Project Grant R42DE030829

A MULTIMODAL PLATFORM FOR ORAL SCREENING OF COVID-19 - THE DEVELOPMENT OF A RAPID AND RELIABLE SENSOR SYSTEM FROM READILY AVAILABLE ORAL SPECIMENS IS CRUCIAL FOR THE SCREENING AND MANAGEMENT OF SARS-COV-2 INFECTION. OTHER THAN TESTS THAT REQUIRE LABORATORY-SCALE INSTRUMENTATION, THE DEVELOPMENT OF RAPID TESTS CAN PLAY A TIMELY ROLE IN THE MANAGEMENT OF AN OUTBREAK. CURRENT RAPID TESTS OFTEN INVOLVE THE ANTIBODIES IN A LATERAL FLOW FORMAT TO DETECT VIRAL PROTEIN COMPONENTS AND, DEPENDING ON THE IMPLEMENTATION, CAN RESULT IN A RELATIVELY HIGH DEGREE OF ERROR. IN PARTNERSHIP WITH MIT, INNOTECH PROPOSES THE DEVELOPMENT OF A MULTIPLEXED SENSOR PLATFORM BASED ON NANOMATERIALS CAPABLE OF MOLECULAR BINDING AND SUBSEQUENT REPORTING. WE WILL DEVELOP AND COMMERCIALIZE A MULTIPLEXED SENSOR PLATFORM USING NANOMATERIAL REPORTERS CAPABLE OF RAPID SIMULTANEOUS DETECTION OF MULTIPLE COMPONENTS OF VIRAL PARTICLES IN A FIELD APPLICABLE ELECTROCHEMICAL DEVICE. FOR OUR PHASE I- AIM 1 WE WILL FOCUS ON THE DEVELOPMENT AND OPTIMIZATION OF SYNTHETIC BIOSENSORS FOR ACCURATE DETECTION OF SARS-COV-2 VIRAL PROTEINS AND NUCLEIC ACID. OUR MILESTONE IS THE DISCOVERY AND VALIDATION AN ARRAY OF MOLECULAR RECOGNITION BIOSENSORS AGAINST BOTH PROTEIN AND NUCLEIC ACID SEGMENTS OF SARS-COV-2. WE WILL COMPLETE THIS PHASE IN 4 MONTHS. IN PHASE II-AIM 1, WE WILL DEVELOP AND VALIDATE THE ELECTROCHEMICAL DETECTORS. WE WILL UTILIZE THE SYNTHETIC BIOSENSORS IDENTIFIED AND VALIDATED IN AIM 1 TO AN ELECTROCHEMICAL PLATFORM FOR THE RAPID DETECTION OF AN ACTIVE SARS-COV-2 INFECTION USING MULTIPLE BIOMARKERS OF THE INFECTION. WE WILL SPECIFICALLY EMPLOY COMMERCIALLY-AVAILABLE, DISPOSABLE ELECTRODE PLATFORMS AND EXISTING POTENTIOSTATS FROM METROHM DROPSENS TO STREAMLINE SCALE-UP AND COMMERCIALIZATION. OUR MILESTONE, TO BE COMPLETED IN YEAR 1 OF PHASE II, IS TO HAVE A MULTIPLEX BIOSENSOR CHIP AND AN ALPHA PROTOTYPE WITH A MULTIPLEX BIOSENSOR CHIP AND A POTENTIOSTAT READER WHICH WE WILL BENCHMARK FOR SENSITIVITY AND QUANTITATIVE ACCURACY AGAINST EXISTING COVID-19 DIAGNOSTICS. IN PHASE II-AIM 2, WE WILL VALIDATE THE PROTOTYPE CHIPS AND DETECTORS WITH RETROSPECTIVE CLINICAL SPECIMENS IN PREPARATION FOR EUA-FDA SUBMISSION. WE WILL DETERMINE THE LOD, CLINICAL PERFORMANCE, AND CROSS-REACTIVITY WITH OTHER RESPIRATORY PATHOGENS AND NORMAL FLORA. THE MILESTONE FOR THIS AIM IS TO DOCUMENT A MULTIPLEX OF AT LEAST TWO PROTEINS AND TWO NUCLEIC ACID BIOSENSORS FOR SARS-COV-2 THAT WILL PROVIDE A LOD OF 5-20 VIRUSES PER MICROLITER IN AN ORAL SPECIMEN AND WILL BE CLINICALLY VALIDATED WITH GREATER THAN 95% CONCORDANCE WITH RT-PCR IN 30 POSITIVE AND 30 NEGATIVE SPECIMENS.