Document Type

Dissertation

Date of Award

8-31-2016

Degree Name

Doctor of Philosophy in Biomedical Engineering - (Ph.D.)

Department

Biomedical Engineering

First Advisor

Raquel Perez-Castillejos

Second Advisor

Treena Livingston Arinzeh

Third Advisor

Kabilan Velliyagounder

Fourth Advisor

Michael Jaffe

Fifth Advisor

Pranela Rameshwar

Abstract

Lab-on-a-chip (LOC) is a device that integrates one or more laboratory functions in a single chip with dimensions ranging from a micrometer to a few millimeters. On-chip optofluidics, which combines microfluidics and tunable micro-optical components, is crucial for bio-sensing applications. However, recently reported optofluidic devices have only two-dimensional (2D) dielectric or metallic regions for sensing cellular activity, which fail to mimic the three-dimensional (3D) in vivo microenvironment of cells.

In this research, a 3D hydrogel-based micro-scale-tissue-analog-chip (µTAC) is fabricated with an integrated optofluidic design for biomedical applications. These 3D hydrogels act as a scaffold for the cellular studies and as a waveguide for increasing the signal efficiency in sensing applications. These 3D waveguides, embedded in a Poly(dimethylsiloxane) elastomer-based optofluidic channel, are composed of Poly(ethylene glycol)-diacrylates (PEGDA). The refractive index of the PEGDA waveguides is higher compared to the water-based cladding that surrounds the waveguide. Because of this refractive index difference, waveguides confine the light waves due to the total-internal-reflection phenomenon (TIR). Initially, the characterizations and the sensing efficiency of the µTAC device are successfully demonstrated with a fluorescein detection study. This study demonstrates that the proposed device is in accordance with Beer-Lambert’s law with a limit of detection of 2.54 µM of fluorescein. Further, the sensing efficiency of the µTAC devices is tested in cellular studies by encapsulating cells inside the waveguides. Cellular studies with µTAC devices prove that the device is capable of efficiently sensing the cell density and the cell viability changes inside the waveguides with a limit of detection of ~27 cells/waveguide. In addition, this study also proves that the proposed µTAC device has a potential for long-term cell monitoring applications without compromising cell-viability. Therefore, with integrated 3D hydrogel waveguides, this µTAC-optofluidic device could be a potential platform with a broad range of applications in the fields of diagnosis and detection.

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