Transforming Renal Diagnosis: Graphene-Enhanced Lab-On-a-Chip for Multiplexed Kidney Biomarker Detection in Capillary Blood

Joaquin F. Diforti, Thomas Cunningham, Zaira Zegalo, Esteban Piccinini, Waldemar A. Marmisollé, Jose M. Piccinini, Omar Azzaroni
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Abstract

Chronic kidney disease (CKD) is a significant global health concern, impacting over 10% of the world population. Despite advances in home-based treatments, CKD diagnosis and monitoring remain centralized in large laboratories. This work reports on the development of a Graphene-based Lab-On-a-Chip (G-LOC) for the self-testing of multiple renal function biomarkers in capillary blood. G-LOC integrates bioelectronic sensors with a 3D-printed microfluidic system that enables the multiplex quantification of urea, potassium, sodium, and chloride, from one drop of blood. The potentials of three graphene sensors modified with ion-selective membranes and enzymes are simultaneously measured. The analytical performance of the test is evaluated in terms of linearity, accuracy, and coefficient of variability (CV). Accuracy values higher than 98.7%, and CV values lower than 10.8% are obtained for all the biomarkers. Correlation and Bland–Altman plots show good correlation (slopes in the range of 0.94–1.15) and high agreement of G-LOC with a reference method. It is also demonstrated that the test can correctly differentiate biomarker levels normally obtained for healthy people, early-stage CKD, and end-stage CKD. Finally, user experience is studied with a group of untrained volunteers who highlight the simple usability of the test and its suitability for at-home diagnostics.

Abstract Image

改变肾脏诊断:石墨烯增强型芯片实验室用于毛细管血液中多重肾脏生物标记物检测
慢性肾脏病(CKD)是全球关注的重大健康问题,影响着全球超过 10% 的人口。尽管家庭治疗取得了进展,但慢性肾脏病的诊断和监测仍集中在大型实验室。这项研究报告了基于石墨烯的片上实验室(G-LOC)的开发情况,该实验室可对毛细血管血液中的多种肾功能生物标志物进行自我检测。G-LOC 将生物电子传感器与 3D 打印微流体系统集成在一起,可从一滴血中对尿素、钾、钠和氯进行多重定量。用离子选择膜和酶修饰的三个石墨烯传感器的电位被同时测量。从线性度、准确度和变异系数(CV)等方面对该测试的分析性能进行了评估。所有生物标记物的准确度均高于 98.7%,变异系数低于 10.8%。相关性和 Bland-Altman 图显示,G-LOC 与参考方法具有良好的相关性(斜率范围在 0.94-1.15 之间)和高度一致性。结果还表明,该测试能正确区分健康人、早期 CKD 和晚期 CKD 的正常生物标记物水平。最后,对一组未经培训的志愿者进行了用户体验研究,他们强调了该测试的简单易用性及其对家庭诊断的适用性。
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