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用于复杂介质中传感与检测的超低污垢和高抗体负载两性离子水凝胶涂层

Ultra-low fouling and high antibody loading zwitterionic hydrogel coatings for sensing and detection in complex media.

作者信息

Chou Ying-Nien, Sun Fang, Hung Hsiang-Chieh, Jain Priyesh, Sinclair Andrew, Zhang Peng, Bai Tao, Chang Yung, Wen Ten-Chin, Yu Qiuming, Jiang Shaoyi

机构信息

Department of Chemical Engineering, University of Washington, Seattle, WA 98195-1750, USA; Department of Chemical Engineering, National Cheng Kung University, Tainan 70101, Taiwan.

Department of Chemical Engineering, University of Washington, Seattle, WA 98195-1750, USA.

出版信息

Acta Biomater. 2016 Aug;40:31-37. doi: 10.1016/j.actbio.2016.04.023. Epub 2016 Apr 16.

DOI:10.1016/j.actbio.2016.04.023
PMID:27090589
Abstract

UNLABELLED

For surface-based diagnostic devices to achieve reliable biomarker detection in complex media such as blood, preventing nonspecific protein adsorption and incorporating high loading of biorecognition elements are paramount. In this work, a novel method to produce nonfouling zwitterionic hydrogel coatings was developed to achieve these goals. Poly(carboxybetaine acrylamide) (pCBAA) hydrogel thin films (CBHTFs) prepared with a carboxybetaine diacrylamide crosslinker (CBAAX) were coated on gold and silicon dioxide surfaces via a simple spin coating process. The thickness of CBHTFs could be precisely controlled between 15 and 150nm by varying the crosslinker concentration, and the films demonstrated excellent long-term stability. Protein adsorption from undiluted human blood serum onto the CBHTFs was measured with surface plasmon resonance (SPR). Hydrogel thin films greater than 20nm exhibited ultra-low fouling (<5ng/cm(2)). In addition, the CBHTFs were capable of high antibody functionalization for specific biomarker detection without compromising their nonfouling performance. This strategy provides a facile method to modify SPR biosensor chips with an advanced nonfouling material, and can be potentially expanded to a variety of implantable medical devices and diagnostic biosensors.

STATEMENT OF SIGNIFICANCE

In this work, we developed an approach to realize ultra-low fouling and high ligand loading with a highly-crosslinked, purely zwitterionic, carboxybetaine thin film hydrogel (CBHTF) coating platform. The CBHTF on a hydrophilic surface demonstrated long-term stability. By varying the crosslinker content in the spin-coated hydrogel solution, the thickness of CBHTFs could be precisely controlled. Optimized CBHTFs exhibited ultra-low nonspecific protein adsorption below 5ng/cm(2) measured by a surface plasmon resonance (SPR) sensor, and their 3D architecture allowed antibody loading to reach 693ng/cm(2). This strategy provides a facile method to modify SPR biosensor chips with an advanced nonfouling material, and can be potentially expanded to a variety of implantable medical devices and diagnostic biosensors.

摘要

未标注

对于基于表面的诊断设备而言,要在血液等复杂介质中实现可靠的生物标志物检测,防止非特异性蛋白质吸附并纳入高负载的生物识别元件至关重要。在这项工作中,开发了一种制备抗污两性离子水凝胶涂层的新方法来实现这些目标。用羧基甜菜碱二丙烯酰胺交联剂(CBAAX)制备的聚(羧基甜菜碱丙烯酰胺)(pCBAA)水凝胶薄膜(CBHTFs)通过简单的旋涂工艺涂覆在金和二氧化硅表面。通过改变交联剂浓度,CBHTFs的厚度可以精确控制在15至150纳米之间,并且这些薄膜表现出优异的长期稳定性。用表面等离子体共振(SPR)测量了未稀释的人血清中蛋白质在CBHTFs上的吸附情况。厚度大于20纳米的水凝胶薄膜表现出超低污垢(<5纳克/平方厘米)。此外,CBHTFs能够进行高抗体功能化以用于特异性生物标志物检测,而不会损害其抗污性能。该策略提供了一种用先进的抗污材料修饰SPR生物传感器芯片的简便方法,并且有可能扩展到各种可植入医疗设备和诊断生物传感器。

重要性声明

在这项工作中,我们开发了一种方法,通过高度交联、纯两性离子的羧基甜菜碱薄膜水凝胶(CBHTF)涂层平台实现超低污垢和高配体负载。亲水性表面上的CBHTF表现出长期稳定性。通过改变旋涂水凝胶溶液中的交联剂含量,可以精确控制CBHTFs的厚度。经表面等离子体共振(SPR)传感器测量,优化后的CBHTFs表现出低于5纳克/平方厘米的超低非特异性蛋白质吸附,并且其三维结构使抗体负载量达到693纳克/平方厘米。该策略提供了一种用先进的抗污材料修饰SPR生物传感器芯片的简便方法,并且有可能扩展到各种可植入医疗设备和诊断生物传感器。

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