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（由适用提供）：微阵列技术对蛋白质相互作用的研究大大提高了，从而导致发现和验证新的生物标志物和治疗药物。通常，蛋白质微阵列在一个设备中用靶分子预先发现，然后使用探针分子使用另一种设备进行测试。在每个测试周期中，整个微阵列都会暴露于探针分子。尽管已证明这种方法对某些应用有效，但它固有地遭受了几个关键局限性，阻碍了它获得更广泛的效用：1）印刷和分析步骤都消耗了大量样品量，这尤其有问题，只有少量蛋白质可用或负担得起； 2）样品解决方案对整个微阵列的暴露限制了一个探针的动力学相互作用分析（仅1倍相互作用），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象，而没有对现场均匀性，目标活动或探针选择性的反馈，这可能会导致不确定的数据，不必要的测试以及获得有效结果的延迟。我们提出了一个集成的微阵列打印和检测系统（IMPDS），以解决限制微阵列技术的分析能力和更广泛外观的关键限制。 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. IMPD依靠将两种核心技术仔细整合到单个仪器中：1）一种新型的超低体积压电液体分配系统和2）专有的，高分辨率的，无失真的表面等离子体共振成像（DF-SPRI）。该项目的成功将导致一项新的可商业化的微阵列技术：1）将微阵列的发现和检测简化为单个仪器，以更简单，更快，更准确的结果，2）基于高密度微阵列的超低体积纳米光谱分析，3）柔性和多重蛋白质的固定元素分析，以实现MID-nabe cell intection KINALIN-4）。 解决。该项目将汇集生物传感器Inc.（BI）的优势（BI）注入和全球高性能SPR仪器的供应商，以及来自亚利桑那州立大学（ASU）生物启动研究所（ASU）的生物电子和生物传感器中心，Pileelectric液体分配技术的发明家。我们将共同将IMPDS开发为一种在高通量蛋白相互作用研究中的商业用途的强大工具，从而导致发现和验证新的分子诊断生物标志物和新的治疗药物。