Optimal Electrode Size for Multi-Scale Extracellular-Potential Recording From Neuronal Assemblies

Advances in microfabrication technology have enabled the production of devices containing arrays of thousands of closely spaced recording electrodes, which afford subcellular resolution of electrical signals in neurons and neuronal networks. Rationalizing the electrode size and configuration in such arrays demands consideration of application-specific requirements and inherent features of the electrodes. Tradeoffs among size, spatial density, sensitivity, noise, attenuation, and other factors are inevitable. Although recording extracellular signals from neurons with planar metal electrodes is fairly well established, the effects of the electrode characteristics on the quality and utility of recorded signals, especially for small, densely packed electrodes, have yet to be fully characterized. Here, we present a combined experimental and computational approach to elucidating how electrode size, and size-dependent parameters, such as impedance, baseline noise, and transmission characteristics, influence recorded neuronal signals. Using arrays containing platinum electrodes of different sizes, we experimentally evaluated the electrode performance in the recording of local field potentials (LFPs) and extracellular action potentials (EAPs) from the following cell preparations: acute brain slices, dissociated cell cultures, and organotypic slice cultures. Moreover, we simulated the potential spatial decay of point-current sources to investigate signal averaging using known signal sources. We demonstrated that the noise and signal attenuation depend more on the electrode impedance than on electrode size, per se, especially for electrodes <10 μm in width or diameter to achieve high-spatial-resolution readout. By minimizing electrode impedance of small electrodes (<10 μm) via surface modification, we could maximize the signal-to-noise ratio to electrically visualize the propagation of axonal EAPs and to isolate single-unit spikes. Due to the large amplitude of LFP signals, recording quality was high and nearly independent of electrode size. These findings should be of value in configuring in vitro and in vivo microelectrode arrays for extracellular recordings with high spatial resolution in various applications

Development of a Dual-Mode CMOS Microelectrode Array for the Simultaneous Study of Electrochemical and Electrophysiological Activities of the Brain

Medical diagnostic devices are in high demand due to increasing cases of neurodegenerative diseases in the aging population and pandemic outbreaks in our increasingly connected global community. Devices capable of detecting the presence of a disease in its early stages can have dramatic impacts on how it can be treated or eliminated. High cost and limited accessibility to diagnostic tools are the main barriers preventing potential patients from receiving a timely disease diagnosis. This dissertation presents several devices that are aimed at providing higher quality medical diagnostics at a low cost. Brain function is commonly studied with systems detecting the action potentials that are formed when neurons fire. CMOS technology enables extremely high-density electrode arrays to be produced with integrated amplifiers for high-throughput action potential measurement systems while greatly reducing the cost per measurement compared to traditional tools. Recently, CMOS technology has also been used to develop high-throughput electrochemical measurement systems. While action potentials are important, communication between neurons occurs by the flow of neurotransmitters at the synapses, so measurement of action potentials alone is incapable of fully studying neurotransmission. In many neurodegenerative diseases the breakdown in neurotransmission begins well before the disease manifests itself. The development of a dual-mode CMOS device that is capable of simultaneous high-throughput measurement of both action potentials and neurotransmitter flow via an on-chip electrode array is presented in this dissertation. This dual-mode technology is useful to those studying the dynamic decay of the neurotransmission process seen in many neurodegenerative diseases using a low-cost CMOS chip. This dissertation also discusses the development of more traditional diagnostic devices relying on PCR, a method commonly used only in centralized laboratories and not readily available at the point-of-care. These technologies will enable faster, cheaper, more accurate, and more accessible diagnostics to be performed closer to the patient