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An integrated microfluidic system for the determination of microalbuminuria by measuring the albumin-to-creatinine ratio

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Abstract

This study presents an integrated microfluidic system for the determination of microalbuminuria (MAU) through the measurements of the albumin-to-creatinine ratios in patients’ urinary samples. Albumin concentrations are determined based on a non-immunological dye binding assay in which the dyes react specifically with albumin to undergo a strong fluorescence enhancement. Creatinine concentrations are determined based on the Jaffé reaction in which the reagents react specifically with creatinine to form orange–red colored complexes. Two calibration curves for determining the concentrations of urinary albumin and creatinine are constructed with assay ranges of 5–220 and 1–100 mg/l, respectively. Using this system to determine the ACRs of collected clinical urine samples, statistical tools including Bland–Altman bias plot and Passing–Bablok regression analysis show that the results obtained by the proposed microfluidic system are in good agreement with those obtained by conventional methods. This simple, automatic, inexpensive, and microchip-based platform demonstrates a promising alternative to the conventional assays for determining MAU and may be suited for clinical applications.

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Abbreviations

AB:

Albumin blue

ACR:

Albumin-to-creatinine ratio

AER:

Albumin excretion rate

BioFET:

Biological field-effect transistor

BUN:

Blood urea nitrogen

CI:

Confidence interval

CNC:

Computer-numerical-controlled

CVs:

Coefficients of variation

DS:

Dextran sulfate

EMVs:

Electromagnetic valves

GFR:

Glomerular filtration rate

HCl:

Hydrogen chloride

HSA:

Human serum albumin

LC–MS/MS:

Liquid chromatography tandem mass spectrometry

LOC:

Lab-on-a-chip

MAU:

Microalbuminuria

NaOH:

Sodium hydroxide

NCVs:

Normally closed valves

PB:

Polybrene

PDMS:

Poly(dimethylsiloxane)

PMMA:

Polymethylmethacrylate

SAM:

Self-assembled monolayer

SD:

Standard deviation

μTAS:

Micro-total-analysis-system

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Acknowledgments

The authors gratefully acknowledge the financial support provided to this study by the National Science Council (NSC 99-2218-E-006-236; NSC 99-2120-M-006-008) and the Department of Health (DOH 99-TD-B-111-102) in Taiwan.

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Authors and Affiliations

  1. Department of Engineering Science, National Cheng Kung University, Tainan, 701, Taiwan

    Chun-Che Lin & Gwo-Bin Lee

  2. Graduate Institute of Biotechnology, National Pingtung University of Science and Technology, Pingtung, 91201, Taiwan

    Jue-Liang Hsu

  3. Division of Nephrology, Department of Internal Medicine, College of Medicine, National Cheng Kung University, Tainan, 701, Taiwan

    Chin-Chung Tseng

Authors
  1. Chun-Che Lin
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  2. Jue-Liang Hsu
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  3. Chin-Chung Tseng
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  4. Gwo-Bin Lee
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Correspondence to Chin-Chung Tseng or Gwo-Bin Lee.

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Lin, CC., Hsu, JL., Tseng, CC. et al. An integrated microfluidic system for the determination of microalbuminuria by measuring the albumin-to-creatinine ratio. Microfluid Nanofluid 10, 1055–1067 (2011). https://doi.org/10.1007/s10404-010-0734-9

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