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A passive flow microreactor for urine creatinine test
Dumitru Tomsa1, Yang Liu1, Amanda Stefanson1
1Department of Physics and Astronomy, University of Manitoba, Winnipeg, MB, R3T 2N2, Canada.
Insights
A new microfluidic chip (uCR-Chip) enables rapid, point-of-care urine creatinine measurement for chronic kidney disease (CKD) assessment. This low-cost, accurate assay integrates with existing albumin tests, offering a viable alternative to lab-based diagnostics.
Area of Science:
- Biomarker detection and microfluidics
- Point-of-care diagnostics for chronic kidney disease (CKD)
Background:
- Chronic kidney disease (CKD) poses a significant global health and economic burden.
- Current CKD diagnostic methods rely on lab-based tests for biomarkers like creatinine.
- Existing tests are regulated and lack point-of-care (PoC) accessibility for routine monitoring.
Purpose of the Study:
- To develop a passive flow microreactor for colorimetric urine creatinine measurement (uCR-Chip).
- To create a PoC assay for CKD assessment by integrating with a microfluidic urine albumin assay.
- To enable rapid, accurate, and accessible CKD biomarker quantification.
Main Methods:
- Developed a passive flow microreactor (uCR-Chip) utilizing a 2-phase pressure compensation (2-PPC) technique.
- Employed microfluidic channel network design and an optimized observation window (OW) for fluidic control and signal stability.
- Utilized custom photomask production and dry-film photoresist lithography for precise chip fabrication; detection via USB microscope platform.
Main Results:
- Achieved a uniform and stable detection signal within 7 minutes.
- Demonstrated a dynamic linear detection range up to 40 mM with a lower limit of detection (LOD) of 0.521 mM.
- Validated the assay with artificial urine, showing acceptable recovery and low matrix effects, comparable to commercial PoC systems.
Conclusions:
- The developed uCR-Chip offers a viable PoC test for chronic kidney disease (CKD) assessment.
- The microreactor provides accurate creatinine quantification, meeting clinical precision requirements.
- This technology platform has potential for measuring various disease biomarkers at the point of care.
Abstract:
Chronic kidney disease (CKD) significantly affects people's health and quality of life and presents a high economic burden worldwide. There are well-established biomarkers for CKD diagnosis. However, the existing routine standard tests are lab-based and governed by strict regulations. Creatinine is commonly measured as a filtration biomarker in blood to determine estimated Glomerular Filtration Rate (eGFR), as well as a normalization factor to calculate urinary Albumin-to-Creatinine Ratio (uACR) for CKD evaluation. In this study, we developed a passive flow microreactor for colorimetric urine creatinine measurement (uCR-Chip), which is highly amenable to integration with our previously developed microfluidic urine albumin assay. The combination of the 2-phase pressure compensation (2-PPC) technique and microfluidic channel network design accurately controls the fluidic mixing ratio and chemical reaction. Together with an optimized observation window (OW) design, a uniform and stable detection signal was achieved within 7 min. The color signal was measured by a simple USB microscope-based platform to quantify creatinine concentration in the sample. The combination of the custom in-house photomask production techniques and dry-film photoresist-based lithography enabled rapid iterative design optimization and precise chip fabrication. The developed assay achieved a dynamic linear detection range up to 40 mM and a lower limit of detection (LOD) of 0.521 mM, meeting the clinical precision requirements (comparable to existing point-of-care (PoC) systems). The microreactor was validated using creatinine standards spiked into commercial artificial urine that mimics physiological matrix. Our results showed acceptable recovery rate and low matrix effect, especially for the low creatinine concentration range in comparison to a commercial PoC uACR test. Altogether, the developed uCR-Chip offers a viable PoC test for CKD assessment and provides a potential platform technology to measure various disease biomarkers.
