ABSTRACT

Neurodegenerative diseases have been becoming increasingly threatening to human life and living quality, especially to elderly people. Ideally, such diseases can be diagnosed using simple diagnostic methods and treated at their early stages using efficient drug delivery methods. Toward these goals, some new MEMS/microfluidic devices have been developed for diagnosing and treating these neurodegenerative diseases including Alzheimer’s Disease and Glaucoma.

One focus of this thesis is the multiplexed monitoring of two promising biomarkers, beta-amyloid (Aβ42) and total tau (T-tau), in both buffer and cerebrospinal fluid (CSF) for Alzheimer's disease (AD) using label-free optical nanosensors. It has been found that 7.8 pg/ml of Aβ42 in buffer and 15.6 pg/ml of T-au in buffer can be readily detected with very good specificity. Based on our measurements, the purchased CSF itself contains Aβ42, whose concentration is estimated to be about 400 pg/ml. Aβ42 and T-tau in the mixtures of Aβ42 and T-tau spiked in CSF have been detected successfully, indicating the feasibility of the optical nanosensors to detect these biomarkers in clinical samples. For these measurements, only a small amount (~1 µl) of the samples is required. This type of sensor is suitable for point-of-care application to diagnose the AD due to its low cost and ease-of-operation.

The other focus of this thesis is to develop a new power-free multifunctional soft contact lens device that can measure intraocular pressure (IOP), achieve extended drug delivery in situ, and detect glaucoma biomarkers, all within the same device. Experiments demonstrate that the contact lens sensor can detect Interleukin 12p70, one possible biomarker for glaucoma, in a concentration as low as 2 pg/ml in artificial tears. The sustained drug release of the contact lens device can last up to 30 days. In ex vivo tests using cadaver pig eyes, the sensor can detect the IOP in a range of 10 to 50 mmHg.