| Summary: | 博士 === 國立清華大學 === 工程與系統科學系 === 93 === This thesis presents a novel micro fluorescence detection chip system for protein microarray detection in parallel applied to a 3-in-1 protein chip system. This portable microchip consists of a monolithic integration of CMOS-based Avalanche Photo Diode (APD) coupled with 3-dimensional (3-D), polymer microlens with high numerical aperture (NA) for signal enhancement. In the current study, a novel approach was proposed to effectively fabricate the aforementioned semi-sphere polymer microlens (SU-8 or UV curable optical oil for better light transparency performance) based on thermal-capillary force and well-defined hydrophobic (rings of Teflon) and hydrophilic (silicone dioxide surface) regions with self-alignment feature. Microlenses as small as 5 μm in radius were successfully fabricated with a coefficient of variation better than 2.8 % for lens-to-lens variation. The NA could reach as large as 0.66. Also, a novel 3-D glycerol-compensated, inclined-exposure technology was adopted to fabricate inclined microstructures, which were incorporated into the microchip later to make one less susceptible to adjacent fluorescent signals. This technology could fabricate 19-90o inclined structures on SU-8 negative tone resist with thickness from 100 to 1000 μm. The surface roughness, measured by atomic force microscope, was below 7 nm for various inclined angles, a roughness good enough for optical applications. With the use of 3-D shadow mask and glycerol-compensated exposure technology, a variety of round surfaces with different radius could be fabricated with well-controlled exposure doses, enabled the realization of spherical micromirrors and plane concave lenses.
Three generation of CMOS-based APD were developed. The device initially consists of a single APD with a 500μm minimum detection diameter, dark current of about 1-2 μA, and avalanche voltage of 95 V. It was consecutively evolved to a 5x5 array of APD with a 20μm minimum detection diameter, lower dark current of tens of nA, and an improved avalanche voltage of 22.5 V. The APDs were later fabricated in such a way that seven single APD were grouped together as a single array for shape detection and arranged in multiple forms of 3x3 (63 APDs) or 4x4 (112 APDs) arrays. A new APD electrical driver circuitry was developed, without the need of voltage converter and capable of producing 0-90 V low noise signal. The developed micro fluorescence detection chip system was tested and found capable of detecting protein concentration as low as 2 ng/μl. With integrated polymer microlens, the sensitivity could reach 39.7 A/W, an improvement of about 25%. The current exploration of the novel integration of APD arrays, polymer microlens arrays, and microfabricated inclined structures on a single microchip proved to be an excellent sensing architecture that hold promise to be inexpensive, portable, parallel, and micro-scale solutions for fluorescence detection.
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