The Bioimaging Science Technology development effort in BER is targeted at creating multifunctional technologies to image, measure, and model organisms, tissues, and key metabolic processes within biological systems of microbial cells and multicellular plant tissues. BER's current focus on developing a scientific basis for plant biomass-based biofuel production requires detailed understanding of the interaction among plant tissues and microbes. In complex communities the identity of cellular and tissue components under different environmental and physical conditions is a necessary first step to prioritize advantageous and deleterious organismal interactions. Further, the ability to track materials and chemical exchanges within and among cells and their environment is crucial to understanding the activity of microbial communities in environmental settings. Grant applications are sought in the following subtopics: a. Automated Bioimaging Devices for Structural and Functional Characterization of Plant and Microbial Communities Applications are invited that develop automated stand-alone imaging and measurement microscopes, instrumentation, or analysis software that can identify microbial species, tissue characteristics and chemical exchanges under different environmental and physical conditions. The output should be derived from imaging systems and should generate and manage large complex data sets. Automated system that characterizes multiple metabolic transformations will provide the integrative systems-level data needed to gain a more predictive understanding of complex biological processes relevant to BER. The instrumentation and devices to be developed for imaging biological systems will have high likelihood to enable an understanding the elements of complex biological systems or ecological niches related to bioenergy or a bioeconomy. The instrumentation would be capable of identifying individual species, tissues, organelles, or biological and structural components in an image and discover the physical conditions, spatial/temporal relationships, physical connections, and chemical exchanges that facilitate the flow of information and materials among organisms or biological components. The primary interest for this solicitation is for innovative bioimaging devices with small footprints, which are fully capable of operation independently of heavy equipment and large instruments (e.g., neutron and light sources, cry electron microscopes, high resolution mass spectrometers), and can be easily deployed in public and private sector to make them accessible to the larger scientific community. Instrumentation could use culture chambers in a laboratory setting with defined biological constructs or could be deployed for field-based evaluation of plants and microbes. The instrumentation should be able to characterize biological systems in controlled physical chemical and environmental conditions for validation and investigate biological systems under experimental conditions that support basic research to understand and optimize biomass-based biofuel production and a bioeconomy. Instrumentation originally developed for biomedical research could be adapted to investigate biological research supported by BER. However, real, or perceived device developments for medical imaging and/or applications including disease diagnostics or therapies in biological, animal and/or human systems are excluded. Algorithm development and software that supports instrumentation for the generation of biological images, data and knowledge would be included in this topic. However, general informatics solutions are not included under this subtopic. However, applications for the management and analysis of large-scale, multimodal, and multiscale data leveraging artificial intelligence and machine learning methods could be submitted under the SBIR/STTR Topic C55-17, Complex Data: Advanced Data Analytic Technologies for Systems Biology and Bioenergy . Tools that support facility-based x-ray, neutron or infrared beamline-based techniques and cryo-EM/ET or micro-ED for determining the 3D structures of macromolecules, macromolecular complexes, cells, cellular components, or tissues are not included under this subtopic. However, tools that ease use, improve results, or overcome obstacles associated with existing technologies could be supported under the SBIR/STTR Topic C5518, Enabling Tools for Structural Biology of Microbial and Plant Systems Relevant to Bioenergy. Questions Contact: Paul Sammak, Paul.Sammak@science.doe.gov b. Quantum Enabled Bioimaging and Sensing Approaches for Bioenergy Applications are invited that employ innovative, use-inspired technologies that exploit quantum phenomena to surpass limitations of classical optics including resolution and detection limits, signal-to-noise ratio, limitations on temporal dynamics, long term signal stability, sample photodamage and limited penetration, or selective biomolecule sensing. Quantum approaches should propose a comparative advantage over competing classical optical methods. Processes of interest to BER include measuring the chemical and physical environment within individual cells or organelles, enzyme function within cells, tracking metabolic pathways in vivo, monitoring the transport of materials into and out of cells or across cellular membranes and, measuring signaling processes between cells and within plant-microbe and microbe-microbe interactions. Current technical limitations and challenges associated with optical imaging and microscopy include: 1) depth imaging - light scattering and diffraction in biological tissue, a major barrier to imaging biological processes deep within tissue (plants or rhizosphere) - restricts optical microscopy to superficial layers, leaving many important biological questions unanswered; 2) photo-damage - classical high flux multiphoton optical imaging causes photo-damage to cellular viability and perturbation to molecular biology for in situ imaging of biological processes in living systems, rendering the sample useless for repeat imaging and measurement of dynamic processes to be performed within the same biological system over different time intervals; and 3) suboptimal stability, brightness and photo-bleaching of the fluorophore when used in combination with an optical imaging approach. Under this subtopic, applications are sought to explore new quantum science-enabled light sources, imaging detectors or biosensors envisioned to overcome the current challenges of in-depth imaging including associated scattering and diffraction problems, and suboptimal stability and photo-bleaching issues to enable prolonged imaging studies. Quantum entanglement imaging could also be combined with quantum sciencebased probes for sensing and measurement. These probes can be tailor-made to have high multiphoton crosssections, multiple chemical functionalities for protein binding and molecular tracking properties, spectrally tunable emission, and quantized absorption/emission states to enable high absorption of multiple entangled photons. Quantum-based biosensors might also detect other physical or chemical cues from the local biological environment and report conditions with photon emissions. Such systems may offer substantial improvement in signal detection and spatial and spectral selectivity by utilizing non-classical properties of light under low excitation power without causing significant photo-damage to cell composition or perturbing the natural biological processes within the cell. This subtopic seeks fundamental research towards development of new quantum science-enabled probes and sensors applicable for imaging of plant and microbial systems relevant to bioenergy and environmental research conducted within BER programs. These quantum approaches and imaging systems would need to visualize cellular structures and processes in a nondestructive manner, and at sufficient resolution to enable the validation of hypotheses of cellular function occurring in depth. Systems capable of cellular dynamics in vivo would be encouraged but not required. Some research areas of major emphasis within BER include understanding plant metabolism impacting cell wall composition/decomposition, deconstruction of plant polymers (lignin, cellulose, hemicellulose) to monomers, engineered microbial pathways for conversion of plant biomass-derived substrates to fuels and chemicals, and signaling and interactions within environmental microbiomes. This subtopic encourages the development of new quantum-based imaging approaches and demonstration of their utility for imaging biological systems of relevance to bioenergy and environmental research. Potential applications should address one or more of the topics according to examples outlined below, for prototype development: New quantum entanglement-based approaches for probes and sensors, to allow the observation and characterization of multiple complex biological processes occurring in depth within plant and microbial systems nondestructively or in living matter in real-time. New quantum entanglement enabled imaging devices with desirable photon intensities and wavelengths to overcome the problems of diffraction and scattering to allow the detection of image signals occurring in depth in a 3D volumetric composition within living plant and microbial systems. EXCLUSIONS/RESTRICTIONS: Real or perceived developments for medical imaging and/or applications including disease diagnostics or therapies in biological, animal and/or human systems are excluded. Standalone development of quantum dots for routine or innovative biological imaging experiments is excluded. The use of commercially available quantum dots (QDs), probes, or sensors as standards for data calibration and to study instrument performance for optical imaging experiments as a part of research proposal, are excluded from consideration.
