An integrated electrochemical POCT platform for ultrasensitive circRNA detection towards hepatocellular carcinoma diagnosis

Bin Zhang; Mingyu Chen; Jiasheng Cao; Yitao Liang; Tingting Tu; Jiahao Hu; Tianyu Li; Yu Cai; Shijie Li; Boqiang Liu; Junjie Xu; Bo Liang; Xuesong Ye; Xiujun Cai

doi:10.1016/j.bios.2021.113500

An integrated electrochemical POCT platform for ultrasensitive circRNA detection towards hepatocellular carcinoma diagnosis

Biosens Bioelectron. 2021 Nov 15:192:113500. doi: 10.1016/j.bios.2021.113500. Epub 2021 Jul 13.

Authors

Bin Zhang¹, Mingyu Chen¹, Jiasheng Cao¹, Yitao Liang², Tingting Tu², Jiahao Hu¹, Tianyu Li³, Yu Cai², Shijie Li¹, Boqiang Liu¹, Junjie Xu¹, Bo Liang⁴, Xuesong Ye⁵, Xiujun Cai⁶

Affiliations

¹ Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, 3 East Qingchun Road, Hangzhou, 310016, Zhejiang Province, China.
² Biosensor National Special Laboratory, Key Laboratory of Biomedical Engineering of Ministry of Education, College of Biomedical Engineering and Instrument Science, Zhejiang University, Hangzhou, 310027, China.
³ Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, 3 East Qingchun Road, Hangzhou, 310016, Zhejiang Province, China; Biosensor National Special Laboratory, Key Laboratory of Biomedical Engineering of Ministry of Education, College of Biomedical Engineering and Instrument Science, Zhejiang University, Hangzhou, 310027, China.
⁴ Biosensor National Special Laboratory, Key Laboratory of Biomedical Engineering of Ministry of Education, College of Biomedical Engineering and Instrument Science, Zhejiang University, Hangzhou, 310027, China. Electronic address: boliang1986@zju.edu.cn.
⁵ Biosensor National Special Laboratory, Key Laboratory of Biomedical Engineering of Ministry of Education, College of Biomedical Engineering and Instrument Science, Zhejiang University, Hangzhou, 310027, China; Key Laboratory of Laparoscopic Technique Research of Zhejiang Province, 3 East Qingchun Road, Hangzhou, 310016, Zhejiang Province, China. Electronic address: yexuesong@zju.edu.cn.
⁶ Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, 3 East Qingchun Road, Hangzhou, 310016, Zhejiang Province, China; Key Laboratory of Laparoscopic Technique Research of Zhejiang Province, 3 East Qingchun Road, Hangzhou, 310016, Zhejiang Province, China; Zhejiang Minimal Invasive Diagnosis and Treantment Thechnology Research Center of Severe Hepatobiliary Disease, 3 East Qingchun Road, Hangzhou, 310016, Zhejiang Province, China; Zhejiang Research and Development Engineering Laboratory of Minimally Invasive Technology and Equipment, 3 East Qingchun Road, Hangzhou, 310016, Zhejiang Province, China. Electronic address: srrsh_cxj@zju.edu.cn.

PMID: 34280653
DOI: 10.1016/j.bios.2021.113500

Abstract

Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related death. Circ-CDYL, one of the circular RNAs (circRNAs), is recognized as an independent marker for HCC early diagnosis. Point-of-care testing (POCT) of circRNA is essential and in great demand for clinical applications. Herein, we report a fully integrated electrochemical POCT platform for circRNA detection based on Au nanoflowers (AuNFs)/peptide nucleic acid (PNA) modified carbon-fiber microelectrode (CFME). PNA is applied as the recognition element, highly specified for a back-splice junction of circRNA. AuNFs increased active site for PNA probes, improving target-capturing efficiency at an ultralow level. The platform provides a linear range of 10 fM to 1 μM, with a detection limit as low as 3.29 fM. This biosensor demonstrates high specificity towards one-base mismatch and is stable for up to 24 days. The analytical performance has also been verified in human serum samples, demonstrating the potential utility in clinical POCT applications for HCC.

Keywords: Carbon-fiber microelectrode; Electrochemical; Peptide nucleic acid (PNA); Point-of-care testing (POCT); circRNA.

MeSH terms

Biosensing Techniques*
Carcinoma, Hepatocellular* / diagnosis
Carcinoma, Hepatocellular* / genetics
Humans
Liver Neoplasms* / diagnosis
Liver Neoplasms* / genetics
Point-of-Care Testing
RNA, Circular

Substances

RNA, Circular