本論文整合半導體元件技術與微機電製程，發展一可攜式、平行檢測之蛋白質微陣列螢光檢測晶片。以漸逝波(Evanescent wave)激發螢光檢體，藉由批次、陣列式設計之檢測晶片，完成螢光點強度及形貌之辨別，進而達到快速且同時檢測多種疾病檢體之目的。光感測器採近距離檢測螢光之方式，除可增加光吸收效率外，亦可免除強激發光源之使用，避免傷害蛋白質檢體。因此，整體設計有別於普遍研究之微流體螢光檢測系統之設計及傳統生醫掃描系統之檢測機制。
此檢測晶片整合互補式金屬-氧化物半導體(CMOS)製程之雪崩型感光二極體(Avalanche Photo Diode, APD)、表面張力暨自我成型之高數值孔徑微透鏡及微傾斜面鏡結構而完成。雪崩型感光二極體作為光電訊號之轉換器。微透鏡作為收光及聚光之結構、增加微弱光訊號之累積、減少表面之光吸收效應並減少介面耦合所產生之光訊號損失。而具多重角度之三維傾斜V型面鏡，採用傾斜曝光技術及光於基材表面反射之特性製作，可區隔相鄰兩螢光點之干擾。此外，為減少外部電源產生之雜訊且縮小檢測晶片之體積，故製作一不需變壓器而能產生0-90V、4mV低雜訊之雪崩型感光二極體微型電源驅動電路(5cm X 5cm)。
雪崩型感光二極體整合微透鏡結構，靈敏度可增加25%，因此將有助於提昇螢光檢測極限(Limit of detection)。目前整合完成之螢光檢測晶片，最小可檢測之蛋白質濃度為2ng/ml。
此蛋白質微陣列螢光檢測晶片，可解決傳統生醫檢測系統過於龐大、昂貴的缺點，以實現Lab on a Chip的理想。

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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