Abstract
In today’s fast-paced world, where timely and accurate medical diagnostics are crucial, the emergence of microfluidic devices has promised a revolutionary shift for point-of-care technologies. These miniaturized marvels that are capable of diagnosing diseases with only a tiny amount of samples offers an amazing potential for a rapid and portable diagnostic testing which could enable healthcare institutions to make swift real-time on-site detection of diseases as well as increasing the accessibility where anyone in the world could reap the benefits even if the location only has limited resources. Despite the clear advantage of these microfluidic devices, the reality is these devices have yet to attain popularity in the market. Usually targeted for laboratory setting, most microfluidic devices have yet to be able to function on their own as a stand-alone unit. Most microfluidic devices either require a syringe pump to allow for a specific working flow rate or a specific reader which commonly comes in the form of a spectrometer which limits accessibility and portability. On the other hand, more portable devices that are popular in the market are limited in how they are able to only provide qualitative or semi-quantitative measurements at best which cannot meet the demand for accurate sensing. Therefore, creating a portable system with a user-friendly interface and the capability to provide an accurate quantitative measurement is crucial for the advancement of point-of-care diagnosis. In this thesis, a rapid test in the form of a microfluidic chip equipped with a thermometer like display was developed based on the accumulation of polystyrene microparticles (PMPs) by forming a trapping bar that can be observed by the naked eye. First, the proposed device is used for the detection of urine albumin to creatinine ratio (uACR) detection. While later on, an accessory is then studied to be able to be added onto the device to be able to automatically process complicated whole blood matrix and integrated with the detection assay.First, the portable microfluidic device is used in tandem with a microparticle assay utilizing polymer microparticles (PMPs) and magnetic microparticles (MMPs) to do a dual detection of urine biomarker albumin and creatinine in order to find the urine albumin-to-creatinine ratio (uACR) that is often used as a marker to determine the progression of CKD. A competitive immunoassay and Fenton’s reaction-based detection in tandem with the microparticle system is used to detect both albumin and creatinine respectively. Through this method, we are able to detect albumin and creatinine with a limit of detection (LOD) of 4.281 mg/L and 165 mg/L respectively. The assay also yields a uACR correlation coefficient of 95.45% compared to clinical golden standard methods.
Second, to explore the utilization of whole blood, which is another sample matrix in the human body, we designed a microfluidic device that can extract blood plasma from whole blood samples. Whole blood samples have been considered as a difficult biomarker to directly process in a point-of-care (POCT) platform due to the difficulty in processing which requires complicated machinery and trained personnel. Here we have designed an autonomous microfluidic based blood plasma extractor that can extract blood plasma from whole blood samples by using a simple plasma separation membrane and a fluid flow programming sequential draining method via geometrical simple geometrical manipulation. By using this device, we have achieved a near perfect separation efficiency and extracting the entire volume of blood plasma from the whole blood sample in around 15 minutes.
Lastly, the blood plasma extractor should then be developed further so that it includes a method to be able to determine the concentration of biomarker. We modified the blood plasma extractor to be able to work together with the microparticle system in order for it to automatically detect the biomarker from blood plasma extracted from the whole blood sample. Modifying the extractor with a rection chamber, pressure balance based valve, magnetic separator, and a PMP accumulation channel, we are able to detect cancer marker alpha-fetoprotein (AFP) from spiked synthetic blood with an LOD of 53.655 ng/mL comparable to a benchtop method of 37 ng/mL in a sample to result time of 30 minutes.
In summary, the autonomous microfluidic platform with a distance bar-based readout method has enabled the visual and quantitative measurement of urine based biomarker in albumin and creatinine obtaining the uACR value as well as successfully implemented and integrated together with the blood plasma extractor that is able to detect cancer marker alpha-fetoprotein from a synthetic whole blood sample. Through the breakthroughs that we have achieved, we believe that the microfluidic platform with a visual bar distance method can be a suitable rapid test alternative that provides quantitative monitoring of multiple disease biomarkers in different matrices.
| Date of Award | 7 Jan 2025 |
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| Original language | English |
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| Supervisor | Ting Hsuan CHEN (Supervisor) |