Real time detection of C reactive protein in interstitial fluid using electrochemical impedance spectroscopy, towards wearable health monitoring

Abstract

Traditional detection methods of C-reactive protein (CRP) inflammation biomarker, in blood are expensive, time-consuming and labor-intensive. Such existing point-of-care CRP detection devices remain invasive, since they need blood sampling (finger-pricking or venous puncture). Here, we propose an electrochemical impedance spectroscopy (EIS)-based sensor for the real-time, fast, specific, sensitive, and label-free detection of C-reactive protein in the interstitial fluid (ISF) that can be accessed with minimally invasive microneedle arrays. The sensor has the potential to be integrated in a wearable device similar with the continuous glucose monitoring, that will detect CRP in interstitial fluid in a non-invasive, inexpensive and straightforward manner. The affinity based assay was tested in both buffer and ISF-like solution. The limit of detection achieved was 0.7 ug/mL of CRP in buffer, and 0.8 ug/mL of CRP in ISF-like solution and the sensor shows excellent linearity up to 10 ug/mL. It is worth noting that the proposed sensor operates in low sample volume (down to 5 uL), and has a response time of 100 seconds.