Monolithic silicon for high spatiotemporal translational photostimulation

Pengju Li, Jing Zhang, Hidenori Hayashi, Jiping Yue, Wen Li, Chuanwang Yang, Changxu Sun, Jiuyun Shi, Judah Huberman-Shlaes, Narutoshi Hibino () and Bozhi Tian ()
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Pengju Li: The University of Chicago
Jing Zhang: The University of Chicago
Hidenori Hayashi: The University of Chicago
Jiping Yue: The University of Chicago
Wen Li: The University of Chicago
Chuanwang Yang: The University of Chicago
Changxu Sun: The University of Chicago
Jiuyun Shi: The University of Chicago
Judah Huberman-Shlaes: The University of Chicago
Narutoshi Hibino: The University of Chicago
Bozhi Tian: The University of Chicago

Nature, 2024, vol. 626, issue 8001, 990-998

Abstract: Abstract Electrode-based electrical stimulation underpins several clinical bioelectronic devices, including deep-brain stimulators1,2 and cardiac pacemakers3. However, leadless multisite stimulation is constrained by the technical difficulties and spatial-access limitations of electrode arrays. Optogenetics offers optically controlled random access with high spatiotemporal capabilities, but clinical translation poses challenges4–6. Here we show tunable spatiotemporal photostimulation of cardiac systems using a non-genetic platform based on semiconductor-enabled biomodulation interfaces. Through spatiotemporal profiling of photoelectrochemical currents, we assess the magnitude, precision, accuracy and resolution of photostimulation in four leadless silicon-based monolithic photoelectrochemical devices. We demonstrate the optoelectronic capabilities of the devices through optical overdrive pacing of cultured cardiomyocytes (CMs) targeting several regions and spatial extents, isolated rat hearts in a Langendorff apparatus, in vivo rat hearts in an ischaemia model and an in vivo mouse heart model with transthoracic optical pacing. We also perform the first, to our knowledge, optical override pacing and multisite pacing of a pig heart in vivo. Our systems are readily adaptable for minimally invasive clinical procedures using our custom endoscopic delivery device, with which we demonstrate closed-thoracic operations and endoscopic optical stimulation. Our results indicate the clinical potential of the leadless, lightweight and multisite photostimulation platform as a pacemaker in cardiac resynchronization therapy (CRT), in which lead-placement complications are common.

Date: 2024
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DOI: 10.1038/s41586-024-07016-9

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