Poster W3 - On-demand Biomolecular Quantification for Bedside Biochemical Monitoring Applications

Introduction: Biosensors that monitor circulating biomarkers have the potential to provide invaluable real-time insights into the health status of patients. This is especially important for patients receiving intensive care, as their condition can change dramatically in a matter of hours or even minutes. Identifying unstable patients early and providing timely interventions is currently the most significant clinical challenge in intensive care. However, the standard methods of diagnosis rely on clinical chemistry laboratories and time-consuming assays, making timely treatment difficult. Furthermore, the sample volume required for standard immunoassay is incompatible with frequent blood sampling, making continuous monitoring of circulating biomarkers challenging. To address these challenges, we have developed a microfluidic platform that can process whole blood and perform bead-based immunoassay to achieve nanomolar quantification in under 10 minutes, with a minimal blood sample volume of only 50 microliters.

Materials and

Methods: We designed a custom reader device, consisting of a microfluidic chip and fluorescence imager, for automated assay readout at the point of care. The microfluidic chip is fabricated using standard PDMS soft lithography and contains three main modules: mixing, depletion, and detection. Blood sample is first mixed with assay reagents through a chaotic mixing module, which generates a fluorescent signal on a microbead corresponding to the analyte concentration. The microbeads are then separated from the interfering blood cells in the depletion module and focused in the detection channel for imaging by the readout device. We optimized the readout device's performance using a microlens array to achieve flat illumination and high signal-to-noise ratio. The device platform is tested in a simulated blood circulation system to verify its performance in bedside biochemical monitoring setting.

Results, Conclusions, and Discussions: In this study, we demonstrate the performance of our assay by measuring two biomarkers, CRP and thrombomodulin, in whole blood. These biomarkers have previously been shown to be related to poor outcomes in critically ill sepsis patients under intensive care. By measuring these biomarkers, we aim to demonstrate our platform's capability to capture the dynamic changes in pathophysiological processes. We believe that our platform has the potential to revolutionize intensive care by providing rapid, sensitive biochemical quantification at the bedside, enabling clinicians to identify unstable patients early and initiate timely interventions.

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