Periodic Reporting for period 4 - NOVELNOBI (Novel Nanoengineered Optoelectronic Biointerfaces )
Reporting period: 2020-01-01 to 2021-06-30
Interfacing with neural tissues continues to be a significant goal for the control and understanding of cellular processes, and for combating nervous-system related diseases (e.g. chronic pain, diabetes, etc.). Among them, retinal degeneration diseases are remarkably difficult to treat. A high-level of design, control and realization capability of these neural interfaces is key to solving these challenging problems, which remain unsolved with current technologies.
The outer retina diseases, such as retinitis pigmentosa, Stargardt’s disease, etc. cause irreversible blindness due to the death of rods and cones. Additionally, age-related macular degeneration (AMD) is the leading cause of severe vision loss in Western societies and affect around 37 million people worldwide. These diseases generate significant life-quality reductions for patients and their families, and limit social interactions and independence. Furthermore, they cause billions of dollars of economic losses including medical costs, other direct costs, and productivity losses. The personal health, societal and economic impact of these diseases will only worsen due to the aging of the European population. Therefore, treatments of outer retina diseases are strongly emphasized by European Technology Platform for photonics, Photonics21. To this end, the health, societal and economic impact of these diseases motivated our research.
Nanotechnology has a significant potential for the development of new neural interfaces. The atomic-level design and control of the nanostructures for neural interfacing can revolutionize the junction between neurons and nanomaterials. In this project, we proposed a totally new approach for understanding fundamental requirements and from this knowledge designing customised nanomaterials with optimised characteristics. These were used to develop and demonstrate unconventional neural interfaces that are ultimately designed, controlled and constructed at the nanoscale. Hence, the key objectives of this proposal were: (1) to use quantum mechanics in a new way to control and explore the neural photostimulation mechanism, (2) to explore, design and synthesize new biocompatible colloidal nanocrystals for neural photostimulation, to overcome the limitations in terms of toxic material contents (e.g. cadmium, lead, mercury, etc.), (3) to demonstrate novel biocompatible neural interfaces with exciton and quantum funnels, and plasmonic nanostructures for enhanced spectral sensitivity and dynamic range. This new approach from quantum mechanical design to nanocrystal assembly enabled exploring, tuning and controlling the underlying physical mechanisms of neural photostimulation. Furthermore, the biocompatible nanomaterials resulted in a more reliable nanobiojunction. The funnel and plasmon structures led to unprecedented spectral sensitivities and dynamic ranges that were far beyond the state-of-the-art optoelectronic interfaces. The project did high impact on diverse fields such as bioelectronics, nanomaterials, and neurotechnology, and led a new paradigm in neural interfacing.
The outer retina diseases, such as retinitis pigmentosa, Stargardt’s disease, etc. cause irreversible blindness due to the death of rods and cones. Additionally, age-related macular degeneration (AMD) is the leading cause of severe vision loss in Western societies and affect around 37 million people worldwide. These diseases generate significant life-quality reductions for patients and their families, and limit social interactions and independence. Furthermore, they cause billions of dollars of economic losses including medical costs, other direct costs, and productivity losses. The personal health, societal and economic impact of these diseases will only worsen due to the aging of the European population. Therefore, treatments of outer retina diseases are strongly emphasized by European Technology Platform for photonics, Photonics21. To this end, the health, societal and economic impact of these diseases motivated our research.
Nanotechnology has a significant potential for the development of new neural interfaces. The atomic-level design and control of the nanostructures for neural interfacing can revolutionize the junction between neurons and nanomaterials. In this project, we proposed a totally new approach for understanding fundamental requirements and from this knowledge designing customised nanomaterials with optimised characteristics. These were used to develop and demonstrate unconventional neural interfaces that are ultimately designed, controlled and constructed at the nanoscale. Hence, the key objectives of this proposal were: (1) to use quantum mechanics in a new way to control and explore the neural photostimulation mechanism, (2) to explore, design and synthesize new biocompatible colloidal nanocrystals for neural photostimulation, to overcome the limitations in terms of toxic material contents (e.g. cadmium, lead, mercury, etc.), (3) to demonstrate novel biocompatible neural interfaces with exciton and quantum funnels, and plasmonic nanostructures for enhanced spectral sensitivity and dynamic range. This new approach from quantum mechanical design to nanocrystal assembly enabled exploring, tuning and controlling the underlying physical mechanisms of neural photostimulation. Furthermore, the biocompatible nanomaterials resulted in a more reliable nanobiojunction. The funnel and plasmon structures led to unprecedented spectral sensitivities and dynamic ranges that were far beyond the state-of-the-art optoelectronic interfaces. The project did high impact on diverse fields such as bioelectronics, nanomaterials, and neurotechnology, and led a new paradigm in neural interfacing.
NOVELNOBI successfully achieved all the proposed aims and work packages, which explored and controlled the neural photostimulation mechanisms by using nanomaterials and introduced novel nanoengineered optoelectronic biointerfaces for the photocontrol of the neural activity. During the project phase, my team and I introduced novel nanocrystals such as AlSb and InP/ZnO core/shell quantum dots, used combinations of nanomaterials in new architectures for efficient devices, explored the fundamentals of photostimulation of neurons and adopted nanophotonic phenomena such as exciton and quantum funnels and plasmonic nanostructures in neural interfaces and demonstrated high-level control of stimulation mechanisms. NOVELNOBI has led to a total journal publications of 20 and the results have now been published in prestigious journals including ACS Nano, Nature Communications Materials, Nano Letters, Chemistry of Materials, Physical Review Applied, ACS Applied Materials & Interfaces (x4), Nano Research, Advanced Materials Interfaces, Frontiers in Neuroscience, Journal of Materials Chemistry C, Biomedical Optics Express (x2), Scientific Reports, Nanotechnology, iScience, Journal of Physical Chemistry C, and Star Protocols.
We successfully completed WP1 by completing all the proposed design, synthesis, and characterization of InP core, InP core/shell, InP/ZnO core/shell quantum dots (QDs), and type-I copper-doped InP/ZnSe core/shell quantum dots (QDs). We successfully did all the proposed synthesis for WP2 (silver, gold and gold/silver alloy nanoparticles). For WP3 we determined the necessary device parameters to coat the substrate with nanomaterial with Langmuir-Blodgett (LB) and layer-by-layer (LbL) deposition techniques by using ligand exchange, which led ultra-sensitive optoelectronic biointerfaces in WP4 and WP5. For WP4, we explored and understood the fundamentals of photostimulation processes such as photocapacitive, photoconductive (Faradaic), exciton-induced electric field based and pseudocapacitive neural photostimulations. For WP5, we demonstrated exciton-quantum funnel, plasmonic photostimulation, exciton-plasmon nanostructures and perovskite based biointerfaces for enhanced dynamic range and spectral sensitivity.
We successfully completed WP1 by completing all the proposed design, synthesis, and characterization of InP core, InP core/shell, InP/ZnO core/shell quantum dots (QDs), and type-I copper-doped InP/ZnSe core/shell quantum dots (QDs). We successfully did all the proposed synthesis for WP2 (silver, gold and gold/silver alloy nanoparticles). For WP3 we determined the necessary device parameters to coat the substrate with nanomaterial with Langmuir-Blodgett (LB) and layer-by-layer (LbL) deposition techniques by using ligand exchange, which led ultra-sensitive optoelectronic biointerfaces in WP4 and WP5. For WP4, we explored and understood the fundamentals of photostimulation processes such as photocapacitive, photoconductive (Faradaic), exciton-induced electric field based and pseudocapacitive neural photostimulations. For WP5, we demonstrated exciton-quantum funnel, plasmonic photostimulation, exciton-plasmon nanostructures and perovskite based biointerfaces for enhanced dynamic range and spectral sensitivity.
In line with the description of the action, we introduced the first biocompatible type-II nanocrystals of InP/ZnO and used it for photoconductive cell stimulation. This study was published by ACS Nano in 2018, which is one of the most respected journals in Nanoscience with a high impact factor (IF) of 15.881. In 2019 my team and I introduced another new nanomaterial of AlSb QDs, which was published in the Chemistry of Materials with an IF of 9.811. In 2021, we introduced the use of aluminum antimonide (AlSb) nanocrystals as the cell interfacing layer for capacitive neural stimulation for the first time and demonstrated successful photostimulation of primary hippocampal neurons below ocular safety limits, which was published in (Nature) Communications Materials. Moreover, the control of the faradaic and capacitive stimulation mechanisms is important for safe modulation of neural activity and we showed that band alignment of the optoelectronic biointerfaces engineers faradaic and capacitive photostimulation of neurons without surface modification, which was published in Physical Review Applied. In addition, we adapted the supercapacitor technology to nanoengineered biointerfaces to enhance the photoresponse of the biointerfaces. Furthermore, inspired by the photosynthetic systems in plants, neural interfaces based on biocompatible quantum funnels were developed that direct the photogenerated charge carriers toward the bionanojunction for efficient photostimulation, which was published in the prestigious journal of Nano Letters.