Highly Sensitive Detection of Protein Biomarkers with Organic Electrochemical Transistors

Abstract

The analysis of protein biomarkers is of great importance in the diagnosis of diseases. Although many convenient and low-cost electrochemical approaches have been extensively investigated, they are not sensitive enough in the detection of protein biomarkers with low concentrations in physiological environments. Here, this study reports a novel organic-electrochemical-transistor-based biosensor that can successfully detect cancer protein biomarkers with ultrahigh sensitivity. The devices are operated by detecting electrochemical activity on gate electrodes, which is dependent on the concentrations of proteins labeled with catalytic nanoprobes. The protein sensors can specifically detect a cancer biomarker, human epidermal growth factor receptor 2, down to the concentration of 10 g mL , which is several orders of magnitude lower than the detection limits of previously reported electrochemical approaches. Moreover, the devices can successfully differentiate breast cancer cells from normal cells at various concentrations. The ultrahigh sensitivity of the protein sensors is attributed to the inherent amplification function of the organic electrochemical transistors. This work paves a way for developing highly sensitive and low-cost biosensors for the detection of various protein biomarkers in clinical analysis in the future.

Ultrasensitive Bioaffinity Electrochemical Sensors: Advances and New Perspectives

“…The electrical double layer is the result of the variation of electrical potential near the surface [54]. Reproduced from [49] with permission from Willey . Polyion complex membrane prepared from oppositely charged polyelectrolytes has been successfully used as effective molecular recognition interfaces for sensor construction.…”

Integration of Biomaterials into Sensors Based on Organic Thin‐Film Transistors

“…f) The sensing mechanism of the OECT‐based biosensors for detecting HER2. Reproduced with permission . Copyright 2017, Wiley‐VCH.…”

“…The rapidly developing immunosensors (antibody–antigen sensors) have been actively applied in such fields as food, industry, environmental monitoring, and clinical examinations due to their high specificity, sensitivity, and stability . Lee et al first demonstrated PEDOT:PSS‐based OECTs for prostate specific antigen (PSA) detection .…”

“…The resultant devices demonstrated a wide range of detection range (six orders of magnitude), low LOD at 220 ng L −1 as well as decent selectivity. Recently, Yan and co‐workers reported a convenient and inexpensive strategy for detecting a cancer biomarker (human epidermal growth factor receptor 2, HER2) by utilizing OECT‐based biosensors . A novel operation mechanism was proposed, as depicted in Figure f, the gate electrode was first modified with monoclonal anti‐HER2 antibody (Ab Capture ), and HER2 captured by Ab Capture was then attached to catalytic nanoprobes for electrochemical activation.…”

“…[31] The rapidly developing immunosensors (antibody-antigen sensors) have been actively applied in such fields as food, industry, environmental monitoring, and clinical examinations due to their high specificity, sensitivity, and stability. [28,29,[36][37][38] Lee et al first demonstrated PEDOT:PSS-based OECTs for prostate specific antigen (PSA) detection. [37] The OSC layer of the devices was modified with gold nanoparticles (Au NPs) conjugated with PSA polyclonal antibody (pAb), realizing a detection limit (LOD) of 1 pg mL −1 , enhanced dynamic range from 10 pg mL −1 to 100 ng mL −1 , and improved sensitivity.…”