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

Summary

An engineered-ACE2 microfluidic device captures intact SARS-CoV-2 from plasma, saliva, and stool with an LOD of ~3 copies/mL and detected virus in 72% of plasma samples across 103 patients. The platform supports longitudinal tracking and is adaptable to other viruses via alternative entry molecules.

Key Findings

• Engineered ACE2 affinity microdevice detects intact SARS-CoV-2 at ~3 copies/mL in complex biofluids.
• Clinical validation across 103 plasma, 36 saliva, and 29 stool samples; 72% positivity in plasma.
• Supports longitudinal plasma monitoring for active infection.
• Platform is adaptable to other viruses by swapping entry molecule ligands.

Clinical Implications

Could augment clinical decision-making by detecting low-level viremia and monitoring antiviral response, and may stratify patients by persistent plasma virions; future adaptation to other pathogens may broaden viral load management.

Limitations

• Single-pathogen focus; generalizability to other viruses requires re-engineering and validation
• Positivity less than 100% in plasma; clinical thresholds for decision-making need definition

Future Directions

Define clinical cutoffs for infectious risk, correlate with culture-based infectivity and outcomes, and extend to multiplex capture for co-infections.