Graduate Thesis Or Dissertation


Comprehensive, Low-Cost Wicking Microfluidic Analytical Devices for Clinical Diagnostics and Environmental Analysis Public Deposited

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  • Analytical techniques are utilized in a wide variety of applications. Traditionally, analytical measurements are achieved by trained personnel in a laboratory setting using expensive scientific instruments, which limits their applicability in resource-limited areas and point-of-care applications. Therefore, the concept of enabling these laboratory-based qualitative and quantitative assays in microfluidic device platforms has been a growing area of research over the past two decades. The main challenges with many of the available microfluidic techniques are the costs and complexities of both device fabrication and post-assay detection. As a result, membrane-based microfluidics (wicking microfluidics) has gained much attention in recent years given their rapidity, simplicity, and low cost. However; the range of applicability of current-generation wicking microfluidic technology is limited due to its inability to incorporate complex fluidic architectures to handle multistep processes. In this work, a new, versatile wicking microfluidic fabrication approach was developed and its potential applications in both low-cost clinical chemistry analysis and environmental pollution monitoring were explored. In the first component of this dissertation, the focus is on a new method of fabricating wicking microfluidic analytical devices. This fabrication approach involves selective exposure of polycaprolactone (PCL)-filled glass microfiber (GMF) membranes to oxygen radicals, which is achieved using an inexpensive tape mask. GMF membranes are inexpensive, temperature stable, pH resistant, chemically inert, hydrophilic substrates made up of microscale borosilicate fibers that can be adapted for use with many different chemistries and assays. Polycaprolactone (PCL) is a biocompatible and biodegradable polyester that is used to define the hydrophobic portions of these devices. Changes in the mask design allow for fabrication of different channel geometries (flow-through, flow-through + lateral flow, and surface-lateral flow). Various combinations of these channel geometries allow for the production of complex multidimensional (2D and 3D) microfluidic devices on a single polymer-filled membrane, enabling unique properties and applications. Depending on the fabrication geometry, the channels will have unique properties and enable various unit operations such as mixing, separations, delay circuits, and timing devices, having features as small as 250 μm. Therefore, much attention was given to investigating possible unit operations that can be achieved using this fabrication technique. Though oxygen radical exposure as a tool for the fabrication of wicking microfluidic devices has been explored, the exact effect that the exposure has on the surface remains only poorly understood. Gaining this understanding is necessary in explaining the performance evidenced in prior experiments, and will aid in the design and integration of assay chemistries on the device. For instance, an improved knowledge of the chemistry of the modified surface will allow for design decisions to be made that could preserve the activity of a given assay, resulting in longer shelf life. Therefore, this dissertation also includes studies that were conducted to elucidate mechanisms and outcomes of oxygen radical exposure of PCL-filled GMF membrane systems. The next portion of this research involved the evaluation of this wicking microfluidic technology in clinical diagnostic applications. The research especially focused on developing simple and inexpensive point-of-care diagnostic devices to detect biomarkers in different body fluids (e.g. urine, blood). Blood tests can reveal valuable information about the cause of a disease and its symptoms, furthermore helping in early detection of critical health changes before they become severe medical conditions (heart disease, cancer, diabetes, etc.) These blood tests often require separation of blood plasma from whole blood, a challenging process and rarely done in microfluidics. Separation of blood plasma from whole blood on a wicking microfluidic platform has to be mastered in order to develop simple, inexpensive, and portable point-of-care diagnostic blood analysis tests. Therefore, in this work, much attention was paid on handling front-end blood samples and separating blood plasma/serum from whole blood. Previously reported colorimetric assay chemistries were adopted in this work, with some modification, in order to quantitatively detect different analytes. A digital image based red (R), green (G), and blue (B) color value analysis approach was used in quantitative data acquisition. Another important area in which wicking microfluidics can make a large contribution as a rapid, inexpensive and portable analytical technique is environmental pollution monitoring. Monitoring of environmental pollutants, such as aqueous toxic metal ions, has become necessary as recent anthropogenic activities have caused elevated environmental concentrations of these toxic metal ions beyond threshold limits, resulting in severe acute and chronic health effects. Such monitoring processes require a novel, inexpensive, simple, and portable analytical technique that can generate reliable qualitative and quantitative data efficiently. The last part of this research focused on detecting aqueous toxic metal ions on the wicking microfluidic platform. There, a new stand-alone approach to quantitative determination of metal pollution in environmental waters was developed. This technique utilized the capability of lateral flow channel fabrication and coupled it with uniquely designed polymer inclusion membrane-based (PIM) assay chemistry where the assay chemistry is introduced as an array of dots using ink-jet deposition along the length of the surface lateral flow channel. This combination enabled the detection of analytes based on dot-counting. The unique fabrication method employed allows the concentration range to be tuned by controlling the wicking channel geometry (width). The accuracy and limit of detection can also be easily adjusted by increasing or decreasing the resolution of the inkjet-dispensed assay dots without the need for further fine-tuning of the reagent composition.
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  • 2019-06-09 to 2020-07-09



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