Ultrasensitive Silicon Nanowire Biosensor with Modulated Threshold Voltages and Ultra-Small Diameter for Early Kidney Failure Biomarker Cystatin C

Overview

Journal Biosensors (Basel)

Specialty Biotechnology

Date 2023 Jun 27

PMID 37367010

Authors

Jiawei Hu

Yinglu Li

Xufang Zhang

Yanrong Wang

Jing Zhang

Jiang Yan

Junjie Li

Zhaohao Zhang

Huaxiang Yin

Qianhui Wei

Qifeng Jiang

Shuhua Wei

Qingzhu Zhang

Affiliations

Soon will be listed here.

Abstract

Acute kidney injury (AKI) is a frequently occurring severe disease with high mortality. Cystatin C (Cys-C), as a biomarker of early kidney failure, can be used to detect and prevent acute renal injury. In this paper, a biosensor based on a silicon nanowire field-effect transistor (SiNW FET) was studied for the quantitative detection of Cys-C. Based on the spacer image transfer (SIT) processes and channel doping optimization for higher sensitivity, a wafer-scale, highly controllable SiNW FET was designed and fabricated with a 13.5 nm SiNW. In order to improve the specificity, Cys-C antibodies were modified on the oxide layer of the SiNW surface by oxygen plasma treatment and silanization. Furthermore, a polydimethylsiloxane (PDMS) microchannel was involved in improving the effectiveness and stability of detection. The experimental results show that the SiNW FET sensors realize the lower limit of detection (LOD) of 0.25 ag/mL and have a good linear correlation in the range of Cys-C concentration from 1 ag/mL to 10 pg/mL, exhibiting its great potential in the future real-time application.

Citing Articles

Silicon-Based Biosensors: A Critical Review of Silicon's Role in Enhancing Biosensing Performance.

Muhammad W, Song J, Kim S, Ahmed F, Cho E, Lee H Biosensors (Basel). 2025; 15(2).

PMID: 39997021 PMC: 11852904. DOI: 10.3390/bios15020119.

Emerging trends in the cystatin C sensing technologies: towards better chronic kidney disease management.

Raveendran J, Gangadharan D, Bayry J, Rasheed P RSC Adv. 2025; 15(7):4926-4944.

PMID: 39957820 PMC: 11826153. DOI: 10.1039/d4ra07197b.

Biomarker analysis from complex biofluids by an on-chip chemically modified light-controlled vertical nanopillar array device.

Rao L, Raz A, Patolsky F Nat Protoc. 2025; .

PMID: 39885332 DOI: 10.1038/s41596-024-01124-6.

Correction: Hu et al. Ultrasensitive Silicon Nanowire Biosensor with Modulated Threshold Voltages and Ultra-Small Diameter for Early Kidney Failure Biomarker Cystatin C. 2023, , 645.

Hu J, Li Y, Zhang X, Wang Y, Zhang J, Yan J Biosensors (Basel). 2024; 14(10).

PMID: 39451727 PMC: 11505775. DOI: 10.3390/bios14100461.

Ultrasensitive 3D Stacked Silicon Nanosheet Field-Effect Transistor Biosensor with Overcoming Debye Shielding Effect for Detection of DNA.

Li Y, Wei S, Xiong E, Hu J, Zhang X, Wang Y Biosensors (Basel). 2024; 14(3).

PMID: 38534249 PMC: 10968264. DOI: 10.3390/bios14030144.

References

Lo Faro M, Leonardi A, Priolo F, Fazio B, Irrera A . Future Prospects of Luminescent Silicon Nanowires Biosensors. Biosensors (Basel). 2022; 12(11). PMC: 9688548. DOI: 10.3390/bios12111052. View

Zhao M, Bai L, Cheng W, Duan X, Wu H, Ding S . Monolayer rubrene functionalized graphene-based eletrochemiluminescence biosensor for serum cystatin C detection with immunorecognition-induced 3D DNA machine. Biosens Bioelectron. 2019; 127:126-134. DOI: 10.1016/j.bios.2018.12.009. View

Desai D, Kumar A, Bose D, Datta M . Ultrasensitive sensor for detection of early stage chronic kidney disease in human. Biosens Bioelectron. 2018; 105:90-94. DOI: 10.1016/j.bios.2018.01.031. View

Yang Z, Zhuo Y, Yuan R, Chai Y . Highly Effective Protein Converting Strategy for Ultrasensitive Electrochemical Assay of Cystatin C. Anal Chem. 2016; 88(10):5189-96. DOI: 10.1021/acs.analchem.6b00210. View

Li G, Wei Q, Wei S, Zhang J, Jin Q, Wang G . Acrylamide Hydrogel-Modified Silicon Nanowire Field-Effect Transistors for pH Sensing. Nanomaterials (Basel). 2022; 12(12). PMC: 9227456. DOI: 10.3390/nano12122070. View

Randers E, Kristensen J, Erlandsen E, Danielsen H . Serum cystatin C as a marker of the renal function. Scand J Clin Lab Invest. 1999; 58(7):585-92. DOI: 10.1080/00365519850186210. View

Gao X, Zheng G, Lieber C . Subthreshold regime has the optimal sensitivity for nanowire FET biosensors. Nano Lett. 2009; 10(2):547-52. PMC: 2820132. DOI: 10.1021/nl9034219. View

Fonseca I, Reguengo H, Oliveira J, Martins L, Malheiro J, Almeida M . A triple-biomarker approach for the detection of delayed graft function after kidney transplantation using serum creatinine, cystatin C, and malondialdehyde. Clin Biochem. 2015; 48(16-17):1033-8. DOI: 10.1016/j.clinbiochem.2015.07.007. View

Shlipak M, Matsushita K, Arnlov J, Inker L, Katz R, Polkinghorne K . Cystatin C versus creatinine in determining risk based on kidney function. N Engl J Med. 2013; 369(10):932-43. PMC: 3993094. DOI: 10.1056/NEJMoa1214234. View

10.

Pergande M, Jung K . Sandwich enzyme immunoassay of cystatin C in serum with commercially available antibodies. Clin Chem. 1993; 39(9):1885-90. View

11.

Jia Y, Wang J, Yosinski S, Xu Y, Reed M . A Fast and Label-Free Potentiometric Method for Direct Detection of Glutamine with Silicon Nanowire Biosensors. Biosensors (Basel). 2022; 12(6). PMC: 9221423. DOI: 10.3390/bios12060368. View

12.

Legrand M, Bell S, Forni L, Joannidis M, Koyner J, Liu K . Pathophysiology of COVID-19-associated acute kidney injury. Nat Rev Nephrol. 2021; 17(11):751-764. PMC: 8256398. DOI: 10.1038/s41581-021-00452-0. View

13.

Li D, Chen H, Fan K, Labunov V, Lazarouk S, Yue X . A supersensitive silicon nanowire array biosensor for quantitating tumor marker ctDNA. Biosens Bioelectron. 2021; 181:113147. DOI: 10.1016/j.bios.2021.113147. View

14.

Elfstrom N, Juhasz R, Sychugov I, Engfeldt T, Karlstrom A, Linnros J . Surface charge sensitivity of silicon nanowires: size dependence. Nano Lett. 2007; 7(9):2608-12. DOI: 10.1021/nl0709017. View

15.

Mi L, Wang P, Yan J, Qian J, Lu J, Yu J . A novel photoelectrochemical immunosensor by integration of nanobody and TiO₂ nanotubes for sensitive detection of serum cystatin C. Anal Chim Acta. 2015; 902:107-114. DOI: 10.1016/j.aca.2015.11.007. View

16.

Lopes P, Costa-Rama E, Beirao I, Nouws H, Santos-Silva A, Delerue-Matos C . Disposable electrochemical immunosensor for analysis of cystatin C, a CKD biomarker. Talanta. 2019; 201:211-216. DOI: 10.1016/j.talanta.2019.04.006. View

17.

Delanaye P, Cavalier E, Morel J, Mehdi M, Maillard N, Claisse G . Detection of decreased glomerular filtration rate in intensive care units: serum cystatin C versus serum creatinine. BMC Nephrol. 2014; 15:9. PMC: 3893362. DOI: 10.1186/1471-2369-15-9. View

18.

Trindade E, Silva B, Dutra R . A probeless and label-free electrochemical immunosensor for cystatin C detection based on ferrocene functionalized-graphene platform. Biosens Bioelectron. 2019; 138:111311. DOI: 10.1016/j.bios.2019.05.016. View

19.

Zhou W, Dai X, Fu T, Xie C, Liu J, Lieber C . Long term stability of nanowire nanoelectronics in physiological environments. Nano Lett. 2014; 14(3):1614-9. PMC: 3960854. DOI: 10.1021/nl500070h. View

20.

Stasyuk N, Smutok O, Demkiv O, Prokopiv T, Gayda G, Nisnevitch M . Synthesis, Catalytic Properties and Application in Biosensorics of Nanozymes and Electronanocatalysts: A Review. Sensors (Basel). 2020; 20(16). PMC: 7472306. DOI: 10.3390/s20164509. View