Drug Screening with Nano-Porous Silicon Optical Biosensors

描述（由申请人提供）：本跨学科项目旨在将生物医学工程方法引入药物滥用领域。提出的研究目标是开发一种生物传感方法来改善药物筛选诊断。纳米结构多孔硅（PSi）由于其低廉的制造成本、固有的光学和滤波特性以及与阵列和微流体技术的兼容性，是一种理想的生物传感材料。PSi的这些特性与目前的筛选技术相比具有优势，因为它具有在护理点（POC）进行简单高通量分析的潜力。PSi免疫传感器内结合靶的量与其折射率有关。折射率的变化是用光学阅读器监测的。长期目标是实现视觉颜色变化读数的临床医生在POC。第一个目标将集中于开发PSi的半定量筛选试验。竞争性结合试验将针对尿液中的阿片类药物作为概念证明。研究将分析与类似结构的阿片类药物的交叉反应性，并量化阴性尿液标本中不相关药物和干扰物的非特异性结合。PSi生物传感器的结果将与患者尿液样本中阿片类筛查的标准临床实验室结果进行比较。这项工作的第二个目标是将aim 1中制定的竞争性结合分析纳入生物活性水凝胶- psi传感器复合装置中，该装置可以开发用于未来的汗液贴片应用。水凝胶-传感器复合材料的原型设计将用于检测水溶液中的阿片类药物，以证明其药物筛选潜力的概念。PSi传感器的直接光学读出将减少当前汗斑的复杂和破坏性处理（提取），并允许POC筛选。在尿液分析和汗液贴片筛选等不同格式中使用PSi传感器突出了其作为药物生物传感方法的多功能性。除了PSi光学检测外，优化设计特征和分析分析结合特性将包括荧光显微镜，酶联免疫吸附测定升，扫描电子显微镜和紫外-可见光谱法。这里开发的方法可以扩展到检测许多其他小分子和药物类别。这项研究开发的新的药物筛选方法有可能在护理点使用，从而省去了将标本送出去进行实验室测试的成本和时间。最终，通过在特定的治疗时间向医生提供结果，这也将使患者受益。

DESCRIPTION (provided by applicant): This interdisciplinary project intends to bring a biomedical engineering approach to the field of drug abuse. The goals of the proposed research are to develop a biosensing methodology to improve drug screening diagnostics. Nano-structured porous silicon (PSi)is an ideal material for biosensing due to its inexpensive fabrication, intrinsic optical and filtering properties, and compatibility with array and microfluidic technologies. These properties of PSi offer advantages over current screening technologies by its potential for uncomplicated high-throughput analysis at point-of-care (POC). The amount of bound target within a PSi immunosensor is related to its refractive index. Changes in the refractive index are monitored using an optical reader. Long term goals are to achieve visual color change readout for clinicians at POC. The first aim will focus on developing a semi-quantitative screening assay in PSi. A competitive binding assay will target opiates in urine as a proof of concept. Studies will analyze assay cross-reactivity with opiates of similar structure and quantify non-specific binding from unrelated drugs and interferents present in negative urine specimens. Results from the PSi biosensor will be compared to standard clinical laboratory results for opiate screens in patient urine specimens. The second aim of the proposed work will incorporate the competitive binding assay worked out in Aim 1 into a bioactive hydrogel-PSi sensor composite device which can be developed into future sweat patch applications. The prototype design of the hydrogel-sensor composite will be used to detect opiates in aqueous solution for proof of concept of its drug screening potential. The direct optical readout of PSi sensors would reduce complicated and destructive processing (extraction) of current sweat patches and allow for POC screening. Using PSi sensors in such different formats as urinalysis and sweat patch screening highlights its versatility as a drug biosensing methodology. Optimization of design characteristics and analysis of assay binding properties in both aims will include fluorescent microscopy, Enzyme-Linked ImmunoSorbent Assay liters, scanning electron microscopy, and UV-vis spectrometry in addition to PSi optical detection. Methodologies developed here could be extended to detect many other small molecules and drug classes. 7 The new drug screening methods developed by this research have the potential to be used at point of care, bypassing the cost and time associated with sending specimens out for laboratory testing. Ultimately this would also benefit the patient by providing doctors with results at the specific time of treatment.