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Direct bioelectronic detection of SARS-CoV-2 from saliva using single-molecule field-effect transistor array

使用单分子场效应晶体管阵列直接生物电子检测唾液中的 SARS-CoV-2

基本信息

批准号：
10320987
负责人：
Kenneth L Shepard
金额：
$ 44.78万
依托单位：
QUICKSILVER BIOSCIENCES, INC.
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-12-21 至 2024-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10320987
关键词：
2019-nCoV Address Binding Proteins Biological Assay Biological Sciences COVID test COVID-19 detection COVID-19 diagnostic COVID-19 pandemic COVID-19 testing Carbon Nanotubes Clinical Communicable Diseases Complex Defect Detection Development Devices Diagnosis Diagnostic tests Differential Diagnosis Electrolytes Gold Hour ImProv Immobilization Immunoassay Individual Infection Infectious Agent Influenza Kinetics Laboratories Llama Membrane Proteins Nanotubes New York Nucleic Acid Amplification Tests Nucleocapsid Proteins Optics Phase Polymerase Chain Reaction Population Surveillance Preparation Process Proteins Public Health Quantitative Reverse Transcriptase PCR Reader Reagent Recombinants Research Personnel Reverse Transcription SARS-CoV-2 transmission Saliva Sampling Semiconductors Sensitivity and Specificity Site Small Business Innovation Research Grant Specificity Specimen Structural Protein Symptoms Technology Testing Time Training Transistors Universities Vaccines Viral Viral Load result Viral Proteins Virus antibody detection antigen detection antigen test base biobank bioelectronics cost design diagnostic assay env Gene Products experimental study improved innovation integrated circuit metal oxide molecular array molecular diagnostics multiplex detection nanobodies particle pathogen point of care point of care testing programs protein structure saliva sample sensor single molecule temporal measurement tool transmission process viral RNA viral detection

项目摘要

Direct bioelectronic detection of SARS-CoV-2 from saliva using single-molecule field-effect transistor array Nucleic acid tests have become the gold-standard for diagnostic testing for COVID-19, usually performed in specialized laboratories. Most are based on reverse-transcription quantitative polymerase chain reaction (qRT-PCR). The time required for specimen transport and processing results in a turnaround time that is typi- cally several days. The few rapid (<1 hour) point-of-care (POC) tests are more expensive, still require sample preparation and specialized reagents, and do not have the throughput needed for population surveillance. Di- rect testing for the virus, which also reduces requirements for multiple reagents, is a necessary step to improv- ing diagnostic testing. While four such antigen tests have been approved for detection of SARS-CoV-2 based on immunoassays to the N protein, sensitivity is limited and no quantitation of viral load is possible. We will address this gap by using DiagnostikosTM, an in-development rapid POC platform for direct, real- time, multiplexed, quantitative bioelectronic detection of biomolecules that employs an all-electronic detection device that functions at the single-molecule level. These single-molecule field-effect transistors (smFETs) are arrayed on a complementary metal-oxide-semiconductor (CMOS) integrated circuit chip. Chips will interface with an envisioned USB-stick-form-factor reader device. Robust single-domain antibodies, known as nanobod- ies and immobilized on these devices, are used for sensitive detection of viral particles and viral debris. The use of multiple nanobodies for a single protein and nanobodies for different proteins in a single assay allows for significant improvements in specificity. Nanobodies will be specific for one or more of the four major struc- tural proteins in SARS-CoV-2; the nucleocapsid (N) protein engulfing the viral RNA, the spike (S) protein, the membrane (M) protein and the envelope (E) protein. No sample preparation or specialized reagents are re- quired for detection, and the device will be designed to operate with saliva, which has very recently been shown to be a reliable medium for detecting SARS-CoV-2. Individual sensor chips can be manufactured at a cost of $35. With the addition of other nanobodies, these large dense arrays can also allow detection of many pathogens in a single test. In this Direct-To-Phase-2 SBIR program we will pursue several key innovations that are required to make such a platform possible, including isolation of nanobodies for key structure proteins of SARS-CoV-2 (Specific Aim 1), development of the smFET platform for antigen detection (Specific Aim 2), development of large CMOS arrays of these smFET devices (Specific Aim 3), and verification of detection in increasingly complex samples up to and including clinical samples (Specific Aim 4). This project is a partnership between university researchers who developed the smFET technology and a venture-based start-up venture, Quicksilver Biosci- ences, spun out to commercialize smFET technology and develop smFET/CMOS arrays for molecular diag- nostic applications.

唾液中SARS-CoV-2的直接生物电子检测