AINCOBIO, LLC

2023-08-23

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Department of Health and Human Services

PA21259, SBIR, PHASE I, DEVELOPMENT OF A RAPID, DIRECT FROM BLOOD, PHENOTYPIC ANTIMICROBIAL SUSCEPTIBILITY ASSAY

306500.00

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2022-08-01

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Department of Health and Human Services

A SCALABLE ELECTROKINETIC FLOW CYTOMETER AND CELL SORTER - PROJECT SUMMARY CURRENT CELL SEPARATION TECHNOLOGIES ARE LIMITED TO SORTING AND ANALYZING HETEROGENOUS CELL POPULATIONS BASED ON DIFFERENCES IN CELL SIZE OR CELL DENSITY OR BY LEVERAGING THE EXPRESSION OF SPECIFIC IMMUNOLOGICAL TARGETS OR RECEPTOR-LIGAND INTERACTIONS. OTHER CYTOPHYSICAL CHARACTERISTICS SUCH AS DEFORMABILITY, ELECTRICAL CHARGE, AND ELECTRICAL POLARIZABILITY ARE CORRELATED WITH IMPORTANT BIOLOGICAL DIFFERENCES BETWEEN SUBPOPULATIONS OF CELLS AND WOULD SERVE AS VALUABLE BIOMARKERS FOR THESE POPULATIONS; HOWEVER, CURRENTLY AVAILABLE INSTRUMENTS LACK THE CAPABILITY TO SEPARATE CELLS BASED ON THESE CYTOPHYSICAL/CYTOELECTRICAL PARAMETERS. AINCOBIO IS DEVELOPING “ELECTROFLOW”, THE FIRST ELECTROKINETIC FLOW CYTOMETER, TO ADDRESS THIS GAP. ELECTROFLOW COMBINES DIELECTROPHORESIS (DEP), AN ELECTRICAL-FIELD-INDUCED FORCE THAT IS WELL-ESTABLISHED AS A METHOD TO SEPARATE AND CHARACTERIZE PARTICLES, WITH FIELD-FLOW-FRACTIONATION (FFF) TO SEPARATE CELLS BASED ON DIFFERENCES IN MEMBRANE POLARIZATION AND OTHER CYTOELECTRIC PHENOTYPES. ELECTROFLOW WILL ALLOW FOR DIFFERENT FORCE COMBINATIONS TO BE PROGRAMMED FOR DIFFERENT CELL TYPES OR DIFFERENT ASPECTS OF CELLS, ACHIEVING SPECIALIZED DIFFERENTIATION OF CELLULAR FEATURES (SIZE, SHAPE, DENSITY, MEMBRANE COMPOSITION AND MORPHOLOGY, SURFACE MARKERS, SURFACE CHARGE, AND CYTOSOL COMPOSITION). THE AINCOBIO TEAM HAS BUILT A PROTOTYPE ELECTROFLOW INSTRUMENT AND DEMONSTRATED PROOF-OF- CONCEPT WITH BOTH EUKARYOTIC AND PROKARYOTIC CELLS AT ~5,000 CELLS/MIN. TO ENABLE SCALING TO ACCOMMODATE LARGE NUMBERS OF CELLS, AINCOBIO HAS APPLIED MULTI-PHYSICS SIMULATIONS TO REDESIGN THE DEVICE CONSTRUCTION AND DEP ELECTRONICS TO ALLOW FOR A 10X SCALE-UP IN NUMBER OF CELLS PER RUN. IN THIS PHASE I SBIR, AINCOBIO WILL LEVERAGE THIS SIMULATION DATA TO 1) BUILD AND BENCH-TEST PROTOTYPE MICROELECTRODE ARRAY CIRCUIT BOARDS AND SIGNAL AMPLIFIER ELECTRONICS, AND 2) IMPROVE THERMAL MANAGEMENT AND VALIDATE PROTOTYPE BY MEASURING SEPARATION EFFICIENCY OF MIXTURES OF ACTIVATED AND RESTING T-CELLS AS A FUNCTION OF VOLTAGE AND IONIC STRENGTH. SUCCESSFUL COMPLETION OF THE PHASE I AIMS WILL ESTABLISH PROOF-OF-CONCEPT FOR A COMMERCIALLY VIABLE INSTRUMENT THAT CAN ANALYZE 106 CELLS IN A 20-MINUTE RUN AND SORT BY CYTOELECTRIC/CYTOPHYSICAL FEATURES. COMMERCIALIZATION OF ELECTROFLOW WILL PROVIDE AN ACCESSIBLE MEANS FOR ALL RESEARCHERS TO STUDY AND HARNESS DIFFERENCES IN CYTOELECTRIC PROPERTIES, OPENING ENTIRELY NEW AVENUES OF BIOLOGICAL RESEARCH AND BIOMEDICAL APPLICATION.

357081.00

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2022-07-29

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Department of Health and Human Services

RAPID AND AUTOMATED DETECTION OF BLOODBORNE PATHOGENS FOR IMPROVED TREATMENT AND ANTIMICROBIAL STEWARDSHIP - PROJECT SUMMARY SEPSIS IS A LIFE-THREATENING CONDITION CAUSED BY BACTERIAL INFECTION OF THE BLOODSTREAM THAT THREATENS NEARLY TWO MILLION LIVES IN THE U.S. ANNUALLY. RISK OF DEATH ESCALATES QUICKLY ONCE BACTERIA OR FUNGI ENTER THE BLOODSTREAM; THUS, QUICK AND ACCURATE DETECTION OF BLOODBORNE PATHOGENS IS CRITICAL TO INFORM IMMEDIATE TAILORED TREATMENT. HOWEVER, THE CURRENT STANDARD PRACTICE TO DETECT BLOODBORNE BACTERIA AND FUNGI REQUIRES IN VITRO CULTURE TO MEASURE MICROBIAL GROWTH, A PROCESS WHICH TAKES 12-120 HOURS, WITH TIMES TO A CONFIRMED NEGATIVE SOMETIMES TAKING AS LONG AS 5 DAYS. POSITIVE CULTURES THEN UNDERGO ADDITIONAL TESTS TO DETERMINE BACTERIAL IDENTITY AND ANTIMICROBIAL SUSCEPTIBILITY. THIS PROTRACTED PROCESS, WHICH INCLUDES SIGNIFICANT PRE-ANALYTICAL DELAYS CAUSED BY SAMPLE TRANSPORT TO OFF-SITE MICROBIOLOGY LABS AND LONG CULTURE TIMES, REPRESENTS A CRITICAL BOTTLENECK IN THE DIAGNOSTIC LABORATORY WORKFLOW, CREATING SIGNIFICANT ECONOMIC AND LABOR BURDEN TO THE HEALTHCARE SYSTEM AND PROLONGING THE TIME THAT PATIENTS MAY BE RECEIVING INAPPROPRIATE TREATMENT (BROAD SPECTRUM ANTIMICROBIAL DRUGS INSTEAD OF TARGETED THERAPY). AINCOBIO IS DEVELOPING A RAPID, NEAR PATIENT IN VITRO DIAGNOSTIC TEST, THE BACTOPHORE, THAT CAN BE DEPLOYED OUTSIDE OF THE CENTRALIZED LAB TO ISOLATE AND DETECT INTACT AND VIABLE LOW-CONCENTRATION BACTERIA AND FUNGI IN BLOOD SPECIMENS IN 2 HOURS. BACTOPHORE ACHIEVES ENHANCED ANALYTICAL SENSITIVITY BY RAPIDLY CONCENTRATING PATHOGENS FOR DETECTION TO DELIVER A POSITIVE RESULT QUICKLY. TO DO THIS, BACTOPHORE INCORPORATES A “LAB-ON-A-CHIP” SYSTEM THAT CAN ISOLATE MICROBES FROM 0.5 ML WHOLE BLOOD USING DIELECTROPHORESIS (DEP) AND DETECT METABOLIC SIGNATURES USING ELECTROCHEMICAL IMPEDANCE SPECTROSCOPY (EIS) WITHIN A LOW-COST CONSUMABLE. A DIAGNOSTIC PROTOTYPE OF THE BACTOPHORE ISOLATES >90% OF TARGET BACTERIA IN 30 MINUTES AND CAN DETECT 100 CFUS OF E. COLI WITHIN 2 HOURS. FURTHER, TARGET MICROBES PRE-CONCENTRATED FROM 10 ML OF WHOLE BLOOD CAN BE TRAPPED BY DEP IN <30 MINUTES, DEMONSTRATING THE POTENTIAL FOR PROCESSING CLINICALLY RELEVANT VOLUMES. IN THIS PHASE I SBIR, AINCOBIO WILL DEMONSTRATE FEASIBILITY OF COMMERCIALIZING THE BACTOPHORE TEST FOR LABEL-FREE, ANTIBODY-INDEPENDENT, AND CULTURE-INDEPENDENT DETECTION, CONCENTRATION, AND ISOLATION OF LOW ABUNDANCE AND VIABLE BACTERIAL AND FUNGAL PATHOGENS BY 1) EVALUATING THE INTEGRATED BACTOPHORE PROTOTYPE WITH COMMON PATHOGENS SPIKED INTO WHOLE BLOOD, AND 2) DEMONSTRATING THAT BACTOPHORE ENABLES RAPID AND SENSITIVE DOWNSTREAM SEQUENCING OF THE TARGET MICROBE BY DEPLETING HOST DNA PRIOR TO EXTRACTION AND LIBRARY PREPARATION. COMPLETION OF THESE AIMS WILL ESTABLISH PROOF-OF-CONCEPT THAT BACTOPHORE HAS ANALYTICAL SENSITIVITY TO CONFIRM INFECTION FROM WHOLE BLOOD WITHIN 2 HOURS AND SIGNIFICANTLY IMPROVE TIME-TO-RESULTS FOR THE ENTIRE DIAGNOSTIC WORKFLOW FROM POSITIVE RESULT TO PATHOGEN IDENTIFICATION.

302714.00

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