Integrated circuit-microfluidic biosensors for blood-based disease diagnostics-A review

Integrated circuit (IC)-integrated microfluidic biosensors have revolutionized blood-based diagnostics by merging precise electronic sensing with on-chip sample manipulation. Over the past decade, continuous progress in IC architectures, signal processing, packaging and microfluidic designs has enabled compact, low-power platforms that detect cardiovascular, infectious disease, and cancer biomarkers directly from microliter volumes of blood or plasma.

Herein we summarized developments over the decade, highlighting advances in IC front-ends (impedance, capacitive, & electrochemical), time- and frequency-encoded conversion (sigma-delta converters, voltage-controlled oscillators, & capacitance-to-digital/time interfaces), and fluidic strategies spanning capillary-driven, pressure-driven, and hybrid configurations. Limits of detection (LOD), dynamic range, response time, sample volume, and power consumption were compared across an array of devices to evaluate their point-of-care (POC) suitability. We further addressed drift-resilient packaging, on-chip calibration, and machine learning-assisted signal processing as emerging solutions for robust field operations.

This review highlights the key design and performance factors that govern the translational potential of IC-integrated microfluidic biosensors for blood diagnostics. It outlines critical challenges in biocompatibility, manufacturability, analytical sensitivity, and standardization, and identifies the co-optimization of circuit design, surface chemistry, and microfluidic operation as essential for translating laboratory prototypes into practical POC diagnostic devices.