An Electrochemical and Raman Scattering Dual Detection Biosensor for Rapid Screening and Biomolecular Profiling of Cancer Biomarkers

Abstract

Detecting circulating biomarkers sensitively and quantitatively is paramount for cancer screening, diagnosis, and treatment selection. Particularly, screening of a panel of circulating protein biomarkers followed by mapping of individual biomarkers could assist better diagnosis and understanding of the cancer progression mechanisms. Herein, we present a miniaturized biosensing platform with dual readout schemes (electrochemical and Surface enhanced Raman scattering (SERS)) for rapid cancer screening and specific biomarker expressional profiling to support cancer management. Our approach utilizes a controlled nanomixing phenomena under alternative current electrohydrodynamic condition to improve the isolation of cancer-associated circulating proteins (i.e., Epidermal growth factor receptor (EGFR), BRAF, Programmed death-ligand 1 (PD-L1)) with antibody functionalized sensor surface for rapid and efficient isolation of the targets and subsequent labelling with SERS nanotags. The method employs Differential Pulse Voltammetry (DPV) for rapidly screening for the presence of the circulating proteins on biosensor surface irrespective of their type. Upon positive DPV detection, SERS is applied for sensitive read-out of individual biomarkers biomarker levels. In a proof-of-concept study, we demonstrate the dual detection biosensor for analysing circulating BRAF, EGFR and PDL-1 proteins and successfully screened both ensemble and individual biomarker expressional levels as low as 10 pg (1 ng/mL). Our findings clearly indicate the potential of the proposed method for cancer biomarker analysis which may drive the translation of this dual sensing concept in clinical settings.