Ratiometric electrochemical OR gate assay for NSCLC-derived exosomes

Fanyu Meng; Wenjun Yu; Minjia Niu; Xiaoting Tian; Yayou Miao; Xvelian Li; Yan Zhou; Lifang Ma; Xiao Zhang; Kun Qian; Yongchun Yu; Jiayi Wang; Lin Huang

doi:10.1186/s12951-023-01833-2

Ratiometric electrochemical OR gate assay for NSCLC-derived exosomes

J Nanobiotechnology. 2023 Mar 24;21(1):104. doi: 10.1186/s12951-023-01833-2.

Authors

Fanyu Meng^#^{1

2}, Wenjun Yu^#¹, Minjia Niu^#², Xiaoting Tian², Yayou Miao², Xvelian Li², Yan Zhou², Lifang Ma¹, Xiao Zhang², Kun Qian³, Yongchun Yu^{4

5}, Jiayi Wang^{6

7}, Lin Huang^{8

9}

Affiliations

¹ Department of Clinical Laboratory Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200030, China.
² Shanghai Institute of Thoracic Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200030, China.
³ State Key Laboratory for Oncogenes and Related Genes, School of Biomedical Engineering, Institute of Medical Robotics and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, 200030, China.
⁴ Department of Clinical Laboratory Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200030, China. yyc2166@sjtu.edu.cn.
⁵ Shanghai Institute of Thoracic Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200030, China. yyc2166@sjtu.edu.cn.
⁶ Department of Clinical Laboratory Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200030, China. jiayi.wang@sjtu.edu.cn.
⁷ Shanghai Institute of Thoracic Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200030, China. jiayi.wang@sjtu.edu.cn.
⁸ Department of Clinical Laboratory Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200030, China. linhuang@shsmu.edu.cn.
⁹ Shanghai Institute of Thoracic Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200030, China. linhuang@shsmu.edu.cn.

^# Contributed equally.

Abstract

Non-small cell lung cancer (NSCLC) is the most common pathological type of LC and ranks as the leading cause of cancer deaths. Circulating exosomes have emerged as a valuable biomarker for the diagnosis of NSCLC, while the performance of current electrochemical assays for exosome detection is constrained by unsatisfactory sensitivity and specificity. Here we integrated a ratiometric biosensor with an OR logic gate to form an assay for surface protein profiling of exosomes from clinical serum samples. By using the specific aptamers for recognition of clinically validated biomarkers (EpCAM and CEA), the assay enabled ultrasensitive detection of trace levels of NSCLC-derived exosomes in complex serum samples (15.1 particles μL^-1 within a linear range of 10²-10⁸ particles μL^-1). The assay outperformed the analysis of six serum biomarkers for the accurate diagnosis, staging, and prognosis of NSCLC, displaying a diagnostic sensitivity of 93.3% even at an early stage (Stage I). The assay provides an advanced tool for exosome quantification and facilitates exosome-based liquid biopsies for cancer management in clinics.

Keywords: Clinical diagnostics; Exosomes; Non-small cell lung cancer; OR logic gate; Ratiometric biosensor.

MeSH terms

Biosensing Techniques
Blood Chemical Analysis / methods
Blood Chemical Analysis / standards
Carcinoma, Non-Small-Cell Lung* / blood
Carcinoma, Non-Small-Cell Lung* / diagnosis
Cell Line, Tumor
Electrochemistry*
Exome*
Humans
Limit of Detection

Abstract

MeSH terms

Grants and funding