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MicroTotal Pre Analytical Systems (MTPAS): Near-patient Approach to the Preparation of Circulating Biomarkers for Next-Generation Sensing

MicroTotal 预分析系统 (MTPAS)：用于下一代传感的循环生物标记物的近患者制备方法

基本信息

批准号：
EP/R00398X/1
负责人：
Maiwenn Kersaudy-Kerhoas
金额：
$ 122.96万
依托单位：
Heriot-Watt University
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2018
资助国家：
英国
起止时间：
2018 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=EP%2FR00398X%2F1
关键词：
MicroTotal Pre Analytical Systems MTPAS

项目摘要

Increased demand on blood sampling requirements has arisen from prolong lifespan and ageing populations. The use of circulating cell-free nucleic acids (cfNAs) as biomarkers for cancer, non-invasive prenatal testing, organ transplant monitoring and more, has grown in popularity since it is non-invasive (simple blood draw) and easily repeated, allowing the possibility to rapidly establish a diagnosis, a prognosis and even used for theranostic applications. So called "liquid biopsies" and cfDNA analysis could for example allow the fourteen millions of cancer patients diagnosed globally each year to access earlier diagnosis and optimised treatments.However, despite numerous translational research programs the detection of cfNA is not currently implemented clinically in daily practice. Several reasons have been emerged for this, including (i) the difficulty in controlling the different biological, environmental and logistic parameters from blood sampling to the analysis of biomarkers (ii) the cost of the currently available techniques, which limit accessibility (iii) the turn-around time needed to be useful for patients and clinicians. Current sample preparation solutions are multi-step which can introduce variations and lead to an erroneous diagnosis. Additionally these solutions are time consuming, not amenable to near-patient extraction following blood draw, and require highly trained technicians. The optimisation of the extraction of cell-free circulating markers is key to their translation from the research setting to clinical deployment. The lack of engineering solutions to address the specificities of circulating cell-free nucleic acid extraction, underpins this programme. To meet the requirements of future healthcare industry, the work proposed will integrate novel advanced materials such as electrospun fibres, packaged with on-chip reagents in a microfluidic cartridge to extract cfNAs from blood. Deployed near-patient, this technology will protect the biomarkers from enzymatic degradation and enrich them against the rest of the nucleic acids present in the sample, allowing an unparalleled standardisation and instant preservation of the true disease state until analysis. The solution proposed involves the use of single-use cartridges, and could generate a significant amount of additional medical waste if implemented. Therefore this programme has a unique sustainable manufacturing component, looking into the use of a naturally-derived plastic (poly-lactic acid) to prototype and manufacture low carbon footprint, disposable, microfluidic cartridges, potential applicable to a large range of point-of-care devices. The solutions developed in this programme have the potential to significantly reduce the overall cost of sample preparation in the field of circulating biomarkers, as well as increasing the robustness and reliability of a range of biomarkers with direct application in clinical diagnostic and biomarker and drug discovery, in a sustainable fashion. Hand-in-hand with novel sensing solutions, this work has the potential to increase life quality from earlier, quicker diagnosis through optimised treatment and better care management. With the global liquid biopsy market forecasts to reach $4.5 billion by 2020, front-end sample preparation constitutes an important area for the UK economy.

由于寿命延长和人口老龄化，对血液取样的需求增加。使用循环无细胞核酸（cfNA）作为癌症的生物标志物，非侵入性产前检测，器官移植监测等，已经越来越受欢迎，因为它是非侵入性的（简单的抽血），易于重复，允许快速建立诊断，预后，甚至用于治疗诊断应用的可能性。例如，所谓的“液体活检”和cfDNA分析可以允许全球每年诊断的一千四百万癌症患者获得早期诊断和优化治疗，然而，尽管有许多转化研究项目，cfNA的检测目前在临床上并没有在日常实践中实施。对此已经出现了几个原因，包括（i）难以控制从血液采样到生物标志物分析的不同生物、环境和逻辑参数（ii）目前可用技术的成本，这限制了可及性（iii）对患者和临床医生有用所需的周转时间。目前的样品制备溶液是多步骤的，这可能会引入变化并导致错误的诊断。此外，这些解决方案是耗时的，不适合在抽血后接近患者提取，并且需要训练有素的技术人员。无细胞循环标志物提取的优化是将其从研究环境转化为临床部署的关键。缺乏工程解决方案来解决循环无细胞核酸提取的特异性，这是该计划的基础。为了满足未来医疗保健行业的要求，提出的工作将整合新型先进材料，如电纺纤维，与微流体盒中的芯片上试剂一起包装，以从血液中提取cfNA。在患者附近部署，这项技术将保护生物标志物免受酶降解，并使其与样本中存在的其余核酸相比较，从而实现无与伦比的标准化，并即时保存真实的疾病状态，直至分析。拟议的解决方案涉及使用一次性药筒，如果实施，可能会产生大量额外的医疗废物。因此，该计划有一个独特的可持续制造部分，研究使用天然塑料（聚乳酸）来原型设计和制造低碳足迹、一次性微流体盒，可能适用于大量现场护理设备。该项目开发的解决方案有可能显著降低循环生物标志物领域样品制备的总体成本，并以可持续的方式提高一系列生物标志物的稳健性和可靠性，直接应用于临床诊断和生物标志物以及药物发现。与新型传感解决方案携手，这项工作有可能通过优化治疗和更好的护理管理，从更早、更快的诊断中提高生活质量。全球液体活检市场预计到2020年将达到45亿美元，前端样本制备是英国经济的重要领域。

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）

The effect of elevated hematocrit on human blood flow in a microchannel

血细胞比容升高对微通道中人体血流的影响

DOI：
发表时间：
2020
期刊：
MicroTAS 2020 - 24th International Conference on Miniaturized Systems for Chemistry and Life Sciences
影响因子：
0
作者：
Haque M.E.
通讯作者：
Haque M.E.

A microfluidic finger-actuated blood lysate preparation device enabled by rapid acoustofluidic mixing

DOI：
10.1101/2022.10.16.512425
发表时间：
2022-10
期刊：
bioRxiv
影响因子：
0
作者：
Md Ehtashamul Haque;A. Conde;W. Macpherson;Stephen R. Knight;R. Carter;M. Kersaudy-Kerhoas
通讯作者：
Md Ehtashamul Haque;A. Conde;W. Macpherson;Stephen R. Knight;R. Carter;M. Kersaudy-Kerhoas

Design, 3D-printing, and characterisation of a low-cost, open-source centrifuge adaptor for separating large volume clinical blood samples

用于分离大容量临床血液样本的低成本开源离心机适配器的设计、3D 打印和表征