CapSense-MIP: Self-operating molecularly imprinted polymer (MIP) biosensor for point-of-care diagnostics

Abstract

Molecularly imprinted polymer (MIP) biosensors hold immense promise for point-of-care (POC) diagnostics due to their exceptional robustness, long shelf-life stability, selectivity, and ability to detect diverse biomarkers across their (patho)physiological ranges. However, their full potential within practical POC devices remains constrained by technical challenges, including the need for precise incubation control, effective washing of non-specific bindings, and consistent fluid handling in miniaturized systems. Without addressing these limitations, their ability to reliably operate in complex bodily fluids and within critical physiological detection ranges is significantly compromised. To address these barriers, we developed the CapSense-MIP, a capillary microfluidic biosensing platform that automates key MIP biosensing steps-sample aliquoting, incubation, washing, and sensing-using a fully integrated and self-powered system driven by sequential liquid delivery to the biosensing chamber. It incorporates an inlet regulator for precise aliquoting and incubation control, a suction-enhanced fiber for optimized washing, and the regulated channels and valve network to ensure high sensitivity and reproducibility, and a wide dynamic detection range that meets (patho)physiological needs. As a proof of concept, the CapSense-MIP was validated for agmatine detection, achieving a wide linear range of 1.0 nM-10 mu M and an impressive limit of detection of 0.1 nM, with optimized protocols for both phosphate-buffered saline and human plasma. By addressing these critical challenges and leveraging the long shelf-life stability of MIP biosensors, the CapSense-MIP not only eliminates traditionally manual workflows but also delivers scalable, rapid, and cost-effective solutions for POC diagnostics, unlocking transformative potential for applications in healthcare and environmental monitoring.