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热塑性聚合物的微成型用于离散、多层微颗粒的直接制造。

Micromolding of Thermoplastic Polymers for Direct Fabrication of Discrete, Multilayered Microparticles.

机构信息

David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.

Beijing National Laboratory for Molecular Science, Key Laboratory of Colloid, Interface and Chemical Thermodynamics, Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100190, China.

出版信息

Small Methods. 2022 Sep;6(9):e2200232. doi: 10.1002/smtd.202200232. Epub 2022 Jun 28.

Abstract

Soft lithography provides a convenient and effective method for the fabrication of microdevices with uniform size and shape. However, formation of an embossed, connective film as opposed to discrete features has been an enduring shortcoming associated with soft lithography. Removing this residual layer requires additional postprocessing steps that are often incompatible with organic materials. This limits adaptation and widespread realization of soft lithography for broader applications particularly in drug discovery and drug delivery fields. A novel and versatile approach is demonstrated that enables fabrication of discrete, multilayered, fillable, and harvestable microparticles directly from any thermoplastic polymer, even at very high molecular weights. The approach, isolated microparticle replication via surface-segregating polymer blend mold, utilizes a random copolymer additive, designed with a highly fluorinated segment that, when blended with the mold's matrix, spontaneously orients to the surface conferring an extremely low surface energy and nonwetting properties to the template. The extremely nonwetting properties of the mold are further utilized to load soluble biologics directly into the built-in microwells in a rapid and efficient manner using an innovative screen-printing approach. It is believed that this approach holds promise for fabrication of large-array, 3D, complex microstructures, and is a significant step toward clinical translation of microfabrication technologies.

摘要

软光刻为具有均匀尺寸和形状的微器件的制造提供了一种方便且有效的方法。然而,与软光刻相关的一个持久的缺点是形成压印的、连续的薄膜而不是离散的特征。去除这个残留层需要额外的后处理步骤,这些步骤通常与有机材料不兼容。这限制了软光刻在更广泛的应用中的适应性和广泛实现,特别是在药物发现和药物输送领域。本文展示了一种新颖且多功能的方法,该方法可直接从任何热塑性聚合物制造离散的、多层的、可填充和可收获的微颗粒,即使是在非常高的分子量下。该方法是通过表面分离聚合物共混物模具复制孤立的微颗粒,利用一种具有高度氟化段的无规共聚物添加剂,当与模具的基质混合时,该添加剂会自发地取向到表面,赋予模板极低的表面能和不润湿特性。模具的极低不润湿特性进一步用于使用创新的丝网印刷方法以快速高效的方式直接将可溶性生物制剂加载到内置的微井中。人们相信,这种方法有望制造大型、3D、复杂的微结构,并且是朝着微制造技术的临床转化迈出的重要一步。

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