Novel Integration of Bipolar Exfoliated Graphene with 3D C-MEMS Microelectrodes for Label-Free Electrochemical Cancer Biomarkers Aptasensors

Abstract

Early detection of cancer can noticeably increase the survival chance of many cancer patients. Quantifying cancer biomarkers detectable from blood is an efficient way for the early detection of cancer diseases. Among various discovered cancer biomarkers, platelet-derived growth factor-BB (PDGF-BB) is an essential biomarker for early detection of cancer and monitoring cancer patients. This biomarker plays a vital role in developing and lymphatic metastasis of solid malignant tumors such as brain, lung, breast, and liver, which enlightens the importance of developing point-of-care (POC) biosensors for the detection of PDGF-BB. In recent years, the application of synthetic DNA or RNA-based bio-recognizers (i.e., aptamers) in cancer biomarker sensor development has been vastly investigated. Electrochemical label-free aptamer-based biosensors (also known as aptasensors) are highly suitable for POC. The well-established C-MEMS (carbon microelectromechanical systems) platforms have distinguishing features which are highly suitable for biosensing applications such as low background noise, high capacitance, high stability when exposed to different physical/chemical treatments, biocompatibility, and good electrical conductivity. Furthermore, the surface of C-MEMS can be modified effectively via depositing nanomaterials which can enhance the electrochemical and sensing performances of the C-MEMS based biosensors. In this study, the integration of bipolar exfoliated (BPE) reduced graphene oxide (rGO) with 3D C-MEMS microelectrodes for developing PDGF-BB label-free aptasensors is investigated. A single setup has been used for exfoliation, reduction, and deposition of rGO on the 3D C-MEMS microelectrodes based on the principle of bipolar electrochemistry of graphite in deionized water. The electrochemical bipolar exfoliation of rGO resolves the drawbacks of commonly applied methods for synthesis and deposition of rGO such as requiring complicated and costly processes, excessive use of harsh chemicals, and complex subsequent deposition procedures. The PDGF-BB affinity aptamers were covalently immobilized by binding amino-tag terminated aptamers and rGO surfaces. The scanning electron microscopy (SEM) analysis confirms that the rGO deposited on 3D C-MEMS microelectrodes has a porous vertically aligned structure with pore sizes of around 100 nm. Cyclic voltammetry (CV) was used for characterizing the aptasensors in different stages of development and their sensing performances. The CV analysis confirms that deposition of BPE-rGO noticeably increases the capacitance of 3D C-MEMS electrodes. The turn-off sensing strategy was implemented by measuring the areal capacitance from CV plots. The aptasensor showed a wide linear range of 1 pM-10 nM, high sensitivity of 3.09 mF cm-2 Logc-1 (unit of c, pM), and a low detection limit of 0.75 pM. This study demonstrated the successful deposition of BPE-rGO on 3D CMEMS microelectrodes. Considering the high potential of C-MEMS technology and BPE technique's simplicity and efficiency, this novel technique is highly promising for developing feasible and mass-producible lab-on-chip and point-of-care cancer diagnosis technologies.