Device for implanting a soft tissue probe

Abstract

Provided herein is a device (100) for implantation of a probe (400) within a soft tissue of a subject comprising: - a shooting tube (200) having a proximal end (10) and distal end (20) comprising a bore (210) having a distal opening (212), wherein the bore (210) is configured for guiding a pressurised gas (502) towards a projectile (300) disposed in the bore (210); and - the projectile (300), configured for propulsion by the pressurised gas (502) through the bore distal opening (212) and for penetration into the soft tissue; wherein the projectile (300) is attached to or configured for attachment to the probe (400).

Description

[0001] DEVICE FOR IMPLANTING A SOFT TISSUE PROBE

[0002] Field

[0003] The invention is broadly in the field of devices for implantation of a probe into soft tissue, in particular into an organ, in particular into a brain of a subject.

[0004] Background

[0005] Stiff probes that are not formed from conformable substrates are able to penetrate the soft tissue without a need for extra support of a carrier structure. However, micromotions of the soft tissue can create scars at an interface with the probe after implantation. Scarring reduces the quality of interaction and creates an inflammatory response.

[0006] Therefore, conformable probes with very small thicknesses are more suitable for implantation. The Young’s modulus and thickness of conformable neural probes impedes pushability. Thus, a carrier structure (such as a needle, microscopic glass pipet, etc) is typically used that provides a stiff tube for advancing probe in the tissue. The both insertion and withdrawal of the long carrier creates scarring, thereby the lowering the quality of stimulation and measurement and further increases inflammation. In particular, implantation of a neural probe requires a very thin probe which is difficult to implant without a carrier structure, whose use (of carrier structure) can increase scarring and inflammation.

[0007] Needed in the art is a device for delivery of a conformable probes that avoids the damage caused by carrier structures.

[0008] Summary

[0009] Provided herein is a device (100) for implantation of a probe (400) within a soft tissue of a subject comprising:

[0010] - a shooting tube (200) having a proximal end (10) and distal end (20) comprising a bore (210) having a distal opening (212), wherein the bore (210) is configured for guiding a pressurised gas (502) towards a projectile (300) disposed in the bore (210); and

[0011] - the projectile (300), configured for propulsion by the pressurised gas (502) through the bore distal opening (212) and for penetration into the soft tissue; wherein the projectile (300) is attached to or configured for attachment to the probe (400). Further provided herein is a device (100) for implantation of a probe (400) within a soft tissue of a human subject comprising:

[0012] - a shooting tube (200) having a proximal end (10) and distal end (20) comprising a bore (210) having a distal opening (212), wherein the bore (210) is configured for guiding a pressurised gas (502) towards a projectile (300) disposed in the bore (210); and

[0013] - the projectile (300), configured for propulsion by the pressurised gas (502) through the bore distal opening (212) and for penetration into the soft tissue;

[0014] - the probe (400); wherein:

[0015] - the projectile (300) is attached to the probe (400);

[0016] - the probe (400) is a neural probe; and

[0017] - the soft tissue is a soft tissue of a brain of the subject.

[0018] Preferably, the projectile (300) has a proximal end (10) and a distal (20) end, and the probe (400) is attached to or configured for attachment to the projectile (300) proximal end (20). Preferably, the projectile (300) has a proximal end (10) and a distal (20) end, and the probe (400) is attached to the projectile (300) proximal end (20).

[0019] Preferably, the device (100) is configured such that movement of the projectile (300) within the bore (210) is limited to longitudinal sliding of the projectile (300) and optionally to axial rotation of the projectile (300).

[0020] Preferably, the projectile (300) is disposed within a proximal (10) half of the bore (210) prior to propulsion.

[0021] Preferably, a longitudinal or maximum length of the projectile (300) is equal to or less than half of a longitudinal length of shaft (402) of the probe (400).

[0022] Preferably, the projectile (300) has at its distal (20) end a penetrative tip, configurated for penetration of the soft tissue.

[0023] The device (100) may further comprise the probe (400). Preferably, the probe (400) comprises:

[0024] - a probe shaft (402) having a proximal end (10) and distal end (20), and

[0025] - a tissue-interfacing element (410) which interacts with soft tissue and is disposed at a distal end (20) of the probe shaft (402).

[0026] Preferably, the tissue-interfacing element (410) comprises one or more electrical contacts for local detection of electrical current in the soft tissue, and / or for local electrical stimulation of the soft tissue.

[0027] Preferably, the shooting tube (200) bore (210) is configured to receive through an inlet port at the proximal end (10) of the bore (210), the pressurised gas (502) which causes the projectile (300) to be propelled through the bore distal opening (212) and to penetrate the soft tissue, thereby implanting the probe (400) attached to the projectile (300) in the soft tissue.

[0028] A quantity of shooting tubes (200) may be one or more than one and the bore (210) of each shooting tube (200) is disposed with a projectile (300) attached to the probe (400).

[0029] Further provided is a system (1000) for implantation of a probe (400) comprising:

[0030] - a device (100) as described herein; and

[0031] - a pneumatic propulsion unit (500) configured provide to the pressurised gas (502) to the bore (210) such that the projectile (300), propelled through the bore distal opening (212), is capable of penetrating the soft tissue and delivering the probe (400) attached to the projectile (300) to the soft tissue.

[0032] The pneumatic propulsion unit (500) may comprise:

[0033] - a reservoir (510) of compressed gas connected to the shooting tube (200);

[0034] - a controllable valve (520), configured to control flow of gas from the reservoir (510) to the shooting tube (200); and

[0035] - a controller (530) configured to control the controllable valve (520), such that the compressed gas in the reservoir (510) is released to provide to the pressurised gas (502) for propelling the projectile (300) through the bore distal opening (212). A shooting pressure - a pressure of gas in the reservoir (510) prior to release into the bore (202) of the shooting tube (200) - may be determined by a set of deployment parameters, wherein the set of deployment parameters comprises:

[0036] - desired travel distance of the projectile (300) into the soft tissue of the subject, and one or more of:

[0037] - one or more characteristics of the projectile (300);

[0038] - one or more characteristics of the probe (400);

[0039] - one or more characteristics of the shooting tube bore (210).

[0040] Preferably, the shooting pressure is determined from a trained machine learning model that predicts, from the set of deployment parameters, the shooting pressure for propelling the projectile (300) through the bore distal opening (212).

[0041] Further provided is a method for attaching a probe (400) to a projectile (300) so as to form a device (100) as described herein, comprising:

[0042] - providing the projectile (300) configured for propulsion by a pressurised gas (502) through the bore distal opening (212) of a shooting tube (200), and penetration into the soft tissue;

[0043] - providing the probe (400);

[0044] - attaching the projectile (300) to the probe (400) by injection over-moulding of the projectile (300) over a distal (20) end the probe (400).

[0045] Further provided is a method for implanting a probe (400) in a soft tissue of a subject comprising:

[0046] - providing a device (100) as described herein or a system (1000) as described herein;

[0047] - adjusting a pose of the bore (210) towards a target in the soft tissue of a subject;

[0048] - propelling the projectile (300) from the bore (210) using the pressurised gas (502) such that the projectile (300) and attached probe (400) penetrates the tissue of the soft tissue, thereby implanting the probe (400) in the soft tissue. Brief description of the drawings

[0049] The following description of the figures of specific embodiments of the invention is merely exemplary in nature and is not intended to limit the present teachings, their application or uses.

[0050] Fig. 1 is a longitudinal cross-sectional representation of device of as described herein, wherein the probe is not yet attached to the projectile.

[0051] Fig. 2 is a longitudinal cross-sectional representation of device of as described herein, wherein the probe is disposed within a bore of a shooting tube.

[0052] Fig. 3 is a longitudinal cross-sectional representation of device of as described herein, wherein the probe is disposed partly within and partly outside the bore of the shooting tube.

[0053] Fig. 4 is a longitudinal cross-sectional representation of a probe as described herein.

[0054] Fig. 5 is a longitudinal cross-sectional representation of a probe as described herein attached at its proximal end to an implantable interface module.

[0055] Fig. 6 is a schematic representation of a system as described herein.

[0056] Fig. 7 is a graph showing influence of shooting pressure on projectile insertion depth.

[0057] Description of embodiments

[0058] As used herein, the singular forms “a”, “an”, and “the” include both singular and plural referents unless the context clearly dictates otherwise.

[0059] The terms “comprising”, “comprises” and “comprised of” as used herein are synonymous with “including”, “includes”, “containing”, or “contains”, and are inclusive or open-ended and do not exclude additional, non-recited members, elements or method steps. The terms also encompass “constituted of”, “consists in”, “consisting of”, and “consists of’, and also the terms “consisting essentially of”, “consisting essentially in” and “consists essentially of’, which enjoy well-established meanings in patent terminology.

[0060] The recitation of numerical ranges by endpoints includes all intervening values between the lower and upper endpoints, as well as the recited endpoints. Intervening values may be integers or, where applicable, fractions, i.e., more broadly any real numbers such as any rational numbers. This applies to numerical ranges irrespective of whether they are introduced by the expression “from... to...” or the expression “between... and...” or another expression. Any numerical range recited herein is intended to include all sub- ranges subsumed therein. For example, each sub-range between any stated value in a stated range and any other stated value in that stated range is also specifically disclosed. Each sub-range between any stated value in a stated range and either the lower endpoint or the upper endpoint of the stated range is also specifically disclosed. The stated value may be an isolated value or an endpoint of a range subsumed by or overlapping with the stated range. For example, for a stated range with lower endpoint L1 and upper endpoint U1 (i.e. , stated range L1-LI1) and a stated sub-range nested within the stated range with lower endpoint L2 and upper endpoint U2 (i.e., stated sub-range L2-LI2), also specifically disclosed are the subranges L1-L2, L1-LI2, L2-U1 , and U2-LI1.

[0061] The terms “about” or “approximately” as used herein when referring to a measurable value such as a parameter, an amount, a temporal duration, and the like, are meant to encompass variations of and from the specified value, such as variations of + / -10% or less, preferably + / -5% or less, more preferably + / -1 % or less, and still more preferably + / -0.1 % or less of and from the specified value, insofar such variations are appropriate to perform in the disclosed invention. It is to be understood that the value to which the modifier “about” or “approximately” refers is itself also specifically, and preferably, disclosed.

[0062] Furthermore, the terms first, second, third and the like in the description and in the claims, are used for distinguishing between similar elements and not necessarily for describing a sequential or chronological order, unless specified. It is to be understood that the terms so used are interchangeable under appropriate circumstances and that the embodiments of the invention described herein are capable of operation in other sequences than described or illustrated herein.

[0063] Whereas the terms “one or more” or “at least one”, such as one or more members or at least one member of a group of members, is clear per se, by means of further exemplification, the term encompasses inter alia a reference to any one of said members, or to any two or more of said members, such as, e.g., any >3, >4, >5, >6 or >7 etc. of said members, and up to all said members. In another example, “one or more” or “at least one” may refer to 1 , 2, 3, 4, 5, 6, 7 or more.

[0064] As used herein, the term “and / or” when used in a list of two or more items, means that any one of the listed items can be employed by itself or any combination of two or more of the listed items can be employed. For example, if a list is described as comprising group A, B, and / or C, the list can comprise A alone, B alone, C alone, A and B in combination, A and C in combination, B and C in combination, or A, B, and C in combination.

[0065] The discussion of the background to the invention herein is included to explain the context of the invention. This is not to be taken as an admission that any of the material referred to was published, known, or part of the common general knowledge in any country as of the priority date of any of the claims.

[0066] Throughout this disclosure, various publications, patents and published patent specifications are referenced by an identifying citation. All documents cited in the present specification are hereby incorporated by reference in their entirety. In particular, the teachings or sections of such documents herein specifically referred to are incorporated by reference.

[0067] Unless otherwise defined, all terms used in disclosing the invention, including technical and scientific terms, have the meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. By means of further guidance, term definitions are included to better appreciate the teaching of the invention. When specific terms are defined in connection with a particular aspect of the invention or a particular embodiment of the invention, such connotation or meaning is meant to apply throughout this specification, i.e., also in the context of other aspects or embodiments of the invention, unless otherwise defined.

[0068] In the following passages, different aspects or embodiments of the invention are defined in more detail. Each aspect or embodiment so defined may be combined with any other aspect(s) or embodiment(s) unless clearly indicated to the contrary. In particular, any feature indicated as being preferred or advantageous may be combined with any other feature or features indicated as being preferred or advantageous.

[0069] Reference throughout this specification to “one embodiment”, “an embodiment” means that a particular feature, structure or characteristic described in connection with the embodiment is included in at least one embodiment of the present invention. Thus, appearances of the phrases “in one embodiment” or “in an embodiment” in various places throughout this specification are not necessarily all referring to the same embodiment, but may. Furthermore, the particular features, structures or characteristics may be combined in any suitable manner, as would be apparent to a person skilled in the art from this disclosure, in one or more embodiments. Furthermore, while some embodiments described herein include some but not other features included in other embodiments, combinations of features of different embodiments are meant to be within the scope of the invention, and form different embodiments, as would be understood by those in the art. For example, in the appended claims, any of the claimed embodiments can be used in any combination.

[0070] Similarly, it should be appreciated that in the description of illustrative embodiments of the invention, various features of the invention are sometimes grouped together in a single embodiment, figure, or description thereof for the purpose of streamlining the disclosure and aiding in the understanding of one or more of the various inventive aspects.

[0071] In the present description of the invention, reference is made to the accompanying drawings that form a part hereof, and in which are shown by way of illustration only of specific embodiments in which the invention may be practiced. Parenthesized or emboldened reference numerals affixed to respective elements merely exemplify the elements by way of example, with which it is not intended to limit the respective elements. Unless otherwise indicated, all figures and drawings in this document are not to scale and are chosen for the purpose of illustrating different embodiments of the invention. In particular the dimensions of the various components are depicted in illustrative terms only, and no relationship between the dimensions of the various components should be inferred from the drawings, unless so indicated.

[0072] While the invention has been described in conjunction with specific embodiments thereof, it is evident that many alternatives, modifications, and variations will be apparent to those skilled in the art in light of the foregoing description. Accordingly, it is intended to embrace all such alternatives, modifications, and variations as follows in the spirit and scope of the appended claims.

[0073] The terms "distal", “distally”, "distal to" or “distal end” are used throughout the specification, and are terms generally understood in the field to mean away (distal) from the user’s (e.g. practitioner’s) side of the device. The terms "proximal", “proximally”, "proximal to" or “proximal end” are used throughout the specification, and are terms generally understood in the field to mean towards (proximal the user’s (e.g. practitioner’s) side of the device. It is understood that components described herein (e.g. shooting tube, bore, projectile, probe) may each separately have a proximal end and a distal end, and the respective ends are denoted with the same numerical indicator (e.g. proximal (10), distal (20)).

[0074] The “subject” refers to a person receiving the implant. The subject is preferably a human subject. The “user” refers to a person or persons applying the implant or measurement tool. The user may be a surgeon, in particular neurological surgeon, clinician, physician, or medical assistant.

[0075] The term “longitudinal” means that refers to a direction of the device or its components in a proximal (10) to distal (20) direction (or vice versa). A dimension of the device in a longitudinal direction is greater than a dimension of the device is a direction perpendicular to the longitudinal direction.

[0076] A “transverse cross-section” refers to a cross section perpendicular to a longitudinal axis. A “longitudinal cross-section” refers to a cross section parallel to a longitudinal axis.

[0077] An “axial rotation” refers to a rotation of the projectile around a longitudinal axis, that is typically a central longitudinal axis of the projectile. Where the projectile has a circular transverse profile, the axial rotation is around an axis that passes through a centre of the circle.

[0078] Provided herein is a device (100) for implantation of a probe (400) within soft tissue of a subject in particular within an organ of the subject, more in particular within a brain of the subject. The device comprises a shooting tube (barrel) (200) and a projectile (300). The projectile (300) is attached to or is attachable to the probe (400). An example of the device is shown in FIGs. 1 to 3. The device is configured to propel the projectile (300) disposed in the shooting tube (barrel) (200) under force of a pressurised gas, such that it penetrates the exterior of the soft tissue (e.g. organ or brain) and delivers the probe (400) to its target.

[0079] By using a projectile that is longitudinally smaller than a carrier structure, there is a reduction in tissue trauma I scarring since the carrier structure is no longer needed. A longer carrier structure simultaneously scars all tissue in contact with the whole length of the carrier during insertion and withdrawal. Since the projectile is smaller than the carrier structure in longitudinal length, insertion of the foreign object causes little scar damage during passage through the tissue. Since there is no withdrawal of the projectile, scar damage is even further minimised. The device allows deployment of very thin probes that have no or insignificant pushability, meaning micromotions of the soft-tissue produces little or no scarring at an interface with the probe after implantation. As the procedure involves less parts ( / .e. no carrier structure), the surgical procedure is more simple, less parts are in contact with the soft tissue, and so there is a lower risk of microbial infection of the soft tissue.

[0080] The shooting tube (200) (also known as barrel) is longitudinal. The shooting tube (200) has a proximal end (10) and distal end (20). The shooting tube (200) comprises a shooting tube body (202) disposed with a bore (210).

[0081] A body of the shooting tube (200), shooting tube body (202), is longitudinal. The shooting tube body (202) has a proximal end (10) and distal end (20). The shooting tube body (202) is preferably linear. The shooting tube body (202) has a longitudinal direction which is in a proximal (10) to distal (20) direction (or vice versa).

[0082] The bore (210) is longitudinal. The bore (210) has a proximal end (10) and distal end (20). The bore (210) is preferably linear. The bore (210) has a longitudinal direction which is in a proximal (10) to distal (20) direction (or vice versa). The bore (210) is open at the distal end (20) i.e. is disposed with a distal opening (212). The bore (210) is configured for guiding a pressurised gas (502) towards the projectile (300) disposed in the bore (210).

[0083] The shooting tube (200) bore (210) is configured to receive through a proximal (10) opening (e.g. an inlet port), the pressurised gas (502) which causes the projectile (300) to be propelled through the bore distal opening (212) and to penetrate the soft tissue (e.g. of the organ, of the brain), thereby implanting the probe (400) attached to the projectile (300) in the soft-tissue.

[0084] The shooting tube (200) or shooting tube body (202), may be provided with an aperture (216) on a side wall (of the shooting tube body (202)) configured for passage of a longitudinal part of the (externally stored) probe (400) during propulsion of the neural probe (400) (see, for instance, FIG. 2). A quantity of shooting tubes (200) in the device (100) may be only one. Alternatively, a quantity of shooting tubes (200) in the device (100) may be more than one (e.g., > 2 and <5000, > 2 and <1000, > 2 and <500, > 2 and <100,) and the bore (210) of each shooting tube (200) is disposed with a (one) projectile (300) attached to a (one) probe (400). The more than one shooting tubes (200) may be arranged in an array (e.g. 1 x n, m x n)

[0085] A shape of a transverse cross-section of the shooting tube bore (210) may be any suitable for a shooting tube, e.g. circular, polygonal (e.g. hexagonal), oval.

[0086] A size and shape of a transverse cross-section of the shooting tube bore (210) is preferably constant along a longitudinal direction of the bore.

[0087] A size and shape of a transverse cross-section of the shooting tube bore (210) is matched to a (maximum) size and shape of a transverse cross-section of the projectile. By matched, it is meant a similar shape (e.g. both circular, both hexagonal, both oval), and the maximum size of a transverse cross-section of the projectile is smaller than a transverse cross-section of the shooting tube bore (210). The maximum size of the transverse cross-section of the projectile may be 0.5% to 10% smaller than the transverse cross-section of the shooting tube bore (210). Where the transverse crosssection of the shooting tube bore (210) and transverse cross-section of the projectile are both circular, the maximum size of the transverse cross-section of the projectile may be 0.1 % to 5% smaller than the maximum size of the transverse cross-section of the shooting tube bore (210).

[0088] As a general guidance, where the probe is a neural probe, a size of a transverse crosssection of the shooting tube bore (210) proximal (10) of the projectile (300) may be 20um2- 20mm2.

[0089] The shooting tube (200) or shooting tube body (202) is made from an expansionresistant material that resists expansion upon shooting. The shooting tube (200) may be rigid. The shooting tube (200) is made from a stiff material. Examples of materials include stainless steel, titanium, carbon fibers, metal powders (for Selective laser melting (SLM) or Direct metal laser sintering (DMLS)), ceramics, polymer. Examples of polymer include PLA (polylactic acid), ABS (Actylonitrile Butadine Styrene), PETG (polyethylene terephthalate glycol), Nylom (Polyamide), TPU / TPE (Thermoplastic Polyurethane / Elastomers), PEEK (polyether ether ketone), LILTEM (polyetherimide), or a combination or two or more of these.

[0090] The pressurised gas (502) travels in a proximal (10) to distal (20) direction along the shooting tube (200) bore (210). The pressurised gas (502) may be a compressed gas pulse or continuous stream of compressed gas. The pressurised gas in the bore (210) applies forces to the bore interior in addition to the projectile. As the projectile (300) is longitudinal slidable within bore (210), the force applied by the gas causes propulsion and sliding of the projectile (300) in a distal direction. The pressurised gas (502) may be any e.g. nitrogen, air, oxygen. It is preferably air which can be readily pressured e.g. using a pneumatic pump.

[0091] The skilled person can readily determine a pressure of gas entering the shooting tube proximal (10) opening in order to propel the projectile. As a general guidance, when the projectile is for a neural probe, a pressure of gas entering the shooting tube proximal (10) opening (e.g. an inlet port), may be 65 kPa - 1 MPa.

[0092] The projectile (300) is configured for propulsion by the pressurised gas (502) through the bore distal opening (212) and for penetration into soft tissue (e.g. of an organ, of the brain). The projectile (300) is attached to the probe (400) such that it remains attached to the projectile (300) under force of propulsion through the longitudinal bore (210) and soft tissue.

[0093] The projectile (300) has a proximal end (10) and a distal (20) end. The probe (400) is attached to the projectile (300) proximal end (10).

[0094] The projectile (300) typically has at its distal end (20) a penetrative tip (302), configured for penetration of the soft tissue (e.g. of an organ, of the brain). The penetrative tip (302) may have any suitable shape for tissue penetration for instance, tapered, or pointed, or rounded.

[0095] The projectile (300) has at its proximal end (10) a pressure-receiving surface for receiving the pressure of the pressurised gas (502). The pressure-receiving surface may have any suitable shape e.g. is flat, rounded (convex), rounded (concave). The projectile (300) may be disposed at any longitudinal position of the bore (210), for instance in a distal (20) half of the bore, in a proximal (10) half of the bore, or in at mid point of the bore (210). Preferably, the projectile (300) may be disposed in a proximal (10) half of the bore. The projectile (300) is preferably retained in the bore (210) (prior to propulsion) by friction.

[0096] The projectile (300) is disposed longitudinally slidable in the bore (210). Friction between the bore (210) interior wall (204) and the projectile (300) body may prevent the projectile (300) from freely sliding within the bore (210) under a force equal to or less than a force of gravity.

[0097] The movement of the projectile (300) within the bore (210) may be limited to longitudinal sliding of the projectile (300) and optionally to axial rotation of the projectile (300). Movement of the projectile (300), other than longitudinal sliding of the projectile (300) and optionally to axial rotation, are constrained by the interior wall (204) of the bore (210). A longitudinal length of the projectile (300) is such that tilting of the projectile (300) within the bore (210) is constrained.

[0098] The projectile (300) is attached or is attachable to the probe (400). The projectile (300) is attached at its proximal end (10) to the probe (400). The attachment may be achieved using any suitable method. The attachment of the probe (400) to the projectile (300) may be mechanical attachment (e.g. interlocking, form fitting parts, over-moulding). Injection over-moulding is a technique well known in the art (see, for instance, htps: / / en.wikipedia.org / wiki / lnjection mouldinq#overmoulding). The projectile (300) may be provided with a mechanical coupling (304) for the probe (see, for instance, FIG. 1). The attachment of the probe (400) to the projectile (300) may be chemical attachment (e.g. adhesive). The probe (400) may be permanently attached to the projectile (300). The probe (400) may be dismountably attached to the projectile (300).

[0099] The projectile (300) is attached to the probe (400) at a distal end (20) of the probe (400). The projectile (300) is attached to the probe (400) distal (20) of the tissue-interfacing element (410) of the probe (400).

[0100] As a general guidance where the soft tissue is soft tissue of the brain, a maximum size of a transverse cross-section of the projectile (300) may be a value in the range 19 .m2to 19.9 mm2. As a general guidance, a transverse cross-section of the projectile (300) preferably has a maximum width (e.g. diameter) in a range 5 .m to 5 mm.

[0101] A shape of a transverse cross-section of the projectile (300) proximal (10) of the penetrative tip may be any suitable for a probe such as circular, hexagonal, polygonal, oval, and the like.

[0102] The projectile may or may not be longitudinal. Where it is not longitudinal, it may be, for instance, spherical, polyhedral, or other irregular shape. Where it is longitudinal, it may contain a cylinder.

[0103] As a general guidance, where the soft tissue is soft tissue of the brain, a (longitudinal or maximum) length of the projectile (300) may be 0.05 cm to 5 cm. A (longitudinal or maximum) length of the projectile (300) is a fraction ( / .e. smaller than) of a longitudinal length of the probe shaft (402), for instance, equal to or less than 0.1 to 0.5 of the longitudinal length of the probe shaft (402), .

[0104] A size and shape of a transverse cross-section of the projectile (300) proximal (10) of the penetrative tip may be constant along a longitudinal direction of the shaft. A shape of the transverse cross-section of the projectile (300) may be any suitable for a probe such as circular, hexagonal, polygonal, oval, and the like.

[0105] The projectile (300) is made substantially from one or more biocompatible materials and is optionally coated with one or more biocompatible materials. Alternatively, the projectile (300) is made substantially from one or more other (less-biocompatible) materials and is coated with one or more biocompatible materials.

[0106] Additionally, it may be made substantially from one or more biodegradable materials. Examples of materials that are both biocompatible and biodegradable include Polyvinyl Alcohol (PVA), Polylactic Acid (PLA), Cellulose-based Materials, Polycaprolactone (PCL), Lignin-Based Composite, Chitosan, Gelatine, Alginate, Silk fibroin.

[0107] Additionally, it may be made substantially from one or more non-biodegradable materials. Examples of materials that are both biocompatible and non-biodegradable include Nylon (type of Polyamide), Thermoplastic Polyurethane (TPU), Polypropylene (PP), Polyethylene (PE), Polymethyl Methacrylate (PMMA), Epoxy resins, Metals {e.g. platinum), Metal Alloys {e.g. Titanium Alloy: Ti-6AI-4V, Magnesium Alloys).

[0108] Examples of other (less-biocompatible) materials include, Stainless Steel, Cobalt- Chromium Alloys, Nickel-Titanium Alloys, Polyurethane, Nickel, Chromium, and PVC. Chromium, Nickel, and Polyvinyl chloride (PVC) are non-biocompatible materials.

[0109] The probe (400) may be any type of soft-tissue implantable probe. The probe is configured to deliver local stimulation e.g. electrical, acoustic, ultrasonic, light, mechanical) to the soft-tissue and / or to measure local activity in the soft tissue {e.g. electrical, chemical, mechanical). The probe (400) is typically longitudinal. The probe (400) may be a neural probe (400). The neural probe (400) may be any type of brainimplantable probe. The probe (400) is untethered to the shooting tube (200). The probe (400) is preferably non-dissolveable or is biodegradable.

[0110] The probe typically comprises a probe shaft (402) having a proximal end (10) and distal end (20). The probe shaft (402) is typically longitudinal. The probe shaft may house one or more electrical conductors, one or more optical fibres conductors, or other types of conductor to transmit signal to / from the tissue-interfacing element (410). The probe shaft (402) is untethered to the shooting tube (200). The probe shaft (402) is preferably non- dissolvable or is biodegradable.

[0111] At a distal end (20) of the probe shaft (402) is a tissue-interfacing element (410), configured to interacts locally with soft tissue {e.g. tissue of the organ, neuronal tissue of the brain). See, for instance, FIGs. 4 and 5. The tissue-interfacing element (410) is configured to provide the local stimulation or to detect the local property for measurement. The tissue-interfacing element may comprise one or more of: one or more electrical contacts {e.g. electrodes) for local detection of electrical current in the soft tissue {e.g. neuronal tissue of the brain), and / or for local electrical stimulation of soft tissue {e.g. tissue of the organ, neuronal tissue of the brain); one or more chemical sensors {e.g. pH, ion, molecule-specific) for detection of local chemical environment in the soft tissue {e.g. tissue of the organ, neuronal tissue of the brain) around the tissue-interfacing element; one or more mechanical sensors for detection of local movement / motion in the soft tissue (e.g. tissue of the organ, neuronal tissue of the brain) around the tissue-interfacing element; one or more sound transducers, for local acoustic stimulation of the soft tissue (e.g. tissue of the organ, neuronal tissue of the brain) around the tissueinterfacing element; one or more ultrasound transducers, for local ultrasonic stimulation of the soft tissue (e.g. tissue of the organ, neuronal tissue of the brain) around the tissueinterfacing element; one or more light transducers, for local light stimulation of the soft tissue (e.g. tissue of the organ, neuronal tissue of the brain) around the tissue-interfacing element; one or more mechanical transducers, for local mechanical stimulation of the soft tissue (e.g. tissue of the organ, neuronal tissue of the brain) around the tissueinterfacing element.

[0112] Where the probe is a neural probe, the neural probe may be a commercially available neural probe, such as that manufactured by Neuralink (US), Blackrock Neurotech (US), NeuroPace Inc (US), Medronic (US), CorTec (GER), Liva Nova PLC (UK), Boston Scientific Corporation (US), Abbott (US), Aleva Neurotherapeutics (Switzerland), Synchron (US, Australia), Inbrain, Neuroelectronics (Spain), Paradromics Inc (US), or Precision Neuroscience (US).

[0113] Electrical signals to / and from the tissue-interfacing element may be transmitted, via one or more electrical conductors disposed in a body of probe shaft (402), to a proximal end (10) of the probe shaft (402). The proximal (10) end of the neural probe (400) may be attached or is attachable to an implantable interface module (450) implantable below the skin of the subject (e.g. on a surface of the brain). See, for instance, FIG. 5. The implantable interface module (450) may comprise one or more of: power source (e.g. battery, induction receiver); signal processing unit; analogue to digital converter; digital to analogue converter; data storage module; telemetry module (a module configured for wireless communication with an exterior device. Typically the telemetry module comprises an antenna and processor).

[0114] The implantable interface module (450) is configured to receive and / or transmit electrical signals from / to the tissue-interfacing element.

[0115] Alternatively or in addition, signals from the tissue-interfacing element may be transmitted wirelessly to an external receiver. Electronic components configured for transmission of wireless signals may be housed in the projectile (300) and / or within the body of the probe shaft (402). Methods and devices for wireless transmission are known it the art. For instance, a power source (e.g. battery, induction receiver), may be housed within in the projectile (300).

[0116] The probe (400) shaft (402) is flexible or conformable. By conformable, it is meant it is able to confirm to a shape of the soft tissue (e.g. brain neuronal tissue).

[0117] According to one aspect, the neural probe (400) shaft (402) has a Young’s modulus, (as measure using ISO 527-1 :2019) from very soft (matching the Neural tissue 1 kPa) to harder materials (1-130 GPa). The lower the Young’s modulus, the more the probe (400) shaft (402) flexibility is matched with the mechanical properties of the tissue and the less the forming injuries.

[0118] A size and shape of a transverse cross-section of the probe (400) shaft (402 is preferably constant along a longitudinal direction of the shaft. The constant size and shape may exclude the tissue-interfacing element (410).

[0119] A shape of the transverse cross-section of the probe (400) shaft (402) may be any suitable shape for a probe such as circular, hexagonal, polygonal, oval, and the like. As a general guidance, where the probe is a neural probe, a maximum size of a transverse cross-section of the neural probe (400) shaft (402) preferably has a maximum width or thickness (e.g. diameter) in a range 5 .m to 5 mm.

[0120] A majority of (a length of) the probe (400), in particular of the probe (400) shaft (402), may be disposed (stored) within the shooting tube (200) bore (210) (prior to propulsion). A majority of (a length of) the probe (400), in particular of the probe (400) shaft (402), may be disposed (stored) outside of the shooting tube (200) bore (210) (prior to propulsion). Where it is stored outside of the shooting tube (200) bore (210), a part of the probe (400) or probe (400) shaft (402) may pass through the aperture (216).

[0121] The probe (400) shaft (exterior wall) is made substantially from one or more biocompatible materials and is optionally coated with one or more biocompatible materials. Alternatively, the probe (400) shaft (exterior wall) is made substantially from one or more other (less- biocompatible) materials and is coated with one or more biocompatible materials.

[0122] Examples of materials that are biocompatible materials include Nylon (type of Polyamide), Thermoplastic Polyurethane (TPU), Polypropylene (PP), Polyethylene (PE), Polymethyl Methacrylate (PMMA), Epoxy resins, Metals (e.g. platinum), Metal Alloys (e.g. Titanium Alloy: Ti-6AI-4V, Magnesium Alloys).

[0123] Examples of other (less-biocompatible) materials include, Stainless Steel, Cobalt- Chromium Alloys, Nickel-Titanium Alloys, Polyurethane, Nickel, Chromium, and PVC. Chromium, Nickel, and Polyvinyl chloride (PVC) are non-biocompatible materials.

[0124] Further provided is a system (1000) for implantation of the probe (400). The system (1000) is shown exemplarily in FIG. 6.

[0125] The system (1000) comprises a device (100) as described herein and a pneumatic propulsion unit (500). The pneumatic propulsion unit (500) configured provide to the pressurised gas (502) to the bore (210) such that the projectile (300), propelled through the bore distal opening (212), is capable of penetrating the soft tissue (e.g. of the brain) and delivering the probe (400) attached to the projectile (300) to (the target in) the soft tissue (e.g. in the brain). The pneumatic propulsion unit (500) is operatively connected to the device (100) e.g. using one or more conduits (512, 522).

[0126] The pneumatic propulsion unit (500) typically comprises a reservoir (510) of compressed gas connected (via one or more conduits (512, 522) to the shooting tube (200). The pneumatic propulsion unit (500) typically further comprises a (signal / electrically) controllable valve (520), configured to control flow of gas from the reservoir (510) to the shooting tube (200) (connected to the controllable valve (520) via a control cable (532)). The pneumatic propulsion unit (500) typically further comprises a controller (530) configured to control the controllable valve (520), such that the compressed gas in the reservoir (510) is released timely to provide to the pressurised gas (502) for propelling the projectile (300) through the bore distal opening (212).

[0127] The pressure of the pressurized gas in the reservoir (510) may be set using feedback from a pressure gauge. The pressure of the pressurized gas in the reservoir (510) may be set to a shooting pressure. Gas may be added to the reservoir (thereby increasing the shooting pressure) using a pneumatic pump. Gas may be removed from the reservoir (thereby reducing the shooting pressure) using a release valve.

[0128] The controllable valve is any capable of controlling flow of gas such that is released from the reservoir (510) to propel the projectile (300) through the bore distal opening (212). For instance, the controllable valve (520) may be a gate (on / off) valve. A movement of the valve OFF-ON-OFF may generate a pressurised gas pulse for propulsion of the projectile. Alternatively movement of the valve OFF-ON releases pressurised gas for propulsion of the projectile which is not necessarily gated / pulsed. The type of valve is not limited to a 2 position, for example, it may have more than 2 positions. Other types of valve include pressure-relief valve, solenoid valves, poppet valves.

[0129] The device (100) is for implantation into soft tissue of a subject. More in particular, the device (100) is for implantation into an organ of the subject. Examples of organs include brain, liver, kidney, muscle.

[0130] A target for local stimulation or measurement is present in the soft tissue, in particular within an organ of the subject; it may have been previously identified by one or more investigative methods (e.g. EEG, medical imaging). The target is also a location in the soft tissue for the distal (20) end, in particular for the tissue-interfacing element (410) of the probe shaft (402). The target in the soft tissue may be at or offset from a location where the projectile is to be implanted. The offset is caused by a distance between the projectile and the tissue-interfacing element (410). The offset is typically known.

[0131] In particular, the device (100) is for implantation of a neural probe (400) within a brain of a subject. By brain, it is meant the organ within the subject which is typically accessed via a burr hole in the skull. It is noted that the dura mater of the brain may be intact or absent (i.e. when absent it may be peeled to the side) prior to propulsion of the projectile (300). A target for local stimulation or measurement is present in the brain of the subject; it may have been previously identified by one or more investigative methods (e.g. EEG, medical imaging). The target is also a location in the brain for the distal (20) end, in particular for the tissue-interfacing element (410) of the neural probe shaft (402). The target in the brain may be at or offset from a location where the projectile is to be implanted. The offset is caused by a distance between the projectile and the tissueinterfacing element (410). The offset is typically known.

[0132] The shooting pressure of the gas determines a desired penetration depth into the soft tissue, in particular the organ tissue, more in particular the brain tissue. A deeper target requires a greater shooting pressure. The shooting pressure refers to a pressure of the compressed gas (e.g. contained by the controllable valve) prior to release into the bore (202) of the shooting tube (200). In particular, the shooting pressure refers to a pressure of the compressed gas in the reservoir (510) (e.g. contained by the controllable valve) prior to release into the bore (202) of the shooting tube (200).

[0133] A shooting pressure may be determined by a set of deployment parameters. The set of deployment parameters comprises:

[0134] - desired travel distance (e.g. straight line distance from point of entry to desired location) of the projectile (300) into the soft-tissue (e.g. organ, brain) of the subject, and

[0135] - one or more of:

[0136] - one or more characteristics of the projectile (300);

[0137] - angle of deployment e.g. tangential or inclined to a surface of the soft tissue (e.g. organ, brain);

[0138] - one or more characteristics of the shooting tube bore (210);

[0139] - one or more characteristics of the probe (400);

[0140] - size of aperture (216) where present.

[0141] Preferably the shooting pressure is determined by a set of deployment parameters, wherein the set of deployment parameters comprises:

[0142] - desired travel distance (e.g. straight line distance from point of entry to desired location) of the projectile (300) into the soft tissue (e.g. organ, brain) of the subject; and

[0143] - one or more characteristics of the projectile (300); and

[0144] - angle of deployment e.g. tangential or inclined to a surface of the soft tissue (e.g. organ, brain);

[0145] - and optionally one or more of: - one or more characteristics of the shooting tube bore (210);

[0146] - one or more characteristics of the probe (400);

[0147] - size of aperture (216) where present.

[0148] In general:

[0149] - a heavier projectile (300), the higher the shooting pressure;

[0150] - a longer projectile (300), the higher the shooting pressure;

[0151] - a larger transverse cross-section of projectile (300), the higher the shooting pressure;

[0152] The set of deployment parameters may additionally include one or more of:

[0153] - one or more characteristics of any spiral grooving of the tube;

[0154] - distance from the distal end of shooting tube to surface of the soft tissue (e.g. organ, brain);

[0155] - distance from the surface of the soft tissue (e.g. organ, brain) to the target;

[0156] - presence or absence of the dura mater;

[0157] - valve speed;

[0158] - type of gas (e.g. nitrogen, air, oxygen).

[0159] The shooting pressure may be determined from a trained machine learning model that predicts, from the set of deployment parameters, the quantity of gas released to provide to the pressurised gas (502) for propelling the projectile (300) through the bore distal opening (212).

[0160] The trained machine learning model is determined comprising:

[0161] - obtaining a plurality of sets of training parameters previously recorded using a training device (100) and a training subject or training subject proxy (e.g. agarose phantom), each set of training parameters comprising:

[0162] - a) a set of training deployment parameters which include one or more of the parameters cited in the above-mentioned set of deployment parameters;

[0163] - b) the shooting pressure such that the distal (20) end of the projectile (300) reaches a location in the soft tissue (e.g. organ, brain) of the training subject or subject proxy such that the distal (20) end or tissue-interfacing element (410) of the probe shaft (402) is at the target; - adjusting weights of an untrained machine learning model until the set of training deployment parameters approaches the shooting pressure.

[0164] The shooting pressure for a test subject ( / .e. the subject who is to receive the probe by the user) may be determined by a method comprising: receiving a set of test deployment parameters which include one or more of the parameters cited in the above-mentioned set of deployment parameters for the device (100) or system (1000) to be applied to the test subject; applying the set of test deployment parameters to the trained machine learning model; and outputting, from the trained machine learning model, the shooting pressure.

[0165] The machine learning model may be any, for instance, regression model or a neural network model. Examples of suitable regression models and protocols for solving them are known in the art, for instance, from Cherian and Kanaga, Journal of Neuroscience Methods, Volume 369, 1 March 2022, 109483 and Vattikonda et al, Communications Biology volume 4, Article number: 1244 (2021). Non-limiting examples of regression models include Lasso regression (linear regression with L1 regularization), Linear SVM, and Bayesian regression.

[0166] Examples of suitable neural network models and protocols for training them are known in the art, for instance, from Cherian and Kanaga, Journal of Neuroscience Methods, Volume 369, 1 March 2022, 109483. Examples of neural network models include Artificial Neural Network (ANN) / Multi Layer Perceptron (MLP), Recurrent Neural Networks (RNN), Convolutional Neural Network (CNN), Gated Recurrent Units (GRU), Long Short Term Memory (LSTM).

[0167] Further provided is a method for attaching a probe (400) to a projectile (300) so as to form the device (100) described herein, comprising:

[0168] - providing the projectile (300) configured for propulsion by a pressurised gas (502) through the bore distal opening (212) of a shooting tube (200), and penetration into the soft tissue (e.g. organ, brain);

[0169] - providing the probe (400);

[0170] - attaching the projectile (300) to the probe (400) by injection over-moulding of the projectile (300) over a distal (20) end the probe (400). Injection over-moulding is a technique well known in the art (see, for instance, https: / / en.wikipedia.Org / wiki / lnjection_moulding#overmoulding).

[0171] Further provided is a method for implanting a probe (400) in soft tissue (e.g. organ, brain)of a subject comprising:

[0172] - providing a device (100) as described herein;

[0173] - adjusting a pose (position and orientation) of the bore (210) towards (a target in) the soft tissue (e.g. organ, brain)of a subject;

[0174] - propelling the projectile (300) from the bore (210) using pressurised gas (502) such that the projectile (300) and attached probe (400) penetrates the soft tissue (e.g. organ, brain) , thereby implanting the probe (400) in the soft tissue (e.g. organ, brain).

[0175] Where the method is for implanting a neural probe (400) in a brain of a subject, the subject is prepared by creating a cranial burr hole in the cranium at a location for access to the target. The burr hole exposes the dura mater. The dura mater may or may not be removed (i.e. peeled to the side).

[0176] The pose (position and orientation) of the bore (210) is adjusted such that the projectile (300) is propelled through the cranial burr hole.

[0177] Examples

[0178] Example 1

[0179] A device as described herein was prepared comprising a shooting tube that was a longitudinal tube with a bore diameter of 2.7 mm and a bore length of 52 mm and a projectile that was a mini stainless steel ball of diameter 2.5mm. A proximal end of the shooting tube bore was operatively attached to an air compressor, having an air outlet controlled by a controllable valve. A brain mimetic (0.6% agarose) was prepared to match mechanical properties of the brain. Air entering the compressor was compressed with the valve closed to different shooting pressures. The shooting tube was aimed at the brain mimetic, the controllable valve opened to release the compressed gas and propel the projectile, and insertion depth of projectile each different shooting pressures was measured. The experiment was repeated for different separation distances between the shooting tube distal opening from the surface of the brain mimetic. The results are shown in FIG. 7. The results show that insertion depth is controllable by an adjustment of the shooting pressure.

[0180] Example 2

[0181] A device as described herein was prepared comprising a shooting tube that was a longitudinal tube with a bore diameter of 2.7 mm, a bore length of 52 mm, a projectile that was a mini stainless steel ball of diameter 2.5mm, and a neural probe mimetic that was a length of flexible electrode was attached by adhesive substance to the projectile. A proximal end of the shooting tube bore was operatively attached to an air compressor, having an air outlet controlled by a controllable valve. A brain mimetic (0.6% agarose) was prepared to match mechanical properties of the brain. Air entering the compressor was compressed with the valve closed to different shooting pressures. The shooting tube was aimed at the brain mimetic, the valve opened to release the compressed gas and propel the projectile, and insertion depth of projectile each different shooting pressures was measured. The results showed that that: i) increasing shooting pressured correlated with a deeper insertion of the projectile and neural probe; ii) the neural probe trailed behind the projectile within the brain mimetic ( / .e. adopted the desired orientation in the brain mimetic); iii) the integrity of the neural probe was maintained within the brain mimetic.

Claims

25Claims1. Device (100) for implantation of a probe (400) within a soft tissue of a human subject comprising:- a shooting tube (200) having a proximal end (10) and distal end (20) comprising a bore (210) having a distal opening (212), wherein the bore (210) is configured for guiding a pressurised gas (502) towards a projectile (300) disposed in the bore (210); and- the projectile (300), configured for propulsion by the pressurised gas (502) through the bore distal opening (212) and for penetration into the soft tissue;- the probe (400); wherein:- the projectile (300) is attached to the probe (400);- the probe (400) is a neural probe; and- the soft tissue is a soft tissue of a brain of the subject.

2. The device (100) according to claim 1, wherein the projectile (300) has a proximal end (10) and a distal (20) end, and the probe (400) is attached to the projectile (300) proximal end (20).

3. The device (100) according to claim 1 or 2, wherein the device (100) is configured such that movement of the projectile (300) within the bore (210) is limited to longitudinal sliding of the projectile (300) and optionally to axial rotation of the projectile (300).

4. The device (100) according to claim 1 or 2, wherein the projectile (300) is disposed within a proximal (10) half of the bore (210) prior to propulsion.

5. The device (100) according to claim 1 to 4, wherein a longitudinal or maximum length of the projectile (300) is equal to or less than half of a longitudinal length of shaft (402) of the probe (400).

6. The device (100) according to any one of claims 1 to 5, wherein the projectile (300) has at its distal (20) end a penetrative tip, configurated for penetration of the soft tissue.

7. The device (100) according to any one of claims 1 to 6, wherein the probe (400) comprises:- a probe shaft (402) having a proximal end (10) and distal end (20), and- a tissue-interfacing element (410) which interacts with the soft tissue and is disposed at a distal end (20) of the probe shaft (402).

8. The device (100) according to claim 7, wherein the tissue-interfacing element (410) comprises one or more electrical contacts for local detection of electrical current in the soft tissue, and / or for local electrical stimulation of the soft tissue.

9. The device (100) according to any one of claims 1 to 8, wherein the shooting tube (200) bore (210) is configured to receive through an inlet port at the proximal end (10) of the bore (210), the pressurised gas (502) which causes the projectile (300) to be propelled through the bore distal opening (212) and to penetrate the soft tissue, thereby implanting the probe (400) attached to the projectile (300) in the soft tissue.

10. The device (100) according to claim 9, wherein a quantity of shooting tubes (200) is one or more than one and the bore (210) of each shooting tube (200) is disposed with a projectile (300) attached to the probe (400).

11. A system (1000) for implantation of a probe (400) comprising:- a device (100) according to any one of claims 1 to 10; and- a pneumatic propulsion unit (500) configured provide to the pressurised gas (502) to the bore (210) such that the projectile (300), propelled through the bore distal opening (212), is capable of penetrating the soft tissue and delivering the probe (400) attached to the projectile (300) to the soft tissue.

12. The system according to claim 11 , wherein the pneumatic propulsion unit (500) comprises:- a reservoir (510) of compressed gas connected to the shooting tube (200);- a controllable valve (520), configured to control flow of gas from the reservoir (510) to the shooting tube (200); and- a controller (530) configured to control the controllable valve (520), such that the compressed gas in the reservoir (510) is released to provide to the pressurised gas (502) for propelling the projectile (300) through the bore distal opening (212).

13. The system according to claim 12, wherein a shooting pressure - a pressure of gas in the reservoir (510) prior to release into the bore (202) of the shooting tube (200) - is determined by a set of deployment parameters, wherein the set of deployment parameters comprises:- desired travel distance of the projectile (300) into the soft tissue of the subject, and one or more of:- one or more characteristics of the projectile (300);- one or more characteristics of the probe (400);- one or more characteristics of the shooting tube bore (210).

14. The system according to claim 13, wherein the shooting pressure is determined from a trained machine learning model that predicts, from the set of deployment parameters, the shooting pressure for propelling the projectile (300) through the bore distal opening (212).

15. A method for attaching a probe (400) to a projectile (300) so as to form a device (100) according to any one of claims 1 to 10, comprising:- providing the projectile (300) configured for propulsion by a pressurised gas (502) through the bore distal opening (212) of a shooting tube (200), and penetration into the soft tissue;- providing the probe (400);- attaching the projectile (300) to the probe (400) by injection over-moulding of the projectile (300) over a distal (20) end the probe (400).

16. A method for implanting a probe (400) in a soft tissue of a subject comprising:- providing a device (100) according to any one of claims 1 to 10 or a system (1000) according to any one of claims 11 to 14;- adjusting a pose of the bore (210) towards a target in the soft tissue of a subject;- propelling the projectile (300) from the bore (210) using the pressurised gas (502) such that the projectile (300) and attached probe (400) penetrates the tissue of the soft tissue, thereby implanting the probe (400) in the soft tissue.

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