Replacement of animal models for tumour biology with a multifunctional microfluidic-based approach

该项目的目的是设计和优化一种新型的微流体装置，在这种装置中，人类肿瘤组织的小活检可以保持存活，用药物治疗，并通过适当的分析技术测试下游的效果。这种人体系统将能够取代制药行业在动物模型上对新药和药物组合进行的一般测试，这些动物模型只能很好地复制人类的生理和代谢。此外，还可以对任何组织类型的正常和病变切片进行活组织检查，这样就可以很容易地评估特异性治疗反应和非特异性副作用。越来越多的证据表明，许多癌症患者，尤其是卵巢癌和胰腺癌患者，血液凝固事件的发生率增加；这些血块可能是致命的。也有证据表明，当患者接受化疗，肿瘤细胞被破坏时，细胞碎片的释放进一步增加了凝血的风险。在这个项目中，我们建议设计一种设备，使用人类卵巢肿瘤模型来分析这些凝血途径。三个分析模块将集成到一个设备上，在该设备上培养组织样本，允许监测不同类型的生物反应，包括表达基因的变化，细胞表面成分和分泌产物。这些不同类型的分析模块展示了这种新平台技术的广泛适用性和潜力。此外，卵巢癌的死亡率相对较高，在过去二十年中生存率没有显著提高。这项新技术不仅将取代大量经证实价值有限的传统动物试验，而且能够对肿瘤样本进行多次试验，即在组织受到药物或其他试验条件影响后，极其接近其来源的肿块，这意味着可以对任何单个肿瘤产生大量信息。当在诊断时获得这些数据时，对临床医生将非常有用。预期的治疗策略可以为患者量身定制，如果没有任何治疗似乎会产生任何治疗效果，则可以与患者讨论，为姑息治疗提供机会，使其成为首选，同时保持最佳的生活质量。

The aim of the project is to design and optimise a novel microfluidic device in which small biopsies of human tumour tissue can be kept alive, treated with drugs and the effects tested downstream by appropriate analysis techniques. This human system will be able to replace the generalised testing of new drugs and combinations of drugs by the pharmaceutical industry, on animal models that only poorly replicate the physiology and metabolism of human beings. In addition it will be possible to test biopsies of both normal and diseased pieces of any tissue type so that both specific therapeutic responses, as well as non-specific side-effects can easily be assessed.There is growing evidence that patients with many cancers, particularly ovarian and pancreas suffer with an increased occurrence of blood clotting events; these clots can be lethal. There is also evidence that when patients undergo chemotherapy and the tumour cells are destroyed the release of cell debris further increases the risk of clotting. In the project we propose to design a device that allows analysis of these clotting pathways, using a human ovarian tumour model. Three analysis modules will be integrated into a device on which a sample of tissue is incubated, allowing different types of biological response to be monitored, including changes in the expressed genes, cell surface components and secreted products. These distinct types of analysis module demonstrate the widespread applicability and potential of this new platform technology. Furthermore, ovarian cancer has a relatively high mortality with survival rates not improving substantially over the past two decades.Not only will the new technology replace a large number of conventional animal tests, of limited proven value, but the capability of undertaking multiple tests on a tumour sample, that is an extremely close representation of the mass from which it came, after the tissue has been subjected to a drug or other test condition, means that a large amount of information can be generated on any individual tumour. Such data will be extremely useful for the clinician when obtained at the time of diagnosis. The intended treatment strategy can be tailored to the patient, and where no treatment appears to give any therapeutic effect, this can be discussed with the patient opening the opportunity for palliative care to be the preferred choice, whilst maintaining the best quality of life.