Optogenetic modulation of cortical neurons using organic light emitting diodes (OLEDs)

Abstract

Objective -There is a need for low power, scalable photoelectronic devices and systems for emerging optogenetic needs in neuromodulation. Conventional light emitting diodes (LEDs) are constrained by power and lead-counts necessary for scalability. Organic LEDs (OLEDs) offer an exciting approach to decrease power and lead-counts while achieving high channel counts on thin, flexible substrates that conform to brain surfaces or peripheral neuronal fibers. In this study, we investigate the potential for using OLEDs to modulate neuronal networks cultured in vitro on a transparent microelectrode array (MEA) and subsequently validate neurostimulation in vivo in a transgenic mouse model. Approach -Cultured mouse cortical neurons were transfected with light-sensitive opsins such as blue-light sensitive channel-rhodopsin (ChR2) and green-light sensitive chimeric channelrhodopsin (C1V1tt) and stimulated using blue and green OLEDs (with 455 and 520 nm peak emission spectra respectively) at a power of 1 mW/mm 2 under pulsed conditions.Main results -We demonstrate neuromodulation and optostimulus-locked, single unit-neuronal activity in neurons expressing stimulating and inhibiting opsins (n=4 MEAs, each with 16 recordable channels). We also validated the optostimulus-locked response in a channelrhodopsin expressing transgenic mouse model, where at least three isolatable single neuronal cortical units respond to OLED stimulation. Significance -The above results indicate the feasibility of generating sufficient luminance fromOLEDs to perform neuromodulation both in vitro and in vivo. This opens up the possibility of developing thin, flexible OLED films with multiple stimulation sites that can conform to the shape of the neuronal targets in the brain or the peripheral nervous system. However, stability of these OLEDs under chronic conditions still needs to be carefully assessed with appropriate packaging approaches.

Organic Bioelectronics for In Vitro Systems

“…Optogenetics is the induction of light-sensitive molecules in cells to allow for modulation of the cell’s activity . As such, OLEDs have been used to optogenetically control different neuronal populations. − Another promising area of work for neuronal modulation is the use of organic optoelectronic materials. Different studies have shown the propensity to initiate neural firing through optoelectronic photostimulation ,,,,− or even silencing .…”

Emerging Biomedical Applications of Organic Light‐Emitting Diodes

“…Optogenetic stimulation of cortical neurons in culture and in vivo was also investigated by Sridharan et al using simultaneous read-out of neuronal activity via microelectrode arrays. [252] For this, blue and green OLEDs on PET substrates were used, which reached power densities exceeding 1 mW mm −2 when driven in pulsed mode at 10 Hz/10 ms at voltages of 12.5 V (blue OLEDs) and 15 V (green OLEDs).…”

Biocompatible and Biodegradable Light‐Emitting Materials and Devices

“…[ 67 ] With the inherent advantages like flexibility, biocompatibility, and adjustable dimensions, recently reported low power OLEDs also integrated with neural tissues and interact with genetically engineered light‐sensitive opsins. [ 68 ] We envision that there will be more investigations about the development of OLED‐based implantable systems for biomedical applications in the future research.…”