Triple Analysis of Blood Clotting using Driven and Diffusing Microbeads

描述(由申请人提供)：人口研究和药物研究需要高通量测量凝块硬度和通透性。20世纪后半叶，美国最大的死因是血栓形成：心脏血栓， 大脑，或肺。评估凝血质量对于研究、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、机械稳定性和通透性。凝块硬度和通透性与一系列疾病相关，但由于它们不适用于高通量筛查(HTS)形式，这些测试没有得到充分应用。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，使大规模人群筛查成为可能，并加快新药的开发。我们预计，这些测量有朝一日将为接受改变血栓活性的治疗的患者提供更好的临床监测。有了这一第一阶段的转变，SBIR莱茵将开发出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米)被困在形成的凝块中来衡量的。机械稳定性是通过使用我们的专利磁力技术拖拽微珠来测量的。渗透率的测量是使用PI/PD发明的一种新技术，其中利用纳米颗粒的受阻扩散来通过应用有效介质理论来推导凝块的渗透率。这一阶段的SBIR将测试高温超导“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：组装一个成像/磁性平台来执行测试，并根据标准凝固仪验证测试。我们不知道现有的系统(商业的或其他的)可以执行所有三个测量，更不用说同时、自动或高吞吐量地执行它们了。在Success中，莱茵三重分析将提供一种硬度分析，与现有技术不同，它可以扩展到高通量(例如，96孔托盘)格式，以及一种渗透性分析，速度高达60倍，完全自动化，并且使用小样本量。莱茵集团在实现这些目标方面处于独特的地位。我们的团队拥有在光学和磁性系统开发、软物质物理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、开发并将其商业化的关键人员，以及成功首次公开募股(IPO)的心血管诊断公司的创始人。 与公共健康相关：Rheonics正在开发一种凝血仪，它将以高通量、小体积的形式同时测量凝血时间、凝块硬度和凝块渗透性，速度比现有技术快60倍。该系统将推进对血栓结构和功能的科学研究，使大规模临床研究成为可能，并加快新药的开发。

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.