基于磁小体链和可调磁场微流控芯片技术提高检测痕量循环肿瘤细胞效率的研究

Tumor invasion and metastasis are the main factors for the high mortality rate of malignant tumors, and detection of circulating tumor cells is one of the most important methods for early detection and diagnosis of tumor invasion and metastasis. However, the current detection methods can’t meet the clinical requirements. To enrich and detect the trace circulating tumor cells from the blood more effectively, this project take the magnetosomes chain which constituted by a biological synthesis of magnetic nanoparticles, called magnetosomes, instead of artificial chemical synthesis of magnetic nanoparticles. Because the magnetosomes are synthesized by magnetotactic bacteria under precise genetic control and surrounded by a lipid bilayer accompanied with specific soluble transmembrane proteins. Compared with engineered magnetic nanoparticles, magnetosomes have specific features such as large-scale production, monodispersity, good biocompatibility, high crystallinity, and close-to-bulk magnetization besides a lipid bilayer covered. And the soft magnetic materials were instead of hard magnetic materials for the magnet used in the microfluidic chip. The magnetic fields intensity and gradient of the micro magnet controlled by applied electromagnetic field according to different circulating tumor cells. This could reduce the nonspecific adsorption of leukocyte cells by the immune magnetosomes and improve the detection accuracy of circulating tumor cells in the blood. This project will build a kind of more efficient and accurate enrichment and detection methods of circulating tumor cells, take advantage of the combination of biochemistry, genetic engineering, immunocytochemical techniques, microfluidic chip technology and electromagnetic technology. It may provide new window for early diagnosis, monitoring of recurrence and metastasis of tumor, and reduce the death rate of malignant tumor.

肿瘤侵袭和转移是恶性肿瘤致死率高的主要因素，循环肿瘤细胞的检测成为早期检测和诊断肿瘤侵袭和转移的重要方法。而目前的检测方法还不能达到临床检测要求。本项目将粒径均一、磁性高、产量高，细胞膜包被而具有良好的分散性、稳定性和生物相容性的生物自身合成的磁纳米颗粒-磁小体构成的磁小体链，代替人工化学合成磁颗粒用于循环肿瘤细胞的富集和检测。并采用软磁材料代替硬磁材料用于微流控芯片微型磁体，利用外加电磁场根据富集和检测循环肿瘤细胞种类的需求，调控微型磁体的磁场强度和梯度降低对白细胞的非特异性吸附提高富集和检测循环肿瘤细胞的精确度。本项目通过生物化学、基因工程、免疫细胞化学技术、微流控芯片技术和电磁技术相结合，构建一种更加高效和精确的循环肿瘤细胞富集和检测方法，为肿瘤的早期诊断、监测肿瘤的复发与转移提供依据，降低恶性肿瘤的致死率。

肿瘤侵袭和转移是恶性肿瘤致死率高的主要因素，循环肿瘤细胞的检测成为早期检测和诊 断肿瘤侵袭和转移的重要方法，而目前的检测方法还不能达到临床检测要求。本项目成功研制设计搭建了可控磁场发生装置，设计加工了微流控芯片；合成了EpCAM磁小体复合体并用于捕获肿瘤细胞；通过优化BMP浓度和EpCAM抗体浓度比例提高CTCs的捕获效率；并研究了微流控芯片在不同磁场强度、流速下捕获肿瘤细胞的效率。本项目研究结果能够为肿瘤的早期诊断、监测肿瘤的复发与转移提供依据，降低恶性肿瘤的致死率。