Title: Novel Microfabrication Techniques Towards Next-Generation In Vitro and In Vivo Medical Devices
Description: Microfabrication has given rise to numerous technologies and has resulted in new paradigms for how science and technology has advanced in recent years. Having originated from the microelectronics industry, microfabrication techniques have increasingly been leveraged in the development of various other fields. Such techniques have an increasing presence in the field of medical devices, especially with the advent of microfluidics. The capability that microfluidics lends to miniaturizing and making portable analytical tools was, and still is, extremely useful in the advancement of medical technologies. In this dissertation, we explore novel microfabrication techniques towards the development of next-generation medical devices. We can broadly classify these devices as devices that function in in vitro and in vivo settings. In vitro devices typically function in a non-invasive manner such as when patient samples are processed externally for diagnostic purposes. In vivo medical devices, on the other hand, normally play a role in disease treatment upon implantation into a patient, such as with stents, pacemakers and drug delivery devices.

Here we demonstrate how microfabrication techniques can be implemented in the improvement of devices involved in diagnosis and treatment; two important branches of medical sciences that go hand in hand. Firstly, microfabrication and microfluidic techniques were implemented in developing a CD4+ T helper cell counter. This integrated device, where capture and analysis are performed on the same platform, also employs a chemiluminescence-based method of detection. This a rather simple and elegant technique that is amenable for miniaturization in future as it does not require the use of external complex light source (such as for fluorescence imaging) nor the use of image/data analysis methods. The second part of this dissertation describes novel microfabrication techniques for the development of a new class of implantable devices- hydrogel MEMS devices. This technique is comparable to additive manufacturing techniques such as 3D printing. Current 3D printing or fabrication techniques for biocompatible materials normally result in standalone structures.

Using our technique, we are not only able to construct microcomponents entirely out of hydrogels but also have the capability to assemble and align various moving components to form a robust MEMS-like device. As these MEMS devices are constructed entirely out of biocompatible PEG-based hydrogels, they are ideal candidates for implantable devices. Once implanted, they can be wirelessly actuated using simple permanent magnets and the operation of the devices do not require onboard power-sources or electronics, which is common for current MEMS-based implantable devices. These devices can also be designed to deliver payloads and this delivery can be actively controlled. We also explore the use of hydrogel MEMS in the in vivo delivery of therapeutics, and assess its efficacy in delivering local, low-doses of a chemotherapeutic drug in a disease model. We envision that these devices, and the technology from which they are borne, will open up a new paradigm in the way implantable devices are developed.