Over the past two centuries, viral pandemics such as COVID-19 have remained a recurring threat to public health. PCR remains the gold standard in detecting low viral concentrations that indicate early infection, allowing for timely control measures. However, PCR is time-consuming and requires specialized personnel and equipment, reducing access in resource-limited settings. Conversely, lateral flow assays can provide results in minutes in a simple, portable format. However, they demonstrate limited ability in detecting low viral loads due to endpoint measurements that fail to capture transient, low-affinity molecular interactions. To address this, we describe fuel-free rolosense, a new class of viral diagnostics that combines mechanical force as a transduction mechanism with biased Brownian motion to provide rapid, sensitive, and specific detection of intact virions. Aptamer-coated microparticles act as both the sensor and transducer. In the absence of viruses, driven by thermal fluctuations and gravity, the microparticles diffuse freely across an aptamer-coated chip, continuously probing the environment for its viral target. In the presence of a target virus, multivalent binding occurs between the virion and aptamers on both the particle and chip, restricting diffusion and indicating detection through stalled particle motion. By observing changes in particle motion from mobile to immobile or transiently immobile states, this strategy allows for dynamic measurements of molecular interactions and a limit of detection as low as 10 3 copies/mL for SARS-CoV-2 variants such as BA.1 and BA.5. We also achieved this limit of detection with roloscope, a 3D printed brightfield microscope, indicating potential for point-of-care applications. Finally, we indicate specificity through the significant difference in detection between specific and non-specific targets such as Influenza A and HCoV OC43. Overall, fuel-free rolosense provides a new motion-based strategy of viral diagnostics that allows for sensitive and specific detection through mechanical transduction.
Piranej et al. (Sun,) studied this question.