Periodic Reporting for period 1 - MESHOPTO (Retinal Mesh Optoelectronics)
Período documentado: 2022-11-01 hasta 2025-04-30
Blindness has a major impact on patients and their families life. Degeneration of photoreceptors due to age macular degeneration and retinitis pigmentosa is a major reason for blindness. A wide variety of strategies including drug injections, stem cells, optogenetics, gene therapy are promising strategies to recover the loss of the photoreceptor cells, but currently, they have significant limitations. Instead, electronic retinal implants, the most mature solution, made significant progress towards aiding large object recognition for blind patients. However, nowadays the production of clinically approved implants of Argus II and Alpha AMS was discontinued due to the unmet expectations of quality of vision (i.e. below legal blindness level in terms of visual acuity and field of view).
Alternatively, retina implants using photovoltaic conversion of light to electricity show high promise for high-quality artificial vision. Photovoltaic retina implant based on silicon is currently under clinical investigation and it demonstrated significant benefits for surgical simplicity and potential for high-resolution artificial vision. Photovoltaic retina implant based on conventional inorganic silicon photodiodes has the advantage of having a high-level charge injection efficiency for cell stimulation, but they are rigid, thick (~30 µm) and have challenges for miniaturization of tandem photodiodes. Conversely, there are also organic photodiodes based polymeric implants that are soft, thin (<1 µm) and can be miniaturized via vertical-stacking of tandem photodiodes, but their charge injection efficiency is significantly lower than silicon. Therefore, there is an urgent need for retinal implants that can simultaneously operate with high efficiency like silicon and can be fabricated via the use of solution-based fabrication technique for large-area, high-resolution and flexible retinal implants.
Toward this aim, we develop efficient, thin, and cellular-sized photovoltaic neural interfaces based on quantum dots and nanowires. For that, non-toxic quantum dots that have strong light absorption at near-infrared are synergized with the nanowires that have unique light-trapping and high surface area for efficient photostimulation of neurons. Then, we translate these devices to porous and flexible tissue-like retinal implants for artificial vision. Starting from the nanomaterial synthesis to optoelectronic device fabrication and bioelectronic mesh formation, this challenging innovation combining nanomaterials, photonics and abiotic-biotic interfaces are explored from primary neurons up to in-vivo experimental models of photoreceptor degeneration in order to move the results toward clinical application.
Alternatively, retina implants using photovoltaic conversion of light to electricity show high promise for high-quality artificial vision. Photovoltaic retina implant based on silicon is currently under clinical investigation and it demonstrated significant benefits for surgical simplicity and potential for high-resolution artificial vision. Photovoltaic retina implant based on conventional inorganic silicon photodiodes has the advantage of having a high-level charge injection efficiency for cell stimulation, but they are rigid, thick (~30 µm) and have challenges for miniaturization of tandem photodiodes. Conversely, there are also organic photodiodes based polymeric implants that are soft, thin (<1 µm) and can be miniaturized via vertical-stacking of tandem photodiodes, but their charge injection efficiency is significantly lower than silicon. Therefore, there is an urgent need for retinal implants that can simultaneously operate with high efficiency like silicon and can be fabricated via the use of solution-based fabrication technique for large-area, high-resolution and flexible retinal implants.
Toward this aim, we develop efficient, thin, and cellular-sized photovoltaic neural interfaces based on quantum dots and nanowires. For that, non-toxic quantum dots that have strong light absorption at near-infrared are synergized with the nanowires that have unique light-trapping and high surface area for efficient photostimulation of neurons. Then, we translate these devices to porous and flexible tissue-like retinal implants for artificial vision. Starting from the nanomaterial synthesis to optoelectronic device fabrication and bioelectronic mesh formation, this challenging innovation combining nanomaterials, photonics and abiotic-biotic interfaces are explored from primary neurons up to in-vivo experimental models of photoreceptor degeneration in order to move the results toward clinical application.
MESHOPTO successfully continues the research activities in agreement with the workplan that are targeted for the first 2-years of the project.
For WP1, we synthesized AgBiS2 core nanocrystals (NCs) and incorporated them into photovoltaic neural interfaces. These devices demonstrated efficient photostimulation of hippocampal neurons under low-intensity near-infrared light. Additionally, we synthesized AgBiS2/ZnS core/shell NCs via hot-injection technique for the first time, which were proven through various structural and optical characterization techniques.
ZnO nanowires (NWs) were grown on indium tin oxide (ITO) by using seeded growth technique, and AgBiS2 nanocrystals were infiltrated into interdigitated ZnO NWs via dip-coating. During the fabrication tetra-methyl-ammonium iodide (TMAI) was applied to exchange long-chain insulating oleate ligands with small-chain iodide ions to enhance the electronic coupling between the NCs for efficient device realization. The interaction between AgBiS2 NCs and ZnO NWs was explored for different NC-NW combinations, and the champion device structure that achieved the highest photocurrent was identified. The total thickness of the active device was under 1 µm as targeted, which showed its potential for flexible device fabrication.
In WP2, we enhanced interfacial capacitance by using pseudocapacitive materials like MnO2, RuO2, and IrO2 for higher charge injection for neuronal stimulation. 3D MnO2 nanoflowers were introduced as a novel material for neurostimulation devices. Optical simulations showed that the synergistic interaction of NC-NW enables strong light-matter interactions. Efforts to develop tandem photodiodes based on AgBiS2 are still ongoing.
In WP3, we successfully developed a microfabrication process for the fabrication of an optoelectronic mesh. This process was done in a clean room, and it was based on photolithography and reactive ion etching techniques. The pixels of various shapes can be produced on rigid substrates and the sizes as small as 15 µm can be achieved.
In WP4, patch-clamp electrophysiology on primary hippocampal neurons under whole-cell configuration revealed that the device efficiently elicited neuron firing at intensity levels more than an order of magnitude below the established ocular safety limits. The device without encapsulation showed a halftime over ten years under passive accelerated aging test and did not show any toxicity on neurons. Additionally, we set up a multielectrode array (MEA) system to record ex-vivo retinal activity. Our devices successfully demonstrated the photostimulation of ex-vivo retinal tissue under near-infrared illumination.
For WP1, we synthesized AgBiS2 core nanocrystals (NCs) and incorporated them into photovoltaic neural interfaces. These devices demonstrated efficient photostimulation of hippocampal neurons under low-intensity near-infrared light. Additionally, we synthesized AgBiS2/ZnS core/shell NCs via hot-injection technique for the first time, which were proven through various structural and optical characterization techniques.
ZnO nanowires (NWs) were grown on indium tin oxide (ITO) by using seeded growth technique, and AgBiS2 nanocrystals were infiltrated into interdigitated ZnO NWs via dip-coating. During the fabrication tetra-methyl-ammonium iodide (TMAI) was applied to exchange long-chain insulating oleate ligands with small-chain iodide ions to enhance the electronic coupling between the NCs for efficient device realization. The interaction between AgBiS2 NCs and ZnO NWs was explored for different NC-NW combinations, and the champion device structure that achieved the highest photocurrent was identified. The total thickness of the active device was under 1 µm as targeted, which showed its potential for flexible device fabrication.
In WP2, we enhanced interfacial capacitance by using pseudocapacitive materials like MnO2, RuO2, and IrO2 for higher charge injection for neuronal stimulation. 3D MnO2 nanoflowers were introduced as a novel material for neurostimulation devices. Optical simulations showed that the synergistic interaction of NC-NW enables strong light-matter interactions. Efforts to develop tandem photodiodes based on AgBiS2 are still ongoing.
In WP3, we successfully developed a microfabrication process for the fabrication of an optoelectronic mesh. This process was done in a clean room, and it was based on photolithography and reactive ion etching techniques. The pixels of various shapes can be produced on rigid substrates and the sizes as small as 15 µm can be achieved.
In WP4, patch-clamp electrophysiology on primary hippocampal neurons under whole-cell configuration revealed that the device efficiently elicited neuron firing at intensity levels more than an order of magnitude below the established ocular safety limits. The device without encapsulation showed a halftime over ten years under passive accelerated aging test and did not show any toxicity on neurons. Additionally, we set up a multielectrode array (MEA) system to record ex-vivo retinal activity. Our devices successfully demonstrated the photostimulation of ex-vivo retinal tissue under near-infrared illumination.
We successfully demonstrated efficient and safe optoelectronic biointerfaces using toxic-free, heavy-metal-free nanocrystals that operate in the near-infrared range. These devices were able to stimulate single primary neurons, recorded via patch-clamp, and ex-vivo retina tissue, recorded using multi-electrode arrays, under near-infrared illumination. This marks a fundamental achievement that could pave the way for a new retinal implant technology to aid patients with photoreceptor degeneration.
We introduced a new methodology for shell growth on AgBiS2 nanocrystals (NCs), which are composed of nontoxic, earth-abundant materials and exhibit an exceptionally high absorption coefficient in the visible to near-infrared range (>105 cm–1). Although these NCs have shown promise for photovoltaic retina implants, they lack photoluminescence (PL) due to intrinsic nonradiative recombination. However, through the shell growth process, we observed the first reported emission from these nanocrystals, opening new possibilities for applications in lighting, display, and bioimaging.
Our novel microfabrication technique using standard clean room processes offers a globally applicable method for colloidal quantum dot-based photodiode arrays. We also introduced 3D MnO2 nanoflowers as a new pseudocapacitive nanomaterial for flexible optoelectronic biointerfaces.
Moving forward, we will focus on achieving high-visual-acuity photostimulation of the retina. Our next steps include microfabricating pixelated devices and testing their photocurrent performance on flexible substrates. We will refine processes for demonstrating efficient device operation on flexible substrates, and once optimized, proceed with in-vivo testing on rats with degenerated photoreceptors.
We introduced a new methodology for shell growth on AgBiS2 nanocrystals (NCs), which are composed of nontoxic, earth-abundant materials and exhibit an exceptionally high absorption coefficient in the visible to near-infrared range (>105 cm–1). Although these NCs have shown promise for photovoltaic retina implants, they lack photoluminescence (PL) due to intrinsic nonradiative recombination. However, through the shell growth process, we observed the first reported emission from these nanocrystals, opening new possibilities for applications in lighting, display, and bioimaging.
Our novel microfabrication technique using standard clean room processes offers a globally applicable method for colloidal quantum dot-based photodiode arrays. We also introduced 3D MnO2 nanoflowers as a new pseudocapacitive nanomaterial for flexible optoelectronic biointerfaces.
Moving forward, we will focus on achieving high-visual-acuity photostimulation of the retina. Our next steps include microfabricating pixelated devices and testing their photocurrent performance on flexible substrates. We will refine processes for demonstrating efficient device operation on flexible substrates, and once optimized, proceed with in-vivo testing on rats with degenerated photoreceptors.