Triple Analysis of Blood Clotting using Driven and Diffusing Microbeads

描述（由申请人提供）：人群研究和药物研究需要高通量测量凝块硬度、渗透性。 世纪后半叶，美国最大的单一死因是血栓形成：心脏中的凝块， 大脑或肺评估凝块质量对于研究、诊断和治疗疾病至关重要。常规的凝血试验可分为三个方面：凝血时间、机械稳定性和渗透性。 凝块硬度和渗透性与广泛的疾病相关，但由于它们不适用于高通量筛选（HTS）格式，因此这些测试应用不足。用于这些测试的HTS系统将阐明疾病病因和血凝块异常的关系，使大规模人群筛查成为可能，并加速新药的开发。我们预期这些测量有一天将为接受改变血栓活性的治疗的患者提供上级临床监测。 在第一阶段，SBIR Rheomics将开发一种使用小珠的凝血三重分析。凝血时间是通过观察微珠（1-5 5 m）被困在形成的凝块中来测量的。机械稳定性通过使用我们的专利磁力技术牵引微珠来测量。使用PI/PD发明的新技术测量渗透性，其中通过应用有效介质理论，使用纳米颗粒的受阻扩散来推导凝块的渗透性。 该第1阶段SBIR将测试HTS“三重分析”的可行性，该“三重分析”将同时自动测量凝块动力学、强度和渗透性。第1阶段SBIR包括两个具体目标：组装成像/磁性平台以执行测试，并根据标准凝血仪验证测试。我们知道没有现有的系统（商业或其他）可以执行所有三个测量，更不用说同时执行，自动或高通量。在成功的情况下，Rheomics三重分析将提供刚度测定，与现有技术不同，可以扩展到高通量（例如，96孔托盘）格式，以及渗透性测定，速度高达60倍，全自动化，并使用小样品体积。 Rheomics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性系统开发、软物质物理学和技术商业化方面的专业知识，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，以及成功IPO的心血管诊断公司的创始人。

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.