Ultrasensitive, Label-free Silicon Nanowire Biosensing Arrays

超灵敏、无标记硅纳米线生物传感阵列

• 批准号: 7670539
• 负责人: SEASON S-S WONG
• 金额: $ 20万
• 依托单位: LYNNTECH, INC.
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-02-15 至 2010-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7670539
• 关键词: Address; Affinity; Antibiotic Resistance; Antibodies; Arts; Binding; Biological; Biological Assay; Biological Markers; Biosensing Techniques; Biosensor; Cancer Diagnostics; Cells; Chemistry; Communicable Diseases; Community Health; Complex; Computer software; DNA; Defect; Detection; Diagnostic; Disease; Electric Conductivity; Electrodes; Electronics; Equipment; Evaluation; Exhibits; Food; Food Contamination; Future; Genomics; Goals; Government; Immobilization; Individual; Industry; Investments; Ions; Label; Laboratories; Lasers; Location; Measurement; Measures; Medical; Methods; Modification; Molecular Conformation; Nanostructures; Nucleic Acid Binding; Nucleic Acid Probes; Nucleic Acids; Peptide Nucleic Acids; Persons; Phase; Plastics; Positioning Attribute; Procedures; Process; Production; Property; Protein Isoforms; Proteins; Radioisotopes; Reaction; Reproducibility; Research; Resistance; Sampling; Silicon; Silicon Dioxide; Single-Stranded DNA; Small Business Innovation Research Grant; Solutions; Specialist; Specificity; Surface; System; Techniques; Time; Toxin; Training; Transistors; United States National Institutes of Health; Water; Width; Work; aptamer; base; commercialization; computerized data processing; cost; cross reactivity; data acquisition; density; fluorophore; interest; microorganism; nanoimprint lithography; nanoimprinting; nanoscale; nanowire; novel; nucleic acid detection; oncology; pandemic influenza; pathogen; public health relevance; safety testing; self assembly; sensor; success

DESCRIPTION (provided by applicant): This NIH Phase I SBIR proposal aims to develop and commercialize a silicon nanowire (SiNW) sensor platform for multiplexed, label-free, biosensing applications. This single platform will provide ultrasensitive, highly specific real-time detection of a wide range of biological species by using addressable NW arrays functionalized with peptide nucleic acid (PNA) or nucleic acid aptamer capture probes. It will provide inexpensive electronic biodetection, whereas current state-of-the-art detection of biological analytes requires expensive laboratory-based equipment and highly trained specialists. In these sensors, the SiNWs act as the gate electrode in a field-effect transistor (FET) configuration and the PNA probes (genomic target) hybridize and capture complementary single-stranded DNA. The aptamer probes are generated by a selective process and immobilized, where they capture other targeted agents (e.g. proteins, toxins, cells) from solution. Captured agents at the SiNW surface generate a change in SiNW electrical conductance, allowing multiplexed detection and analysis using standard signal processing. The tunable conducting properties of semiconducting NWs combined with the ability to bind analytes on their surface makes SiNWs particularly attractive for cheap, sensitive electronic biosensor applications, and they have shown repeated success. Complementary PNA binds to DNA with great affinity and specificity, and aptamers exhibit high target affinity and exceptional specificity, allowing for detection of multiple analytes in the same reaction chamber. This exceptional binding precision enables more complete sample analyses and benefits diagnostics in, for example, oncology (protein and DNA biomarkers) and food contamination (pathogen cells and toxigenic products). PNA and aptamer immobilization chemistry is well-established, and silica (and thus SiNW) substrates are ideal for surface modification. Multiple SiNW arrays (integrated into the same circuit) will be functionalized with multiple PNA/aptamer probes, and each array will be individually addressable in hardware/software, making captured analytes easily identifiable through their matching address. Most SiNW studies have been based on a combination of "bottom-up" and "top-down" processes and have difficulties with integration, requiring delicate transfer and positioning of individual nanostructures. Other difficulties include controlling NW doping and contact resistance. This proposal will use a nanoimprint lithography (NIL) fabrication method for integrating biosensors into high-density Si circuits that excludes transporting, aligning and wiring individual SiNWs and overcomes the doping and contact resistance issues, decreasing manufacturing costs and increasing commercialization potential. Our goal in this Phase I proposal is to demonstrate the possibility of fabricating ultrasensitive, real-time, label-free, nanoscale sensors that can be economically produced and easily integrated with off-the-shelf signal processing components. We anticipate substantial commercialization opportunities and return on investment. PUBLIC HEALTH RELEVANCE: Successful commercialization of this SiNW biosensor array will allow the medical and health community to offer high-quality disease and cancer diagnostics that provide cheaper, faster and more sensitive results than all current standards. It will help guard against the spread of infectious diseases (e.g., pandemic flu), can be deployed to perform food and water safety testing, and can help arrest the propagation of antibiotic-resistant microorganisms.

描述（由申请人提供）：该NIH第I阶段SBIR提案旨在开发和商业化硅纳米线（SiNW）传感器平台，用于多路复用、无标记、生物传感应用。该单一平台将通过使用用肽核酸（PNA）或核酸适体捕获探针功能化的可寻址NW阵列来提供对广泛的生物物种的超灵敏、高度特异性的实时检测。它将提供廉价的电子生物检测，而目前最先进的生物分析物检测需要昂贵的实验室设备和训练有素的专家。在这些传感器中，SiNW作为场效应晶体管（FET）配置中的栅电极，PNA探针（基因组靶标）杂交并捕获互补的单链DNA。适体探针通过选择性过程产生并固定，其中它们从溶液中捕获其他靶向试剂（例如蛋白质、毒素、细胞）。在SiNW表面捕获的试剂产生SiNW电导的变化，允许使用标准信号处理进行多路检测和分析。半导体纳米线的可调导电特性与其表面上结合分析物的能力相结合，使得硅纳米线对于廉价、灵敏的电子生物传感器应用特别有吸引力，并且它们已经显示出反复的成功。互补PNA以极大的亲和力和特异性与DNA结合，并且适体表现出高靶标亲和力和优异的特异性，允许在同一反应室中检测多种分析物。这种卓越的结合精度能够实现更完整的样品分析，并有利于肿瘤学（蛋白质和DNA生物标志物）和食品污染（病原体细胞和致癌产物）等领域的诊断。PNA和适体固定化化学是公认的，并且二氧化硅（并且因此SiNW）基底对于表面改性是理想的。多个SiNW阵列（集成到同一电路中）将用多个PNA/适体探针功能化，并且每个阵列将在硬件/软件中单独寻址，使得捕获的分析物通过其匹配地址容易地识别。大多数硅纳米线研究都是基于“自下而上”和“自上而下”工艺的组合，并且难以集成，需要精细转移和定位单个纳米结构。其他困难包括控制NW掺杂和接触电阻。该提案将使用纳米压印光刻（NIL）制造方法将生物传感器集成到高密度Si电路中，该方法排除了单个SiNW的传输，对齐和布线，并克服了掺杂和接触电阻问题，降低了制造成本并增加了商业化潜力。我们在第一阶段提案中的目标是证明制造超灵敏，实时，无标签，纳米级传感器的可能性，这些传感器可以经济地生产，并且易于与现成的信号处理组件集成。我们期待着巨大的商业化机会和投资回报。公共卫生关系：这种SiNW生物传感器阵列的成功商业化将使医疗和健康界能够提供高质量的疾病和癌症诊断，提供比所有现有标准更便宜，更快和更灵敏的结果。它将有助于防止传染病的传播（例如，大流行性流感），可用于执行食品和水安全测试，并可帮助阻止抗药性微生物的繁殖。