细胞器靶向的多参数协同精准分析光学传感器研究

Multi-parameter combination analysis has a great application in life science and medical applications. In this project, we are aiming to solve the vital problems in the field of multi-parameter sensing and imaging, which includes signal fast-decay, poor measurement stability, low precision, usage of large number and many kinds of sensors, uncontrollable distribution of sensors, and high imaging background. Simultaneously sensing and imaging intracellular key parameters (including oxygen, pH and temperature) was selected as an example to show our strategy in designing the targeted multiple nanosensor. We will start our research from screening and synthesizing high-performance fluorescent probes and sensing materials. The multiple nanosensor was constructed based on a new strategy called "space division". Sensing material will be divided into different functional regions according to their functionalities. Their surface will be modified with protecting polymer and targeting groups to form core/shell nanostructure and specifically direct the multiple sensor at an intracellular site of interest. This external surface will also act as a barrier to protect the internal optical probes and prevent their cross-talking to ions and other small molecules. This specially designed structure will allow all sensors have their optimized performances. The multiple optical signals will be analyzed using fluorescence lifetime based sensing and imaging technology, which can significantly improve sensor stability and measurement precision, greatly reduce imaging background, make signal separation easier, and prevent signal cross-talking. Through multi-parameter joint, compensation and reference analysis, we can use less sensors to gain more intracellular key parameters, which enables high-precision sensing at specific sites of interest, and makes real-time monitoring intracellular activities become possible. The application of these targeted multiple sensors will be extended to life science and disease diagnosis.

多参数联合分析在探究生命过程和疾病诊疗领域具有极其重要的生物学和医学价值，本项目针对多参数荧光成像分析中信号衰减快、测量稳定性差、准确度低、传感器使用种类多、数量大、细胞内分布不可控、无法定位分析、荧光成像背景过高等关键难题，以氧气、pH和温度多参数检测传感器为例，筛选、合成高性能荧光探针和传感材料，并以“空间分割”新策略为主线，对同一纳米材料根据功用进行三维空间划区和修饰，构建具有靶向细胞器/受体能力的多参数协同检测纳米传感器，使各传感器能发挥其最佳性能。并建立以荧光寿命测量为核心的多通道协同精准成像分析新技术，通过多参数联合、补偿和参比分析，解决多参数分析中信号串扰和分离难题，提高传感器的稳定性和测量精度，大幅度降低成像背景干扰，实现使用更少传感器得到细胞内更多参数的高空间分辨、精确定位的精准成像分析，使实时跟踪细胞内动态变化成为可能，并拓展多参数传感器在生命科学和疾病综合诊疗中的应用