Label-free capacitive biosensor for the detection of a panel of disease biomarkers using microelectrode arrays

Disease biomarker panel that include C-reactive protein (CRP), TNF, IL-1 and IL-6 have strong and consistent relationships between markers of inflammation and future cardiovascular risk (CVR) events. Early detection of these biomarkers enables prevention of the prevailing disease risk. Here, we present label-free and sensitive detection of multiple biomarkers using interdigitated (IDA) capacitor arrays immobilized with specific antibodies. Two different lab-on-a-chip formats have been employed for multiple biomarker detection on arrays of IDA-capacitors; (I) each IDA-capacitor in an array was immobilized with a specific antibody and (II) each IDA-capacitor was immobilized with multiple antibodies in equimolar ratios in arrays (Fig. 1). Detection of single and multiple protein biomarkers on format I and II, respectively was performed by capacitive/dielectric constant measurements. Our initial results for detection of single biomarkers (format I) showed the detection range 25 ng/ml-25 pg/ml for CRP, 25-500 pg/ml for TNF and IL-6, and 1-25 ng/ml for IL-1. Further, detection of multiple biomarkers (format II) was carried out by immobilizing equimolar ratio’s of three types of antibodies (CRP, TNF, IL-6) and the resulting response to the mixture of biomarkers was lower in three orders compared to that found with IDA-capacitor immobilized with pure antibodies (format I) (Fig. 2A and B). The capacitive biosensor for panels of inflammation and CVR markers show significant clinical value and provide great potential for detection of protein markers in suspected subjects for early diagnosis.