The Design and Manufacturability of Metastasis Mimetic Devices Used for Cancer Research

Abstract

Metastatic cancer causes the death in 80% of its patients, due to the failure of detecting the metastatic events early enough and the failure to effectively treat and eliminate the metastatic cancer cells. A limited understanding of the molecular and cellular mechanisms of the metastatic disease inhibits the development of effective therapies and the ability to prematurely diagnose metastatic disease. There have been numerous in-vitro devices and experimental approaches invented in the past to mimic individual stages of the metastatic disease, but not the entire cellular migration. In this thesis, the development of six distinct metastatic devices will be described to replicate multiple aspects of metastatic cell behavior and mimicking multiple steps of the metastatic process. These new in-vitro devices have been designed to overcome the current challenges of previous devices. All of the designs were constructed with a new and innovative way of incorporating a porous membrane filter into a metastatic device. The first three designs include the use of two chambers that can hold cells or tissue, which are connected by an optically clear channel mounted on top or embedded into the base plate. All of the designs presented were able to accurately replicate the multiple steps of the progression of metastatic cancer such as cell proliferation, migration, invasion, intravasation, extravasation, and colonization of other tissues. The Type II and Type V devices worked the best, due to the greatest number of cells that migrated to the other side and the most consistent results.