Novel Diagnostic Method for Personalized Treatment of Cancer

Abstract

Point-Of-Care (POC) devices, due to their better portability and easy-to-use functions, have already found their way into the domestic house hold appliances. The technologies developed for these devices have enabled the mankind to monitor the health related problems at home such as the blood pressure, glucose, hemoglobin, cholesterol level in the blood and many more. The efforts are now being made to develop a Point-Of-Care Technology (POCT) that can detect cancer at an early and potentially treatable stage. To fulfill this requirement, a highly sensitive sensing technology is needed that can detect very small amount of cancer markers in the blood drop to be used in a POC device. Silicon Nanowires (SiNW) in a field effect setup have been demonstrated as a highly sensitive tool that can be used to detect very small amount of biomolecules. However, the manufacturing method to produce them relies on highly expensive tools e.g. e-beam lithography, and expensive substrates e.g. Silicon-On-Insulator (SOI) which poses hurdle in cheap and fast production of the devices that can be used for both research purposes and for domestic use. In this project, a novel fabrication method, using in-situ doped polysilicon, has been developed for SiNW based devices that does not require the above mentioned expensive tools and resources thereby enabling faster and cost effective production of devices as compared to the already developed methods. In addition to this, the device has been made even more compact and portable by using a novel polyimide based technology to integrate microfluidics on top of SiNW sensor. Various generations of prototype devices have been used for bio-sensing experiments to detect antibodies and DNA hybridization that has shown very promising results and potential application of the device in clinical and patient level diagnostics. In the first part of this thesis, the fabrication process of producing the SiNW based devices is explained in detail where three generations of the process are developed in order to obtain highly sensitive device. Different characterization techniques have been used to ensure better reproducibility and high throughput while keeping the sensitivity of the SiNW to a high level. In the second part, the fabrication process to produce microfluidic channel on top of bio sensors by using polyimide is developed. The fabrication process to integrate closed-microfluidic system on top of SiNW is demonstrated. The durability of the microfluidic system has also been tested. In the third part, different functionalization methods are explained and used to demonstrate the bio sensing on the SiNW sensor. The detection of cancer biomarker is also tested on these devices. Lastly, the alternative fabrication processes developed during this PhD project are discussed along with the problems faced during the development. These devices could not be tested due to time constraints.