Date of Graduation

2016

Document Type

Thesis

Degree Type

MS

College

Statler College of Engineering and Mineral Resources

Department

Mechanical and Aerospace Engineering

Committee Chair

Nianqiang Wu

Committee Co-Chair

Yuxin Liu

Committee Member

Ismail Celik

Abstract

Lateral flow devices (LFD) have been used and are promising in many applications, including point-of-care diagnosis in medical, clinical, food and environmental control and monitoring. In particular, disposable paper-based lateral flow strips utilize low-cost materials and do not require expensive fabrication instruments. Many examples of diagnostic tests have been developed using microfluidics paper analytical devices (muPADs), including tests for the detection of total glucose and protein in urine (colorimetric), detection of beta-galactosidase (fluorescence), and liver enzyme tests for monitoring the health of patients been treated with multiple medications for HIV and/or tuberculosis that can cause hepatotoxicity. However, there are constraints on tuning the flow rate and immunoassays functionalization in paper as well as technical challenge in integration of sensors and concentration units for low-abundant molecular detection. In the present work, we demonstrated an integrated lateral flow device that applied the capillary forces with functionalized polymer-based microfluidics as a strategy to realize a portable, simplified, and self-powered LFD with minimizing the need for off-chip equipment. The LFD combined the ability to separate plasma from human whole blood and create controlled and steady flow using capillary forces. Lateral flow relies on surface tension and hydrophilic natural of the flow channel, and controlled flow is also a key variable for immunoassay-based applications for providing enough time for protein binding to antibodies. To render polydimethylsiloxane (PDMS) surface of hydrophilicity as well as to control the flow rate, PDMS was functionalized with different concentrations of Pluronic F127. The results show that, in an integrated LFD, the flow rate was regulated by the combination of multiple factors, including Pluronic F127 functionalized surface properties of microchannels, resistance of the integrated flow resistor, the dimensions of the microstructures and the spacing between them in the capillary pump, the contact angles, and viscosity of the fluids. The resistance of the flow resistor had the greatest effect on the flow rate of the fluids. Plasma flow rates ranging between 0.43 and 18.60 nL/s were achieved in the flow resistor, and between 0.99 and 61.30 nL/s in the whole device. In addition, human plasma was separated from whole blood by using a highly asymmetric plasma separation membrane, which captured the cellular components of the blood (red cells, white cells, and platelets), without lysis, so that only high quality plasma could flow down into the smaller pores on the downstream side of the membrane, and into the first capillary pump. The developed LFD can be used as a flexible and versatile platform and has the potential for detecting circulating biomarkers from whole blood; sandwich-immunoassays can be performed directly on the LFD by patterning receptors for analytes on the glass chip, and detection can be performed using a variety of methods ranging from colorimetric and fluorescence methods to more complex methods such as Surface-enhanced Raman spectroscopy (SERS) depending on the limit of detection of the target biomarker. The bio sensing technology being described presents an alternative for point of care testing using small samples of human whole blood; it could benefit regions with limited access to healthcare, where delays in diagnosis can lead to the quick deterioration of the quality of life and increase the morbidity and mortality.

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