Imaging of drugs in cells: an on-chip system for development and testing of new therapies

细胞内药物成像：用于开发和测试新疗法的片上系统

• 批准号: 1648192
• 金额: --
• 依托单位: University of Nottingham
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2015
• 资助国家: 英国
• 起止时间: 2015 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-1648192
• 关键词: Imaging; drugs; cells; chip; system

A model cell culture tool designed to represent the in vivo environment will be developed to enable the examination of toxicological affects in vitro, changes to cells when in a perturbed state and quantitative analysis of endogenous and exogenous chemical species inside cells. This will allow us to develop methods to test drug efficacy in cell culture to produce greater mechanistic information and reduce animal use in the search for new medicines to treat patients with, for example, respiratory, inflammatory and cardiovascular diseases.We have recently demonstrated the 3 dimensional cellular distributions of small molecules in a variety of cells using Time of Flight Secondary Ion Mass Spectrometry (ToF SIMS). Current sample preparation involves freezing and dehydrating adherent cells but the system does not yet have sufficient spatial resolution to determine the distribution of the dosed molecule at the organelle level. This work is being performed in collaboration between GSK, the University of Nottingham and the National Physical Laboratory. We propose to combine this study with the 3D printing and cell manipulation expertise at the University to enable the imaging of small molecules within cells grown in a more relevant 3 dimensional culture tool. The goal of this project is to use 3D printing to generate a hydrogel chip containing cells spatially arrayed within a printed structure supplied with micro fluidic channels to dose individual cells. Compounds will be passed along the channels and allowed to incubate with cells within the matrix to enable real time observation using microscopy.

将开发设计用于代表体内环境的模型细胞培养工具，以检查体外毒理学影响、细胞在扰动状态下的变化以及细胞内内源性和外源性化学物质的定量分析。这将使我们能够开发出在细胞培养中测试药物功效的方法，以产生更多的机制信息，并减少在寻找治疗呼吸系统、炎症和心血管疾病等患者的新药时使用动物。我们最近使用飞行时间二次离子质谱（ToF西姆斯）证明了小分子在各种细胞中的三维细胞分布。目前的样品制备涉及粘附细胞的冷冻和脱水，但该系统还没有足够的空间分辨率来确定在细胞器水平上给药分子的分布。这项工作是由葛兰素史克、诺丁汉大学和国家物理实验室合作进行的。我们建议将这项研究与该大学的3D打印和细胞操作专业知识结合联合收割机，以实现在更相关的三维培养工具中生长的细胞内小分子的成像。该项目的目标是使用3D打印来生成水凝胶芯片，该水凝胶芯片包含在打印结构内空间排列的细胞，该打印结构具有微流体通道以给单个细胞提供剂量。化合物将沿通道沿着通过，并允许与基质内的细胞一起孵育，以使得能够使用显微镜进行真实的观察。