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: 7674144
• 负责人: Lisa Bonanno
• 金额: $ 4.12万
• 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 2011-05-05
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7674144
• 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（由申请人提供）：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。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) 因其制造成本低廉、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 的这些特性比当前的筛选技术更具优势，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标的量与其折射率相关。使用光学读取器监测折射率的变化。长期目标是为临床医生在 POC 中实现视觉颜色变化读数。第一个目标将集中于开发 PSi 的半定量筛选方法。竞争性结合测定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，并量化阴性尿液样本中存在的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，该装置可开发为未来的汗贴应用。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且破坏性的处理（提取），并允许进行 POC 筛查。在尿液分析和汗斑筛查等不同形式中使用 PSi 传感器凸显了其作为药物生物传感方法的多功能性。除了 PSi 光学检测之外，设计特征的优化和分析结合特性的分析还将包括荧光显微镜、酶联免疫吸附分析升、扫描电子显微镜和紫外-可见光谱测定。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在护理点使用，从而避免了将样本送去实验室检测所需的成本和时间。最终，通过向医生提供特定治疗时间的结果，患者也将受益。