A microfluidic platform for personalized throughput drug screening using cancer spheroids

使用癌症球体进行个性化通量药物筛选的微流控平台

基本信息

批准号：
530375-2018
负责人：
Kumacheva, Eugenia
金额：
$ 9.11万
依托单位：
University of Toronto
依托单位国家：
加拿大
项目类别：
Idea to Innovation
财政年份：
2018
资助国家：
加拿大
起止时间：
2018-01-01 至 2019-12-31
项目状态：
已结题

来源：
https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=656101
关键词：
microfluidic platform personalized throughput drug

项目摘要

Cancer remains the leading cause of death worldwide. For many patients, standard-of-care therapy involves surgical removal of the primary tumour, however the surgery is often followed by the growth of secondary microtumours at distant locations. Therapies are required that are either toxic toward micrometastases or that lock them in the dormant state, yet there is a challenge to assess the effectiveness of drugs for microtumors grown in different environments with varying protective properties. ** Currently, there is lack of tools that recreate micrometastasis for the evaluation of therapeutic agents. Animal models are expensive, labor- and time-consuming; generally, provide only endpoint analyses and arguably, are not relevant for humans. Two-dimensional cell culture yields microtumor models that differ considerably in their properties and phenotype from those grown in physiological 3D environments, and thus may not serve as an efficient model for drug screening. Multicellular cancer spheroids (MCS) bridge 2D cell culture and animal models, and have very promising applications in drug screening however presently used MCS models for drug screening suffer from a number of limitations. ** This proposal aims at the development of a microfluidic (MF) platform for screening of new drugs and optimization of existing drug formulations for therapeutic cancer treatment. The technology utilizes large arrays of uniformly-sized MCSs derived from patient-derived cells that are grown in a biomimetic hydrogel in a MF device, the delivery of drugs to these MCSs under close-to-physiological flow conditions, and throughput screening of drug efficacy for MCS treatment. The MF-MCS platform includes multiple parallel rows of microwells, with up to 100 MCSs in each row. The platform enables systematic variation of a particular factor between different rows, thus enabling screening of drug efficacy for MCSs grown from a particular cell type in a specific environment, and the effect of drug dosages and combinations, to name just a few, all in one series of experiments conducted in a single MF device. **************

癌症仍然是全世界死亡的主要原因。对于许多患者来说，标准治疗包括手术切除原发性肿瘤，但手术后往往会在远处出现继发性微肿瘤的生长。需要对微转移具有毒性或将其锁定在休眠状态的疗法，但评估药物对在不同环境中生长且具有不同保护特性的微肿瘤的有效性仍然是一个挑战。 ** 目前，缺乏重建微转移的工具来评估治疗药物。动物模型价格昂贵、费工费时；一般来说，仅提供终点分析，并且可以说与人类无关。二维细胞培养产生的微肿瘤模型在特性和表型上与生理 3D 环境中生长的微肿瘤模型有很大不同，因此可能无法作为药物筛选的有效模型。多细胞癌球体 (MCS) 连接了 2D 细胞培养和动物模型，在药物筛选中具有非常有前景的应用，但目前用于药物筛选的 MCS 模型存在许多局限性。 ** 该提案旨在开发微流控 (MF) 平台，用于筛选新药和优化现有药物配方，用于癌症治疗。该技术利用源自患者细胞的大量大小均匀的 MCS，这些细胞在 MF 装置的仿生水凝胶中生长，在接近生理流动条件下将药物输送到这些 MCS，并通过通量筛选药效用于 MCS 治疗。 MF-MCS 平台包括多排平行的微孔，每排最多有 100 个 MCS。该平台能够对不同行之间的特定因素进行系统变化，从而能够筛选在特定环境中由特定细胞类型生长的 MCS 的药物功效，以及药物剂量和组合的影响，仅举几例，全部合而为一在单个 MF 设备中进行的一系列实验。 **************