Reagentless aptamer based impedance biosensor for monitoring a neuro-inflammatory cytokine PDGF

Abstract

Neural prostheses often suffer from undesired chronic inflammatory tissue response. This can lead to neuronal loss and formation of glial scar tissue, which would serve as a barrier to neural signal transduction. In situ monitoring of neuro-inflammatory cytokines may improve our understanding of device induced inflammatory responses. Furthermore, early detection of the onset and degree of inflammation and releasing drugs accordingly may lead to improved long term performance of such implanted devices. For this reason, biosensor applying aptamer as probe and non-faradic electrochemical impedance spectroscopy (NIS) as the detection method has been developed. Aptamers, certain kinds of DNA or RNA molecules which can bind variety of molecules at high specificity, have the overwhelming advantages over antibodies of low cost and ease of use. Platelet-derived growth factor BB (PDGF-BB), one of the important cytokines involved in neural inflammation, has been selected as our detection target. Binding of PDGF to its aptamer immobilized on the silicon electrode surface lead to a decrease in capacitance measured by NIS. A good linear relationship between the decrease of capacitance and the logarithm of protein concentration was obtained, which proves the feasibility of quantitative measurements. By sweeping the applied electrode potential of potentiostatic EIS, −0.1 V to +0.1 V was determined to be the optimal range for achieving best discrimination between specific target binding and non-specific protein adsorption on aptamer-modified silicon surface. Under such conditions, the specificity of the detection measured by the ratio of the positive to negative control is around 10:1 and the detection limit is ∼1 μg/ml (40 nM). The online measurement result exhibited negligible response for non-specific adsorption but significant signal changes for the specific target. Since the non-faradic strategy does not require any reagent to be loaded when performing the test, together with the ability of online measurements, this biosensor design is promising for in vivo monitoring.