基于微纳光电子器件的植入式荧光计研究

An implantable fluorometer, which dynamically monitors biological activities by detecting the fluorescence change inside the body, shows promise in various biomedical applications, especially in the area of neuronal signal detection. Compared to its waveguide-coupled counterparts, a fluorometer based on implantable microscale optoelectronic devices is more advantageous due to its small footprint, low power consumption, high spatial resolution and wireless operation. The proposed work is focused on the development of an implantable fluorometer based on thin-film microscale InGaN LEDs and InGaP photodetectors, aiming to achieve highly sensitive fluorescence signal detection of the neuronal indicator GCaMP in multiple regions in the deep brain tissue of living animals. By investigating light and tissue interactions, we will try to understand the process of light propagation, absorption and emission inside mammalian brain tissues, and establish mathematical optical models for the device design. Specific optical structures will be simulated and implemented onto LEDs and photodetectors, optimizing the detection sensitivity of fluorescence signals. Advanced manufacturing methods including epitaxial liftoff and transfer printing will be explored to fabricate thin-film, mechanically stacked microscale LEDs and detectors, assembling the device array onto flexible and injectable substrates. In addition, we plan to integrate the devices with miniaturized circuits, which control and read out signals wirelessly. Furthermore, the device lifetime, toxicity, operation temperature, signal stability will be investigated in simulated biological fluids as well as inside the brain of freely moving animals. The proposed research will utilize the fundamental light-matter interaction in biological systems for the development of advanced optical neural interfaces that realize highly sensitive neural activity readout in vivo.

植入式的荧光计通过检测荧光物质发光变化来探测生物活动，在生物医疗领域特别是神经信号活动监测方面有着广泛的应用前景。与光波导耦合的荧光计相比，运用微型光电子器件集成的荧光计直接把器件植入生物体内，具有尺寸小、能耗低、无线便携、适合多点检测等特点。本项目拟从探索光与生物组织相互作用入手，理解光信号在生物脑内的传播过程，并以此为基础设计开发基于微型薄膜式InGaN LED和InGaP光电探测器的植入式荧光计；通过设计堆叠器件的光学结构，优化荧光计对神经荧光蛋白的探测灵敏度；开发薄膜光电器件的剥离和转移技术，实现器件阵列在柔性植入式基底上的集成；设计小型无线控制电路进行光电信号的采集；最终实现在活体动物深层脑组织内多区域的荧光信号高灵敏探测。本项目的开展，对深入理解光电器件与生物组织的相互作用，用光电信号实现生物神经活动的监测，开发新型的生物医疗器件，都具有重要的指导意义。

植入式的荧光计通过检测荧光物质发光变化来探测生物活动，在生物医疗领域特别是神经信号活动监测方面有着广泛的应用前景。与光波导耦合的荧光计相比，运用微型光电子器件集成的荧光计直接把器件植入生物体内，具有尺寸小、能耗低、无线便携、适合多点检测等特点。本项目从探索光与生物组织相互作用入手，理解光信号在生物脑内的传播过程，并以此为基础设计开发了基于微型薄膜式InGaN LED和InGaP光电探测器的植入式荧光计；通过设计器件的光学结构，优化荧光计对神经荧光蛋白的探测灵敏度；开发薄膜光电器件的剥离和转移技术，实现器件阵列在柔性植入式基底上的集成；设计小型无线控制电路进行光电信号的采集；最终实现在活体动物深层脑组织内不同脑区进行钙荧光信号和多巴胺信号的无线高灵敏探测。本项目的开展，对深入理解光电器件与生物组织的相互作用，用光电信号实现生物神经活动的监测，开发新型的生物医疗器件，都具有重要的指导意义。