光学生物传感器集成化阵列化关键器件研究

In this research, through the optimization of the mixing structures, precise control of array samples is achieved. Through morphology control and hot embossing process optimization, low-cost and mass production of microlens array is achieved. By using the fluorescence immunological method, high sensitivity biological detection is achieved. Therefore, low-cost and multi-channel array diagnose becomes possible. The detailed layout of irregular mixing microstructure is realized by using the layout optimization method. During the analysis of the antibody-antigen binding dynamic process, the effective convection will be introduced; mass transfer efficiency of the analyte to each detecting spot and the detection efficiency are improved. Based on the principle of total internal reflection fluorescence, we design and built the polymer planar waveguide with prisms to obtain the uniform excitation for detection. By optimizing the aspheric polymer microlens array and the optical path, the collection efficiency of fluorescent signals and the detection sensitivity are improved effectively. The polymeric microlens arrays are fabricated using PDMS mold-based hot embossing process. By changing the air pressure and the deformation of the membrane, the shape of microlens can be controlled effectively. We integrate biosensors with CCD detector, the parallel detection becomes possible. Therefore, we can build multi-parameter measurement bio-sensing system, which can find lots of fields of applications, such as clinic diagnosis and disease prevention.

本项目针对低成本多通道阵列化诊断的需求，拟通过微混合结构的优化，实现阵列样本的精确控制；通过形貌调控和热压工艺优化，完成非球面微透镜阵列和平板波导等关键器件的低成本批量化制备；通过荧光免疫学检测，实现高灵敏度的生物探测。采用微通道内不规则混合结构的布局优化设计，以及抗体-抗原动态结合过程的分析，有效地引入对流，提高被测物到各个探测点的传质效率，提高检测效率；采用带有棱镜的聚合物平板波导的设计与制备，利用全内反射荧光检测的方法，实现阵列探测信号的均匀激励；通过非球面聚合物微透镜阵列的设计，完成阵列探测光路的优化，有效提高荧光信号的收集效率，提高检测的灵敏度；采用弹性模具热压的方法，通过弹性力和气体压力共同调控，完成形貌可控的微透镜阵列的制备；并与CCD探测器集成，形成平行探测通道，实现生物传感系统的多参数阵列化检测，用于现场即时检测以及疾病的早期诊断、预防和控制。

近些年，微流控芯片技术由于其样品用量少、分析时间短、灵敏度高、廉价、轻便等特点，在化学、生物化学、医疗诊断等方面具有广泛的应用。本项目以微流控芯片内阵列样本的集成检测为目标，以微加工技术和表面化学修饰为手段，通过关键器件和关键技术的研究，实现微流控系统的阵列化检测。我们将生物传感技术与微流控技术相结合，通过芯片内的流动控制和阵列探测信号的激励与收集，实现样本的多参数阵列化检测。. 通过流道内微纳结构的构筑和表面化学修饰，完成芯片内的流动操控，实现芯片内流体样本的精确控制。通过负压调控和弹性模具热压的方法，制备形貌可控的聚合物微透镜阵列，并通过非平面光刻和剥离的方法，制备了光阑集成式聚合物微透镜阵列，用于阵列荧光样本的检测；通过湿法腐蚀和弹性模具热压，制备带有耦合棱镜的平板波导芯片，完成阵列探测信号的均匀激励，从而完成阵列探测点的荧光激励与检测。通过光刻、刻蚀和软光刻的技术，完成阵列芯片的制备与集成，并通过被测物抗体固定方法的研究，实现了阵列生物样本固定，从而完成了芯片内阵列样本的荧光检测。. 本项目针对微流控芯片和生物传感技术相结合的快速检测系统开展研究，旨在实现高灵敏度、阵列化微量样品的检测，推进微流控芯片在生物化学和疾病诊断等领域的实用化进程。研究过程中，我们在阵列芯片设计与制作方面取得了新的进展，为阵列芯片在医学诊断，药物合成与分析，细胞培养与操控等领域的应用奠定了良好的基础。