CMOS Nanoelectrode Array for High Throughput Electrocardiography

Nanoelectrode;CMOS;Nano-bio Interface;Intracellular

Ye, Tianyang ; Park, Hongkun,Ham, Donhee

University:Havard University

Department:Engineering and Applied Sciences - Applied Physics

关键词: Nanoelectrode;    CMOS;    Nano-bio Interface;    Intracellular;   

Others  :  https://dash.harvard.edu/bitstream/handle/1/37365149/YE-DISSERTATION-2020.pdf?sequence=1&isAllowed=y

美国|英语

来源: Digital Access to Scholarship at Harvard

【 摘 要 】

It has been a perpetual desire for human being to understand our own intelligence. Following the series of breakthroughs in the 20th century, neuroscience has enjoyed the spotlight being one of the most promising and rewarding field of science in the 21st century. Yet the steps of neuroscience have slowed down partly due to the lack of appropriate tools. Electrophysiology is one of the most fundamental aspects of brains sciences as neurons use electrical signals to perform computations in a network, many also believed these electrical signals are the underlying mechanism of higher functions like memories. Electrode based techniques are the most universal tools used in neuron electrophysiology, and they can be categorized into two large groups: intracellular electrodes and extracellular electrodes. Intracellular electrode, e.g. patch clamp electrode, can provide detailed information of a neuron’s full electrical signal but they are hard to operate and almost impossible to scale up. Extracellular electrode, e.g. Multi-electrode-array, can command thousands of electrodes in parallel yet their signals are often noisy and mixed up. Facing this challenge, this dissertation work strives to combing the intracellular power of nanoscale electrode with the multiplexing capability of Complimentary-Metal-Oxide-Semiconductor (CMOS) electronics and build a platform of high-throughput electrophysiology. Chapter one gives a more detailed introduction of the development of electrophysiology for neuroscience and the challenges facing electrode-based techniques. It also provides a review of the state-of-the-art development for both intracellular techniques and extracellular techniques. Chapter two describes our experimental efforts for the CMOS Nano Electrode Array (CNEA) device platforms. It starts with the inception of idea and the advantage of introducing CMOS electronics into nanoelectrode arrays. Then we discussed in detail the CMOS circuit design, fabrication and packaging of the device. Finally, we demonstrated the platform’s capability of massively intracellular recording on neonatal rat cardiomyocyte cells. Chapter three continues on the same concept with the new generation of CMOS Neuro-Electrode Interface (CNEI) device system. In addition to basic CMOS circuit design and the fabrication process, this chapters emphasizes the improvements we made for this new generation. These improvements enable us to study the more delicate and yet more interesting neonatal rat neuron cultures and finally perform mapping of their synaptic connections. Chapter four represents one of the later developments of the platform where we customize the electrode interface and use it for brain slice applications.