Nanoparticle organic semiconductor compositions
Nanoparticulate organic semiconductor compositions with overlapping absorbance spectra and therapeutic agents address the limitations of silicon-based implants by providing a flexible, power-independent retinal prosthetic device that restores vision and promotes neuron health.
Patent Information
- Authority / Receiving Office
- WO · WO
- Patent Type
- Applications
- Current Assignee / Owner
- Filing Date
- 2025-09-16
- Publication Date
- 2026-03-19
AI Technical Summary
Silicon-based retinal implants are stiff, brittle, and require bulky external power and signal processing units, failing to replicate the natural softness and curvature of the retina, leading to blurry images and potential eye tissue damage.
Nanoparticulate organic semiconductor compositions comprising organic electron donor-acceptor materials with overlapping optical absorbance spectra with human retina photoreceptors, integrated with therapeutic agents, allowing direct neural interfacing and eliminating external power requirements.
The compositions mimic the retina's functionality, restoring color vision without external power or signal processing, promoting neuron attachment and growth, and reducing eye tissue strain.
Smart Images

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Abstract
Description
Nanoparticle organic semiconductor compositionsCross reference to related application
[0001] This application is related to Australian provisional application no. 2024902949 filed on 19 September 2024, the contents of which are incorporated herein by reference in their entirety.Field
[0002] The present disclosure relates to organic semiconductor compositions comprising nanoparticulate organic electron donor-acceptor materials and devices derived therefrom. The present disclosure also relates to methods of fabricating the organic semiconductor compositions and devices. In one form, the device may be a retinal prosthetic device.Background
[0003] The retina, located at the back of the eye, contains specialized cells that absorb incoming light and then couple with neuronal cells to convert the absorbed optical energy into a nerve signal. These nerve impulses travel through the optic nerve and into the brain, where the visual cortex decodes the signals into visual images.
[0004] Diseases such as age-related macular degeneration (AMD), diabetic retinopathy and retinitis pigmentosa can damage or destroy retinal tissue, resulting in severe vision impairment or complete blindness. There is no cure for many of these diseases, but silicon-based artificial vision implants may be used to restore partial vision in some patients.
[0005] However, such devices are stiff, flat and brittle, making it difficult for them to replicate the natural softness and curved surface of the retina. As a result, silicon-based retinal implants produce blurry or distorted images and can cause long-term strain or damage to surrounding eye tissue. Furthermore, the devices require bulky external power and signal processing units, which must always be carried by the patient.
[0006] For these reasons, there is interest in improved artificial retina devices.1006145770
[0007] Reference to any prior art in the specification is not an acknowledgment or suggestion that this prior art forms part of the common general knowledge in any jurisdiction or that this prior art could reasonably be expected to be understood, regarded as relevant, and / or combined with other pieces of prior art by a skilled person in the art.Summary
[0008] Disclosed herein are new nanoparticulate organic semiconductor compositions and methods for their preparation. Also disclosed is their use in an organic semiconductor device and manufacture of the device. The organic semiconductor compositions comprise one or more pairs of organic electron donor-acceptor materials, wherein at least one is in the form of nanoparticles, said nanoparticles comprising, in some embodiments, at least one therapeutic agent. The optical absorbance spectra of these materials overlap with the optical absorbance spectra of short, medium, or long wavelength cone photoreceptors, or the rod photoreceptors in a human retina.
[0009] In one aspect, the present disclosure provides an organic semiconductor composition comprising one or more pairs of organic electron donor-acceptor materials, wherein at least one of either the organic electron donor or the organic electron acceptor material is in the form of nanoparticles, and wherein the optical absorbance spectra of at least one of the one or more pairs of organic electron donor-acceptor materials overlap with the optical absorbance spectra of short, medium, or long wavelength cone photoreceptors, or rod photoreceptors in a human retina.
[0010] In embodiments, the nanoparticles comprise a combination of both organic electron donor and organic electron acceptor materials.
[0011] In embodiments, the organic electron donor-acceptor materials are, at least in part, intermixed within a nanoparticle.
[0012] In embodiments, the distance between at least one of the organic electron donors and at least one of the organic electron acceptors within the nanoparticle is from about 5 nm to about 50 nm.
[0013] In embodiments, the organic semiconductor composition comprises two or more pairs of organic electron donor-acceptor materials.1006145770
[0014] In embodiments, the optical absorbance spectra of the two or more pairs of organic electron donor-acceptor materials independently overlap with at least two of the optical absorbance spectra of short, medium and long wavelength cone photoreceptors in a human retina.
[0015] In embodiments, the organic semiconductor composition comprises three or more pairs of organic electron donor-acceptor materials.
[0016] In embodiments, the optical absorbance spectra of the three or more pairs of organic electron donor-acceptor materials independently overlap with the optical absorbance spectra of short, medium, and long wavelength cone photoreceptors in a human retina.
[0017] In embodiments, the organic semiconductor composition comprises four or more pairs of organic electron donor-acceptor materials.
[0018] In embodiments, the optical absorbance spectra of the four or more pairs of organic electron donor-acceptor materials independently overlap with the optical absorbance spectra of short, medium, and long wavelength cone photoreceptors, and rod photoreceptors in a human retina.
[0019] In embodiments, the average particle size of the nanoparticles is from about 10 nm to about 500 nm, or from about 20 nm to about 200 nm.
[0020] In embodiments, the optical absorbance spectra of at least one or more pairs of the organic electron donor-acceptor materials overlap with a wavelength of between about 370 nm to about 480 nm, or between about 440 nm to about 600 nm, or between about 500 nm to about 650 nm.
[0021] In embodiments, the nanoparticles further comprise at least one therapeutic agent.
[0022] In embodiments, the therapeutic agent comprises one or more neuroprotective agents.
[0023] In embodiments, the therapeutic agent comprises nerve growth factor.1006145770
[0024] In embodiments, the therapeutic agent comprises one or more antiinflammatory agents.
[0025] In embodiments, the one or more anti-inflammatory agents comprise dexamethasone.
[0026] In embodiments, the therapeutic agent comprises one or more antioxidants.
[0027] In embodiments, at least one of either the organic electron donor or the organic electron acceptor material in the form of nanoparticles comprises a single therapeutic agent.
[0028] In embodiments, the one or more pairs of organic electron-donor acceptor materials comprise poly(9,9-dioctylfluorene-a / f-bithiophene) (F8T2), [6,6] phenyl-C61- butyric acid methyl ester (PCBM), poly(3-hexylthiophene-2,5-diyl) (P3HT), spirobifluorene-2,7-bis-perylenediimide (SF-PDI), poly[2,3-bis-(3- octyloxyphenyl)quinoxaline-5,8- diyl-a / f-thiophene-2,5-diyl] (TQ1 ) and poly{[ / V, / '-bis(2- octyldodecyl)-naphthalene-1 ,4,5,8-bis(dicarboximide)-2,6-diyl]-a / f-5,5'-(2,2'- bithiophene)} (N2200), or derivatives and / or structural analogues thereof.
[0029] In embodiments, the one or more pairs of organic electron-donor acceptor materials comprise poly(9,9-dioctylfluorene-a / f-bithiophene) (F8T2), [6,6] phenyl-C61- butyric acid methyl ester (PCBM), poly(3-hexylthiophene-2,5-diyl) (P3HT), spirobifluorene-2,7-bis-perylenediimide (SF-PDI), poly[2,3-bis-(3- octyloxyphenyl)quinoxaline-5,8- diyl-a / f-thiophene-2,5-diyl] (TQ1 ), poly{[ / V, / \ / '-bis(2- octyldodecyl)-naphthalene-1 ,4,5,8-bis(dicarboximide)-2,6-diyl]-a / f-5,5'-(2,2'- bithiophene)} (N2200), and violanthrone-79, or derivatives and / or structural analogues thereof.
[0030] In embodiments, at least one of the one or more pairs of organic electron donoracceptor materials whose optical absorbance spectra overlap the optical absorbance spectra of short wavelength cone photoreceptors in a human retina comprises a lambda max between about 400 nm to about 450 nm.
[0031] In embodiments, at least one of the one or more pairs of organic electron donoracceptor materials whose optical absorbance spectra overlap the optical absorbance1006145770spectra of medium wavelength cone photoreceptors in a human retina comprises a lambda max between about 510 nm to about 570 nm.
[0032] In embodiments, at least one of the one or more pairs of organic electron donoracceptor materials whose optical absorbance spectra overlap the optical absorbance spectra of long wavelength cone photoreceptors in a human retina comprises a lambda max between about 540 nm to about 600 nm.
[0033] In embodiments, two or more pairs of organic electron donor-acceptor materials comprise two or more F8T2:PCBM, P3HT:SF-PDI, and TQ1 :N2200 pairs.
[0034] In embodiments, two or more pairs of organic electron donor-acceptor materials comprise two or more F8T2:PCBM, P3HT:PCBM, P3HT:SF-PDI, and TQ1 :N2200 pairs.
[0035] In embodiments, the three or more pairs of organic electron donor-acceptor materials comprise F8T2:PCBM, P3HT:SF-PDI, and TQ1 :N2200 pairs.
[0036] In embodiments, the three or more pairs of organic electron donor-acceptor materials comprise F8T2:PCBM, P3HT:PCBM, P3HT:SF-PDI, and TQ1 :N2200 pairs.
[0037] In another aspect, the present disclosure provides a method of producing an organic semiconductor nanoparticle comprising the step of combining an aqueous surfactant solution with a solution of organic donor and / or acceptor material in an organic solvent.
[0038] In embodiments, the method further comprises the addition of one or more therapeutic agents.
[0039] In some embodiments, the aqueous surfactant solution comprises sodium dodecyl sulphate.
[0040] In some embodiments, the aqueous surfactant solution has a surfactant concentration from about 0.1 mg / mL to about 20 mg / mL, or about 0.2 mg / mL to about 15 mg / mL, or about 0.3 mg / mL to about 12 mg / mL.
[0041] In another aspect, the present disclosure provides a method of producing organic semiconductor nanoparticles comprising combining an aqueous surfactant1006145770solution with a solution of an organic donor and / or acceptor material and an additional therapeutic agent in an organic solvent.
[0042] In another aspect, the present disclosure provides a method of producing organic semiconductor nanoparticles comprising combining an aqueous surfactant solution comprising an additional therapeutic agent with a solution of an organic donor and / or acceptor material in an organic solvent.
[0043] In some embodiments, the aqueous surfactant solution comprises sodium dodecyl sulphate.
[0044] In some embodiments, the aqueous surfactant solution has a surfactant concentration from about 0.1 mg / mL to about 20 mg / mL, or about 0.2 mg / mL to about 15 mg / mL, or about 0.3 mg / mL to about 12 mg / mL.
[0045] In another aspect, the present disclosure provides an organic semiconductor device comprising:(a) a substrate layer;(b) a first layer disposed on a surface of the substrate, said first layer comprising one or more first organic semiconductor materials;(c) a second layer disposed on the first layer, said second layer comprising one or more second organic semiconductor materials; wherein at least one of the first organic semiconductor materials and the second semiconductor materials together form an organic semiconductor composition according to the present disclosure.
[0046] In embodiments, the organic semiconductor device further comprises a positive charge selective transporting layer, a negative charge selective transporting layer, or both.
[0047] In another aspect, the present disclosure provides an organic semiconductor device comprising:(a) a substrate layer;1006145770(b) a positive charge selective transporting layer disposed on a surface of the substrate;(c) a donor material layer disposed on the positive charge selective transporting layer, said donor material layer comprising one or more first organic semiconductor materials;(d) an acceptor material layer disposed on the donor material layer, said acceptor material layer comprising one or more second organic semiconductor materials;(e) a negative charge selective transporting layer disposed on the acceptor material layer; or(a) substrate layer;(b) a negative charge selective transporting layer disposed on a surface of the substrate;(c) an acceptor material layer disposed on the negative charge selective transporting layer, said acceptor material layer comprising one or more first organic semiconductor materials;(d) a donor material layer disposed on the acceptor material layer, said donor material layer comprising one or more second organic semiconductor materials;(e) a positive charge selective transporting layer disposed on the donor material layer; wherein at least one of the first organic semiconductor materials and the second semiconductor materials together form an organic semiconductor composition according to the present disclosure.
[0048] In some embodiments, the organic semiconductor device further comprises a silane crosslinker with (i) the positive charge selective transporting layer disposed on a surface of the substrate or (ii) the negative charge selective transporting layer disposed1006145770on a surface of the substrate. In some embodiments, the silane crosslinker comprises (3-glycidyloxypropyl)trimethylsilane (GOPS).
[0049] In some embodiments of the organic semiconductor device according to the present disclosure, the first layer and the second layer, and / or the donor material layer and the acceptor material layer are disposed as an intermixed nanoparticle layer.
[0050] In some embodiments of the organic semiconductor device according to the present disclosure, the first layer and the second layer, and / or the donor material layer and the acceptor material layer are disposed as a nanoparticle layer, said nanoparticles comprising a combination of both organic electron donor and organic electron acceptor materials.
[0051] In another aspect, the present disclosure provides a method of fabricating an organic semiconductor device comprising the steps of:(a) depositing at least one first organic semiconductor material layer onto a surface of a substrate;(b) depositing at least one second organic semiconductor material layer onto the first layer; wherein at least one of the first organic semiconductor material and the second semiconductor material together form an organic semiconductor composition according to the present disclosure.
[0052] In some embodiments, the method further comprises the step of depositing a charge selective transport layer onto the surface of the substrate prior to step (a) and / or depositing a charge selective transport layer onto the at least one second organic semiconductor material layer after step (b).
[0053] In some embodiments, the method further comprises adding a silane crosslinker to the charge selective transport layer deposited prior to step (a). In some embodiments, the silane crosslinker comprises (3-glycidyloxypropyl)trimethylsilane (GOPS).1006145770
[0054] In some embodiments, the device further includes a pixelated array formed from the first organic semiconductor material layer and the second organic semiconductor material layer.
[0055] In some embodiments, the method further comprises UV-Ozone treatment or plasma ion implantation of the at least one first organic semiconductor material layer and / or the at least one second organic semiconductor material layer.
[0056] In another aspect, the present disclosure provides a method of fabricating an organic semiconductor device comprising the steps of:(a) depositing a positive charge selective transport layer onto a surface of a substrate;(b) depositing a donor material layer onto the positive charge selective transport layer, said donor material layer comprising one or more first organic semiconductor materials;(c) depositing an acceptor material layer onto the donor material layer, said acceptor material layer comprising one or more second organic semiconductor materials;(d) depositing a negative charge selective transport layer onto the acceptor material layer; or(a) depositing a negative charge selective transport layer onto a surface of a substrate;(b) depositing an acceptor material layer onto the negative charge selective transport layer, said acceptor material layer comprising one or more first organic semiconductor materials;(c) depositing a donor material layer onto the acceptor material layer, said donor material layer comprising one or more second organic semiconductor materials;(d) depositing a positive charge selective transport layer onto the donor material layer;1006145770wherein at least one of the first organic semiconductor material and the second semiconductor material together form an organic semiconductor composition according to the present disclosure.
[0057] In some embodiments of the method, the method further comprises adding a silane crosslinker to (i) the positive charge selective transport layer or (ii) the negative charge selective transport layer prior to step (a). In some embodiments, the silane crosslinker comprises (3-glycidyloxypropyl)trimethylsilane (GOPS).
[0058] In embodiments of the method, the first organic semiconductor material layer and / or the second organic semiconductor material layer are deposited by 3D printing, inkjet printing, vacuum deposition, spin-coating, blade coating, spray coating, slot die coating or laser patterning / etching.
[0059] In embodiments of the method, the steps of depositing the first organic semiconductor material layer and the second organic semiconductor material layer, and / or the steps of depositing the donor material layer and the acceptor material layer are performed together, such that the materials are deposited as an intermixed nanoparticle layer.
[0060] In some embodiments, the steps of depositing the first organic semiconductor material layer and the second organic semiconductor material layer, and / or the steps of depositing the donor material layer and the acceptor material layer are performed together, such that the materials are deposited as nanoparticles, said nanoparticles comprising a combination of both organic electron donor and organic electron acceptor materials.
[0061] In some embodiments of the method, the method further comprises treating the acceptor material layer and / or the donor material layer with UV-Ozone treatment or plasma ion implantation.
[0062] In embodiments, the substrate is biocompatible.
[0063] As used herein, a “substrate” can be described as a synthetic or natural material suitable to replace a part of a living system or to function in intimate contact with living tissue. Hence, a “biocompatible substrate” can be described as a substrate which does not cause any significant adverse bodily reactions when introduced into a1006145770mammalian body, such as any significant reaction of the immune system. Accordingly, said substrate may be constructed to interact with the mammalian body and to facilitate its introduction.
[0064] In embodiments, the substrate is flexible.
[0065] As used herein, flexible describes the ability of a flexible segment of the substrate to flex and allows a length of the substrate to bend at an angle that falls, for example, between and including about 0.2 degrees to about 150 degrees relative to the longitudinal axis from a substantially straight position. In some preferred embodiments, the angle is between and including about 0.2 degrees to about 50 degrees relative to the longitudinal axis from a substantially straight position.
[0066] In embodiments, the substrate is electrically conductive.
[0067] In embodiments, the substrate comprises one or more of polymer, fabric, graphene, MXene, metal or conductive oxide.
[0068] In another aspect, the organic semiconductor devices according to the present disclosure find use in a retinal prosthetic device.
[0069] In embodiments the device comprises nerve growth factor.
[0070] In embodiments the device is configured to couple into one or more of functional retinal neurons, horizontal cells, bipolar cells, retinal ganglion cells, optical nerves, and / or the visual cortex of patients.
[0071] In embodiments, the device does not require a power source, signal processing capability, or connections that are external to a patient.
[0072] In another aspect, the present disclosure provides a method of treating eye disease or disorder comprising implanting in the eye of a human subject an organic semiconductor device according to the present disclosure.
[0073] In another aspect, the organic semiconductor device according to the present disclosure is used in the manufacture of a retinal prosthetic device for the treatment of eye disease or disorder in a human subject.1006145770
[0074] In embodiments of the method, the eye disease or disorder is selected from macular degeneration, age-related macular degeneration, diabetic retinopathy, and retinitis pigmentosa.
[0075] In embodiments of the method, wherein the device comprises nerve growth factor (NGF), the device provides an improvement in neuron attachment and neuron growth.
[0076] Advantages of the presently disclosed organic semiconductor compositions, devices and methods of their fabrication include one or more of the following:• Low cost to manufacture.• The device couples directly into fully functional retinal neurons, optical nerves and visual cortex of patients, which are collectively responsible for vision processing.• The device does not require any complex signal processing to restore neural functionality.• Simple surgery as the device requires no external connections and contains neurotrophic factors which help it self-connect to retinal ganglion cells.• No external power requirements as the optical power generated by the absorbed external light directly triggers the in-tact retinal neuron cells that pass vision signals to the brain.• Mimics absorbed wavelengths of the human eye and so is capable of restoring colour vision.
[0077] Any embodiment herein shall be taken to apply mutatis mutandis to any other embodiment unless specifically stated otherwise.
[0078] The present disclosure is not to be limited in scope by the specific embodiments described herein, which are intended for the purpose of exemplification only.Functionally equivalent compositions, devices and processes are clearly within the scope of the disclosure as described herein.1006145770
[0079] Further aspects of the present disclosure and further embodiments of the aspects described in the preceding paragraphs will become apparent from the following description, given by way of example and with reference to the accompanying drawings.Brief description of the drawings
[0080] Figure 1. Optical absorbance spectra of organic semiconductor solutions and films compared to previously reported spectra of human photoreceptors. A) Previously reported absorbance spectra of human photoreceptors. From left to right the traces represent S cones, Rods, M Cones and L Cones; B) Comparison of S cone absorbance spectrum (middle trace) with film and solution absorbance spectra for F8T2 (right trace) and PC61 BM (left trace) materials; C) Comparison of M cone absorbance spectrum with film and solution absorbance spectra for P3HT and SF-PDI materials. All traces substantially overlap, trace with circles represents M Cones; D) Comparison of L cone absorbance spectrum (trace with circles) with film and solution absorbance spectra for TQ1 (left hand peaks) and N2200 materials (right hand peaks).
[0081] Figure 2 shows a schematic diagram of an organic semiconductor device with a bilayer structure, according to one embodiment of the present disclosure.
[0082] Figure 3 shows a schematic diagram of a generic structure for an organic semiconductor device with charge transport layers present, according to one embodiment of the present disclosure.
[0083] Figure 4 shows the UV-visible absorption spectra for (a) P3HT and PCBM solutions in chloroform and films cast from neat chloroform solutions. Left hand solid trace and dotted trace represent PCBM, right hand solid trace and dotted trace represent P3HT, and (b) aqueous nanoparticles dispersions of P3HT, PCBM and P3HT:PCBM. Traces from top to bottom are PCBM, P3HT:PCBM and P3HT respectively. The insert graph shows the normalised absorbance, the traces from top to bottom at about 550 nm are P3HT, P3HT:PCBM and PCBM respectively.
[0084] Figure 5 is a graph showing the cumulative release of [3-NGF from F8T2 films. The graph shows passive release of [3-NGF over time from F8T2 thin films (bottom line) and F8T2 nanoparticles (NP) thin films (top line).1006145770
[0085] Figure 6 shows the maximum neurite length (pm) of primary neurites from a single neuronal cell co-cultured on ITO / Glass control for an ITO / Glass control, F8T2 thin films, F8T2 thin films + NGF, F8T2 NP films and F8T2 NP films + NGF after 3 days in culture (DIC) (**p <0.001 ).
[0086] Figure 7 shows photoluminescence (PL) measurements of P3HT NP and P3HT NP + TPA / TSBTPA / TSB, samples corrected using individual absorbance fraction. The PL / absorbance profile is shown for NPs synthesised with different amounts of SDS a) 1 mg, b) 2 mg, c) 10 mg, and d) 33 mg. In a) and b) P3HT NP without antioxidants are shown as the bottom traces and P3HT NP + TPA / TSB are shown as the top traces. In c) and d) P3HT NP without antioxidants are shown as the top traces and P3HT NP + TPA / TSB are shown as the bottom traces.Detailed description of the embodiments
[0087] It will be understood that the disclosure described and defined in this specification extends to all alternative combinations of two or more of the individual features mentioned or evident from the text or drawings. All of these different combinations constitute various alternative aspects of the disclosure.
[0088] One skilled in the art will recognize many methods and materials similar or equivalent to those described herein, which could be used in the practice of the present disclosure. The present disclosure is in no way limited to the methods and materials described. It will be understood that the disclosure described and defined in this specification extends to all alternative combinations of two or more of the individual features mentioned or evident from the text or drawings. All of these different combinations constitute various alternative aspects of the disclosure.
[0089] For purposes of interpreting this specification, terms used in the singular will also include the plural and vice versa.Definitions
[0090] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by those of ordinary skill in the art to which the present disclosure belongs. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present disclosure,1006145770preferred methods and materials are described. For the purposes of the present disclosure, the following terms are defined below.
[0091] As used herein, except where the context requires otherwise, the term "comprise" and variations of the term, such as "comprising", "comprises" and "comprised", are not intended to exclude further additives, components, integers or steps.
[0092] The articles “a” and “an” are used herein to refer to one or to more than one (i.e. to at least one) of the grammatical object of the article. By way of example, “an organic gas” means one organic gas or more than one organic gas.
[0093] As used herein, the term “and / or”, e.g., “X and / or Y” will be understood to mean either “X and Y” or “X or Y” and shall be taken to provide explicit support for both meanings or for either meaning.
[0094] As used herein, the term “about” refers to a quantity, value, dimension, size, or amount that varies by as much as 10%, 5%, 1% or 0.1 % to a reference quantity, value, dimension, size, or amount.
[0095] Ranges: throughout this disclosure, various aspects of the disclosure can be presented in a range format. It should be understood that the description in range format is merely for convenience and brevity and should not be construed as an inflexible limitation on the scope of the disclosure. Accordingly, the description of a range should be considered to have specifically disclosed all the possible subranges as well as individual numerical values within that range. For example, description of a range such as from 1 to 6 should be considered to have specifically disclosed subranges such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6 etc., as well as individual numbers within that range, for example, 1 , 2, 2.7, 3, 4, 5, 5.3, and 6. This applies regardless of the breadth of the range.
[0096] As used herein, “derivative” refers to a material structure that is derived from a similar material structure by a chemical reaction.
[0097] As used herein, “structural analogue” refers to chemical structures that arise from another compound. For example, if one atom or group of atoms is replaced with another atom or group of atoms.1006145770
[0098] It will be understood that the disclosure described and defined in this specification extends to all alternative combinations of two or more of the individual features mentioned or evident from the text. All of these different combinations constitute various alternative aspects of the disclosure.
[0099] The present disclosure relates to new organic semiconductor compositions and their preparation. The present disclosure also relates to the use of organic semiconductor compositions in organic semiconductor devices and the devices fabrication. The organic semiconductor compositions comprise one or more pairs of organic electron donor-acceptor materials, wherein at least one is in the form of nanoparticles, said nanoparticles comprising, in some embodiments, at least one therapeutic agent. The optical absorbance spectra of these materials overlap with the optical absorbance spectra of short, medium, or long wavelength cone photoreceptors, or rod photoreceptors in a human retina.
[0100] Without being bound by theory, the nanoparticles allow for two improvements in comparison to native organic materials deposed into neat films from organic solvents:(1 ) Photophysics: In theory, the donor and acceptor in a neat organic film could be in very close proximity in a mixed film, but in practice they very rarely are. This is because the materials have quite different properties in the solid solution. In mixed film solid solutions, as the film is crystallising from its solution state, the two materials spontaneously separate out inside the film to form large domains of donor and acceptor materials. There are strategies to try and prevent this separation, (intricate post-deposition heating, solvent treatment, additives etc), but these strategies need to be uniquely developed for every new combination of donor and acceptor. For neat organic films this limits the thickness of the device to ~50 nm, resulting in an intrinsic limit to how much light can be absorbed and thus how much charge can be generated for the purpose of neural interfacing.In contrast, when the donor and acceptor materials are intermixed within a nanoparticle, the donor-acceptor pairs are advantageously within close proximity (5- 50 nm) of each other. Combining the donor and acceptor intimately within a nanoparticle ensures the two materials are locked into a configuration where they are within the required proximity of each other. This is due to the materials not being1006145770able to move beyond the boundaries of the nanoparticles once crystallised from solution, forming more intricately intermixed solid films. Therefore, much thicker films can be made from packing multiple nanoparticles together whilst still satisfying the proximity requirement. This improves the signal strength and may lead to an improved device.(2) Biocompatibility: Inclusion of neuroprotective or therapeutic chemicals and biomolecules that are compatible with the body often requires an aqueous medium for dissolution (as the native environment of the body is predominantly water). This is incompatible with typical organic materials, which require dissolution in organic solvents. Fabricating nanoparticles from the organic materials allows a dispersion of the organic materials into an aqueous phase, thus enabling incorporation of neuroprotective agents and chemicals into films prepared from the nanoparticles that could not otherwise be included if the films were cast from neat organic materials dissolved in organic solvents.Organic semiconductor compositions
[0101] The present disclosure relates to an organic semiconductor composition comprising one or more pairs of organic electron donor-acceptor materials, wherein at least one of either the organic electron donor or the organic electron acceptor material is in the form of nanoparticles, and wherein the optical absorbance spectra of at least one of the one or more pairs of organic electron donor-acceptor materials overlap with the optical absorbance spectra of short, medium, or long wavelength cone photoreceptors, or rod photoreceptors in a human retina.
[0102] In embodiments, the nanoparticles comprise a combination of both organic electron donor and organic electron acceptor materials.
[0103] The organic electron donor-acceptor materials may be, at least in part, intermixed within a nanoparticle.
[0104] The distance between at least one of the organic electron donors and at least one of the organic electron acceptors within the nanoparticle may be from about 5nm to about 50 nm. This is advantageous because these materials (either the donor or the acceptor) do not create free electronic charge when they absorb light. Instead, they1006145770create an “exciton”, which is a positive charge and a negative charge bound together. Overall, this species is neutral and is therefore not electronically active, but it can move through a material across a range of 5-50 nm before it loses its energy and disappears. When an exciton reaches an interface between a donor and acceptor, it can split apart to move the positive charge into the donor and the negative charge into the acceptor. There is now a free electronic charge that can move to opposite electrodes and create an electronic response. If there are two neat films, there is only one interface - positioned in the middle of the two layers. So, if the individual layers are any thicker than ~50 nm, the excitons created when light is absorbed will not be able to reach this interface as the distance they are required to move through a layer is too great, and they relax and lose energy before reaching the interface to split apart. In the compositions of the present disclosure, there are interfaces within each nanoparticle, and thus when the nanoparticles are used to make a film, there is an enormous number of interfaces contained throughout the entire thickness and width of the film. Therefore, the compositions can much more effectively split the excitons and create significantly more charge.
[0105] The composition may comprise two or more pairs of organic electron donoracceptor materials.
[0106] When the composition comprises two or more pairs, the optical absorbance spectra of the two or more pairs of organic electron donor-acceptor materials may independently overlap with at least two of the optical absorbance spectra of short, medium, and long wavelength cone photoreceptors in a human retina.
[0107] The composition may comprise three or more pairs of organic electron-donor acceptor materials.
[0108] When the composition comprises three or more pairs, the optical absorbance spectra of the three or more pairs of organic electron donor-acceptor materials independently overlap with the optical absorbance spectra of short, medium, and long wavelength cone photoreceptors in a human retina.
[0109] Without being bound by theory, two or more pairs of donor-acceptor pairs, each of which absorbs light in the wavelength ranges where the other pairs have minimal absorption (i.e. different colours of light excite only one pair at a time) would provide a1006145770workable retinal prosthetic device that could possibly produce colour vision in a human. The full mimic of a human retina would require at least three pairs corresponding to short, medium and long wavelength cone photoreceptors.
[0110] The organic semiconductor compositions may comprise four or more pairs of organic electron donor-acceptor materials.
[0111] When the composition comprises four or more pairs, the optical absorbance spectra of the four or more pairs of organic electron donor-acceptor materials independently overlap with the optical absorbance spectra of short, medium, and long wavelength cone photoreceptors, and rod photoreceptors in a human retina.
[0112] The average particle size of the nanoparticles may be from about 10 nm to about 500 nm, or from about 10 nm to about 350 nm, or from about 10 nm to about 200 nm, or from about 20 nm to about 500 nm, or from about 20 nm to about 350 nm, or from about 20 nm to about 200 nm.
[0113] At least one of the one or more pairs of organic electron donor-acceptor materials whose optical absorbance spectra may overlap the optical absorbance spectra of short wavelength cone photoreceptors in a human retina may comprise a lambda max between about 400 nm to about 450 nm, or between about 410 nm to about 430 nm.
[0114] At least one of the one or more pairs of organic electron donor-acceptor materials whose optical absorbance spectra may overlap the optical absorbance spectra of medium wavelength cone photoreceptors in a human retina may comprise a lambda max between about 510 nm to about 570 nm, or between about 510 nm to about 550 nm, or between about 530 nm to about 550 nm.
[0115] At least one of the one or more pairs of organic electron donor-acceptor materials whose optical absorbance spectra may overlap the optical absorbance spectra of long wavelength cone photoreceptors in a human retina may comprise a lambda max between about 540 nm to about 600 nm, or between about 540 nm to about 580 nm, or between about 560 nm to about 580 nm.1006145770Therapeutic agents
[0116] The nanoparticles may further comprise at least one therapeutic agent.
[0117] The therapeutic agent may comprise one or more neuroprotective agents. Neuroprotective agents are used to save ischemic neurons in the brain from irreversible injury or offer protection against cell degeneration to the neuronal cells. The person skilled in the art would be able to determine whether a substance is a neuroprotective agent. For instance, examples of neuroprotective agents could include any of several proteins found in the natural extracellular matrix, proteoglycans, heparin sulphate, and any number of nerve growth factors.
[0118] The therapeutic agent may comprise nerve growth factor. In some embodiments, the nerve growth factor may include brain derived neurotrophic factor (BDNF), Beta nerve growth factor (NGF), neurotrophins, such as NT-3, NT-4 / 5 and NT- 6, Cyclosporin A, FK506, and / or C3 siRNA.
[0119] The therapeutic agent may comprise one or more anti-inflammatory agents. Anti-inflammatory agents or antiphlogistic agents are substances that reduce inflammation or swelling. Anti-inflammatory drugs, also called anti-inflammatories, make up about half of analgesics. The person skilled in the art would be able to determine whether a substance is an anti-inflammatory agent.
[0120] The anti-inflammatory agents may comprise dexamethasone. Other suitable anti-inflammatory agents known in the art are contemplated.
[0121] The therapeutic agent may comprise one or more antioxidants. Antioxidants are compounds that scavenge and neutralise free radicals. The person skilled in the art would be able to determine whether a substance is an antioxidant. In some embodiments, the antioxidant may be selected from resveratrol, vitamin E, indigoidine and triphenylamine. In some embodiments, the antioxidant may be selected from resveratrol, vitamin E, indigoidine, trans-stilbene, and triphenylamine. Other antioxidants known in the art are contemplated.
[0122] In some embodiments, at least one of either the organic electron donor or the organic electron acceptor material in the form of nanoparticles comprises a single therapeutic agent.1006145770Electron donor-acceptor materials
[0123] The optical absorbance spectra of at least one or more pairs of the organic electron donor-acceptor materials may overlap with a wavelength of between about 370 nm to about 480 nm, or between about 440 nm to about 600 nm, or between about 500 nm to about 650 nm.
[0124] The one or more pairs of organic electron donor-acceptor materials may comprise poly(9,9-dioctylfluorene-a / f-bithiophene) (F8T2), [6,6] phenyl-C61 -butyric acid methyl ester (PCBM), poly(3-hexylthiophene-2,5-diyl) (P3HT), spirobifluorene-2,7-bis- perylenediimide (SF-PDI), poly[2,3-bis-(3-octyloxyphenyl)quinoxaline-5,8- diyl-a / f- thiophene-2,5-diyl] (TQ1 ), poly{[ / V, / V'-bis(2-octyldodecyl)-naphthalene-1 ,4,5,8- bis(dicarboximide)-2,6-diyl]-a / f-5,5'-(2,2'-bithiophene)} (N2200), and violanthrone-79, or derivatives and / or structural analogues thereof. Other suitable materials known in the art are contemplated.
[0125] In exemplified compositions, pairs of organic electron donor-acceptor materials may comprise F8T2:PCBM, P3HT:PCBM, P3HT:SF-PDI, and TQ1 :N2200 pairs. Other suitable pairs are contemplated.Methods of producing an organic semiconductor nanoparticle
[0126] The present disclosure further relates to a method of producing an organic semiconductor nanoparticle comprising the step of combining an aqueous surfactant solution with a solution of organic donor and / or acceptor material in an organic solvent.
[0127] The method may further comprise the addition of one or more therapeutic agents.
[0128] In some embodiments, the aqueous surfactant solution may comprise sodium dodecyl sulphate.
[0129] In some embodiments, the aqueous surfactant solution may have a surfactant concentration from about 0.1 mg / mL to about 20 mg / mL, or about 0.2 mg / mL to about 20 mg / mL, or about 0.3 mg / mL to about 20 mg / mL, or about 0.1 mg / mL to about 15 mg / mL, or about 0.1 mg / mL to about 12 mg / mL, or about 0.2 mg / mL to about 151006145770mg / mL, or about 0.2 mg / mL to about 12 mg / mL, or about 0.3 mg / mL to about 15 mg / mL, or about 0.3 mg / mL to about 12 mg / mL.
[0130] The present disclosure further relates to a method of producing an organic semiconductor nanoparticle comprising combining an aqueous surfactant solution with a solution of an organic donor and / or acceptor material and an additional therapeutic agent in an organic solvent.
[0131] In some embodiments, the aqueous surfactant solution may comprise sodium dodecyl sulphate.
[0132] In some embodiments, the aqueous surfactant solution may have a surfactant concentration from about 0.1 mg / mL to about 20 mg / mL, or about 0.2 mg / mL to about 20 mg / mL, or about 0.3 mg / mL to about 20 mg / mL, or about 0.1 mg / mL to about 15 mg / mL, or about 0.1 mg / mL to about 12 mg / mL, or about 0.2 mg / mL to about 15 mg / mL, or about 0.2 mg / mL to about 12 mg / mL, or about 0.3 mg / mL to about 15 mg / mL, or about 0.3 mg / mL to about 12 mg / mL.
[0133] The present disclosure further relates to a method of producing an organic semiconductor nanoparticle comprising combining an aqueous surfactant solution comprising an additional therapeutic agent with a solution of an organic donor and / or acceptor material in an organic solvent.
[0134] In some embodiments, the aqueous surfactant solution may comprise sodium dodecyl sulphate.
[0135] In some embodiments, the aqueous surfactant solution may have a surfactant concentration from about 0.1 mg / mL to about 20 mg / mL, or about 0.2 mg / mL to about 20 mg / mL, or about 0.3 mg / mL to about 20 mg / mL, or about 0.1 mg / mL to about 15 mg / mL, or about 0.1 mg / mL to about 12 mg / mL, or about 0.2 mg / mL to about 15 mg / mL, or about 0.2 mg / mL to about 12 mg / mL, or about 0.3 mg / mL to about 15 mg / mL, or about 0.3 mg / mL to about 12 mg / mL.Organic semiconductor devices
[0136] The present disclosure further relates to organic semiconductor devices comprising:1006145770(a) a substrate layer;(b) a first layer disposed on a surface of the substrate, said first layer comprising one or more first organic semiconductor materials;(c) a second layer disposed on the first layer, said second layer comprising one or more second organic semiconductor materials; wherein at least one of the first organic semiconductor materials and the second semiconductor materials together may form an organic semiconductor composition according to the present disclosure.
[0137] In some embodiments, the organic semiconductor device may further comprise a silane crosslinker (for example (3-glycidyloxypropyl)trimethylsilane) with (i) the positive charge selective transporting layer disposed on a surface of the substrate or (ii) the negative charge selective transporting layer disposed on a surface of the substrate. In some embodiments, the silane crosslinker comprises (3- glycidyloxypropyl)trimethylsilane (GOPS).
[0138] The organic semiconductor device may further comprise a positive charge selective transporting layer, a negative charge selective transporting layer, or both.
[0139] As used herein, a “positive charge selective transporting layer” refers to any material where the highest occupied molecular orbital (HOMO) energy is higher (more positive on the typical energy scale used in the art) than the HOMO energy of the organic electron donating material. For example, PEDOT:PSS (poly-ethylene- dioxythiophene doped with polystyrene sulfonate), Spiro-OMeTAD, polytetraarylamine (PTAA), rubrene, or 9,9-di[4-(di-p-tolyl)aminophenyl]fluorine (DTAF). Other suitable materials known in the art are contemplated.
[0140] As used herein, a “negative charge selective transporting layer” refers to any material where the lowest unoccupied molecular orbital (LIIMO) energy of the material is lower (more negative on the typical energy scale used in the art) than the LIIMO energy of the organic electron donating material. For example, zinc oxide nanoparticles, azacene derivatives, poly-diimide derivatives, or perylene (PDI) as the core and amino (PDIN) or N-oxide (PDINO) as the terminal substitute. Other suitable materials known in the art are contemplated.1006145770
[0141] The present disclosure further relates to an organic semiconductor device comprising:(a) a substrate layer;(b) a positive charge selective transporting layer disposed on a surface of the substrate;(c) a donor material layer disposed on the positive charge selective transporting layer, said donor material layer comprising one or more first organic semiconductor materials;(d) an acceptor material layer disposed on the donor material layer, said acceptor material layer comprising one or more second organic semiconductor materials;(e) a negative charge selective transporting layer disposed on the acceptor material layer; or(a) a substrate layer;(b) negative charge selective transporting layer disposed on a surface of the substrate;(c) an acceptor material layer disposed on the negative charge selective transporting layer, said acceptor material layer comprising one or more first organic semiconductor materials;(d) a donor material layer disposed on the acceptor material layer, said donor material layer comprising one or more second organic semiconductor materials;(e) a positive charge selective transporting layer disposed on the donor material layer; wherein at least one of the first organic semiconductor materials and the second semiconductor materials together may form an organic semiconductor composition according to the present disclosure.1006145770
[0142] In some embodiments, the organic semiconductor device may further comprise a silane crosslinker (for example (3-glycidyloxypropyl)trimethylsilane) with (i) the positive charge selective transporting layer disposed on a surface of the substrate or (ii) the negative charge selective transporting layer disposed on a surface of the substrate. In some embodiments, the silane crosslinker comprises (3- glycidyloxypropyl)trimethylsilane (GOPS).
[0143] In some embodiments of the organic semiconductor device according to the present disclosure, the first layer and the second layer, and / or the donor material layer and the acceptor material layer may be disposed as an intermixed nanoparticle layer.
[0144] In some embodiments of the organic semiconductor device according to the present disclosure, the first layer and the second layer, and / or the donor material layer and the acceptor material layer may be disposed as a nanoparticle layer, said nanoparticles comprising a combination of both organic electron donor and organic electron acceptor materials.
[0145] The substrate may be biocompatible.
[0146] The substrate may be flexible.
[0147] The substrate may be electrically conductive.
[0148] The substrate may comprise one or more of polymer, fabric, graphene, MXene, metal or conductive oxide.
[0149] For devices comprising nerve growth factor, the device may couple into functional retinal neurons, horizontal cells, bipolar cells, retinal ganglion cells, optical nerves, and / or the visual cortex of patients.
[0150] Preferably, the device does not require signal processing or connections that are external to a patient.Methods of fabricating organic semiconductor devices
[0151] The present disclosure further relates to a method of fabricating an organic semiconductor device comprising the steps of:1006145770(a) depositing at least one first organic semiconductor material layer onto a surface of a substrate;(b) depositing at least one second organic semiconductor material layer onto the first layer; wherein at least one of the first organic semiconductor material and the second semiconductor material together may form an organic semiconductor composition according to the present disclosure.
[0152] In some embodiments, the method may further comprise the step of depositing a charge selective transport layer onto the surface of the substrate prior to step (a) and / or depositing a charge selective transport layer onto the at least one second organic semiconductor material layer after step (b). In some embodiments, the device further includes a pixelated array formed from the first organic semiconductor material layer and the second organic semiconductor material layer.
[0153] In some embodiments, the method may further comprise adding a silane crosslinker to the charge selective transport layer deposited prior to step (a). In some embodiments, the silane crosslinker comprises (3-glycidyloxypropyl)trimethylsilane (GOPS).
[0154] In some embodiments, the method may further comprise UV-Ozone treatment or plasma ion implantation of the at least one first organic semiconductor material layer and / or the at least one second organic semiconductor material layer.
[0155] The present disclosure further relates to a method of fabricating an organic semiconductor device comprising the steps of:(a) depositing a positive charge selective transport layer onto a surface of a substrate;(b) depositing a donor material layer onto the positive charge selective transport layer, said donor material layer comprising one or more first organic semiconductor materials;1006145770(c) depositing an acceptor material layer onto the donor material layer, said acceptor material layer comprising one or more second organic semiconductor materials;(d) depositing a negative charge selective transport layer onto the acceptor material layer; or(a) depositing a negative charge selective transport layer onto a surface of a substrate;(b) depositing an acceptor material layer onto the negative charge selective transport layer, said acceptor material layer comprising one or more first organic semiconductor materials;(c) depositing a donor material layer onto the acceptor material layer, said donor material layer comprising one or more second organic semiconductor materials;(d) depositing a positive charge selective transport layer onto the donor material layer; wherein at least one of the first organic semiconductor material and the second semiconductor material together may form an organic semiconductor composition according to the present disclosure.
[0156] In some embodiments of the method, the method may further comprise adding a silane crosslinker to (i) the positive charge selective transport layer or (ii) the negative charge selective transport layer prior to step (a). In some embodiments, the silane crosslinker comprises (3-glycidyloxypropyl)trimethylsilane (GOPS).
[0157] The first organic semiconductor material layer and / or the second organic semiconductor material layer may be deposited by 3D printing, inkjet printing, vacuum deposition, spin-coating, blade coating, spray coating, slot die coating or laser patterning / etching. Other suitable methods are contemplated.
[0158] The steps of depositing the first organic semiconductor material layer and the second organic semiconductor material layer, and / or the steps of depositing the donor1006145770material layer and the acceptor material layer may be performed together, such that the materials are deposited as an intermixed nanoparticle layer.
[0159] The steps of depositing the first organic semiconductor material layer and the second organic semiconductor material layer, and / or the steps of depositing the donor material layer and the acceptor material layer may be performed together, such that the materials may be deposited as nanoparticles, said nanoparticles comprising a combination of both organic electron donor and organic electron acceptor materials.
[0160] In some embodiments of the method, the method may further comprise treating the acceptor material layer and / or the donor material layer with UV-Ozone treatment or plasma ion implantation.Use of organic semiconductor devices
[0161] The present disclosure provides an organic semiconductor device for use in a retinal prosthetic device.
[0162] The present disclosure provides a method of treating eye disease or disorder comprising implanting in the eye of a human subject an organic semiconductor device according to the present disclosure.
[0163] The present disclosure provides the use of an organic semiconductor device according to the present disclosure in the manufacture of a retinal prosthetic device for treating eye disease or disorder in a human subject.
[0164] The eye disease or disorder may be selected from macular degeneration, age- related macular degeneration, diabetic retinopathy, and retinitis pigmentosa. Other eye disease or disorders known in the art are contemplated.
[0165] When the device comprises nerve growth factor (NGF), the device may provide an improvement in neuron attachment and neuron growth.Certain embodiments
[0166] Embodiment 1 : An organic semiconductor composition comprising one or more pairs of organic electron donor-acceptor materials, wherein at least one of either the organic electron donor or the organic electron acceptor material is in the form of1006145770nanoparticles, and wherein the optical absorbance spectra of at least one of the one or more pairs of organic electron donor-acceptor materials overlap with the optical absorbance spectra of short, medium, or long wavelength cone photoreceptors, or rod photoreceptors in a human retina.
[0167] Embodiment 2: The organic semiconductor composition according to embodiment 1 , wherein the nanoparticles comprise a combination of both organic electron donor and organic electron acceptor materials.
[0168] Embodiment 3: The organic semiconductor composition according to embodiment 1 or embodiment 2, wherein the organic electron donor-acceptor materials are, at least in part, intermixed within a nanoparticle.
[0169] Embodiment 4: The organic semiconductor composition according to embodiment 3, wherein the distance between at least one of the organic electron donors and at least one of the organic electron acceptors within the nanoparticle is from about 5 nm to about 50 nm.
[0170] Embodiment 5: The organic semiconductor composition according to any one of embodiments 1 to 4, wherein the composition comprises two or more pairs of organic electron donor-acceptor materials.
[0171] Embodiment 6: The organic semiconductor composition according to embodiment 5, wherein the optical absorbance spectra of the two or more pairs of organic electron donor-acceptor materials independently overlap with at least two of the optical absorbance spectra of short, medium, and long wavelength cone photoreceptors in a human retina.
[0172] Embodiment 7: The organic semiconductor composition according to embodiment 1 or embodiment 2, wherein the composition comprises three or more pairs of organic electron donor-acceptor materials.
[0173] Embodiment 8: The organic semiconductor composition according to embodiment 7, wherein the optical absorbance spectra of the three or more pairs of organic electron donor-acceptor materials independently overlap with the optical absorbance spectra of short, medium, and long wavelength cone photoreceptors in a human retina.1006145770
[0174] Embodiment 9: The organic semiconductor composition according to any one of embodiments 1 to 8, wherein the average particle size of the nanoparticles is from about 10 nm to about 500 nm, or from about 20 nm to about 200 nm.
[0175] Embodiment 10: The organic semiconductor composition according to any one of embodiments 1 to 9, wherein the optical absorbance spectra of at least one or more pairs of the organic electron donor-acceptor materials overlap with a wavelength of between about 370 nm to about 480 nm, or between about 440 nm to about 600 nm, or between about 500 nm to about 650 nm.
[0176] Embodiment 11: The organic semiconductor composition according to any one of embodiments 1 to 10, wherein the nanoparticles further comprise one or more therapeutic agents, neuroprotective agents, nerve growth factors, anti-inflammatory agents and / or antioxidants.
[0177] Embodiment 12: The organic semiconductor composition according to embodiment 11 , wherein at least one of either the organic electron donor or the organic electron acceptor material in the form of nanoparticles comprises a single therapeutic agent.
[0178] Embodiment 13: The organic semiconductor composition according to any one of embodiments 1 to 12, wherein the one or more pairs of organic electron donoracceptor materials comprise poly(9,9-dioctylfluorene-alt-bithiophene) (F8T2), [6,6] phenyl-C61 -butyric acid methyl ester (PCBM), poly(3-hexylthiophene-2,5-diyl) (P3HT), spirobifluorene-2,7-bis-perylenediimide (SF-PDI), poly[2,3-bis-(3- octyloxyphenyl)quinoxaline-5,8- diyl-alt-thiophene-2,5-diyl] (TQ1 ), poly{[N,N'-bis(2- octyldodecyl)-naphthalene-1 ,4,5,8-bis(dicarboximide)-2,6-diyl]-alt-5,5'-(2,2'- bithiophene)} (N2200), violanthrone-79, or derivatives and / or structural analogues thereof.
[0179] Embodiment 14: The organic semiconductor composition according to any one of embodiments 1 to 12, wherein at least one of the one or more pairs of organic electron donor-acceptor materials whose optical absorbance spectra overlap the optical absorbance spectra of short wavelength cone photoreceptors in a human retina comprises a lambda max between about 400 nm to about 450 nm.1006145770
[0180] Embodiment 15: The organic semiconductor composition according to any one of embodiments 1 to 12, wherein at least one of the one or more pairs of organic electron donor-acceptor materials whose optical absorbance spectra overlap the optical absorbance spectra of medium wavelength cone photoreceptors in a human retina comprises a lambda max between about 510 nm to about 570 nm.
[0181] Embodiment 16: The organic semiconductor composition according to any one of embodiments 1 to 12, wherein at least one of the one or more pairs of organic electron donor-acceptor materials whose optical absorbance spectra overlap the optical absorbance spectra of long wavelength cone photoreceptors in a human retina comprises a lambda max between about 540 nm to about 600 nm.
[0182] Embodiment 17: The organic semiconductor composition according to any one of embodiments 5 to 16 wherein two or more pairs of organic electron donor-acceptor materials comprise two or more F8T2:PCBM, P3HT:PCBM, P3HT:SF-PDI, and TQ1 :N2200 pairs.
[0183] Embodiment 18: A method of producing organic semiconductor nanoparticles according to any one of embodiments 1 to 17 comprising the step of combining an aqueous surfactant solution with a solution of organic donor-acceptor material in an organic solvent.
[0184] Embodiment 19: The method according to embodiment 18, further comprising the addition of one or more therapeutic agents.
[0185] Embodiment 20: The method according to embodiment 18 or embodiment 19, wherein the aqueous surfactant solution comprises sodium dodecyl sulphate.
[0186] Embodiment 21: The method according to any one of embodiments 18 to 20, wherein the aqueous surfactant solution has a surfactant concentration from about 0.1 mg / mL to about 20 mg / mL, or about 0.2 mg / mL to about 15 mg / mL, or about 0.3 mg / mL to about 12 mg / mL.
[0187] Embodiment 22: A method of producing organic semiconductor nanoparticles according to any one of embodiments 11 to 17 comprising combining an aqueous surfactant solution with a solution of an organic donor-acceptor material and an additional therapeutic agent in an organic solvent.1006145770
[0188] Embodiment 23: A method of producing organic semiconductor nanoparticles according to any one of embodiments 11 to 17 comprising combining an aqueous surfactant solution comprising an additional therapeutic agent with a solution of an organic donor-acceptor material in an organic solvent.
[0189] Embodiment 24: An organic semiconductor device comprising:(a) a substrate layer;(b) a first layer disposed on a surface of the substrate, said first layer comprising one or more first organic semiconductor materials;(c) a second layer disposed on the first layer, said second layer comprising one or more second organic semiconductor materials; wherein at least one of the first organic semiconductor materials and the second semiconductor materials together form an organic semiconductor composition according to any one of embodiments 1 to 17.
[0190] Embodiment 25: An organic semiconductor device according to embodiment24, further comprising a positive charge selective transporting layer, a negative charge selective transporting layer, or both.
[0191] Embodiment 26: The organic semiconductor device according to embodiment25, wherein the organic semiconductor device further comprises a silane a crosslinker (for example (3-glycidyloxypropyl)trimethylsilane) with (i) the positive charge selective transporting layer or (ii) the negative charge selective transporting layer disposed on a surface of the substrate.
[0192] Embodiment 27: An organic semiconductor device comprising:(a) a substrate layer;(b) a positive charge selective transporting layer disposed on a surface of the substrate;1006145770(c) a donor material layer disposed on the positive charge selective transporting layer, said donor material layer comprising one or more first organic semiconductor materials;(d) an acceptor material layer disposed on the donor material layer, said acceptor material layer comprising one or more second organic semiconductor materials;(e) a negative charge selective transporting layer disposed on the acceptor material layer; or(a) a substrate layer;(b) a negative charge selective transporting layer disposed on a surface of the substrate;(c) an acceptor material layer disposed on the negative charge selective transporting layer, said acceptor material layer comprising one or more first organic semiconductor materials;(d) a donor material layer disposed on the acceptor material layer, said donor material layer comprising one or more second organic semiconductor materials;(e) a positive charge selective transporting layer disposed on the donor material layer; wherein at least one of the first organic semiconductor materials and the second semiconductor materials together form an organic semiconductor composition according to any one of embodiments 1 to 17.
[0193] Embodiment 28: The organic semiconductor device according to embodiment 27, wherein the organic semiconductor device further comprises a silane crosslinker (for example (3-glycidyloxypropyl)trimethylsilane) with (i) the positive charge selective transporting layer disposed on a surface of the substrate or (ii) the negative charge selective transporting layer disposed on a surface of the substrate.1006145770
[0194] Embodiment 29: An organic semiconductor device according to any one of embodiments 24 to 28, wherein the first layer and the second layer, and / or the donor material layer and the acceptor material layer are disposed as an intermixed nanoparticle layer.
[0195] Embodiment 30: An organic semiconductor device according to any one of embodiments 24 to 28, wherein the first layer and the second layer, and / or the donor material layer and the acceptor material layer are disposed as a nanoparticle layer, said nanoparticles comprising a combination of both organic electron donor and organic electron acceptor materials.
[0196] Embodiment 31: A method of fabricating an organic semiconductor device comprising the steps of:(a) depositing at least one first organic semiconductor material layer onto a surface of a substrate;(b) depositing at least one second organic semiconductor material layer onto the first layer; wherein at least one of the first organic semiconductor material and the second semiconductor material together form an organic semiconductor composition according to any one of embodiments 1 to 17.
[0197] Embodiment 32: The method according to embodiment 31 , wherein the method further comprises the step of depositing a charge selective transport layer onto the surface of the substrate prior to step (a) and / or depositing a charge selective transport layer onto the at least one second organic semiconductor material layer after step (b).
[0198] Embodiment 33: The method according to embodiment 32, wherein the method further comprises adding (3-glycidyloxypropyl)trimethylsilane as a cross-linking agent to the charge selective transport layer deposited prior to step (a).
[0199] Embodiment 34: The method according to any one of embodiments 31 to 33, wherein the method further comprises UV-Ozone treatment or plasma ion implantation1006145770of the at least one first organic semiconductor material layer and / or the at least one second organic semiconductor material layer.
[0200] Embodiment 35: A method of fabricating an organic semiconductor device comprising the steps of:(a) depositing a positive charge selective transport layer onto a surface of a substrate;(b) depositing a donor material layer onto the positive charge selective transport layer, said donor material layer comprising one or more first organic semiconductor materials;(c) depositing an acceptor material layer onto the donor material layer, said acceptor material layer comprising one or more second organic semiconductor materials;(d) depositing a negative charge selective transport layer onto the acceptor material layer; or(a) depositing a negative charge selective transport layer onto a surface of a substrate;(b) depositing an acceptor material layer onto the negative charge selective transport layer, said acceptor material layer comprising one or more first organic semiconductor materials;(c) depositing a donor material layer onto the acceptor material layer, said donor material layer comprising one or more second organic semiconductor materials;(d) depositing a positive charge selective transport layer onto the donor material layer; wherein at least one of the first organic semiconductor material and the second semiconductor material together form an organic semiconductor composition according to any one of embodiments 1 to 17.1006145770
[0201] Embodiment 36: The method according to embodiment 35, wherein the method further comprises adding (3-glycidyloxypropyl)trimethylsilane as a cross-linking agent to (i) the positive charge selective transport layer or (ii) the negative charge selective transport layer prior to step (a).
[0202] Embodiment 37: The method according to any one of embodiments 31 to 36, wherein the first organic semiconductor material layer and / or the second organic semiconductor material layer are deposited by 3D printing, inkjet printing, vacuum deposition, spin-coating, blade coating, spray coating, slot die coating or laser patterning / etching.
[0203] Embodiment 38: The method according to any one of embodiments 31 to 37, wherein the steps of depositing the first organic semiconductor material layer and the second organic semiconductor material layer, and / or the steps of depositing the donor material layer and the acceptor material layer are performed together, such that the materials are deposited as an intermixed nanoparticle layer.
[0204] Embodiment 39: The method according to any one of embodiments 31 to 37, wherein the steps of depositing the first organic semiconductor material layer and the second organic semiconductor material layer, and / or the steps of depositing the donor material layer and the acceptor material layer are performed together, such that the materials are deposited as nanoparticles, said nanoparticles comprising a combination of both organic electron donor and organic electron acceptor materials.
[0205] Embodiment 40: The method according to any one of embodiments 35 to 39, wherein the method further comprises treating the acceptor material layer and / or the donor material layer with UV-Ozone treatment or plasma ion implantation.
[0206] Embodiment 41: The organic semiconductor device according to any one of embodiments 24 to 30, or the method of any one of embodiments 31 to 40, wherein the substrate comprises one or more of polymer, fabric, graphene, MXene, metal or conductive oxide.
[0207] Embodiment 42: An organic semiconductor device according to any one of embodiments 24 to 30 or 41 , for use in a retinal prosthetic device.1006145770
[0208] Embodiment 43: A method of treating eye disease or disorder comprising implanting in the eye of a human subject an organic semiconductor device according to any one of embodiments 24 to 30 or 41 .
[0209] Embodiment 44: The method of according to embodiment 43, wherein the eye disease or disorder is selected from macular degeneration, age-related macular degeneration, diabetic retinopathy, and retinitis pigmentosa.
[0210] Embodiment 45: The method according to embodiment 43 or 44, wherein the device comprises nerve growth factor (NGF), the device provides an improvement in neuron attachment and neuron growth.ExamplesExample 1 - Materials and methods
[0211] Organic semiconductors (PCBM, F8T2, P3HT, SF-PDI, N2200, TQ1 ) were obtained commercially (Ossila). ITO-coated glass substrates (22 x 22 mm, thickness of 1.1 mm, Rsheet < 15 £) / □) were obtain from Xin Yang Technology. Silicon sealant (Dowsil 732) was obtained from Dow Silicones. Dexamethasone was obtained from Sigma Aldrich. Nerve growth factor was obtained from commercial sources. Chloroform, sodium dodecylsulphate, o-dichlorobenzene, paraformaldehyde and sodium azide were obtained from commercial sources.Inkjet Printing Organic Arrays
[0212] Inkjet printing of nanoparticle materials was performed using organic semiconductor nanoparticles dispersed in o-dichlorobenzene at a concentration of 8 mg mL’1. Printing was performed using a Sonoplot Microplotter with the dispensing pipette tip size varied from 10-20 pm. Resolution and print quality tests were performed by depositing ink patterns onto both glass and Kapton substrates, with the resulting print quality and spatial resolution subsequently analysed using an optical microscope.Cell Viability Assay
[0213] Retinal tissue was cultured on organic semiconductor films cast from nanoparticle materials (3 - 7 days in culture (DIC)) and then incubated in cell viability1006145770assay solution (ab115347, Abeam) for 10 minutes before being imaged on an epifluorescence microscope (Nikon). Counts of live and dead cells were done in Imaged (NIH Image) by analysing images (200x total magnification, n = 10 per sample) using a pixel brightness filter and an automatic moment-preserving threshold process to remove background noise. The cut-off value for the pixel brightness filter was kept consistent between and within sample analysis. A watershed image processing algorithm was applied to create boundaries between overlapping cells and individual cells were then counted using the particle analysis function. Minimum size of allowed individual particles was kept consistent between and within samples. Green (live cell) and red (dead cell) channel images were processed separately using an automated macro and results were checked manually for each image.Brn3a Retinal Ganglion Cell Staining and Neurite Analysis
[0214] Retinal tissue cultures (3 or 7-8 DIC) were fixed (4% paraformaldehyde) for 15 minutes following the cell viability assay and stored in phosphate buffered saline (PBS, 0.1 M) with sodium azide (0.1 %). Fixed cell cultures were incubated in Brn3a primary antibody (Abeam, ab81213) overnight, then incubated in biotinylated donkey-anti-rabbit IgG antibody (Jackson ImmunoResearch, cat no. 711 -065-152) for 2 hours. Cells cultures were then incubated in an avidin-biotin-horseradish peroxidase complex solution (Vector Laboratories, PK-1600). Horseradish peroxidase activity was visualised with nickel-diaminobenzidine.
[0215] Representative images of individual neurons were captured with differential interference contrast microscopy on a Nikon microscope. Low-magnification, large-area images were captured on a confocal bright field microscope (Zeiss LSM 900) for quantitative anatomical analysis. A semi-automated tiling process was used to capture an 8.4 x 8.3 mm image of the central region of each cell culture at a total magnification of 200x. A random sampling technique was used for neuron count and neurite analysis whereby 5 random grids were selected from 12 x 12 grids of squares. Anatomical analysis for each neuron within the grid was performed with basic tools in ImageJ (NIH Image).1006145770Nanoparticle synthesis
[0216] The synthesis procedure involved dissolution of the organic semiconductor materials into chloroform (although alternative organic solvents are suitable) before combining these solutions with an aqueous solution containing the surfactant sodium dodecyl sulphate (SDS). The organic-water mixture was ultrasonicated for 2 minutes with a power of 20-30W delivered to the solution, resulting in the creation of nanoparticles of the organic semiconductors suspended in water that were verified by UV-visible photospectrometery, dynamic light scattering particle size analysis, and scanning electron microscopy.
[0217] In an exemplary embodiment of synthesising the organic semiconductor nanoparticles, 30 mg of total organic semiconductor mass was dissolved into 0.5 mL of chloroform. In instances of composite materials containing both donor and acceptor, the total mass of donor and acceptor together summed to 30 mg, in a ratio of 1 :1 by mass. This solution was combined with 2.7 mL of aqueous solution containing SDS and then the mixture (now 3.2 mL in total) was sonicated.UV-visible photospectrometry
[0218] UV-visible absorbance spectra were measured using a Varian Cary 6000i spectrophotometer. The spectra for aqueous nanoparticle dispersions were determined by filling quartz cuvettes with a 1 cm pathlength. The spectra for thin films were measured by spin coating the organic semiconductors from either chloroform solutions (10 mg / mL) or aqueous nanoparticle dispersions onto glass slides.Dynamic light scattering (DLS) particle size analysis
[0219] DLS measurements were performed on a Malvern Zetasizer Nano Z, with particle size determined initially on an intensity basis, and in instances of inhomogeneity, corrections for a number average particle size using Mie transformations from the raw intensity signal.Scanning electron microscopy
[0220] Scanning electron microscopy was performed by spin coating 2.5 pL of nanoparticle dispersion onto carbon studs and coating with 5 nm of platinum. SEM1006145770images were captured using both a Zeiss Sigma VP and a Zeiss Sigma HD VP operating at accelerating voltages of 2-5 kV to investigate the nanoparticle shape, size, and uniformity.Example 2 - Organic Semiconducting Nanoparticles with Incorporated Neuroprotective Drugs
[0221] Figure 1 shows the optical absorbance spectra of organic semiconductor solutions and films compared to previously reported spectra of human photoreceptors. Native films (ie, films without the semiconductor material incorporated into a nanoparticle) should have a similar spectrum to the nanoparticle materials as they will behave like solid materials. Therefore, there would not be a shift from going from a native film to a nanoparticle film for the same material.
[0222] The large shift in the absorbance between the film and solution of P3HT shown in Figure 1 (C) is due to the polymer physics / chemistry. In many polymers, the structure in solution tends towards an "amorphous" structure, ie long strands of molecules randomly dispersed in space. When the polymers are cast into solid films, these strands begin to align to form repetitive crystalline structures, and this causes the optical absorbance to shift. Different polymers will show different shifts depending on the degree to which they start as amorphous, and the degree to which they can regularly pack to form crystals. For P3HT, this change is on the more extreme end, and thus the large apparent shift.
[0223] Organic conductors were synthesized into nanoparticles dispersed in aqueous solutions with precisely tuned dimensions using a miniemulsion technique as reported previously (Mohsen Ameri et al., ACS Applied Materials & Interfaces, 2019, 11, 10074- 10088). Four different concentrations of surfactant molecule sodium dodecylsulphate (SDS; 11 .87 mg mL-1 , 3.57 mg mL-1 , 0.71 mg mL-1 and 0.36 mg mL-1 ) were dissolved into an aqueous phase of 2.80 mL, designed to obtain nanoparticles with varied sizes. The aqueous phase was then combined with an organic phase, prepared by dissolving 30 mg of the organic semiconductor in either 560 pL or 1080 pL anhydrous CHCh to produce smaller (less than 100 nm) and larger nanoparticles (more than 100 nm), respectively. The mixtures were stirred at 100 rpm at 35 °C for 5 minutes, then stirred at1006145770the same temperature, at an elevated spin speed of 500 rpm for 25 minutes. Finally, the samples were sonicated in an ultrasonic bath at 60 °C for 25 minutes.
[0224] Both the anti-inflammatory glucocorticosteroid drug dexamethasone and the neuroprotective nerve growth factor (NGF) could be incorporated into nanoparticles during the first phase of the emulsification process. This was achieved via two separate pathways; 1 ) addition of an organic-soluble dexamethasone into the organic phase of the emulsion at the same 10 wt.% ratio. 2) Inclusion of NGF directly into the final mixture.
[0225] Dexamethasone release kinetics were initially probed using an uncontrolled passive release mechanism. The kinetics showed a sharp rise in release from 0 to 9.1 pg mL’1immediately upon immersion into water, which is due to the surface-adsorbed unbound drug molecules (i.e. not fully encapsulated inside the nanoparticles) being washed from the film surface.
[0226] Subsequently the release profile shows a customary Langmuir-Blodgett release profile, rising slowly to a total drug release of 15.2 pg mL’1after an hour, and then showing further slowing of the kinetics to a total drug release of 21.4 pg mL’1after 5 hours. To accelerate the release kinetics and extract more dexamethasone from the dexamethasone containing nanoparticles, the nanoparticle films were connected to an external voltage stimulus. Application of this approach to the nanoparticles found a significant increase in dexamethasone released when the films were electrically stimulated using a bias voltage of 2V compared to a passive release protocol.Disregarding the initial 1 min period where surface-adsorbed molecules are released, electrical stimulation released dexamethasone at a rate of ~3.8 pg mL’1min-1 in the first 10 minutes after application of the bias. By comparison, the passive release over the same period occurred at a rate of 0.2 pg mL’1min’1.
[0227] Inclusion of NGF into organic nanoparticles showed strong evidence for a 2-3 fold improvement in the neuron attachment and growth of the longest neurites, providing strong evidence that this approach improves attachment of neurons at the organic semiconducting interface.1006145770Example 3 - Biocompatibility of the organic semiconductor nanoparticle compositions
[0228] Dissociated human retinal tissue cultures were established on the six different organic semiconductor thin films and a glass control. The viability of cell survival on organic semiconductor films was assessed at both 3 and 7-8 days in culture (DIC).
[0229] At both time points measured, cell viability of human retinal cell cultures established on organic semiconductor thin films was observed to be similar to that of human retinal tissue cultures established on glass control samples. At both time points measured, cell viability of human retinal tissue cultures established on organic semiconductor nanoparticle films appear promising (>90% live cells for all materials), with similar cell viability for human retinal tissue cultures established on poly-D-lysine (PDL) coated organic semiconductor materials and PDL coated glass controls.
[0230] The retinal ganglion cell (RGC)-specific cell marker Brn3a was immunolabelled in fixed retinal tissue cultures and visualised with diaminobenzidine (DAB) immunohistochemistry. At 7-8 DIC, individual Brn3a+ neurons and neurite extensions were observed in cultures on all organic semiconductor nanoparticle films tested. This result suggests retinal ganglion cell growth is compatible with all organic semiconductor nanoparticle materials over this acute timeframe. To further support this finding, the organic semiconductor nanoparticle - retinal cell co-cultures were methodically imaged, and a rigorous quantitative analysis was performed on the anatomical properties of individual human RGC neurons.Example 4 - Fabrication of organic semiconductor devices with nanoparticle compositions
[0231] Figure 2 shows a schematic of a device (10) made according to the method of the present disclosure. The bottom layer (11) represents a flexible electrode / substrate, onto which the middle layer (12) is deposited, the middle layer containing organic donor material nanoparticles. Onto the middle layer, a further layer (13) containing organic electron accepting material nanoparticles is deposited. The middle layer and further layer may be deposited as a single intermixed layer. This device can then be implanted into the body where neurons (14) (shown on top of the further layer (13) in the magnified inset) interface with the outward facing layer.1006145770
[0232] Figure 3 shows a further layout for a device according to the present disclosure (20), containing charge transport layers. On a negative charge transport layer, an organic electron acceptor material is deposited, followed by an organic electron donor material. After the electron donor material is deposited a positive charge transport layer is added. Finally, a flexible electrode / substrate is added on the top of the device. Each layer is labelled in Figure 3 may have the order of the listed layers shown below the flexible electrode reversed and still produce a functional device.Example 5 - P3HT Donor, PCBM Acceptor, and Composite P3HT:PCBM Nanoparticles
[0233] Nanoparticles composed of pure donor material P3HT and pure acceptor material PCBM were made in accordance with Example 1 . Additionally, the donor and acceptor were blended together into a combined composite nanoparticle where both materials were present. Particle size and electron microscopy data revealed nanoparticles with an approximate size of 60-80 nm for the pure materials (75 ± 29 nm for P3HT and 70 ± 24 nm for PCBM) and 135 ± 49 nm for the composite material.
[0234] UV-visible photospectrometry data indicated that the unique absorption signal from both the pure P3HT and pure PCBM materials were present in the blended nanoparticles (Figure 4). Furthermore, comparison of the nanoparticle absorption spectra to that of the neat materials dissolved in organic solvents showed that the aqueous nanoparticle dispersions containing P3HT have this material present in its solid-state form. This verified that the nanoparticle dispersions consist of solid organic semiconductor materials dispersed in an aqueous solution, rather than simple molecular solutions in water.
[0235] Measurement of the water contact angle for thin films (20 -100 nm) created by spin coating a layer of organic semiconductor onto a glass slide (spin speed 2000 rpm, acceleration 1500 rpm s_1) showed that the native organic semiconductor materials were hydrophobic (water contact angle approaching 90°), which is known to result in poor interactions with hydrophilic cells in the aqueous environment of the human body. However, once the films were created from the aqueous nanoparticle dispersions, the films became significantly more hydrophilic (water contact angles of 10-30°), which facilitates much more effective interactions with hydrophilic neural cells in the human1006145770body, enabling direct interfacing of these materials with cells without the need for any cell adhesion layers.Example 6 - F8T2 Nanoparticles
[0236] Aqueous nanoparticle dispersions from organic semiconductor material poly(9,9-dioctylfluorene-alt-2,2'-bithiophene) (F8T2) were also prepared as per the method outlined in Example 1 . This material was selected due to the close overlap between its absorption spectrum and that of the S cones present in the human retina. Nanoparticles produced from F8T2 were round (as indicated by scanning electron microscopy images). Consequently, due to their spherical shape, their size could be reliably characterised using dynamic light scattering.
[0237] F8T2 NPs of varying size were produced by emulsification using different concentrations of SDS surfactant. F8T2 nanoparticles are referred here according to the SDS content used to produce them, 1 , 2, 10, and 33 mg of SDS. These nanoparticles were then characterised by dynamic light scattering (DLS). DLS measurements of size from F8T2 nanoparticle materials showed a consistent and uniform average size. Table 1 shows the size of F8T2 nanoparticles prepared using various concentrations of SDS.Table 1: size of F8T2 Nanoparticles prepared using various concentrations of SDS.Example 7 - Cell viability of F8T2 Nanoparticles
[0238] F8T2 nanoparticles synthesised with 10 mg SDS were used for Biocompatibility Assessment and nerve growth factor (NGF) release.
[0239] The viability of cells on films cast from aqueous F8T2 nanoparticle dispersions was established after culturing primary dorsal root ganglion (DRG) cells on F8T2 thin films for time periods of 3 and 7 days. Live dead assay results revealed F8T21006145770nanoparticle films had a cell viability of 89% at 3 days in culture (DIC) and 88% at 7 DIC. The glass control group showed high cell viability, with 95% at 3 DIC and 96% at 7 DIC. This result demonstrated the high biocompatibility of F8T2 nanoparticle films with primary DRG neurons.
[0240] The live and dead assay is an excellent tool for determining cell viability of primary neuronal cultures on OSC thin films. However, a disadvantage of this technique is that it lacks specificity. The live - dead assay determines whether cells are alive or dead and stains all cell types present in the culture. To go one step beyond this analysis, cell populations were immunolabelled with primary antibodies against neuronal markers. This technique also allowed specific examination of the growth of primary neurite extensions from the cell bodies over time. After processing for the live - dead assays, cells cultured on the films were fixed and then neurons were subsequently labelled using a neuronal marker called microtubule-associated protein 2 (MAP2).MAP2 is highly expressed in primary sensory DRG neuronal, as it promotes rearrangements of microtubules it will label both soma and neurite extensions.
[0241] Analysis of the neurites from this immunolabelling showed average neurite lengths of 23 pm after 3 DIC, and 51 pm after 7 DIC for the films cast from F8T2 aqueous nanoparticle dispersions. In comparison, the average neurite lengths for cells grown on a glass slide control were 15 pm after 3 DIC, and 23 pm after 7 DIC. The longer neurite length on the F8T2 samples compared to the glass slides highlights that these nanoparticle films were excellent at supporting the adhesion and proliferation of neuronal cell populations.Example 8 - Treatments to avoid nanoparticle delamination and promote cell adhesionGOPS Crosslinking
[0242] A potential issue with layered structures is the delamination from water-miscible organic materials from electrode surfaces, causing destruction of devices in an aqueous operating environment. To address this, a strategy of adding a cross-linking agent, (3- glycidyloxypropyl)trimethylsilane (GOPS) to the bottom susceptible charge transport layer, PEDOT:PSS was explored.1006145770
[0243] When GOPS was mixed into the PEDOT:PSS solution at a weight ratio of 1 %, it showed an ability to prevent delamination of the PEDOT:PSS from electrode surfaces under incubation (37°C and 50% humidity), under ultrasound mixing / agitation, and after sitting in water for up to 1 week.UV-Ozone treatment
[0244] The organic semiconductor materials are known to be hydrophobic and thus face potential issues when interfacing with cells. Creation of the nanoparticle dispersions may assist in addressing this, as the surfactant lowers the water contact angle as described above. However, this relies on keeping residual surfactant in the nanoparticle dispersions. UV-ozone treatment is an approach shown to modulate the water contact angle precisely in these organic semiconductor materials.
[0245] Nanoparticle films of test material P3HT were prepared and exposed to a UV- ozone treatment (instrument from Ossila) for varying amounts of time, with the contact angle (WCA) of a water droplet on the nanoparticle film measured at various time points. The original P3HT surface is highly hydrophobic (WCA = 96°) without any treatment, however, the contact angle with water can be precisely tuned down to 25° (highly hydrophilic) with up to 10 mins of UV-ozone treatment. This result represents an alternative pathway to enabling improved cell interactions and adhesions with the organic semiconductors.
[0246] X-ray photoelectron spectroscopy was performed to understand the origin of this effect. It is clear that the UV-Ozone treatment creates new functional groups on the surface of the nanoparticle films that are rich in oxygen and nitrogen, enabling a more polar surface that interacts with water, and thus neuronal cells, more effectively.Plasma ion implantation
[0247] As an alternative surface treatment to UV-ozone, it was also demonstrated that plasma ion implantation (PH) in a nitrogen environment could be used to modulate the surface energy of semiconductor material N2200 and improve its interactions with cells. Nanoparticle films were treated in a customised plasma chamber using a nitrogen environment and accelerating voltage of 10 kV between the electrode plates. The nitrogen PH treatment demonstrated an ability to tune the contact angle of the N2200 to1006145770make the nanoparticle films more hydrophilic, which was confirmed to be related to creation of polar function groups on the surface of the nanoparticle film under the PH treatment.
[0248] Untreated N2200 surfaces could not sustain cellular growth due to their hydrophobicity. Successful culturing of dorsal root ganglion cells onto the PH treated surfaces was demonstrated and used immunolabelling with a neuronal marker called microtubule-associated protein 2 (MAP2) to highlight neuron growth. MAP2 is highly expressed in primary sensory DRG neuronal, as it promotes rearrangements of microtubules it will label both soma and neurite extensions. All treatment times showed adhesion and growth of neural cells was not present in the untreated nanoparticle films.Example 9 - Integration of biomolecules with nanoparticles and generation of electronic charge
[0249] The ability to incorporate and release nerve growth factor (NGF) from F8T2 nanoparticles was also demonstrated. To avoid degradation, NGF, was added into F8T2 nanoparticles immediately prior to the preparation of thin films by spin-coating. A working solution of NGF (100 pl of 833 ng / ml) was added to 600 pl of F8T2 NP, for a final NGF composition of 119 ng / ml. The solution was sonicated at 37°C for 25 minutes to incorporate NGF. Thin films were then made immediately, by spin coating. The same method was also used to prepare thin F8T2 films without F8T2 nanoparticles.
[0250] Results obtained from ELISA assays (Figure 5) showed a continuous passive release of NGF from samples tested. An average 2.6 ng / ml I hour of NGF was passively released from F8T2 nanoparticle films, compared to a lower release of 1 .5 ng / ml I hour of NGF for F8T2 thin films spun from chloroform (no nanoparticles). This release was constant for up to 12 hours. Over the next 12 hours (between 12 hours and 24 hours), NGF release per hour decreased to 1 .42 ng / ml / hour and 1 .12 ng / ml / hour for F8T2 nanoparticles and F8T2, respectively. After 24 hours, the passive release of NGF plateaued and a total amount of 48 ng / ml NGF was released from F8T2 nanoparticle thin films compared to 31 ng / ml for F8T2 thin films. After 24 hours, samples were taken every 24 hours for a total of 166 hours (7 days) to calculate NGF release over this 7-day time period.1006145770
[0251] These results demonstrate the capacity of F8T2 nanoparticle thin films to passively release approximately 30% of the total amount of NGF incorporated in the devices, to the extracellular environment over time compared to approximately 19% for F8T2 thin film samples.
[0252] After culturing dorsal root ganglion neuron cells on these films for 3 days, a Kruskal-Wallis test showed there was a statistically significant difference in neurite length between device architectures,2(4, N = 300) = 57.22, p<0.0001. Using Dunn’s multiple comparisons, the difference in the length of the primary neurite between ITO / glass and F8T2 thin films or F8T2 nanoparticle thin films was determined to be not significant. This suggests during 3 DIC, F8T2 by itself, does not enhance primary neurite growth. However, including NGF within the films resulted in a significant increase in the length of primary neurites compared to ITO and to F8T2 thin films and F8T2 nanoparticle thin films without NGF (Figure 6).
[0253] The effect of illuminating the F8T2 nanoparticles both with and without the incorporation of NGF was investigated. The results from Kelvin Probe Force microscopy (KPFM) analysis of F8T2 nanoparticle and F8T2 thin film devices demonstrated a good signal upon light stimulation at 460 nm of these materials, showing a spontaneous charge was generated. Using direct photo-stimulation, a strong photocurrent was observed. The average surface photocurrent difference transitioning from dark to light (460 nm) was measured as 141 mV for F8T2 nanoparticles + NGF and 94 mV for F8T2 nanoparticles alone. This result demonstrated the generation of capacitive charge that is sufficient to communicate with electrogenic cells such as neurons.Example 10 - Incorporation and release of antioxidants from P3HT nanoparticles
[0254] A promising approach to reduce the effect of photochemical oxidation of organic semiconductors and the consequent reduction in charge performance in aqueous environments is the use of antioxidants.
[0255] To examine the effects of antioxidants on photoluminescence (PL), two antioxidant agents were chosen. The selected antioxidant complexes, triphenylamine (TPA) and trans-stilbene (TSB) were combined (1 :1 ratio of TPA:TSB) and mixed into1006145770the organic phase during the mini-emulsion nanoparticle synthesis preparation method to incorporate into P3HT nanoparticles.
[0256] P3HT nanoparticle samples prepared with the highest amount of surfactant (SDS), showed a characteristic “glue like” appearance with nanoparticles aggregating in clusters throughout the sample. Similar aggregation of nanoparticles was observed when TPA / TSB was incorporated to P3HT nanoparticles for samples prepared with 10 and 33 mg SDS. P3HT nanoparticles and P3HT nanoparticles + TPA / TSB prepared using 1 and 2 mg SDS did not appear to agglutinate.
[0257] To evaluate the impact of TPA / TSB incorporation into P3HT nanoparticles on charge generation stability in nanoparticle thin films, the photoluminescence output responses in native P3HT nanoparticles and P3HT nanoparticles + TPA / TSB samples was compared. This comparison, however, required normalization of the absorbed photon signal to account for potential variations in nanoparticle concentration across different samples. Differing concentrations can influence the number of absorbed photons and, consequently, the initial exciton population. If there is a higher concentration (density) of nanoparticles within a sample, a higher PL intensity will typically be recorded (neglecting self-quenching mechanisms), due to a greater number of excited states. To account for this, the absorbance spectra of all P3HT nanoparticles and P3HT nanoparticles + TPA / TSB materials synthesised with 1 , 2, 10, and 33 mg of SDS, was measured using UV-visible spectroscopy. This UV-visible spectroscopy result was then used to correct the PL output spectrum (see equation below). The final corrected PL spectrum then represents the number of excited states decaying per “unit absorbed photon” in the nanoparticle sample.PLNormalised PL= -1 - Log (A)
[0258] In the case of larger P3HT nanoparticles + TPA / TSB (~115 nm to ~ 150 nm synthesised with 1 and 2 mg SDS, respectively), the incorporation of TPA / TSB resulted in a ~50% enhancement in PL intensity compared to P3HT nanoparticles without the addition of antioxidants (Figure 7). These data points suggested that the presence of antioxidants mitigates excited state quenching in P3HT nanoparticle systems. This was likely attributable to the suppression of oxygen-mediated degradation pathways. The1006145770implication for functional devices, such as bilayer films or neural interfaces, is significant. Improving the created charge longevity increases the likelihood of achieving exciton dissociation into free charges, thereby enhancing charge generation and potentially improving electrical coupling with biological tissue.
[0259] DRG neurons were cultured on P3HT nanoparticles and P3HT nanoparticles + TPA / TSB samples of different nanoparticle size for 3 or 7 days. Cell viability of DRG neurons cultured on P3HT nanoparticles for 7 DIC, ranges between 88% and 94% across all nanoparticle sizes. There were no statistically significant differences in cell viability for nanoparticles synthesised by different amounts of SDS. For P3HT nanoparticles + TPA / TSB cultured for 7 DIC, cell viability ranged between 88% and 95% for all nanoparticle sizes. Similar to the data for the native P3HT nanoparticles (no antioxidants), there were no statistically significant differences in cell viability across any P3HT nanoparticles + TPA / TSB samples. While cell viability remained high for all samples tested, the highest concentration of SDS (33 mg) resulted in the lowest cell viability for both P3HT nanoparticles and P3HT nanoparticles + TPA / TSB samples. This suggests that despite the presence of SDS (either attached or freely floating), it did not have an adverse effect on cell viability or survival of DRG neurons cultured on P3HT nanoparticles or P3HT nanoparticles + TPA / TSB samples cultured for 7 DIC.1006145770
Claims
CLAIMS1 . An organic semiconductor composition comprising one or more pairs of organic electron donor-acceptor materials, wherein at least one of either the organic electron donor or the organic electron acceptor material is in the form of nanoparticles, and wherein the optical absorbance spectra of at least one of the one or more pairs of organic electron donor-acceptor materials overlap with the optical absorbance spectra of short, medium, or long wavelength cone photoreceptors, or rod photoreceptors in a human retina.
2. The organic semiconductor composition according to claim 1 , wherein the nanoparticles comprise a combination of both organic electron donor and organic electron acceptor materials.
3. The organic semiconductor composition according to claim 1 or claim 2, wherein the organic electron donor-acceptor materials are, at least in part, intermixed within a nanoparticle.
4. The organic semiconductor composition according to claim 2 or claim 3, wherein the distance between at least one of the organic electron donors and at least one of the organic electron acceptors within the nanoparticle is from about 5 nm to about 50 nm.
5. The organic semiconductor composition according to any one of claims 1 to 4, wherein the composition comprises two or more pairs of organic electron donoracceptor materials.
6. The organic semiconductor composition according to claim 5, wherein the optical absorbance spectra of the two or more pairs of organic electron donor-acceptor materials independently overlap with at least two of the optical absorbance spectra of short, medium, and long wavelength cone photoreceptors in a human retina.
7. The organic semiconductor composition according to any one of claims 1 to 4, wherein the composition comprises three or more pairs of organic electron donoracceptor materials.
8. The organic semiconductor composition according to claim 7, wherein the optical absorbance spectra of the three or more pairs of organic electron donor-acceptor1006145770materials independently overlap with the optical absorbance spectra of short, medium, and long wavelength cone photoreceptors in a human retina.
9. The organic semiconductor composition according to any one of claims 1 to 8, wherein the average particle size of the nanoparticles is from about 10 nm to about 500 nm, or from about 20 nm to about 200 nm.
10. The organic semiconductor composition according to any one of claims 1 to 9, wherein the optical absorbance spectra of at least one or more pairs of the organic electron donor-acceptor materials overlap with a wavelength of between about 370 nm to about 480 nm, or between about 440 nm to about 600 nm, or between about 500 nm to about 650 nm.11 . The organic semiconductor composition according to any one of claims 1 to 10, wherein the nanoparticles further comprise one or more therapeutic agents, neuroprotective agents, nerve growth factors (NGFs), anti-inflammatory agents and / or antioxidants.
12. The organic semiconductor composition according to any one of claims 1 to 11 , wherein the one or more pairs of organic electron donor-acceptor materials comprise poly(9,9-dioctylfluorene-a / f-bithiophene) (F8T2), [6,6] phenyl-C61 -butyric acid methyl ester (PCBM), poly(3-hexylthiophene-2,5-diyl) (P3HT), spirobifluorene-2,7-bis- perylenediimide (SF-PDI), poly[2,3-bis-(3-octyloxyphenyl)quinoxaline-5,8- diyl-a / f- thiophene-2,5-diyl] (TQ1 ), poly{[ / V, / V'-bis(2-octyldodecyl)-naphthalene-1 ,4,5,8- bis(dicarboximide)-2,6-diyl]-a / f-5,5'-(2,2'-bithiophene)} (N2200), violanthrone-79, or derivatives and / or structural analogues thereof.
13. The organic semiconductor composition according to any one of claims 1 to 12, wherein:(i) at least one of the one or more pairs of organic electron donor-acceptor materials whose optical absorbance spectra overlap the optical absorbance spectra of short wavelength cone photoreceptors in a human retina comprises a lambda max between about 400 nm to about 450 nm; and / or(ii) at least one of the one or more pairs of organic electron donor-acceptor materials whose optical absorbance spectra overlap the optical absorbance spectra of medium1006145770wavelength cone photoreceptors in a human retina comprises a lambda max between about 510 nm to about 570 nm; and / or(iii) at least one of the one or more pairs of organic electron donor-acceptor materials whose optical absorbance spectra overlap the optical absorbance spectra of long wavelength cone photoreceptors in a human retina comprises a lambda max between about 540 nm to about 600 nm.
14. The organic semiconductor composition according to any one of claims 5 to 13 wherein two or more pairs of organic electron donor-acceptor materials comprise two or more F8T2:PCBM, P3HT:PCBM, P3HT:SF-PDI, and TQ1 :N2200 pairs.
15. A method of producing organic semiconductor nanoparticles according to any one of claims 1 to 14 comprising the step of combining an aqueous surfactant solution with a solution of organic donor and / or acceptor material in an organic solvent.
16. A method of producing organic semiconductor nanoparticles according to any one of claims 11 to 14 comprising combining an aqueous surfactant solution with a solution of an organic donor and / or acceptor material and an additional therapeutic agent in an organic solvent.
17. A method of producing organic semiconductor nanoparticles according to any one of claims 11 to 14 comprising combining an aqueous surfactant solution comprising an additional therapeutic agent with a solution of an organic donor and / or acceptor material in an organic solvent.
18. An organic semiconductor device comprising:(a) a substrate layer;(b) a first layer disposed on a surface of the substrate, said first layer comprising one or more first organic semiconductor materials;(c) a second layer disposed on the first layer, said second layer comprising one or more second organic semiconductor materials;1006145770wherein at least one of the first organic semiconductor materials and the second semiconductor materials together form an organic semiconductor composition according to any one of claims 1 to 14.
19. An organic semiconductor device according to claim 18, further comprising a positive charge selective transporting layer, a negative charge selective transporting layer, or both.
20. An organic semiconductor device comprising:(a) a substrate layer;(b) a positive charge selective transporting layer disposed on a surface of the substrate;(c) a donor material layer disposed on the positive charge selective transporting layer, said donor material layer comprising one or more first organic semiconductor materials;(d) an acceptor material layer disposed on the donor material layer, said acceptor material layer comprising one or more second organic semiconductor materials;(e) a negative charge selective transporting layer disposed on the acceptor material layer; or(a) a substrate layer;(b) a negative charge selective transporting layer disposed on a surface of the substrate;(c) an acceptor material layer disposed on the negative charge selective transporting layer, said acceptor material layer comprising one or more first organic semiconductor materials;(d) a donor material layer disposed on the acceptor material layer, said donor material layer comprising one or more second organic semiconductor materials;1006145770(e) a positive charge selective transporting layer disposed on the donor material layer; wherein at least one of the first organic semiconductor materials and the second semiconductor materials together form an organic semiconductor composition according to any one of claims 1 to 14.21 . An organic semiconductor device according to any one of claims 18 to 20, wherein the first layer and the second layer, and / or the donor material layer and the acceptor material layer are disposed as an intermixed nanoparticle layer.
22. A method of fabricating an organic semiconductor device comprising the steps of:(a) depositing at least one first organic semiconductor material layer onto a surface of a substrate;(b) depositing at least one second organic semiconductor material layer onto the first layer; wherein at least one of the first organic semiconductor material and the second semiconductor material together form an organic semiconductor composition according to any one of claims 1 to 14.
23. A method of fabricating an organic semiconductor device comprising the steps of:(a) depositing a positive charge selective transport layer onto a surface of a substrate;(b) depositing a donor material layer onto the positive charge selective transport layer, said donor material layer comprising one or more first organic semiconductor materials;(c) depositing an acceptor material layer onto the donor material layer, said acceptor material layer comprising one or more second organic semiconductor materials;(d) depositing a negative charge selective transport layer onto the acceptor material layer; or1006145770(a) depositing a negative charge selective transport layer onto a surface of a substrate;(b) depositing an acceptor material layer onto the negative charge selective transport layer, said acceptor material layer comprising one or more first organic semiconductor materials;(c) depositing a donor material layer onto the acceptor material layer, said donor material layer comprising one or more second organic semiconductor materials;(d) depositing a positive charge selective transport layer onto the donor material layer; wherein at least one of the first organic semiconductor material and the second semiconductor material together form an organic semiconductor composition according to any one of claims 1 to 14.
24. The method according to any one of claims 22 or 23, wherein the steps of depositing the first organic semiconductor material layer and the second organic semiconductor material layer, and / or the steps of depositing the donor material layer and the acceptor material layer are performed together, such that the materials are deposited as an intermixed nanoparticle layer.
25. An organic semiconductor device according to any one of claims 18 to 21 , for use in a retinal prosthetic device.
26. A method of treating eye disease or disorder comprising implanting in the eye of a human subject an organic semiconductor device according to any one of claims 18 to 21.
27. The method according to claim 26, wherein when the device further comprises nerve growth factor (NGF), the device provides an improvement in neuron attachment and neuron growth.1006145770