Ultrasensitive detection of intact SARS-CoV-2 particles in complex biofluids using microfluidic affinity capture
Measuring virus in biofluids is complicated by confounding biomolecules coisolated with viral nucleic acids. To address this, we developed an affinity-based microfluidic device for specific capture of intact severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Our approach used an engineered angiotensin-converting enzyme 2 to capture intact virus from plasma and other complex biofluids. Our device leverages a staggered herringbone pattern, nanoparticle surface coating, and processing conditions to achieve detection of as few as 3 viral copies per milliliter. We further validated our microfluidic assay on 103 plasma, 36 saliva, and 29 stool samples collected from unique patients with COVID-19, showing SARS-CoV-2 detection in 72% of plasma samples. Longitudinal monitoring in the plasma revealed our device's capacity for ultrasensitive detection of active viral infections over time. Our technology can be adapted to target other viruses using relevant cell entry molecules for affinity capture. This versatility underscores the potential for widespread application in viral load monitoring and disease management.
Authors
- Dasol Lee
- Genevieve Marie Boland (ORCID: https://orcid.org/0000-0002-7522-6173)
- Marcia B. Goldberg (ORCID: https://orcid.org/0000-0003-4266-9733)
- Alona Muzikansky (ORCID: https://orcid.org/0000-0001-7585-8181)
- Aaron F. Carlin (ORCID: https://orcid.org/0000-0002-1669-8066)
- Alex E. Clark (ORCID: https://orcid.org/0000-0003-1687-416X)
- Uyen Ho
- James A. Wells (ORCID: https://orcid.org/0000-0001-8267-5519)
- Diane E. Capen (ORCID: https://orcid.org/0000-0001-7254-788X)
- Adarsh Choudhury (ORCID: https://orcid.org/0000-0002-3288-9356)
- Jochen K. Lennerz (ORCID: https://orcid.org/0000-0003-2434-4978)
- Shannon L. Stott (ORCID: https://orcid.org/0000-0002-0349-0522)
- Xu G. Yu (ORCID: https://orcid.org/0000-0002-8295-884X)
- Peggy S. Lai (ORCID: https://orcid.org/0000-0001-9501-8606)
- Jeff E. Glasgow (ORCID: https://orcid.org/0000-0001-6699-8983)
- William A. Michaud (ORCID: https://orcid.org/0000-0002-3664-2094)
- Douglas S. Kwon (ORCID: https://orcid.org/0000-0001-8521-8735)
- Daniel C. Rabe (ORCID: https://orcid.org/0000-0001-6126-2280)
- Aaron F. Garretson (ORCID: https://orcid.org/0000-0003-3855-4482)
- Evelyn G. Luciani (ORCID: https://orcid.org/0009-0000-8194-6399)
- Anh Hoang (ORCID: https://orcid.org/0000-0002-3196-7455)
- Sara Veiga
- Elizabeth A. Flynn (ORCID: https://orcid.org/0009-0001-1061-1214)
- Yves Theriault
- N. R. Hartmann
- S. Rabi
Institutions
- Broad Institute (US)
- Harvard University (US)
- University of California, San Francisco (US)
- Ragon Institute of MGH, MIT and Harvard (US)
- University of California San Diego (US)
- Qualcomm (United States) (US)
- Massachusetts General Hospital (US)
- Center for Cancer Research (US)
- Center for Systems Biology (US)
- Massachusetts Institute of Technology (US)
Publication Details
- Journal
- Science Advances
- Published
- 2025-01-10
- DOI
- https://doi.org/10.1126/sciadv.adh1167
- Citations
- 10
- Primary Topic
- SARS-CoV-2 detection and testing
- Type
- article
- Field-Weighted Citation Impact
- 13.96