微流控芯片与癌症治疗

传统上，癌症等疾病的治疗方法都是从简单的体外细胞培养模型开始，然后才转移到动物身上。不幸的是，大多数治疗都失败了，相关成本很高，这在很大程度上是因为模型既不能准确地代表疾病的复杂病理生理学，也不能准确地代表正常的宿主生理学。器官是复杂的三维(3D)结构，由许多不同类型的细胞以独特的空间排列组成，与细胞外基质交织在一起。在赫尔大学，该方法一直是在连续灌注模型中维持和“审问”离体人体组织，目的是保存组织在体内的3D结构，保留复杂的细胞与细胞和细胞与基质的相互作用。我们研究的人体组织包括:头颈部鳞状细胞癌(HNSCC);大肠癌和正常组织;卵巢癌;间皮瘤，胶质母细胞瘤和心脏。这种方法的局限性是组织可以维持的时间，这因不同的组织/肿瘤类型和每个肿瘤个体而异。长达4天，几乎没有观察到所有组织的病理变化，功能似乎没有受损。 For drug toxicity studies a 9-day incubation period was used on HNSCC to show the additive effect of using multiple chemotherapy drugs on cell death. For studying irradiation effects on colorectal and HNSCC biopsies a 4-day time frame was used; these are measured by immunohistochemical analysis (Ki67, ?H2AX, M30) of the tissue post-irradiation. As expected higher doses or fractionated delivery caused increased cell death. The major challenge now is to undertake the correlative or pseudo-clinical trials in which the tissue-on-chip treatments are compared with the patient response following delivery of the same treatment regimen. An advantage of the lab-on-a-chip approach is that simultaneously other treatments can be tested.