On-Demand Targeted Light Generation in Bio-Compatible Elastomers Using High-Intensity Focused Ultrasound for Optogenetic Application

Currently most optogenetic activations are triggered by LED that usually requires invasive optical fiber implants, which presents challenges for in vivo studies and biomedical applications. Herein we introduce a new targeted, remote light generation platform based on high-intensity focused ultrasound (HIFU) that exploits polymer mechanochemistry to spatiotemporally control the remote emission of light (1). As a proof of concept, 1.5 wt% of covalently incorporated 1,2-dioxetane mechanophore was embedded as a crosslinker in a 5 mm thick PDMS film. Upon scission of the dioxetane, the mechanophore generated an excited state ketone and in the process emitted luminescence. The luminescence was enhanced by an energy acceptor, 9,10-diphenylanthracene (DPA). In a tank of degassed water, a HIFU transducer (550 kHz) was employed to generate continuous wave ultrasound for 5 seconds that triggered the prepared dioxetane functionalized PDMS film. Blue luminescence (ca. 470 nm) was observed from the PDMS film through remote, non-invasive control via HIFU. However, the measured intensity (ca. 0.2 μW/cm²) was weaker than the reported threshold (ca. 1~10 mW/cm²) for optogenetic applications (2). This low intensity is due to the weakly-dispersible DPA and can be overcome by adopting a more soluble hexyl-functionalized DPA (HDPA). Incorporating 7.5 wt% HDPA into PDMS improved the solubility of the energy acceptor and the emitted light intensity by two orders of magnitude. We believe this increased intensity could be promising for optogenetic applications. This study explores HIFU as a potential stimulus that is capable of triggering on-demand, spatiotemporally resolved mechanoluminescent transduction to leverage the advantages of existing optogenetic technologies.

References

1. Kim G, et al. (2019) High-intensity focused ultrasound-induced mechanochemical transduction in synthetic elastomers. Proc Natl Acad Sci 116(21):1021410222.

2. Raman R, et al. (2016) Optogenetic skeletal muscle-powered adaptive biological machines. Proc Natl Acad Sci 113(13):34973502.