Drug Screening with Nano-Porous Silicon Optical Biosensors

使用纳米多孔硅光学生物传感器进行药物筛选

• 批准号: 7877730
• 负责人: Lisa Bonanno
• 金额: $ 1.21万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-06 至 2010-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7877730
• 关键词: Antibodies; Area; Behavior; Binding; Biological Assay; Biomedical Engineering; Biosensing Techniques; Biosensor; Bypass; Characteristics; Chemicals; Chemistry; Clinical; Collaborations; Collection; Color; Competitive Binding; Dermal; Detection; Development; Devices; Diagnostic; Drug Controls; Drug Formulations; Drug abuse; Encapsulated; Engineering; Enzyme-Linked Immunosorbent Assay; Enzymes; Forensic Medicine; Foundations; Future; Gas Chromatography; Goals; Human; Hydrogels; Immobilization; Immunoassay; Interdisciplinary Study; Label; Laboratories; Light; Link; Liquid substance; Medical; Medicine; Membrane; Methodology; Methods; Microfluidics; Microscopy; Modeling; Monitor; Nanostructures; Opiates; Optical Readers; Optics; Pathology; Patients; Performance; Pharmaceutical Preparations; Pharmacology; Polymers; Preclinical Drug Evaluation; Process; Property; Refractive Indices; Reporter; Research; Sampling; Scanning Electron Microscopy; Science; Screening procedure; Silicon; Solutions; Specific qualifier value; Specificity; Specimen; Spectrometry; Structure; Substance Abuse Detection; Surface; Sweat; Sweating; Swelling; System; Techniques; Technology; Testing; Time; United States Substance Abuse and Mental Health Services Administration; Universities; Urinalysis; Urine; Visual; Water; Work; addiction; aqueous; base; cost; cross reactivity; design; high throughput analysis; high throughput screening; improved; innovative technologies; nano; nanostructured; novel; point of care; polyacrylamide hydrogels; porous hydrogel; prototype; response; sensor; small molecule; technology development

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.

描述(由申请者提供)：这个跨学科项目旨在将生物医学工程方法引入药物滥用领域。这项拟议研究的目标是开发一种生物传感方法来改进药物筛选诊断。纳米结构多孔硅(PSI)由于其廉价的制备、固有的光学和过滤特性以及与阵列和微流控技术的兼容性，是一种理想的生物传感材料。PSI的这些特性提供了优于当前筛查技术的优势，因为它具有在护理点(POC)进行简单的高通量分析的潜力。PSI免疫传感器中结合靶点的数量与其折射率有关。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。第一个目标将专注于发展一种PSI的半定量筛选试验。竞争性结合分析将以尿液中的阿片类药物为目标，作为概念的证明。研究将分析与结构相似的阿片类药物的检测交叉反应，并量化存在于阴性尿样中的无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样中阿片类药物筛查的标准临床实验室结果进行比较。拟议工作的第二个目标是将目标1中设计的竞争性结合分析纳入生物活性水凝胶-PSI传感器复合设备，该设备可开发用于未来的汗片应用。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数将减少对当前汗斑的复杂和破坏性处理(提取)，并允许POC筛查。使用不同格式的PSI传感器，如尿液分析和汗片筛查，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，设计特征的优化和检测结合特性的分析将包括荧光显微镜、酶联免疫吸附分析试剂盒、扫描电子显微镜和UV-Vis光谱，此外还包括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这项研究开发的新药物筛选方法有可能在护理点使用，绕过了将样本送往实验室进行检测的成本和时间。最终，这也将使患者受益，因为它会在特定的治疗时间向医生提供结果。