title: A closed-loop electrical stimulation system for cardiac cell cultures.
abstract: An integrated electrical stimulation and recording system was designed for closed-loop control and analysis of cardiac cultures on planar microelectrode arrays. Stimulated action potentials from HL-1 clonal myocyte cultures were digitized, stimulation artifacts were removed using nulling and filtering methods, and analysis was performed to determine stimulation efficacy in real time. Results of this analysis were used to determine future stimulation waveform parameters such as polarity, amplitude, pulse duration, and rate or pattern. Algorithms were designed utilizing real-time analysis and control to maintain a desired electrophysiological response of the culture, such as an arbitrary capture fraction value. This paper presents the hardware and software design of the stimulus pulse circuitry, artifact extraction, analysis, and control components of the system. Applications of this technology include the study of cardiac cell physiology, improving the speed and accuracy of traditional open-loop stimulation protocols, pharmacological screening, and improving the performance of biosensors based on sensing electrical activity in cardiac cultures.
authors.affiliation: Department of Electrical Engineering, Stanford University, CIS-206X, Stanford, CA 94305, USA. whitt@stanford.edu
authors.forename: R Hollis
authors.initials: RH
authors.lastname: Whittington
authors.forename: Laurent
authors.initials: L
authors.lastname: Giovangrandi
authors.forename: Gregory T A
authors.initials: GT
authors.lastname: Kovacs
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D002304:Cardiac Pacing, Artificial / Q000379:methods; D018929:Cell Culture Techniques / Q000295:instrumentation* / Q000379:methods; D002478:Cells, Cultured; D004558:Electric Stimulation / Q000295:instrumentation* / Q000379:methods; D004562:Electrocardiography / Q000295:instrumentation* / Q000379:methods; D004867:Equipment Design; D019544:Equipment Failure Analysis; D005246:Feedback / Q000502:physiology; D051379:Mice; D009200:Myocardial Contraction / Q000502:physiology*; D032383:Myocytes, Cardiac / Q000502:physiology*; D010138:Pacemaker, Artificial