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In-fiber production of polymeric particles for biosensing and encapsulation

机译:在纤维内生产用于生物传感和封装的聚合物颗粒

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摘要

Polymeric micro- and nanoparticles are becoming a mainstay in biomedicine, medical diagnostics, and therapeutics, where they are used in implementing sensing mechanisms, as imaging contrast agents, and in drug delivery. Current approaches to the fabrication of such particles are typically finely tuned to specific monomer or polymer species, size ranges, and structures. We present a general scalable methodology for fabricating uniformly sized spherical polymeric particles from a wide range of polymers produced with complex internal architectures and continuously tunable diameters extending from the millimeter scale down to 50 nm. Controllable access to such a wide range of sizes enables broad applications in cancer treatment, immunology, and vaccines. Our approach harnesses thermally induced, predictable fluid instabilities in composite core/cladding polymer fibers drawn from a macroscopic scaled-up model called a “preform.” Through a stack-and-draw process, we produce fibers containing a multiplicity of identical cylindrical cores made of the polymers of choice embedded in a polymer cladding. The instability leads to the breakup of the initially intact cores, independent of the polymer chemistry, into necklaces of spherical particles held in isolation within the cladding matrix along the entire fiber length. We demonstrate here surface functionalization of the extracted particles for biodetection through specific protein–protein interactions, volumetric encapsulation of a biomaterial in spherical polymeric shells, and the combination of both surface and volumetric functionalities in the same particle. These particles used in distinct modalities may be produced from the desired biocompatible polymer by changing only the geometry of the macroscopic preform from which the fiber is drawn.
机译:聚合物微粒和纳米颗粒正成为生物医学,医学诊断和治疗学中的主流,它们被用于实现传感机制,成像造影剂和药物递送。制造此类颗粒的当前方法通常可以根据特定的单体或聚合物种类,尺寸范围和结构进行微调。我们提出了一种通用的可扩展方法,该方法用于从由复杂内部结构和从毫米级到50 nm的连续可调直径范围生产的多种聚合物中制备尺寸均匀的球形聚合物颗粒。可控制地访问如此大范围的尺寸可在癌症治疗,免疫学和疫苗中广泛应用。我们的方法利用了从称为“预成型坯”的宏观放大模型得出的复合纤芯/包层聚合物纤维中的热诱导可预测的流体不稳定性。通过堆叠和拉伸过程,我们生产出的纤维包含多个相同的圆柱形芯,这些芯由嵌入聚合物覆层中的所选聚合物制成。不稳定性导致与聚合物化学性质无关的最初完整的纤芯分解为沿整个光纤长度隔离地保持在包层基质内的球形颗粒项链。我们在这里展示了提取的颗粒的表面功能化,用于通过特定的蛋白质-蛋白质相互作用,生物材料在球形聚合物壳中的体积封装以及同一颗粒中表面和体积功能的结合来进行生物检测。可以通过仅改变从中拉出纤维的宏观预成型件的几何形状,从所需的生物相容性聚合物中产生用于不同形态的这些颗粒。

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