Wide Area Uniform Illumination Scheme Using LED Matrix for Optogenetic Cardiac Pacing

Control of heart rhythm is vital in the case of arrhythmia. Cardiac optogenetics is a promising technique to replace electrical stimulation in a next generation of pacemakers and defibrillators. Therefore, further research towards optimizing light delivery methods is essential. A major requirement is the uniform stimulation of all cells in the area of interest while reducing side effects such as photodamage. Here, a 2 x 2 blue (470 nm, InGaN-based) light-emitting diode (LED) optoelectronic module for uniform ex vivo cardiac muscle illumination is demonstrated. It satisfies two important requirements in optogenetics, which are high illumination homogeneity and high irradiance. CCD camera images show an average 90% homogeneity over the central illumination area of close to 38 mm2 at 1 cm distance from the light source. The module is used to perform physiological experiments on channelrhodopsin 2-expressing Langendorff-perfused mouse hearts. Successful ventricular pacing is obtained for an optical power density threshold below 2 mW/mm2 with light pulses as short as 1 ms. For 10 ms long pulses, the threshold was below 0.2 mW/mm2. The large homogeneous illumination area enabled optogenetic pacing with less than half the optical power of previous attempts with smaller areas of 2 mm2 and thus, presumably, will result in less phototoxicity.