Development of microfluidic passive flow assays for point-of-care quantification of chronic kidney disease biomarkers in urine and serum

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Date
2025-06-01
Authors
Tomsa, Dumitru
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Abstract

Chronic kidney disease (CKD) significantly affects people's health and life quality and presents a high economic burden worldwide. However, the existing diagnostic test methods remain complicated and cost-prohibitive. This research addresses critical gaps in CKD diagnostics through the development of innovative microfluidic platforms for point-of-care (PoC) testing. We present complementary approaches targeting key CKD biomarkers: a passive flow microreactor for urinary creatinine measurement (uCR-Chip) and microfluidic devices for serum cystatin C (CYS-C) quantification. The uCR-Chip employs a 2-phase pressure compensation technique, optimized observation window (OW), and channel network design to control fluidic mixing and chemical reactions precisely. A stable signal is achieved within 7 minutes, with the dynamic range up to 40 mM and a lower limit of detection of 0.521 mM. This performance meets clinical precision requirements and demonstrates acceptable recovery rates in artificial urine matrices, particularly at lower creatinine concentrations, making it highly amenable to integration with previously developed microfluidic urine albumin assays. For CYS-C, recommended as a superior estimated glomerular filtration rate (eGFR) biomarker due to minimal influence from non-filtration factors like muscle mass, we developed a PDMS-based immunoturbidity chip enabling side-scattering optical measurement. We demonstrated that the CYS-C chip meets the clinical requirements for detection range and limits while integrated into a custom-developed reader for PoC applications. Validation studies using CKD patient samples demonstrated comparable agreement levels with the traditional well plate-based immunoturbidity assay test results, determining eGFR range across clinically relevant group criteria. Together, these microfluidic platforms offer viable solutions for decentralized CKD assessment, providing potential technology for measuring various disease biomarkers with advantages in accessibility, speed, and precision compared to existing clinical methods.

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Chronic kidney disease, CKD, Creatinine, Cystatin C, Microfluidics, Chip, Point of Care, POC
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