An Integrated Microarray Printing and Detection System

集成微阵列打印和检测系统

• 批准号: 9447968
• 负责人: Nguyen Ly
• 金额: $ 60万
• 依托单位: BIOSENSING INSTRUMENT, INC.
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-04-15 至 2020-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9447968
• 关键词: Address; Affinity; Arizona; Automation; B-Lymphocytes; Binding; Binding Proteins; Biological Assay; Biological Markers; Biosensing Techniques; Biosensor; Cell Line; Cells; Data; Detection; Development; Devices; Dissociation; Drops; Feedback; Institutes; Kinetics; Label; Lead; Liquid substance; Measures; Membrane Proteins; Methods; Microarray Analysis; Mind; Modeling; Molecular Analysis; Pathway interactions; Performance; Pharmaceutical Preparations; Phase; Printing; Protein Analysis; Protein Microchips; Proteins; Proteomics; Reaction; Receptors, Antigen, B-Cell; Research; Resolution; Sampling; Spottings; Surface Plasmon Resonance; System; Technology; Testing; Therapeutic; Time; Universities; Validation; base; commercialization; density; design; diagnostic biomarker; flexibility; high throughput analysis; high throughput technology; imaging system; innovation; instrument; molecular diagnostics; nanoDroplet; nanolitre; novel; novel therapeutics; prototype; public health relevance; success; tool

 DESCRIPTION (provided by applicant): Microarray technology has dramatically advanced the study of protein interactions leading to discovery and validation of new biomarkers and therapeutic drugs. Typically, protein microarrays are pre-spotted with target molecules in one device and then tested with probe molecules using another device. During each testing cycle, the entire microarray becomes exposed to the probe molecules. Though this approach has been shown to be effective for some applications, it inherently suffers from several key limitations that hinder it from gaining broader utility: 1) both the printing and analysis steps consume large sample volumes, which is particularly problematic where only small amounts of proteins are available or affordable; 2) the exposure of sample solution to the entire microarray restricts the kinetic interaction analysis of only one probe to N targets (1XN interactions only), significantly limiting the types of applications and analytical power of microarrays; and 3) complete microarrays must be pre-printed blindly with no feedback on spot uniformity, target activity, or probe selectivity which may lead to inconclusive data, unnecessary tests, and delays in obtaining effective results. We propose an Integrated Microarray Printing and Detection System (IMPDS) to address the key limitations restricting the analytical power and broader appeal of microarray technology. IMPDS will have the ability to incorporate feedback of microarray formation and testing in order to generate more relevant results sooner, perform high resolution droplet-based testing with ultra-low nanoliter volume samples, conduct a more versatile M x N (many-to-many) protein kinetic interaction analysis of high density microarrays, and measure molecular interactions and binding kinetics in cell-based microarrays. IMPDS relies upon the careful integration of two core technologies into a single instrument: 1) a novel ultra-low volume piezoelectric liquid dispensing system and 2) a proprietary, high-resolution, distortion-free surface plasmon resonance imaging (DF-SPRi) system. The success of this project will lead to a new commercializable microarray technology capable of: 1) streamlining microarray spotting and detection into a single instrument for simpler, faster, more accurate results, 2) ultra-low volume nanodroplet-based analysis of high density microarrays, 3) flexible and multiplexed M x N label-free protein interaction kinetic analyses in real time, 4) cell-based microarray analyses with single cell resolution. This project will bring together strengths from Biosensing Instrument Inc. (BI) an innovator and global supplier of high-performance SPR instruments, and from the Center for Bioelectronics and Biosensors, the Biodesign Institute at Arizona State University (ASU), inventors of the piezoelectric liquid dispensing technology. Together we will develop IMPDS into a powerful tool for commercial use in high-throughput protein interaction studies leading to the discovery and validation of new molecular diagnostic biomarkers and new therapeutic drugs.

 描述（由申请人提供）：微阵列技术极大地推进了蛋白质相互作用的研究，从而促进了新生物标志物和治疗药物的发现和验证。通常，蛋白质微阵列在一个装置中预先点样目标分子，然后使用探针分子进行测试。在每个测试周期中，整个微阵列都会暴露在探针分子中，尽管这种方法已被证明对某些应用有效，但它本质上存在几个阻碍其获得更广泛用途的关键限制：1）打印和分析步骤消耗大量样品，这在只有少量蛋白质可用或负担得起的情况下尤其成问题2)样品溶液暴露于整个微阵列限制了仅一个探针对N个靶标的动力学相互作用分析（1XN相互作用）；仅），显着限制了微阵列的应用类型和分析能力；3）完整的微阵列必须盲目预印，没有关于斑点均匀性、目标活性或探针选择性的反馈，这可能导致不确定的数据，不必要的我们提出了一种集成微阵列打印和检测系统（IMPDS），以解决限制微阵列技术分析能力和更广泛吸引力的关键限制，IMPDS 将能够整合微阵列形成和测试的反馈。为了更快地生成更多相关结果，使用超低纳升体积样品进行高分辨率液滴测试，进行更通用的高密度 M x N（多对多）蛋白质动力学相互作用分析微阵列，并测量基于细胞的 IMPDS 中的分子相互作用和结合动力学，依赖于将两项核心技术仔细集成到单个仪器中：1）新型超低容量压电液体分配系统和 2）专有的高通量。该项目的成功将带来一种新的可商业化的微阵列技术，该技术能够：1）简化微阵列点样和分析。在一台仪器中进行检测，以获得更简单、更快、更准确的结果，2) 基于超低体积纳米液滴的高密度微阵列分析，3) 灵活且多重的 M x N 无标记蛋白质相互作用动力学实时分析，4)该项目将汇集高性能 SPR 仪器的创新者和全球供应商 Biosensing Instrument Inc. (BI) 以及生物电子学中心和Biosensors 是亚利桑那州立大学 (ASU) 的生物设计研究所，压电液体分配技术的发明者，我们将共同将 IMPDS 开发成一种强大的工具，用于高通量蛋白质相互作用研究的商业用途，从而发现和验证新的分子诊断。生物标志物和新的治疗药物。