A point-of-care device using Single Molecule Array (Simoa) to measure viral antigens in nasal swabs, saliva, and blood - PROJECT SUMMARY/ABSTRACT
The goal of this project is to develop a simple-to-use, low-cost, and small instrument and associated
consumable for point-of-care (POC) diagnoses based on the ultrasensitive detection of proteins. The
proposed system will combine detection of proteins using the Single Molecule Array (Simoa; Quanterix
Corporation) technology and assay processing using digital microfluidics (DMF) to enable POC immunoassays
with the sensitivity and specificity of nucleic acid amplification tests without the need for nucleic acid
purification or amplification, and with the simplicity, sample type flexibility, and diagnostic performance to
deliver central lab diagnostic quality in POC settings. The proposed system would be composed of a sample-
to-answer, random access, benchtop instrument utilizing a universal consumable design accepting a broad
range of minimally processed samples relevant to POC diagnosis of disease, including swab, saliva, and blood
(including fingerstick) samples. We will first apply this technology to the diagnosis of COVID-19 and influenza,
optimizing existing assays for SARS-CoV-2 N-protein and developing new multiplexed assays for influenza A
and B antigens, along with simple sample preparation methods, for testing of nasal/nasopharyngeal (NP) swab
(SARS-CoV-2/influenza) and saliva/blood (SARS-CoV-2 only) samples. This project—a collaboration between
Quanterix (Dr. Duffy, co-PI), Boston Children's Hospital (Dr. Pollock, co-PI), and University of Toronto (Dr.
Wheeler, co-investigator)—has four specific aims to achieve these goals. First, we will develop the key
technologies to enable the POC system, namely: a low-cost Simoa imager with a small form factor; single
molecule labels that do not require sealing in microwell arrays; and, the DMF building blocks for assay
processing, resulting in an integrated Simoa-DMF device. Second, we will design, develop, and test Simoa
POC instruments and consumables, first in prototype and then for test validation. Third, we will
optimize/develop and validate analytically Simoa assays (including sample preparation options) for SARS-
CoV-2 (nasal swab, saliva, blood) and multiplex influenza A/B (NP swab) antigens, and test them on the
prototype Simoa POC system. Finally, we will clinically validate the POC antigen tests against gold-standard
molecular tests for all sample types using discarded/banked clinical samples, and evaluate performance of the
POC system in POC settings using contrived clinical samples. User feedback will inform development
throughout the proposal. The long-term objective of this research is to develop a broadly enabling technology
that would allow the diagnosis of diseases using ultrasensitive protein detection at the POC in a small, low-cost
benchtop system. This type of capability is available for molecular testing but not for protein detection, and
would combine high sensitivity with low cost and an alternative supply chain to support diagnosis of infectious
diseases in diverse clinical settings. This system would be a critical new diagnostic tool ready both for routine
POC diagnosis of infectious diseases and to benefit the world in the event of the next pandemic.
