Peptide aptamer-modified single-walled carbon nanotube-based transistors for high-performance biosensors

Nguyen Thanh Tung,Phan Trong Tue,Koichi Nishigaki,Yuzuru Takamura,Manish Biyani,Truong Thi Ngoc Lien,Yasuhide Ohno,Kazuhiko Matsumoto,Kenzo Maehashi

doi:10.1038/s41598-017-18169-1

Abstract

Biosensors employing single-walled carbon nanotube field-effect transistors (SWCNT FETs) offer ultimate sensitivity. However, besides the sensitivity, a high selectivity is critically important to distinguish the true signal from interference signals in a non-controlled environment. This work presents the first demonstration of the successful integration of a novel peptide aptamer with a liquid-gated SWCNT FET to achieve highly sensitive and specific detection of Cathepsin E (CatE), a useful prognostic biomarker for cancer diagnosis. Novel peptide aptamers that specifically recognize CatE are engineered by systemic in vitro evolution. The SWCNTs were firstly grown using the thermal chemical vapor deposition (CVD) method and then were employed as a channel to fabricate a SWCNT FET device. Next, the SWCNTs were functionalized by noncovalent immobilization of the peptide aptamer using 1-pyrenebutanoic acid succinimidyl ester (PBASE) linker. The resulting FET sensors exhibited a high selectivity (no response to bovine serum albumin and cathepsin K) and label-free detection of CatE at unprecedentedly low concentrations in both phosphate-buffered saline (2.3 pM) and human serum (0.23 nM). Our results highlight the use of peptide aptamer-modified SWCNT FET sensors as a promising platform for near-patient testing and point-of-care testing applications.

Highlights

IntroductionOur device exhibited good selectivity (no response for bovine serum albumin (BSA) and cathepsin K (CatK)) and a low detection limit
The emergence of biosensor devices that convert a biological response into an electrical signal can address the rapidly increasing need in the point-of-care testing (POCT) market and achieve wide-scale application
This work details the successful fabrication and demonstration of a liquid-gated SWCNT field-effect transistors (FETs) sensor modified with Cathepsin E (CatE)-binding peptide aptamers as an attractive platform for POCT application for the detection of unreached disease biomarkers such as serum CatE, which has recently been highlighted as a novel prognostic biomarker for cancer because the reduction of serum level of CatE has been associated with poor prognosis in breast cancer patients[20]

Summary

Introduction

Our device exhibited good selectivity (no response for bovine serum albumin (BSA) and cathepsin K (CatK)) and a low detection limit The sensitivity of this device could improve the limit of detection of CatE in human serum by at least three orders of magnitude compared with a conventional ELISA-based system using a similar peptide aptamer[19]. This work details the successful fabrication and demonstration of a liquid-gated SWCNT FET sensor modified with CatE-binding peptide aptamers as an attractive platform for POCT application for the detection of unreached disease biomarkers such as serum CatE, which has recently been highlighted as a novel prognostic biomarker for cancer because the reduction of serum level of CatE has been associated with poor prognosis in breast cancer patients[20]. To the best of our knowledge, this work represents the first report of an FET-type sensor utilizing peptide aptamer-modified SWCNTs; this novel sensor can lead to the development of a portable and affordable sensing system for high-performance near-patient testing

Methods

Results

Conclusion