Drug Screening with Nano-Porous Silicon Optical Biosensors

描述（由申请人提供）：这个跨学科的项目旨在将生物医学工程方法引入药物滥用领域。拟议的研究的目标是开发一种生物传感方法，以提高药物筛选诊断。纳米结构多孔硅（PSi）由于其廉价的制造、固有的光学和过滤特性以及与阵列和微流体技术的兼容性而成为生物传感的理想材料。PSi的这些性质通过其在护理点（POC）进行简单的高通量分析的潜力提供了优于当前筛选技术的优势。PSi免疫传感器内结合靶标的量与其折射率有关。使用光学读取器监测折射率的变化。长期目标是为POC的临床医生实现视觉颜色变化读数。第一个目标将集中于开发PSi中的半定量筛选测定。竞争性结合试验将靶向尿液中的阿片类药物作为概念验证。研究将分析与类似结构的阿片类药物的检测交叉反应性，并量化阴性尿液标本中存在的不相关药物和干扰物的非特异性结合。来自PSi生物传感器的结果将与患者尿液标本中阿片类药物筛查的标准临床实验室结果进行比较。所提出的工作的第二个目的将把目标1中制定的竞争性结合测定纳入生物活性水凝胶-PSi传感器复合装置中，该复合装置可以开发成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液块的复杂和破坏性处理（提取），并允许POC筛查。使用PSi传感器以不同的形式，如尿液分析和汗液斑筛查，突出了其作为药物生物传感方法的多功能性。在这两个目标中，设计特征的优化和测定结合特性的分析将包括荧光显微镜、酶联免疫吸附测定液、扫描电子显微镜和紫外可见光谱法以及PSi光学检测。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。7本研究开发的新药物筛选方法有可能用于护理点，绕过与发送样本进行实验室检测相关的成本和时间。最终，这也将通过在特定的治疗时间为医生提供结果而使患者受益。

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.