Ultrasensitive sensing urinary cystatin C via an interface-engineered graphene extended-gate field-effect transistor for non-invasive diagnosis of chronic kidney disease

Xiaofen Chen; Yirou Liang; Ning Tang; Canye Li; Yongheng Zhang; Feng Xu; Guoyue Shi; Min Zhang

doi:10.1016/j.bios.2024.116016

Ultrasensitive sensing urinary cystatin C via an interface-engineered graphene extended-gate field-effect transistor for non-invasive diagnosis of chronic kidney disease

Biosens Bioelectron. 2024 Apr 1:249:116016. doi: 10.1016/j.bios.2024.116016. Epub 2024 Jan 9.

Authors

Xiaofen Chen¹, Yirou Liang¹, Ning Tang², Canye Li³, Yongheng Zhang¹, Feng Xu⁴, Guoyue Shi⁵, Min Zhang⁶

Affiliations

¹ School of Chemistry and Molecular Engineering, Shanghai Key Laboratory for Urban Ecological Processes and Eco-Restoration, East China Normal University, Dongchuan Road 500, Shanghai, 200241, China.
² Precision Research Center for Refractory Diseases in Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China. Electronic address: ntang@sjtu.edu.cn.
³ Department of Pharmacy, 6th People's Hospital South Campus, Shanghai Jiao Tong University, Shanghai, 201499, China.
⁴ Department of Pharmacy, 6th People's Hospital South Campus, Shanghai Jiao Tong University, Shanghai, 201499, China. Electronic address: xuf@smu.edu.cn.
⁵ School of Chemistry and Molecular Engineering, Shanghai Key Laboratory for Urban Ecological Processes and Eco-Restoration, East China Normal University, Dongchuan Road 500, Shanghai, 200241, China. Electronic address: gyshi@chem.ecnu.edu.cn.
⁶ School of Chemistry and Molecular Engineering, Shanghai Key Laboratory for Urban Ecological Processes and Eco-Restoration, East China Normal University, Dongchuan Road 500, Shanghai, 200241, China. Electronic address: mzhang@chem.ecnu.edu.cn.

PMID: 38217967
DOI: 10.1016/j.bios.2024.116016

Abstract

Early chronic kidney disease (CKD) has strong concealment and lacks an efficient, non-invasive, and lable-free detection platform. Cystatin C (Cys C) in urine is closely related to the progress of CKD (especially at the early stage), which is an ideal endogenous marker to evaluate the impairment of renal function. Thus, the accurate detection of urinary Cys C (u-Cys C) is great significant for early prevention and treatment and delaying the course of the disease of CKD patients. Herein, we developed an extended-gate field-effect transistor (EG-FET) sensor for ultrasensitive detection of u-Cys C, which consists of a monolithic interface-engineered graphene EG electrode array and a commercially available MOSFET. Laser-induced graphene (LIG) loaded with sputtered Au NPs in the presence of adhesive Cr (Au NPs/Cr/LIG) boosts the electrical performance of the EG electrode. Meanwhile, Au NPs also serve as linkers to immobilize papain that can selectively form protein complexes with Cys C. Supported by the synergistic effect of multilevel interface-engineered graphene, our sensor exhibits a good linear correlation within the u-Cys C concentration range of 5 ag/μL to 50 ng/μL with low detection limit of 0.05 ag/μL. Our work makes accurate, specific and rapid detection of u-Cys C feasible and promising for early screening for CKD.

Keywords: Chronic kidney disease; Extended-gate field-effect transistor; Non-invasive diagnosis; Urinary cystatin C.

MeSH terms

Biosensing Techniques*
Body Fluids*
Cystatin C / urine
Graphite*
Humans
Renal Insufficiency, Chronic* / diagnosis
Renal Insufficiency, Chronic* / urine

Substances

Cystatin C
Graphite