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Principal Investigator: OLGA A AMOSOVA
Organization: ACTOPROBE, LLC
Fiscal Year: 2024
Award: $295,308
Funding agency: National Institute of Biomedical Imaging and Bioengineering
Abstract: Understanding molecular mechanisms of diseases and manipulating them to achieve cure
constitutes one of the "holy Grail" of biomedical science. Infectious (and parasitic) diseases are responsible
for ~30% of premature deaths, especially in low- and middle-income countries. Studies of the pathogenic agents
require high-resolution and high-sensitivity microscopy and spectroscopy equipment, ideally capable of
detecting single molecules of interest (i.e., DNA bases, proteins on viral capsids, etc.). Scanning near-field
optical microscopy (SNOM) combined with near-field nano-spectroscopy- Tip-Enhanced Raman spectroscopy
(TERS) is the best technology for visualization of such nanoscale details. However, the spatial resolution and
chemical sensitivity levels are currently insufficient to detect and identify single molecules in an ambient
environment (air or liquid). Current methods for the identification of infectious agents rely on traditional
methods that include growing of bacteria and fungi, isolation of viruses in cell culture, and then identification of
the agent biochemically, antigenically, or genetically (which require the availability of specific antibodies for
ELISA tests and specific DNA primers for PCR). These methods make the identification of newly emerging
pathogens particularly difficult. New approaches to diagnostics are overdue. Actoprobe LLC proposes such an
approach: to develop, validate, and commercialize a novel class of probes for Scanning Probe Microscopy (SPM)
based on silicon nitride photonics with a diode laser, a pulse compressor, and a detector, all inside the SPM
probe. The ultimate goal is to dramatically (>10X) increase SNOM's sensitivity and spatial resolution for
rapid identification of infectious agents. With its strong research experience and expertise in TERS and SNOM,
Actoprobe is in an ideal position to address this technical challenge. This new TERS tool's capabilities will allow
studying the biochemical components, morphology, and nanomechanical structures of viruses, bacteria,
and fungi at the single-molecule level, substantially improving early infectious disease detection and
identification. We expect the proposed technology will enable substantially improved early pathogenic disease
agent detection and lead to a marketable, cost-effective diagnostic/identification tool. Our primary customers
will be medical laboratories and clinical research institutions. Phase I will prove the technical feasibility of
developing the ultrasensitive optical SPM probes and testing these probes on several non-pathogenic viruses.
Terms: <2-photon><A fumigatus><A. fumigatus><Address><Air><Antibodies><Area><Aspergillus fumigatus><Atomic Force Microscopes><Bacteria><Baculoviridae><Baculoviruses><Biochemical><COVID-19 outbreak><COVID19 outbreak><Capsid><Cell Communication and Signaling><Cell Culture Techniques><Cell Signaling><Cessation of life><Chemicals><Classification><Clinical><Clinical Research><Clinical Study><Communicable Diseases><DNA><DNA Primers><DNA seq><DNA sequencing><DNAseq><Death><Dedications><Deoxyribonucleic Acid><Detection><Diagnostic><Disease><Disorder><ELISA><Electric Field Microscopes><Environment><Enzyme-Linked Immunosorbent Assay><Equipment><Generalized Growth><Genus staphylococcus><Goals><Growth><Height><IR/UV/Raman Spectroscopy><Image><Imaging technology><Infection><Infectious Agent><Infectious Disease Pathway><Infectious Diseases><Infectious Disorder><Institution><Intracellular Communication and Signaling><LMIC><Label><Laboratory Research><Laser Electromagnetic><Laser Radiation><Lasers><Lateral><Lateral Force Microscopes><Lipids><Liquid substance><Magnetic Force Microscopes><Marketing><Measurement><Measures><Medical><Membrane Protein Gene><Membrane Proteins><Membrane-Associated Proteins><Methods><Microscopy><Molecular><Morphology><NIH><Nanoscopy><National Institutes of Health><Noise><Non-Polyadenylated RNA><Oligodeoxyribonucleotide Primers><Optics><Organism><Outcome><Pathogenicity><Patients><Phase><Photons><Physiologic pulse><Position><Positioning Attribute><Prevention><Principal Component Analyses><Principal Component Analysis><Property><Proteins><Pulse><RNA><RNA Gene Products><RNA Seq><RNA sequencing><RNAseq><Raman Spectroscopy><Raman Spectrum Analysis><Raman imaging><Raman spectrometry><Rapid diagnostics><Research><Resolution><Ribonucleic Acid><SARS-CoV-2 outbreak><SBIR><Sampling><Scanning><Scanning Probe Microscopes><Scanning Probe Microscopy><Scanning Thermal Microscopes><Scanning Tunneling Microscopes><Science><Semiconductors><Severe acute respiratory syndrome coronavirus 2 outbreak><Si3N4><Signal Transduction><Signal Transduction Systems><Signaling><Small Business Innovation Research><Small Business Innovation Research Grant><Spectroscopy><Spectrum Analyses><Spectrum Analysis><Speed><Staphylococcus><Structure><Surface><Surface Proteins><Systematics><Technology><Testing><Time><Tissue Growth><Tobacco Mosaic Virus><United States National Institutes of Health><Variant><Variation><Viral><Virion><Virus><Virus Particle><Visualization><base><bases><biological signal transduction><cell culture><cell cultures><commercialization><coronavirus disease 2019 outbreak><coronavirus disease-19 outbreak><cost><cost effective><data quality><design><designing><detection method><detection procedure><detection sensitivity><detection technique><detector><diagnostic approach><diagnostic strategy><disease control><disorder control><emerging pathogen><enzyme linked immunoassay><experience><fluid><fungus><high level production><high scale production><high volume manufacturing><high volume production><identification of viruses><imaging><improved><infectious organism><innovate><innovation><innovative><instrument><interest><liquid><living system><low and middle-income countries><mechanical properties><microorganism><molecular diagnostics><nano><nano mechanics><nano meter scale><nano meter sized><nanomechanics><nanometer scale><nanometer sized><nanoscale><near field microscopy><new approaches><new pathogen><novel><novel approaches><novel pathogen><novel strategies><novel strategy><ontogeny><operation><operations><optical><outbreak of SARS-CoV-2><photonics><premature><prematurity><prototype><resolutions><silicon nitride><single molecule><success><tool><transcriptome sequencing><transcriptomic sequencing><two-photon><viral detection><virus detection><virus identification>