Device for implantation into the human or animal eye

Abstract

A device for implantation into the human or animal eye is disclosed, the device comprising a substrate and a plurality of photocapacitors disposed on the substrate. The plurality of photocapacitors comprise at least first, second and third types of photocapacitor configured to develop an electric field for stimulating one or more retinal cells upon absorbing electromagnetic radiation within a respective range of wavelengths. By providing different types of photocapacitor in this way, the device can enable a subject to perceive different wavelengths (e.g. different colours) of light. Specifically, each photocapacitor of the first type is configured to exhibit stronger absorption within a first range of wavelengths compared to photocapacitors of the second and third types, each photocapacitor of the second type is configured to exhibit stronger absorption within a second range of wavelengths compared to photocapacitors of the first and third types, and each photocapacitor of the third type is configured to exhibit stronger absorption within a third range of wavelengths compared to photocapacitors of the first and second types.

Description

[0001] Device for Implantation into the Human or Animal Eye

[0002] Technical Field

[0003] The present invention relates to devices for implantation into the human or animal eye, and to methods of treating retinal disease in a human or animal subject using such devices.

[0004] Background

[0005] The incidence of blindness worldwide is forecast to double by 2050, with visual impairment set to triple. Blindness due to the deterioration of photoreceptor cells from genetic defect as with Retinitis Pigmentosa (RP), or from advancing age such as age-related macular degeneration (AMD), results in the loss of vision from failed cells which are responsible for absorbing light and initiating the visual pathway.

[0006] In recent years, there has been interest in developing so-called "artificial retina" devices which could be implanted into the eye and take over the function of the failed cells, in other words, by absorbing light and initiating the visual pathway. However, thus far such devices have only been able to provide monochrome vision. It would therefore be desirable to provide an improved artificial retina device, in comparison to existing solutions.

[0007] The invention is made in this context.

[0008] Summary of the Invention

[0009] According to a first aspect of the present invention, there is provided a device for implantation into the human or animal eye, the device comprising: a substrate; and a plurality of photocapacitors disposed on the substrate, the plurality of photocapacitors comprising at least first, second and third types of photocapacitor configured to develop an electric field for stimulating one or more retinal cells upon absorbing electromagnetic radiation within a respective range of wavelengths, wherein each photocapacitor of the first type is configured to exhibit stronger absorption within a first range of wavelengths compared to photocapacitors of the second and third types, wherein each photocapacitor of the second type is configured to exhibit stronger absorption within a second range of wavelengths compared to photocapacitors of the first and third types, and wherein each photocapacitor of the third type is configured to exhibit stronger absorption within a third range of wavelengths compared to photocapacitors of the first and second types. In some embodiments according to the first aspect, the first range of wavelengths encompasses at least wavelengths between 410-430 nanometres.

[0010] In some embodiments according to the first aspect, the second range of wavelengths encompasses at least wavelengths between 524-544 nanometres.

[0011] In some embodiments according to the first aspect, the third range of wavelengths encompasses at least wavelengths between 554-574 nanometres.

[0012] In some embodiments according to the first aspect, each photocapacitor of the first type, and / or each photocapacitor of the second type, and / or each photocapacitor of the third type, comprises a bulk heterojunction, BHJ, formed of a donor material and an acceptor material.

[0013] In some embodiments according to the first aspect, the acceptor material comprises a fullerene.

[0014] In some embodiments according to the first aspect, the fullerene is PC70BM.

[0015] In some embodiments according to the first aspect, the donor material comprises a polymer.

[0016] In some embodiments according to the first aspect, in each photocapacitor of the first type said polymer is poly[bis(4-phenyl)(2,4,6-trimethylphenyl)amine], PTAA or indenofluorene-phenanthrene copolymer, PIFPA.

[0017] In some embodiments according to the first aspect, in each photocapacitor of the second type said polymer is poly[2-methoxy-5-(2-ethylhexyloxy)-l,4- phenylenevinylene], MEH-PPV or poly(3,6-dialkylthieno(3,2-b)thiophene-co- thieno[3,2-b]thiophene), P-DATT.

[0018] In some embodiments according to the first aspect, in each photocapacitor of the third type said polymer is poly(N-9'-heptadecanyl-2,7-carbazole-alt-5,5-(4',7'-di-2- thienyl-2',l',3'-benzothiadiazole)), PCDTBT or poly[(2,6-(4,8-bis(5-(2-ethylhexyl-3- fluoro)thiophen-2-yl)-benzo(l,2-b:4,5-b')dithiophene))-alt-(5,5-(l',3'-di-2-thienyl- 5',7'-bis(2-ethylhexyl)benzo(l',2'-c:4',5'-c')dithiophene-4,8-dione)], PM6. In some embodiments according to the first aspect, the plurality of photocapacitors comprises a fourth type of photocapacitor configured to exhibit stronger absorption within a fourth range of wavelengths compared to photocapacitors of the first, second and third types.

[0019] In some embodiments according to the first aspect, a full-width half-maximum, FWHM, width of an absorption peak of the fourth type of photocapacitor is wider than a FWHM width of respective absorption peaks of the first, second and third types of photocapacitor.

[0020] In some embodiments according to the first aspect, each photocapacitor has a lateral dimension in a plane of the substrate of not more than 50 micrometres.

[0021] In some embodiments according to the first aspect, said lateral dimension is between 5 and 50 micrometres.

[0022] In some embodiments according to the first aspect, the photocapacitors of the first, second and third types are arranged in a central zone of the substrate.

[0023] In some embodiments according to the first aspect, the photocapacitors of the fourth type are arranged in a peripheral zone of the substrate surrounding the central zone.

[0024] In some embodiments according to the first aspect, the substrate and the central zone are substantially circular in shape.

[0025] In some embodiments according to the first aspect, a diameter of the central zone is between 3-5 millimetres.

[0026] In some embodiments according to the first aspect, the substrate has a diameter of at least 10 millimetres.

[0027] In some embodiments according to the first aspect, the substrate is flexible such that the device can be folded or rolled, so as to reduce a maximum external physical dimension of the device prior to implantation.

[0028] In some embodiments according to the first aspect, the substrate comprises an electrically-conducting layer. In some embodiments according to the first aspect, the substrate comprises a holeblocking layer.

[0029] In some embodiments according to the first aspect, the hole-blocking layer is disposed on the electrically-conducting layer and the plurality of photocapacitors are disposed on the hole-blocking layer, such that the plurality of photocapacitors are separated from the electrically-conducting layer by the hole-blocking layer.

[0030] In some embodiments according to the first aspect, the hole-blocking layer comprises zinc oxide, ZnO.

[0031] According to a second aspect of the present invention, there is provided a method of treating retinal disease in a human or animal subject, the method comprising: implanting a device according to the first aspect beneath a surface of the retina in an eye of said human or animal subject, such that the device is disposed between a layer of bipolar cells and a layer of photoreceptor cells.

[0032] In some embodiments according to the second aspect, the retinal disease being treated is age-related macular degeneration, AMD, or retinitis pigmentosa, RP.

[0033] Brief Description of the Drawings

[0034] Embodiments of the present invention will now be described, by way of example only, with reference to the accompanying drawings, in which:

[0035] Figure 1 illustrates a perspective view of a device for implantation into the human or animal eye, according to an embodiment of the present invention;

[0036] Figure 2 illustrates a cross-sectional view of the retina of a subject after implantation of the device of Fig. 1, according to an embodiment of the present invention;

[0037] Figure 3 illustrates a cross-section through a device according to an embodiment of the present invention;

[0038] Figure 4 is a graph showing spectral width profiles of five LEDs used in transient experiments on materials for use in devices according to embodiments of the present invention;

[0039] Figure 5 is a graph showing absorption profiles of thin films of acceptor molecules in optical density mode, according to an embodiment of the present invention;

[0040] Figure 6 is a graph showing energy levels for acceptor molecules in the order of lower LUMO levels, and polymers ordered in terms of spectral characterisation due to band gap, together with three active electrode potentials, according to an embodiment of the present invention; Figure 7 is a graph showing thin film optical density for pristine PTAA, PTAA with ITIC, and PTAA with PC70BM, with the photoreceptor target range colour denoted as a vertical line, according to an embodiment of the present invention;

[0041] Figure 8 is a graph showing thin film optical density for pristine PIFPA, PIFPA with ITIC, and PIFPA with PC70BM, with the photoreceptor target range colour denoted as a vertical line, according to an embodiment of the present invention;

[0042] Figure 9 is a graph showing thin film optical density for pristine F8T2, F8T2 with ITIC, and F8T2 with PC70BM, with the photoreceptor target range denoted as a vertical line, according to an embodiment of the present invention;

[0043] Figure 10 is a graph showing thin film optical density for pristine MEH-PPV, MEH-PPV with ITIC, and MEH-PPV with PC70BM, with the photoreceptor target range colour denoted as a vertical line, according to an embodiment of the present invention;

[0044] Figure 11 is a graph showing thin film optical density for pristine PCDTBT, PCDTBT with ITIC, and PCDTBT with PC70BM, with the photoreceptor target range colour denoted as a vertical line, according to an embodiment of the present invention;

[0045] Figure 12 is a graph showing thin film optical density for pristine PM6, PM6 with ITIC, and PM6 with PC70BM, with the photoreceptor target range colour denoted as a vertical line, according to an embodiment of the present invention;

[0046] Figure 13 is a graph showing transient photocurrent and photovoltage for high intensity incident light for a photocapacitor comprising PTAA and PC70BM in a ratio of 1 : 1, according to an embodiment of the present invention;

[0047] Figure 14 is a graph showing transient photocurrent and photovoltage for high intensity incident light for a photocapacitor comprising PIFPA and PC70BM in a ratio of 1 : 1, according to an embodiment of the present invention;

[0048] Figure 15 is a graph showing transient photocurrent and photovoltage for high intensity incident light for a photocapacitor comprising F8T2 and PC70BM in a ratio of 1 : 1, according to an embodiment of the present invention;

[0049] Figure 16 is a graph showing transient photocurrent and photovoltage for high intensity incident light for a photocapacitor comprising MEH-PPV and PC70BM in a ratio of 1 :2, according to an embodiment of the present invention;

[0050] Figure 17 is a graph showing transient photocurrent and photovoltage for high intensity incident light for a photocapacitor comprising PCDTBT and PC70BM in a ratio of 1 :2, according to an embodiment of the present invention;

[0051] Figure 18 is a graph showing transient photocurrent and photovoltage for high intensity incident light for a photocapacitor comprising PM6 and PC70BM in a ratio of 1 :2, according to an embodiment of the present invention; Figure 19 is a graph showing photocurrent density versus incident power density for different BHJ polymer-acceptor combinations comprising PTAA, according to embodiments of the present invention;

[0052] Figure 20 is a graph showing photovoltage versus incident power density for different BHJ polymer-acceptor combinations comprising PTAA, according to embodiments of the present invention;

[0053] Figure 21 is a graph showing photocurrent density versus incident power density for different BHJ polymer-acceptor combinations comprising PIFPA, according to embodiments of the present invention;

[0054] Figure 22 is a graph showing photovoltage versus incident power density for different BHJ polymer-acceptor combinations comprising PIFPA, according to embodiments of the present invention;

[0055] Figure 23 is a graph showing photocurrent density versus incident power density for different BHJ polymer-acceptor combinations comprising F8T2, according to embodiments of the present invention;

[0056] Figure 24 is a graph showing photovoltage versus incident power density for different BHJ polymer-acceptor combinations comprising F8T2, according to embodiments of the present invention;

[0057] Figure 25 is a graph showing photocurrent density versus incident power density for different BHJ polymer-acceptor combinations comprising MEH-PPV, according to embodiments of the present invention;

[0058] Figure 26 is a graph showing photovoltage versus incident power density for different BHJ polymer-acceptor combinations comprising MEH-PPV, according to embodiments of the present invention;

[0059] Figure 27 is a graph showing photocurrent density versus incident power density for different BHJ polymer-acceptor combinations comprising PCDTBT, according to embodiments of the present invention;

[0060] Figure 28 is a graph showing photovoltage versus incident power density for different BHJ polymer-acceptor combinations comprising PCDTBT, according to an embodiment of the present invention;

[0061] Figure 29 is a graph showing photocurrent density versus incident power density for different BHJ polymer-acceptor combinations comprising PM6, according to embodiments of the present invention;

[0062] Figure 30 is a graph showing photovoltage versus incident power density for different BHJ polymer-acceptor combinations comprising PM6, according to embodiments of the present invention; and

[0063] Figures 31a to 31n illustrate the chemical structures of the polymers and acceptor molecules listed in Table 1. Detailed Description

[0064] In the following detailed description, only certain exemplary embodiments of the present invention have been shown and described, simply by way of illustration. As those skilled in the art would realise, the described embodiments may be modified in various different ways, all without departing from the scope of the present invention. Accordingly, the drawings and description are to be regarded as illustrative in nature and not restrictive. Like reference numerals designate like elements throughout the specification.

[0065] Referring now to Fig. 1, a device for implantation into the human or animal eye is illustrated in a perspective view, according to an embodiment of the present invention. The device 100 comprises a substrate 110 and a plurality of photocapacitors disposed on the substrate. The plurality of photocapacitors comprises at least first, second and third types of photocapacitor configured to develop an electric field upon absorbing electromagnetic radiation within a respective range of wavelengths.

[0066] Figure 2 illustrates a cross-sectional view of the retina of a subject after implantation of the device of Fig. 1. The retina comprises photoreceptors 210 (cone cells and rod cells), bipolar cells 220 and retinal ganglion cells 230. The visual pathway involves activation of the photoreceptor cells 210 by incident light on the retina, which in turn stimulate the adjacent bipolar cells 220. The signals generated by the bipolar cells 220 are carried to the optic nerve via the retinal ganglion cells 230. In the present embodiment the photocapacitors in the device 100 are configured to stimulate bipolar cells 220. In other embodiments the photocapacitors in the device may be configured to directly stimulate the retinal ganglion cells 230, in effect bypassing both the photoreceptors 210 and the bipolar cells 220 in the visual pathway. However, a benefit of stimulating the bipolar cells 220 as opposed to directly stimulating the retinal ganglion cells 230 is that it is currently unknown whether retinal ganglion cells 230 can interpret colour directly. Hence, more reliable colour perception may be achieved by using photocapacitors to stimulate the bipolar cells 230.

[0067] A layer structure of the device 100 is illustrated schematically in Fig. 3. In the present embodiment the substrate 110 comprises a support layer 310, an electrically- conducting layer 320 disposed on the support layer 310, and a hole-blocking layer 330 disposed on the electrically-conducting layer 320. In the present embodiment the electrically-conducting layer 320 comprises Indium Tin Oxide (ITO) and the holeblocking layer 330 comprises a metal oxide, for example zinc oxide (ZnO) or titanium dioxide (TiC ). However, in other embodiments other materials may be used for the electrically-conducting layer 320 and / or the hole-blocking layer 330. Furthermore, in some embodiments one or both of the electrically-conducting layer 320 and the holeblocking layer 330 may be omitted as appropriate, e.g. depending on the particular combinations of materials used in any given device 100. The support layer 310 may comprise biocompatible material (e.g. a biopolymer material, such as an organic semiconductor), to add in effectively implanting the device 100. The substrate 110 may be flexible, such that the device 100 can be folded or rolled so as to reduce a maximum external physical dimension of the device prior to implantation. Being able to fold or roll the device 100 in this way can enable easier implantation of the device 100, for example by reducing the length of incision needed to be able to insert the device 100 into the eye.

[0068] Continuing with reference to Fig. 3, in the present embodiment the hole-blocking layer 330 is disposed on the electrically-conducting layer 320, and an active layer 340 comprising the plurality of photocapacitors 341-344 is disposed on the hole-blocking layer 330. In this way, the plurality of photocapacitors 341-344 are separated from the electrically-conducting layer 320 by the hole-blocking layer 330. The inclusion of the hole-blocking layer 330 lowers the work function and allows for improved electron collection, and can be used to tune the charge transfer mechanism to ensure a capacitive process. The hole-blocking layer 330 can be formed of a material having a relatively deep conduction band that effectively blocks the transmission of holes and enhances the transfer of negative charge to the working electrode (i.e. the electrically- conducting layer 320). A layer of positive charge then builds at the interface between the active layer 340 and the electrolyte present in the eye, forming a Helmholtz double capacitive layer that prevents further charge injection into the electrolytic environment.

[0069] The electric field that is developed by each photocapacitor upon absorbing electromagnetic radiation is capable of stimulating one or more retinal cells in proximity to that photocapacitor, i.e. after the device 100 has been implanted and is operating in-situ in the eye. For example, bipolar cells 220 have a resting voltage of between -60 mV and -40 mV, and respond to an extracellular electric field caused by a change in potential. In the embodiment illustrated in Figs. 1 and 2, sub-retinal implantation is used, meaning that the device 100 is implanted between layers of the retina. Specifically, as shown in Fig. 2, the device 100 is implanted between the photoreceptors 210 and the bipolar cells 220. In the present embodiment, the device 100 is implanted with the photocapacitors on the side of the substrate 110 facing the bipolar cells 220. This arrangement ensures that the photocapacitors are placed as close as possible to the bipolar cells 220, and consequently the bipolar cells 220 will be exposed to a higher electric field when the photocapacitors absorb electromagnetic radiation. In other embodiments the device may be configured to be implanted in the reverse orientation to that shown in Fig. 2, such that the photocapacitors are on the side facing the photoreceptors 210. For example, such an orientation may be feasible in embodiments where the electric field generated by the photocapacitors is capable of penetrating the substrate 110 to stimulate the bipolar cells 220 on the other side of the substrate 110.

[0070] In the present embodiment, the plurality of photocapacitors comprise first, second, third and fourth types of photocapacitors, which are respectively configured to emulate the behaviour of short wavelength (S) cone cells, medium wavelength (M) cone cells, long wavelength (L) cone cells, and rod cells in the human or animal eye. In more detail, each photocapacitor of the first type 341 is configured to exhibit stronger absorption within a first range of wavelengths compared to photocapacitors of the second and third types 342, 343. Each photocapacitor of the second type 342 is configured to exhibit stronger absorption within a second range of wavelengths compared to photocapacitors of the first and third types 341, 343. Each photocapacitor of the third type 343 is configured to exhibit stronger absorption within a third range of wavelengths compared to photocapacitors of the first and second types 341, 342.

[0071] For example, since the average human S cone cell has a peak response at a wavelength of around 420 nm, in some embodiments the first range of wavelengths may encompass at least wavelengths between 410-430 nanometres. Similarly, since the average human M cone cell has a peak response at a wavelength of around 534 nm, in some embodiments the second range of wavelengths may encompass at least wavelengths between 524-544 nanometres. Additionally, since the average human L cone cell has a peak response at a wavelength of around 564 nm, in some embodiments the second range of wavelengths may encompass at least wavelengths between 554-574 nanometres. In this way, the photocapacitors of the first type 341 can be most sensitive to incident light at a similar range of wavelengths to S cone cells, the photocapacitors of the second type 342 can be most sensitive to incident light at a similar range of wavelengths to M cone cells, and the photocapacitors of the third type 343 can be most sensitive to incident light at a similar range of wavelengths to L cone cells. However, in some embodiments the first, second and / or third ranges of wavelengths may differ from the numerical ranges given above. For example, in some embodiments one of the first, second or third ranges may be selected to be significantly different to a range of wavelengths at which cone cells are normally responsive, potentially to enhance the subject's vision at specific wavelengths (e.g. near-infrared wavelengths).

[0072] In embodiments in which photocapacitors of the fourth type 344 are provided in addition to the first, second and third types of photocapacitor 341, 342, 343, the photocapacitors of the fourth type 344 may be configured to exhibit stronger absorption within a fourth range of wavelengths compared to photocapacitors of the first, second and third types 341, 342, 343. In this way, the photocapacitors of the fourth type 344 can more accurately emulate the behaviour of the rod cells that they are intended to replace in the visual pathway, which have a broader range of response compared to cone cells. For example, in terms of the full-width half-maximum (FWHM) value, the FWHM of an absorption peak of the fourth type of photocapacitor 344 may be wider than a FWHM of respective absorption peaks of the first, second and third types of photocapacitor 341, 342, 343.

[0073] Furthermore, in some embodiments the photocapacitors of the first, second, third and / or fourth types 341, 342, 343, 344 may make up different proportions of a total number of photocapacitors in the device 100, for example different proportions of the total number of photocapacitors in the central zone 111 and different proportions of the total number of photocapacitors in the peripheral zone 112. Taking the example of a human eye, the typical relative proportions of S, M and L cone cells across the retina are around 64% L cone cells, 32% M cone cells and 2% S cone cells. Accordingly, to more accurately replicate the behaviour of the biological retina, in some embodiments of the artificial retina device 100 the photocapacitors of the first type 341 may comprise around 50-70% of the total number of photocapacitors in the central zone 111 (or across the entire substrate 110), and / or the photocapacitors of the second type 342 may comprise around 20-40% of the total number of photocapacitors in the central zone 111 (or across the entire substrate 110), and / or the photocapacitors of the third type 343 may comprise around 1-10% of the total number of photocapacitors in the central zone 111 (or across the entire substrate 110).

[0074] By configuring the first, second and third types of photocapacitors 341, 342, 343 to mimic the response of S, M and L cone cells to incident light, the device 100 can enable colour vision, since different combinations of bipolar cells 220 will be stimulated when different photocapacitors are activated (i.e. absorb light). In the present embodiment the fourth type of photocapacitor aims to replace the lost functionality of rod cells in damaged areas of the retina, improving the subject's vision at low light levels. However, in other embodiments the fourth type of photocapacitor may be omitted, whilst still enabling the subject to distinguish between different wavelengths of light (i.e. different colours) due to the provision of the first, second and third types of photocapacitors.

[0075] The plurality of photocapacitors 341-344 comprise the first type of photocapacitor 341, the second type of photocapacitor 342, the third type of photocapacitor 343, and the fourth type of photocapacitor 344. When considered as a whole, the plurality of photocapacitors 341-344 may be arranged in the form of pixels in a regular pattern, which can be referred to as a pixel array. However, in some embodiments the distribution of each type of photocapacitor 341-344 across the surface of the substrate 110 may not be uniform, but instead may vary. The size of each pixel (i.e. each photocapacitor 341, 342, 343, 344) may vary depending on the implementation, for instance depending on the particular fabrication technology used to manufacture a particular device. In some embodiments, each photocapacitor may have a lateral dimension in a plane of the substrate of not more than 50 micrometres (pm), for example between 5 pm and 50 pm. As the size of each photocapacitor is reduced, the number of bipolar cells that will be stimulated by each photocapacitor will reduce commensurately, resulting in improved visual acuity (i.e. the subject's ability to distinguish finer-scale features).

[0076] For example, in the embodiment illustrated in Fig. 1, the photocapacitors of the first, second and third types 341, 342, 343 are arranged in a central zone 111 of the substrate 110. Since the first, second and third types of photocapacitor 341, 342, 343 are configured to emulate the response of the S, M and L cone cells respectively, which are concentrated in the central region (macula) of the retina, providing the highest concentration of the first, second and third types of photocapacitor 341, 342, 343 within the central region 111 ensures that the artificial retina device 100 can more accurately replicate the structure and function of the biological retina. For the same reason, the fourth type of photocapacitor 344, which is configured to emulate the response of the rod cells, may be arranged in a peripheral zone 112 of the substrate 110 that surrounds the central zone 111, replicating the spatial distribution of rod cells in the biological retina. The substrate 110 and / or the central zone 111 may both be substantially circular in shape, to more accurately replicate the shape of the biological retina. However, in some embodiments the substrate 110 and / or central zone 111 may have a noncircular shape, for example a polygonal shape or irregular shape. For devices configured for implantation into the adult human eye, a diameter of the central zone 111 may typically be between about 3 mm and about 5 mm. The overall diameter of the substrate 110 may be about 10 mm or greater. It should however be understood that these dimensions are merely provided by way of example, and in other embodiments different dimensions may be used as appropriate (e.g. depending on the physical dimensions of the retina / eye of the subject into which the device 100 is to be implanted).

[0077] Depending on the embodiment, all of the photocapacitors of the first, second and third types 341, 342, 343 may be confined to the central zone 111, or the photocapacitors of the first, second and third types 341, 342, 343 may be distributed across the substrate 110 so as to have a higher concentration of the first, second and third types 341, 342, 343 in the central zone 111 and a lower concentration in the peripheral zone 112. Similarly, depending on the embodiment, all of the photocapacitors of the fourth type 344 may be confined to the peripheral zone 112, or the photocapacitors of the fourth type 344 may be distributed across the substrate 110 so as to have a lower concentration in the central zone 111 and a higher concentration in the peripheral zone 112.

[0078] Referring now to Figs. 4 to 30, experimental data is presented for a number of different photocapacitor materials and layer combinations that may be used in devices according to embodiments of the present invention. The photocapacitor materials tested include narrowband polymers that may be particularly suited to emulating human photoreceptors, which exhibit a narrow absorption band in specific regions of the visible spectrum. Details of seven such polymers are given in Table 1, together with acceptor molecules that may be used in combination with any of the seven polymers (or indeed, with any other suitable donor material). Acceptor molecules are also photoactive, with their own absorption and photoresponse spectra. The selected acceptors here are readily available and comprise both fullerene and non-fullerene compounds. The combination of a donor material (e.g. the seven polymers listed in Table 1) and an acceptor material forms a bulk heterojunction (BHJ).

[0079] TABLE 1

[0080] In Table 1, the short name of each polymer denotes the type of photocapacitor in for which that polymer may be particular suitable. For example, the "BC" in P-BC1 and P- BC2 stands for "Blue Cone", indicating that the polymers are candidate materials for use in the first type of photocapacitor 341. Similar, P-RD denotes a candidate polymer for the fourth type of photocapacitor 344, which is configured to emulate the behaviour of a rod cell. P-GC1 and P-GC2 stands for "Green Cone" to denote candidate polymers for the second type of photocapacitor 342, whilst P-RC1 and P- RC2 stands for "Red Cone" denote candidate polymers for the third type of photocapacitor 343. An "A" in the short name denotes an acceptor material (e.g. A- ITIC).

[0081] Figures 31a to 31n illustrate the chemical structures of the polymers and acceptor molecules listed in Table 1. Specifically, Fig. 31a shows the structure of PTAA, Fig. 31b shows the structure of PIFPA, Fig. 31c shows the structure of F8T2, Fig. 31d shows the structure of MEH-PPV, Fig. 31e shows the structure of P-DATT, Fig. 31f shows the structure of PM6, Fig. 31g shows the structure of PCDTBT, Fig. 31h shows the structure of ITIC, Fig. 31i shows the structure of Y6, Fig. 31j shows the structure of PC70BM, Fig. 31k shows the structure of PC60BM, Fig. 311 shows the structure of C70, Fig. 31m shows the structure of C60, and Fig. 31n shows the structure of ICBA.

[0082] Although each of the donor materials tested here comprises a polymeric material, in other embodiments the first, second, third and / or fourth type of photocapacitors 341,

[0083] 342, 343, 344 may comprise a material other than a polymer. For example, in some embodiments the first, second, third and / or fourth type of photocapacitors 341, 342,

[0084] 343, 344 may comprise a conjugated small molecule material instead of a polymer, either alone or in combination with an acceptor material (e.g. any of the acceptor materials listed in Table 1, or any other suitable material). In general, any acceptor material may be used that has a lower LUMO level (i.e. higher electron affinity) compared to the paired donor material, including fullerenes and non-fullerenes. Examples of other fullerenes that may be used as electron acceptors in a photocapacitor in embodiments of the present invention include, but are not limited to: Ceo (LUMO 4.5 eV, HOMO 6.2 eV); C70 (LUMO 4.6 eV, HOMO 6.2 eV); ICBA (LUMO 3.67 eV); and PCeoBM (LUMO 3.7 eV, HOMO 6.1 eV). In the case of Ceo and C70, in some embodiments the solubility of Ceo or C70 may be improved by modifying the cage with groups that enhance solubility and retard crystallisation when mixed with a conjugated polymer. For example, improving the solubility of Ceo or C70 in this way can make it easier to form photocapacitors comprising such materials via deposition techniques such as printing.

[0085] It should also be appreciated that the "donor" and "acceptor" terminology used herein applies to photocapacitors that comprise a bulk heterojunction (BHJ), but embodiments of the present invention are not limited to BHJ photocapacitors. For example, in some embodiments the first, second, third and / or fourth type of photocapacitors 341, 342, 343, 344 may comprise a single material (e.g. any of the polymers listed in Table 1, in the pristine state) without being combined with an acceptor material to form a BHJ.

[0086] Hence, as indicated by the nomenclature of the "short names" in Table 1, in some embodiments the first type of photocapacitor 341 may comprise PTAA or PIFPA, the second type of photocapacitor 342 may comprise MEH-PPV or P-DATT, the third type of photocapacitor 343 may comprise PCDTBT or PM6, and / or the fourth type of photocapacitor 344 may comprise F8T2. As will become clear from the results discussed below, in some embodiments such polymers may be used on their own in a photocapacitor, or may be used in combination with another material (e.g. any of the acceptor materials listed in Table 1, or any other suitable alternative). It was not possible to obtain results for P-GC2 due to problems with crystallisation when attempting to fabricate samples. However, it is believed that this was a limitation of the equipment used, and based on its properties P-GC2 (P-DATT) is still expected to be suitable for use in the second type of photocapacitor in embodiments of the present invention.

[0087] Absorption measurements were carried out using a Cary 5000 UV-Vis-NIR spectrophotometer in ambient conditions in optical density mode. Thin films were fabricated on ITO covered glass, and the same ITO covered glass was used as a reference. Organic semiconducting films were tested with thickness in the range of 50-200 nm to ensure efficient absorption of light. This technique makes use of the Bouguer-Beer-Lambert Law which relates the attenuation of light to the material through which the light is travelling over a series of wavelengths where A is the wavelength, a is the absorption coefficient and / is the path length:

[0088] 7(A) = 70(A)e-“Wt

[0089] Measurements of light intensity, path length and material's absorption coefficient are used in the relationship:

[0090] « = logioy = - logic T where Io is the incident light intensity, I is the intensity through the sample, and T is the transmission through the sample. The optical bandgap Eccan be inferred from the spectral absorption trailing edge, as that would indicate the point where there is no longer any absorption or excitation, and is given by:

[0091] Where h is Planck's constant and c is the speed of light.

[0092] Photocurrent spectra of samples immersed in PBS were measured over the range from 350 to 800 nm by using a 100 W Bentham quartz-halogen lamp connected to a

[0093] Bentham triple-grating monochromator TMC-300 equipped with an optical chopper (75 Hz typical), and recorded using a Signal Recovery 7265 lock-in amplifier. The spectrometer output line width was approximately 3 nm (full width half maximum, FWHM). The typical output optical power level of this system varies across different wavelengths from 6.1 to 41.8 |jW mm'2, and is about 21.7 |jW mm'2at 500 nm. The spectral photocurrent measurements were conducted by immersing the samples in a cuvette, where the area of the incident beam was significantly smaller than the size of the sample. In this case, the dimensions of the focal spot were measured and recorded. These values are linearly interpolated and used in incident power density calculations, with the measured values given in Table 2:

[0094] TABLE 2

[0095] The dynamic nature of photocurrent and photovoltage can best be shown by inspection of the transient response, by identifying the time-dependent response characteristics in terms of the collection of either negative or positive charge at the working electrode (in the present case, an ITO / glass substrate. For transient data, samples were illuminated by LEDs about 2 cm away from the source of wavelengths 405 nm, 534 nm, and 634 nm through an aperture of 1 cm2to ensure a homogeneous irradiance. Photocurrent, in short circuit mode, from the ITO interface was fed through a Thorlabs AMP120 100 kV / A transampedance amplifier and collected by a Keysight DSOX2014A oscilloscope. Likewise, photovoltage was measured in opencircuit mode without amplification as observed with the oscilloscope. Most measurements were taken with a 100 ms period and 20 ms width, since these values mimic the response time of a human photoreceptor cell yet are long enough to interpret characteristic electrical responses. Typical peak incident light ranged from sub-pW mm-2to around 40 pW mnr2as measured with a Gentec XLP12 Thermopile Detector. The individual spectral profile shapes of five surface mounted LEDs were determined by measuring their respective emission spectra with an Oceaninsight spectrometer, as shown in Fig. 4.

[0096] Figure 5 is a graph showing absorption profiles of thin films of two of the acceptor molecules listed in Table 1, ITIC and PC70BM (sometimes referred to herein as PCBM70), in optical density mode. ITIC shows a characteristic peak at 704 nm, while PCBM70 has a broader profile with a peak at 383 nm. When acceptor molecules such as ITIC and PC70BM are used in combination with a donor material, such as the polymers listed in Table 1, the optical properties may be further tuned by adjusting the relative proportions of the donor and acceptor materials in the photocapacitor 341, 342, 343, 344.

[0097] Figure 6 is a graph showing energy levels for acceptor molecules in the order of lower LUMO levels, and polymers ordered in terms of spectral characterisation due to band gap, together with three active electrode potentials (PEIE / ZnO / ITO, ITO alone, and PEDOT / ITO). In Fig. 6, the energy levels for the materials listed in Table 1 are plotted based on the known HOMO and LUMO energies. For the active electrode materials (PEIE / ZnO / ITO, ITO alone, and PEDOT / ITO), surface potential measurements were carried out using a single-point KP20 Kelvin probe from KP Technology, on the assumption that substrate films were morphologically homogenous. Surface potential probing is an indirect technique using a vibrating tip as a counter electrode to form a parallel plate capacitor with the surface under study. Electrons flow towards the material with the higher work function in the external circuit as the tip vibrates. Work function difference is determined by adding an external voltage called the backing potential (Vb). The traditional method for determining the work function difference between two surfaces involved adjusting Vb until a zero or null output was obtained. However, this mode of detection is highly sensitive to noise. Instead, the "off-null" detection method was used, which takes advantage of the changing capacitance from which the output voltage becomes sinusoidal, meaning that its peaks may be measured as peak-to-peak voltages or VPtP. If VPtPis tested under a wide range of voltages, (e.g. -5 V to +5 V), its relationship with Vb is linear, and the backing voltage can be interpolated through the zero or balance point. This method reduces the effects of other surfaces that are in capacitive coupling with the tip-sample system.

[0098] A typical ITO sample had a surface potential of -4765 ± 0.24 mV (each of 100 points was an average of 30 over three separate readings), and a sample of ZnO / ITO earthed to the metal oxide (i.e. ZnO) layer had a surface potential of -4368 ± 1.68 mV (each of 100 points was an average of 30 over four separate readings). These results show that the addition of a ZnO interlayer lowers the work function and allows for improved electron collection.

[0099] In relation to the ITO / PEDOT and ITO / ZnO / PEIE samples tested, a typical PEDOT / ITO substrate had a work function of 4870 mV and another with PEIE / ZnO / ITO dropped to 4226 mV. This would imply that PEDOT may facilitate hole transfer, whilst PEIE in combination with ZnO and ITO might block holes but favour electron transfer. In practice the photoresponse was reduced by the addition of PEIE to the ZnO / ITO layer, although it is believed that this was due to a relatively large thickness of the resistive PEIE layer, in which case the reduction in photoresponse may be mitigated by using a thinner PEIE layer.

[0100] Referring now to Figs. 7 to 12, graphs are illustrated showing the thin film optical density for the polymers listed in Table 1 (P-BC1, P-BC2, P-RD, etc.) in pristine form, in combination with ITIC, and in combination with PCBM70, according to embodiments of the present invention. In each of Figs. 7 to 12, the photoreceptor target range for the respective type of photocapacitor is illustrated as a thick vertical line (e.g. blue wavelengths for P-BC1 and P-BC2, which are particularly suited for use in the first type of photocapacitor 341). As shown in Figs. 7 to 12, the addition of ITIC as an acceptor material generally results in an additional absorption peak towards the red end of the visible spectrum (e.g. around 600-700 nm). No such additional peak is observed when using PCBM70 as the acceptor material, indicating that PCBM70 can readily be incorporated in photocapacitors of the first, second, third and fourth types 341, 342, 343, 344 without any significant impact on the position of the absorption peak (i.e. relative to the pristine polymer).

[0101] For each polymer in Table 1, the transient photocurrent and photovoltage was measured for samples of the polymer in combination with: ITIC as the acceptor; PCBM70 as the acceptor, in a 1: 1 ratio with the donor polymer; PCBM70 as the acceptor, in a 1 :2 ratio with the donor polymer; and Y6 as the acceptor. Here, the ratio refers to the volume ratios of the precursor solutions of the respective materials, which were blended in the stated ratios before forming the respective photocapacitors via a printing technique. When preparing a blend of precursor solutions, for example a first precursor solution comprising PTAA and a second precursor solution comprising PCBM70, the same solvent ratio was used for each precursor solution (e.g. 50 mg of PTAA or PCBM70 to 2 ml of solvent). The first and second precursor solutions were then blended in the given volume ratio, for example 1: 1 or 1:2.

[0102] The combination which gave the highest photovoltage for each donor polymer is listed in Table 3.

[0103] TABLE 3

[0104] The corresponding results for each such combination of donor-acceptor materials are illustrated in Figs. 13 to 18, which show the transient photocurrent (left-hand axis) and photovoltage (right-hand axis) for high intensity incident light for BHJ photocapacitors comprising the donor-acceptor combinations listed in Table 3. Specifically, Fig. 13 illustrates the results for ITO / ZnO / PTAA:PC7oBM with a 1: 1 donor to acceptor ratio, Fig. 14 illustrates the results for ITO / ZnO / PIFPA:PC?oBM with a 1 : 1 donor to acceptor ratio, Fig. 15 illustrates the results for ITO / ZnO / F8T2:PC?oBM with a 1 : 1 donor to acceptor ratio, Fig. 16 illustrates the results for ITO / ZnO / MEH- PPV:PC?oBM, with a 1 :2 donor to acceptor ratio, Fig. 17 illustrates the results for ITO / ZnO / PCDTBT:PC?oBM with a 1 :2 donor to acceptor ratio, and Fig. 18 illustrates the results for ITO / ZnO / PM6:PC?oBM with a 1 :2 donor to acceptor ratio. In Figs. 13 and 14, the results were obtained with a light intensity of 39.3 pW mm-2, comprising light with a wavelength of 405 nm pulsed at 20 ms every 100 ms. In Figs. 15 and 16, the results were obtained with a light intensity of 30.1 pW mm-2, comprising light with a wavelength of 534 nm pulsed at 20 ms every 100 ms. In Figs. 17 and 18, the results were obtained with a light intensity of 14.9 pW mm-2, comprising light with a wavelength of 634 nm light pulsed at 20 ms every 100 ms.

[0105] Referring now to Figs. 19 to 30, graphs are plotted showing the photocurrent density and photovoltage versus incident power density for different BHJ donor-acceptor combinations. Figures 19 to 22 illustrate the photocurrent density and photovoltage for different samples comprising P-BC1 (PTAA) and P-BC2 (PIFPA), for which the results were obtained using incident light of intensity 39.3 ± 0.2 pW mm-2, comprising light with a wavelength of 405 nm at 20 ms pulses every 100 ms. Figures 23 to 26 illustrate the photocurrent density and photovoltage for different samples comprising P-RD (F8T2) and P-GC1 (MEH-PPV), for which the results were obtained using incident light of intensity 30.1 ± 0.2 pW mm-2, comprising light with a wavelength of 534 nm at 20 ms pulses every 100 ms. Figures 27 to 30 illustrate the photocurrent density and photovoltage for different samples comprising P-RC1 (PCDTBT) and P-RC2 (PM6), for which the results were obtained using incident light of intensity 14.9 ± 0.2 pW mm-2, comprising light with a wavelength of 634 nm at 20 ms pulses every 100 ms. The results presented above in Table 3 and Figs. 7 to 30 therefore demonstrate that photocapacitors comprising these respective combinations of materials exhibit a sufficient high peak photovoltage to be capable of stimulating retinal bipolar cells.

[0106] Embodiments of the invention have been described in which a device for implantation into the human or animal eye comprises a substrate and a plurality of photocapacitors disposed on the substrate, the plurality of photocapacitors comprising at least first, second and third types of photocapacitor. Such devices can be used in the treatment of retinal disease in a human or animal subject, by acting as an "artificial retina" that can stimulate retinal bipolar cells in place of damaged cone cells (e.g. in an area 211 of the retina in which photoreceptors 210 have been damaged due to retinal disease, and are no longer capable of stimulating their respective bipolar cells 220). Hence, a method of treating retinal disease in a human or animal subject can comprise implanting such a device beneath a surface of the retina in an eye of said human or animal subject, such that the device is disposed between a layer of bipolar cells and a layer of photoreceptor cells. For example, such a method may be used to treat retinal diseases including, but not limited to, age-related macular degeneration (AMD) and retinitis pigmentosa (RP).

[0107] Whilst certain embodiments of the invention have been described herein with reference to the drawings, it will be understood that many variations and modifications will be possible without departing from the scope of the invention as defined in the accompanying claims.

Claims

Claims1. A device for implantation into the human or animal eye, the device comprising: a substrate; and a plurality of photocapacitors disposed on the substrate, the plurality of photocapacitors comprising at least first, second and third types of photocapacitor configured to develop an electric field for stimulating one or more retinal cells upon absorbing electromagnetic radiation within a respective range of wavelengths, wherein each photocapacitor of the first type is configured to exhibit stronger absorption within a first range of wavelengths compared to photocapacitors of the second and third types, wherein each photocapacitor of the second type is configured to exhibit stronger absorption within a second range of wavelengths compared to photocapacitors of the first and third types, and wherein each photocapacitor of the third type is configured to exhibit stronger absorption within a third range of wavelengths compared to photocapacitors of the first and second types.

2. The device according to claim 1, wherein the first range of wavelengths encompasses at least wavelengths between 410-430 nanometres.

3. The device according to claim 1 or 2, wherein the second range of wavelengths encompasses at least wavelengths between 524-544 nanometres.

4. The device according to claim 1, 2 or 3, the third range of wavelengths encompasses at least wavelengths between 554-574 nanometres.

5. The device according to any one of the preceding claims, wherein each photocapacitor of the first type, and / or each photocapacitor of the second type, and / or each photocapacitor of the third type, comprises a bulk heterojunction, BHJ, formed of a donor material and an acceptor material.

6. The device according to claim 5, wherein the acceptor material comprises a fullerene.

7. The device according to claim 6, wherein the fullerene is PC70BM.

8. The device according to any one of claims 5 to 7, wherein the donor material comprises a polymer.

9. The device according to claim 8, wherein in each photocapacitor of the first type said polymer is poly[bis(4-phenyl)(2,4,6-trimethylphenyl)amine], PTAA or indenofluorene-phenanthrene copolymer, PIFPA.

10. The device according to claim 8 or 9, wherein in each photocapacitor of the second type said polymer is poly[2-methoxy-5-(2-ethylhexyloxy)-l,4- phenylenevinylene], MEH-PPV or poly(3,6-dialkylthieno(3,2-b)thiophene-co- thieno[3,2-b]thiophene), P-DATT.

11. The device according to claim 8, 9 or 10, wherein in each photocapacitor of the third type said polymer is poly(N-9'-heptadecanyl-2,7-carbazole-alt-5,5-(4',7'-di-2- thienyl-2',l',3'-benzothiadiazole)), PCDTBT or poly[(2,6-(4,8-bis(5-(2-ethylhexyl-3- fluoro)thiophen-2-yl)-benzo(l,2-b:4,5-b')dithiophene))-alt-(5,5-(l',3'-di-2-thienyl- 5',7'-bis(2-ethylhexyl)benzo(l',2'-c:4',5'-c')dithiophene-4,8-dione)], PM6.

12. The device according to any one of the preceding claims, wherein the plurality of photocapacitors comprises a fourth type of photocapacitor configured to exhibit stronger absorption within a fourth range of wavelengths compared to photocapacitors of the first, second and third types.

13. The device according to claim 12, wherein a full-width half-maximum, FWHM, width of an absorption peak of the fourth type of photocapacitor is wider than a FWHM width of respective absorption peaks of the first, second and third types of photocapacitor.

14. The device according to any one of the preceding claims, wherein each photocapacitor has a lateral dimension in a plane of the substrate of not more than 50 micrometres.

15. The device according to claim 14, wherein said lateral dimension is between 5 and 50 micrometres.

16. The device according to any one of the preceding claims, wherein the photocapacitors of the first, second and third types are arranged in a central zone of the substrate.

17. The device according to claim 16 when dependent on claim 12 or 13, wherein the photocapacitors of the fourth type are arranged in a peripheral zone of the substrate surrounding the central zone.

18. The device according to claim 16 or 17, wherein the substrate and the central zone are substantially circular in shape.

19. The device according to any one of claims 16 to 18, wherein a diameter of the central zone is between 3-5 millimetres.

20. The device according to any one of the preceding claims, wherein the substrate has a diameter of at least 10 millimetres.

21. The device according to any one of the preceding claims, wherein the substrate is flexible such that the device can be folded or rolled, so as to reduce a maximum external physical dimension of the device prior to implantation.

22. The device according to any one of the preceding claims, wherein the substrate comprises an electrically-conducting layer.

23. The device according to any one of the preceding claims, wherein the substrate comprises a hole-blocking layer.

24. The device according to claim 23 when dependent on claim 22, wherein the hole-blocking layer is disposed on the electrically-conducting layer and the plurality of photocapacitors are disposed on the hole-blocking layer, such that the plurality of photocapacitors are separated from the electrically-conducting layer by the holeblocking layer.

25. The device according to claim 23 or 24, wherein the hole-blocking layer comprises zinc oxide, ZnO.

26. A method of treating retinal disease in a human or animal subject, the method comprising: implanting a device according to any one of the preceding claims beneath a surface of the retina in an eye of said human or animal subject, such that the device is disposed between a layer of bipolar cells and a layer of photoreceptor cells.

27. The method of claim 26, wherein the retinal disease being treated is age- related macular degeneration, AMD, or retinitis pigmentosa, RP.

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