Lab on Chip:微流控芯片细胞水平药物代谢研究进展

发布者：大连化物所 发布时间：2009-1-3

秦建华研究员和林炳承研究员领导的微流控芯片研究组在以微流控芯片为平台的细胞水平药物代谢研究方面取得进展。研究结果发表在最新一期Lab on Chip杂志上，并被选为封面文章。
目前大多数药物经肝脏代谢为主，本研究设计制备了一种多层集成化微流控芯片，将肝微粒体固定在芯片上，药物通过芯片固定化的肝微粒体进行代谢，并与下游的芯片电泳和细胞培养单元相集成。利用该芯片可同时完成对药物的代谢物检测和代谢物的细胞毒性评价，显示了微流控芯片研究药物代谢等复杂过程的能力，为新药发现、药理学和毒理学研究，以及细胞水平药物筛选提供了一个重要的技术平台。
该项工作是研究组前期开展微流控芯片细胞水平药物筛选研究基础上的一个重要突破。这是该研究组工作在一年时间内第三次被Lab on Chip杂志作为封面报道。Lab on a Chip是当前国际上集中反映微流控芯片实验室学术成果的最重要刊物，近几年影响因子一直在5.0  以上。最近，林炳承研究员应邀出任Lab on Chip杂志编委，也是该杂志唯一的中国编委。
Lab Chip, 2009, 9, 232 - 238, DOI: 10.1039/b809117j
Characterization of drug metabolites and cytotoxicity assay simultaneously using an integrated microfluidic device
Bo Ma, Guohao Zhang, Jianhua Qin and Bingcheng Lin
An integrated microfluidic device was developed for the characterization of drug metabolites and a cytotoxicity assay simultaneously. The multi-layer device was composed of a quartz substrate with embedded separation microchannels and a perforated three-microwell array containing sol-gel bioreactors of human liver microsome (HLM), and two PDMS layers. By aligning the microwell array on the quartz substrate with cell culture chambers on the bottom PDMS layer, drug metabolism studies related to functional units, including metabolite generation, detection and incubation with cultured cells to assess metabolism induced cytotoxicity, were all integrated into the microfluidic device. To validate the feasibility of drug metabolism study on the microfluidic chip, UDP-glucuronosyltransferase (UGT) metabolism of acetaminophen (AP) and its effect on hepG2 cytotoxicity were studied first. Then metabolism based drug-drug interaction between AP and phenytoin (PH), which resulted in increased hepG2 cytotoxicity, was proved on this device. All this demonstrated that the developed microfluidic device could be a potential useful tool for drug metabolism and metabolism based drug-drug interaction research.