Particle Filtration and Accumulation by Solute-driven Transport (FAST) for bio-analysis in microfluidic devices

通过溶质驱动传输 (FAST) 进行颗粒过滤和积累，用于微流体装置中的生物分析

• 批准号: EP/S013865/1
• 负责人: Guido Bolognesi
• 金额: $ 25.59万
• 依托单位: Loughborough 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%2FS013865%2F1
• 关键词: Particle; Filtration; Accumulation; Solute; driven

The outcomes of many health interventions critically depend on the ability to identify the disease in a timely manner so the most appropriate therapy can be chosen promptly. Consequently, there is an immediate and growing need to develop healthcare technologies for rapid and accurate detection of bio-markers, associated with specific diseases, and/or disease causative agents, such as pathogenic microorganisms. Microfluidics and lab-on-a-chip technology offer a huge potential for the development of next generation fast and ultra-sensitive bio-analytical devices for diagnostic and therapeutic applications.Particle handling operations - including separation, filtration, concentration, trapping and sorting - are ubiquitous in microfluidic diagnostic technologies and can ultimately dictate the speed, accuracy and selectivity of testing devices. An ideal particle handling technique would be fast (high-throughput), selective (i.e. targeting only the particles of interest), easy to integrate into a multifunctional microfluidic device and, most importantly, not reliant on the use of external fields. This proposal aims to introduce an innovative particle manipulation technique to address all these requirements. This research will also demonstrate the proof-of-concept for using this technique to develop fast and sensitive diagnostic testing devices.Rapid filtration, trapping and accumulation of target particles within the cavities of micro-structured surfaces will be achieved in continuous flow settings by harvesting the chemical energy associated with salt contrast generated by parallel multi-component flows. The mechanisms governing the particle dynamics will be investigated through a combination of experimental and numerical techniques. The dependence of trapping and concentration efficiency on particle properties (especially size and surface chemistry) will be elucidated. The output of this study will be an optimally-designed microfluidic platform, through which two in-vitro diagnostic devices will be developed. One device will enable the rapid filtration of cell-like particles (e.g. liposomes) based on their lipid membrane composition which is an important indicator of a cell's state of health. This assay will offer new opportunities for early detection of drug induced cell death and rapid drug pharmacokinetics screening. Another device will enable the fast and ultrasensitive detection of a biomarker indicative of pathological conditions, including atherosclerosis, pancreatitis and some forms of cancers. Synthetic bio-compatible particles will be incubated in a sample solution where the specific interaction with the disease biomarkers will cause i) the fluorescent signal emission from the particle and ii) a change in particle surface chemistry. The latter effect is intended to enable the conversion of the chemical energy - stored in the form of salt contrast - into particle motion. As a result, the biomarker-activated fluorescent particles will be rapidly trapped and accumulated within target regions of the device whereas the non-fluorescent particles will remain unaffected by the presence of the salt. This will enable a massive signal amplification for the diagnostic assay and, consequently, a fast and accurate detection of biomarker concentration in the analysed sample.In summary, this research will lay the foundation for the development of a new family of low-cost, portable bio-analytical devices based on particle filtration and accumulation by solute-driven transport (FAST) for diagnostic and therapeutic applications. These innovative and highly-sensitive diagnostic tools will enable clinicians to perform rapid and accurate diagnosis and, hence, make timely and informed clinical treatment decisions which are more likely to lead to successful health outcomes.

许多卫生干预措施的结果关键取决于及时识别疾病的能力，以便能够迅速选择最合适的治疗方法。因此，迫切需要开发用于快速和准确地检测与特定疾病和/或疾病病原体（例如病原微生物）相关的生物标志物的健康护理技术。微流控和芯片实验室技术为开发下一代快速、超灵敏的诊断和治疗用生物分析设备提供了巨大的潜力。颗粒处理操作--包括分离、过滤、浓缩、捕获和分选--在微流控诊断技术中无处不在，并最终决定了测试设备的速度、准确性和选择性。理想的颗粒处理技术将是快速的（高通量），选择性的（即仅靶向感兴趣的颗粒），易于集成到多功能微流体装置中，最重要的是，不依赖于使用外部场。该提案旨在引入一种创新的粒子操纵技术来满足所有这些要求。该研究还将证明使用该技术开发快速和灵敏的诊断测试设备的概念验证。通过收集与平行多组分流产生的盐对比度相关的化学能，将在连续流设置中实现微结构表面空腔内目标颗粒的快速过滤，捕获和积累。粒子动力学的机制将通过实验和数值技术相结合的研究。将阐明捕集和浓缩效率对颗粒性质（特别是尺寸和表面化学）的依赖性。这项研究的成果将是一个优化设计的微流体平台，通过它将开发两种体外诊断设备。一种装置将能够基于细胞样颗粒（例如脂质体）的脂质膜组成快速过滤细胞样颗粒（例如脂质体），所述脂质膜组成是细胞健康状态的重要指标。该检测方法为早期检测药物诱导的细胞死亡和快速药物药代动力学筛选提供了新的机会。另一种设备将能够快速和超灵敏地检测指示病理状况的生物标志物，包括动脉粥样硬化、胰腺炎和某些形式的癌症。合成的生物相容性颗粒将在样品溶液中孵育，其中与疾病生物标志物的特异性相互作用将导致i）颗粒的荧光信号发射和ii）颗粒表面化学的变化。后一种效应旨在使化学能-以盐对比度的形式储存-转化为粒子运动。结果，生物标记物激活的荧光颗粒将被快速捕获并积聚在装置的靶区域内，而非荧光颗粒将保持不受盐存在的影响。这将使大量的信号放大的诊断检测，因此，一个快速和准确的检测生物标志物的浓度在分析sample.In总结，这项研究将奠定基础，为开发一个新的家庭的低成本，便携式生物分析设备的基础上，颗粒过滤和积累溶质驱动的运输（FAST）的诊断和治疗应用。这些创新和高度敏感的诊断工具将使临床医生能够进行快速准确的诊断，从而做出及时和明智的临床治疗决定，这更有可能导致成功的健康结果。

项目成果

Manipulation of colloidal particles by solute gradients in continuous-flow microfluidic devices

在连续流微流体装置中通过溶质梯度操纵胶体颗粒

• 发表时间: 2021
• 作者: Singh Naval

Continuous manipulation and characterization of colloidal beads and liposomes via diffusiophoresis in single- and double-junction microchannels

通过单连接和双连接微通道中的扩散电泳对胶体珠和脂质体进行连续操作和表征

• DOI: 10.48550/arxiv.2302.05800
• 发表时间: 2023
• 作者: Chakra A

Reversible Trapping of Colloids in Microgrooved Channels via Diffusiophoresis under Steady-State Solute Gradients.

• DOI: 10.1103/physrevlett.125.248002
• 发表时间: 2020-07
• 期刊: Physical review letters
• 影响因子: 8.6
• 作者: Naval Singh;G. Vladisavljević;F. Nadal;C. Cottin-Bizonne;C. Pirat;G. Bolognesi

Enhanced Accumulation of Colloidal Particles in Microgrooved Channels via Diffusiophoresis and Steady-State Electrolyte Flows.

• DOI: 10.1021/acs.langmuir.2c01755
• 发表时间: 2022-11-22
• 期刊: LANGMUIR
• 影响因子: 3.9
• 作者: Singh, Naval;Vladisavljevic, Goran T.;Nadal, Francois;Cottin-Bizonne, Cecile;Pirat, Christophe;Bolognesi, Guido
• 通讯作者: Bolognesi, Guido

Reversible Trapping of Colloids in Microgrooved Channels via Diffusiophoresis under Steady-State Solute Gradients

稳态溶质梯度下通过扩散电泳可逆捕获微槽通道中的胶体

• DOI: 10.48550/arxiv.2007.11114
• 发表时间: 2020
• 作者: Singh N