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Novel Nanoengineered Optoelectronic Biointerfaces

Periodic Reporting for period 2 - NOVELNOBI (Novel Nanoengineered Optoelectronic Biointerfaces )

Reporting period: 2017-01-01 to 2018-06-30

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 affects 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 and the rising potential of these diseases. Therefore, treatment of outer retina diseases is strongly emphasized by European Technology Platform for photonics, Photonics21. To this end, the health, societal and economic impact of these diseases motivates 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 propose a totally new approach for understanding fundamental requirements and from this knowledge designing customised nanomaterials with optimised characteristics. These will be 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 are: (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 will enable exploring, tuning and controlling the underlying physical mechanisms of neural photostimulation. Furthermore, the biocompatible nanomaterials will result in a more reliable nanobiojunction. The funnel and plasmon structures will lead to unprecedented spectral sensitivities and dynamic ranges that are far beyond the state-of-the-art optoelectronic interfaces. The project is therefore expected to have high impact and may herald a new paradigm in neural interfacing. NOVELNOBI is expected to attract significant attention of researchers from diverse fields such as photonics, nanomaterials, photomedicine and neuroscience.
In summary, NOVELNOBI progresses in agreement with the expected work plan. Workpackage 1 (WP1), WP2 and WP3 are finished. WP4 is partially finished and continues as proposed. WP5 is started and continues as proposed.

WP1. Inorganic nanomaterials design and synthesis (Time plan:0-1.5 year): We successfully completed the work package 1 (WP1). In this work package, we designed, synthesized and characterized type-II InP/ZnO core/shell nanocrystals, type-I InP/ZnS core/shell nanocrystals and type-I InP core nanocrystals, which are used to explore the photocapacitive, photoconductive and exciton-induced electric field based neural photostimulation. We also did quantum mechanical simulation of nanocrystals. Through these experiments, we demonstrated a novel type-II nanostructure of InP/ZnO core/shell nanocrystals. The manuscript entitled “Effective Neural Photostimulation Using Indium-based Type-II Quantum Dots”, which contains the first demonstration of the biocompatible type-II nanocrystals and their application for neural interfaces, is submitted to ACS Nano, which is one of the most respected journal in Nanoscience with a high impact factor of 13.942. It is reviewed by five different reviewers due to the multidisciplinary nature of the manuscript, and they received positive feedback by the reviewers (i.e. two out of five reviewers directly ranked the first version of the manuscript as in the top 5% of manuscripts in the field). The manuscript revision is currently in progress. Moreover, we further controlled the ZnO shell growth for efficient energy harvesting, and the results are currently under review in another prestigious journal of ACS Applied Materials and Interfaces with a high impact factor of 7.504.

WP-2. Metal nanoparticles design and synthesis (Time plan:0-1.5 year): We successfully synthesized all the proposed metallic nanoparticles of silver, gold and gold/silver alloy nanoparticles that can induce plasmonic effects for neural photostimulation (WP2). At the same time we did the electromagnetic simulation of the nanoparticles. Hence, we prepared the necessary nanoparticles and understanding/tuning of the optical and electronic properties of nanoparticles. In addition, we fabricated metallic gold nanoislands, which are prepared by the physical deposition of the thin metallic film (2-3 nm), which self-assemble into nanoislands as plasmonic substrates.

WP-3. Nanoassembly design and fabrication (Time plan:1-2 year): In WP3 we determined the necessary device parameters to coat the substrate with nanomaterial with Langmuir-Blodgett (LB) and layer-by-layer (LbL) deposition techniques. We did the ligand exchange of the nanoparticles for surface coating. The manuscript entitled “Effective Neural Photostimulation Using Indium-based Type-II Quantum Dots” uses both the layer-by-layer deposition and ligand exchange for photoelectrode fabrication, which is made of type-II InP/ZnO core/shell quantum dots. Moreover, another manuscript entitled “Excitonic Energy Transfer within InP/ZnS Core/Shell Quantum Dot Superlattices” is currently under review in The Journal of Physical Chemistry C, in which we fabricated InP/ZnS core/shell quantum dot (QD) superlattices via Langmuir-Blodgett technique and studied the excitonic energy transfer within the quantum dots with controlled ZnS shell thickness. In addition, the substrates that will interface with biological cells need to be biocompatible, which can be achieved by using biopolymers. For that among a wide variety of possible options, silk fibroin protein, which is transparent and biocompatible, is an appropriate material. We developed a new and biocompatible technique to pattern silk fibroin substrates. The results of this technique are also currently under review in the respected journal of ACS Biomaterials Science & Engineering.

WP-4. Investigation of photostimulation effects (Time plan:1.5-4.5 year): For this work package we started the exploration of photocapaciti
Interfacing with neural tissues is an important scientific goal to understand cellular processes and to combat nervous-system related diseases. 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.

For the first time, we demonstrated Cd-free and type-II InP/ZnO core/shell nanocrystals, in which electron localizes in the shell and hole is confined in the core. To prove the structure we used bright-field high-resolution transmission electron microscopy (HRTEM), X-ray photoelectron spectroscopy (XPS) and X-ray diffraction (XRD). We also confirmed the structure by steady-state and time-resolved fluorescence spectroscopy. The results of these characterizations are also supported by quantum mechanical simulations. Thus, we proved the new nanostructure via structural and optical characterizations.

Light-induced stimulation of neurons via photoactive surfaces offers rich opportunities for the development of new therapeutic methods and high-resolution retinal prosthetic devices. Quantum dots serve as an attractive building block for such surfaces, as they can be easily functionalized to match the biocompatibility and charge transport requirements of cell stimulation. Although indium-based colloidal quantum dots with Type-I band alignment have attracted significant attention as a non-toxic alternative to cadmium-based ones, little attention has been paid to their photovoltaic potential as Type-II heterostructures. Herein, we demonstrate Type-II indium phosphide/zinc oxide core/shell quantum dots that are incorporated into a photoelectrode structure for neural photostimulation. This induces a hyperpolarizing bioelectrical current that triggers the firing of a single neuronal cell at 4 µW mm-2, 26-fold times lower than the ocular safety limit for continuous exposure to visible light. These findings show that nanomaterials can induce a biocompatible and effective biological junction and can open up a new route in the use of quantum dots in photoelectrode architectures for artificial retinal prostheses.

In addition, we demonstrated for the first time the Stokes-shift-engineered indium phosphide quantum dots for efficient luminescent energy harvesting. Stokes shift engineering of quantum dots is a favorable approach to suppress reabsorption losses; however, the use of highly-toxic heavy metals in quantum dots constitutes a serious concern for bio-environment. Here, we report luminescent solar concentrators (LSCs) based on cadmium-free InP/ZnO core/shell quantum dots with Type-II band alignment that allow for suppression of reabsorption by Stokes shift engineering. The spectral emission and absorption overlap was controlled by the growth of a ZnO shell on an InP core. At the same time, the ZnO layer also facilitates the photostability of the quantum dots within the host matrix. We analyzed the optical performance of indium-based LSCs and identified the optical efficiency as 1.45%. The transparency, flexibility, and cadmium-free content of the LSCs hold promise for efficient and environmental-friendly energy harvesting.

We demonstrated the first excitonic energy transfer within InP/ZnS core/shell quantum dot superlattices. Interparticle energy transfer offer great promise to a diverse range of applications ranging from directed energy transfer for artificial neural interfaces to nanoscale ruler in biology. For the first time we fabricated InP/ZnS core/shell quantum dot (QD) superlattices via Langmuir-Blodgett technique and studied the excitonic energy transfer within the quantum dots. Two types of InP based core/shell quantum dot superlattices, one with a thin ZnS shell (~0.8 nm) and other with a thick ZnS shell (~3 nm), were prepared. The structural and optical properties of quantum dots revealed the successful multiple shell growth, and atomic force micros