Smart multimodal neuroscience platform for enabling untethered behavioural experiments

该计划旨在开发新的工具，通过先进的无线、多模式、大脑接口技术，显著简化和加快针对神经退行性疾病的创新疗法的发现。我们建议开发一种创新的无线平台，通过以高空间分辨率探测自由行为啮齿动物的大脑微电路，并在毫秒级的时间尺度上，通过单细胞电生理学技术、光遗传学能力和脑成像手段，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型无线脑机接口(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集成电路将为该BMI提供大规模传感、光遗传刺激和荧光成像能力，以及智能，与新的多功能生物MEMS接口，使其能够访问微米和纳米级的大组神经元。我们预计，通过利用CMOS技术和多技术集成，这款BMI的尺寸、重量和能耗将降至前所未有的水平(分别为1立方米、1克和10兆瓦)。所有组件将通过CMC微系统公司的学术服务进行开发，并在欧洲经委会系高级生物医学微系统集成设施中集成到一个可长期植入的自主微系统中。在拉瓦尔大学。*除了在微系统设计、无线通信、能量采集和生物医学工程方面实现多项创新和应对关键挑战外，该计划还将在无线仪器技术方面开发独特的世界级专业知识，这将成为加拿大医药和生物医学行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，通过实时观察行为自由的受试者的大脑微电路，加速对阿尔茨海默氏症和帕金森氏症、癫痫、抑郁症和慢性疼痛等脑部疾病的新疗法的开创性研究，这将通过降低医疗保健成本、启用新疗法和提供新工具来推进研究，对加拿大人的财富产生可衡量的影响。事实上，能够在毫秒级的时间尺度上精确测量大脑对药物的直接反应，但在行为过程中，这种能力将为提高药物效率提供一个直接的绩效指标。从长远来看，这项研究将通过培训、聘用和留住生物医学工程方面的高素质人员而留下持久的贡献。

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.