Point of care nanotechnology for early blood clot detection and characterisation in disease screening, theranostic and self monitoring applications

用于疾病筛查、治疗诊断和自我监测应用中早期血凝块检测和表征的护理点纳米技术

基本信息

  • 批准号:
    EP/G061882/1
  • 负责人:
  • 金额:
    $ 115.51万
  • 依托单位:
  • 依托单位国家:
    英国
  • 项目类别:
    Research Grant
  • 财政年份:
    2009
  • 资助国家:
    英国
  • 起止时间:
    2009 至 无数据
  • 项目状态:
    已结题

项目摘要

Thromboembolic disease and associated blood coagulation abnormalities cause significant morbidity and mortality in Western society, with stroke being the third leading cause of death in the UK. The incidence of stroke increases markedly with age and is often higher in socially deprived areas. In stroke, the processes of endothelial and vascular damage, activation of the coagulation cascade and decreased fibrinolysis result in abnormal clots, often with excessively cross-linked fibrin networks. An unsatisfactory aspect of work in this area is that the microstructures of such clots are usually reported in only adjectival terms (e.g., dense or tight ) - usually on the basis of a visual inspection of fragments of dessicated clots in SEM micrographs. Early detection of clots is vital. Early clotting events may contribute to a pro-thrombotic state which exacerbates the disease state and thrombotic states can be followed rapidly by haemorrhagic states due to adverse changes in clot structure. The available therapeutic options informed by early detection and characterisation are greatly enhanced.New technology is essential to address shortcomings in this area. This project will exploit our recent advances in blood clot detection and ultra-sensitive nanomaterials development for device applications to overcome these shortcomings. Under a Royal Society Brian Mercer Award and an EPSRC Portfolio Partnership Award, in collaboration with the NHS, we have developed a new haemorheological technique for the early detection and characterisation of blood clots. This has led to the discovery that the incipient clot's fractal microstructure is a biomarker for the conditions of clot formation, including therapeutic intervention. The significance of this discovery stems from the incipient clot's role as the microstructural template for ensuing clot development. In parallel work we have demonstrated the controlled reproducible growth of vertical arrays of ZnO nanowires and have confirmed their electrical current generation capabilities. Our Grand Challenge proposal involves combining this nanotechnology with our haemorheological work to develop the first point of care (POC) device capable of the early detection and characterisation of abnormal clots. By a point of care device we refer to technology suitable for widespread use outside hospitals (i.e., within pharmacies and surgeries) and which will ultimately be developed for use by patients at home. This will exploit the piezoelectric properties of ZnO nanowire arrays as a transducer to detect shear wave propagation within coagulating blood. Our aim is to drastically improve the sensitivity of early clot detection for more accurate assessments of (i) coagulation abnormalities and (ii) therapeutic targeting of abnormal clots at the earliest stage of development. The project involves in vivo and in vitro disease model (Stroke) work at University of London, and work intended to enable our device to perform a therapeutic function. In this way we propose to lay the foundations for a POC system for Patient Self Assessment and Patient Self Management in anticoagulant applications, in addition to a new technological basis for thromboembolic disease screening. The project also includes anticoagulated Stroke patient volunteers at Morriston NHS Hospital.We have a highly multidisciplinary Team with internationally leading expertise in rheometry and haemorheology; nanotechnology, nanomaterials and nanofabrication; nanomedicine and drug delivery; and human-device interaction aspects of medical instrument design. We have two partners. The first is the NHS who will provide clinical facilities and governance of clinical research. Our second partner is Boots Centre for Innovation (BCI) whose involvement anticipates healthcare provision involving POC applications in next-generation pharmacies. BCI's role is to inform design relating to customer needs/experience, the POC market and environment.
血栓栓塞性疾病和相关的凝血异常在西方社会引起显著的发病率和死亡率,其中中风是英国的第三大死亡原因。中风的发病率随着年龄的增长而明显增加,在社会贫困地区往往更高。在中风中,内皮和血管损伤、凝血级联激活和纤维蛋白溶解减少的过程导致异常凝块,通常具有过度交联的纤维蛋白网络。在这一领域的工作的一个不令人满意的方面是,这种凝块的微观结构通常仅以形容词的形式报道(例如,致密或紧密)-通常基于SEM显微照片中干燥凝块碎片的目视检查。早期发现血栓至关重要。早期凝血事件可能导致血栓形成前状态,这会加重疾病状态,并且血栓形成状态之后可能由于凝块结构的不良变化而迅速出现出血状态。通过早期检测和表征提供的可用治疗选择大大增强。新技术对于解决这一领域的缺陷至关重要。该项目将利用我们最近在血凝块检测和超敏感纳米材料开发方面的进展,以克服这些缺点。根据皇家学会布赖恩美世奖和EPSRC组合合作奖,与NHS合作,我们开发了一种新的血液流变学技术,用于早期检测和表征血栓。这导致发现,初始凝块的分形微结构是凝块形成条件的生物标志物,包括治疗干预。这一发现的重要性源于早期凝块作为随后凝块发展的微观结构模板的作用。在平行的工作中,我们已经证明了可控的可重复生长的垂直阵列的ZnO纳米线,并确认其电流产生能力。我们的大挑战提案涉及将这种纳米技术与我们的血液流变学工作相结合,以开发能够早期检测和表征异常凝块的第一个护理点(POC)设备。通过护理点设备,我们指的是适合在医院外广泛使用的技术(即,在药房和外科手术中),并且最终将被开发用于患者在家中使用。这将利用ZnO纳米线阵列的压电特性作为换能器来检测血液中的剪切波传播。我们的目标是大幅提高早期血凝块检测的灵敏度,以便更准确地评估(i)凝血异常和(ii)在发育的最早阶段对异常血凝块进行治疗靶向。该项目涉及伦敦大学的体内和体外疾病模型(中风)工作,以及旨在使我们的设备能够执行治疗功能的工作。通过这种方式,我们建议为抗凝应用中的患者自我评估和患者自我管理的POC系统奠定基础,此外还为血栓栓塞性疾病筛查提供了新的技术基础。该项目还包括Morriston NHS医院的抗凝中风患者志愿者。我们拥有一支高度多学科的团队,在流变学和血液流变学;纳米技术,纳米材料和纳米纤维;纳米医学和药物输送;以及医疗器械设计的人-设备交互方面具有国际领先的专业知识。我们有两个合作伙伴。第一个是NHS,它将提供临床设施和临床研究的管理。我们的第二个合作伙伴是Boots创新中心(BCI),该中心的参与预计将在下一代药店中提供涉及POC应用的医疗保健服务。BCI的作用是为与客户需求/体验、POC市场和环境相关的设计提供信息。

项目成果

期刊论文数量(10)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
An Electric-Field Responsive Microsystem for Controllable Miniaturised Drug Delivery Applications
用于可控小型药物输送应用的电场响应微系统
  • DOI:
    10.1016/j.proeng.2011.12.242
  • 发表时间:
    2011
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Liu Y
  • 通讯作者:
    Liu Y
Fractal analysis of viscoelastic data with automated gel point location and its potential application in the investigation of therapeutically modified blood coagulation
通过自动凝胶点定位对粘弹性数据进行分形分析及其在治疗改良凝血研究中的潜在应用
  • DOI:
    10.1007/s00397-010-0472-7
  • 发表时间:
    2010
  • 期刊:
  • 影响因子:
    2.3
  • 作者:
    Evans P
  • 通讯作者:
    Evans P
The development of rheometry for strain-sensitive gelling systems and its application in a study of fibrin-thrombin gel formation
应变敏感凝胶体系流变测定法的发展及其在纤维蛋白-凝血酶凝胶形成研究中的应用
  • DOI:
    10.1007/s00397-010-0473-6
  • 发表时间:
    2010
  • 期刊:
  • 影响因子:
    2.3
  • 作者:
    Hawkins K
  • 通讯作者:
    Hawkins K
A new biomarker quantifies differences in clot microstructure in patients with venous thromboembolism
  • DOI:
    10.1111/bjh.13173
  • 发表时间:
    2015-02-01
  • 期刊:
  • 影响因子:
    6.5
  • 作者:
    Lawrence, Matthew J.;Sabra, Ahmed;Evans, Phillip A.
  • 通讯作者:
    Evans, Phillip A.
Rheometrical and molecular dynamics simulation studies of incipient clot formation in fibrin-thrombin gels: An activation limited aggregation approach
  • DOI:
    10.1016/j.jnnfm.2011.04.016
  • 发表时间:
    2011-09-01
  • 期刊:
  • 影响因子:
    3.1
  • 作者:
    Curtis, D. J.;Brown, M. R.;Williams, P. R.
  • 通讯作者:
    Williams, P. R.
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Rhodri Williams其他文献

The effect of tyramine infusion and exercise on blood flow, coagulation and clot microstructure in healthy individuals.
酪胺输注和运动对健康个体血流、凝血和凝块微观结构的影响。
  • DOI:
  • 发表时间:
    2018
  • 期刊:
  • 影响因子:
    7.5
  • 作者:
    M. Lawrence;Gareth R. Davies;M. Nyberg;J. Whitley;V. Evans;Rhodri Williams;Y. Hellsten;P. Evans
  • 通讯作者:
    P. Evans
An orbital depth guide for repair of the orbital floor
  • DOI:
    10.1016/j.bjoms.2007.11.018
  • 发表时间:
    2008-06-01
  • 期刊:
  • 影响因子:
  • 作者:
    Khaleeq-Ur Rehman;Suresh Shetty;Rhodri Williams
  • 通讯作者:
    Rhodri Williams
Simultaneous measurements of photocurrents and H2O2 evolution from solvent exposed photosystem 2 complexes.
同时测量溶剂暴露的光系统 2 复合物的光电流和 H2O2 释放。
  • DOI:
  • 发表时间:
    2016
  • 期刊:
  • 影响因子:
    2.1
  • 作者:
    T. Vöpel;En Ning Saw;Volker Hartmann;Rhodri Williams;F. Müller;W. Schuhmann;N. Plumeré;M. Nowaczyk;S. Ebbinghaus;M. Rögner
  • 通讯作者:
    M. Rögner
Main title: The effect of tyramine infusion and exercise on blood flow, coagulation and clot microstructure in healthy individuals Short title: The effect of catecholamine’s on coagulation
主标题:酪胺输注和运动对健康个体血流、凝血和凝块微观结构的影响短标题:儿茶酚胺对凝血的影响
  • DOI:
  • 发表时间:
    2018
  • 期刊:
  • 影响因子:
    0
  • 作者:
    M. Lawrence;Gareth R. Davies;M. Nyberg;J. Whitley;Vanessa;Evans;Rhodri Williams;Y. Hellsten;P. Evans
  • 通讯作者:
    P. Evans
Can fractal dimension (d<sub>f</sub>) as a haemostatic biomarker guide crystalloid replacement therapy in major trauma?
  • DOI:
    10.1016/j.ijsu.2013.06.047
  • 发表时间:
    2013-10-01
  • 期刊:
  • 影响因子:
  • 作者:
    Jakub Kaczynski;Matthew Lawrence;Sophie Stanford;Gareth Davies;Karl Hawkins;Rhodri Williams;Adrian Evans
  • 通讯作者:
    Adrian Evans

Rhodri Williams的其他文献

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{{ truncateString('Rhodri Williams', 18)}}的其他基金

EPSRC Healthcare Impact Partnership for new blood clotting diagnostics and management
EPSRC 医疗保健影响合作伙伴关系致力于新的凝血诊断和管理
  • 批准号:
    EP/L024799/1
  • 财政年份:
    2014
  • 资助金额:
    $ 115.51万
  • 项目类别:
    Research Grant

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