Novel Parylene Filters for Biomedical Applications

Abstract

Medical engineering plays a more and more important role in driving the fundamental biology research moving forward. The work presented in this thesis targets at engineer smart parylene filters for various biomedical applications. Three novel parylene membranes are discussed. The first device is parylene magnesium-embedded filter for circulating tumor cells isolation. Circulating tumor cells (CTCs) are cells that slough off the edges of a primary tumor and are swept away by the bloodstream or lymphatic system into the vasculature. They constitute seeds for subsequent growth of additional tumors in vital distant organs, triggering a mechanism that is responsible for the vast majority of cancer-related deaths. Thus CTCs in peripheral blood have been investigated as a valuable biomarker for patients with various types of cancers. However, CTCs are difficult targets to probe owing to their extremely low concentration in peripheral blood. Although rare, CTCs represent a potential approach for the detection, characterization and monitoring of non-haematologic cancers. Therefore, CTCs capture from whole blood has been identified to be an unmet need for cancer research and effective cell separation methods are required to facilitate the study of CTCs. In this study, we developed a novel design applying a buried sacrificial Magnesium (Mg) layer underneath the original microfilter. After filtration, the filter was immersed in DMEM. When the thin-film Mg was dissolved, the cells were released and thus were ready for further biology analysis. The second device is parylene based microelectrode filter for single-islet electroisletogram. Other than direct insulin injection, one promising treatment for Type I diabetes is islet transplantation. However, one of the key lacking technologies of islet transplantation is high-throughput islet screening since each transplantation requires about one million islets. Islets, which are heterogeneous by nature, are currently screened as whole populations containing a range of functioning and dysfunctional characteristics. This work represents the first attempt to develop a MEMS technology for the screening of every single islet so as to guarantee no bad islet at all, which should improve results of islet transplant therapy. Here we report the first MEMS device designed for in vitro measuring of electroisletogram (EIG) of individual rat islets. Strong EIG signals in millivolt range are obtained. This work proves the feasibility of using MEMS and EIG for high-throughput screening, in contrast to patch-clamp measurements, of islets for transplantation to treat diabetes. The third device is parylene-on-PDMS membrane for vaccine production. A parylene-on-PDMS design is proposed to supply oxygen to CV-1 cells for vaccine production. Because the cells are seeded and attached right onto the surface of the device, extra oxygen is provided through permeation from the PDMS and thin parylene layers. The permeation is studied and cell growth experiments are performed to demonstrate the feasibility of the device. Compared to commercialized bioreactors, this novel design could have large cell density because oxygen are supplied locally and shear force is not a limiting factor any more. Besides the three devices, parylene properties are also studied and a novel origami design is proposed, which can potentially increase the surface areas of the membranes by fold the 2D flat film into 3D structures. Details are discussed in the following chapters.