Oncoslice: A Microfluidic Platform for Personalized Cancer Care and Drug Development

Abstract

Improving efficacy, minimizing the adverse side effects of drugs, and overcoming acquired resistance to drug treatment have been major goals and emphases in cancer therapy. Existing models of drug activity (based on tumor cells in culture or animal models) cannot accurately predict how drugs would act in individual patients. Presonalized medicine has received considerable attention and enthusiasm as it has potential to offer new therapeutic measures based on tailored therapies for individual patients. Personalized approaches could lower treatment toxicity, improve patient’s quality of life, and, most importantly, reduce mortality. Prof. Folch’s lab developed Oncoslice, a platform has the potential to allow for identifying the subset of therapies of greatest potential to individual patients, on a timescale rapid enough to guide therapeutic decision-making. This new method would allow for testing treatment efficacy on the patient’s own tumor tissue in a timeline that allows for the results to influence a patient’s therapeutic strategy. However, the platform was fabricated with conventional soft-lithography techniques, which are not readily translatable for mass manufacturing. Here we present a redesigned architecture of Oncoslice and new manufacturing techniques that will facilitate its fabrication on the larger scale necessary for clinical use. We shifted our focus to CO2 laser micromachining as the main fabrication technique and we were able to develop a new fabrication protocol with rapid turnaround time, low operational costs, mask/cast-less processes, and agile design processing. We focused on poly (methyl methacrylate) (PMMA) as the fabrication material of the platform due to its biocompatibility, low-cost, and optical properties. This thesis reports a detailed description of the complete fabrication process including CO2 laser optimization, post-processing, and solvent bonding techniques for assembly. Moreover, it also presents alternative bonding procedures commonly utilized for rapid-prototyping, such as indirect transfer adhesive bonding and lamination. Finally, we demonstrate the functionality of the platform through a series of characterization experiments and illustrate its potential through a set of biological experiments utilizing glioblastoma multiforme xenografts and human cancer biopsies.