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Research Interests |
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The Biosystems Research department is conducting research in the following areas :
More detail for each subject area can be found by exploring the "Researchers" link to the left. Biodefense
(a) Late stage of infection of RAW 264.7 macrophages with Francisella novicida Utah 112 expressing fluorescent reporters (b) A microchip used to study cell signaling in immune cells infected with bacteria. Pictures courtesy of Todd Lane (panel a) and Nimisha Srivastava (panel b). We are one of the leading departments at Sandia involved in basic and applied research in biodefense. Our efforts span basic research in host-pathogen interactions and studying virulence mechanisms of pathogens as well as applied research in developing medical diagnostic and biosensors for biological agents, high-throughput screening for therapeutic targets and proteomic platforms for biomarker discovery and verification. We lead a multi-disciplinary and multi-departmental grand-challenge project (Microscale Immune Studies laboratory; PDF, 156Kb) to develop novel experimental and computational tools to elucidate the molecular mechanisms of the innate immune response to pathogens such as bacteria and viruses at the single cell level. Our approach utilizes a high-throughput microfluidic platform to provide a controlled environment for manipulating cells and to perform high-resolution hyperspectral confocal imaging and proteomic analysis. Predictive computational modeling is then used to integrate the data to construct a system-level understanding of innate immunity pathways. Our microengineered platform provides the biological research community with a miniaturized, versatile, and modular tool to perform single-cell analysis for many applications including infectious disease research and drug discovery. In the news
BiofuelsThe development of cheap renewable alternatives to fossil fuel derived transportation fuels would reduce our dependence on imported petroleum. “Energy crops” and agriculture waste are preferred long-term solutions for renewable, cheap and globally available feedstocks for biofuels. Researchers in our group are developing novel technologies and processes for production of biofuels production from cellulosic biomass. Our approach combines computational modeling, genomics, protein engineering and synthetic biology of extremophilic organisms to address the enzymatic breakdown and fermentation of cellulosic biomass. In additon it has been recognized that microalgal biodiesel has the potential of replacing much of the heavy transportation fuel. The development of a method by which algal biodiesel can be produced with high efficiency and low cost would be a disruptive development that would have far-reaching impact. The major bottleneck today is the triacylglyceride production and conversion. We are investigating and developing new techniques for the extraction and conversion of triacylglycerides as well as developing algae with increased triacylglyceride content. Our researchers are also playing key roles in the recently established Joint Bio-energy Institute (JBEI) funded by Office of Science in the US Department of Energy. For more information on JBEI, please visit http://jbei.lbl.gov Medical DiagnosticsUsing microfluidic chip-based assays, researchers in our group are developing portable devices for early diagnosis of diseases and exposure to pathogens. These devices are geared towards first-responders as well as healthcare professionals in primary care. Only a tiny drop of blood or saliva is required and results can be obtained in less than 10 minutes. The fully automated, self-contained device is controlled by either a laptop computer or a touch screen on the device. Test results digitally indicate the:
A prototype weighing approximately 5 lbs. being developed for point-of-care diagnostics The heart of the device is a microfluidic chip that, in a few minutes, performs electrophoretic immunoassays prior to sensitive (~10-12 molar detection limit) laser-induced fluorescence detection requiring only a few microliters of sample. The chip is integrated with miniaturized electronics, optical elements, fluid-handling components, and data acquisition software to provide a portable, self-contained device. The microfluidic chip houses microchannels that are 20-40 micron deep, 100 micron wide and a few centimeters long (similar in scale to human hair). Numerous sample manipulation steps are required to complete the detailed analysis. 
Microfluidic chips allows rapid and sensitive detection of salivary markers of periodontal disease The beauty and power of our approach is the seamless integration of all necessary steps — sample loading, mixing of sample with fluorescent detection antibody, concentration (to improve detection limit) and electrophoretic separation of bound and unbound antibody – into one instrument making operation “hands-free”. The entire device, including the microfluidic core, photomultiplier, and electronics, is a hand-held package that weighs less than five pounds, thus providing the features required for point-of-care applications: sensitivity, portability, and the ability to run tests quickly. For more information
ProteomicsProteins are where the action is in a cell – they are the active end products of the genome. As such, direct, large-scale characterization of cellular proteins is key to understanding many biological processes where important information about protein expression, activity, or modification cannot be obtained at the DNA/RNA level. We have a number of efforts ongoing as listed below: 
Two-dimensional gel electrophoresis of soluble proteins in sulfate-reducing microbe Desulfovibrio vulgaris (photo courtesy Rajat Sapra)
We maintain state of the art equipment for proteomics research including 3 mass spectrometers (Applied Biosystems Voyager DE PRO, Waters QTOF Ultima, Thermo LCQ), liquid chromatography capability (HP1100, Waters CapLC, Eksigent nano2DLC), and high throughput sample preparation robotics (Typhoon gel imager, Ettan spot picker, Genomic Solutions ProPrep). Microfluidics
SDS-PAGE in a chip High-throughput experimental biology increasingly demands large numbers of experiments performed in a shorter period of time. Microfluidics or “Lab-on-a-Chip” devices are an enabling technology that allows researchers to study complex biological problems that would be difficult, tedious, labor-intensive, or otherwise cost-prohibitive using conventional bench-scale techniques. Microfludics offers high sensitivity with inherently low reagent consumption, and can be automated to perform a variety of complex, multi-step analyses with only minimal user intervention. The Biosystems Research department has developed expertise in several areas of microfluidics, with an emphasis on applying proven lab-on-a-chip technology to solving relevant biological problems. Our strength in fundamental biology provides important insight and direction in choosing problems and developing techniques that will make an impact in the way researchers study biology. Our collaborations with the Microfluidics and Microsystems Engineering departments (8324 and 8125) provide additional strength in developing robust, miniaturized, user-friendly, automated systems for studying complex biological problems. Areas of expertise in microfluidics within the Biosystems Research department include:
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