ARTIFICIAL EYE ASSEMBLY FOR STUDYING OCULAR PHARMACOKINETICS

Abstract

An artificial eye assembly (100) comprising: ⋅an anterior layer (50) comprising an anterior cavity (52); ⋅a flow con-stricting (40) layer comprising a first aperture (42), and wherein the first aperture (42) is in fluid communication with the anterior cavity (52); ⋅a shaping layer (30) comprising a second aperture and a shaping structure (32), wherein the shaping structure (32) is located within, partially within, or outside of the second aperture, and wherein the shaping structure comprises (32) one or more webs (33), the webs (33) connecting the structure (32) to the rest of the shaping layer (30), and wherein the second aperture is in fluid communication with the first aperture (42); ⋅a flow resistive layer (20) comprising pores, and wherein pores of the layer are in fluid communication with the second aperture; ⋅a posterior layer (10) comprising a posterior cavity (12), and wherein the posterior cavity (12) is in fluid communication with pores of the flow resistive layer (20); ⋅a fluid inlet (13) located in the anterior and/or posterior cavity (12, 52), or located in or adjacent to the second aperture; ⋅a fluid outlet (54) located in the anterior cavity; ⋅and an injection inlet (14) located in the posterior cavity and/or located in the anterior cavity, and wherein the anterior cavity (52) and the posterior cavity (12) are in fluid communication with one another via a fluid path formed through the layers (10, 20, 30, 40 50); and wherein, in use, a fluid introduced under pressure into the assembly via the fluid inlet (13) will flow along the fluid path and exit the assembly via the fluid outlet (54) with a first flow rate.

Claims

1. An artificial eye assembly comprising: an anterior layer comprising an anterior cavity; a flow constricting layer comprising a first aperture, wherein the first aperture is in fluid communication with the anterior cavity; a shaping layer comprising a second aperture and a shaping structure, wherein the shaping structure is located within, partially within, or outside of the second aperture, and wherein the shaping structure comprises one or more webs, the webs connecting the structure to the rest of the shaping layer, wherein the second aperture is in fluid communication with the first aperture; a flow resistive layer comprising pores, wherein pores of the layer are in fluid communication with the second aperture; a posterior layer comprising a posterior cavity, wherein the posterior cavity is in fluid communication with pores of the flow resistive layer; a fluid inlet located in the anterior and/or posterior cavity, or located in or adjacent to the second aperture; a fluid outlet located in the anterior cavity; and an injection inlet located in the posterior cavity and/or located in the anterior cavity, wherein the anterior cavity and the posterior cavity are in fluid communication with one another via a fluid path formed through the layers; and wherein, in use, a fluid introduced under pressure into the assembly via the fluid inlet will flow along the fluid path and exit the assembly via the fluid outlet with a first flow rate.

2. The artificial eye assembly of claim 1, wherein the shaping layer is absent and pores of the flow resistive layer are in fluid communication with the first aperture or the flow constricting layer is absent and the second aperture is in fluid communication with the anterior cavity.

3. The artificial eye assembly according to claim 1, wherein the posterior cavity comprises one or more cavity apertures, and the assembly further comprises: a second flow resistive layer comprising pores, wherein pores of the second flow resistive layer are in fluid communication with the one or more cavity apertures; an outlet layer comprising a posterior outlet, wherein the posterior outlet is in fluid communication with pores of the second flow resistive layer; and a flow balancing conduit in fluid communication with the posterior outlet, wherein the posterior cavity and the flow balancing conduit are in fluid communication with one another via a second fluid path, wherein, in use, the fluid introduced under pressure into the assembly via the fluid inlet will also flow along the second fluid path and exit the assembly via the posterior outlet with a second flow rate, and wherein a flow balancing fluid is configured to pass through the flow balancing conduit with a third flow rate, such that the sum of the second and third flow rates will be equal to the first flow rate.

4. The artificial eye assembly according to claim 1 wherein the anterior cavity comprises a third aperture and the assembly further comprises: an elastic layer sealing the third aperture; and a retaining layer configured to secure the elastic layer in place and which comprises a purse limiting means, wherein, in use, the fluid introduced under pressure into the assembly is configured to cause the elastic layer to purse, and wherein the purse limiting means limits the degree of pursing.

5. The artificial eye assembly according to claim 4, wherein the purse limiting means is a fourth aperture in the retaining layer, and wherein the elastic layer is sized to cover the fourth aperture.

6. The artificial eye assembly according to claim 1 wherein the assembly further comprises a temperature regulator configured to control or maintain the temperature within the assembly, or to induce a temperature difference within the assembly.

7. The artificial eye assembly according to claim 6, wherein the temperature regulating means comprises a volume for containing a thermally regulated fluid; and a heat or cooling means to adjust the temperature of the thermally regulated fluid, when present, wherein the volume is in thermal contact with, and/or encompasses, one or more of: the outlet layer; the posterior layer; and the shaping layer, wherein, in use, the thermally regulated fluid is introduced into the volume and is maintained at a constant temperature, thereby transferring heat to, or from, the thermally contacted layers.

8. The artificial eye assembly according to claim 6, wherein the volume encompasses and/or extends through the outlet layer and the posterior layer, and abuts the shaping layer.

9. The artificial eye assembly according to claim 1, wherein, when the fluid inlet is located in, or adjacent to, the second aperture and the shaping layer is in thermal contact with the volume, the fluid passing through the inlet is arranged to flow in a circuitous fluid path through the shaping layer.

10. The artificial eye assembly according to claim 6 wherein, in use, the temperature regulating means causes thermal convection currents in a volume of fluid situated between the second aperture and the anterior cavity.

11. The artificial eye assembly according to claim 1, wherein the assembly further comprises a pump configured to pump the fluid under pressure through the assembly via the first fluid path and also via the second fluid path, when the second fluid path is present.

12. The artificial eye assembly according to claim 1, wherein in use, a cavity volume between the flow resistive layer and the posterior cavity is filled with a fluid permeable packing material.

13. The artificial eye assembly according to claim 12, wherein the fluid permeable packing material is hyaluronic acid, collagen, agar, silicon oil, chitosan, alginates, or polysaccharides.

14. The artificial eye assembly according to claim 1, wherein one or more of the layers of the assembly are formed together as a single layer or 3D printed.

15. The artificial eye assembly according to claim 1, wherein the layers are modular units and may be combined to form the assembly.

16. The artificial eye assembly according to claim 1, wherein the anterior cavity, posterior cavity, first aperture, and shaping structure are substantially shaped and/or sized to replicate corresponding parts of the human eye.

17. The artificial eye assembly according to claim 3, wherein the posterior outlet is arranged orthogonally to the flow balancing conduit.

18. The artificial eye assembly according to claim 1, wherein the assembly further comprises a means to rock, twist, or agitate the assembly.

19. The artificial eye assembly according to claim 1, wherein the anterior cavity comprises a plurality of drainage holes in fluid communication with the fluid outlet.

20. The artificial eye assembly according to claim 1, wherein the flow constricting layer is capable of binding to a drug or active agent.

21. The artificial eye assembly according to claim 1, wherein the shaping layer is capable of binding to a drug or active agent.

22. The artificial eye assembly according to claim 1, wherein the second aperture comprises a plurality of inlet holes in fluid communication with the fluid inlet.

23. The artificial eye assembly according to claim 1, wherein the flow resistive layer comprises a membrane, the membrane comprising the pores.

24. The artificial eye assembly according to claim 23 wherein, in use, the membrane contacts the shaping structure and is shaped by the shaping structure.

25. The artificial eye assembly according to claim 3 wherein the second flow resistive layer comprises a second membrane, the second membrane comprising the pores.

26. The artificial eye assembly according to claim 3, wherein the flow rate permitted by the flow resistive layer is greater, equal, or less than the flow rate permitted by the second flow resistive layer under the same conditions.

27. The artificial eye assembly according to claim 4 wherein the elastic layer comprises, or consists of silicone.

28. A kit of parts comprising the artificial eye assembly of claim 1, wherein the layers are provided as separate layers which may be combined to form the assembly.

29. Use of an artificial eye assembly as defined in claim 1 to study ocular drug kinetics.

30. A method of studying ocular drug kinetics in an eye using an assembly as defined in claim 1 the method comprising: (i) pumping fluid into the fluid inlet of the assembly; (ii) establishing a steady state first flow rate out of the fluid outlet; (iii) when present, establishing a steady state second flow rate out of the posterior outlet and adjusting the third flow rate of the balancing fluid, such that the sum of the second and third flow rates will be equal to the first flow rate; (iv) injecting a drug into the assembly via the injection inlet; (v) measuring the rate at which the drug exits the assembly via the fluid outlet; (vi) when present, measuring the rate at which the drug exits the assembly via the posterior outlet; (vii) adding a thermally regulated fluid to the volume to control the temperature of the assembly or part of the assembly; and (viii) rocking, agitating or twisting the assembly to simulate eye saccades, head movement, waking and sleeping cycles.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0073] FIG. 1 shows an exploded perspective view of a first embodiment (100) of the invention.

[0074] FIG. 2 shows a perspective view of the assembled embodiment shown in FIG. 1.

[0075] FIG. 3 shows a cross-sectional view taken through the assembly shown in FIG. 2.

[0076] FIGS. 4a to 4c shows cross-sectional views of the posterior layer (10) shown in FIG. 1.

[0077] FIGS. 5a to 5c shows cross-sectional views of the shaping layer (30) shown in FIG. 1.

[0078] FIGS. 6a and 6b shows cross-sectional views of the anterior layer (50) shown in FIG. 1.

[0079] FIG. 7 shows an exploded perspective view of a second embodiment (200) of the invention.

[0080] FIGS. 8a to 8c shows cross-sectional views of the posterior layer (210) shown in FIG. 7.

[0081] FIGS. 9a to 9c shows cross-sectional views of the outlet layer (270) shown in FIG. 7.

[0082] FIG. 10 shows an exploded perspective view of a third embodiment (300) of the invention.

[0083] FIGS. 11a to 11c shows cross-sectional views of the posterior layer (310) shown in FIG. 10.

[0084] FIG. 12 shows an exploded perspective view of a fourth embodiment (400) of the invention.

[0085] FIGS. 13a to 13c shows cross-sectional views of the shaping layer (430) shown in FIG. 12.

[0086] FIG. 14 shows an exploded perspective view of a fifth embodiment (500) of the invention.

[0087] FIG. 15 shows the reverse face of the anterior layer (550) shown in FIG. 14.

[0088] FIGS. 16a and 16b shows cross-sectional views of the anterior layer (550) shown in FIG. 14.

[0089] FIGS. 17a and 17b shows cross-sectional views of the shaping layer (530) shown in FIG. 14.

[0090] FIGS. 18a and 18b shows cross-sectional views of the posterior layer (510) shown in FIG. 14.

[0091] FIG. 19 shows the reverse face of the outlet layer (570) shown in FIG. 14.

[0092] FIGS. 20a and 20b shows cross-sectional views of the outlet layer (570) shown in FIG. 14.

[0093] Like parts and features have been given like reference numerals.

DETAILED DESCRIPTION OF THE INVENTION

[0094] FIG. 1 is an exploded perspective view of a first embodiment of the invention (100). The artificial eye assembly (100) comprises a posterior layer (10), a flow resistive layer (20), a shaping layer (30), a flow constricting layer (40), and an anterior layer (50).

[0095] The posterior layer (10) comprises a region that is shaped/dimensioned to mimic the back of the eye. The posterior layer (10) is made of 3D-printed resin. The posterior layer has a circular plate body region (11), which stands on a flattened base region (18). The circular plate region (11) has a diameter of 50 mm and is 6 mm thick at the base (18). The plate has a centrally located bowl-shape cavity region (12), which starts at the circular plate region. The bowl-shaped cavity (12) has an internal diameter of 22 mm and a depth of 14 mm. The bowl is 2 mm thick in the region where it extends from the plate. The posterior cavity (12) is fed by a side-mounted fluid inlet (13). Fluid may also be injected into the posterior cavity (12) via a top-mounted injection inlet (14). The side-mounted inlet (13), which is orthogonal to the top-mounted injection inlet (14), is 5 mm wide and tapers to 3 mm at its end and contains a 2 mm wide fluid conduit. The top-mounted inlet (14) is 5 mm wide and tapers to 3 mm at its end and contains a 2 mm wide fluid conduit. The body region (11) contains eight evenly spaced screw holes (19), the holes passing through the body (11). The screw holes have a diameter of 6.5 mm to accommodate M6 screws.

[0096] The flow resistive layer (20) is a thin disc (21) made of cellulose ester. It has a radius of 25 mm and is between 0.01 and 2 mm thick. The disc has a molecular weight cut off of 300 kDa. The body region (21) contains eight evenly spaced screw holes (29), the holes passing through the body (21). The screw holes have a diameter of 6.5 mm to accommodate M6 screws. In an alternative embodiment, the eight screw holes (29) can be omitted and the disc can be sandwiched in place.

[0097] The shaping layer (30) is made of 3D-printed resin. The shaping layer has a plate body region (31), which stands on a flattened base region (38). The plate region has a diameter of 50 mm and is 6 mm thick at the base (38). The plate has a bowl-shaped bore through its centre (i.e. second aperture), which has an internal diameter of 21 mm and a depth of 6 mm. Centrally located with respect to the bowl-shaped bore is a shaping structure (32), which is connected to the body (31) by four evenly spaced ribs/webs (33). The shaping structure (32) is broadly shaped/dimensioned to mimic the shape of a human lens. The shaping structure (32) has a radius of curvature for the anterior-facing surface of 10 mm and the radius of curvature for the posterior-facing surface of 6 mm, the apexes of the anterior-facing and posterior-facing surfaces being 9 mm apart. The body region (31) contains eight evenly spaced screw holes (39), the holes passing through the body (31). The screw holes have a diameter of 6.5 mm to accommodate M6 screws.

[0098] The flow constricting layer (40) contains a region broadly shaped/dimensioned to mimic the iris and pupil of the human eye. The flow constricting layer (40), is made of silicone. The flow constricting layer has a circular plate body region (41). The plate region has a diameter of 50 mm and is 0.4 mm thick. The plate has a bore through its centre (42), which has a diameter of 4 mm. The body region (41) contains eight evenly spaced screw holes (49), the holes passing through the body (41). The screw holes have a diameter of 6.5 mm to accommodate M6 screws.

[0099] The anterior layer (50) contains a region broadly shaped/dimensioned to mimic the front of the eye. The anterior layer (50) is made of 3D-printed resin. The anterior layer has a circular plate body region (51), which stands on a flattened base region (58). The circular plate region has a diameter of 50 mm and is 6 mm thick at the base (58). The plate has a centrally located bowl-shape cavity region (52) within the circular plate region. The bowl-shaped cavity (52) has a diameter of 15.4 mm and a depth of 3 mm. The anterior cavity (52) connects to eight drainage holes (53) located in the plate body (51). The eight drainage holes (53) connect to a common torus-shaped drainage conduit in the plate body (51), which surrounds the anterior cavity. The common drainage conduit in turn connects to a top-mounted fluid outlet (54). The top-mounted fluid outlet (54) is 5 mm wide and tapers to 3 mm at its end and contains a 2 mm wide fluid conduit. The body region (51) contains eight evenly spaced screw holes (59), the holes passing through the body (51). The screw holes have a diameter of 6.5 mm to accommodate M6 screws. FIG. 2 shows a perspective view of the assembled embodiment shown in FIG. 1, and FIG. 3 shows a cross-sectional view taken through the assembly shown in FIG. 2.

[0100] In use, the layers shown in FIG. 1 are assembled by bringing the parts together and securing them in place in a fluid-tight manner with a maximum of eight M6 screws. That is, the posterior face of the anterior layer (50) is brought into contact with the anterior face of the flow constricting layer (40);

[0101] the posterior face of the flow constricting layer (40) is brought into contact with the anterior face of the shaping layer (30); and the posterior face of the shaping layer (30) is brought into contact with the anterior face of the posterior layer (10), and in so doing the thin flow resistive layer (20) is sandwiched between the shaping layer (30) and the posterior layer (10). The screws pass through the aligned screw holes (19, 29, 39, 49 and 59). When assembled, the assembly rests on the base portions (18, 38 and 58). The flow resistive layer (20) is screwed in place by punching eight holes for the M6 screws, and is sandwiched between the posterior layer (10) and the shaping layer (30) to make it fluid tight. Optionally, a fluid permeable packing material, e.g. hyaluronic acid, is placed in the posterior cavity (12) either during or after assembly. Typically, in use, a fluid is pumped into the posterior cavity via the fluid inlet (13). The fluid passes through the various layers under pressure and is collected via the fluid outlet (54). In particular, pressure (e.g. 2-50 mmHg) is required to cause the fluid to pass through the pores in the flow resistive layer (20). Pressure also causes the movable flow resistive layer (20) onto/against the shaping body (32) of the shaping layer (30). In use, a drug containing fluid can be injected into the posterior cavity via the injection inlet (14). The top-mounted injection inlet (14) is closed by a valve. The fluid collected from the fluid outlet (54) is sent for analysis. For example, the drug can be monitored in real-time via a suitably calibrated UV, IR or MS sensor-based system. Alternatively, periodic samples can be gathered and analysed, e.g. by HPLC.

[0102] FIGS. 4a to 4c show cross-sectional views of the posterior layer (10) as shown in FIG. 1. FIG. 4a shows an anterior-facing cross-section of the posterior layer (10). FIG. 4b is a vertical section taken along A-A of FIG. 4a. FIG. 4c is a horizontal section taken along B-B of FIG. 4a.

[0103] FIGS. 5a to 5c show cross-sectional views of the shaping layer (30) shown in FIG. 1. FIG. 5a shows an anterior-facing cross-section of the shaping layer (30). FIG. 5b is a vertical section taken along A-A of FIG. 5a. FIG. 5c shows a magnified central portion of FIG. 5a, in particular showing the shaping body (32) and the four connecting webs (33).

[0104] FIGS. 6a and 6b show cross-sectional views of the posterior layer (50) shown in FIG. 1. FIG. 6a shows a posterior-facing cross-section of the anterior layer (50). FIG. 5b is a vertical section taken along section A-A of FIG. 6a.

[0105] FIG. 7 is an exploded perspective view of a second embodiment of the invention (200). The artificial eye assembly (200) comprises an outlet layer (270), second flow resistive layer (260), a posterior layer (210), a flow resistive layer (20), a shaping layer (30), a flow constricting layer (40), and an anterior layer (50).

[0106] The flow resistive layer (20), shaping layer (30), flow constricting layer (40), and the anterior layer (50) are substantially the same as described in FIGS. 1 to 6 above, and so are not further discussed here.

[0107] The posterior layer (210) comprises a region that is shaped/dimensioned to mimic the back of the eye. The posterior layer (210) is made of 3D-printed resin. The posterior layer has a circular plate body region (211), which stands on a flattened base region (218). The circular plate region has a diameter of 50 mm and is 6 mm thick at the base (218). The plate has a centrally located bowl-shape cavity region (212), which starts at the circular plate region. The bowl-shaped cavity (212) has a diameter of 22 mm and a depth of 15 mm (including the circular plate region). The bowl is 1 mm thick in the region where it extends from the plate. The posterior cavity has a centrally located cavity aperture (215) that passes through the bowl-shaped structure. The cavity aperture (215) has an aperture diameter of 5 mm. The posterior cavity (212) is fed by a side-mounted fluid inlet (213). Fluid may also be injected in to the posterior cavity (212) via a top-mounted injection inlet (214). The side-mounted inlet (213), which is orthogonal to the top-mounted injection inlet (214), is 5 mm wide and tapers to 3 mm at its end and contains a 2 mm wide fluid conduit. The top-mounted inlet (214) is 5 mm wide and tapers to 3 mm at its end and contains a 2 mm wide fluid conduit. The body region (211) contains eight evenly spaced screw holes (219), the holes passing through the body (211). The screw holes have a diameter of 6.5 mm to accommodate M6 screws.

[0108] The second flow resistive layer (260) is a thin disc made of reconstituted cellulose. It has a radius of 25 mm. The disc has a molecular weight cut off of 13 kDa. The body region (261) contains eight evenly spaced screw holes (269), the holes passing through the body (261). The screw holes have a diameter of 6.5 mm to accommodate M6 screws. In an alternative embodiment, the eight screw holes (269) can be omitted and the disc can be sandwiched in place.

[0109] The anterior face of the outlet layer (270) is broadly shaped/dimensioned to mate with the posterior face of the posterior layer (210). The outlet layer (270) is made of 3D-printed resin. The outlet layer has a circular plate body region (271), which stands on a flattened base region (278). The circular plate region has a diameter of 50 mm and is 3 mm thick at the base (278). The plate has a centrally located bowl-shape mating cavity region (272), which starts at the circular plate region. The mating cavity (272) has a diameter of 24 mm and a depth of 9 mm. The wall of the mating cavity is 1 mm thick in the region where it extends from the plate. The mating cavity has a centrally located posterior outlet (275) that passes through the bowl-shaped structure. The posterior outlet (275) has substantially a funnel shape and feeds into the side of a substantially orthogonally arranged flow balancing conduit (273), the flow balancing conduit having an internal diameter of 2 mm. The body region (271) contains eight evenly spaced screw holes (279), the holes passing through the body (271). The screw holes have a diameter of 6.5 mm to accommodate M6 screws.

[0110] In use, the layers shown in FIG. 7 are assembled by bringing the parts together and securing them in place in a fluid-tight manner with eight M6 screws. The screws pass through the aligned screw holes (279, 269, 219, 39, 49 and 59). When assembled the assembly rests on base portions (278, 218, 38 and 58). The flow resistive layer (20) and second flow resistive layer (260) are screwed in place by punching eight holes for the M6 screws, and are sandwiched between adjacent layers to make it fluid tight. Optionally, a fluid permeable packing material e.g. hyaluronic acid, is placed in the posterior cavity (212) either during or after assembly. Typically, in use, a fluid is pumped into the posterior cavity via the fluid inlet (213). The fluid passes through the various layers under pressure and is collected via the fluid outlet (54). Pressure is required to cause the fluid to pass through the pores in the flow resistive layer (20). Pressure also causes the flow resistive layer (20) onto/against the shaping body (32) of the shaping layer (30). Pressure is also required to cause the fluid to pass through the pores in the second flow resistive layer (260). If the rate of flow through the second flow resistive layer is lower than the rate of flow through the first flow resistive layer, then fluid can be passed through the flow balancing conduit (273) to balance the rate of flows collected from the front (anterior) and back (posterior) of the eye assembly. In use, a drug containing fluid can be injected into the posterior cavity via the injection inlet (214). The fluid collected from the fluid outlet (54) and/or via the flow balancing conduit (273) are sent for analysis as discussed above with reference to the first embodiment (100).

[0111] FIGS. 8a to 8c show cross-sectional views of the posterior layer (210) shown in FIG. 7. FIG. 8a shows an anterior-facing cross-section of the posterior layer (210). FIG. 8b is a vertical section taken along A-A and FIG. 8c is a horizontal section taken along B-B of FIG. 8a.

[0112] FIGS. 9a to 9c show cross-sectional views of the outlet layer (270) shown in FIG. 7. FIG. 9a shows an anterior-facing cross-section of the outlet layer (270). FIG. 9b is a vertical section taken along A-A and FIG. 9c is a horizontal section taken along B-B of FIG. 9a.

[0113] FIG. 10 is an exploded perspective view of a third embodiment of the invention (300). The artificial eye assembly (300) comprises an outlet layer (370), second flow resistive layer (260), a posterior layer (310), a flow resistive layer (20), a shaping layer (30), a flow constricting layer (40), and an anterior layer (50).

[0114] The second flow resistive layer (260), flow resistive layer (20), shaping layer (30), flow constricting layer (40), and the anterior layer (50) are substantially the same as described in FIGS. 7 to 9 above, and so are not further discussed in detail here. The posterior layer (310) in the third embodiment (300) is substantially the same as the posterior layer (210) in the second embodiment (200) as shown in FIGS. 7 and 8. The substantive difference being that the centrally located cavity aperture (215) in the second embodiment (200) is replaced with a plethora (i.e. 26) of substantially evenly spaced apertures (315) in the third embodiment (300). As such, the bowl-shaped cavity (312) resembles the bowl region of a colander. The outlet layer (370) in the third embodiment (300) is substantially the same as the outlet layer (270) in the second embodiment (200) as shown in FIGS. 7 and 9. The substantive differences being that (i) the cavity region (372) is slightly bigger in the third embodiment (300) as compared to the cavity region (272) in the second embodiment (200). This is done to allow room for a fluid to pass through the plethora of holes (315) in the posterior layer (310); and (ii) and the flow balancing conduit (373) is shorter on one side as compared to the other.

[0115] In use, the third embodiment (300) is substantially assembled and used like the second embodiment (200) as described above. The exception being that fluid passes through a plethora of holes (315) in the posterior layer.

[0116] FIGS. 11a to 11c show cross-sectional views of the posterior layer (310) shown in FIG. 10. FIG. 11a shows a posterior-facing cross-section of the posterior layer (310). FIG. 11b is a vertical section taken along A-A of FIG. 11a. FIG. 11c is a horizontal section taken along B-B of FIG. 11a.

[0117] FIG. 12 is an exploded perspective view of a fourth embodiment of the invention (400). The artificial eye assembly (400) comprises an outlet layer (370), second flow resistive layer (260), a posterior layer (410), a flow resistive layer (20), a shaping layer (430), a flow constricting layer (40), and an anterior layer (50).

[0118] The outlet layer (370), second flow resistive layer (260), flow resistive layer (20), flow constricting layer (40), and the anterior layer (50) are substantially the same as described in FIGS. 10 and 11 above, and so are not further discussed in detail here.

[0119] The posterior layer (410) in the fourth embodiment (400) is substantially the same as the posterior layer (310) in the third embodiment (300). The substantive difference is that there is no side-mounted flow inlet in the posterior layer (410) of the fourth embodiment (400), which would otherwise correspond to the flow inlet (313) of the third embodiment (300).

[0120] The shaping layer (430) in the fourth embodiment (400) is substantially the same as the shaping layer (30) in the third embodiment (300) as shown in FIG. 10. The substantive difference being that a side-mounted flow inlet (434) has been added, with the inlet feeding into the side of the central bowl-like bore (i.e. second aperture). In effect, the substantive difference between the third embodiment (300) and the fourth embodiment (400), is that the side-mounted fluid inlet has been moved from the posterior layer to the shaping layer.

[0121] In use, the fourth embodiment (400) is substantively assembled and used like the third embodiment (300) as described above; with the exception that fluid enters the eye assembly at the shaping layer (430) and not at the posterior layer (410). If necessary, capillary tubing can be added at (or after) the fluid outlet (54), to generate a head of pressure, which would normally be generated by the flow resistive layer (20). If necessary, the collector reservoir can also be elevated to create a head of pressure.

[0122] FIGS. 13a to 13c show cross-sectional views of the shaping layer (430) shown in FIG. 12. FIG. 13a shows an anterior-facing cross-section of the posterior layer (430). FIG. 13b is a vertical section taken along A-A of FIG. 13a. FIG. 13c is a horizontal section taken along B-B of FIG. 13a.

[0123] FIG. 14 is an exploded perspective view of a fifth embodiment of the invention (500). The artificial eye assembly (500) comprises an outlet layer (570), second flow resistive layer (260), a posterior layer (510), a flow resistive layer (20), a shaping layer (530), a flow constricting layer (40), and an anterior layer (550), elastic layer (580) and a retaining layer (590).

[0124] The second flow resistive layer (260), flow resistive layer (20) and flow constricting layer (40) are substantially the same as described in FIG. 12 above, and so are not further discussed in detail here.

[0125] The anterior face of the outlet layer (570) is broadly shaped/dimensioned to mate with the posterior face of the posterior layer (510). The outlet layer (570) is made of 3D-printed resin.

[0126] The outlet layer (570) has a circular plate body region (571) and has a diameter of 37 mm and is 3 mm thick. The plate has a centrally located bowl-shaped mating cavity region (572), which starts at the circular plate region. The mating cavity (572) has a diameter of 26 mm and a depth of 7 mm. The bowl is 1.5 mm thick in the region where it extends from the plate body (571).

[0127] The plate body region (571) connects to a surrounding ring-shaped support plate (577) by three 13 mm long spaced apart ribs/webs. The ring-shaped support plate (577) is a ring with an outer diameter of 86 mm and an inner diameter of 64 mm and is 13 mm thick. The ring-shaped support plate (577) stands on a base region (578). The ring-shaped plate (577) contains eight evenly spaced screw holes (579), the holes passing through the body (577). The screw holes have a diameter of 6.5 mm to accommodate M6 screws. The posterior-facing surface of the support plate (577) is closed off by a thin sheet of 3D printed resin (574). The mating cavity (572) has a centrally located posterior outlet (575) that passes through the bowl-shaped structure and through the sheet of 3D printed resin (574). The posterior outlet (575) has substantially a funnel shape that feeds into the side of a substantially U-shaped vertically aligned flow balancing conduit (573); the flow balancing conduit having an internal diameter of 2 mm. The volume of space between the plate body region (571) and the ring-shaped plate (577) is fed by a side-mounted volume feed inlet (576), the volume feed inlet (576) is 4 mm wide and tapers to 2.5 mm at its end and contains a 2 mm wide fluid conduit.

[0128] The posterior layer (510) has a region that is broadly shaped/dimensioned to mimic the back of the eye. The posterior layer (510) is made of 3D printed resin. The posterior layer has a circular plate body region (511). The circular plate region has an external diameter of 37 mm and lowest internal diameter of 21 mm and is 6 mm thick. The plate has a centrally located bowl-shape cavity region (512), which starts at the circular plate region. The bowl-shaped cavity (512) has a diameter of 22 mm and a depth of 9 mm. The bowl is 1 mm thick in the region where it extends from the plate.

[0129] The plate body region (511) connects to a surrounding ring-shaped support plate (517) by three 14 mm long spaced apart ribs/webs (516). The ring-shaped plate (517) is a ring with an outer diameter of 86 mm and an inner diameter of 64 mm and is 6 mm thick. The ring-shaped support plate (517) stands on a base region (518). The ring-shaped support plate (517) contains eight evenly spaced screw holes (519), the holes passing through the body (517). The screw holes have a diameter of 6.5 mm to accommodate M6 screws. The posterior cavity (512) has a plethora (i.e. 16) of substantially evenly spaced apertures (515) that pass through the bowl-shaped structure. As such, the bowl-shaped cavity (512) resembles the bowl region of a colander.

[0130] Fluid may be injected into the posterior cavity (512) via a top-mounted injection inlet (514), which has a fluid conduit that extends from outside of the ring-shaped support plate (517) into the cavity (512). The injection inlet (514) contains a 5 mm wide fluid conduit.

[0131] The shaping layer (530) is made of 3D-printed resin. The shaping layer has a plate body region (531). The plate region has an external diameter of 37 mm and a lowest internal diameter of 21 mm and is 6 mm thick. The plate body region has a bowl shape through its centre, which has a diameter of 22 mm. Centrally located with respect to the bore is a shaping structure (532), which is connected to the plate body region (531) by four evenly spaced ribs/webs. The shaping structure (532) is broadly shaped/dimensioned to mimic the shape of a human lens. The shaping structure (532) has a radius of curvature for the anterior-facing surface of 10 mm and the radius of curvature for the posterior-facing facing surface of 6 mm, the apexes of the anterior-facing and posterior-facing surfaces being 9 mm apart.

[0132] The plate body region (531) connects to a surrounding ring-shaped support plate (537) via a spiralling fluid conduit. The ring-shaped plate (537) is a ring with an outer diameter of 86 mm and an inner diameter of 64 mm and is 6 mm thick. The ring-shaped support plate (537) stands on a base region (538). The ring-shaped plate (537) contains eight evenly spaced screw holes (539), the holes passing through the body (537). The screw holes have a diameter of 6.5 mm to accommodate M6 screws. The anterior-facing surface of the ring-shaped support plate (537) is closed off by a thin sheet of 3D-printed resin, except that it has a hole matching and corresponding to the bowl shape in the plate body region (531).

[0133] Fluid may enter the central bore of the plate body region (531) (adjacent to the shaping body (532)), via a top-mounted fluid inlet (534). The fluid conduit travels via a circuitous route to feed the central bowl-like bore of the plate body region (531). The conduit passes through the body of the ring-shaped plate (537), spirals before entering into the body of the plate body region (531). The conduit then bifurcates forming a square-shaped loop located within the plate body region (531). The square-shaped loop in turn has twelve spaced apart conduits (535) that feed into the central bore of the plate body region (531).

[0134] The anterior face of the ring-shaped plate (537) is equipped with eight evenly spaced peg-like protrusions (536), which cooperate with eight recesses (556) in the anterior layer (550), and pass through the eight holes (49) in the flow constricting layer (40).

[0135] The anterior layer (550) has a region broadly shaped/dimensioned to mimic the front of the eye. The anterior layer (550) is made of 3D-printed resin. The anterior layer has a circular plate body region (551) which stands on a flattened base region (558). The circular plate region has a diameter of 86 mm and is 1 mm thick at the base (558). The plate has a centrally located bowl-shape cavity region, the anterior cavity (552). The anterior cavity (552) has a diameter of 15.4 mm and a depth of 2.2 mm. The anterior cavity has a centrally located aperture (555), that passes through the bowl-shaped structure. The aperture (i.e. third aperture) has a diameter of 7.5 mm. The anterior cavity (552) has eight evenly spaced drainage holes (553), which connect to a torus-shaped drainage conduit (557) that surrounds the anterior cavity. This in turn connects to a second torus-shaped drainage conduit, which surrounds the first torus-shaped conduit. The second torus-shaped conduit in turn connects to a side-mounted fluid outlet (554), which is located at the apex of the circular body region (551). The fluid outlet (554) is 4 mm wide and tapers to 2.5 mm at its end, and contains a 2 mm wide fluid conduit. The body region (551) contains eight evenly spaced screw holes (559), the holes passing through the body (551). The screw holes have a diameter of 6.5 mm to accommodate M6 screws. As previously mentioned, the body region (551) contains eight recesses (556), which mate with projections (536) on the shaping layer (530).

[0136] The elastic layer (580) is a thin disc (581) made of clear silicone. It has a radius of 22 mm and is 0.5 mm thick with a Shore Hardness A.

[0137] The retaining layer (590) is made of 3D printed resin. The retaining layer has a circular plate body region (591). The plate region has a diameter of 44 mm and is 3 mm thick. The plate has a bore (593) through its centre on its anterior face. The bore (i.e. fourth aperture) has a diameter of 6.5 mm. On the posterior face, it has a bowl-shaped structure of diameter 15.4 mm and a depth of 0.2 mm. The plate body region (591) connects to a surrounding ring-shaped support plate (597) by four evenly spaced bridges (592). The bridges are 10.5 mm long and 7 mm wide. The ring-shaped plate (597) is a ring with an outer diameter of 86 mm and an inner diameter of 64 mm. The ring-shaped plate (597) has an aperture (594) at its apex to receive the side-mounted fluid outlet (554). The ring-shaped support plate (597) stands on a base region (598). The ring-shaped plate (597) contains eight evenly spaced screw holes (599), the holes passing through the body (597). The screw holes have a diameter of 6.5 mm to accommodate M6 screws.

[0138] In use, the layers shown in FIG. 14 are assembled by bringing the parts together and securing them in place in a fluid-tight manner with eight M6 screws. The screws pass through the aligned screw holes (579, 519, 539, 559 and 599). When assembled, the assembly rests on base portions (578, 518, 538, 558 and 598). The flow resistive layer (20), second flow resistive layer (260), flow constricting layer (40) and the elastic layer (580) are not screwed in place, but rather are sandwiched between adjacent layers. Optionally, a fluid permeable packing material e.g. hyaluronic acid, is placed in the posterior cavity (512), either during or after assembly. Typically, in use, a fluid is pumped into the bore of the shaping layer (530) via the fluid inlet (534). The fluid passes through the various layers under pressure and is collected via the fluid outlet (554). Pressure as well as diffusion is required to cause the fluid to pass through the pores in the flow resistive layer (20). Diffusion and pressure is required to cause the fluid to pass through the pores in the second flow resistive layer (260). If necessary, capillary tubing can be added at (or after) the fluid outlet (554) to generate a head of pressure. If the rate of flow out of the posterior outlet (575) is lower than the rate of flow through the fluid outlet (554), then fluid can be passed through the flow balancing conduit (573) to balance the rate of flows collected from the front (anterior) and back (posterior) of the eye assembly. In use a drug containing fluid can be injected into the posterior cavity via the injection inlet (514). The fluid collected from the fluid outlet (554) and/or via the flow balancing conduit (573) are sent for analysis as discussed above with reference to the first embodiment (100). In addition, a thermally regulated fluid can be introduced into the volume of space between the outlet layer (570) and shaping layer (530) via the volume feeding inlet (576). The thermally regulated fluid surrounds the circular plate body region (511) of the posterior layer (510) and surrounds the plate body region (531) of the shaping layer (inclusive of the spiralling fluid conduit of the shaping layer). In effect, in use, a gasket is created between the shaping layer (530) and the outlet layer (570), and so the volume of space created there within holds the thermally regulated fluid in a fluid tight manner.

[0139] FIG. 15 shows a perspective view of the anterior face of the anterior layer (550) as shown in FIG. 14. The side-mounted fluid outlet (554) can be seen more clearly from this view point.

[0140] FIGS. 16a and 16b show cross-sectional views of the anterior layer (550) shown in FIG. 14. FIG. 16a shows a posterior-facing cross-section of the anterior layer (550). FIG. 16b is a vertical section taken along section A-A of FIG. 16a.

[0141] FIGS. 17a and 17b show cross-sectional views of the shaping layer (530) shown in FIG. 14. FIG. 17a shows a posterior-facing cross-section of the shaping layer (530). FIG. 15b is a vertical section taken along section A-A of FIG. 17a.

[0142] FIGS. 18a and 18b show cross-sectional views of the posterior layer (510) shown in FIG. 14. FIG. 18a shows a posterior-facing cross-section of the posterior layer (510). FIG. 18b is a vertical section taken along section A-A of FIG. 18a.

[0143] FIG. 19 shows a perspective view of the anterior face of the outlet layer (570) shown in FIG. 14.

[0144] FIGS. 20a and 20b show cross-sectional views of the outlet layer (570) shown in FIG. 14. FIG. 20a shows a posterior-facing cross-section of the outlet layer (570). FIG. 20b is a vertical section taken along section A-A of FIG. 20a.

EXAMPLES

1. Method of Assembling an Eye Assembly Embodiment Comprising a Single Flow Restrictive Layer (e.g. see FIG. 1)

Preparing Membranes

[0145] Cut the membrane of the flow restrictive layer into a round shape with a 50 mm diameter. [0146] Create eight holes in the membrane for the screws using a punch and hammer.

Assembly

[0147] Align along the holes the anterior layer, flow constricting layer, shaping layer, flow restrictive layer and the posterior layer. [0148] Fix the 8×M6 screws in position along the holes. [0149] Tighten the screws to assemble the eye assembly embodiment.

Filling

[0150] Fill the posterior cavity of the posterior layer with the fluid packing material (e.g. hyaluronic acid) using a syringe with a 29 G needle via the injection inlet. [0151] Fill the anterior cavity of the anterior layer with buffer (PBS, pH 7.4, 0.05% sodium azide) using a syringe with a 29 G needle via the fluid outlet. [0152] Connect capillary tubes (e.g. 1.0 mm ID) to the fluid inlet, injection inlet and fluid outlet. [0153] Put a valve on the injection inlet and close it.

2. Method of Assembling an Eye Assembly Embodiment Comprising Two Flow Restrictive Layers (e.g. Dee FIG. 7)

Preparing Membranes

[0154] Prepare the membrane of the (first) flow restrictive layer and the membrane of the second flow restrictive layer as per Example 1.

Assembly

[0155] Align along the holes the anterior layer, flow constricting layer, shaping layer, (first) flow restrictive layer, posterior layer, second flow restrictive layer and outlet layer. [0156] Fix the 8×M6 screws in position along the holes. [0157] Tighten the screws to assemble the eye assembly embodiment.

Filling

[0158] Fill the posterior cavity and anterior cavity as described in Example 1 above.

3. Method of Assembling an Eye Assembly Comprising Two Flow Restrictive Layers, Elastic Layer and a Retaining Layer (e.g. see FIG. 14)

Preparing Membranes

[0159] Prepare the membrane of the (first) flow restrictive layer and the membrane of the second flow restrictive layer as per Example 1.

Assembly

[0160] Fix the membrane of the (first) flow restrictive layer between the shaping layer and the posterior layer. [0161] When present, use the protrusions on the shaping layer to fix the flow constricting layer in place. [0162] Fix the membrane of the second flow restrictive layer between the posterior layer and the outlet layer. [0163] Align the 8×M6 screws in position along the anterior layer, flow constricting layer, shaping layer, posterior layer and outlet layer. [0164] Place the anterior layer, elastic layer and retaining layer in turn on to the flow constricting layer. [0165] Tighten the screws to assemble the eye assembly embodiment.

Filling the Eye Assembly with Filling Materials

[0166] Fill the posterior cavity and anterior cavity as described in Example 1 above.

4. Use of Eye Assembly

Eye Assembly

[0167] Assemble the eye assembly embodiment as described above in Examples 1 to 3, ensuring that it is fluid tight (i.e. it has no leaks).

Rocking Platform

[0168] If using the rocking platform, place the assembly on top of a rockable platform and secure the assembly to the platform.

External Temperature Control

[0169] If using a hot bath, fill the bath with distilled water and switch on the heating plate setting the temperature to 37° C. (or the desired temperature), and place the eye assembly embodiment in the bath. Allow the eye assembly embodiment to thermally equilibrate for 24 hours.

Internal Temperature Control

[0170] If using an internal temperature controlling system (e.g. an eye assembly embodiment with a gasket; e.g. see FIG. 14), connect the volume feed inlet to the column of water (i.e. the thermally regulated fluid) and place the eye assembly on a heating plate. Allow the thermally regulated fluid to enter into the volume of space between the outlet layer and shaping layer via the volume feeding inlet.

Pumping Fluids

[0171] Connect the fluid inlet to the microfluidic system. Connect the fluid outlet to a reservoir. If using a flow balancing conduit, connect a capillary tube (e.g. 1.0 mm ID) to the flow balancing conduit. Set the pump pressure, and allow to run at a fixed pressure for 24 hours at the selected temperature. If present, adjust the flow into the flow balancing conduit such that the rate of flow out of the flow balancing conduit matches the rate of flow coming out of the flow outlet.

Drug Delivery

[0172] Once the system has temperature and pressure equilibrated, usually allowing this to happen over 24 hours or more, inject the desired drug/formulation into the eye assembly embodiment via the injection inlet and then seal the valve.

Rocking Experiments

[0173] If using a rocking platform, turn on the rocking and launch the waking and sleeping cycle program.

Data Acquisition

[0174] After the drug has been administered, record the temperature, pressure, and the flow rate in, and flow rates out of the assembly, via the inlets and outlets, using the microfluidic and temperature software.

Collection of Samples

[0175] At designated times, collect samples from the outlets in collection vials, and store the vials in a freezer (−20° C.). Samples may then be analysed by the chosen assay, e.g. by high performance liquid chromatography (HPLC).