Time-Domain Integrated-Circuit-Based Biosensors on an Integrated Microfluidic System for Detecting Cardiovascular Biomarkers

A new integrated-circuit-based (IC-based) biosensor integrated with a microfluidic system for sample pretreatment has been developed to quantify cardiovascular disease (CVD) biomarkers such as C-reactive protein (CRP). Aptamers specific to CRP were immobilized on the surface of interdigitated electrodes (IDE) on the IC-based biosensor for quantification of CRP. An integrated microfluidic system, capable of performing plasma filtration from whole blood, metering, and fluidic delay, was utilized for sample pretreatment. The time variation, which was caused from the capture of the target protein (i.e. CRP) by the coated aptamers with high affinity and specificity, was measured during the conversion of voltage signals into time-domain signals by manipulating the charging and discharging rates in the IC chips, thereby enhancing the accuracy and sensitivity of the measurements. As a demonstration, CRP measurements covering cut-off values indicating individuals at risk of CVD were performed.