New Microfluidic Device can Detect SARS-Cov-2 with Revolutionary Sensitivity

By Dr. Chinta SidharthanReviewed by Lily Ramsey, LLMJan 30 2025

A drop of blood or saliva can now tell you more about an active viral infection than ever before. In a recent study published in Science Advances, a research team encompassing scientists from Harvard Medical School, the Massachusetts General Hospital, and the University of California developed a groundbreaking microfluidic device capable of detecting intact severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) particles with unmatched sensitivity, even in complex biofluids such as plasma, saliva, and stool.

This innovation could identify as few as three viral copies per milliliter, offering new possibilities for diagnosing, monitoring, and managing viral infections.

By isolating intact viruses instead of mere fragments of ribonucleic acid (RNA), the study also paved the way for more accurate assessments of disease states and transmission risks, underscoring its potential as a global diagnostic tool.

​​​​​​​Study: Ultrasensitive detection of intact SARS-CoV-2 particles in complex biofluids using microfluidic affinity capture. Image Credit: H_Ko/Shutterstock.com

Viral Detection

Detecting viruses in bodily fluids is essential for understanding infections and improving patient care. Current techniques often measure viral RNA, but these cannot differentiate between intact viruses and residual RNA fragments, making it unclear whether patients are still infectious.

This distinction is especially important for managing diseases such as coronavirus disease 2019 (COVID-19), where prolonged shedding of viral RNA in nasopharyngeal swabs complicates diagnoses.

Plasma and other biofluids are rich in immune and infection markers but pose technical challenges for detecting whole viruses due to interfering biomolecules. Saliva and stool, which are easier to collect, are emerging as valuable alternatives.

Recent advances in microfluidics — a field leveraging miniaturized fluid channels for precise particle manipulation — are offering innovative ways to isolate viruses.

The Current Study

In the present study, the researchers developed and tested a novel microfluidic device, the ^virusHB-Chip, designed to isolate intact SARS-CoV-2 particles from biofluids such as plasma, saliva, and stool.

This device features a staggered herringbone pattern that promotes the passive mixing of fluids, enhancing interactions between viral particles and the chip's surface. The surface is functionalized with an engineered angiotensin-converting enzyme 2 (ACE2) receptor optimized for high-affinity binding to the viral spike protein.

To validate the device, the researchers spiked biofluids with inactivated SARS-CoV-2 and tested different configurations to optimize viral capture. They also compared capture efficiencies using ACE2 and other moieties, including engineered ACE2 receptors.

Viral RNA was then extracted from captured particles using droplet digital polymerase chain reaction (ddPCR) for quantification. The device was further assessed for its ability to detect SARS-CoV-2 variants and distinguish it from other respiratory viruses.

The team also addressed practical considerations, such as optimizing RNA extraction methods to improve sensitivity and ensuring compatibility with whole blood for point-of-care use.

Automation was incorporated into the processing steps to make the device suitable for clinical laboratories handling large volumes. A series of blinded tests were also conducted to determine the detection limit.

Finally, clinical samples were collected from patients at different stages of COVID-19 to demonstrate the chip’s capability to detect intact viral particles across a range of conditions, biofluids, and clinical severities.

Results and Implications

The results revealed that the novel ^virusHB-Chip could detect intact SARS-CoV-2 particles with extraordinary sensitivity, identifying as few as three viral copies per milliliter.

Among patient samples, the device demonstrated a 72% positivity rate in plasma collected within three days of diagnosis. Viral detection rates declined over time, correlating with lower viral loads during later stages of infection.

In saliva, the chip achieved higher sensitivity, detecting 3,530 copies per milliliter on average, while stool samples showed persistent viral presence for up to 14 days.

Furthermore, the chip effectively captured all tested SARS-CoV-2 variants, including Delta and Omicron, despite differences in their spike protein structures. Cross-reactivity tests confirmed the device's specificity, as it successfully distinguished SARS-CoV-2 from other respiratory viruses.

Importantly, the study revealed that plasma viral levels did not significantly correlate with common COVID-19 risk factors such as age, sex, or comorbidities, suggesting that viral load in biofluids could serve as an independent predictor of disease severity and therapeutic needs.

Serial testing also demonstrated the chip’s potential for monitoring viral kinetics, with some patients showing sustained viral loads despite treatment.

Conclusions

Overall, the ^virusHB-Chip represents a significant advancement in viral diagnostics, providing ultrasensitive detection of intact SARS-CoV-2 particles in various biofluids.

Its ability to differentiate between active infections and residual RNA offers new insights into disease progression and management.

The study demonstrated the potential of this versatile platform to transform diagnostic capabilities for numerous viral infections, paving the way for better-informed treatment strategies, enhanced monitoring of viral kinetics, and improved outcomes in infectious disease care worldwide.