancer Institute, and the Universities of California, Arizona, and Alabama in Birmingham. The growing database from these collaborations provides fundamental information applicable to development of cell products, manipulation of immune cell response, bone cell growth and mineralization, and other processes altered by low-gravity. Contacts with biotechnology and biopharmaceutical companies are being increased to reach uninformed potential SSF users, provide access through the CMDS to interested users for feasibility studies, and to continue active involvement of current participants. We encourage and actively seek participation of private sector companies, and university and government researchers interested in biopharmaceuticals, hardware development and fundamental research in microgravity.

Lewis, Marian L.↗

NASA NTRS2004

Evaluation of a Multi-Parameter Sensor for Automated, Continuous Cell Culture Monitoring in Bioreactors

Compact and automated sensors are desired for assessing the health of cell cultures in biotechnology experiments in microgravity. Measurement of cell culture medium allows for the optirn.jzation of culture conditions on orbit to maximize cell growth and minimize unnecessary exchange of medium. While several discrete sensors exist to measure culture health, a multi-parameter sensor would simplify the experimental apparatus. One such sensor, the Paratrend 7, consists of three optical fibers for measuring pH, dissolved oxygen (p02), dissolved carbon dioxide (pC02) , and a thermocouple to measure temperature. The sensor bundle was designed for intra-arterial placement in clinical patients, and potentially can be used in NASA's Space Shuttle and International Space Station biotechnology program bioreactors. Methods: A Paratrend 7 sensor was placed at the outlet of a rotating-wall perfused vessel bioreactor system inoculated with BHK-21 (baby hamster kidney) cells. Cell culture medium (GTSF-2, composed of 40% minimum essential medium, 60% L-15 Leibovitz medium) was manually measured using a bench top blood gas analyzer (BGA, Ciba-Corning). Results: A Paratrend 7 sensor was used over a long-term (>120 day) cell culture experiment. The sensor was able to track changes in cell medium pH, p02, and pC02 due to the consumption of nutrients by the BHK-21. When compared to manually obtained BGA measurements, the sensor had good agreement for pH, p02, and pC02 with bias [and precision] of 0.02 [0.15], 1 mm Hg [18 mm Hg], and -4.0 mm Hg [8.0 mm Hg] respectively. The Paratrend oxygen sensor was recalibrated (offset) periodically due to drift. The bias for the raw (no offset or recalibration) oxygen measurements was 42 mm Hg [38 mm Hg]. The measured response (rise) time of the sensor was 20 +/- 4s for pH, 81 +/- 53s for pC02, 51 +/- 20s for p02. For long-term cell culture measurements, these response times are more than adequate. Based on these findings , the Paratrend sensor could offer automated, continuous monitoring of cell cultures with a temporal resolution of 1 minute, which is not attainable by sampling via handheld blood analyzer (i-STAT). Conclusion: The resulting bias and precision found in these cell culture-based studies is comparable to Paratrend sensor clinical results. Although the large error in p02 measurements (+/-18 mm Hg) may be acceptable for clinical applications, where Paratrend values are periodically adjusted to a BGA measurement, the O2 sensor in this bundle may not be reliable enough for the single-calibration requirement of sensors used in NASA's bioreactors. The pH and pC02 sensors in the bundle are reliable and stable over the measurement period, and can be used without recalibration to measure cell cultures in rn.jcrogravity biotechnology experiments. Future work will test additional Paratrend sensors to provide statistical assessment of sensor performance.

Pappas, D.↗

NASA NTRS2018

Developing a Cas9-Based Tool to Engineer Native Plasmids in Synechocystis sp. PCC 6803

The oxygenic photosynthetic bacterium Synechocystis sp. PCC 6803 (S6803) is a model cyanobacterium widely used for fundamental research and biotechnology applications. Due to its polyploidy, existing methods for genome engineering of S6803 require multiple rounds of selection to modify all genome copies, which is time consuming and inefficient. In this study, we engineered the Cas9 tool for onestep, segregationfree genome engineering. We further used our Cas9 tool to delete three of seven S6803 native plasmids. Our results show that all three smallsize native plasmids, but not the largesize native plasmids, can be deleted with this tool. To further facilitate heterologous gene expression in S6803, a shuttle vector based on the native plasmid pCC5.2 was created. The shuttle vector can be introduced into Cas9containing S6803 in one step without requiring segregation and can be stably maintained without antibiotic pressure for at least 30 days. Moreover, genes encoded on the shuttle vector remain functional after 30 days of continuous cultivation without selective pressure. Thus, this study provides a set of new tools for rapid modification of the S6803 genome and for stable expression of heterologous genes, potentially facilitating both fundamental research and biotechnology applications using S6803.

biotechnology↗

NASA NTRS1986

Space bio-technology in housing

Gas chromatography and mass spectrometry data obtained from monitoring atmospheric pollutants in Skylab spurred studies of indoor pollutants in terrestrial buildings. Subsequent studies of techniques for removing the pollutants from space habitats have led to building concepts which achieve the same purpose on earth. The Skylab data indicated that the synthesized organic materials used in many modern buildings, furnishings, personal clothing and aerosols add significant amounts of chemicals to the indoor atmosphere. Lowered circulation and ventilation rates to conserve energy have caused trapping of these substances in buildings. Studies of methods for space modules which will use plants and microbes to absorb airborne and wastewater pollutants have defined biotechnology designs which can be applied to remove pollutants from air and wastewater organically. Plant roots trap pollutants from wastewater and leaves readily absorb air pollutants, as well as improve the overall energy efficiency of buildings. Several designs which incorporate biotechnology to enhance both the aesthetics and efficiency of homes and office buildings are illustrated.

Wolverton, B. C.↗

NASA NTRS1988

Development of Bio-GAS systems

Four experiment systems which have fundamental significance in the field of biotechnology are developed for the Get Away Special (GAS). Unique considerations were necessary to develop the systems which carry out biotechnological experiments under GAS's restricted conditions: delicate thermal control, fluid handling and protection from contamination. All experimental processes are controlled by internal sequencers and results of the experiments are recorded as images and numerical data within the systems. The systems are standardized in order to enable repeated use with a variety of experiments by replacement of the experiment modules and modification of experiment sequencing programs.

Takayanagi, M.↗

NASA NTRS1990

Low-gravity materials experiments in the Space Station Freedom

The science and hardware programs laying the science and technology framework for experiments to be conducted aboard SSF are described. Six microgravity facilities planned for the Laboratory Module encompass the Fluid Physics/Dynamics Facility, investigating fundamental fluid behavior; the Advanced Protein Crystal Growth Facility, growing high-quality crystals for pharmaceutical, medical, chemical, and biotechnology applications; the Biotechnology Facility, investigating microgravity effects on biological processes and living organisms at the cellular level and on the purification and production of biological materials; the Space Station Furnace Facility, conducting metal and alloy solidification experiments; the Modular Containerless Processing Facility, supporting experiments through levitation techniques; and the Modular Combustion Facility, performing studies of fundumental combustion processes.

Chassay, Roger P.↗

NASA NTRS1992

Advanced Manufacturing and Value-added Products from US Agriculture

An objective of the US Department of Agriculture (USDA) Agriculture Research Service (ARS) is to develop technology leading to a broad portfolio of value-added marketable products. Modern scientific disciplines such as chemical engineering are brought into play to develop processes for converting bulk commodities into high-margin products. To accomplish this, the extremely sophisticated processing devices which form the basis of modern biotechnology, namely, genes and enzymes, can be tailored to perform the required functions. The USDA/ARS is a leader in the development of intelligent processing equipment (IPE) for agriculture in the broadest sense. Applications of IPE are found in the production, processing, grading, and marketing aspects of agriculture. Various biotechnology applications of IPE are discussed.

Villet, Ruxton H.↗

NASA NTRS1992

Research objectives, opportunities, and facilities for microgravity science

Microgravity Science in the U.S.A. involves research in fluids science, combustion science, materials science, biotechnology, and fundamental physics. The purpose is to achieve a thorough understanding of the effects of gravitational body forces on physical phenomena relevant to those disciplines. This includes the study of phenomena which are usually overwhelmed by the presence of gravitational body forces and, therefore, chiefly manifested when gravitational forces are weak. In the pragmatic sense, the research involves gravity level as an experimental parameter. Calendar year 1992 is a landmark year for research opportunities in low earth orbit for Microgravity Science. For the first time ever, three Spacelab flights will fly in a single year: IML-1 was launched on January 22; USML-1 was launched on June 25; and, in September, SL-J will be launched. A separate flight involving two cargo bay carriers, USMP-1, will be launched in October. From the beginning of 1993 up to and including the Space Station era (1997), nine flights involving either Spacelab or USMP carriers will be flown. This will be augmented by a number of middeck payloads and get away specials flying on various flights. All of this activity sets the stage for experimentation on Space Station Freedom. Beginning in 1997, experiments in Microgravity Science will be conducted on the Space Station. Facilities for doing experiments in protein crystal growth, solidification, and biotechnology will all be available. These will be joined by middeck-class payloads and the microgravity glove box for conducting additional experiments. In 1998, a new generation protein crystal growth facility and a facility for conducting combustion research will arrive. A fluids science facility and additional capability for conducting research in solidification, as well as an ability to handle small payloads on a quick response basis, will be added in 1999. The year 2000 will see upgrades in the protein crystal growth and fluids science facilities. From the beginning of 1997 to the fall of 1999 (the 'man-tended capability' era), there will be two or three utilization flights per year. Plans call for operations in Microgravity Science during utilization flights and between utilization flights. Experiments conducted during utilization flights will characteristically require crew interaction, short duration, and less sensitivity to perturbations in the acceleration environment. Operations between utilization flights will involve experiments that can be controlled remotely and/or can be automated. Typically, the experiments will require long times and a pristine environment. Beyond the fall of 1999 (the 'permanently-manned capability' era), some payloads will require crew interaction; others will be automated and will make use of telescience.

Bayuzick, Robert J.↗

NASA NTRS1992

Characterization of surfaces

Low gravity biotechnology experiments indicate a need to better understand and control a host of liquid-solid interfacial phenomena which reduce the efficiency of bioseparations methods on earth as well as in space. We have improved and utilized polymeric and silane derivatives, developed in association with MSFC, in order to control such phenomena. The objectives of the proposed research have been obtained. They were to improve NASA-patented coatings capable of controlling macromolecular adsorption, electroosmosis, and particle electrophoresis over a wide range of pH, and to further characterize the ability of polymeric coatings to control wall wetting interactions. To date this research has resulted in six publications and four abstracts. It has also aided researchers at MSFC with studies on the electrophoresis of large DNA molecules in free solution. It will continue to enhance NASA's efforts to exploit the space environment to enhance knowledge of phenomena relevant to biotechnology, and obtain bioseparations currently unobtainable on Earth. Abstracts from the 1994 ACS Meeting in Birmingham are attached.

Vanalstine, James M.↗

NASA NTRS1996

STS-79 Flight Day 5

On this fifth day of the STS-79 mission, the flight crew, Cmdr. William F. Readdy, Pilot Terrence W. Wilcutt, Mission Specialists, Thomas D. Akers, Shannon Lucid, Jay Apt, and Carl E. Walz, in the first full day of joint Shuttle/Mir operations begin in with the transfer of a biotechnology investigation and logistical supplies from Atlantis to Mir. The Biotechnology System, an investigation that will study the long-term development of cartilage cells in microgravity, was transported to Mir early this morning. During his planned four-month stay on Mir, John Blaha will take weekly samples of the culture which may provide researchers with information on engineering cartilage cells for possible use in transplantation. They also took time out of their schedules to talk with Good Morning America's Elizabeth Vargas in a brief interview. Prior to beginning the day's transfer activities, all nine astronauts and cosmonauts participated in a joint planning session to outline the day's schedule.

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NASA NTRS1997

Microgravity Science and Applications: Program Tasks and Bibliography for Fiscal Year 1996

NASA's Microgravity Science and Applications Division (MSAD) sponsors a program that expands the use of space as a laboratory for the study of important physical, chemical, and biochemical processes. The primary objective of the program is to broaden the value and capabilities of human presence in space by exploiting the unique characteristics of the space environment for research. However, since flight opportunities are rare and flight research development is expensive, a vigorous ground-based research program, from which only the best experiments evolve, is critical to the continuing strength of the program. The microgravity environment affords unique characteristics that allow the investigation of phenomena and processes that are difficult or impossible to study an Earth. The ability to control gravitational effects such as buoyancy driven convection, sedimentation, and hydrostatic pressures make it possible to isolate phenomena and make measurements that have significantly greater accuracy than can be achieved in normal gravity. Space flight gives scientists the opportunity to study the fundamental states of physical matter-solids, liquids and gasses-and the forces that affect those states. Because the orbital environment allows the treatment of gravity as a variable, research in microgravity leads to a greater fundamental understanding of the influence of gravity on the world around us. With appropriate emphasis, the results of space experiments lead to both knowledge and technological advances that have direct applications on Earth. Microgravity research also provides the practical knowledge essential to the development of future space systems. The Office of Life and Microgravity Sciences and Applications (OLMSA) is responsible for planning and executing research stimulated by the Agency's broad scientific goals. OLMSA's Microgravity Science and Applications Division (MSAD) is responsible for guiding and focusing a comprehensive program, and currently manages its research and development tasks through five major scientific areas: biotechnology, combustion science, fluid physics, fundamental physics, and materials science. FY 1996 was an important year for MSAD. NASA continued to build a solid research community for the coming space station era. During FY 1996, the NASA Microgravity Research Program continued investigations selected from the 1994 combustion science, fluid physics, and materials science NRAS. MSAD also released a NASA Research Announcement in microgravity biotechnology, with more than 130 proposals received in response. Selection of research for funding is expected in early 1997. The principal investigators chosen from these NRAs will form the core of the MSAD research program at the beginning of the space station era. The third United States Microgravity Payload (USMP-3) and the Life and Microgravity Spacelab (LMS) missions yielded a wealth of microgravity data in FY 1996. The USMP-3 mission included a fluids facility and three solidification furnaces, each designed to examine a different type of crystal growth.

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NASA NTRS2000

Microgravity Research Results and Experiences from the NASA Mir Space Station Program

The Microgravity Research Program Office (MRPO) participated aggressively in Phase I of the International Space Station Program using the Russian Mir Space Station. The Mir Station offered an otherwise unavailable opportunity to explore the advantages and challenges to long duration microgravity space research. Payloads with both NASA and commercial backing were included as well as cooperative research with the Canadian Space Agency (CSA). From this experience, much was learned about dealing with long duration on orbit science utilization and developing new working relationships with our Russian partner to promote efficient planning, operations, and integration to solve complexities associated with a multiple partner program. Microgravity participation in the NASA Mir Program began with the first joint NASA Mir flight to the Mir Space Station. The earliest participation setup acceleration measurement capabilities that were used throughout the Program. Research, conducted by all Microgravity science disciplines, continued on each subsequent increment for the entire three-year duration of the Program. The Phase I Program included the Microgravity participation of over 30 Fluids, Combustion, Materials, and Biotechnology Sciences and numerous commercially sponsored research payloads. In addition to the research gained from Microgravity investigations, long duration operation of facility hardware was tested. Microgravity facilities operated on Mir included the Space Acceleration Measurement System (SAMS), the Microgravity Glovebox (MGBX), the Biotechnology System (BTS) and the Canadian Space Agency sponsored Microgravity Isolation Mount (MIM). The Russian OPTIZONE Furnace was also incorporated into our material science research. All of these efforts yielded significant and useful scientific research data. This paper focuses on the microgravity research conducted onboard the Mir space station. It includes the Program preparation and planning necessary to support this type of cross increment research experience; the payloads which were flown; and summaries of significant microgravity science findings. Most importantly this paper highlights the various disciplines of microgravity research conducted during the International Space Station, Phase 1 Program onboard the Mir Station. A capsulation of significant research and the applicability of our findings are provided. In addition, a brief discussion of how future microgravity science gathering capabilities, hardware development and payload operations techniques have enhanced our ability to conduct long duration microgravity research.

Schagheck, R. A.↗

NASA NTRS2000

Overview of Nanobiotechnology

The ability to manipulate matter at the atomic and molecular levels is likely to change the way almost everything is designed and made, from computers to engineering systems to objects not yet imagined. For nanometer-scale objects, biological systems provide a rich storehouse of interesting ideas and strategies, and this is why there has been synergistic coupling between nanotechnology and biotechnology. The field of nanobiotechnology is garnering much interest around the world. In January 2000, the President announced the establishment of the National Nanotechnology Initiative and has made it a top priority. An attempt is made in this overview to define some of the buzzwords and set the stage for the succeeding presentations. This presentation is divided into four parts. The first part identifies the major characteristics of future aerospace systems that distinguish them from the current systems. The second and third parts describe the revolutionary and key technologies and future research and learning environments required for the realization of future systems. The fourth part lists the objectives of the workshop and the sources of information about nano and biotechnologies. This document consists of viewgraphs with an explanation for each slide.

Ahmed K. Noor↗

NASA NTRS2002

First Commerical Operations on the International Space Station

As part of NASA's mission of furthering the commercial development of space, the Space Product Development Office has sponsored the flight of seven commercial payloads to the International Space Station (ISS) during calendar year 2001. Most of these payloads, which are among the first users of this new laboratory, build upon successful commercial investigations that previously were restricted to the limited flight duration of the Space Shuttle. These commercial operations range from multi-media, in the form of Dreamtime, to biotechnology such as in Advanced Astroculture, to advanced materials such as Zeolite Crystal Growth. Industry investment in the commercial program has continued to remain high, while awaiting long term access to space, which the ISS provides. While the majority of early commercial use of the ISS is in the area of biotechnology, there is a significant shift towards commercial materials research over the next two years. In order to take fall advantage of the ISS, much of the commercial hardware is designed to be left on Station, while the Shuttle brings samples up and down. This not only makes good use of this valuable space resource, it has the added benefit of having commercial hardware available on the ISS for scientific users. In order to provide benefit to the entire NASA microgravity program, the scientific community on a space available basis can use a variety of commercial apparatus at very low cost. In addition to the solution crystal growth capability of Creosote Crystal Growth, in 2002 containerless processing will be available in the form of Space-DRUMS, and in 2003, thermophysical properties research can be performed in the Vulcan furnace. The first commercial operations on the ISS provides not only a much needed capability to the commercial development of space program, it also has the potential to augment the science program as well.

Nall, Mark E.↗

NASA NTRS2003

Space Station Science Supported by Marshall Space Flight Center

The science program at Marshall Space Flight Center will be reviewed in the context of the overall NASA science program. An overview will be given on how Marshall science supports the International Space Station research program. The Microgravity research capabilities at Marshall's Biological and Physical Space Research Laboratory will be reviewed. The environment in orbit provides a unique opportunity to study Materials Science and Biotechnology in the absence of sedimentation and convection. There are a number of peer-selected investigations that have been selected to fly on the Space Station that have been conceived and are led by Marshall civil service and contractor scientists. In addition to Microgravity research the Station will enable research in New Initiative Research Areas that focus on enabling humans to live, work, and explore the solar system safely. The specific scientific instruments that have been developed for Materials Science and Biotechnology Research on the International Space Station will be discussed.

Whitaker, Ann F.↗

NASA NTRS2006

Technological Innovations from NASA

The challenge of human space exploration places demands on technology that push concepts and development to the leading edge. In biotechnology and biomedical equipment development, NASA science has been the seed for numerous innovations, many of which are in the commercial arena. The biotechnology effort has led to rational drug design, analytical equipment, and cell culture and tissue engineering strategies. Biomedical research and development has resulted in medical devices that enable diagnosis and treatment advances. NASA Biomedical developments are exemplified in the new laser light scattering analysis for cataracts, the axial flow left ventricular-assist device, non contact electrocardiography, and the guidance system for LASIK surgery. Many more developments are in progress. NASA will continue to advance technologies, incorporating new approaches from basic and applied research, nanotechnology, computational modeling, and database analyses.

Pellis, Neal R.↗

NASA NTRS2016

Biomolecular Analysis Capability for Cellular and Omics Research on the International Space Station

International Space Station (ISS) assembly complete ushered a new era focused on utilization of this state-of-the-art orbiting laboratory to advance science and technology research in a wide array of disciplines, with benefits to Earth and space exploration. ISS enabling capability for research in cellular and molecular biology includes equipment for in situ, on-orbit analysis of biomolecules. Applications of this growing capability range from biomedicine and biotechnology to the emerging field of Omics. For example, Biomolecule Sequencer is a space-based miniature DNA sequencer that provides nucleotide sequence data for entire samples, which may be used for purposes such as microorganism identification and astrobiology. It complements the use of WetLab-2 SmartCycler"TradeMark", which extracts RNA and provides real-time quantitative gene expression data analysis from biospecimens sampled or cultured onboard the ISS, for downlink to ground investigators, with applications ranging from clinical tissue evaluation to multigenerational assessment of organismal alterations. And the Genes in Space-1 investigation, aimed at examining epigenetic changes, employs polymerase chain reaction to detect immune system alterations. In addition, an increasing assortment of tools to visualize the subcellular distribution of tagged macromolecules is becoming available onboard the ISS. For instance, the NASA LMM (Light Microscopy Module) is a flexible light microscopy imaging facility that enables imaging of physical and biological microscopic phenomena in microgravity. Another light microscopy system modified for use in space to image life sciences payloads is initially used by the Heart Cells investigation ("Effects of Microgravity on Stem Cell-Derived Cardiomyocytes for Human Cardiovascular Disease Modeling and Drug Discovery"). Also, the JAXA Microscope system can perform remotely controllable light, phase-contrast, and fluorescent observations. And upcoming confocal microscopy capability will allow for optical sectioning of biological tissues to determine microanatomical localization of biomarkers. Furthermore, NASA's geneLAB effort addresses integration of genomic, epigenomic, transcriptomic, proteomic and metabolomic datasets, by applying an innovative open source science platform for multi-investigator high throughput utilization of the ISS. In sum, the expanding ISS capability for analysis of biomolecules is enabling innovative research in a broad spectrum of areas such as cellular and molecular biology, biotechnology, tissue engineering, biomedicine, and Omics, providing manifold benefits for humanity.

Guinart-Ramirez, Y.↗