CBET-EPSRC: Hybrid organic-CMOS devices for optogenetic simulation and lens-free fluorescence imaging of the brain
Lead Research Organisation:
University of St Andrews
Department Name: Physics and Astronomy
Abstract
Brain functions such as perception, motor control, learning, and memory arise from the coordinated activation of neuronal assemblies distributed across multiple brain areas. While major progress has been made in understanding the response properties of individual cells, circuit interactions remain poorly understood. One of the fundamental obstacles to understanding these interactions has been the difficulty of observing the activity of large distributed populations of neurons in freely behaving animals. By combining highly engineered genetically encoded light-sensitive ion channels (typically Channelrhodopsins, ChRs) with fluorescent voltage or calcium sensors, it has become possible to achieve precise, non-invasive and high-speed control and monitoring of neuronal networks with optical techniques, both in cell culture and in live and awake animals. Conventional microscopy approaches have been employed for building these optical interfaces, resulting in very complex implementation which makes freely behaving animal studies difficult. In addition, conventional microscopy techniques, even those that use two photon techniques or light-sheet imaging, are limited by scattering and absorption in the brain tissue, allowing only superficial coverage for brains as small as that of the mouse.
In this proposal, we will develop an approach for light delivery that surmounts these limitations. It enables complete coverage of all neurons within a target volume, permits functional imaging with cellular resolution in highly scattering brain tissue, and has long-term prospects for human applications. Our approach is based on distributing a dense 3-D lattice of emitter and detector pixels within the brain itself. These pixel arrays are embedded onto neural probes, realized as implantable, ultra-narrow shanks. These probes are readily producible though existing CMOS (complementary metal-oxide-semiconductor) foundries augmented by organic LED (OLED) technology. This hybrid device platform for optogenetic stimulation and recording combines angle-sensitive CMOS single-photon avalanche diodes (A-SPADs) for detection and angle-emitting OLEDs for light generation. Due to their amorphous morphology, the organic materials used in OLEDs can be deposited directly onto silicon chips, without lattice matching constraints, thus facilitating true monolithic integration of light sources on CMOS technology.
In this proposal, we will develop an approach for light delivery that surmounts these limitations. It enables complete coverage of all neurons within a target volume, permits functional imaging with cellular resolution in highly scattering brain tissue, and has long-term prospects for human applications. Our approach is based on distributing a dense 3-D lattice of emitter and detector pixels within the brain itself. These pixel arrays are embedded onto neural probes, realized as implantable, ultra-narrow shanks. These probes are readily producible though existing CMOS (complementary metal-oxide-semiconductor) foundries augmented by organic LED (OLED) technology. This hybrid device platform for optogenetic stimulation and recording combines angle-sensitive CMOS single-photon avalanche diodes (A-SPADs) for detection and angle-emitting OLEDs for light generation. Due to their amorphous morphology, the organic materials used in OLEDs can be deposited directly onto silicon chips, without lattice matching constraints, thus facilitating true monolithic integration of light sources on CMOS technology.
Planned Impact
In this proposal, the PIs will train graduate and undergraduate students in a truly cross-disciplinary international research environment combining circuit design, biophotonics, and nanotechnology with applications in neuroscience. The work will influence curriculum development in bioelectronics and biophotonics and there is a robust outreach effort involving both PIs. The new science possible with this platform will further our understanding of the functioning of the brain with an impact in hundreds of neuroscience labs. Dissemination will begin with introduction of prototypes into selected labs. Wider dissemination may happen through a start-up venture, similar to dissemination approaches used by the PIs in other activities.
People |
ORCID iD |
Malte Gather (Principal Investigator) |
Publications
Graf A
(2018)
Infrared Organic Light-Emitting Diodes with Carbon Nanotube Emitters.
in Advanced materials (Deerfield Beach, Fla.)
Keum C
(2018)
The Role of Metallic Dopants in Improving the Thermal Stability of the Electron Transport Layer in Organic Light-Emitting Diodes
in Advanced Optical Materials
Murawski C
(2019)
Narrowband Organic Light-Emitting Diodes for Fluorescence Microscopy and Calcium Imaging.
in Advanced materials (Deerfield Beach, Fla.)
Morton A
(2019)
Photostimulation for In Vitro Optogenetics with High-Power Blue Organic Light-Emitting Diodes.
in Advanced biosystems
Chen D
(2019)
Bipyridine-Containing Host Materials for High Performance Yellow Thermally Activated Delayed Fluorescence-Based Organic Light Emitting Diodes with Very Low Efficiency Roll-Off
in Advanced Optical Materials
Li Z
(2019)
1,3,4-Oxadiazole-based Deep Blue Thermally Activated Delayed Fluorescence Emitters for Organic Light Emitting Diodes
in The Journal of Physical Chemistry C
Keum C
(2020)
Organic Light-Emitting Diodes Based on a Columnar Liquid-Crystalline Perylene Emitter
in Advanced Optical Materials
Archer E
(2020)
Accurate Efficiency Measurements of Organic Light-Emitting Diodes via Angle-Resolved Spectroscopy
in Advanced Optical Materials
Deng Y
(2020)
Development of Very High Luminance p-i-n Junction-Based Blue Fluorescent Organic Light-Emitting Diodes
in Advanced Optical Materials
Sharma N
(2020)
Exciton efficiency beyond the spin statistical limit in organic light emitting diodes based on anthracene derivatives
in Journal of Materials Chemistry C
Description | With support from this grant we have developed and improved ways of integrating organic LED technology on silicon chips. Specifically, we have improved the stability of organic LEDs to elevated temperature. This is important to allow the use of thin film encapsulation methods which protect organic LEDs from environmental influence. Suitable encapsulation methods have been identified and optimized for use with organic LEDs. Support from this grant has also allowed for a feasibility study demonstrating that light generated by organic LEDs is of sufficient brightness to control firing of neurons in cell culture. This is an important prerequisite for the later use of organic LEDs integrated on silicon chips to control the behavior of complex neuronal networks. With support from this award, organic LEDs have now been successfully been integrated on silicon chips. Characterization of these devices is ongoing. |
Exploitation Route | Results from this grant will inform the development of future neuroprosthesis that use light to control relevant networks within the brain. |
Sectors | Electronics,Healthcare,Pharmaceuticals and Medical Biotechnology |
Description | As a direct result of this award, we have been contacted by a large SME based in France that is interested in using technology used/developed in part during this award. We are in ongoing exchange with this company. |
First Year Of Impact | 2018 |
Sector | Healthcare,Pharmaceuticals and Medical Biotechnology |
Impact Types | Economic |
Title | 1,3,4-Oxadiazole-based Deep-blue Thermally Activated Delayed Fluorescence Emitters for Organic Light Emitting Diodes (dataset) |
Description | |
Type Of Material | Database/Collection of data |
Year Produced | 2019 |
Provided To Others? | Yes |
Title | A substrateless, flexible, and water-resistant organic light-emitting diode (dataset) |
Description | |
Type Of Material | Database/Collection of data |
Year Produced | 2020 |
Provided To Others? | Yes |
URL | https://risweb.st-andrews.ac.uk:443/portal/en/datasets/a-substrateless-flexible-and-waterresistant-o... |
Title | Accurate efficiency measurements of organic light-emitting diodes via angle-resolved spectroscopy (dataset) |
Description | The accurate characterization of thin-film LEDs - including organic light emitting diodes (OLEDs), perovskites and quantum dot LEDs - is crucial to our understanding of the factors that influence their efficiency and thus to the fabrication of LEDs with improved performance and stability. In addition, detailed information about the angular characteristics of LED emission is useful to assess the suitability of individual architectures, e.g. for display applications. Here, the implementation of a goniometer-based measurement system and corresponding protocol are described that allow to accurately determine the current-voltage-luminance characteristics, external quantum efficiency and luminous efficacy of OLEDs and other emerging thin-film LEDs. The system allows recording of angle-resolved electroluminescence spectra and accurate efficiency measurements for devices with both Lambertian and non-Lambertian emission characteristics. A detailed description of the setup and a protocol for assembling and aligning the required hardware are provided. Drawings of all custom parts and the open-source Python software required to perform the measurement and to analyze the data are included. |
Type Of Material | Database/Collection of data |
Year Produced | 2020 |
Provided To Others? | Yes |
URL | https://risweb.st-andrews.ac.uk:443/portal/en/datasets/accurate-efficiency-measurements-of-organic-l... |
Title | Bipyridine-containing Host Materials for High Performance Yellow Thermally Activated Delayed Fluorescence-based Organic Light Emitting Diodes with Very Low Efficiency Roll-Off (dataset) |
Description | |
Type Of Material | Database/Collection of data |
Year Produced | 2019 |
Provided To Others? | Yes |
Title | Data underpinning - "Infrared organic light-emitting diodes with carbon nanotube emitters" |
Description | |
Type Of Material | Database/Collection of data |
Year Produced | 2018 |
Provided To Others? | Yes |
Title | Data underpinning - "Photostimulation for in vitro optogenetics with high power blue organic light-emitting diodes" |
Description | Data underpinning - "Photostimulation for in vitro optogenetics with high power blue organic light-emitting diodes" |
Type Of Material | Database/Collection of data |
Year Produced | 2019 |
Provided To Others? | Yes |
Impact | N/A |
Title | Development of very high luminance p-i-n junction-based blue fluorescent organic light-emitting diodes (dataset) |
Description | |
Type Of Material | Database/Collection of data |
Year Produced | 2019 |
Provided To Others? | Yes |
URL | https://risweb.st-andrews.ac.uk/portal/en/datasets/development-of-very-high-luminance-pin-junctionba... |
Title | Exciton efficiency beyond the spin statistical limit in organic light emitting diodes based on anthracene derivatives (dataset) |
Description | |
Type Of Material | Database/Collection of data |
Year Produced | 2020 |
Provided To Others? | Yes |
URL | https://risweb.st-andrews.ac.uk:443/portal/en/datasets/exciton-efficiency-beyond-the-spin-statistica... |
Title | High brightness, highly directional organic light-emitting diodes as light sources for future light-amplifying prosthetics in the optogenetic management of vision loss (dataset) |
Description | |
Type Of Material | Database/Collection of data |
Year Produced | 2022 |
Provided To Others? | Yes |
URL | https://risweb.st-andrews.ac.uk/portal/en/datasets/high-brightness-highly-directional-organic-lighte... |
Title | Identification of the Key Parameters for Horizontal Transition Dipole Orientation in Fluorescent and TADF Organic Light-Emitting Diodes (dataset) |
Description | |
Type Of Material | Database/Collection of data |
Year Produced | 2021 |
Provided To Others? | Yes |
URL | https://risweb.st-andrews.ac.uk/portal/en/datasets/identification-of-the-key-parameters-for-horizont... |
Title | Improving the thermal stability of top-emitting organic light-emitting diodes by modification of the anode interface (dataset) |
Description | |
Type Of Material | Database/Collection of data |
Year Produced | 2020 |
Provided To Others? | Yes |
URL | https://risweb.st-andrews.ac.uk:443/portal/en/datasets/improving-the-thermal-stability-of-topemittin... |
Title | Narrowband Organic Light-Emitting Diodes for Fluorescence Microscopy and Calcium Imaging (dataset) |
Description | |
Type Of Material | Database/Collection of data |
Year Produced | 2019 |
Provided To Others? | Yes |
Title | Organic Long Persistent Luminescence from a Thermally Activated Delayed Fluorescence Compound (dataset) |
Description | Organic long persistent luminescence (OLPL) is one of the most promising methods for longlived emission applications. However, present room-temperature OLPL emitters are mainly based on a bi-molecular exciplex system which usually needs an expensive small molecule such as PPT as the acceptor. In this study, we designed a new TADF compound, CzPhAP, which also shows OLPL in many well-known hosts such as PPT, TPBi and PMMA, without any exciplex formation and its OLPL duration reached more than 1 hour at room temperature. Combining the low cost of PMMA manufacture and flexible designs of TADF molecules, pure organic, large scale, color tunable and low-cost room temperature OLPL applications become possible. Moreover, we found that the onset of the 77 K afterglow spectra from a TADF emitter doped film is not necessarily reliable for determining the lowest triplet state (T1) energy level. This is because in some TADF emitter doped films, optical excitation can generate charges (electron and holes) that can later recombine to form singlet excitons during the phosphorescence spectrum measurement. The spectrum taken in the phosphorescence time window at low temperature may consequently consist of both singlet and triplet emission |
Type Of Material | Database/Collection of data |
Year Produced | 2020 |
Provided To Others? | Yes |
URL | https://risweb.st-andrews.ac.uk:443/portal/en/datasets/organic-long-persistent-luminescence-from-a-t... |
Title | Organic light-emitting diodes based on a columnar liquid-crystalline perylene emitter (dataset) |
Description | Liquid crystalline materials possessgreat potential as emitters inorganic light-emitting diodes (OLEDs) due to their self-assembling property,which may lead to anisotropic films and improved charge transport. Here, weinvestigate key photophysical properties of the columnar liquid crystallineemitter perylene-3,4,9,10-tetracarboxylic tetraethyl ester (PTCTE) and implementthe material into OLEDs. We find that vacuum-deposited PTCTE films exhibitpreferential horizontal orientation of the transition dipole moment. Embeddingthe emitter into different host materials leads to increased photoluminescencequantum yield but reduces molecular orientation compared to the neat film.OLEDs containing PTCTE doped into an exciplex-forming co-host achieve very highluminance exceeding 10,000 cd m-2 at 5.7 V, which isamongst the best performance of OLEDs based on columnar liquid crystallineemitters reported so far. |
Type Of Material | Database/Collection of data |
Year Produced | 2020 |
Provided To Others? | Yes |
URL | https://risweb.st-andrews.ac.uk:443/portal/en/datasets/organic-lightemitting-diodes-based-on-a-colum... |
Title | The role of metallic dopants in improving the thermal stability of the electron transport layer in organic light-emitting diodes (dataset) |
Description | |
Type Of Material | Database/Collection of data |
Year Produced | 2018 |
Provided To Others? | Yes |
Description | University of Columbia, Electrical Engineering, Prof Ken Shepard |
Organisation | Columbia University |
Department | Electrical Engineering |
Country | United States |
Sector | Academic/University |
PI Contribution | This collaborative proposal by international teams in the US and the UK develops an optical imaging approach to study freely-behaving animals and potentially humans. The proposal explores original and transformative approaches for overcoming current barriers of functional imaging of the brain. If successful, the platform developed by this project will be critical to many research projects, which will further understanding of the functioning of the brain as well as various brain disease mechanisms. My team has an extensive track record of developing and applying highly efficient OLEDs and in developing micro-photonic devices for biophotonics. Within the project we develop and further improve optical switching of ChR with OLEDs. My group is one of the few world-wide with expertise in molecular doping of charge transport layers for OLEDs. This allows us to dramatically reduce the OLED operating voltage compared to non-doped devices and thus facilitates high device brightness at the relatively voltage available from CMOS chips developed by the team at Columbia. |
Collaborator Contribution | The Shepard Lab at Columbia has world-leading expertise in CMOS bioelectronics, which has included applications to molecular diagnostics, microbiology, and neuroscience. Besides electrochemical and electrophysiological interfaces, this also included development of imagers based on both photodiodes and SPADs and their application for time-gated fluorescence detection. Within the current effort, the Shepard Lab designs SPAD based imagers and CMOS integrated drivers for OLEDs. |
Impact | The work is still ongoing and there have not yet been joint publications or other joint outcomes. |
Start Year | 2016 |