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芯片上的多聚电解质涂层到磁性液滴 - 实现药物输送胶囊的连续流组装。

On-chip polyelectrolyte coating onto magnetic droplets - towards continuous flow assembly of drug delivery capsules.

机构信息

School of Mathematics and Physical Sciences, University of Hull, Cottingham Road, Hull, HU6 7RX, UK.

出版信息

Lab Chip. 2017 Nov 7;17(22):3785-3795. doi: 10.1039/c7lc00918f.

DOI:10.1039/c7lc00918f
PMID:28991297
Abstract

Polyelectrolyte (PE) microcapsules for drug delivery are typically fabricated via layer-by-layer (LbL) deposition of PE layers of alternating charge on sacrificial template microparticles, which usually requires multiple incubation and washing steps that render the process repetitive and time-consuming. Here, ferrofluid droplets were explored for this purpose as an elegant alternative of templates that can be easily manipulated via an external magnetic field, and require only a simple microfluidic chip design and setup. Glass microfluidic devices featuring T-junctions or flow focusing junctions for the generation of oil-based ferrofluid droplets in an aqueous continuous phase were investigated. Droplet size was controlled by the microfluidic channel dimensions as well as the flow rates of the ferrofluid and aqueous phases. The generated droplets were stabilised by a surface active polymer, polyvinylpyrrolidone (PVP), and then guided into a chamber featuring alternating, co-laminar PE solutions and wash streams, and deflected across them by means of an external permanent magnet. The extent of droplet deflection was tailored by the flow rates, the concentration of magnetic nanoparticles in the droplets, and the magnetic field strength. PVP-coated ferrofluid droplets were deflected through solutions of polyelectrolyte and washing streams using several iterations of multilaminar flow designs. This culminated in an innovative "Snakes-and-Ladders" inspired microfluidic chip design that overcame various issues of the previous iterations for the deposition of layers of anionic poly(sodium-4-styrene sulfonate) (PSS) and cationic poly(fluorescein isothiocyanate allylamine hydrochloride) (PAH-FITC) onto the droplets. The presented method demonstrates a simple and rapid process for PE layer deposition in <30 seconds, and opens the way towards rapid layer-by-layer assembly of PE microcapsules for drug delivery applications.

摘要

用于药物输送的聚电解质 (PE) 微胶囊通常通过在牺牲模板微颗粒上交替电荷的 PE 层的层层 (LbL) 沉积来制造,这通常需要多次孵育和洗涤步骤,使过程重复且耗时。 在这里,研究了铁磁流体液滴作为模板的一种优雅替代物,这些模板可以通过外部磁场轻松操作,并且只需要简单的微流控芯片设计和设置。 研究了具有 T 型接头或流动聚焦接头的玻璃微流控器件,用于在连续水相中的油基铁磁流体液滴的生成。 通过微流控通道尺寸以及铁磁流体和水相的流速来控制液滴尺寸。 生成的液滴由表面活性剂聚合物聚乙烯吡咯烷酮 (PVP) 稳定,然后引导至一个室中,该室具有交替的、共层的 PE 溶液和洗涤流,并通过外部永磁体将其偏转到它们上。 通过流速、液滴中磁性纳米粒子的浓度和磁场强度来调整液滴的偏转角。 使用几种多层流设计的迭代,通过聚电解质溶液和洗涤流来偏转会聚电解质包覆的铁磁流体液滴。 这最终导致了一种创新的“蛇梯棋”启发的微流控芯片设计,克服了前几代迭代中用于将阴离子聚(4-苯乙烯磺酸钠) (PSS) 和阳离子聚(荧光素异硫氰酸酯烯丙胺盐酸盐) (PAH-FITC) 层沉积到液滴上的各种问题。 所提出的方法在<30 秒内展示了一种简单快速的 PE 层沉积过程,并为用于药物输送应用的 PE 微胶囊的快速层层组装开辟了道路。

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