Pixel Array–Based Urine Biosensor for Real-Time Detection of Trimethylamine N-Oxide and Glucose in Early Diabetic Kidney Disease

 

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https://storage.unitedwebnetwork.com/files/1099/706f8d2de077ab4de613d49aa3fa66f0.pdf
Pixel Array–Based Urine Biosensor for Real-Time Detection of Trimethylamine N-Oxide and Glucose in Early Diabetic Kidney Disease

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Mei-Ching
Yu
Mei-Ching Yu mc.yu@cgmg.org.tw Lin-Kou Chang Gung Memorial Hospital Pediatric Nephrology Taoyuan Taiwan * Chang Gung University College of Medicine Taoyuan Taiwan
Wei-Cheng Lin weiclin@mail.cgu.edu.tw Chang Gung University Department of Electrical Engineering Taoyuan Taiwan -
Chi-Jen Lo chijenlo@mail.cgu.edu.tw Chang Gung University Metabolomics Core Laboratory, Healthy Aging Research Center Taoyuan Taiwan -
Fu-Sung Lo lofusu@cgmh.org.tw Lin-Kou Chang Gung Memorial Hospital Pediatric Endocrinology and Genetics Taoyuan Taiwan -
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Trimethylamine N-oxide (TMAO), a gut microbiota–derived metabolite, has emerged as a biomarker linking metabolic dysregulation, cardiovascular risk, and kidney disease progression. Its urinary excretion reflects renal filtration and metabolic stress, potentially enabling early detection of diabetic kidney disease (DKD). This study presents a novel pixel array–based electrochemical biosensor designed to simultaneously detect urinary TMAO and glucose and assess their relationship with urinary albumin–creatinine ratio (UACR) in type 1 diabetes (T1D) patients.

The biosensor consists of a 2×2 pixel array integrating TorA and glucose oxidase enzymes on a SiNx-protected electrode platform. It operates via electrical field modulation triggered by redox reactions of TMAO and glucose, measured through a custom system-on-chip (SoC) readout circuit. Urine samples from  T1D patients (disease duration >10 years) were stratified by UACR (<30, 30–300, and >300 mg/g). TMAO and glucose signals were analyzed for linearity, sensitivity, and correlation with renal functional indices.

The biosensor exhibited exceptional analytical performance, achieving a detection limit of 0.1 μM and a sensitivity of 41 ADC counts/μM (≈ 4.5 mV/μM). It demonstrated a rapid 1-second response time, 98 % reproducibility, and long-term stability for 63 days with minimal signal drift (0.3 mV). A robust linear correlation (R² = 0.996) was identified between urinary TMAO and UACR values up to 1100 mg/g, whereas urinary glucose showed variable increases beyond 30 mg/g. Only 5 μL of urine was required for simultaneous quantification of TMAO and glucose, supporting its applicability for rapid, low-volume point-of-care testing.

This pixel array urine biosensor offers a rapid, precise, and minimally invasive platform for assessing renal metabolic injury in diabetes. The strong linkage between urinary TMAO and albuminuria underscores its potential as a point-of-care diagnostic platform for early DKD detection and precision kidney health monitoring.

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