基于介电泳和电热流动的血液细菌即时诊断机理研究

The point-of-care (POC) diagnostics of blood bacteria is a significant way to decrease the septicemia mortality of clinical patients. The traditional microfluidic POC technologies using alternating current (AC) electrokinetics should dilute the blood to generate positive dielectrophoresis (pDEP) and AC electroosmosis (ACEO) for bacterium capture. However, this approach decreases the bacterium concentration in the blood sample, and the aqueous solution with low ion concentration could cause the irreversible damage of bacterial cell. As a consequence, the bacterium detection efficiency is decreased. This project applies the AC electrothermal force to drive the flow of high conductivity blood. By combining the negative dielectrophoresis (nDEP), an efficient separation and detection technique of blood cell and bacteria is developed without lowering the sample bacteria concentration and damaging the bacteria viability. The current project focuses on the mass transfer of bacteria in high conductivity blood under AC electrokinetic phenomena by developing an immersed boundary-lattice Boltzmann multiphase model and experimental methods. The effects of rheological characteristic of non-Newtonian blood and its frequency-dependent dielectric property on the blood flow mechanism is investigated. The swimming mechanism of bacteria with helical flagella under the influence of DEP is clarified. In addition, the blood bacterium capture efficiency and viability are studied with respect to different AC voltages and frequencies, microfluidic chip configurations, physical properties of blood and bacteria. This project consolidates the theory of microscale heat and mass transfer under AC electrokinetics, and it has important value on simplifying the clinical operation procedure of blood bacteria detection.

血液细菌的即时诊断是降低败血症患者临床死亡率的重要途径。传统的交流电动微流控即时诊断方法依靠高倍稀释血液后所产生的P型介电泳和电渗力进行细菌捕捉，该方法会导致血液样本细菌浓度降低以及低离子浓度环境下细菌结构的不可逆破坏，降低了细菌检测效率。本项目提出采用交流电热力驱动高电导率全血液流动、结合N型介电泳进行细菌高效采集，在维持血液样本细菌浓度和细菌活性的基础上，提出血细胞和细菌的高效分离检测方法。本项目围绕电动现象作用下高电导率血液中细菌传质问题，构建浸入边界-格子玻尔兹曼多相数值模型，结合微流控实验，阐释非牛顿血液流变特性、频率相关的介电特性影响下的血液流动机理；揭示介电泳对螺旋鞭毛细菌游动机理的影响机制;获得交流电压强度和频率、微流控芯片结构、血液和细菌物性参数对血液细菌捕捉效率和细菌活性的影响规律。本项目丰富了交流电动现象下的微尺度传热传质理论，对简化血液细菌检测临床操作具有应用价值。

临床医学诊治过程中的严重创伤或侵入性医疗操作会引起细菌性血液感染造成败血症，导致一些免疫功能低下的患者死亡。血液细菌的即时高效诊断是降低败血症患者死亡率的关键因素。本项目针对介电泳和电热流动耦合作用下的全血液细菌即时诊断开展了系统研究工作，取得的主要学术成果包括：1.发展了基于浸入边界-格子玻尔兹曼的交流电动多相传质模型，分析了微通道高电导率生理溶液内的细菌交流电热输运机制，避免了电渗流驱动下稀释生理溶液后引起的细胞溶解现象，提出了有效防止细菌群在电动迁移过程中产生团聚的城堡状电极结构。在此基础上，分析了微通道内介电泳和电热流动耦合作用下的细菌悬浮机制，明晰了强化介电电泳力是实现细菌稳定悬浮和分析检测的关键因素。2.建立了非牛顿全血液电热流动格子玻尔兹曼模型，并利用显卡实现高效并行计算，在800万网格条件下与单核心CPU计算相比，运算效率可加速557.09倍；结合比例分析法，阐明了全血液非牛顿特性及其基于交流电频率的介电特性对微流控电热泵驱动效率的影响机制，研究表明具有剪切稀化特性的全血液电热流速随交流电压强度的增幅远大于牛顿特性生理溶液，并指出全血液电热驱动能力会随着交流电频率的增加而显著减弱，提出了基于环形电极的高效全血液微流控电热泵，有效控制了焦耳热引起的高电导率全血液温升幅度，保障了交流电动现象作用下全血液内富集细菌的生理活性。3.将非牛顿全血液电热流动格子玻尔兹曼方法和郎之万动力学模型结合，开展了微流控交流电动效应下全血液内金黄色葡萄球菌连续性富集检测机理研究，设计了基于N型介电泳的四电极细菌富集结构，明确了同步加强介电电泳力和交流电热流动拖曳力是提高细菌富集效率的关键，实现了微流控芯片不同工况下全血液内68.4%-74.5%的稳定细菌富集率。本项目丰富了交流电动现象下的微尺度传热传质理论和数值方法，提出了介电泳和电热流动耦合作用下的全血液细菌高效富集机制，对优化临床微流控败血症即时检测效率具有重要意义。