# A Rapid and Sensitive Technology for Direct Sensing of Intact SARS-CoV-2 Virions Using Designer DNA Nanostructure Probes and a Smartphone Fluorimeter

> **NIH NIH R21** · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · 2021 · $422,226

## Abstract

Abstract
The rapid development of the COVID-19 pandemic reveals the shortcomings of current technologies for
diagnosis. The limited availability, insufficient sensitivity and/or specificity of gene-based and antigen/antibody-
based tests resulted in relatively high rates of false negative/positive test results, which further led to failure of
patient quarantine and confusion among health authorities and the public. The fundamental limitations of current
gene-based assays stem from their reliance upon amplification and detection of specific nucleic acid sequences
within the viral genome. The current test requires labor-intensive, laboratory-based sample preparation protocols
for virus lysis, extraction of genetic materials, purification of the isolated materials, thermal cycling for enzymatic
amplification of viral nucleic acid sequences, and interpretation of complex results by professionals. We seek a
new paradigm for rapid and direct pathogen detection, identification, and quantification in which the intact virions
are directly recognized through their distinct surface epitope features, and the resultant fluorescent signal is
immediately captured by a portable, smartphone-based fluorimeter. To achieve specific recognition of SARS-
CoV-2 virions, we customized a designer DNA nanostructure (DDN)-based capture probe that harbors a
macromolecular “net” whose vertices precisely match the intra- and inter-spatial pattern of SARS-CoV-2 trimeric
spike glycoprotein clusters, and integrates a net-shaped array of SARS-CoV-2 spike specific-targeting aptamers
that are designed for maximum affinity and specificity when binding with spikes in a polyvalent and pattern-
matching fashion. When exposed to a test sample, such as saliva or nasopharyngeal swab material in solution,
the DNA rhombus-shaped “virus nets” rapidly and selectively bind intact virions to trigger the release of
fluorescence. We have successfully developed a smartphone-based instrument that can detect and quantify
fluorescent signals in point-of-care (POC) settings. Thus, the fluorescent signal released from the virus net upon
binding to SARS-CoV-2 can be readily detected by our smartphone-based fluorimeter in POC settings. We
propose to combine DDN capture probes and a smartphone fluorimeter for the first time, to develop and
demonstrate a rapid, room temperature, single-step, virus-specific, and ultrasensitive diagnostic assay for
COVID-19 that can be performed immediately after sample collection at the point of care, and provide a result
in < 5 minutes. Our aims include development of a COVID-19 assay in POC settings, and statistically robust
characterization of its sensitivity, specificity, reproducibility and cost-effectiveness. Our study will conclude with
a preliminary validation of the system using clinical specimens and direct comparison against a gold-standard
laboratory PCR test.

## Key facts

- **NIH application ID:** 10196257
- **Project number:** 1R21EB031310-01
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
- **Principal Investigator:** Brian T. Cunningham
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $422,226
- **Award type:** 1
- **Project period:** 2021-09-08 → 2024-09-07

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10196257

## Citation

> US National Institutes of Health, RePORTER application 10196257, A Rapid and Sensitive Technology for Direct Sensing of Intact SARS-CoV-2 Virions Using Designer DNA Nanostructure Probes and a Smartphone Fluorimeter (1R21EB031310-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10196257. Licensed CC0.

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