Triple Analysis of Blood Clotting using Driven and Diffusing Microbeads

使用驱动和扩散微珠对血液凝固进行三重分析

• 批准号: 8513403
• 负责人: Richard Chasen Spero
• 金额: $ 23.99万
• 依托单位: REDBUD LABS, INC.
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-01 至 2015-05-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8513403
• 关键词: Adopted; Adoption; Animal Model; Area; Basic Science; Biological Assay; Blood; Blood Clot; Blood coagulation; Blood coagulation tests; Brain; Breathing; Cardiovascular system; Cause of Death; Chemicals; Childhood; Clinical; Clinical Research; Coagulation Process; Development; Diagnosis; Diagnostic; Diffuse; Diffusion; Disease; Electronics; Environment; Etiology; Event; Gel; Heart; Hematologist; Human Resources; Image; Kinetics; Legal patent; Lung; Magnetism; Market Research; Marketing; Measurement; Measures; Mechanics; Microscope; Microscopy; Microspheres; Normal Range; Optics; Pathologist; Patient Monitoring; Performance; Permeability; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Physics; Plasma; Population; Population Study; Positioning Attribute; Price; Protocols documentation; Qualifying; Research; Resolution; Sampling; Scientific Advances and Accomplishments; Small Business Innovation Research Grant; Speed; Structure; System; Systems Development; Techniques; Technology; Testing; Time; Work; base; commercialization; cost; design; drug discovery; high throughput screening; innovation; instrument; nanoparticle; novel; prototype; research study; success; theories

DESCRIPTION (provided by applicant): Population studies and drug research require a high-throughput measurement of clot stiffness, permeability. The single largest cause of death in the US over the latter half of the 20 century was and still is a thrombotic event: a clot in the heart, brain, or lungs. Assessing clot quality is essential for studying, diagnosing, and treating disease Conventional blood coagulation tests can be grouped into three areas: clotting time, mechanical stability, and permeability. Clot stiffness and permeability are correlated with a broad range of diseases, but because they are not available in high throughput screening (HTS) format, the tests are under-applied. An HTS system for these tests would illuminate the relationship of disease etiology and abnormalities of blood clots, enable large- population screens, and speed development of new pharmaceuticals. We anticipate that these measurements will one day provide superior clinical monitoring for patients receiving treatment that modifies thrombotic activity. With this Phase 1 SHIFT SBIR Rheomics will develop a triple-analysis of clotting that uses small beads. Clotting time is measured by seeing microbeads (1-5 5m) become trapped in a forming clot. Mechanical Stability is measured by tugging on microbeads using our patented magnetic force technology. Permeability is measured using a novel technique invented by the PI/PD, in which hindered diffusion of nanoparticles is used to derive the clot's permeability by applying the effective medium theory. This Phase 1 SBIR will test the feasibility of an HTS "triple-analysis" that will simultaneously and automatically measure clot kinetics, strength, and permeability. This Phase 1 SBIR comprises two specific aims: assembling an imaging/magnetics platform to perform the tests, and validating the tests against standard coagulometers. We are aware of no existing system (commercial or otherwise) that can perform all three measurements, let alone perform them simultaneously, automatically, or in high throughput. In success, the Rheomics triple-analysis will deliver a stiffness assay that, unlike existing techniques, can be scaled to high throughput (eg, 96-well tray) format, and a permeability assay that is up to 60x faster, fully automated, and uses small sample volumes. Rheomics is uniquely positioned to deliver on these aims. Our team features an intersection of expertise in optical and magnetic systems development, soft-matter physics, and technology commercialization, including key personnel who patented, developed, and transferred for commercialization the technology behind the widely adopted CoaguChek(R) System, and who founded Cardiovascular Diagnostics, a successful IPO.

描述（由申请人提供）：人群研究和药物研究需要对凝块硬度、渗透性进行高通量测量。 20 世纪后半叶美国最大的单一死因过去是、现在仍然是血栓事件：心脏中的血栓、 大脑，或者肺。评估凝块质量对于研究、诊断和治疗疾病至关重要传统的凝血测试可分为三个领域：凝血时间、机械稳定性和渗透性。 凝块硬度和渗透性与多种疾病相关，但由于它们无法以高通量筛选 (HTS) 形式提供，因此这些测试并未得到充分应用。用于这些测试的 HTS 系统将阐明疾病病因和血栓异常之间的关系，实现大规模筛查，并加速新药物的开发。我们预计这些测量有一天将为接受改变血栓活动治疗的患者提供卓越的临床监测。 通过这一第一阶段的转变，SBIR Rheomics 将开发一种使用小珠子的凝血三重分析方法。凝血时间是通过观察微珠 (1-5 5m) 被困在正在形成的凝块中来测量的。机械稳定性是通过使用我们的专利磁力技术拉动微珠来测量的。渗透性是使用 PI/PD 发明的新技术进行测量的，其中通过应用有效介质理论，利用纳米粒子的受阻扩散来推导凝块的渗透性。 第一阶段 SBIR 将测试 HTS“三重分析”的可行性，该分析将同时自动测量凝块动力学、强度和渗透性。第一阶段 SBIR 包括两个具体目标：组装成像/磁学平台来执行测试，并根据标准凝血计验证测试。我们知道没有任何现有系统（商业或其他）可以执行所有这三种测量，更不用说同时、自动或高吞吐量地执行它们。如果成功，流变组学三重分析将提供一种刚度测定，与现有技术不同，该测定可以扩展到高通量（例如 96 孔托盘）格式，以及一种速度高达 60 倍、完全自动化且使用小样本量的渗透性测定。 流变学在实现这些目标方面具有独特的优势。我们的团队拥有光学和磁系统开发、软物质物理和技术商业化方面的专业知识，其中包括为广泛采用的 CoaguChek(R) 系统背后的技术申请专利、开发和商业化转让的关键人员，以及创建 Cardioangio Diagnostics（并成功首次公开募股）的关键人员。