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Molecularly Engineered Surfaces for Early Cancer Diagnosis

机译：分子工程表面用于早期癌症诊断

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摘要

Early detection of cancer can have immediate and significant impact on effective treatments for cancer patients and better disease prognosis. In the early stage of cancer, symptoms are initially expressed at molecular and cellular scales. Identification and capture of cancer cells can greatly advance cancer research. This research work is aimed to introduce novel biosensors and technologies for early cancer detection. We developed a one-step method to create nanotextured polymer substrates and showed the effect of surface nanotexture on cancer cell adhesion and cell surface interactions. The nanotextured surface was functionalized with an antibody to selectively capture cancer cells from a cell mixture. Nanotextured PDMS showed higher cell adhesion strength and enhanced cell capture. We also demonstrated a reversible sealed modular device approach to integrate nanotextured substrates into microfluidics for cell capture applications. The modular approach simplified cell capture workflow, provided easy assembly, and enabled a user-friendly method to access cells for post-capture analysis. We also observed that cancer cells showed distinct morphology on biofunctionalized surfaces. We developed a technique to quantify cell gestures using dynamic morphology from time-lapse optical micrographs of cells on functionalized surface. We used a supervised machine learning method to develop an automated system to identify cancer cells from their gestures. The system offered rapid, efficient, and novel identification of brain cancer cells and can be extended to classify many other types of tumor cells. Both of these detection mechanisms were based on the expression of protein biomarkers on the cell surface. A nanopore sensor is a unique platform for detecting protein biomarkers from ionic current signatures. The underlying mechanism of protein translocation through the nanopore is very difficult to understand from outside. We constructed a molecular dynamics model to simulate protein translocation through a nanopore to reveal the interatomic interactions and investigate the deformation mechanisms of thrombin inside a nanopore due to externally applied electric fields. We investigated the structural integrity of protein and its deformation dynamics inside a nanopore. The development of this technique has advanced nanopore research by providing insights about molecular level information to complement macroscopic measurements in the laboratory.
机译：癌症的早期发现会对癌症患者的有效治疗和更好的疾病预后产生直接而重大的影响。在癌症的早期阶段，症状最初是在分子和细胞尺度上表达的。癌细胞的识别和捕获可以大大促进癌症研究。这项研究工作旨在介绍用于早期癌症检测的新型生物传感器和技术。我们开发了一种一步方法来创建纳米纹理的聚合物基材，并显示了表面纳米纹理对癌细胞粘附和细胞表面相互作用的影响。纳米结构化表面用抗体功能化，以从细胞混合物中选择性捕获癌细胞。纳米纹理的PDMS显示出更高的细胞粘附强度和增强的细胞捕获能力。我们还展示了一种可逆的密封模块化设备方法，可将纳米纹理化的基质整合到微流体中，用于细胞捕获应用。模块化方法简化了细胞捕获工作流程，提供了易于组装的方法，并使用户友好的方法可以访问细胞以进行捕获后分析。我们还观察到癌细胞在生物功能化表面上显示出独特的形态。我们开发了一种技术，可以根据功能化表面上细胞的延时光学显微照片使用动态形态学来量化细胞手势。我们使用一种监督式机器学习方法来开发一个自动化系统，以从其手势识别癌细胞。该系统提供了快速，有效和新颖的脑癌细胞识别方法，并且可以扩展为对许多其他类型的肿瘤细胞进行分类。这两种检测机制均基于细胞表面蛋白质生物标志物的表达。纳米孔传感器是用于从离子电流特征中检测蛋白质生物标志物的独特平台。从外部很难理解蛋白质通过纳米孔的潜在机制。我们构建了分子动力学模型，以模拟蛋白质通过纳米孔的移位，以揭示原子间的相互作用，并研究由于外部施加的电场，凝血酶在纳米孔内部的变形机理。我们研究了蛋白质的结构完整性及其在纳米孔中的变形动力学。通过提供有关分子水平信息的见解，以补充实验室的宏观测量，这项技术的发展已经进行了先进的纳米孔研究。

著录项

  • 作者

    Hasan, Mohammad Raziul.;

  • 作者单位

    The University of Texas at Arlington.;

  • 授予单位 The University of Texas at Arlington.;
  • 学科 Electrical engineering.;Biomedical engineering.;Materials science.
  • 学位 Ph.D.
  • 年度 2017
  • 页码 162 p.
  • 总页数 162
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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