dbGaP Study Accession: phs002550

NIH Institute/Center: NIDCR

RADx Data Program: RADx-rad

DOI: 10.60773/0pp8-qx15

Release Date: 07/25/2022

Updated Date: 12/09/2022

Study Description: 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 typically 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. Direct testing for the virus, which also reduces requirements for multiple reagents, is a necessary step to improving 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. This gap was addressed by DiagnostikosTM, an in-development rapid POC platform for direct, real-time, multiplexed, quantitative bioelectronic detection of biomolecules that employed 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 were interfaced with an envisioned USS-stick-form-factor reader device. Robust single-domain antibodies, known as nanobodies and immobilized on these devices, were 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 allowed for significant improvements in specificity. Nanobodies were specific for one or more of the four major structural 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 were required for detection, and the device were designed to operate with saliva, which has very recently been shown to be a reliable medium for detecting SARS-CoV-2. Individual sensor chips could manufactured at a cost of $35. With the addition of other nanobodies, these large dense arrays also allow detection of many pathogens in a single test. In this Direct-To-Phase-2 SBIR program, several key innovations that are required to make such a platform possible were pursued, 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 was a partnership between university researchers who developed the smFET technology and a venture-based start-up, Quicksilver Biosciences, spun out to commercialize smFET technology and develop smFET/CMOS arrays for molecular diagnostic applications.

Principal Investigator: Young, Erik F

Has Data Files: Yes

Study Domain: Point-of-Care (POC) Testing; Virological Testing; Rapid Diagnostic Test (RDT); Medical Device/Tool Development

Data Collection Method: Antigen Testing Device

Keywords: Assay; Near Patient Testing; Electronic Detection Device; Nanotube; Single Molecule

Study Design: Device Verification Study

Multi-Center Study: TRUE

Study Sites: Columbia University

Data Types: Immunological; Other

Data Types, Other: Current traces versus time (voltage)

Study Start Date: 12/21/2020

Study End Date: 11/30/2022

Species: Non-Human Data

Estimated Cohort Size: 10

Study Population Focus: N/A

Acknowledgement Statement: This study was supported through funding, 4R44DE030841-02, for the National Institute of Dental and Craniofacial Research (NIDCR) as part of the RADx-rad program. This study was in collaboration with Columbia University. A special acknowledgment to our collaborators and to the study participants that made this project possible. Approved users should acknowledge the provision of data access by dbGaP for accession phs002550.v1.p1, and the NIH RADx Data Hub. Approved users should also acknowledge the specific version(s) of the dataset(s) obtained from the NIH RADx Data Hub.

Funding Opportunity Announcement (FOA) Number: RFA-OD-20-020

NIH Grant or Contract Number(s): 4R44DE030841-02

Consent/Data Use Limitations: General Research Use