Background

Around 8–16% of population worldwide suffer from chronic kidney disease (CKD). The cause of CKD varies but some most common factors include diabetes, high blood pressure, cardiovascular disease. Optimal detection and risk assessment of CKD requires simultaneous estimation of both kidney function (e.g. glomerular filtration rate [GFR]) and kidney damage (e.g. albuminuria or proteinuria). Albuminuria is a pathological condition wherein the protein albumin is abnormally presented in the urine. Thirty microgram per millilitre (30µg/ml) or higher of albumin in urine is an indicator of kidney damage. The measurement of urine albumin level is necessary for early diagnosis and monitoring of kidney disease. The urine collection is non-invasive, which makes it an ideal sample for point-of-care (POC) detection. There are a variety of methods for assessing urinary albumin excretion, ranging from the colorimetric dipstick method to immunoassays and to high-performance liquid chromatography (HPLC) methods. The dipstick test is inexpensive and easy to perform while its accuracy is limited. Immunoassays and HPLC methods are more accurate but suffer from complicated test procedures and high facility requirement.

Technology Overview

Microfluidics enables advanced sample processing, manipulation and analysis in miniaturized fluidic devices. The combined attractive features of microfluidic technology in low sample and reagent consumption, high-throughput, low-cost, integration and portability make it suitable for disease biomarker detection. There are several good examples showing the development of microfluidic devices in detection CKD biomarkers, including serum CRP, urine albumin and creatinine. But there is still room to further improve the performance of the fluorescent albumin test in terms of easy-use, high accurate and signal stability.

The University of Manitoba has developed a fluorescent microfluidic urinary albumin chip (UAL-Chip) based the non-immunological fluorescent assay. In this chip, researchers constructed a passive and continuous mixing module, in which the loading process requires only an inexpensive dropper, and the signal is stable over time. The researchers applied a pressure-balancing strategy based on the immiscible oil coverage which highly improves the precision in controlling of the mixing ratio of sample and dye. The UAL-Chip has achieved an estimated limit of detection (LOD) of 8.4 µg/ml using albumin standards. Researchers assessed the albumin level in 12 CKD patients’ urine samples. The results measured by UAL-chip is consistent with the traditional well-plate measurements and clinical results. The University of Manitoba believes there is a great potential of UAL-chip in assessing a variety of other biomarkers.

Technical Description

A fluorescent microfluidic urinary albumin chip (UAL-Chip) that exploits the nonimmunological fluorescent assay to rapidly measure albumin in urine is described. In this chip, researchers constructed a passive and continuous mixing module, in which the loading process requires only an inexpensive dropper, and the signal is stable over time. The researchers applied a pressure-balancing strategy based on the immiscible oil coverage which highly improves the precision in controlling the mixing ratio of sample and dye. The UAL-Chip has achieved an estimated limit of detection (LOD) of 8.4 µg/ml using albumin standards, which is below the 30 µg albumin per ml urine level considered to be indicative of kidney damage.

Figure 1. Illustration of working principle of the UAL-Chip.

Stage of Development

Technology Readiness Level (TRL): 7

Benefits

The advantages of the proposed method includes: 1) the operation is easy; 2) precise volume metering equipment is not necessary; 3) the signal is stable over time. Although this method is based on continuous flow, the consumption of reagent is very little due to the low flow rate in the microfluidic device. Researchers have verified that 10µl of sample and reagent could maintain the signal stable for more than 1 hour. Researchers successfully measured the albumin levels from the CKD patients’ urine samples. The low LOD of 8.4 µg/ml makes this method suitable for diagnosing and monitoring the progression of kidney disease.

The method used in UAL-Chip could become a general method for the detection of other target markers which reply on the similar mixing strategy between the test sample and a reacting chemical. The mixing ratio can be easily tuned by changing the length of the branch channels. This method can be further improved in the future:

The portable imaging system can be developed to make the system suitable for POC test
Integration of smartphone
More mixing units could be integrated together to improve the throughput

Applications

UAL-Chip represented a portable and disposable microfluidic based tool for determining urinary albumin. The microchip is easy to fabricate at low cost and the operation is simple for end-users. Further integration of the portable detectors with UAL-Chip will lead to fully standalone diagnostic devices for routine POC analysis of urinary albumin in CKD patients.

Opportunity

The University of Manitoba is actively seeking a licensee to license the patent to move this technology to the market.

The University of Manitoba would also readily welcome interactions with any investor or entrepreneur that would like to license the patent to create of a start‑up based in Manitoba, or outside of the province.

Microfluidic Urinary Albumin Chip (UAL-Chip) for Chronic Kidney Disease Assessment

Patents

IP Status

Seeking