Numerical Simulation and Microfluidic Experiments for Biological Concentration, Characterization and Biomolecule Identification

Y R, Manjoosha and Unni, H N (2019) Numerical Simulation and Microfluidic Experiments for Biological Concentration, Characterization and Biomolecule Identification. PhD thesis, Indian institute of technology Hyderabad.

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Abstract

Microfluidic lab-on-a-chip technologies show remarkable potential for accessible and affordable solutions in the field of medical diagnostics and therapeutics, with the advancements in fabrication processes and precision control. A strong fundamental understanding of cell transport in microfluidic devices is essential for the design and operation of chip scale analytical devices. Thus, the work presented in this thesis can be divided into three parts – one part aimed at phenomenological modeling of particle/cell transport in microfluidic devices, and the second part focused on dielectric characterization of cancer cells through microfluidic cell concentration. The third part of the thesis is focused on the development of a paper based microfluidic device for the quantification of biological markers associated with a prevalent bone disease, Osteoporosis. A numerical model was developed for studying dielectrophoretic particle concentration in pressure driven flow through a parallel plate microfluidic channel, where interdigitated electrodes are embedded on bottom surface. The convection-diffusion equation incorporating Dielectrophoretic field gradient terms was derived and the resulting equation was numerically solved using variable transformation based non-uniform mesh. The effect of applied voltage on particle concentration in the vicinity of electrodes was studied in detail. A microfluidic device with an interdigitated electrode pattern on ITO-coated glass and a PDMS channel was designed and fabricated. Two types of cancer cells, A549 (human lung adenocarcinoma cells) and MCF7 (human breast cancer cells), were trapped at different voltages and frequencies and critical voltages corresponding to both cancer cells were identified. Frequency dependent Clausius Mossotti (CM) factor values for the cancer cells were estimated and the compartment dielectric properties of the cells were ix calculated. Aggregation behaviour of cancer cells in response to varying voltages and frequencies was discussed. The third part of this thesis focused on the design and development of a microfluidic paper-based analytical device (µPAD) for the simultaneous quantification of multiple biomarkers associated with the onset of Osteoporosis. A multi-reservoir µPAD was designed and fabricated. Antibody immobilization and nano-tagging was employed for the identification of serum calcium, alkaline phosphatase and Vitamin D. Smartphone based image processing was employed for colorimetric quantification of the analytes. In addition, real blood sample was tested for calcium and alkaline phosphatase.

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