多核双乳液滴的电场调控融合机理及其在抗肿瘤组合药物筛选中的应用

Conducting chemotherapy using two or more kinds of antineoplastic drugs simultaneously, can effectively avoid drug resistance of human body and enormous poisonous side effect. However, how to seek the most appropriate matching combination of chemotherapy among the large amount of drug types and their corresponding concentration data, has become the bottleneck of antineoplastic drug screening. Droplet based microfluidics possess excellent potential of both high-throughput and high efficiency, and is expected to achieve the goal of fast screening of antineoplastic drugs. For such, this project utilizes double emulsion droplets of multiple cores as carriers and alternating current electric field as regulatory tools. We first investigate electro-coalescence of the multiple cores within double emulsion droplets in static condition, explore the deformation regularity and merging sequence of droplet cores, pinpoint the work conditions of different physical mechanisms; On this basis, we develop the fully-coupled dynamic model of electro-coalescence of multiple cores within double emulsion droplet in dynamic flow condition, study the features of fusion of multiple cores; Subsequently, we experimentally validate the high-throughput electro-coalescence of the multiple cores within double emulsion droplet, the experimental parameters are made clear, the theoretical formulations are corrected; At last, bearing different drugs with different cores of double emulsion drops, we conduct experimental investigation on screening of antineoplastic combination drugs based upon the fusion of multiple cores within double emulsion drops. This project involves the origin of electro-coalescence of liquid cores within the confined space of enclosed droplets, will provide theoretical foundation for screening of new type anticancer combination drugs.

同时利用两种或多种抗肿瘤药物进行化疗，可有效避免由单一药物化疗导致的机体耐药性及巨大的毒副作用。然而，如何在大量的药物类型及其浓度数据中寻求最合适的化疗配比组合，则是抗肿瘤药物筛选的瓶颈。液滴微流控具有优异的高通量及高效潜能，有望实现抗肿瘤药物的快速筛选目标。为此，本项目以多核双乳液滴为载体，以交流电场为调控工具，首先研究静态条件下电场调控双乳液滴中多内核融合的机理，探究液滴内核的形变规律及融合顺序，明确不同机制的作用条件；在此基础上，建立动态条件下电场调控多核双乳液滴融合的全耦合动力学模型，仿真研究多内核的融合特征；随后，开展电场调控高通量多核双乳液滴融合的验证性实验研究，明确实验参数，修正理论公式；最后，以双乳液滴的不同内核承载不同药物，开展基于多核双乳液滴融合的抗肿瘤组合药物筛选试验研究。本项目涉及封闭液滴空间内电场调控内核融合的本源，将为新型抗肿瘤组合药物的筛选提供理论依据。

药物化疗是目前公认用于治疗恶性肿瘤的核心手段。传统方法使用单一抗肿瘤药物进行化疗，具有极大的局限性，而同时利用多种抗肿瘤药物进行化疗可有效解决这一问题。然而，如何在大量的药物类型及其浓度数据中寻求最合适的化疗配比组合，则是抗肿瘤药物筛选的瓶颈。以双乳液滴为代表液滴微流控技术具有超低样本消耗、高通量、高效性等显著优势，其独特的核‐壳结构在保证了所有内核药物载体相互独立，内核间反应的环境相同，从而有效避免融合过程中的交叉污染，有望实现抗肿瘤药物的快速筛选目标。为此，本项目以多核双乳液滴为载体，以交流电场为调控工具，首先研究静态条件下电场调控双乳液滴中多内核融合的机理，探究液滴内核的形变规律及融合顺序，明确不同机制的作用条件；在此基础上，建立动态条件下电场调控多核双乳液滴融合的全耦合动力学模型，仿真研究多内核的融合特征；随后，搭建双核及多核液滴生成的基础PDMS微流控芯片系统，开展电场调控高通量多核双乳液滴融合的验证性实验研究，明确实验参数，修正理论公式；最后，以双乳液滴的不同内核承载不同药物，搭建多核液滴生成与可控融合的微流控平台，开展基于多核双乳液滴融合的抗肿瘤组合药物筛选试验研究。本项目涉及封闭液滴空间内电场调控内核融合的本源，将为新型抗肿瘤组合药物的筛选提供前期技术支撑。