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Sci Adv . Ultrasensitive detection of intact SARS-CoV-2 particles in complex biofluids using microfluidic affinity capture

tetano

Editor, Senior Moderator
Sci Adv


. 2025 Jan 10;11(2):eadh1167.
doi: 10.1126/sciadv.adh1167. Epub 2025 Jan 10. Ultrasensitive detection of intact SARS-CoV-2 particles in complex biofluids using microfluidic affinity capture

Daniel C Rabe[SUP] 1 2 3 4 [/SUP], Adarsh Choudhury[SUP] 1 2 [/SUP], Dasol Lee[SUP] 1 2 [/SUP], Evelyn G Luciani[SUP] 1 2 [/SUP], Uyen K Ho[SUP] 1 2 [/SUP], Alex E Clark[SUP] 5 [/SUP], Jeffrey E Glasgow[SUP] 6 [/SUP], Sara Veiga[SUP] 1 2 3 4 [/SUP], William A Michaud[SUP] 7 [/SUP], Diane Capen[SUP] 8 [/SUP], Elizabeth A Flynn[SUP] 1 2 [/SUP], Nicola Hartmann[SUP] 1 2 [/SUP], Aaron F Garretson[SUP] 5 [/SUP], Alona Muzikansky[SUP] 9 [/SUP], Marcia B Goldberg[SUP] 4 10 11 12 [/SUP], Douglas S Kwon[SUP] 13 [/SUP], Xu Yu[SUP] 3 13 [/SUP], Aaron F Carlin[SUP] 5 [/SUP], Yves Theriault[SUP] 14 [/SUP], James A Wells[SUP] 6 [/SUP], Jochen K Lennerz[SUP] 15 [/SUP], Peggy S Lai[SUP] 3 [/SUP], Sayed Ali Rabi[SUP] 7 [/SUP], Anh N Hoang, Genevieve M Boland[SUP] 1 4 7 [/SUP], Shannon L Stott[SUP] 1 2 3 4 [/SUP]



Affiliations
Abstract

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.


 
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