Periodic Reporting for period 1 - solLED (Solution-phase lighting-emitting devices for optogenetic control of the peripheral nervous system)
Reporting period: 2021-08-01 to 2023-07-31
Delivering light deep into tissue is of importance to technology in biophotonics, in particular in the context of optogenetics. One of the significant challenges is the development of bio-implantable optical probes that stimulate transgenic neurons expressing light-sensitive opsin protein (channelrhodopsin) located in deep tissues and simultaneously record eletrical, optical, or behavioral responses of neurons. Therefore, there has been a high demand for optical devices that are capable of convenient manufacturing, various form factors, and integration on a bio-implantable architecture. In addition, the mechanical robustness and some extent of flexibility of the device are important factors for bioimplants.
This project proposed a radically different device concept, a solution-phase light-emitting device (sol-LED) with a simple structure that can readily assume various forms and shapes and thus is of particular relevance to novel applications in the biomedical context. Specifically, the project addresses the following three objectives: 1) demonstration of sol-LEDs, 2) device optimization and color extension, 3) applications to stimulation of neurons in vitro and in vivo. The project has achieved most of its objectives for the period, with relatively minor deviations (details in the next section).
The MSCA project has significantly impacted the fellow’s professional career path both in scientific and non-scientific aspects. Within the project, the fellow acquired excellent experimental training and engaged in interactions with many experts. The experimental tools and resources supplied by the hosting group greatly helped the fellow create an innovative device named sol-LED and consequently become a leader of this research. In addition, the fellow was able to take a step toward biophotonics and obtained great opportunities to collaborate and discuss with people from the biological background. The outcomes achieved during the fellowship led to high-impact publications and presentations, increasing his reputation in the society of chemistry and bioengineering. In addition, the project provided a valuable opportunity for the fellow to collaborate with prominent professionals in various fields, including Prof. Kenneth Shepard on biophysics and neuroengineering at Columbia University, Prof. Karl Deisseroth on neurobiology and optogenetics at Stanford University, and Prof. Klaus Meerholz on physical chemistry and electrochemistry at Cologne University. The scientific publications, joint research, and presentations produced through the fellowship will greatly help him start a professorship in academia.
This project proposed a radically different device concept, a solution-phase light-emitting device (sol-LED) with a simple structure that can readily assume various forms and shapes and thus is of particular relevance to novel applications in the biomedical context. Specifically, the project addresses the following three objectives: 1) demonstration of sol-LEDs, 2) device optimization and color extension, 3) applications to stimulation of neurons in vitro and in vivo. The project has achieved most of its objectives for the period, with relatively minor deviations (details in the next section).
The MSCA project has significantly impacted the fellow’s professional career path both in scientific and non-scientific aspects. Within the project, the fellow acquired excellent experimental training and engaged in interactions with many experts. The experimental tools and resources supplied by the hosting group greatly helped the fellow create an innovative device named sol-LED and consequently become a leader of this research. In addition, the fellow was able to take a step toward biophotonics and obtained great opportunities to collaborate and discuss with people from the biological background. The outcomes achieved during the fellowship led to high-impact publications and presentations, increasing his reputation in the society of chemistry and bioengineering. In addition, the project provided a valuable opportunity for the fellow to collaborate with prominent professionals in various fields, including Prof. Kenneth Shepard on biophysics and neuroengineering at Columbia University, Prof. Karl Deisseroth on neurobiology and optogenetics at Stanford University, and Prof. Klaus Meerholz on physical chemistry and electrochemistry at Cologne University. The scientific publications, joint research, and presentations produced through the fellowship will greatly help him start a professorship in academia.
O1. Demonstration of sol-LEDs: We were able to sort out candidates of organic solvent for sol-LEDs and select the best candidates in terms of high boiling temperature, low vapor pressure, and high solubility. We discovered the formation of exciplex from a mixed solution of toluene and acetonitrile dissolving TAPC of 30 mM and TPBi of 30 mM, featured by a red-shifted emission PL spectrum and delayed fluorescence in transient PL decay. Adding 10 mM of yellow-emissive TBRb to the solution resulted in an efficient energy transfer from the exciplex to the dye. We manufactured sandwich-type sol-LEDs using the TAPC:TPBi:TPBi mixed solution. The device operating by ECL based on the exciplex formation showed enhanced brightness (max. 1250 cd/m2), luminous efficacy (max. 1.17 lm/W), and operational lifetime (a half-life of 78 seconds at an initial brightness of 100 cd/m2) compared to a sol-LED without exciplex materials operating by a conventional ECL pathway based on annihilation.
O2. Device optimization and color extension: We tested several charge injection layers for sol-LED and discovered the increase in performance when a mesoporous TiO2 electrode is applied to one of the ITO electrodes. We optimized the fabrication process for a 32-μm-thick mesoporous TiO2 layer with micrometer-sized TiO2 clusters uniformly coated on top of the ITO-coated glass substrate. Consequently, the device exhibited improved performance with a maximum brightness of 3780 cd/m2, a maximum luminous efficacy of 3.71 lm/W, and a half-life of 312 seconds at an initial brightness of 300 cd/m2.
We applied the same operating principle to sol-LEDs with red, yellow, light green, and green emission using dyes of Ir(MDQ)2acac, TBRb, Ir(ppy)2acac, and C545T, respectively. Furthermore, we demonstrated a soft-form sol-LED using PMDS and chemical-vapor-deposited AZO electrodes. We were able to demonstrate MSCA-logo patterned emission from the soft device by bump patterning on the PMDS structure that adjusted the distance between AZO electrodes so that a higher electric field was applied to the closer AZO-gap region.
O3. Applications to stimulation of neurons in vitro and in vivo: Driving the yellow sol-LED by a biphasic voltage pulse ensured a super high brightness of 25,000 cd/m2 (or 180 mW/mm2). We summarized the energy density of photon emission per pulse by parameters of pulse heights and pulse widths. We carried out Ca2+ imaging of neurons by fluorescence microscopy in vitro. A sandwich-type sol-LED was placed underneath the neuron-cultured dish and simultaneously on top of the objective of inverted microscope. Both excitation and fluorescence light passed through the device in this microscopy. Confirming the imaging technique and emission by sol-LED sufficiently bright to activate ChRmine-expressing neurons, we are preparing an optical pacing of contraction of transgenic cardiomyocytes expressing ChRmine using the light emission by sol-LED and simultaneous observation of the contraction by microscope.
Needle-shaped optical probes carrying out the stimulation of neurons in vivo were manufactured by monolithic integration of OLEDs on silicon probes with four 6-mm-long subshanks and 1024 CMOS backplanes. A robust passivation that combines the deposition of Al2O3/ZrO2 nanolaminates and parylene-C layers was performed after the device integration. The probes were implanted into the brain of anesthetized mice and performed the optical manipulation of neuronal activity located deep in the brain and recorded the electrical responses from the neurons in parallel.
As a result of the project, three scientific papers were published in high-impact journals including Advanced Materials and Nature Electronics.
O2. Device optimization and color extension: We tested several charge injection layers for sol-LED and discovered the increase in performance when a mesoporous TiO2 electrode is applied to one of the ITO electrodes. We optimized the fabrication process for a 32-μm-thick mesoporous TiO2 layer with micrometer-sized TiO2 clusters uniformly coated on top of the ITO-coated glass substrate. Consequently, the device exhibited improved performance with a maximum brightness of 3780 cd/m2, a maximum luminous efficacy of 3.71 lm/W, and a half-life of 312 seconds at an initial brightness of 300 cd/m2.
We applied the same operating principle to sol-LEDs with red, yellow, light green, and green emission using dyes of Ir(MDQ)2acac, TBRb, Ir(ppy)2acac, and C545T, respectively. Furthermore, we demonstrated a soft-form sol-LED using PMDS and chemical-vapor-deposited AZO electrodes. We were able to demonstrate MSCA-logo patterned emission from the soft device by bump patterning on the PMDS structure that adjusted the distance between AZO electrodes so that a higher electric field was applied to the closer AZO-gap region.
O3. Applications to stimulation of neurons in vitro and in vivo: Driving the yellow sol-LED by a biphasic voltage pulse ensured a super high brightness of 25,000 cd/m2 (or 180 mW/mm2). We summarized the energy density of photon emission per pulse by parameters of pulse heights and pulse widths. We carried out Ca2+ imaging of neurons by fluorescence microscopy in vitro. A sandwich-type sol-LED was placed underneath the neuron-cultured dish and simultaneously on top of the objective of inverted microscope. Both excitation and fluorescence light passed through the device in this microscopy. Confirming the imaging technique and emission by sol-LED sufficiently bright to activate ChRmine-expressing neurons, we are preparing an optical pacing of contraction of transgenic cardiomyocytes expressing ChRmine using the light emission by sol-LED and simultaneous observation of the contraction by microscope.
Needle-shaped optical probes carrying out the stimulation of neurons in vivo were manufactured by monolithic integration of OLEDs on silicon probes with four 6-mm-long subshanks and 1024 CMOS backplanes. A robust passivation that combines the deposition of Al2O3/ZrO2 nanolaminates and parylene-C layers was performed after the device integration. The probes were implanted into the brain of anesthetized mice and performed the optical manipulation of neuronal activity located deep in the brain and recorded the electrical responses from the neurons in parallel.
As a result of the project, three scientific papers were published in high-impact journals including Advanced Materials and Nature Electronics.
Sol-LEDs operating based on the exciplex-formation ECL ensured strong light emission, the convenience of manufacture, and applicability to soft electronic devices, therefore we prospect that the sol-LED technology developed within this MSCA project will play an essential role in future display, lighting, and biophotonics technologies. It is expected that industry-oriented follow-up research focusing on automation and standardization of device manufacturing methods will secure intellectual property rights and the prototype will contribute to the industry. To improve public access to the results of this project, we advertised this work with the production of videos on sol-LED and needle-shaped optical probes and communicated with the public through social media.