Rapid Conductometric Sensing of Chronic Kidney Disease Biomarkers: Specific and Precise Detection of Creatinine and Cystatin C in Artificial Saliva

Mingjie Yang, Ganganath Perera, Shanmuga Sundar Dhanabalan, Sanje Mahasivam, Dashen Dong, Ying Zhi Cheong, Chenglong Xu, Peter Francis Mathew Elango, Sagar Borkhatariya, Sharath Sriram, Madhu Bhaskaran
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Abstract

Chronic kidney disease (CKD) has asymptomatic early stages, whereby early detection is crucial to prevent its complications and progression. Creatinine and cystatin C (cysC) assays are known for assessing kidney function but there are limited point-of-care diagnostics which are rapid, precise, and easy to use. Here, high resistivity silicon conductometric sensors for detection of creatinine and cysC with a 10 min sample incubation is introduced. The sensors provide resistance-based signals that can be quantified and measured wirelessly. The sensors successfully detect creatinine and cysC in both phosphate buffer saline (PBS) and artificial saliva in the nanomolar range, being able to distinguish their critical concentrations at 8.8 and 20 nm, respectively, for diagnosis of early stage of CKD. The detection limit for both creatinine and cysC is determined as 0.01 nm which is more than 500× and 1000× times lower than critical concentrations for the two biomarkers, respectively. Finally, these sensors are incorporated into a battery-free, miniaturized electronic device for wireless biomarker detection as a proof-of-concept demonstration of a point-of-care tool for assessing kidney functionality.

Abstract Image

慢性肾病生物标记物的快速电导检测:特异而精确地检测人工唾液中的肌酸酐和胱抑素 C
慢性肾脏病(CKD)早期并无症状,因此早期检测对预防并发症和病情发展至关重要。众所周知,肌酐和胱抑素 C (cysC) 检测法可用于评估肾功能,但快速、精确且易于使用的床旁诊断方法却很有限。这里介绍的高电阻率硅电导传感器可在 10 分钟的样品孵育时间内检测肌酐和胱抑素 C。该传感器提供基于电阻的信号,可通过无线方式进行量化和测量。该传感器能成功地检测出磷酸盐缓冲盐水(PBS)和人工唾液中纳摩尔范围内的肌酐和 cysC,并能区分它们分别在 8.8 纳米和 20 纳米的临界浓度,用于诊断早期 CKD。肌酐和 cysC 的检测限均为 0.01 纳米,分别比这两种生物标记物的临界浓度低 500 倍和 1000 倍以上。最后,这些传感器被集成到一个无需电池的微型电子设备中,用于无线生物标志物检测,作为评估肾功能的护理点工具的概念验证演示。
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