Design and Investigation of Capillary-Gravitational Valve in an Integrated Urine-Chip for Creatinine Detection
Date Issued
2011
Date
2011
Author(s)
Fang, Po-Hsuan
Abstract
The prevalence of chronic kidney disease (CKD) has become an important issue in Taiwan. This is mainly due to the lack of prevention awareness, which may lead to critical delays in treatment. Point-of-care testing (POCT) allows for diagnostic testing near the site of the patients, and may avoid the need for hemodialysis. Therefore, it is necessary to develop a POCT device to evaluate the renal function.
Creatinine is a chemical found in steady levels in humans, so the concentration in blood and urine is a standard to evaluate the renal function. Since blood is not easily obtained in point-of-care testing, we aim to quantitatively measure the concentration of urinary creatinine. This can be done by integrating the process of biochemical analysis in the hospital onto a small device based on the concept of “lab-on-a chip”. Though the concentration of creatinine fluctuates with the volume of urine, other analyses such as albumin assay can be measured as well to determine the renal function.
There has been much research using expensive immunoassay to enhance the specificity of the biochemical analysis. To lower the cost of the analysis, chemical reagents were used instead. Since we aim to quantitatively measure urinary creatinine, metering and sequential steps on chip are required to increase the precision of the chemical assay.
Centrifugal microfluidics is considered one of the most commonly used platform for lab-on-a-chip. It allows a serial process to perform on a plastic substrate without complex fabrication. In this research, we applied a novel and simple approach to control the liquid on the microfluidic chip. Gravitational force, instead of centrifugal force, is used to overcome the capillary force generated at the capillary valve. This valve is called the “capillary-gravitational valve”. There has been, however, no research focusing on integrating the serial process of detecting urinary creatinine onto a microfluidic system by such an approach. And this simple method is power-saving, and can be operated without electricity.
Furthermore, PMMA was used as the substrate to reach disposability. No external components were mounted onto the chip, reducing the time and the cost of fabrication. By analyzing the parameters of the capillary-gravitational valve and altering the geometry of the microchannels, metering, adding catalytic and colorimetric reagents sequentially, and mixing could be done by simply rotating the chip to certain angles. The concentration of creatinine was determined by measuring the change of optical density at 510 nm.
The optical system was calibrated by first measuring the optical density corresponding to different concentrations of the red dye. The calibration curve shows good linearity. The on-chip creatinine assay was also compared with the creatinine assay processed by the standard in-lab method. Good consistency of the two results indicates the feasibility of the approach we proposed.
The serial functions were demonstrated by this device and the process was performed within 20 minutes according to the standard process performed in the hospital. Real urine samples from different people were measured and compared with clinical methods, showing high consistency. This novel approach can be further incorporated with the detection of albumin to derive the urine albumin to creatinine ratio (ACr). In this case, the device can be used to the real time determination of renal function for point-of-care use in practice.
Subjects
Chronic Kidney Disease
Urinary Creatinine
Quantitative Analysis
Serial Process
Lab-on-a-Chip
Optical Density
SDGs
Type
thesis
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