Researchers from the Shenzhen Institutes of Advanced Technology (SIAT), Chinese Academy of Sciences, along with multiple collaborators, have developed a compact diagnostic platform that can evaluate antibody protection against COVID-19 using only a single microliter of fingertip blood. Known as the Tip Optofluidic Immunoassay (TOI), the system delivers a comprehensive immune profile—measuring both antibody binding and viral inhibition—in just 40 minutes.
As new SARS-CoV-2 variants continue to emerge and individual vaccination or infection histories grow more complex, there is an urgent need for accessible tools that can assess immune protection quickly and accurately. The TOI platform addresses this challenge by combining microfluidic biosensing and chemiluminescence detection in a portable format suitable for both clinical and field use.
At the core of the platform are high-affinity polystyrene microfluidic immuno-reactors that interface directly with standard pipette tips. These reactors are paired with a portable chemiluminescent imaging station, creating a simple yet powerful workflow. This design supports the rapid and quantitative evaluation of IgG binding levels, binding kinetics, and virus inhibition capacity—all using only a small drop of fingertip blood, without the need for complex laboratory equipment or large sample volumes.
Compared with traditional assays such as ELISA or virus neutralization tests (VNTs), TOI significantly reduces testing time and operational demands. It achieves a detection sensitivity of approximately 0.1 ng/mL, spans a dynamic range of 3 to 4.5 orders of magnitude, and delivers a signal-to-noise ratio exceeding 10,000. These features enable accurate, high-resolution immune analysis at the point of care.
A key innovation in the methodology is the development of RIVIA 2.0, a rapid in vitro inhibition assay that emulates viral neutralization. Central to this advance is the rational protein engineering of SARS-CoV-2 spike ectodomain (S-ECD) trimers, synthetically optimized with orientation-specific Avi-biotin tags to ensure consistent and functional surface presentation. These engineered protein probes, paired with human ACE2-Fc receptors, form a highly controlled binding interface that enables precise measurement of neutralizing antibody activity within just 20 minutes. By applying synthetic biology principles to optimize these probes, RIVIA 2.0 significantly improves the speed, reproducibility, and scalability of functional immune testing over conventional neutralization assays.
The system was validated with 135 samples from 113 individuals, including a subset followed over six months. The results confirmed TOI's ability to detect broad-spectrum and high-titer antibody responses, particularly among individuals with hybrid vaccine regimens. Importantly, the researchers proposed a preliminary IgG concentration threshold (~20 ng/mL) associated with reduced short-term infection risk, highlighting TOI's potential for predictive immune monitoring.
Beyond COVID-19, the platform could be adapted for other infectious diseases such as influenza, hepatitis, or future viral threats. Its low sample requirements and portable design make it particularly valuable for decentralized testing in clinics, communities, and resource-limited settings. It also holds promise for therapeutic antibody development and vaccine efficacy studies.
This study demonstrates how TOI bridges the gap between advanced laboratory diagnostics and real-world application. By combining speed, sensitivity, and multi-dimensional immune assessment in a highly compact format, TOI sets a new benchmark for personalized and scalable infectious disease management.
The research was led by SIAT in collaboration with Peking University, Changping Laboratory, Shenzhen University, the National Innovation Center for Advanced Medical Devices, Sino Biological Inc., University of Michigan, and the Institute of Zoology, Chinese Academy of Sciences.
About Author: (Briefly outline the corresponding author's academic achievements and research contributions) (One author only)
Dr. Xiaotian Tan is an Associate Professor at the Institute of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology (SIAT), Chinese Academy of Sciences. He also serves as Assistant Director of the Bionic Sensing Research Center at SIAT. Dr. Tan received his Ph.D. in Biomedical Engineering from the University of Michigan in 2020 and completed postdoctoral training there from 2020 to 2021. His research focuses on the development of high-performance optofluidic biomolecular sensors, with innovations spanning molecular recognition, microreactor engineering, and optical signal transduction. Dr. Tan has authored more than 30 peer-reviewed publications in journals such as Nature Biomedical Engineering, ACS Sensors, Analytical Chemistry, Lab on a Chip, Biosensors and Bioelectronics and hLife, including 10 as first or co-first author. His work has been cited more than 1000 times.
