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Stimulation of isolated ventricular myocytes within an open architecture microarray
Norbert Klauke1, Godfrey L Smith, Jonathan M Cooper
1Department of Elecronics and Electrical Engineering, Rankine Building, University of Glasgow, Glasgow G12 8LT, UK. norbert@elec.gla.ac.uk
IEEE Transactions on Bio-Medical Engineering
|March 12, 2005
Summary
This study developed microfluidic chambers for studying heart cell physiology, enabling prolonged electrical stimulation and functional excitation-contraction coupling (EC coupling) in isolated myocytes.
Area of Science:
- Biomedical Engineering
- Cardiovascular Physiology
- Microfluidics
Background:
- Investigating the physiological responses of single heart cells requires precise control over the cellular microenvironment.
- Existing methods may not adequately support long-term studies of cellular electrophysiology and contractility.
Purpose of the Study:
- To develop and validate a microfluidic system for the prolonged electrical stimulation of isolated adult cardiac myocytes.
- To assess the functional integrity of excitation-contraction coupling (EC coupling) under controlled microfluidic conditions.
- To enable drug screening and multiplexed optical detection for cardiac cell research.
Main Methods:
- Fabrication of polydimethylsiloxane (PDMS) microfluidic chambers using replica molding against SU-8 masters.
- Integration of gold microelectrodes for electrical stimulation of myocytes within the chambers.
- Micropipetting of isolated rabbit ventricular myocytes into defined volumes (4 nL to 4 μL).
- Optical monitoring of action potential duration (APD), intracellular Ca2+ transients, and cell shortening using sensitive dyes.
Main Results:
- Demonstrated sustained, functional excitation-contraction coupling (EC coupling) in isolated cardiac myocytes within microfluidic chambers.
- Observed constant amplitude of Ca2+ transients and cell shortening during prolonged stimulation (up to 20 min in larger volumes).
- Recorded prolonged action potential duration (APD) at higher pacing frequencies (1 Hz vs. 0.5 Hz).
- Showcased the system's capability for drug dispensation and multiplexed optical detection without crosstalk.
Conclusions:
- The developed microfluidic system supports prolonged electrical stimulation of cardiac myocytes with unimpaired EC coupling.
- This platform is suitable for studying cardiac cell electrophysiology, Ca2+ handling, and contractility.
- The open architecture facilitates drug screening and high-throughput analysis of cardiac cell function.