Smart multimodal neuroscience platform for enabling untethered behavioural experiments

该项目旨在开发新的工具，通过先进的无线、多模式、脑接口技术，显著简化和加速发现针对神经退行性疾病的创新疗法。我们建议开发一种创新的无线平台，通过单细胞电生理技术、光遗传学能力和脑成像手段，在一个长期植入的设备内，以高空间分辨率和毫秒时间尺度探测自由行为的啮齿动物的大脑微电路，实时提取大脑对药物的直接反应。这个智能平台包括一个可植入小鼠体内的轻量级无线脑机接口（BMI）和一个无线电力传输系统，以避免频繁的动物操作。我们团队开发的定制CMOS集成电路将为这种BMI提供大规模传感、光遗传刺激和荧光成像能力，以及智能，与一种新的多功能生物医学系统（BioMEMS）接口，该生物医学系统将在微纳米尺度上访问大量神经元。我们期望通过利用CMOS技术和多技术集成，将BMI的尺寸、重量和能耗降至前所未有的水平（分别为1 cm3、1g和10 mW）。所有组件将通过CMC微系统的学术服务开发，并在拉瓦尔大学欧洲经委会高级生物医学微系统集成设施中集成到一个长期可植入的自主微系统中。***除了在微系统设计、无线通信、能量收集和生物医学工程方面实现一些创新和解决关键挑战外，该项目还将在无线仪器技术方面发展独特的世界级专业知识，这将成为加拿大医学和生物医学产业光遗传学和神经科学研究平台发展的基石。这项新技术将提供一个独特的平台，通过实时观察自由行为受试者的大脑微电路，加速对阿尔茨海默病、帕金森病、癫痫、抑郁症和慢性疼痛等脑部疾病的新治疗方法的突破性研究，这将通过降低医疗保健成本、实现新疗法和为推进研究提供新工具，对加拿大人的财富产生可衡量的影响。事实上，在毫秒时间尺度上精确测量单个神经元对药物的直接反应的能力，以及在行为过程中，将为提高药物效率提供直接的性能指标。从长远来看，这项研究将通过培训、雇用和留住高素质的生物医学工程人员而做出持久的贡献。

This program aims to develop new tools that will significantly ease and accelerate discovery of innovative therapeutics against neurodegenerative diseases through advanced wireless, multimodal, brain-interfacing technology. We propose to develop an innovative wireless platform to extract the direct brain responses to drugs in real time by probing brain microcircuits of freely behaving rodents with high spatial resolution, and at millisecond time-scale, through single cell electrophysiology technology, optogenetic capabilities, and brain imaging means, all combined within a single chronically implantable device.***This smart platform includes a lightweight wireless brain-computer interface (BMI) that is implantable in the body of mice and a wireless power transmission system to avoid frequent animal manipulations. A custom CMOS integrated circuits developed by our team will provide this BMI with large-scale sensing, optogenetic stimulation and fluorescence imaging capability, as well as intelligence, to interface with a new multifunctional BioMEMS that will give access to large groups of neurons at the micro and nano scale. We anticipate to scale down the size, the weight and the energy consumption of this BMI to unprecedented levels (1 cm3, 1g and 10 mW, respectively) by exploiting CMOS technology and multitechnology integration. All components will be developed through CMC Microsystems' academic services and integrated within a chronically implantable, autonomous microsystem, at the Advanced Biomedical Microsystem Integration Facility of the ECE Dept. in Laval University. ***In addition to enable several innovations and to address key challenges in microsystem design, wireless communications, energy harvesting and biomedical engineering, this program will develop a unique and world-class expertise in wireless instrumentation technology that will become the corner stone for the development of optogenetics and neuroscience research platforms for medicine and biomedical industries in Canada. This new technology will provide a unique platform to accelerate ground breaking research towards new treatments for brain diseases like Alzheimer's and Parkinson's disease, epilepsy, depression, and chronic pain, by enabling observation of brain microcircuits of freely behaving subjects in real time, which will have a measurable impact on the wealth of Canadians by reducing costs of healthcare, enabling new therapies and providing new tools to advance research. Indeed, the capability of precisely measuring the direct response of the brain to drugs at the scale of individual neurons at millisecond time-scale, yet during behaviour, will provide a direct performance indicator to increase drugs efficiency. On the long term, this research will leave a durable contribution by training, hiring, and retaining highly qualified personnel in biomedical engineering.