A novel approach for electrical tuning of nano-textured zinc oxide surfaces for ultra-sensitive troponin-T detection

Abstract

We have developed a label-free, non-Faradaic, electrochemical sensor for ultra-sensitive detection of cardiac biomarker, troponin-T by utilizing the stoichiometric surface compositions of nanotextured zinc oxide (ZnO) thin films. In this study, we show how the performance of a nanotextured zinc oxide based non-Faradaic biosensor is modulated by differences in the fabrication parameters of the metal oxide thin film as well as the choice of cross-linkers. Two cross-linking molecules, dithiobis succinimidyl propionate and 3-aminopropyl triethoxysilane, demonstrate significantly different binding chemistries with zinc oxide. The non-Faradaic electrochemical behaviour of the sensor due to the two linkers is compared by analyzing the troponin-T dose response using electrochemical impedance spectroscopy (EIS). Sensor performance associated with both linkers is compared based on dynamic range and limit of detection. The sensor utilizing zinc surface terminations demonstrated a wider dynamic range between the two linkers. This range extended from 26% to 54% in phosphate buffered saline and from 21% to 65% in human serum, for a concentration range from 10 fg/mL to 1 ng/mL of troponin-T. The limit of detection was found to be at 10 fg/mL and has potential utility in the development of point-of-care (POC) diagnostics for cardiovascular diseases. Fluorescence quantification analysis was also performed to further validate the specificity of linker binding to the ZnO films. An ultrasensitive troponin-T biosensor can be designed by leveraging the zinc termination based surface chemistry for selective protein immobilization.

Optical biosensors based on ZnO nanostructures: advantages and perspectives. A review

“…The use of thiol compounds to form Zn-S surface bonds was reported by Jacobs et al [88] and Munje et al [87]. The cross-linking agent (dithiobis succinimydyl propionate (DSP) dissolved in dimethyl sulfoxide (DMSO)) forms amine groups which are further occupied by proteins [88,87].…”

“…The cross-linking agent (dithiobis succinimydyl propionate (DSP) dissolved in dimethyl sulfoxide (DMSO)) forms amine groups which are further occupied by proteins [88,87].…”

“…The covalent binding involves a cross-linking agent between ZnO surface and molecules of the bioselective layer, which provides a significant structure of the bioselective layer and improves the biorecognition [89,47,78,81,87,88].…”

“…Nanostructured ZnO films have been widely used as template in electrochemical biosensors before demonstrating good sensitivity and low detection limit [30,39,55,88,90,[92][93][94], while ZnO nanowires, nanorods etc. have been widely used recently as the sensing element in FET biosensors [29,33,87].…”

“…Nowadays, the most developed and used biosensor platforms are electrical [29,32,33,37,42,46,47,56,87] and electrochemical [16,30,31,38,39,55,88,90,[92][93][94]. Electrical in particular are based on their Field Effect Transistor (FET) platforms demonstrate high level of detection but require additional input of lithography and nanotechnology, what makes these devices more complex and expensive.…”