Cardiac arrhythmia remains a major cause of morbidity and mortality worldwide, yet current diagnostic and research tools lack the spatial and temporal resolution necessary to fully characterize the underlying electrical mechanisms. This dissertation presents a suite of high density microelectrode array (MEA) technologies and CMOS integrated circuits and systems that enable high resolution electrophysiological investigation in both in vivo and in vitro settings. Three MEA systems are developed for cardiac interfaces, spanning the whole heart, through living myocardial slices, and down to single cell resolution, while integrating multichannel biopotential acquisition, impedance and capacitance spectroscopy, and electrical stimulation. Collectively, these MEA systems advance the capabilities of cardiac and neural electrophysiology by providing high density, multifunctional platforms suitable for diagnostics, drug screening, and disease modeling.

In this paper, we present an equivalent circuit model that integrates a living myocardial slice (LMS) cultured on a microelectrode array (MEA) to effectively simulates a heart-on-a-chip (HoC) within Electronic Design Automation (EDA) software. The cardiac fiber model consists of cardiomyocytes interconnected by gap junctions to simulate the action potential (AP) conduction in the longitudinal direction. We systematically explored several parameters, including gap junction resistors, seal resistors, and electrode diameters, to assess their effects on local field potential (LFP). The model accuracy was validated through in vitro experiments using mouse LMS, confirming its potential for guiding HoC design in cardiac research.

This paper presents the main circuit design considerations for power-efficient and safe implantable electrical neurostimulators. Related to medical applications, low-frequency (LF) stimulation for generating new action potentials and kilohertz-frequency alternating current (KHFAC) for blocking unwanted neural activity are introduced, respectively. For implantable medical devices, the choice of energy source type is important as it has an influence on the total size of the device and device comfort, thereby affecting the quality of life of the patients. In order to lengthen the lifetime of the stimulator, power-efficient designs using the ultra-high frequency (UHF) pulsed technique are proposed. To avoid tissue damage and electrode degradation caused by residual charge on the electrode-tissue interface (ETI), charge balancing (CB) techniques are adopted. Active CB control is shown to be a promising method both for LF and KHFAC stimulation.

Kilohertz frequency alternating current (KHFAC) stimulation can induce fast-acting, reversible and repeatable nerve conduction block, and is a candidate therapeutic method for diseases caused by undesired neural activities, such as urinary retention. In this paper, we first show that ultra-high frequency (UHF) current pulses can also lead to successful nerve conduction block, based on simulation results using the McIntyre-Richardson-Grill (MRG) model. This model describes a myelinated axon of mammalian animals. Second, we present a prototype of a power efficient neural stimulator using UHF current pulses with active charge balancing (CB). The stimulator is built using off-the-shelf components and can be battery-powered. It uses a DC-DC boost converter without a big filtering capacitor, for generating UHF current pulses. The power efficiency of the complete system is up to 98% when testing with an equivalent circuit model of electrode tissue interface (ETI). Safety measurement results show that the electrode offset voltage can be as high as 1.3 V without charge balancing, in in vitro experiments with titanium electrodes in a phosphate buffered saline (PBS) solution. However, this electrode offset voltage can be successfully lowered to less than 42.5 mV, by means of negative-feedback duty cycle control of the H-bridge clock. The active CB is adopted for KHFAC stimulation for the first time.