用于外泌体一体化分离、检测的自供能微流控检测器的研制

Exosomes are associated with tumorigenesis, tumor metastasis, immunosuppression, angiogenesis，and they can be regarded as important accomplices of the invasion and distant metastasis to the normal cells from tumor cells, thus it can be used as one of the main objects for liquid biopsy. This project will propose a novel strategy and method for liquid biopsy mainly towards the detection and monitoring for the exosome. Microfluidic chips with corresponding multi-functions will be designed according to the relevant physical and chemical properties of exosomes in different stages and heterogeneity situation for various cancers. Efficient separation of exosomes can be achieved even under the situation with little or microscale amount sample, which will benefit for efficient separation of scarce samples and also for further downstream research. At the same time, the photosensitive nano-materials with photoelectric conversion property will be used as the active source for signal output of the microfluidic chip to realize effective detection of exosomes with a low detection limit and high throughput, if so, the current problem, that the separation and detection cannot be effectively carried out simultaneously, will be thoroughly solved. The photosensitivity of nano-photoelectric material or light source generated by the internal active chemical material will benefit for solving the bottleneck problem in miniaturization and the energy self-supply of the chip. This project will provide a novel idea for the integration of separation and detection of exosomes, and it can expand the application scope of microfluidic chip, which will provide a powerful approach for separation and detection with high efficiency for other disease markers.

外泌体与肿瘤发生发展、肿瘤转移、免疫反应抑制、血管生成等过程相关，可看作是肿瘤细胞侵袭和远处播散转移的重要帮凶，可作为液体活检的主要被检测物之一。本项目提出一种以外泌体为主要对象的液体活检新策略及新技术：依据不同癌症、不同时期及发生异质化等状况下的外泌体的相关理化特性设计具备相应功能的微流控芯片，在少量或微量样品条件下实现外泌体的高效分离，再以具有光电转换效应的纳米材料作为微流控芯片上外泌体的信号产出的活性物质，实现外泌体的高灵敏、高通量检测，解决目前分离、检测不能有效同时进行的难题。同时利用纳米光电材料的光敏性或内部活性物质所产生的化学光源将芯片的能量自供给化，可解决器件难以微小型化的瓶颈问题。本项目的实施将为分离、检测外泌体一体化提供新的思路，可拓展微流控芯片的应用范围，也为其他疾病标志物高效分离、检测方法的构建提供有力的借鉴。

癌症的早期有效诊断仍为降低死亡率的最有效方法，因此从癌细胞产生到发生转移之前的这段时间，是检测和诊断癌症的黄金窗口期，而外泌体可提供一项稳定的RNA标志物用于疾病的诊断、预后以及治疗监控。本项目在正对外泌体为主要对象的高灵敏度及高通量检测、利用纳米光电材料的光敏性实现微流控检测器件自供能等方面取得了一定进展。研究内容主要有：（1）构建了基于Mo:BiVO4的并行时空高通量检测三种与结直肠癌相关的IncRNA（L1，UCA1和AF079515）的自供能一体化传感芯片，大大提高结直肠癌早检的准确性，可有效避免假阳性造成的误诊，目前已着手将相关技术推向产业化及市场；（2）构建基于Zn:SnO2/SnS2的超灵敏自供能传感芯片用于阿尔茨海默病的早期诊断，所构建的自供能传感器实现了展现出较好的性能；（3）对于自供能传感芯片连接的性能提升提出了有效利用Au−Se界面的策略，有效解决了传统的Au−S界面上信号易于失真、扭曲的问题，同时显示了较高的电荷转移效率；（4）构建了一系列基于光阳、阴极材料的针对乳腺癌lncRNA自供能传感芯片，在此基础上开发了异质结光响应双通道传感芯片，并申请知识产权保护，以期对乳腺癌的早期风险判定和精准治疗提供一定的理论及产业支撑，目前已着手将相关技术推向产业化及市场；（5）在项目积累的理论研究的基础上，项目负责人已开始研制针对胃癌、风湿疾病等癌症的早检的自供能一体化传感芯片。项目在外泌体等疾病标志物的液体活检构建策略上进行大量有益的探索，为外泌体等疾病标志物的高效分离、检测提供新的思路及基础，具有较强的可行性和广阔的市场应用前景，也为其他疾病标志物高效检测方法的构建提供有力的借鉴。