ENGINEERING A MICROFLUDIC PLATFORM AS A PRE-CLINICAL MODEL FOR BIOMEDICAL APPLICATIONS

Nevena Milivojević, D. Caballero, M. Carvalho, M. Zivanovic, N. Filipovic, Rui R Reis, J. Oliveira
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Abstract

Further technological advances are in great need for improving our understanding about critical biological and fundamental pathological processes, such as tissue development and cancer progression, or for the discovery and screening of novel pharmacological drugs. Preclinical experimentation demands for highly reliable and physiologically-relevant systems capable of recapitulating the complex human physiology. Traditional in vitro models, albeit widely employed, fail to reproduce the complexity of the native scenario with cells displaying aberrant gene expressions. Similarly, in vivo animal models, such as mice, poorly mimic the human condition and are ethically questionable. During the last decades, a new paradigm in preclinical modelling has emerged aiming to solve the limitations of the aforementioned methods. The combination of advanced tissue engineering, nanotechnology, and cell biology has resulted in the development of cutting-edge microfluidics-based models with an unprecedented ability to recreate within a microfluidic device the native habitat of cells within a microengineered chip. A diverse variety of micro- and bio-fabrication techniques is available for the development of microfluidic devices. Among all them, UV-photolithography and soft lithography is the considered the gold-standard method for the fabrication of chips due to its simplicity, versatility, and rapid prototyping. In this work, we describe the step-by-step fabrication procedure of a microfluidic chip by UV-photolithography and replica molding and discuss about their potential applications in the biomedical field.
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设计微流体平台作为生物医学应用的临床前模型
需要进一步的技术进步来提高我们对关键的生物学和基本病理过程的理解,如组织发育和癌症进展,或发现和筛选新的药理药物。临床前实验需要高度可靠和生理相关的系统,能够概括复杂的人体生理。传统的体外模型虽然被广泛使用,但无法再现细胞表现异常基因表达的自然情况的复杂性。同样,体内动物模型,如小鼠,很难模仿人类的状况,在伦理上也有问题。在过去的几十年里,一种新的临床前建模模式已经出现,旨在解决上述方法的局限性。先进的组织工程、纳米技术和细胞生物学的结合导致了尖端微流体模型的发展,这些模型具有前所未有的能力,可以在微流体装置内重建微工程芯片内细胞的原生栖息地。微流控器件的发展有多种多样的微制造技术和生物制造技术。其中,uv光刻和软光刻被认为是制造芯片的黄金标准方法,因为其简单,多功能性和快速原型。本文介绍了微流控芯片的紫外光刻和复制成型工艺,并讨论了其在生物医学领域的应用前景。
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