Needle insertion device for electroporation of object in eye

Abstract

To provide an insertion device for inserting an electrode needle of an electroporation device for injecting an object in the ciliary muscle of an eye.SOLUTION: A device includes: a support body 4 provided with a support body base part 10, the support body base part 10 defining a spherical base part contact surface extending along a virtual ball S and a circular rim extending in a rim flat surface; and a first needle 8a and a second needle 8b movable on the support body between first and second extraction positions where the first and second needles are outside the virtual ball and first and second insertion positions where the first and second needles are maximally inserted in the virtual ball respectively. At a position between first and second puncture positions, the first and second needles extend along first insertion axis Δ8a and second insertion axis Δ8b respectively.SELECTED DRAWING: Figure 1

Description

Technical Field

[0001] The present invention relates to an insertion device for inserting a needle into the eye, in particular an insertion device for inserting the electrode needle of an electroporation device for injecting an object into the ciliary muscle of the eye.

Background Art

[0002] International Publication No. 2016 / 166172 pamphlet discloses an electroporation device for injecting an object into the ciliary muscle of the eye. This device enables accurate and stable positioning of the electrode needle into the eye.

[0003] However, each needle is inserted substantially tangentially to the surface of the eye. Therefore, the impact of the needle when it hits the surface may cause rotation of the eye, which hinders the insertion of the needle.

Summary of the Invention

Problems to be Solved by the Invention

[0004] Clamps for holding the eye are known. However, they are large and cumbersome to handle and require an additional operator.

[0005] A solution is needed to facilitate the insertion of the needle without the drawbacks mentioned above.

[0006] The object of the present invention is to meet this need.

Means for Solving the Problems

[0007] For this purpose, the present invention proposes a device, preferably an electroporation device, which device comprises a support with a support base, where the support base has a spherical base contact surface extending along a virtual sphere having a radius of 10 to 15 mm so as to fit the outer surface of the eye, and A circular rim having a radius greater than 5 mm and less than 8 mm and extending in the rim plane, fitting the edge of the eye, defining a first needle and a second needle each having a first tip and a second tip, wherein the first needle and the second needle are on the support via first and second intermediate puncture positions, the first and second extraction positions where the first and second needles are each outside the virtual sphere, the first and second insertion positions where the first and second needles are each inserted maximally into the virtual sphere and are movable between, At the first and second intermediate puncture positions, the first and second needles extend along the first and second insertion axes respectively, and the first and second tips are located at first and second insertion points respectively belonging to the first and second hemispheres of the virtual sphere, and the first and second hemispheres are separated by a plane containing the axis X and a central point in the middle length of the rim, that is, the median radial plane of the rim. is provided with.

[0008] In a first aspect of the invention, during the insertion operation starting from the first and second extraction positions and ending at the first and second insertion positions, when the first and second needles reach the first and second intermediate puncture positions, the first and second needles are movable on the support so as to push, i.e., "pinch", the virtual sphere towards the median radial plane of the rim.

[0009] Preferably, the angle θ between the median radial plane of the rim and either of the first and second insertion axes is greater than 10°, preferably greater than 20°, preferably greater than 30°, preferably greater than 40°, preferably greater than 50°, and / or less than 170°, preferably less than 160°, preferably less than 150°, preferably less than 140°, preferably less than 130°, preferably less than 120°, preferably less than 110°.

[0010] In a second aspect of the invention, the angle between the median radial plane of the rim and either of the first and second insertion axes is greater than 70° and less than 110°. This embodiment is particularly advantageous when the first and second needles are straight, as shown in FIGS. 1-6.

[0011] Therefore, regardless of the aspect of the invention, when the spherical contact surface extends on the outer surface of the eye, the first and second tips press the eye as they are pressed on the outer surface of the eye.

[0012] As will become apparent in the following description, this pressing action advantageously limits the risk of rotation of the eye during the insertion of the first and second needles. Also, the pressing of the eye may be simultaneous with the insertion of the tips into the eye, and thus both the pressing action and the insertion action can be achieved by a single operator.

[0013] A device according to a second aspect of the invention may also have one or several of the following optional and preferred features: the median radial plane of the rim and, the insertion axis of the first needle, preferably any first needle, and / or the insertion axis of the second needle, preferably any second needle, and the angle therebetween is greater than 70°, greater than 80°, or greater than 85°, and / or less than 110°, less than 100°, or less than 95°, preferably about 90°, where the first needle and the second needle are preferably aligned in a row; the rim plane and, the first needle, preferably any first needle, and / or the second needle, preferably any second needle, and the angle therebetween is less than 20°, preferably less than 10°, preferably less than 5°; the device comprises first and / or second elastic members arranged to act on the first and / or second needles respectively to move the first and / or second needles towards their respective first and / or second extraction positions; The device comprises first and second elastic members configured to apply substantially the same force to the first and second needles respectively, the force being greater than 1 Newton and less than 10 Newtons; When all of the first and second needles are in the insertion position, the first needle intersects the second needle and / or, preferably, within the virtual sphere, the first needle extends substantially along the entire length of the second needle and vice versa; Alternatively, when all of the first and second needles are in the insertion position, the distance between the first tip of the first needle and the second tip of the second needle is less than 1 mm, preferably less than 0.5 mm; The device is an electroporation device and comprises an electric generator and an invasive electrode electrically connected to a first terminal of the generator and comprising the first and second needles, the support also comprising a flat electrode connected to a second terminal of the generator and defining a flat electrode contact surface extending along the virtual sphere; The device preferably comprises a plurality of first needles extending in a first needle plane, preferably extending parallel to each other, and / or a plurality of second needles extending in a second needle plane, preferably extending parallel to each other, all of the first and second needles preferably extending in a common needle plane, preferably parallel to each other; The first needle plane and / or the second needle plane and / or the common needle plane is at an angle greater than 70°, greater than 80°, or greater than 85°, and / or less than 110°, less than 100°, or less than 95°, preferably about 90°, with the median radial plane of the rim, and / or at an angle greater than 40° and less than 80° with the rim plane defining; The device is an electroporation generator comprising first and second terminals having different polarities, and An invasive electrode that is electrically connected to the first terminal and has the first and second needles, A flat electrode that is fixed to the support, connected to the second terminal, and defines a flat electrode contact surface that extends along the virtual sphere, where the dimensions of the flat electrode contact surface are preferably such that the flat electrode contact surface extends substantially within a common flat electrode plane, Comprising; The first needle plane and / or the second needle plane and / or the common needle plane is substantially parallel to the flat electrode plane; The flat electrode extends within a plane, and the first needle plane and / or the second needle plane and / or the common needle plane is substantially parallel to the plane of the flat electrode; When all of the first and second needles are in their insertion positions, i.e., in the configuration of complete insertion of the needles, the distance between the needles and the flat electrode plane is 2.0 to 1.3 mm, preferably 1.8 to 1.5 mm, preferably 1.7 to 1.6 mm, and preferably substantially constant regardless of which point of the flat electrode is considered; The distance between the rim and any point of the flat electrode contact surface is greater than 2 mm and less than 6 mm; The device comprises an injection needle, and the support base is provided with a guide adapted to guide the sliding of the injection needle between a capture position where the tip of the injection needle is outside the virtual sphere and an injection position where the tip of the injection needle is inside the virtual sphere; Preferably, at the injection position, a portion of the injection needle extending inside the virtual sphere extends within a plane, preferably a median plane, preferably parallel to the first and second needles, between the common needle plane and the flat electrode plane; The flat electrode extends in contact with the outer surface of the eye, the rim extends on the edge of the eye, and when the injection needle is fully inserted (injection position), the discharge orifice of the injection needle opens within the ciliary muscle of the eye; The first and second needles are each fixed to first and second comb bases, and the first and second comb bases are substantially symmetric with respect to the central radial plane of the rim at the insertion positions of the first and second needles; At the inserted positions of the first and second needles (i.e., the fully inserted configuration, i.e., the "insertion position"), when the device is observed along an observation direction perpendicular to the flat electrode plane, each needle appears to cross the entire flat electrode contact surface.

[0014] Features of different aspects of the present invention can be combined. In particular, any optional features of the device according to the second aspect of the present invention can be applied to the device according to the first aspect of the present invention.

[0015] The device according to the first or second aspect of the present invention may also have one or several of the following optional and preferred features: The device comprises first and second comb bases to which the first and second needles are rigidly fixed, respectively; The device comprises first and second arms supporting the first and second needles (or the first and second comb bases), respectively, the second arm being rotatably attached to the first arm about an axis, or the first and second arms being rotatably attached to the support base about different respective axes, or the first and second arms being preferably attached to translate on the support base along a common direction; The device comprises springs that elastically direct the needles towards the first and second extraction positions, respectively, the springs acting, for example, on the first and second comb bases; The device comprises a synchronization mechanism for synchronizing the movement of the first and second needles during the insertion operation, in particular a synchronization mechanism for synchronizing the movement of the first and second comb bases to which the first and second needles are rigidly fixed, respectively; The synchronization mechanism comprises a connector having first and second branches mechanically coupled to first and second comb bases to which the first and second needles are rigidly fixed respectively; The first and second branches define first and second pins mounted to slide within first and second guide rails respectively defined by the first and second comb bases, or the first comb base and the second comb base are connected by an elastic joint, and the first and second branches are mounted to slide on the first and second comb bases respectively, thereby pushing the first and second comb bases against the action of the elastic joint; the first and second comb bases and the elastic joint together form a leaf spring; The device comprises an actuatable lock for locking the synchronization mechanism, at least in an extraction configuration in which the first and second needles are in the first and second extraction positions, and / or in an insertion configuration in which the first and second needles are in the first and second insertion positions; The device comprises an actuator configured for an operator to act on the synchronization mechanism so as to move the first and second needles simultaneously; The device comprises a drive mechanism defining a plurality of predetermined positions in which the first and second needles can be immobilized during the insertion operation.

[0016] In one embodiment, the first needle and / or the second needle is preferably curved so as to extend along a common circle, which is particularly advantageous when the first and second needles are arranged to rotate on the support about a common axis of rotation preferably close to or including the center of the circle during the insertion operation. Preferably, the distance between the common axis of rotation and the center of the circle is less than 5 mm, preferably less than 3 mm, preferably less than 2 mm, preferably less than 1 mm.

[0017] Preferably, at the insertion position of the curved first needle, the distance between any point of the first needle facing the flat electrode and the flat electrode is more than 0.8 mm, preferably more than 0.9 mm, preferably more than 1.0 mm, and / or less than 2.0 mm, preferably less than 1.9 mm, preferably less than 1.8 mm, preferably less than 1.7 mm.

[0018] Preferably, at the insertion position of any of the curved first needles, the distance between any point of the first needle facing the flat electrode and the flat electrode is more than 0.8 mm, preferably more than 0.9 mm, preferably more than 1.0 mm, and / or less than 2.0 mm, preferably less than 1.9 mm, preferably less than 1.8 mm, preferably less than 1.7 mm.

[0019] Preferably, at the insertion position of any of the curved second needles, the distance between any point of the second needle facing the flat electrode and the flat electrode is more than 0.8 mm, preferably more than 0.9 mm, preferably more than 1.0 mm, and / or less than 2.0 mm, preferably less than 1.9 mm, preferably less than 1.8 mm, preferably less than 1.7 mm.

[0020] Preferably, at the insertion position of one or more first needles, the distance between any point of the one or more first needles facing the flat electrode and the flat electrode is substantially constant. In particular, in one embodiment, one or more of the first needles are curved and the flat electrode is curved, whereby the distance between any point of the one or more first needles facing the flat electrode and the flat electrode is substantially constant. In particular, the flat electrode can be convex, i.e., can have a center of curvature outside the virtual sphere.

[0021] Definition The "pushing force" corresponds to the force applied to the surface by the needle when the needle moves from the extraction position to the insertion position and pushes it before piercing the surface of the eye.

[0022] The "insertion point" of the needle is the point at which, at the puncture position, the insertion axis along which the needle extends intersects the virtual sphere carrying the contact surface.

[0023] Two needles are "aligned" when they extend on the same axis.

[0024] The "quarter circle of the hemisphere" refers to one-fourth of the surface of the hemisphere obtained by cutting the hemisphere with two perpendicular planes intersecting along the major axis of the hemisphere.

[0025] At the first and second insertion positions of the first and second needles, the device is in an "insertion configuration" or a "fully inserted configuration". At the first and second extraction positions of the first and second needles, the device is in an "extraction configuration".

[0026] "First" and "second", or "upper" and "lower", or "right" and "left" are used to distinguish corresponding elements from each other and do not limit the present invention.

[0027] In this description, unless otherwise specified, "comprising" does not imply exclusivity.

[0028] Other features and advantages of the present invention will become apparent by reading the following non-limiting detailed description and considering the non-limiting accompanying drawings.

Brief Description of the Drawings

[0029]

Figure 1

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[0030] In the above figures, the same reference numerals are used to denote the same or similar elements.

[0031] The device according to the present invention is particularly well - adapted for electroporation. In the present application, it preferably comprises an electric generator 2 configured for electroporation of a pharmaceutical composition, a support 4, and first and second combs 6a and 6b movable along a sliding direction Δ6.

[0032] The first and second combs 6a and 6b each comprise first and second electrode needles 8a and 8b. All of these electrode needles are electrically connected to a first terminal 9a of the electric generator 2. Together, they define an invasive electrode.

[0033] The support 4 comprises a support base 10 and a flat electrode 12 fixed to the support base and electrically connected to a second terminal 9b of the electric generator, the second terminal having a polarity opposite to that of the first terminal.

[0034] Therefore, the electrical generator is adapted to polarize the flat electrode and the invasive electrode differently to generate an electric field that enables electrotransport.

[0035] Support Support base The support base 10 is preferably made of a polymer material. It is preferably made of a non-conductive material. It is preferably made of a transparent material for better observation by the user.

[0036] The support base defines a spherical base contact surface 18 that extends along a virtual sphere S having a radius of curvature R that is 10 mm to 15 mm, preferably 11 mm to 14 mm, preferably 12 mm to 13 mm, preferably about 12.5 mm. The virtual sphere S corresponds to the outer surface of the eye O in the service configuration such that the base contact surface can rest on this outer surface.

[0037] Therefore, the stability of the support on the eye is significantly improved.

[0038] To further improve the stability of the support on the eye, the spherical base contact surface 18 preferably carries one, preferably several, spikes that protrude from the surface and are designed to limit the sliding of the support on the eye. The support preferably has more than 2, more than 5, more than 10, more than 20 spikes. The height of the spikes is preferably more than 0.1 mm and / or less than 0.5 mm, or less than 0.3 mm.

[0039] Preferably, the base contact surface 18 is more than 50 mm 2 more than preferably 100 mm 2 more than preferably 120 mm 2 more than preferably 140 mm 2 more than preferably 150 mm 2 more than preferably 160 mm 2 more than and / or 200 mm 2Less than, preferably 180 mm 2 Having a surface area of less than. Preferably, the base contact surface 18 does not extend beyond one - quarter of a hemisphere.

[0040] When viewed from the front, the contact surface 18 can have a substantially parallelepiped contour, for example a rectangular contour, or a substantially trapezoidal contour.

[0041] Preferably, the support base 10 defines a circular rim 20 that partially defines the boundary of the contact surface 18 and extends within the rim plane P 20 and extends within the rim plane P.

[0042] The rim 20 has the shape of an arc of a circle C having an axis X and a radius R 20 and a radius R 20 The radius R 20 is greater than 5 mm, preferably greater than 5.5 mm, preferably greater than 5.8 mm, and less than 8.0 mm, preferably less than 7.0 mm, preferably less than 7.5 mm, preferably less than 6.0 mm. Such a rim has a shape that substantially corresponds to the edge of the eye. It can be placed in contact with this edge so as to partially surround the edge.

[0043] The stability of the support is significantly improved when the rim 20 is designed to rest on the edge of the eye.

[0044] Preferably, the rim extends laterally over an angular sector α greater than 45°, preferably greater than 60°, preferably greater than 80°, preferably greater than 100°, preferably greater than 120°, preferably greater than 130°, preferably greater than 135°, and / or less than 180°, preferably less than 170°, preferably less than 160°, preferably less than 150°, preferably less than 140° (see Figure 2). 20 extends laterally over an angular sector α (see Figure 2).

[0045] The support base may preferably comprise a support handle that is gripped, for example, between the thumb and index finger of one hand. However, preferably, the support handle is alternatively provided on the comb.

[0046] Flat electrode The flat electrode 12 is fixed to the support base 10. It defines a flat electrode contact surface 24 that is intended to rest on the outer surface of the eye at the service position. Therefore, it preferably extends along the virtual sphere S, as shown, for example, in FIG. 8.

[0047] The surface area of the flat electrode contact surface is preferably greater than 3 mm 2 greater than 4 mm 2 greater than 5 mm 2 greater than 6 mm 2 greater than 8 mm 2 greater than 10 mm 2 greater than 11 mm 2 greater than 12 mm 2 greater than 15 mm 2 greater than 17 mm 2 greater than and / or less than 90 mm 2 less than 60 mm 2 less than 30 mm 2 less than 20 mm 2 and less than.

[0048] Preferably, the flat electrode contact surface 24 does not extend beyond one quadrant of a hemisphere. Preferably, it is within an angular sector α centered on the axis X of the rim that is less than 90°, preferably less than 60°, preferably less than 50°, preferably less than 45°, preferably less than 35°, preferably less than 30°, and / or preferably greater than 10°, preferably greater than 15°, preferably greater than 20° (see FIG. 1). 24 and extends therein (see FIG. 1).

[0049] In a front view, the flat electrode contact surface preferably has a substantially rectangular shape.

[0050] The radius of curvature R is large with respect to the surface area of the flat electrode contact surface, and thus the flat electrode contact surface extends substantially within a general flat electrode plane P 24 and extends therein.

[0051] Preferably, the distance between any point on the rim 20 and the flat electrode contact surface 24 is greater than 2 mm, preferably greater than 2.5 mm, preferably greater than 3 mm, preferably greater than 3.5 mm, preferably greater than 4.0 mm, and / or less than 6 mm, preferably less than 5 mm, preferably less than 4.5 mm.

[0052] The flat electrode 12 can be a conductive layer that partially covers the support base. Preferably, it is not integral with the support base, i.e., it is initially separate from the support base and then is the part that is attached to the support base.

[0053] Comb The first comb 6a and the second comb 6b are very similar or identical and are assembled on the support in the same or very similar manner. Therefore, only the first comb and its configuration are described in detail hereinafter.

[0054] The reference numeral of the second comb is the same as that of the first comb, but with the subscript "b" instead of "a".

[0055] The first comb 6a has a first comb base 30a and a linear first electrode needle 8a fixed to the first comb base 30a and preferably a first guide rod 32a fixed to the first comb base 30a and preferably a first elastic member, such as a helical spring 34a or a flat spring, configured to forcibly move the first electrode needle towards its extraction position and comprises.

[0056] Preferably, all of the first electrode needles have the same structure.

[0057] Preferably, the diameter of the first electrode needle, preferably any one of the first electrode needles, is less than 0.5 mm, preferably less than 0.4 mm, preferably less than 0.35 mm. This property is particularly advantageous when the electrode needle is inserted into the eye in a substantially tangential direction with respect to the surface of the eye, as in the preferred embodiment. For the same reason, the first tip 36a of the first electrode needle, preferably any one of the first electrode needles, is preferably beveled.

[0058] The first comb may include one or several, preferably 3, 4 or 5, preferably 4, preferably parallel, preferably in the same plane, preferably linear, first electrode needles 8a. The distance between the axes of two adjacent parallel first electrode needles 8a is preferably greater than 0.5 mm, preferably greater than 0.6 mm, preferably greater than 0.7 mm, preferably greater than 0.8 mm, and / or less than 5 mm, preferably less than 3 mm, preferably less than 1.5 mm, preferably less than 1.2 mm, preferably less than 1.0 mm, preferably less than 0.9 mm.

[0059] Preferably, the first electrode needle 8a extends in a first needle plane P8, and the first needle plane P8 forms an angle greater than 40°, greater than 45°, preferably greater than 50°, and / or less than 80°, preferably less than 70°, preferably less than 60°, preferably less than 55° with the rim plane P of the rim 20. 20 Preferably, the first needle plane P8 is substantially perpendicular to the median radial plane Pm of the rim, that is, the plane including the axis X and including a point in the middle length of the rim (the 90° angle θ in FIG. 1). In other words, the first electrode needles are in the same plane as each other, and preferably each extends substantially parallel to the plane P of the rim.

[0060] Preferably, the first needle plane P8 is substantially perpendicular to the median radial plane Pm of the rim, that is, the plane including the axis X and including a point in the middle length of the rim (the 90° angle θ in FIG. 1). In other words, the first electrode needles are in the same plane as each other, and preferably each extends substantially parallel to the plane P of the rim. 20 Preferably, the first electrode needles each extend substantially parallel to the flat electrode 12. The angle between the first needle plane P8 and the flat electrode plane P 20 is preferably greater than 40°, greater than 45°, preferably greater than 50°, and / or less than 80°, preferably less than 70°, preferably less than 60°, preferably less than 55°.

[0061] Preferably, the first electrode needles each extend substantially parallel to the flat electrode 12. The first needle plane P8 and the flat electrode plane P 24The angle between them is preferably less than 20°, preferably less than 15°, preferably less than 10° or less than 5°. The first needle plane P8 is preferably substantially parallel to the flat electrode plane P 24 with respect to it.

[0062] The distance δ between these two planes is preferably 2.0 - 1.3 mm, preferably 1.8 - 1.5 mm, preferably 1.7 - 1.0 mm, preferably about 1.65 mm.

[0063] Each first electrode needle 8a is movable and is guided within the guide of the support base 10 by the sliding of the first guide rod 32a between a first insertion position (i.e., the extreme position where the electrode needle protrudes into the virtual sphere S, i.e., limited by contact) and a first extraction position where the electrode needle does not protrude.

[0064] Preferably, at the first insertion position, any first electrode needle defines an angle ω that is less than 40°, preferably less than 25°, preferably less than 10° with respect to the outer surface of the eye. Therefore, the first electrode needle enters the eye substantially in a tangential direction.

[0065] Preferably, the length of the first electrode needle is determined such that, at the insertion position, when viewed from the front, i.e., perpendicular to the first needle plane P8, the first electrode needle 8a appears to substantially completely cross the flat electrode contact surface (i.e., extend from one side of the flat electrode contact surface to the opposite side).

[0066] Preferably, the length of the first electrode needle is greater than 4 mm, preferably greater than 6 mm, preferably greater than 8 mm, preferably greater than 10 mm, preferably greater than 11 mm, and / or less than 15 mm, preferably less than 14 mm, preferably less than 13 mm.

[0067] Preferably, the first comb 6a comprises a first comb handle 38a extending substantially parallel to the median radial plane of the rim and preferably substantially perpendicular to the first needle plane P8, so that the operator can push the first comb 6a towards the support without being obstructed by the patient's nose.

[0068] Preferably, the force required to move the first comb against the spring 34a is greater than 1 Newton, preferably greater than 4 Newtons, and / or less than 20 Newtons, preferably less than 10 Newtons. Advantageously, the spring 34a limits the risk of injury when the operator operates the device.

[0069] The second comb is similar to the first comb and is preferably substantially identical. Preferably, the second comb base is configured to be substantially symmetric with the first comb base with respect to the median radial plane of the rim at the insertion positions of the first and second needles.

[0070] The second electrode needle extends in a second needle plane parallel to, preferably identical to, the first needle plane. To avoid collision between the first electrode needle and the second electrode needle, their respective axes must be offset. Preferably, they are interleaved with each other, i.e., in the needle plane, the first electrode needle alternates with the second needle as shown in Figure 5a.

[0071] Preferably, as shown in Figure 1, the second comb 6b comprises a second comb handle 38b, preferably a second comb handle 38b parallel to the first comb handle 38a. The convergence of the two combs towards the support, i.e., the movement when the combs are pushed towards the support, is made easier and possible with one hand.

[0072] According to the present invention, at the puncture position where the flat electrode contact surface 24 is placed on the outer surface of the eye, and the rim 20 is placed on the edge of the eye, and the tips of the first and second electrode needles are placed on the outer surface of the eye, the two combs are slidable relative to the support so that the first and second tips can push the eye when the first and second combs are simultaneously pushed toward the support.

[0073] At the puncture position, the first and second electrode needles extend along the first and second insertion axes Δ 8a and Δ 8b and are placed on the virtual sphere S at the first and second insertion points M 8a and M 8b .

[0074] All of the first tips 36a of the first electrode needle together exert a first pushing force F 36a along the first pushing axis Δ 36a acting on the first pushing point M 36a .

[0075] All of the second tips 36b of the second electrode needle together exert a second pushing force F 36b along the second pushing axis Δ 36b acting on the second pushing point M 36b .

[0076] The first and second pushing axes Δ 36a and Δ 36b are substantially parallel to the first and second insertion axes.

[0077] The angle between the planes perpendicular to the first and second pushing axes is preferably less than 40°, preferably less than 20°, preferably less than 10°, preferably less than 5°. The first pushing axis and the second pushing axis are preferably parallel. Preferably, the distance between the first pushing axis and the second pushing axis is less than 5 mm, preferably less than 3 mm, preferably less than 1 mm. Preferably, the first pushing axis and the second pushing axis are aligned in a row.

[0078] Thereby, the risk of rotation of the eye during the insertion of the electrode needle is significantly reduced.

[0079] Injection needle Preferably, the device comprises an injection needle 42. The injection needle may in particular have one or several features of the injection needles disclosed in International Application No. PCT / EP2016 / 058138, International Publication No. 2009 / 122030 pamphlet, or U.S. Patent Application No. 12 / 921,979, which are incorporated herein by reference. It preferably comprises, conventionally, an injection channel having a discharge orifice.

[0080] The injection needle is preferably neither the first electrode needle nor the second electrode needle.

[0081] It is guided by the support base 10 between the capture position and the injection position. The injection position is preferably defined such that the discharge orifice comes between the first needle plane P8 and the flat electrode plane P 24 and preferably at an intermediate length between those planes, preferably substantially opposite the center of the flat electrode contact surface. At the injection position of the injection needle, the injection needle preferably extends parallel to the electrode needle.

[0082] Preferably, the injection needle is configured such that when the flat electrode extends in contact with the outer surface of the eye, and the rim extends on the edge of the eye, and the injection needle is fully inserted, the discharge orifice of the injection needle opens into the ciliary muscle of the eye.

[0083] Pharmaceutical composition The object to be injected can in particular be any of the pharmaceutical compositions described in WO 2006 / 123248, which is incorporated herein by reference, in particular a nucleic acid for the treatment of interest, preferably a deoxyribonucleic acid (DNA) molecule (cDNA, gDNA, synthetic DNA, artificial DNA, recombinant DNA, etc.), or a ribonucleic acid (RNA) molecule (mRNA, tRNA, RNAi, RNAsi, catalytic RNA, antisense RNA, viral RNA, etc.). In one embodiment, the composition contains circular DNA fragments.

[0084] In a particularly preferred embodiment, the polynucleotide is a double-stranded circular DNA, such as a plasmid, encoding a bioactive substance for the object. Preferred bioactive substances include, but are not limited to, the bioactive polypeptides or proteins disclosed in WO 2006 / 123248.

[0085] In another particular embodiment, the electroporation device of the present invention is particularly suitable for performing gene replacement. Therefore, the nucleic acid can encode a viable protein so as to replace a defective protein that is naturally expressed in the target tissue. Typically, the defective genes that can be replaced include, but are not limited to, the genes causing the diseases disclosed in WO 2006 / 123248.

[0086] Kit According to the present invention, a kit is envisioned. Such a kit comprises a device and a pharmaceutical composition according to the present invention, and optionally an instruction manual.

[0087] The pharmaceutical composition is preferably selected from the pharmaceutical compositions described above.

[0088] Within the kit, the components can be packaged or contained separately.

[0089] The instructions can be in the form of a written document, video, or audio, and can be included as a reference to paper, electronic media, or even another source, such as a website or reference manual.

[0090] Similarly, other components, such as excipients, carriers, other drugs or adjuvants, instructions for the administration of the active substance or composition, and administration or infusion devices can be supplied within the kit.

[0091] Method The method of the present invention can be used to treat eye diseases in a subject, where the pharmaceutical composition is preferably selected from the pharmaceutical compositions described above in this specification.

[0092] To use the electroporation device according to the present invention, the operator can proceed with the following steps.

[0093] First, the operator connects a reservoir filled with the pharmaceutical composition to the injection needle, and electrically connects the first electrode (all of the electrode needles 8a and 8b) and the second electrode (flat electrode 12) to the first terminal and the second terminal of the generator 2.

[0094] Initially, the first and second electrode needles are in the first and second extraction positions, preferably partially within the support base 10. The rigidity of the springs 34a and 34b is determined such that both the first and second electrode needles are maintained in the extraction positions, especially when the operator operates the device by means of the handles 38a and 38b.

[0095] To position the device, the operator places the rim 20 on the edge of the eye O. Placing the rim 20 on the corneal edge and placing the spherical flat electrode contact surface 24 on the sclera ensures good stability and very accurate positioning of the device. Since the angle between the electrode needles 8a and 8b and / or the injection needle 42 on one hand and the spherical flat electrode contact surface on the other hand is very small at the insertion point, i.e., the needles are inserted almost tangentially to this surface, which makes the insertion difficult, stabilization is very important for this particular application.

[0096] Next, the operator presses the first and second combs 6a and 6b towards each other against the action of the first and second springs 34a and 34b respectively until they are in the puncture configuration, where the electrode needles are at their respective puncture positions and their respective tips are in contact with the outer surface of the eye.

[0097] In the puncture configuration, when the operator continues to press the first and second combs 6a and 6b towards each other, the operator applies a push to the eye. This push is the result of the action of the first electrode needle, which, along with the reaction of the second electrode needle, is a first pushing force acting along the first pushing axis Δ 36a at the first pushing point M 36a and the reaction is a second pushing force acting along the second pushing axis Δ 36b at the second pushing point M 36b on the eye.

[0098] The spring stiffness is determined such that the tips of both the first and second electrode needles contact the outer surface before either of them punctures the outer surface of the eye. Preferably, the force applied to the first comb 6a by the first spring 34a is the same as the force applied to the second comb 6b by the second spring 34b, and thus the tips of both the first and second electrode needles contact the outer surface of the eye substantially simultaneously. Therefore, at the puncture position, they press against the said surface, which effectively prevents rotation of the eye with respect to the support base 10.

[0099] Next, the operator continues to press the first and second combs 6a and 6b towards each other until the electrode needle penetrates the outer surface of the eye.

[0100] The guide rods 32a and 32b are slidably attached to the support base 10 and guide the movement of the electrode needle until they reach their respective insertion positions.

[0101] Next, the first and second electrode needles together define a grid that extends substantially parallel to the flat electrode contact surface 24 along the entire length of the flat electrode contact surface 24.

[0102] Preferably, the first and second electrode needles are staggered as shown in FIG. 5a, B of FIG. 23, or D of FIG. 23.

[0103] Alternatively, at their respective inserted positions, the first and second electrode needles are not staggered but are adjacent to each other as shown in FIG. 5b, A of FIG. 23, or C of FIG. 23. The distance between the tip of the first electrode needle, or "first tip", and the tip of the second electrode needle, or "second tip", is preferably less than 2 mm, 1 mm, less than 0.5 mm, and preferably less than 0.2 mm. The first tip of the first electrode needle may face the second tip of the second electrode needle as in FIGS. 5b and C of FIG. 23, or may not face as shown in C of FIG. 23.

[0104] Next, the operator inserts the injection needle to the corresponding injection position within the corresponding insertion guide. The prior insertion of the electrode needle allows for a very stable position of the support during the insertion of the injection needle.

[0105] In one embodiment, the injection needle includes a needle stop for determining an injection position in front of the grid of the electrode needle, preferably in front of the center of the grid, where one or more of the discharge orifices open into the ciliary muscle.

[0106] Next, the operator can inject the composition.

[0107] Next, the device is in the service configuration and the operator sends a suitable electrical signal, such as a suitable electrical impulse, to create an electric field within the injection zone that promotes electroporation using the generator.

[0108] In certain embodiments, an electric field composed of one or more electrical pulses is applied as described in International Application No. PCT / EP2016 / 058138.

[0109] When the electroporation of the object is complete, the operator electrically disconnects the electrode and the generator.

[0110] As is clear here, the device according to the invention enables the following. Restriction or even suppression of any rotation of the eye while the needle is inserted into the eye, Intervention by a single operator, Accurate and stable positioning of the electrode, Accurate guidance of the invasive electrode while entering the eye, Accurate injection into the eye relative to the edge, Efficient and homogeneous generation of a large electric field.

[0111] Of course, the invention is not limited to the described, illustrated embodiments provided as examples.

[0112] In particular, various embodiments can be combined.

[0113] Also, any feature of the device disclosed in International Application No. PCT / EP2016 / 058138 can be applied to the device according to the invention, except when it is not compatible with the invention.

[0114] Also, the handling means is not limited to the comb handle 38a described above in this specification.

[0115] In addition, the device preferably includes a synchronization mechanism 50 for synchronizing the movement of the first and second comb bases from the first and second extraction positions to the first and second insertion positions, respectively. Preferably, the synchronization mechanism 50 also synchronizes the movement of the first and second comb bases from the first and second insertion positions to the first and second extraction positions, respectively.

[0116] Preferably, the first and second comb bases are rotatably mounted on the support base about a common axis Y, and the device includes a synchronization linkage for mechanically linking the movement of the first and second comb bases.

[0117] The synchronization linkage preferably includes a connector 54, preferably a rigid connector, configured to slide simultaneously on the first and second comb bases, preferably on the first and second guide rails 56 of the first and second comb bases (FIGS. 8 and 9), or outside the first and second surfaces 571 and 572 of the first and second comb bases (FIGS. 10 and 11).

[0118] The connector 54 preferably has a "Y" shape. In particular, the first and second branches of the connector 54 can define first and second pins 58 that slide within the first and second guide rails 56 of the first and second combs (FIG. 8).

[0119] In particular, the device of FIG. 8 includes a support base 10, a push button 60 slidably and elastically attached to the support base 10, and a connector 54. The connector 54 has a "Y" shape and is rigidly fixed to the button 60, and the first and second pins 58 cooperate with the first and second comb bases such that the sliding movement of the button 60 is coupled to the movement of the first and second comb bases between the first and second insertion positions and the first and second extraction positions, respectively.

[0120] More precisely, the first and second comb bases are rotatably mounted on the support base about a common axis Y and define first and second guide rails 56 for the first and second pins 58 of the first and second branches of the connector 54, i.e., the branches form an inverted "V". Thereby, the translation of the rod 54 along its axis Z relative to the support base 10 is converted into a synchronized rotational movement of the first and second comb bases.

[0121] The device may comprise first and second arms 611 and 612 respectively supporting the first and second comb bases, wherein the movement of the second arm is guided relative to the first arm. Preferably, the second arm is rotatably attached to the first arm about an axis W, particularly like the two arms of a pair of tweezers, as shown in FIG. 14.

[0122] The movements of the first and second arms may be independent of each other. In particular, the first and second arms may be rotatably mounted on the support base about respective and different axes W1 and W2, as shown in FIG. 15.

[0123] Alternatively, the first and second arms may be attached to the support base so as to be movable relative to the support base by translating, preferably along a common direction (the horizontal direction in FIGS. 16 and 17), as shown in FIGS. 16 and 17.

[0124] Preferably, the first and second electrode needles are circular in shape, i.e., extend along a circle C (see FIG. 11). The axis Y preferably intersects the center of the above circle. The insertion axis of the curved electrode needle is the local direction of the electrode needle at the insertion point. Therefore, when the axis Y intersects the center of the above circle, the insertion axes of the first and second electrode needles do not change during the insertion operation, and thus the entry of the first and second electrode needles is less harmful to the patient.

[0125] The operator can act directly on the comb base, as in the example of FIG. 9 (see the arrow), and / or the device preferably controls the synchronization mechanism (e.g., FIGS. 8 or 9), or acts directly on the first and second comb bases (FIGS. 14 to 17), and is provided with an actuator 60. The actuator 60 can be, for example, a push button or a slider.

[0126] Preferably, the device is provided with a spring 62 in order to be able to automatically move the first and second electrode needles towards the first and second extraction positions respectively. Therefore, the action of the spring is opposite to any action of the operator on the comb base for inserting the first and second electrode needles, either directly or via the actuator.

[0127] The spring 62 can be placed between the synchronization mechanism and the support base, for example, between the actuator 60 and the support base 10 (FIG. 8), or between the first comb base and the second comb base.

[0128] In the embodiment of FIG. 11, the spring 62 is an elastic joint 62' connecting the first and second comb bases. The first and second comb bases and the elastic joint can be leaf springs.

[0129] In a preferred embodiment, the device is provided with an actuatable lock 64 for locking the synchronization mechanism, preferably the actuator 60 or the connector 54, or more generally the first and second electrode needles, in a certain configuration, preferably at least in the extraction configuration and / or the insertion configuration.

[0130] In the embodiment of FIG. 9, the lock 64 is actuated when the operator pulls the knob 65, so that the projection 67 of the connector 54 is forced through the opening 69 of the base support.

[0131] In a preferred embodiment, the device is provided with a drive mechanism 66 for controlling the insertion depth of the electrode needles during insertion into the eye.

[0132] FIG. 12 shows an example of a drive mechanism 66 having a ratchet 68 configured to lock the connector in a predetermined position in cooperation with the teeth 70 of the connector 54. The number of predetermined positions, i.e., the number of teeth of the ratchet, is preferably more than 2, more than 5 or more than 10, and / or less than 1000, less than 500, less than 100, or less than 50. The connector 58 can be unlocked by pressure on a button 60 accessible to the operator's hand through an opening 74 in the support base 10 (see the vertical arrow in FIG. 12). The opening 74 allows translation of the connector 58 relative to the support base 10 for changing the position of the connector (see the horizontal arrow in FIG. 12).

[0133] FIG. 13 shows an example of a drive mechanism 66 having a toothed plate 76 formed on the connector 54 and driven in translation by the teeth of a first pinion 78. In the embodiment of FIG. 13, a second pinion 80 is mechanically connected to the first pinion 78 and the actuator 60 (i.e., the thumbwheel) accessible to the operator's hand through the opening 74 in the support base 10. When the operator turns the actuator 60 and thus turns the second pinion 80 (see the arrow in FIG. 13), the connector 54 moves in translation.

[0134] Further improvements Summary of the further improvements According to a further improvement, the present invention also a support having a support base, wherein the support base a spherical base contact surface extending along a virtual sphere having a radius of 10 - 15 mm so as to fit the outer surface of the eye, and a circular rim having a radius greater than 5 mm and less than 8 mm and extending in the rim plane so as to fit the edge of the eye, along the axis X, defining a first needle having a first tip, wherein the first needle passes through a first intermediate puncture position on the support and a first extraction position where the first needle is outside the virtual sphere, between a first insertion position where the first needle is inserted maximally into the virtual sphere and is movable, at the first intermediate puncture position, the first tip is located at a first insertion point belonging to a first hemisphere of the virtual sphere, a device comprising the device comprises an opposing base defining an opposing contact surface extending along a second hemisphere of the virtual sphere, the first and second hemispheres being separated by the median radial plane of the rim, the first needle is movable on the support, such that during an insertion movement starting from the first extraction position and ending at the first insertion position, the first needle and the opposing contact surface push, i.e., "pinch", the virtual sphere towards the median radial plane of the rim when the first needle reaches the first intermediate puncture position, regarding the above device.

[0135] The device according to the further improvement may also have one or several of the following optional and preferred features: the opposing contact surface includes a point that is symmetric with respect to the median radial plane of the rim to the insertion point of the first needle; the opposing contact surface includes a point at the intersection of the virtual sphere and a first insertion axis along which the first needle locally extends at the first insertion point at the first intermediate puncture position; the opposing contact surface carries at least one spike protruding from the opposing contact surface and configured to limit the sliding of the support on the eye, the spike preferably having a height greater than 0.1 mm and less than 0.5 mm; the opposing base is movable on the support base, preferably rotatably attached to the support base or fixed relative to the support base, and the opposing base may be part of the support base; The device preferably comprises several first needles, preferably at least three first needles, fixed to a common first comb base, extending parallel to each other, preferably within a common first needle plane, such that at the first insertion position, they extend substantially parallel to a flat electrode contact surface defined by a flat electrode fixed to the support base and extending along the virtual sphere. The device comprises a synchronization mechanism for synchronizing the movement of one or more of the first needles and the opposing base during the insertion operation.

[0136] This device may also comprise one or several features of other embodiments of the present invention.

[0137] Detailed description of the further improvements The basic principle of the present invention is to "push" the eye during the insertion operation of the electrode needles in order to immobilize and stabilize the support above the eye. As explained above, according to a preferred embodiment of the present invention, the first and second combs are used for this pushing.

[0138] In an alternative embodiment, all of the electrode needles of the device are carried by the first comb base, and the second comb is replaced by an opposing base for counteracting, i.e., opposing, the action of the first electrode needles on the eye.

[0139] The opposing base can be fixed relative to the support, at least during the insertion operation, as in the embodiments of FIGS. 18 to 20.

[0140] An example of such an alternative embodiment is shown in FIG. 18. This embodiment is similar to the embodiment of FIG. 8, but the second comb is replaced by an opposing base 90. There is no second electrode needle.

[0141] All of the features described above that are not directly or indirectly related to the second needle can be applied to this alternative embodiment.

[0142] The opposing base 90 is relative to the median radial plane Pm of the rim 20 and defines an opposing contact surface 92 that includes a point M that is symmetric with the insertion point M of at least one first electrode pin 8a of the at least one first electrode pin 92 in the median radial plane Pm of the rim

[0143] Preferably, the device comprises several parallel first electrode pins fixed to a common first comb base. Preferably, the first electrode pins are arranged to extend in a plane facing the flat electrode 12 at the first insertion position, preferably substantially parallel to the flat electrode, as shown for example in FIG. 19

[0144] Along a direction D perpendicular to the general plane P8 (first needle plane) of the first electrode pin at the first insertion position, the opposing contact surface 92 preferably extends beyond the insertion point M 8a and preferably beyond any insertion point of the first needle (see FIG. 19). Preferably, the distance d between the insertion point and the end 93 of the opposing contact surface 92 along the direction D 93 is greater than 1 mm, preferably greater than 2 mm, preferably greater than 3 mm, and / or less than 10 mm, preferably less than 5 mm

[0145] The opposing contact surface 92 is preferably part of the spherical base contact surface 18 of the support and extends along a virtual sphere S having a radius R of 10 - 15 mm to fit the outer surface of the eye

[0146] The opposing contact surface 92 may have a smooth surface with no roughness and is preferably a material that is not aggressive to the surface of the eye, such as a silicone polymer, sponge, particularly a synthetic sponge, polyester, polyorthoester, polymethyl methacrylate, or any other flexible medical grade polymer. Preferably, it carries one, preferably several, spikes 94 that protrude from the surface and are designed to limit the sliding of the support on the eye (FIG. 19). The opposing contact surface 92 preferably comprises more than 2, more than 5, more than 10, more than 20, and / or less than 1000, less than 500, or less than 100 spikes 94. The height of the spikes is preferably more than 0.1 mm and / or less than 0.5 mm or less than 0.3 mm.

[0147] FIG. 20 shows an exemplary embodiment of a device having an opposing contact surface 92 in the service position on the eye O.

[0148] When the support base 10 is maintained over the operator's eye and the operator pushes the first comb 6a towards the median radial plane Pm of the rim, i.e., when the first comb and the support base are pushed towards each other (see the large vertical arrow in FIG. 20), the opposing contact surface 92 reacts to the force exerted by the first needle and provides a force that at least partially antagonizes the eye. 20 When the support base 10 is maintained over the operator's eye and the operator pushes the first comb 6a towards the median radial plane Pm of the rim, i.e., when the first comb and the support base are pushed towards each other (see the large vertical arrow in FIG. 20), the opposing contact surface 92 reacts to the force exerted by the first needle and provides a force that at least partially antagonizes the eye.

[0149] The opposing base can be relatively movable with respect to the support base, at least during the insertion operation, as in the embodiment of FIG. 21.

[0150] This embodiment also explains how the movement of one or more of the first electrode needles and the movement of the opposing base can be synchronized by a synchronization mechanism similar to the mechanism described above for synchronizing the movement of the first and second electrode needles during the insertion operation.

[0151] In one embodiment, the device comprises the above-mentioned opposing base, but also comprises a second electrode needle, which can be particularly movable on the opposing base between the second extraction position and the insertion position.

[0152] All the features described previously may also be applicable to this last embodiment.

[0153] Of course, the present invention is not limited to the described and illustrated embodiments provided as examples.

[0154] In particular, various embodiments can be combined.

[0155] For any embodiment of the present invention, the plane perpendicular to the axis X, and the plane perpendicular to the overall direction of one or more of the first needles at the first insertion position, the angle between them is preferably greater than 70° and less than 110°, preferably greater than 80° and less than 100°.

[0156] For any embodiment of the present invention, the plane containing the axis X and perpendicular to the median radial plane of the rim, and the local direction of the first needle at the first insertion point of the first needle at the first intermediate puncture position, preferably the local direction of any of the first needles, and / or the overall direction of one or more of the first needles at the first insertion position the angle between them is less than 45°, preferably less than 30°, preferably less than 20°, preferably less than 10°, preferably less than 5°, preferably about 0°.

[0157] When the flat electrode 12 extends along the spherical virtual sphere S (Figure 8), it conforms to the surface of the eye, so the contact with the eye is uniform and comfortable, and the risk of injury is limited.

[0158] However, the flat electrode 12 does not necessarily extend along the spherical virtual sphere. In particular, it is advantageous for it to extend parallel to the first and / or second needles when the first and / or second needles are in their respective first and second insertion positions, i.e., when the first and / or second needles are in their first and second insertion positions, the flat electrode extends such that the distance between the flat electrode and the portion of the first and / or second needle facing the flat electrode is constant. The region facing the flat electrode when the first and / or second needles are in their first and second insertion positions is the vertical dotted line L in FIGS. 8 and 22 12 is bounded by.

[0159] Advantageously, the uniformity of the electric field between the invasive electrode created by the first and / or second needles and the flat electrode is improved.

[0160] In particular, in one embodiment, the first and / or second needles extend in a common plane when in their first and second insertion positions, and the flat electrode extends in a plane parallel to the plane of the first and / or second needles.

[0161] In one embodiment, when the first and / or second needles are in their first and second insertion positions, the first and / or second needles extend along a common sphere C 14 as shown in FIG. 22 or D in FIG. 23, and the flat electrode 12 extends along a sphere C 14 having the same center as the common sphere C 12 In this embodiment, therefore, the flat electrode 12 is convex. It protrudes within the virtual sphere S by a distance, for example, greater than 0.1 mm, greater than 0.2 mm, or greater than 0.5 mm. The distance δ between the first and / or second needles and the flat electrode 12 is constant and is the difference in the radii of the spheres C 14 and C 12 ​

Claims

1. A device comprising: a support (4) having a support base (10), where the support base (10) has: a spherical base contact surface (18) extending along a virtual sphere (S) having a radius (R) of 10 to 15 mm so as to conform to the outer surface of the eye, and A circular rim (20) having a radius greater than 5 mm and less than 8 mm and having an axis X and extending within a rim plane (P) so as to conform to the edge of the eye ２０ ). defining a first needle (8a) and a second needle (8b) each having a first tip and a second tip (36a; 36b), where the first needle and the second needle (8a; 8b) are on the support and pass through first and second intermediate puncture positions to first and second extraction positions where the first and second needles are respectively outside the virtual sphere, and first and second insertion positions where the first and second needles are respectively inserted maximally into the virtual sphere and are movable therebetween, At the first and second intermediate puncture positions, the first and second needles extend along first and second insertion axes (Δ ８ａ ; Δ ８ｂ ), respectively, and the first and second tips are located at first and second insertion points (M ８ａ ; M ８ｂ ), respectively, belonging to the first and second hemispheres of the virtual sphere. The first and second hemispheres are separated by a plane that includes the axis X and a central point in the middle length of the rim, that is, the median radial plane of the rim (Pm ２０ ). where the angle (θ) between the median radial plane of the rim and either of the first and second insertion axes is greater than 70° and less than 110°, the said device.

2. The device according to claim 1, wherein the angle is greater than 80° and less than 100°.

3. The device according to claim 1 or 2, wherein the first needle and the second needle are aligned in a row.

4. The angle between the rim plane and the first needle and / or the second needle is less than 20°, preferably less than 10°, preferably less than 5°, the device according to any one of claims 1 to 3.

5. To move the first and / or second needles towards the first and / or second extraction positions respectively, first and / or second elastic members (34 ａ ; 34 ｂ ) are provided, the device according to any one of claims 1 to 4.

6. The first and second elastic members are configured to apply substantially the same force to the first and second needles respectively, the said force being preferably greater than 1 Newton and less than 10 Newtons, the device according to claim 5.

7. When the first and second needles are respectively in the first and second insertion positions, the first needle extends substantially along the entire length of the second needle, and vice versa, the device according to any one of claims 1, 2, and 4 to 6.

8. When the first and second needles are respectively in the first and second insertion positions, the distance between the first tip of the first needle and the second tip of the second needle is less than 1 mm, preferably less than 0.5 mm, the device according to any one of claims 1 to 6.

9. A plurality of first needles, preferably extending in a first needle plane and preferably extending parallel to each other, and / or a plurality of second needles, preferably extending in a second needle plane and preferably extending parallel to each other, wherein all of the first needles and the second needles preferably extend in a common needle plane (P ８ ), preferably parallel to each other, the device according to any one of claims 1 to 8.

10. The first needle plane and / or the second needle plane and / or the common needle plane is / are An angle greater than 70°, greater than 80°, or greater than 85°, and / or less than 110°, less than 100°, or less than 95°, preferably about 90°, between the rim and the median radial plane thereof, and / or The rim plane (P ２０ ) forms an angle greater than 40° and less than 80° with it The device according to claim 9, which defines.

11. The device according to claim 9 or 10, wherein when the first and second needles are in the first and second insertion positions respectively, the first needle intersects the second needle.

12. An electroporation generator (2) having first and second terminals (9a, 9b) with different polarities, An invasive electrode electrically connected to the first terminal and having the first and second needles, A flat electrode (12) fixed to the support, connected to the second terminal, and defining a flat electrode contact surface (24) extending along the virtual sphere, wherein the dimensions of the flat electrode contact surface are preferably such that the flat electrode contact surface extends substantially within a general flat electrode plane. The device according to any one of claims 1 to 11, comprising.

13. The first needle plane and / or the second needle plane and / or the common needle plane is substantially parallel to the flat electrode plane, and / or The distance between the rim and any point on the flat electrode contact surface is greater than 2 mm and less than 6 mm. The device according to claim 12 when claims 9 and 12 are applied.

14. The device according to any one of claims 1 to 13, wherein the device comprises an injection needle, and the support base is adapted to guide the sliding of the injection needle (42) between a capture position where the tip of the injection needle is outside the virtual sphere (S) and an injection position where the tip of the injection needle is inside the virtual sphere (S).

15. The device according to claim 14 when claims 9 and 12 are applied, wherein at the injection position, a part of the injection needle extending inside the virtual sphere extends within a plane, preferably a median plane, between the common needle plane and the flat electrode plane.

16. A plane containing the axis X and perpendicular to the median radial plane of the rim, The local direction of the first needle at the first insertion point of the first needle, preferably the local direction of any first needle, and / or the local direction of the second needle at the second insertion point of the second needle, preferably the local direction of any second needle, The device according to any one of claims 1 to 15, defining an angle that is less than 45°, preferably less than 30°, preferably less than 20°, preferably less than 10°, preferably less than 5°, preferably about 0°.

17. A device, a support (4) having a support base (10), where the support base (10) extends along a spherical base contact surface (18) having a radius (R) of 10 to 15 mm along a virtual sphere (S) that fits the outer surface of the eye, and A circular rim (20) having a radius greater than 5 mm and less than 8 mm and having an axis X that extends within a rim plane (P ２０ ) and that fits the edge of the eye. defines, a first needle and a second needle (8a; 8b) each having a first tip and a second tip (36a; 36b), where the first needle and the second needle (8a; 8b) are on the support, via first and second intermediate puncture positions, the first and second extraction positions where the first and second needles are each outside the virtual sphere, and the first and second insertion positions where the first and second needles are each inserted maximally into the virtual sphere and are movable therebetween, At the first and second intermediate puncture positions, the first and second needles extend along first and second insertion axes (Δ ８ａ ; Δ ８ｂ ), respectively, and the first and second tips are located at first and second insertion points (M ８ａ ; M ８ｂ ), which belong to the first and second hemispheres of the virtual sphere, respectively. The first and second hemispheres are separated by a plane that includes the axis X and a center point in the middle length of the rim, that is, the mid-radial plane of the rim (Pm ２０ ). the first and second needles are movable on the support, such that during an insertion operation starting from the first and second extraction positions and ending at the first and second insertion positions, the first and second needles push the virtual sphere towards the median radial plane of the rim when the first and second needles reach the first and second intermediate puncture positions, the said device comprising.

18. The device according to any one of claims 1 to 17, wherein the first and second needles are curved.

19. The device according to claim 18, wherein the first and second needles extend along a common circle (C) and are arranged to rotate on the support.

20. The device according to claim 19, wherein the first and second needles are arranged to rotate on the support about a common axis of rotation (Y), and the distance between the center of the circle (C) and the axis of rotation is less than 5 mm.

21. One or more of the first needles are curved and the flat electrode is curved, such that the distance between any point of one or more of the first needles facing the flat electrode and the flat electrode is substantially constant, and / or one or more of the second needles are curved and the flat electrode is curved, such that the distance between any point of one or more of the second needles facing the flat electrode and the flat electrode is substantially constant, the device according to claims 18 to 20.

22. The first and second arms (61 １ , 61 ２ ) for supporting the first and second needles respectively, and The second arm is rotatably attached to the first arm about an axis (W), or The first and second arms are rotatably attached to the support base about respective different axes (W １ , W ２ ), or The device according to any one of claims 1 to 21, wherein the first and second arms are attached so as to translate on the support base along a common direction.

23. The device according to any one of claims 1 to 22, comprising a spring (62) that elastically presses the first and second needles respectively toward the first and second extraction positions.

24. The device according to any one of claims 1 to 23, comprising a synchronization mechanism that synchronizes the movement of the first and second needles during the insertion operation.

25. The device according to claim 24, wherein the synchronization mechanism comprises a connector (54) having first and second branches mechanically coupled to first and second comb bases where the first and second needles are rigidly fixed respectively.

26. The first and second branches define first and second pins (58) that slide within first and second guide rails (56) defined respectively by the first and second comb bases, or The first comb base and the second comb base are connected by an elastic joint (62'), and the first and second branches slide on the first and second comb bases respectively, thereby pushing the first and second comb bases against the action of the elastic joint. The device according to claim 25.

27. The device according to claim 26, wherein the first and second comb bases and the elastic joint together constitute a leaf spring.

28. At least in an extraction configuration where the first and second needles are in the first and second extraction positions, and / or in an insertion configuration where the first and second needles are in the first and second insertion positions, an actuatable lock (64) for locking the synchronization mechanism. The device according to any one of claims 24 to 27.

29. The device according to any one of claims 24 to 28, comprising an actuator (60) configured for an operator to act on the synchronization mechanism so as to move the first and second needles simultaneously.

30. The device according to any one of claims 1 to 29, comprising a drive mechanism (66) that defines a plurality of predetermined positions for the first and second needles.

31. A device, A support (4) comprising a support base (10), where the support base (10) is A spherical base contact surface (18) extending along a virtual sphere (S) having a radius (R) of 10 to 15 mm so as to conform to the outer surface of the eye, and A circular rim (20) having a radius greater than 5 mm and less than 8 mm and having an axis X that extends within a rim plane (P ２０ ) and that fits along the edge of the eye. defining a first needle (8a) having a first tip (36a), wherein the first needle (8a) is on the support and passes through a first intermediate puncture position, a first extraction position where the first needle is outside the virtual sphere, a first insertion position where the first needle is inserted maximally into the virtual sphere is movable between, At the first intermediate puncture position, the first tip is located at a first insertion point (M ８ａ ) that belongs to the first hemisphere of the virtual sphere, The device comprises an opposing base defining an opposing contact surface extending along a second hemisphere of the virtual sphere, the first and second hemispheres being separated by a plane containing the axis X and a central point at the mid-length of the rim, i.e., the mid-radial plane of the rim (Pm ２０ ), the first needle is movable on the support, whereby during an insertion operation starting from the first extraction position and ending at the first insertion position, the first needle and the opposing contact surface push, i.e., clamp, the virtual sphere towards the median radial plane of the rim when the first needle reaches the first intermediate puncture position, comprising the said device.

32. The opposing contact surface (92) is, relative to the median radial plane (Pm ２０ of the rim, a point (M ８ａ ) that is symmetric with respect to the insertion point (M ９２ ) of the first needle, the device according to claim 31.

33. The opposing contact surface (92) includes a point (M ８ａ ), which is at the intersection of the virtual sphere and a first insertion axis (Δ ９２ ) along which the first needle extends at the first intermediate puncture position. The device according to claim 32

34. The device according to any one of claims 31 to 33, wherein the opposing contact surface (92) carries at least one spike (94) protruding from the opposing contact surface and configured to limit sliding of the support on the eye, the spike having a height greater than 0.1 mm and less than 0.5 mm.

35. The device according to any one of claims 31 to 34, wherein the opposing base is movable on the support base (10), preferably rotatably attached to the support base or fixed relative to the support base, and the opposing base can be part of the support.

36. The device according to claim 35, comprising a synchronization mechanism for synchronizing the movement of one or more of the first needles and the opposing base during the insertion operation.

37. a second needle (8b) having a second tip (36b), wherein the second needle (8b) is on the support and passes through a second intermediate puncture position, a second extraction position where the second needle is outside the virtual sphere, a second insertion position where the second needle is inserted maximally into the virtual sphere, is movable between, At the second intermediate puncture position, the second needle extends along a second insertion axis (Δ ８ｂ ), and the second tip is located at a second insertion point (M ８ｂ ) belonging to the second hemisphere. comprising the device according to any one of claims 31 to 36.

38. a second needle (8b) having a second tip (36b), wherein the second needle (8b) is on the support and passes through a second intermediate puncture position, a second extraction position where the second needle is outside the virtual sphere, a second insertion position where the second needle is inserted maximally into the virtual sphere, is movable between, At the second intermediate puncture position, the second needle extends along a second insertion axis (Δ ８ｂ ), and the second tip is located at a second insertion point (M ８ｂ ) belonging to the second hemisphere. The device according to any one of claims 30 to 35, which does not include

39. An electroporation generator (2) having first and second terminals (9a, 9b) with different polarities, An invasive electrode that is electrically connected to the first terminal and includes one or more of the first needles and, when claim 37 applies, one or more of the second needles, A flat electrode (12) that is fixed to the support, connected to the second terminal, and defines a flat electrode contact surface (24) that extends along the virtual sphere, where the dimensions of the flat electrode contact surface are preferably such that the flat electrode contact surface extends substantially within a general flat electrode plane, The device according to any one of claims 31 to 38, which includes

40. At the first insertion position, several first needles extending parallel to each other, preferably within a common first needle plane (P, extend substantially parallel to the flat electrode contact surface (24). ８ The device according to claim 39, comprising several first needles extending within).

41. The plane perpendicular to the axis X, The plane perpendicular to the overall direction of one or more of the first needles at the first insertion position, The angle between them is greater than 70° and less than 110°. The device according to any one of claims 1 to 40.

42. The plane that includes the axis X and is perpendicular to the median radial plane of the rim, The local direction of one or more of the first needles at one or more of the first insertion points of one or more of the first needles at the first intermediate puncture position and / or the overall direction of one or more of the first needles at the first insertion position, The angle between them is less than 45°. The device according to any one of claims 1 to 41.

43. The plane that includes the axis X and is perpendicular to the median radial plane of the rim, The local direction of one or more of the first needles at one or more of the first insertion points of one or more of the first needles at the first intermediate puncture position and / or the overall direction of one or more of the first needles at the first insertion position, The angle between them is less than 10°. The device according to claim 42.

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