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: 8253139
• 负责人: Richard Chasen Spero
• 金额: $ 24.11万
• 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 2014-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8253139
• 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. PUBLIC HEALTH RELEVANCE: Rheomics is developing a coagulometer that will simultaneously measure clotting time, clot stiffness, and clot permeability in a high throughput, small volume format that is up to 60x faster than existing techniques. This system will advance scientific research into blood clot structure and function, enable large-population clinical research studies, and speed development of new pharmaceuticals.

描述（由申请人提供）：人群研究和药物研究需要对凝块刚度，渗透性进行高通量测量。 在20世纪后半段，美国最大的死亡原因是，仍然是一个血栓形成事件：心脏中的凝块， 大脑或肺。评估凝块质量对于研究，诊断和治疗疾病常规血液凝血测试至关重要，可以分为三个领域：凝结时间，机械稳定性和渗透性。 凝块刚度和渗透率与广泛的疾病相关，但是由于它们以高吞吐量筛选（HTS）格式不可用，因此测试的应用不足。这些测试的HTS系统将阐明疾病病因和血块异常的关系，使大量筛查以及新药的速度开发。我们预计，这些测量结果将有一天为接受治疗的患者提供卓越的临床监测，以修饰血栓性活动。 使用此阶段1 Shift Shift Sbir SBIR，流变学将对使用小珠的凝结进行三重分析。通过看到微粒（1-5 5M）被困在形成的凝块中，可以测量凝血时间。通过使用我们的专利磁力技术在微粒上拉扯微头，可以测量机械稳定性。使用PI/PD发明的新技术测量渗透性，其中使用阻碍的纳米颗粒扩散来通过应用有效的培养基理论来得出凝块的渗透性。 该阶段1 SBIR将测试HTS“三重分析”的可行性，该HTS将同时且自动测量凝块动力学，强度和渗透性。该阶段1 SBIR包括两个具体的目的：组装成像/磁化平台以执行测试并验证测试针对标准凝结仪。我们知道没有现有的系统（商业或其他系统）可以执行所有三个测量值，更不用说同时，自动或高吞吐量执行它们。在成功的过程中，风湿病三分析将提供刚度测定法，与现有技术不同，可以将其缩放到高吞吐量（例如，96孔托盘）格式，以及渗透性测定法，该测定速度更快，完全自动化和使用小样品量。 风湿病具有独特的位置，可以实现这些目标。我们的团队具有光学和磁系统开发，软体物理和技术商业化方面的专业知识，包括为商业化专利，开发和转让的关键人员，该技术在广泛采用的Coaguchek（R）系统背后，以及创立心血管诊断的成功人员，成功的IPO。 公共卫生相关性：风湿病正在开发一种凝结计，该凝结仪将同时测量高吞吐量，小体积格式的凝血时间，凝块刚度和凝块渗透性，比现有技术快60倍。该系统将推进对血块结构和功能的科学研究，使大型人口研究临床研究以及新药的速度开发。