Device for the formation of a helical coil

Abstract

A device (100) comprising a body (101), said body (101) comprising: a first opening (102), a second opening (104) and an inner lumen (106) extending from the first opening (102) to the second opening and wherein the inner lumen (106) follows a bent path between the first opening (102) and the second opening (104) of the body. The device (100) is configured to receive a coil-forming component at the first opening (102) of the body, and the rotational advancement of the coil-forming component through the inner lumen (106) and out of the second opening (104) of the body (101) results in the formation of a helical coil. The device (100) is particularly suitable for the in situ formation of a helical coil.

Description

[0001] DEVICE AND METHOD FOR THE FORMATION OF A HELICAL COIL

[0002] FIELD OF THE INVENTION

[0003] The present invention relates to a device for the formation of a helical coil, especially to a device suitable for the in situ formation of a helical coil, such as in the body of a patient. The present invention further relates to a kit comprising said device and to a method of forming a helical coil at a target location.

[0004] BACKGROUND

[0005] Minimally invasive surgery involves performing surgical procedures with minimal disruption to surrounding tissues. This approach aims to reduce trauma, pain, and recovery time compared to traditional open surgeries, while still achieving effective treatment outcomes.

[0006] The benefits of minimally invasive surgery include reduced trauma to the local tissue from the skin to the end organ, this results in less tissue damage and scarring compared to open surgery. Minimally invasive approaches also allow for a faster recovery with shorter hospital stays, less postoperative pain, and quicker recovery times. In addition, there is a lower risk of complication. By minimising trauma to surrounding tissues, minimally invasive surgery may reduce the risk of complications such as infection and bleeding.

[0007] In certain circumstances, minimally invasive surgery is the only option due to the vulnerability or potential risk to surrounding structures. An example of this is procedures used to treat neurological diseases including Parkinson’s disease (PD), Huntington’s disease and stroke.

[0008] Parkinson's disease is characterized by a variety of motor symptoms, such as tremors, bradykinesia (slowness of movement), rigidity, and postural instability. However, it can also involve a range of non-motor symptoms, including cognitive impairment, mood disorders, and autonomic dysfunction. The exact cause of PD is not yet fully understood, but it is believed to involve a combination of genetic and environmental factors. One key pathological feature of PD is the loss of dopamine-producing neurons in a region of the brain called the substantia nigra. Dopamine is a neurotransmitter involved in regulating movement, among other functions.

[0009] First line treatment of PD is medical therapy and involves Dopamine agonists, levodopa, and other drugs that can help alleviate motor symptoms by increasing dopamine levels in the brain. When these therapies fail, Deep brain stimulation (DBS) can be of benefit. DBS involves implanting electrodes in specific areas of the brain to help regulate abnormal brain activity and reduce symptoms. In addition to DBS, cell replacement therapy has been described to improve outcomes. Given the anatomical location of the surgical target, it is not feasible to approach this using open surgery and the operator is restricted to a minimally invasive procedure. Both surgical approaches involve stereotactically inserting a single small gauge straight needle to the putamen. This restriction leads to limitations in the approach, for example, restricting the amount of target tissue that can be treated. In the context of cell delivery, where their relatively large size prevents them from dispersing any distance through tissue, the volume of delivery is limited to the finite area at the tip of the minimally invasive needle. With a straight needle, cell delivery to the larger target volumes of human brain requires several independent brain penetrations to achieve adequate coverage. On average, 6 to 12 injections of certain therapies are required, while some patients with PD have received up to 16 separate penetrations for transplantation to the putamen. Every transcortical brain penetration injures normal brain tissue and leads to an increased risk of haemorrhagic stroke.

[0010] The restriction of the area that can be treated is a common theme in a number of pathologies, including cancer where the surrounding structures are too eloquent or delicate and require a minimally invasive approach. Medical therapies that are dispensed into a volume of the tissue often have limited penetration or dispersal volumes. Therefore, to effectively treat a volume of tissue whose size is greater than the dispersal distance, the therapy must be deposited at multiple locations. Multiple depositions are achieved through the use of multiple insertion devices, typically needles, each of which injects at an individual site. Multiple injections can cause severe trauma to otherwise healthy tissue along the route to the site of treatment.

[0011] A further problem with at least some prior systems is that the delivered media may not stay at the desired delivery site. In a phenomenon called reflux, a portion of the media may flow back up the catheter or delivery needle, significantly reducing the amount of media that remains at the treatment site. Indeed, attempts to inject large volumes of therapeutics / cells to a single location leads to significant reflux. Additionally, the implantation of a large mass of cells within a confined location can severely impair graft viability, resulting in necrosis at the centre of the transplant.

[0012] Another approach has been to insert a large host catheter, which is comprised of a number of internal passages, or lumens for the advancement of micro-catheters. These internal passages within the host catheter exit at specified distal orifice locations around the distal end to allow the delivery of a media to a desired target area. Using this approach, the host catheter is inserted into the centre of the desired target, or delivery area in the patient. Then, the micro-catheters are inserted into the various lumens, where multiple doses can be delivered to each of the distal orifice locations along the elongate member. This method allows a larger target area to be covered without the need for multiple cranial penetrations. However, the introduction of a relatively large host catheter displaces a larger amount of tissue and the use of multiple microcatheters makes the ability to deliver a metered injection more difficult due to their variable lengths.

[0013] BRECKNELL JE, FAWCETT JW, A Device for the Implantation of Multiple Cellular Deposits into a Large Volume of Brain from a Single Cannula Site, Experimental Neurology, 1996, Vol. 138, p338-343 describes a device for positioning a Teflon tube sideways from the end of a steel cannula. The device has a distal end which is bent and allows for multiple cell deposits around a single needle passage. The Teflon tube deviates from the long axis of the cannula, but no plastic deformation occurs.

[0014] US10,888,688B2 discloses an insertion device for delivering media inside a patient. The insertion device includes an outer guide tube having a side port and an inner guide tube nested within the outer guide tube and movable axially within the outer guide tube. The inner guide tube includes a deflector at an end within the outer guide tube. A catheter can be advanced axially within the inner guide tube and the deflector deflects the dispensing end of the catheter outward through the opening in the outer guide tube. A therapeutic delivery cannula may be nested within the catheter, such that the deflected end of the catheter determines the direction of travel of the therapeutic delivery cannula into patient tissue when the cannula emerges from the catheter. While US US10,888,688B2 provides a reduced bleed risk owing to fewer tissue passes, it is still necessary to perform multiple deployment and retraction steps to ensure delivery to the entire tissue volume, and reflux remains problematic owing to the straight catheter trajectories.

[0015] Intravascular needles and treatment devices are known in the art. US2020 / 337765A1 describes devices, systems and methods for modulating targeted nerve fibers (e.g., hepatic neuromodulation) or other tissue. The systems may be configured to access tortuous anatomy of or adjacent hepatic vasculature. The tissue modulation device comprises an elongated shaft having a guidewire lumen, and a first monopolar electrode positioned along the elongated shaft and a shape-set portion located along a distal end portion of the elongated shaft. The shape- set portion may be adapted such that it forms a spiral shape in the deployed configuration. The distal portion is shape-set during manufacture to have a pre-formed pigtail (e.g., spiral or corkscrew) shape. The distal portion of the catheter remains in a straight or substantially straight shape as it is advanced to a target location over the guidewire. Upon retraction of the guidewire, the shape-set portion of the catheter “springs” into a three-dimensional curve. The shape-set portion is formed by incorporating a shaped elastic member, such as from a metal or metal alloy (e.g., nitinol), or may be formed with a thermoplastic material using heat shaping techniques. WO2022 / 207849A1 also describes a system which includes a guide catheter which is configured to be intravascularly positioned within a main vessel, and an inner catheter positioned within the lumen of the guide catheter. The inner catheter has four energy delivery elements for the delivery of energy at a treatment site. When the inner catheter is in the deployed configuration within the vessel, the inner catheter may be extended away from the guide catheter and a distal portion of the inner catheter may extend into a helical or spiral configuration.

[0016] Helical needles have been used for targeted laser ablation of the hippocampus, particularly in the treatment of epilepsy. GRANNA J et al., Targeting Epilepsy Through the Foreman Ovale: How Many Helical Needles are Needed? BMES, May 2022, Vol. 50, No. 5, p499-506, describes the use of a new access path through the foremen ovale, using a helical needle, which minimizes the amount of healthy brain tissue the needle must pass through on its way to the hippocampus, and also enables the needle to follow the medial axis of the hippocampus more closely. The helical ablation needle is a superelastic nitinol pre-curved tube which is inserted through a straight docking tube and into the brain. These helical coils are pre-formed or shapeset during manufacture from elastic materials, particularly shape-memory metals, which allow the coils to spring into their pre-formed shape after deployment.

[0017] It is an object of the present invention to improve the delivery of therapies to a target tissue volume via a single access needle using a minimally invasive approach. In pursuance of this desired improvement the present inventors arrived at a new device for the formation of a helical coil as described herein, particularly for the in situ formation of a helical coil. New methods for the in situ formation of the helical coil and for the delivery of therapies (therapeutics, ablation, suturing etc.) to a target tissue volume are also disclosed. This technique reduces trauma to the patient as well as the time required to undertake such a procedure. It is applicable to the treatment of a variety of tissue volumes and shapes, and particularly suited to the treatment of volumes which are approximately cylindrical in shape. While the above background has been discussed with regards to medical applications (including veterinary medicine), it will be readily apparent to the skilled person that an improved device and methods for forming a helical coil might be useful for any application where helical coil formation is desired, particularly in situ coil formation. Present methods for forming helical coils or coil springs use a process of coiling; winding of a wire around a mandrel, or winding of the wire without a mandrel (generally using a central navigation computer, CNC, spring coiling machine). CNC coiling machines are widely used as they allow tight control over winding parameters and enable complex spring shapes and patterns. These machines adjust automatically to different wire diameters, pitches and coil geometries. Coiling can be done hot or cold, with the choice being predominantly determined by the wire size that needs to be coiled. The device and methods of the present invention may be advantageously used in the formation of helical coils having customised parameters (such as pitch and diameter). Applications include helical coils and springs used in sectors including aerospace, automotive, constructions, electronics, agriculture, oil and gas extraction, and general manufacturing.

[0018] SUMMARY OF THE INVENTION

[0019] According to a first aspect of the present invention, there is provided a device for the formation of a helical coil, said device comprising a body, said body comprising: a first opening, a second opening, and an inner lumen extending from the first opening to the second opening and wherein the inner lumen follows a portion of a helical path between the first opening and the second opening of the body (a “helical inner lumen”). The device is configured to receive a coilforming component at the first opening of the body, and the advancement of the coil-forming component through the inner lumen and out of the second opening of the body results in the formation of a helical coil.

[0020] According to a second aspect of the present invention, there is provided a device and method for the formation of a helical coil, said device comprising a body, said body comprising: a first opening, a second opening, and an inner lumen extending from the first opening to the second opening and wherein the inner lumen follows a bent path between the first opening and the second opening of the body (a “bent inner lumen”). The device is configured to receive a coilforming component at the first opening of the body, and the advancement of the coil-forming component through the inner lumen and out of the second opening of the body under rotation results in the formation of a helical coil. The method comprises applying rotation to a coil-forming component during advancement of the coil-forming component into the first opening of the body, through the inner lumen and out of the second opening of the body; and forming a helical coil from the coil-forming component. The rotation may comprise a rotation about a longitudinal or medial axis of the coil-forming component. The applied rotation may be referred to as an axial rotation. As the coil-forming component is advanced through the inner lumen with the applied rotation, it will experience both linear and rotational motion as it transits into the bent inner lumen. This induces a torsional load on the coil-forming component as it transits through the bent path of the inner lumen. The coil-forming component will undergo both plastic and elastic deformation. The elastic component of this deformation may be recovered upon exit of the curve (“springback”).

[0021] The term “bent” as used herein when referring to the path of the inner lumen refers to the shape of the path being non-linear. For example, the “bent path” may have a shape that includes a continuous curve, a non-continuous curve, and / or linear sections arranged at angles relative to one another. Thus, in some embodiments, a bent path comprises a continuous curve. In some embodiments, a bent path comprises a non-continuous curve. In some embodiments, a bent path comprises linear sections arranged at angles relative to one another. The skilled person will appreciate that a “bent” inner lumen may be produced using any suitable method of manufacture (e.g. by moulding, 3D printing, bending or any other suitable method).

[0022] Inner Lumen

[0023] The lumen is a central cavity in the body which extends from the first opening to the second opening. The inner lumen may have a circular or oval cross-section. For non-medical applications, the inner lumen may have a diameter in the range of micrometres to metres. For medical applications, the inner lumen may have a diameter in the range of micrometres to tens of millimetres. The diameter of the inner lumen may be 0.001 to 10 mm, 0.05 mm to 2 mm, 0.8 to 1 .2 mm, or 4 to 6 mm. For non-circular cross-sections, a “diameter” is intended to capture the longest cross-section dimension.

[0024] The shape of the helical coil formed can be tuned by changing the design parameters of the inner lumen of the body, as well as the materials of the coil-forming component.

[0025] In a first aspect of the invention, by varying the dimensions, such as pitch (the vertical distance between successive turns) and diameter, of the helical path the shape of the helical coil can be tuned. The diameter (or “neutral diameter”) of the helical path refers to the diameter of the medial path of the inner lumen. The portion of the helical path is a fraction of an individual rotation of the resultant helical coil. That is, the portion of the helical path can be short in comparison to the diameter and pitch of a full helix. The portion of a helical path can be typically less than an eighth-turn of a helix, or a quarter-turn of a helix or a half-turn of a helix. The inner lumen may take the form of a “twisted J”. The portion of the helical path may be constrained by the outer dimensions of the body of the device. For medical applications, it is preferred that the portion of a helical path is minimised while enabling helical coil formation. The body may be inserted into the patient with minimal damage to surrounding tissue. In this case, a small diameter insertion needle may be used. As such, the portion of the helix may be confined to a portion which can be confined within the diameter of the insertion needle. For example, a smaller dimension insertion passage requires a smaller body, and thus a smaller portion of a helical path such as an eighth-turn of a helix would be more suitable than a body with a lumen following a path which is a quarter-turn of a helix.

[0026] The coil-forming component may be advanced through the helical inner lumen under application of an axial rotation (discussed in detail below). If the rate of rotation is varied, then a helical coil of varied pitch and diameter can be produced (a “progressive helix”). For example, increasing the rate of rotation increases the pitch and decreases the diameter of the resulting helical coil. Variation in either pitch or diameter will result in coring / destruction of the tissue as the coil progresses. In particular, the formation of a helical coil having a pitch which approaches zero can result in the coring of tissue into which the coil is inserted. As discussed above, for medical applications, a consistent pitch and diameter is desirable to minimise damage to the tissue. However, the coring of tissue may have clinical applications, for example, in devascularising a tumour, or performing a biopsy.

[0027] In a second aspect of the invention the bent path is a curved path. The curved path may have just one dimension of curvature, unlike the two dimensions of curvature of a helical path. The curved path may be planar. As the coil-forming component is advanced through the inner lumen, its medial axis may lie in a two-dimensional plane. The curved path may be an arc of a circle. The radius of curvature of the curved path may depend on the use of the desired helical coil. The curved path may have a radius of curvature of at least 1 pm, at least 1 mm or at least 10 mm, for example at least 1 .5 mm. The curved path may have a radius of curvature of no more than 100 mm, no more than 10 mm or no more than 100 pm, for example no more than 8 mm. The curved path may have a radius of curvature in the range of 1.5 to 8 mm. The radius of curvature may be dependent on a maximum strain that the coil-forming component can endure (yield strain). For example, for coil-forming components having an outer diameter of 0.9 mm, the radius of curvature of the curved path may be in the range of 1 .5 to 8 mm. Alternatively, the bent path comprises a first section and a second section, wherein the second section is arranged at an angle to the first section. The angle of the second section may be tangential to the desired curve of the helical coil. The angle of the second section may an acute angle, in other words greater than 0 degrees and less than 90 degrees. The bent path may be a sloped or ramped path. The bent path may be planar. As the coil-forming component is advanced through the inner lumen, its medial axis may lie in a two-dimensional plane.

[0028] In the second aspect of the invention, the coil-forming component experiences both linear and rotational motion as it transits the inner lumen. The rotation may be applied at or near to a proximal end of the coil-forming component. The rotation and advancement induce a torsional load on the coil-forming component. For example, the rotation may be applied by means of providing a rotation about the normal medial axis of the coil-forming component. The angle of rotation per mm of linear advancement of the coil-forming component (rotation rate, a) may be no more than 500 degrees / mm (no more than 8.7 radians / mm), no more than 100 degrees / mm (no more than 1 .7 radians / mm), or no more than 20 degrees / mm (0.3 radians / mm). The rotation rate may be in the range of 1 to 20 degrees / mm (0.02 to 0.3 radians / / mm). Where the curved path of the inner lumen has a radius of curvature of 4 mm, the rotation rate applied to the coilforming component may be in the range 0 to 500 degrees / mm (0 to 8.7 radians / mm). The angle of rotation per mm linear advancement of the coil-forming component may be selected based on an outer diameter of the coil-forming component and a predetermined diameter and pitch for the resulting helical coil.

[0029] A consistent rate of rotation may be applied to the coil-forming component to form a helical coil with a consistent pitch and diameter along its length. That is, a consistent rate of rotation may be applied to the coil-forming component as it advances into the first opening of the body, through the inner lumen and out of the second opening of the body. The rate of rotation may be defined as an angular displacement per unit time or an angular displacement per unit linear advancement of the coil-forming component.

[0030] The formation of the coil may be effectively described using the Frenet-Serret framework. The coil-forming component may be modelled as a line (i.e. with zero thickness). The curved path of the inner lumen may have a constant radius of curvature, rpath. The curvature, kpath, of the inner lumen may be described as 1

[0031] Kpath — „

[0032] • path

[0033] This fixed radius of curvature of the inner lumen sets the curvature of the resulting helical coil, as discussed below. For a constant helical coil, the curvature of the coil K, depends on the radius of the helical coil and the spacing between its coils (the pitch, p): r

[0034] K =~ r2 - + c 2

[0035] P where c is the vertical rise per radian, C = —

[0036] 271

[0037] The rotation about the longitudinal axis of the coil-forming component (“axial rotation”) may induce a torsional load (torque) on the coil-forming component as it advances through the body. This rotation causes the coil-forming component to twist out of the osculating plane, introducing torsion into the coil-forming component. Torsion of the helical coil is described as: c

[0038] T =~ r2 - + c 2

[0039] Therefore,

[0040] K r

[0041] T C

[0042] For an inner lumen of a device having a fixed radius of curvature, and thus curvature, kpath, the curvature K of the resulting helical coil is constant irrespective of the rotation rate of the coilforming component. The curvature of the inner lumen is thus related to the curvature of the resulting helical coil by a compensation factor, f.

[0043] K fKpath

[0044] Rotation rate, a, may be approximately equal to the torsion, T.

[0045] The following equations were found to govern the relation between pitch, p, and diameter, d, of the resulting helical coil to the rotation rate, a, and the curvature, kpath, of the inner lumen of the device:

[0046] As can be seen from the above, an applied rotation rate or torsion can be utilised to vary the dimensions of the as-formed helical coil, for example, to vary the pitch or diameter of the coil. To maintain uniform pitch (and diameter) constant torsion (rotational rate) is applied to the coilforming component during its advancement. More specifically, rotation is applied to the coilforming component such that the rotation rate (torsion) of the coil-forming component as it enters and advances through the inner lumen is constant. Alternatively, if the torsion is varied during advancement of the coil-forming component, then a helical coil of varied pitch and diameter can be produced (a “progressive helix”).

[0047] As the coil-forming component advances through the bent inner lumen it experiences a rotation about its medial axis, and a rotation about the centre of rotation of the bent inner lumen. The rotation or twisting acts to impart a torsional strain onto the coil-forming component. The walls of the bent inner lumen constrain the coil-forming component to the shape of the bent path during the application of the rotation. In other words, as the coil-forming component is advanced during the application of the rotation, it engages the walls of the inner lumen such that each portion of the coil-forming component passing through the inner lumen experiences a curved deformation (according to the bent / curved shape of the inner lumen) and a torsion (rotation about its medial axis). This combination of the curved deformation and axial rotation results in a helical shape as the coil-forming component exits the inner lumen. The coil-forming component will undergo both plastic and elastic deformation. The elastic component of this deformation may be recovered upon exit from the inner lumen (“springback”).

[0048] The resulting helical coil may have a diameter of 1 to 50 mm, 20 to 50 mm, 5 to 25 mm, 10 to 25 mm, 2 to 10 mm, or 6 to 8 mm. The resulting helical coil may have a pitch of 1 to 50 mm, 20 to 50 mm, 5 to 25 mm, 10 to 25 mm, 2 to 10 mm, or 6 to 8 mm. These pitches and diameters are non-limiting, and the skilled person would appreciate that the helix pitch and diameter may each be in the range of micrometres to metres for non-medical applications, or micrometres to tens of millimetres for medical applications.

[0049] Diameter and pitch values as well as diameter and pitch combinations may be selected for specific applications. For non-medical applications, large diameter and pitch helices may be envisaged. For example, helical coils with diameters and pitches in the centimetre and metre ranges might be formed. For medical applications, smaller diameters and pitches are suitable. In the delivery of therapy to the putamen, a helical coil having a pitch of 5 to 15 mm and diameter of 5 to 15 mm is suitable, and a pitch of 6 to 8 mm and diameter of 6 to 8 mm is preferred. The diameter and pitch may be the same. The helical coil may have a pitch of 8 mm and diameter of 8 mm or a pitch of 6 mm and diameter of 6 mm. This ensures that no portion of the putamen is more than 4 mm from the helical coil and / or administered therapy.

[0050] In the treatment of Parkinson’s disease, a helical coil having a pitch of 5 to 15 mm and diameter of 5 to 15 mm is preferred, most preferably a pitch of 6 to 8 mm and diameter of 6 to 8 mm. In the treatment of epilepsy, a pitch of 5 to 10 mm and diameter of 5 to 10 mm is preferred. In the treatment of Alzheimer’s, a pitch of 5 to 15 mm and diameter of 5 to 15 mm is preferred. In the treatment of Huntington’s disease, a pitch of 3 to 8 mm and diameter of 10 to 20 mm is preferred. In the treatment of brain tumours, a pitch of 5 to 10 mm and diameter of 10 to 15 mm is preferred. In the treatment of solid organ malignancy (for example, of the lung, kidney, or liver), a pitch of 5 to 15 mm and diameter of 10 to 25 mm is preferred. In the treatment of diabetes through islet cell transplantation into an organ (for example the liver), a pitch of 5 to 20 mm and diameter of 10 to 50 mm is preferred. In the treatment of muscular dystrophy, a pitch of 5 to 10 mm and diameter of 10 to 30 mm is preferred. In bone-to-bone fixation in the treatment of fracture, or in the injection of therapies into bone, a pitch of 5 to 10 mm and diameter of 10 to 20 mm is preferred. In a suturing application, a pitch of 1 to 2 mm and diameter of 2 to 5 mm is preferred. Similar pitch and diameters are envisaged for applications of the device in the field of veterinary medicine.

[0051] A larger diameter helical coil is more flexible than a smaller diameter helical coil. Insertion of a larger diameter helical coil into the tissue of a patient may result in deviation of the helical coil from its intended trajectory.

[0052] The device and method may be capable of forming any number of turns of the helical coil. The number of turns in the helical coil may be 10 or more, 6 or more, 3 or more, preferably 3 to 10, or 3 to 6. Longer coils may be useful in elongate tissues, for example, for use in the repair of a spinal cord injury.

[0053] The helical coil may be formed with a consistent pitch and diameter along its length. In the first aspect of the invention, the geometry of the inner lumen following a portion of a helical path provides a consistent helical coil. In the second aspect of the invention, a consistent rotation results in the formation of a consistent helical coil. For medical applications, a consistent pitch and diameter can minimise damage to the tissue. For example, a conical helical coil or a helical coil with varying pitch may destroy the tissue as it was advanced into it.

[0054] The coil-forming component may be advanced through the inner lumen at a rate of a few to tens of millimetres per second. An advancement rate may be an average of 4.4 mm / s. These advancement speeds may be beneficial for introducing the coil into a tissue or other sensitive material. Faster advancement speeds may be utilised in non-medical applications. The rate of advancement may be limited by friction-induced heat generation as the coil-forming component passes through the inner lumen.

[0055] The portion of the helical path or bent path may terminate at the second opening of the body. The first opening may be at a proximal end of the body and the second opening may be spaced apart from the first opening. The first opening may be at a proximal end of the body and the second opening may be in the region of a distal end of the body.

[0056] The body may be a tubular or cylindrical shape. When the body is a tubular or cylindrical shape, the first opening may be located at a base of the cylinder. The second opening may be located on the curved surface of the cylinder, in the region of the distal end of the body. Locating the second opening on the curved surface of the cylinder may minimise tissue trauma when the device is inserted for in situ coil formation. A second opening on the curved surface of the cylinder may minimise the potential for tissue to block the opening.

[0057] The body may comprise one or more additional inner lumens. The one or more additional inner lumens may follow a portion of a helical path from a proximal end of the body to a region of a distal end of the body. Alternatively, the one or more additional inner lumens may follow a straight path from a proximal end of the body to a distal end of the body. The one or more additional inner lumens may extend from the first opening of the body, or the one or more additional inner lumens may each extend from an independent, third opening in a proximal end of the body. The one or more additional inner lumens may each extend to an independent, fourth opening at the distal end of the body or in the region of the distal end of the body.

[0058] The surface of the inner lumen may comprise a coating. The coating may comprise one or more of a non-stick coating, low friction coating, anti-wear coating and an antibacterial coating.

[0059] Body

[0060] The body may be a tubular body, preferably a cylindrical body. The tubular body may have a circular or oval cross-section. The body may be a flattened tube. The tubular body may have a central axis.

[0061] For non-medical applications, large diameter tubular bodies may be desirable. For example, the outer diameter of the tubular body may be in the centimetre and metre range. For medical applications, a tubular or cylindrical body provides a smooth outer surface for ease of insertion into a patient. For medical applications, the tubular body may have an outer diameter in the range of micrometres to tens of millimetres. The tubular body may have an outer diameter of 0.1 to 30 mm, 1 to 10 mm, 1 to 2 mm, 2 to 4 mm, 4 to 6 mm, 6 to 10 mm. Preferably, the outer diameter may be 2 to 2.4 mm, 2 to 2.2 mm or 2 to 2.11 mm. It is to be understood that other dimension tubular bodies may be used for treatment of human organs, in particular, the human brain, or in the treatment of animals which may be larger or smaller than humans. These diameters are non-limiting, and the skilled person would appreciate that the tubular body inner diameter and outer diameter may each be in the range of micrometres to metres, depending on the application.

[0062] Guide Section and tip

[0063] The device may also include a guide section. The guide section comprises: a first opening at a proximal end of the guide section; a second opening at a distal end of the guide section; and a guide section inner lumen extending from the first opening to the second opening. The distal end of the guide section is coupled to the proximal end of the body, such that the second opening of the guide section is coupled to the first opening of the body. The guide section inner lumen is continuous with the inner lumen of the body.

[0064] Coupling of the guide section with the body may include joining the distal end of the guide section to the proximal end of the body or manufacturing the guide section and body as a single piece. Manufacturing as a single piece can be used to create a device where the guide section and body are fully integrated, and preferably undetachable.

[0065] The body and guide section may be manufactured as separate pieces or as a single piece. Techniques for manufacturing as separate or a single piece(s) can include direct laser metal sintering, machining (particularly CNC machining), forging, casting, stereolithography, 3D- printing and injection moulding. Joining techniques include methods including mechanical joining, welding, fusing, soldering, brazing, or the use of adhesives.

[0066] At least a portion of the guide section inner lumen may be straight between the proximal end of the guide section and the distal end of the guide section. Alternatively, at least a portion of the guide section inner lumen may follow a curved path between the proximal end of the guide section and the distal end of the guide section. The portion of the guide section inner lumen following the curved path may be at the distal end of the guide section. The curved path may provide a gradual lead into the helical path or bent path followed by the inner lumen of the body. For example, the curved path may easily accept the coil-forming component and then progress to the portion of the helical path with a smaller diameter and pitch that is required for the coilforming component to take its final shape. For example, the curved path may easily accept the coil-forming component and then progress to the bent path that constrains the coil-forming component and allows it to take its final shape. This initial curved path allows for a more gradual change in the deformation the coil-forming component experiences and can result in a smoother ramp of the axial force required to push the coil-forming component through the helical inner lumen. At least a portion of the guide section inner lumen may be tapered between the proximal end of the guide section and the distal end of the guide section.

[0067] The straight portion of the guide section inner lumen may be parallel to a central axis of the guide section. The straight portion of the guide section inner lumen may be parallel to and offset from a central axis of the guide section. Alternatively, the straight portion of the guide section inner lumen may be at an angle to a central axis of the guide section. A straight portion of the guide section inner lumen being parallel to and offset from a central axis of the guide section gives the most space in the device for the inner lumen of the body to follow a portion of a helical path or a bent path.

[0068] The straight portion of the inner lumen of the guide section may have the same cross-section as the first opening of the body. The straight portion of the inner lumen of the guide section may have the same cross-section as the inner lumen of the body. The guide section inner lumen cross-section may be circular or oval.

[0069] The tapered portion of the guide section inner lumen may extend from the first opening at a proximal end of the guide section to an intermediate position along the length of the guide section. The first opening of the guide section may be larger in diameter than the second opening of the guide section. A tapered guide section inner lumen reduces friction on the coilforming component. A straight portion of the guide section inner lumen may extend from the intermediate position along the length of the guide section to the second opening at a distal end of the guide section.

[0070] The first opening and / or second opening of the guide section may be circular or oval. Preferably, the first opening and second opening of the guide section are dimensioned to match the cross- sectional dimensions of the guide section inner lumen. The second opening of the guide section may have the same shape and / or dimensions as the first opening of the body.

[0071] The guide section may be tubular in shape. A tubular guide section may be referred to in this application as a “guide tube”. The guide tube may assist with the positioning and / or advancement of the body of the device, for example, when inserted into a patient.

[0072] For medical applications, the outer diameter of the guide tube may be in the range of micrometres to tens of millimetres. The outer diameter of the guide tube may be 0.1 to 30 mm, 1 to 10 mm, 1 to 2 mm, 2 to 4 mm, 4 to 6 mm, 6 to 10 mm. Preferably, the outer diameter of the guide tube may be 2 to 2.4 mm, 2 to 2.2 mm or 2 to 2.11 mm. The inner diameter of the guide tube may be a dimension corresponding to the outer diameter of the coil-forming component. The inner diameter of the guide tube may be 0.001 to 10 mm, 0.05 mm to 2 mm, 0.8 to 1.2 mm, or 4 to 6 mm. The length of the guide tube may be suitable to position the helical coil in situ, the length may be about 36 cm or more. The guide tube may be appropriately sized for specialist treatments. For example, for neurosurgical applications, the outer diameter of the guide tube can be 2.2 mm. It is to be understood that other sizes may be used for treatment of human organs, in particular, the human brain, or in the treatment of animals which may be larger or smallerthan humans. For non-medical applications, the guide tube may have an outer diameter and an inner diameter in the range of micrometres to metres. These diameters and lengths are non-limiting, and the skilled person would appreciate that the guide tube inner diameter and guide tube outer diameter may each be in the range of micrometres to metres, depending on the application.

[0073] An insertion tip may be coupled to a distal end of the body. Such an insertion tip may assist in the insertion of the device into a target location, for example, into the tissue of a patient. The insertion tip may include a sharpened distal end, optionally a needle point at the distal end. Coupling of the insertion tip with the body may include joining the insertion tip to the distal end of the body or manufacturing the insertion tip and body as a single piece. The body and insertion tip may be manufactured as separate pieces or as a single piece. As discussed previously, techniques for manufacturing as separate or a single piece(s) can include direct laser metal sintering, machining (particularly CNC machining), forging, and casting, stereolithography, 3D- printing and as well as injection moulding. Joining techniques include methods including mechanical joining, welding, fusing, soldering, brazing, or the use of adhesives.

[0074] Preferably, the guide section is suitable for insertion into the tissue of a patient. The guide section may be an insertion needle or a part thereof. Preferably the device, comprising the guide section and body, is a distal part of an insertion needle. The proximal end of the guide section may be coupled to a distal end of a delivery tube such that the device and delivery tube comprise an insertion needle.

[0075] Coil-forming Component

[0076] The coil-forming component may comprise a solid wire. The solid wire may include an insertion tip at its distal end. The coil-forming component may comprise a tube. The tube may be a catheter, or an injection catheter.

[0077] The tube may include a removable core. The removable core may be of the same or a different material to the tube. The removable core may be a surgical probe. Optionally, the surgical probe may extend beyond the distal end of the tube. Alternatively, the removable core may be a stylet, such as a wire or rod. The stylet may be a rigid or malleable wire or rod. The stylet may be used to assist in curving of the tube as it is advanced through the inner lumen of the body. The removable core may be a catheter. The removable core may not extend beyond the distal end of the tube. The removable core may alternatively extend beyond the distal end of the tube. A core which extends beyond the distal end of the tube could be used to further increase the volume of tissue accessed by the device. For example, in critical limb ischaemia the coil-forming component could form a coil around the artery and a removable core could extend from the end of the helical coil to delivery therapy into a large volume of tissue around the artery. A removable core may be beneficial in maintaining the rigidity and / or the patency of the tube.

[0078] The tube may include a single aperture at the distal end of the tube. In addition, or in the alternative, the tube may include one or more apertures in a wall of the tube. A tube having apertures only in the side walls might permit a smooth-entry tip, with the potential to reduce tissue trauma.

[0079] The coil-forming component may comprise a material having a low yield strain. Preferably the material has a yield strain (sy) of less than 10%, less than 1%, preferably about 0.2%. The yield strain of the material is determined at room / body temperature (22°C). The yield strain of the material can be determined by tensile strength testing, for example using ISO 6892-1 :2019 or ASTM E8. The breaking strain (fracture strain, EB) of the material will be sufficiently high to avoid straining to the point where the material breaks.

[0080] According to a first aspect of the invention, the relationship between maximum applied strain (£m<«) within a segment of tube or wire of circular cross-section passing through the portion of the helical path prescribed by the inner lumen is given below.

[0081] The inner lumen’s helical path is described by its neutral diameter (0>ieiara<) and its pitch (p). The coil-forming component which is a tube or wire has an outer diameter (OD).

[0082] A given material can be used for the coil-forming component provided the maximum strain (£mnz) for the tube or wire passing through the inner lumen is greater than the yield strain of that material (the point at which permanent deformation occurs), yet smaller than its strain at break. The geometry of the body of the device can be used to determine the materials which are suitable for the coil-forming component.

[0083] Coil-forming components formed from materials with a higher yield strain may be combined with helical paths which have smaller diameters. This is referred to as an “over-tight” helical path. Over-tight helical paths can combat the increased yield strain and force a helix to form.

[0084] For medical applications, there will be defined constraints on the helical path diameter ( pitch (p) and the outer diameter of the coil-forming component (OD). For example, constraints on the diameter and pitch of the helical path, ( and P), and thus resulting helical coil, may be driven by the size of the treatment area and / or the diffusion reach of the therapeutics. For certain neurological applications, the diameter and pitch may each be 5 to 10 mm or 6 to 8 mm, preferably 8 mm. For certain neurological applications, the OD may be in the region of 0.001 to 6 mm, 0.001 to 0.05 mm, 0.05 to 2 mm, 0.8 to 1 .2 mm, or 4 to 6 mm, preferably 0.9 mm. For a diameter and pitch of 8 mm, and coil-forming component outer diameter of 0.9 mm, this results in a maximum strain ( >nax) of 0.102 for the tube passing through this inner lumen geometry.

[0085] Any material that has a yield strain below the maximum strain for the specific inner lumen geometry, and that has a breaking strain which exceeds the maximum strain will be suitable. For the specific neurological application example above with maximum strain ) of 0.102, suitable materials are set out in table 1 .

[0086] Table 1

[0087] The skilled person will appreciate that any material suitable for forming a coil when passed through the device could be used. For example, with appropriate selection of the parameters of helical diameter, helical pitch and tube / wire outer diameter, suitable materials can be determined. The coil-forming component may comprise a metal selected from one or more of stainless steel, aluminium alloy, titanium, platinum, copper, and other metallic alloys. Preferably the coil-forming component comprises titanium. Titanium can facilitate the use of intra-operative MRI. The coil-forming component may comprise a low yield strain plastic, for example, acrylonitrile butadiene styrene (ABS). The above list of suitable coil-forming component materials is exemplary, but not exhaustive.

[0088] The tube may be a plastic tube having a removable core. The removable core may comprise a metal having a low yield strain.

[0089] The tube may be a plastic tube having a metal wire running through the tube wall. The metal wire may be non-magnetic (for example titanium or stainless steel) to facilitate the use of intraoperative MRI. The solid wire or tube may comprise a material suitable for electrical conduction, for example, solid steel, copper, gold, silver, platinum, titanium and or a metal alloy. At least a portion of the solid wire or tube may be surrounded by insulation. A portion of the solid wire or tube not surrounded by insulation may be suitable for the conduction of electric current, for example, for the delivery of radiofrequency ablation to a target site. Radiofrequency ablation can be useful in the burning of problematic tissue such as tumours or epileptogenic foci in the brain.

[0090] The solid wire may be used to create a helical coil for mechanical purposes, such as fixation of bone. For mechanical fixation, materials with high stiffness (e.g. stainless steels) are desirable.

[0091] For non-medical applications, the solid wire coil-forming component may have a diameter (outer diameter) in the range of micrometres to metres. For medical applications, the solid wire coilforming component may have a diameter (outer diameter) of micrometres to tens of millimetres. The solid wire coil-forming component may have a diameter of 0.001 to 10 mm, 0.001 to 0.05 mm, 0.05 to 2 mm, 0.8 to 1 .2 mm, or 4 to 6 mm.

[0092] For non-medical applications, the tube coil-forming component may have an outer diameter, an inner diameter and tube wall thickness each in the range of micrometres to metres. For medical applications, the tube coil-forming component may have a diameter of micrometres to tens of millimetres. The outer diameter of the coil-forming component may be constrained by the diameter below which fluidic shear stress results in excessive stem cell death. The tube may have an outer diameter of 0.001 to 10 mm, 0.001 to 0.05 mm, 0.05 to 2 mm, 0.8 to 1 .2 mm, or 4 to 6 mm. The tube may have an inner diameter of 0.0005 mm to 5 mm, 0.05 to 0.6 mm, 1 to 2 mm, 0.6 to 2.7 mm, or 4 to 5 mm. The tube is preferably a thin-walled tube. The tube wall thickness may be 0.05 to 1 mm.

[0093] These diameters of the solid wire coil-forming component and tube coil-forming component, and wall thickness of the tube are non-limiting, and the skilled person would appreciate that the dimensions may be in the range of micrometres to metres, depending on the application.

[0094] Tubes may be used to deliver therapy selected from one or more of cells, therapeutics (including gene therapy), drugs and growth factors to a tissue. Tubes with a larger inner diameter (0.6 to 2.7 mm or 3 to 5 mm) might be preferred for spheroid or organoid delivery. Tubes with a smaller inner diameter (0.05 to 0.6 mm) might be preferred for single cell suspensions. For certain neurological applications, the OD may be in the region of 0.001 to 6 mm, 0.001 to 0.05 mm, 0.05 to 2 mm, 0.8 to 1 .2 mm, or 4 to 6 mm, preferably 0.9 mm.

[0095] Tubes may also be used to deliver suture material along a join line between two tissues to facilitate wound closure.

[0096] The coil-forming component may further comprise a drug-impregnated coating. The coating may be biodegradable. A drug-impregnated coating may reduce inflammation at the delivery site of the coil. The degradation rate of the biodegradable coating can be tailored to facilitate the delayed release of therapeutics. The coating may include antibiotics, antimicrobials, immunotherapies (e.g. immune checkpoint inhibitors), antisense oligonucleotides, growth factors and chemotherapeutic agents. Chemotherapeutic agents may include agents for the treatment of primary and metastatic brain cancer, including but not limited platinum compounds (e.g. cisplatin), alkylating agents (e.g. carmustine) and plant alkaloids (e.g. etoposide). Other compounds may be incorporated in the coating, specific for the application. For example, antisense oligonucleotides for the treatment of neurodegenerative disorders or growth factors e.g. GDNF for the treatment of Parkinson’s disease, may be included.

[0097] The coil-forming component may include a frangible or detachable portion at a predetermined position along its length. The frangible portion may be a portion of the coil-forming component of reduced cross-section. For example, the frangible portion may be an indentation or nick in the surface of the coil-forming component. The frangible portion may be a portion of the coilforming component comprising a brittle material. The frangible portion may be a portion of the coil-forming component comprising a material which is able to break upon passing of a current through the coil-forming component.

[0098] The frangible / detachable portion may allow release of the helical coil once formed. In medical applications, a frangible / detachable portion allows release of the helical coil for deployment in the target location. The coil-forming component may alternatively or additionally include a pusher rod which is configured to push the coil-forming component into at least the inner lumen of the body (and optionally, the inner lumen of the guide section) and form the helical coil. Retraction of the pusher rod leaves the as-formed helical coil in situ.

[0099] The as-formed helical coil can be retracted through the body of the device. A rotation may be applied to the coil-forming component (of the formed helical coil) during retraction. During withdrawal, the coil-forming component may be configured to return to a straight conformation or to a straighter conformation having a greater radius of curvature than the formed helical coil. For example, the coil-forming component may retain at least some curvature when being drawn back through the inner lumen of the body. According to a second aspect of the invention, the rotation applied during retraction may be equal in magnitude and opposite in direction to the rotation applied when forming the coil.

[0100] Certain properties of the coil-forming component make it suitable for a specific application. For example:

[0101] For radiofrequency ablation in the brain, suitable coil-forming components include a solid wire of solid steel, titanium or alloy having a diameter of 0.05 to 2 mm, and further comprising suitable insultation surrounding at least a portion of the wire.

[0102] For cell therapy in the brain, suitable coil-forming components include a thin-walled tube having a single aperture at the distal end of the tube, wherein the tube is made of stainless steel, titanium or alloy having an inside diameter of 0.6 to 2.7 mm.

[0103] For gene therapy in the brain, suitable coil-forming components include a thin-walled tube having multiple apertures along the length of the tube, wherein the tube is made of stainless steel, titanium or alloy having an inside diameter of 0.05 to 0.6 mm.

[0104] For combination therapy such as gene / cell therapy with radiofrequency ablation, suitable coil-forming components include a thin-walled tube having at least one aperture along the length of the tube, wherein the tube is made of stainless steel, titanium or alloy having an inside diameter of 0.05 to 2.7 mm, and further comprising suitable insultation surrounding at least a portion of the tube.

[0105] For the delivery of therapeutics, suitable coil-forming components include a thin-walled tube having at least one aperture along the length of the tube, wherein the tube is made of stainless steel, titanium or allow, having an inside diameter of 0.05 to 2.7 mm.

[0106] For delayed drug release, suitable coil-forming components include a solid metal wire with a drug-impregnated coating, wherein a distal end of the wire is detachable, allowing release of the helical coil once formed.

[0107] For bone-to-bone fixation in the treatment of fractures, suitable coil-forming components include a solid metal wire (with or without a drug-impregnated coating), wherein a distal end of the wire is detachable allowing release of the helical coil once formed.

[0108] For wound closure (suturing), suitable coil-forming components include a thin-walled tube having a single aperture at the distal end of the tube, wherein the tube is made of stainless steel, titanium or alloy, having an inside diameter of 0.2 to 1 .0 mm. The materials and dimensions of the coil-forming component, geometry of the inner lumen and applied rotation which result in the formation of a helical coil can be readily determined. For example, the coil-forming component can be advanced through the inner lumen of the body and out of the second opening of the body. A resulting helical coil provides positive confirmation.

[0109] Kit

[0110] According to a third aspect of the present invention, there is provided a kit comprising the device for the formation of a helical coil of the first aspect of the invention and a coil-forming component.

[0111] The kit may further comprise a syringe, attachable to a proximal end of the coil-forming component, when the coil-forming component is a tube. The syringe may contain therapeutics. The syringe may contain a cell suspension, gene therapy, drugs, growth factors and the like.

[0112] The kit may further comprise an RF source and / or a power supply. The RF source and / or power supply may be connectable to the coil-forming component, when the coil-forming component comprises a material suitable for electrical conduction.

[0113] According to a fourth aspect of the present invention, there is provided a method for the formation of a helical coil using a kit according to a third aspect of the invention comprising the device for the formation of a helical coil of the first aspect of the invention and a coil-forming component, said method comprising: advancing a coil-forming component into the first opening of the body, through the inner lumen and out of the second opening of the body; and forming a helical coil from the coil-forming component.

[0114] The coil-forming component may be advanced under axial loading. Alternatively, the coilforming component may be advanced through the inner lumen under application of a rotation. The rotation may be applied about the longitudinal axis of the coil-forming component. The rotation may be an axial rotation with a consistent rate of rotation. The rotation may induce a torque or torsional load in the coil-forming component as it advances through the inner lumen. The applied rotation can be utilised to vary the dimension of the as-formed helical coil, for example, to vary the pitch or diameter of the coil. The rotation may be applied to the coil-forming component by means of providing a rotation about its normal medial axis. The rate of rotation applied to the coil-forming component is kept constant as the coil-forming component is passed through the helical inner lumen. To maintain uniform pitch (and diameter) a constant rate of rotation (torsion) is applied to the coil-forming component during its advancement. For example, the rotation applied to the coil-forming component may be controlled such that the rotation rate (torsion) of the coil-forming component as it enters and advances through the inner lumen is constant. If the rotational rate is varied, then a helical coil of varied pitch and diameter can be produced (a “progressive helix”). Variation in either pitch or diameter will result in coring / destruction of the tissue as the coil progresses.

[0115] Method for in situ coil formation

[0116] The method of the second or fourth aspect of the invention can be used for the in situ formation of a helical coil at a target location, where the method further comprises positioning the device at the target location. The formation of the helical coil from the coil-forming component takes place at the target location. The target location may be a tissue of a patient and the device includes a guide tube. Positioning the device at the target location may comprise inserting the device into the body of the patient and positioning the second opening of the body adjacent said target location. The method may further include advancing the coil-forming component into the first opening of the guide tube, through the inner lumen of the guide tube and out of the second opening of the guide tube, into the first opening of the body. The coil-forming component is then advanced through the inner lumen and out of the second opening of the body to form a helical coil at the target location.

[0117] The advancement of the coil-forming component through the helical inner lumen of the body of the device according to the first aspect of the invention causes the coil-forming component to deform and to take on a helical shape. The advancement of the coil-forming component through the bent inner lumen of the body of the device with the application of a rotation according to the second aspect of the invention causes the coil-forming component to deform and to take on a helical shape. As the coil-forming component advances, the helical coil takes shape. The advancement of the helical coil winds the coil into the tissue. Intra-operative imaging can confirm the trajectory of the helical coil. When the desired number of turns of the helical coil has been achieved, advancement may be halted.

[0118] The position of the second opening of the body is important to ensure that the helical is deployed to the precise location in the tissue of the patient. The body must be positioned so that the helical coil can exit the second opening and enter the tissue in the correct direction.

[0119] The method may further comprise retracting the helical coil through the inner lumen of the body of the device. A rotation may be applied to the coil-forming component (of the formed helical coil) during retraction. The rotation applied during retraction may be equal in magnitude and opposite in direction to the rotation applied when forming the coil. During retraction, the coilforming component may be configured to return to a straight conformation or to a straighter conformation having a greater radius of curvature than the formed helical coil. For example, the coil-forming component may retain at least some curvature when being drawn back through the inner lumen of the body.

[0120] The coil-forming component may comprise a frangible or detachable portion at a predetermined position, and the method may further comprise detaching the helical coil from the remainder of the coil-forming component once formed. The method may further comprise retracting the remainder of the coil-forming component and leaving the detached as-formed helical coil at the target location.

[0121] The coil-forming component may alternatively or additionally include a pusher rod. The method may comprise pushing the pusher rod to advance the coil-forming component through the helical path of the inner lumen and out of the second opening of the body to form the helical coil. The method may comprise attaching the pusher rod to the coil-forming component and pushing the pusher rod under rotation to advance the coil-forming component through the bent path of the inner lumen and out of the second opening of the body to form the helical coil. The pusher rod may be configured to transfer linear and rotational motion to the coil-forming component. The pusher rod may be configured to engage the coil-forming component via a mating engagement, such as via a tongue and groove interface or screwdriver-like attachment. The method may further comprise retracting the pusher rod and leaving the as-formed helical coil at the target location.

[0122] The device can be used for the in situ deposition of cells and / or therapeutics in a helical pattern. Specifically, a method of administering therapy into the tissue of a patient in a helical pattern is disclosed, comprising the in situ formation of a helical coil and further comprising the administration of therapeutics to the patient via the helical coil.

[0123] The coil-forming component may be a tube, and the method includes withdrawing the helical coil from the target location while administering therapeutics through the tube. Therapeutics are administered into the void left in the tissue by the helical coil. Therapeutics may include one or more of a suspension of cells for cell therapy, organoids for therapy, pharmaceutical agents including drugs, nucleic acids, growth factors, fluids, and other suitable components. Therapeutics may be packaged, for example in nanoparticles, micelles, virus particles (e.g. Adeno-Associated Virus (AAV)).

[0124] The withdrawing of the tube includes withdrawing the tube into the inner lumen of the body. The tube is withdrawn at a rate which may allow controlled delivery of the therapeutics to the target location. Withdrawing of the helical tube from the tissue is along the same path as insertion of the helical tube into the tissue. The rate of retraction may avoid coring of the tissue. The rate of retraction may be around 1.1 mm / s.

[0125] During withdrawal or retraction, the coil-forming component may be configured to return to a straight conformation or to a straighter conformation having a greater radius of curvature than the formed helical coil. For example, the coil-forming component may retain at least some curvature when being drawn back through the inner lumen of the body. Rotation may be applied to the coil-forming component during withdrawal of the helical coil from the target location. Preferably, the rotation is equal in magnitude (rate of rotation) and opposite in direction (clockwise / anticlockwise) to the rotation applied when forming the helical coil. This may return the coil-forming component to a straight conformation (or a straighter conformation than when formed as the helical coil).

[0126] Withdrawal of the tube and administration of the therapeutics can be simultaneous. Synchronous withdrawal and delivery can allow for uniform delivery of the therapeutics into the helical space left by the coil. Alternatively, withdrawal of the tube and administration of the therapeutics can be non-concurrent. The tube may be withdrawn a small distance and then therapeutics administered. This may be repeated until the whole of the helical coil has been withdrawn from the target location.

[0127] The device is suitable for use in convection enhanced delivery (CED) of therapeutics, particularly for gene therapies and antisense oligonucleotides. The tubular coil-forming component can be used to deliver therapeutics under pressure to a target location. CED may be advantageously used to deliver therapeutics using bulk flow rather than conventional administration by diffusion. The tubular coil-forming component may comprise a plurality of apertures in the wall of the tube, a porous tip, a tip with a diameter which is smaller than the rest of the tube, or a balloon at its distal end. The method may be used for the treatment of a number of diseases, including neurological diseases (including, for example, Parkinson’s disease, Huntington’s disease or multiple sclerosis), metabolic diseases (e.g. diabetes), musculoskeletal diseases (e.g. muscular dystrophy or critical limb ischaemia) and cancer. The tissue to be treated may be the brain (including, e.g. the putamen, the striatum, or the region or regions of disease-related demyelination), the kidney, lung, heart, liver, symptomatic muscle, or lower limb tissue adjacent to diseased involved artery or arteries.

[0128] The coil-forming component may be a metal tube or a solid metal wire, and the method includes administering electrotherapy by passing an electric current through the helical coil. This method provides in situ delivery of electrotherapy and / or radioablation to a patient.

[0129] The helical coil may itself form an electrode; the solid wire or tube may comprise a material suitable for electrical conduction. Alternatively, the helical coil may comprise electrodes positioned along its length to administer electrotherapy and / or radioablation from discrete points.

[0130] According to a fifth aspect of the invention, cells are disclosed for use in a method of treating disease, wherein said cells are administered to the tissue of a patient in a helical pattern. The cells may be e.g. stem cells, or pancreatic islet cells. The method comprising the in situ formation of a helical coil at a target location using the device for the formation of a helical coil, comprising a guide tube, and a coil-forming component which is a tube. The method comprises inserting the device into the body of the patient and positioning the second opening of the body adjacent said target location; advancing the coil-forming component into the first opening of the guide tube, through the inner lumen of the guide tube and out of the second opening of the guide tube, into the first opening of the body; advancing the coil-forming component through the inner lumen and out of the second opening of the body and forming a helical coil from the coilforming component at the target location. The method further comprises withdrawing the helical coil from the target location while administering the cells through the tube.

[0131] The cells for use in a method of treating disease according to the fourth aspect, wherein the disease is a neurological disease. The disease may be Parkinson’s disease and the tissue to be treated is the putamen. The disease may be Huntington’s disease and the tissue to be treated is the striatum. The disease may be multiple sclerosis and the tissue to be treated is the region or regions of disease-related demyelination of the individual undergoing therapy. The cells for use in a method of treating disease according to the fifth aspect, wherein the disease is metabolic. The disease may be diabetes and the tissue to be treated is the liver.

[0132] The cells for use in a method of treating disease according to the fifth aspect, wherein the disease is musculoskeletal. The disease may be muscular dystrophy and the tissue to be treated is any symptomatic muscle. The disease may be critical limb ischaemia and the tissue to be treated is affected or adjacent lower limb tissue to the involved artery or arteries.

[0133] Application

[0134] To use the device and method, the user preferably plans an insertion trajectory into the tissue of the patient. The insertion may be planned and accomplished using stereotactic surgery techniques. The device, including a guide section and insertion tip (and optionally a delivery tube to form an insertion needle), may be attached to a stereotactic frame. The device can then be advanced into the brain.

[0135] The above methods may be performed robotically. That is, the device may be robotically driven or controlled. Accordingly, rather than a clinician manipulating the device to advance / retreat the coil-forming component, a robot is used to manipulate the device and form the helical coil. The device may be part of a robotic surgical system comprising the device, a robotic arm assembly holding the device, a master manipulator and a controller configured to control movement of the device in response to user operation of the master manipulator in such a manner that the device can be positioned at a target location. The controller may be further configured to control advancement of a coil-forming component through the inner lumens of the guide section and body of the device in response to user operation of the master manipulator. Where the coilforming component is advanced under a rotation, the controller may also be configured to control applied rotation (or torque) of the coil-forming component.

[0136] When the coil-forming component is a tube, the controller may be further configured to control withdrawal of the helical coil from the target location while administering therapeutics through the tube. The controller may be further configured to control withdrawal of the helical coil from the target location at a rate synchronised with the delivery of therapeutics administered through the tube. FIGURES

[0137] The invention is further illustrated with reference to the following figures in which:

[0138] Figure 1 shows a device for the formation of a helical coil. Figure 1 A shows a body having an inner lumen following a quarter-turn of a helical path. Figure 1 B shows a body having an inner lumen following a half-turn of a helical path.

[0139] Figure 2A shows a device for the formation of a helical coil, and Figure 2B shows the same device with a coil-forming component in the inner lumen. The device includes the body and a guide tube.

[0140] Figures 3A, 3B and 3C show cross-sectional views of a device for the formation of a helical coil, the device comprising the body and a guide tube.

[0141] Figure 4 shows a perspective view of a device for the formation of a helical coil, and a representative helical path for the helical coil.

[0142] Figures 5A and 5B show a perspective view of a device for the formation of a helical coil, and a helical coil formed by the device.

[0143] Figures 6A and 6B show perspective and cross-sectional views of a device for the formation of a helical coil under application of rotational advancement. The device includes a body and a guide tube. Figure 60 shows the device of Figures 6A and 6B coupled to a delivery tube.

[0144] Figure 7A illustrates a perspective view of a device for the formation of a helical coil under application of rotational advancement (arrow indicating rotation), and Figure 7B illustrates an orthogonal view of the device of Figure 7A including a helical coil formed by the device.

[0145] Figure 8A is a schematic illustrating a potential use of the device, which is part of an insertion needle, to create an in situ helical coil and Figure 8B is a CT image of the device and helical coil in situ in a human skull.

[0146] Figure 9A is an image of the device and as-formed helical coil. Figure 9B shows the dispensing of fluid from the helical coil. Figures 9C to 9E are images of comparative devices dispensing fluid. Figures 10A to C are images of the in situ formation of a helical coil at a target location using the device at time points of 10s, 40s and 90s respectively after the start of helical coil administration. Figures 10D to F are images of the withdrawal of the helical coil and administration of fluid at time points of 10s, 60s and 150s after the start of withdrawal. Administration is in the void created by the helical coil.

[0147] Figures 11A to F are images of the as-formed helical coil as deployed in agarose blocks of different concentrations (0.4%, 0.6%, 0.8%, 1.5%, 3% and 4% respectively). The front injected view in each of Figures 11A to F show the dispensing of fluid from the helical coil in each of the agarose blocks.

[0148] Figures 12A, 12B, 12C, and 12D show fluorescence-activated cell sorting viability data for T- cells from the spleen of a C57 / BL6 mouse. The images show viability data for cells after passing through no device (12A), the helical coil (12B), a 20-gauge straight needle (12C), and a 24- gauge straight needle (12D).

[0149] DETAILED DESCRIPTION

[0150] The present invention will now be further elaborated by reference to the figures which are nonlimiting.

[0151] Figure 1A and 1 B illustrate a device 100 for the formation of a helical coil 109. The device 100 includes a tubular body 101 , having a proximal end 103 and a distal end 105. The tubular body

[0152] 101 also includes an inner lumen 106 extending from a first opening 102 of the body to a second opening 104 of the body. The first opening 102 is placed at the proximal end 103 of the body and the second opening 104 is located at a distance from the distal end 105 of the body. A guide tube 200 is coupled to the proximal end 103 of the body.

[0153] In Figure 1A, the inner lumen 106 follows a quarter-turn of a helical path between the first opening 102 and the second opening 104 of the body. The helical path terminates at the second opening 104. The second opening 104 is located on a side wall of the body 101.

[0154] In Figure 1 B, the inner lumen 106 follows a half-turn of a helical path between the first opening

[0155] 102 and the second opening 104 of the body. The helical path terminates at the second opening 104. The guide tube 200 comprises a first opening 202 at a proximal end 203 of the guide tube, a second opening 204 at a distal end 205 of the guide tube and a guide tube inner lumen 206 extending from the first opening 202 to the second opening 204. The second opening 204 of the guide tube is coupled to the first opening 102 of the body and the guide tube inner lumen 206 is continuous with the inner lumen 106 of the body. A portion of the guide tube inner lumen 206 is straight and parallel to the central axis of the guide tube. The diameter of the guide tube inner lumen 206 is larger than the diameter of the inner lumen 106 of the body. This reduces friction on the coil-forming component 108.

[0156] The device 100 is configured to receive a coil-forming component 108 at the first opening 202 of the guide tube and into the guide tube inner lumen 206 and through the first opening 102 of the body. The advancement of the coil-forming component 108 through the inner lumen 106 and out of the second opening 104 of the body results in the formation of a helical coil.

[0157] The tubular body 101 may be rigid or semi-rigid, and may be made for example of stainless steel, titanium, copper and its alloys, silicon, polyetheretherketone (PEEK), or another suitable material.

[0158] The Figures are not necessarily to scale. The diameters of the components are exaggerated for clarity of illustration. The tubular body 101 may have an outer diameter and the inner lumen 106 may have a diameter suitable for the intended use of device 100.

[0159] The guide tube 200 may also be rigid or semi-rigid, and may be made example of stainless steel, titanium, copper and its alloys, silicon, polyetheretherketone (PEEK), or another suitable material.

[0160] Figures 2A and 2B provide a view of a device 100 for the formation of a helical coil. The device 100 includes a tubular body 101 , having a proximal end 103 and a distal end 105. The tubular body 101 also includes an inner lumen 106 extending from a first opening 102 of the body to a second opening 104 of the body. The first opening 102 is placed at the proximal end 103 of the body and the second opening 104 is located at a distance from the distal end 105 of the body. The inner lumen 106 follows an eighth-turn of a helical path between the first opening 102 and the second opening 104 of the body. The device 100 further includes a guide tube 200. The guide tube 200 comprises a first opening 202 at a proximal end 203 of the guide tube, a second opening 204 at a distal end 205 of the guide tube and a guide tube inner lumen 206 extending from the first opening 202 to the second opening 204. The guide tube 200 and tubular body 101 are made as a single piece, such that the guide tube and body are fully integrated. The distal end 205 of the guide tube is coupled to the proximal end 103 of the body and the second opening 204 of the guide tube is coupled to and continuous with the first opening 102 of the body. The guide tube inner lumen 206 is continuous with the inner lumen 106 of the body. The guide tube inner lumen 206 and the tubular body inner lumen 106 (below the surface) are shown in dashed lines.

[0161] A portion of the guide tube inner lumen 206 is straight. A portion of the guide tube inner lumen 206 is tapered. The tapered portion of the guide tube inner lumen extends 206 from the first opening 202 at a proximal end 203 of the guide tube to an intermediate position 207 along the length of the guide tube. The first opening 202 of the guide tube is larger in diameter than the second opening 204 of the guide tube. The tapered guide section inner lumen 206 reduces friction on the coil-forming component 108 as it advances into the guide tube and along the guide tube inner lumen 206. The straight portion of the guide tube inner lumen 206 extends from the intermediate position 207 along the length of the guide tube to the second opening 204 at the distal end 205 of the guide section. The straight portion of the guide tube inner lumen 206 is parallel to and offset from a central axis of the guide tube 200. This provides space for the inner lumen 106 of the body to follow an eighth-turn of a helical path.

[0162] An insertion tip 300 is coupled to the distal end 105 of the body. The insertion tip 300 is configured to facilitate insertion of the device 100.

[0163] The device 100, comprising the tubular body 101 , guide tube 200 and insertion tip 300, is a distal part of an insertion needle. The proximal end 203 of the guide tube is coupled to a distal end of a delivery tube 400 such that the device 100 and delivery tube 400 comprise an insertion needle.

[0164] As shown in Figure 2B, a coil-forming component 108 can be advanced through the delivery tube 400. The device 100 is configured to receive the coil-forming component 108 at the first opening 202 of the guide tube and into the guide tube inner lumen 206 and through the first opening 102 of the body. The advancement of the coil-forming component 108 through the inner lumen 106, following the eighth-turn helical path, and out of the second opening 104 of the body results in the formation of a helical coil.

[0165] The coil-forming component 108 is a tube 110, such as a catheter or injection catheter. The coilforming component 108 may be made, for example, of a metal having a low yield strain such as stainless steel, titanium, platinum and metallic alloy. The coil-forming component 108 may have an inner diameter of 0.6 to 2.7 mm, but other suitable dimensions may be used.

[0166] Figures 3A and 3C show side views of the device 100 of Figure 2, with the guide tube inner lumen 206 and the tubular body inner lumen 106 (below the surface) shown in dashed lines. The device 100 includes a tubular body 101 , having a proximal end 103 and a distal end 105, and a guide tube 200, having a proximal end 203 and a distal end 205. The guide tube 200 and tubular body 101 are made as a single piece, such that the guide tube and tubular body are fully integrated. The guide tube 200 includes a guide tube inner lumen 206 having a straight portion and a tapered portion. The guide tube inner lumen 206 is continuous with the inner lumen 106 of the body. An insertion tip 300 is coupled to the distal end 105 of the body. The insertion tip 300 and tubular body 101 are made as a single piece, such that the insertion tip 300 and body 101 are fully integrated. Figure 3A includes a representative helical path for the helical coil 109 after exiting the second opening 104 of the body.

[0167] Figure 3B shows a cross-section through the device 100 along line G-G in Figure 3A. The tapered portion of the guide tube inner lumen extends 206 from the first opening 202 at a proximal end 203 of the guide tube to an intermediate position 207 along the length of the guide tube. The first opening 202 of the guide tube is larger in diameter than the second opening 204 of the guide tube. The straight portion of the guide tube inner lumen 206 extends from the intermediate position 207 along the length of the guide tube to the second opening 204 at the distal end 205 of the guide section. The straight portion of the guide tube inner lumen 206 is parallel to and offset from a central axis of the guide tube 200. Figure 3B shows that the offset of the straight portion provides space for the inner lumen 106 of the body to follow an eighthturn of a helical path.

[0168] Figure 4 illustrates a perspective view of a device 100 for the formation of a helical coil and a representative helical path for the helical coil 109 after exiting the second opening 104 of the body.

[0169] Figures 5A and 5B show a deployed position of the device of Figure 2, in which a helical coil 109 formed by the device 100 protrudes from the second opening 104 of the tubular body 101. The device 100, comprising the tubular body 101 , guide tube 200 and insertion tip 300, is a distal part of an insertion needle. The proximal end 203 of the guide tube is coupled to a distal end of a delivery tube 400 such that the device 100 and delivery tube 400 comprise an insertion needle.

[0170] The coil-forming component 108 is a tube 110 with a single aperture 112 at the distal end. The coil-forming component 108 may be made, for example, of a metal having a low yield strain such as stainless steel, titanium, platinum and metallic alloy. During use, the advancement of the tube 110 through the inner lumen 206 of the guide tube, through the inner lumen 106 of the body along an eighth-turn of a helical path and out of the second opening 104 of the body, results in the formation of a helical coil 109. The tube 110 deforms to take on the helical shape of the inner lumen 106 of the body.

[0171] To use the device 100, the user preferably plans an insertion trajectory into the tissue of the patient. Where feasible, the insertion may be planned and accomplished using stereotactic surgery techniques. Whatever means are used to guide the insertion, at least guide tube 200 and body 101 are inserted into the patient tissue to the target location. Preferably an insertion needle is used to position the device at the target location. The insertion needle comprises a delivery tube 400 coupled to the device 100, the device comprising the tubular body 101 , guide tube 200 and insertion tip 300. The second opening 104 of the tubular body is positioned at the target location, preferably at a desired insertion depth. Once positioned, the position of the device 100 and delivery tube 400 may be locked. The coil-forming component comprising a tube

[0172] 110 may be present within the delivery tube 400, optionally within the inner lumen 206 of the guide tube and within the inner lumen 106 of the body, during the insertion. Or the tube 110 may be inserted later.

[0173] Tube 110 is advanced through the delivery tube 400 and device 100 so that it emerges from the second opening 104 and into the tissue, forming a helical coil 109 in situ. The tube 110 deforms to take on the helical shape of the inner lumen 106 of the body, and as the tube 110 progresses it forms a helical coil 109. The advancement of the helical coil 109 winds the coil into the tissue. Intra-operative imaging can confirm the trajectory of the helical coil. When the desired number of turns of the helical coil 109 has been achieved, the advancement is halted.

[0174] The tube 110 can be loaded with therapeutics to be administered to the patient tissue. For example, the tube 110 can be loaded with a suspension of cells to be used for cell therapy. Alternatively, the tube 110 may be coupled to a syringe (not shown) containing therapeutics for delivery to the tissue. After in situ formation of the helical coil 109 at the desired target location, the helical coil 109 can be withdrawn from the tissue while administering therapeutics through the aperture 112 at the distal end of the tube 110. The therapeutics are deposited in a helical pattern within the patient tissue. A single insertion of the device 100 can thus result in a large deposition area. The withdrawal is at a clinically acceptable pace, preferably at slow pace, preferably at a rate of retraction of 0.1 to 10 mm / s.

[0175] The device may then be repositioned for delivery of therapeutics to a second treatment site. In particular, the device might be repositioned to treat the opposite hemisphere of the brain.

[0176] It will be recognized that variations on this basic procedure are possible. For example, while device 100 is held in a single orientation, it may be rotated to deploy the or another coil-forming component 108 to a second or further positions with therapeutics being administered in a helical pattern at each of these positions. This requires only one penetration of patient tissue by the device. In another variation, coil-forming component 108 may be withdrawn and loaded with additional or alternative therapeutics, and re-inserted into the inner lumen 206 of the guide tube and inner lumen 106 of the body during the procedure. This technique may be especially useful for complex treatment volumes.

[0177] In addition to the delivery of therapeutic agents, other kinds of therapy may be delivered. For example, an electric therapeutic such as an electrode may be delivered in place of or through the tubular coil-forming component 108. Where the coil-forming component 108 (tube 110 or solid wire) is metallic or made of a material able to conduct electrical currents, once the helical coil 109 is formed in situ, an electric current can be passed through the coil 109. Electrotherapy or radioablation can additionally or alternatively be delivered to the tissue.

[0178] Figures 6A-6C show a device 100’ for the formation of a helical coil under application of a rotation. The device 100’ includes a tubular body 101 ’, having a proximal end and a distal end 105’. The tubular body 101 ’ also includes an inner lumen 106’ extending from a first opening 102’ of the body to a second opening 104’ of the body. The first opening 102’ is placed at the proximal end of the body and the second opening 104’ is located at a distance from the distal end 105’ of the body. The inner lumen 106’ follows a curved path between the first opening 102’ and the second opening 104’ of the body. The device 100’ further includes a guide tube 200’. The guide tube 200’ comprises a first opening 202’ at a proximal end 203’ of the guide tube, a second opening 204’ at a distal end 205’ of the guide tube and a guide tube inner lumen 206’ extending from the first opening 202’ to the second opening 204’. The guide tube 200’ and tubular body 101 ’ are made as a single piece, such that the guide tube and body are fully integrated. The distal end 205’ of the guide tube is coupled to the proximal end 103’ of the body and the second opening 204’ of the guide tube is coupled to and continuous with the first opening 102’ of the body. The guide tube inner lumen 206’ is continuous with the inner lumen 106’ of the body.

[0179] A portion of the guide tube inner lumen 206’ is straight. A portion of the guide tube inner lumen 206’ is tapered. The tapered portion of the guide tube inner lumen extends 206’ from the first opening 202’ at a proximal end 203’ of the guide tube to an intermediate position 207’ along the length of the guide tube. The first opening 202’ of the guide tube is larger in diameter than the second opening 204’ of the guide tube. The tapered guide section inner lumen 206’ reduces friction on the coil-forming component as it advances into the guide tube and along the guide tube inner lumen 206’. The straight portion of the guide tube inner lumen 206’ extends from the intermediate position 207’ along the length of the guide tube to the second opening 204’ at the distal end 205’ of the guide section. The straight portion of the guide tube inner lumen 206’ is parallel to and offset from a central axis of the guide tube 200’.

[0180] An insertion tip 300’ is coupled to the distal end 105’ of the body. The insertion tip 300’ is configured to facilitate insertion of the device 100’. The device 100’, comprising the tubular body 101 ’, guide tube 200’ and insertion tip 300’, is a distal part of an insertion needle. As shown in Figure 6C, the proximal end 203’ of the guide tube may be coupled to a distal end of a delivery tube 400’ such that the device 100’ and delivery tube 400’ comprise an insertion needle.

[0181] Figure 7A shows a perspective view of a device 100’ of Figures 6A-6C for the formation of a helical coil under application of a rotation (arrow indicating rotation). The device comprises a tubular body 101’, comprising a first opening 102’ (not shown) and a second opening 104’. An inner lumen 106’ extends from the first opening 102’ to the second opening 104’, and follows a curved path between the first opening 102’ and the second opening 104’ of the body. The device 100’ further comprises a guide tube 200’ having a first opening 202’ and an inner lumen 206’.

[0182] The coil-forming component 108’ is advanced through a first opening 202’ of the guide tube. A rotation is applied to the coil-forming component 108’ during advancement of the coil-forming component into the first opening 202’ of the guide tube, through the guide tube inner lumen 206’, into the first opening 102’ of the body, through the inner lumen 106’ of the body and out of the second opening 104’ of the body. The rotation is applied to the coil-forming component 108’ about its normal medial axis as indicated by the arrow. A helical coil is formed as a result.

[0183] Figure 7B shows an orthogonal view of a deployed position of the device 100’ of Figure 7A, in which the device 100’ is coupled to a delivery tube 400’ and a helical coil 109 formed by the device 100’ protrudes from the second opening 104’ of the tubular body 101 ’. In particular, the curved path of the inner lumen 106’ of the body 101 ’ defines a plane that is perpendicular to the view shown in Figure 7B and to a longitudinal axis of the delivery tube 400’.

[0184] As the coil-forming component 108’ advances through the body 101 ’ of the device 100’, the coilforming component 108’ is constrained by the walls of the inner lumen 106’ to follow a planar curved path. In other words, the curved path of the inner lumen 106’ of the body 101 ’ has a single dimension of curvature. For example, in Figure 7B, the curved path defined by the inner lumen 106’, and followed by the coil-forming component 108’ during coil formation, is shown as straight (within the plane of the figure) and does not curve left or right.

[0185] As a result of the rotation applied to the coil-forming component 108’, twisting (torsion) is induced along the coil-forming component 108’. Therefore, as the coil-forming component 108’ advances through the inner lumen 106’, it experiences a combination of rotational motion and deformation through the planar curved path, which results in a helical coil 109 when it exits the device 100’ at the opening 104’. As explained above, the pitch and diameter of the helical coil 109 may be controlled based on the rate of rotation (torsion) applied to the coil-forming component 108’.

[0186] Figure 8A is a schematic illustrating a potential use of the device 100, 100’, which is part of an insertion needle, to create an in situ helical coil 109. With a single penetration, the device 100, 100’ can reach a target location, preferably the putamen of a brain, and position a helical coil 109 therein as shown in the CT image of the device and helical coil in situ in a human skull in Figure 8B (CT image with 1 mm section volume scans).

[0187] An insertion device and method of insertion according to aspects of the invention may promote rapid cell delivery into the helical coil withdrawal space leading to significant reductions in procedure time. Therapeutics can be delivered to a target tissue volume via a single access needle using a minimally invasive approach, and with the ability to administer cells to a larger treatment volume using the helical pattern delivery, a single pass can be used to treat each hemisphere. A single-pass procedure reduces both surgical and anaesthetic risks to the patient. The reduced procedure time also results in reduced costs.

[0188] Examples

[0189] One advantage of a device of the present invention, as compared with previous systems, may be that reflux of the administered therapeutics is significantly reduced or eliminated. In an experimental evaluation, an insertion device embodying the invention was used to insert a helical coil in situ and inject red food dye into a 0.8% agarose gel (Invitrogen UltraPure Agarose) that mimics the gross structural characteristics of brain. The gel had been refrigerated and then placed on the lab bench. The gel temperature was therefore between 5°C and room temperature (24°C). The coil-forming component was a 20-gauge 304 stainless steel tube having an inner diameter of 0.6 mm and 0.9 mm outer diameter. The body of the device was formed by stereolithography printing. A 10 mm diameter, 2 mm pitch helical coil was deployed (approximately 7 to 11 mm under the surface), and subsequently withdrawn. During manual withdrawal of the helical coil, dye was infused using a syringe. No dye was observed to reflux back up the tube, although some reflux occurred in the target volume treatment zone as a result of non-synchronous withdrawal of the coil and administration of the fluid. This absence of reflux may be a direct consequence of the administration of the dye at the same time as withdrawing the coil. By contrast, delivery of food dye through a 20-gauge cannula-syringe system inserted to a similar depth resulted in significant reflux of dye back up the injection passage. Results of the experimental evaluation are demonstrated in Figure 9.

[0190] Figure 9A is an image of the device 100 and as-formed helical coil 109. Figure 9B shows the dispensing of fluid from the helical coil 109. In particular, Figure 9B shows the in vitro administration of red food dye from the aperture 112 of a helical coil 109 which is a tube 110. The food dye is administered into the substrate in helical pattern through a single penetration of the device 100 into the substrate. The food dye fills the void that was left by the helical coil 109. In this specific example, the substrate is 0.8% agarose gel. The density and hydration of the substrate are selected to represent brain tissue.

[0191] Figure 9C is an image of a comparative device, a straight needle, being passed into the 0.8% agarose gel (creating an insertion hole). In Figure 9D food dye is injected into the agarose with the needle tip at the desired depth and at the same time, food dye can be seen to reflux out of the insertion end of the insertion hole. In Figure 9E, the injected food dye is in the insertion hole as well as refluxing out of the end.

[0192] In a further experimental evaluation, an insertion device embodying the invention was used to inject red food dye into a 0.8% agarose gel (Invitrogen UltraPure Agarose). The coil-forming component was a 20-gauge 304 stainless steel tube having an inner diameter of 0.6 mm and 0.9 mm outer diameter. The body of the device was formed by stereolithography printing. A 10 mm diameter, 2 mm pitch helical coil was deployed with the second opening of the body placed 7-11 mm below the gel surface. Figures 10A to C are images of the in situ formation of a helical coil 109 at a target location using the device 100 at time points of 10s, 40s and 90s respectively after the start of helical coil administration. The helical coil was subsequently manually withdrawn. During manual withdrawal of the helical coil, dye was infused. Figures 10D to F are images of the withdrawal of the helical coil 109 and administration of a red food dye at time points of 10s, 60s and 150s after the start of withdrawal. Administration is into the void created by the helical coil 109. No dye was observed to reflux back up the tube.

[0193] In a further experimental evaluation, an insertion device embodying the invention was used to inject red food dye into different concentration and hydration agarose gels (Invitrogen UltraPure Agarose). Concentrations of agarose used were 0.4%, 0.6%, 0.8%, 1.5%, 3% and 4%, with results illustrated in Figures 11A, B, C, D, E and F respectively. A helical coil of 11-13 mm diameter and 2.4-3.4 mm pitch was deployed (approximately 13 to 24 mm under the surface of the agarose gel), and subsequently withdrawn. Figures 11A to F show the deployment of the helical coil and the front injected view shows the dispensing of food dye from the helical coil into each of the agarose blocks. The density and hydration were selected to be representative of different tissues (where most tissue can be considered represented by agarose of concentration 0.8 to 2%). No damage to the agarose gel was demonstrated on retraction of the coil.

[0194] To confirm the ability of the helical coil to deliver cells without cell apoptosis, a comparative viability test was performed. T-cells were obtained from the spleen of a C57 / BL6 mouse. Cells were isolated and passed through a 70 pm cell strainer and washed in hibernate A low fluorescense (HALF) medium. Cells were then passed through either no device, a 20-gauge helical coil formed using the device 100 of the invention (having a helical inner lumen), a 20- gauge straight needle and a 24-gauge straight needle. Cells were collected and left for 1 hour. Cells from each experimental condition were then processed for Fluorescence-activated cell sorting (FACS) and stained with two independent cell viability markers (405 nm Violet) and (750 nm NIR). The cell suspension was washed twice by spinning it in HALF for 10 min. After the second wash-spin cycle, the cell pellet was resuspended in HALF. Flow cytometry was performed for each experimental condition on the Attune NxT Flow Cytometer (Thermo Fisher). The viability test was repeated four times per experimental condition (each repeat was a biological replicates, using cells from the same mice for each experimental condition). Cell viability was used to assess cell death not only from mechanical shearing, but also from cell stress after passage through the helical coil or straight needle.

[0195] Figures 12A, 12B, 12C, and 12D show viability data for cells as passed through no device (FIG. 12A), the 20-gauge helical coil (FIG. 12B), a 20-gauge straight needle (FIG. 12C), and a 24- gauge straight needle (FIG. 12D). Data show that there is no significant change in the cell viability after passing through the 20-gauge helical coil (24.4%), a 20-gauge straight needle (25.5 %) and a 24-gauge straight needle (26.9%) compared to control samples through no device (23.4%). The results show no significant differences in cell viability across all delivery methods.

[0196] Although device 100 (having a helical inner lumen, according to a first aspect of the invention) has been used for these experimental evaluations (Figures 9 to 12), it will be appreciated that a helical coil 109 may be inserted using an insertion device (such as device 100’) having an inner lumen which follows a bent path and with the application of a rotation to a coil-forming component according to the second aspect of the invention. Similar results to those of Figures 9 to 12 would also be replicated for helical coils inserted using a rotation applied to a coil-forming component advanced through a device (such as device 100’) having a bent inner lumen.

[0197] General

[0198] As used herein, the term "comprising" encompasses "including" as well as "consisting" and "consisting essentially of' e.g. a composition "comprising" X may consist exclusively of X or may include something additional e.g. X + Y.

[0199] As used herein, the words "a" or "an" are not limited to the singular but are understood to include a plurality, unless the context requires otherwise.

[0200] It will be appreciated that any item, feature, parameter or component described herein may, where appropriate, relate to any of the aspects of the present invention. Aspects and examples of the invention have now been described in detail for the purposes of clarity and understanding. However, those skilled in the art will appreciate that certain changes and modifications may be practiced within the scope of the appended claims. It is to be understood that all workable combination of the components and features described herein are considered to be disclosed.

[0201] The invention is defined in the appended claims.

Claims

CLAIMS1 . A method for the formation of a helical coil using a device comprising, a body, said body comprising: a first opening; a second opening; and an inner lumen extending from the first opening to the second opening and wherein the inner lumen follows a bent path between the first opening and the second opening of the body; said method comprising applying rotation to a coil-forming component during advancement of the coil-forming component into the first opening of the body, through the inner lumen and out of the second opening of the body; and forming a helical coil from the coil-forming component.

2. The method according to claim 1 , wherein the bent path is a curved path.

3. The method according to claim 1 , wherein the bent path comprises a first section and a second section, wherein the second section is arranged at an angle to the first section.

4. The method according to any of claims 1 to 3, wherein the rotation is applied at or near to a proximal end of the coil-forming component.

5. The method according to any of claims 1 to 4, wherein the rotation and advancement induce a torsional load on the coil-forming component.

6. The method according to claim 5, wherein the angle of rotation per mm linear advancement of the coil-forming component is no more than 500 degrees / mm, preferably no more than 20 degrees / mm.

7. The method according to claim 5 or 6, wherein the angle of rotation per mm linear advancement of the coil-forming component is selected based on an outer diameter of the coil-forming component and a predetermined diameter and pitch for the resulting helical coil.

8. The method according to any preceding claim, wherein a consistent rate of rotation is applied to the coil-forming component to form a helical coil with a consistent pitch and diameter along its length.

9. The method according to any preceding claim, wherein the walls of the bent inner lumen constrain the coil-forming component to the shape of the bent path during application of the rotation.

10. The method according to any preceding claim, wherein the resulting helical coil has a diameter of 1 to 50 mm, 20 to 50 mm, 5 to 25 mm, 10 to 25 mm, 2 to 10 mm, or 6 to 8 mm, and / or wherein the helix has a pitch of 1 to 50 mm, 20 to 50 mm, 5 to 25 mm, 10 to 25 mm, 2 to 10 mm, or 6 to 8 mm.11 . The method according to any preceding claim, wherein the device further comprises a guide section, said guide section comprising: a first opening at a proximal end of the guide section; a second opening at a distal end of the guide section; and a guide section inner lumen extending from the first opening to the second opening; wherein the distal end of the guide section is coupled to a proximal end of the body, such that the second opening of the guide section is coupled to the first opening of the body, and the guide section inner lumen is continuous with the inner lumen of the body, wherein the method further comprises advancing the coil-forming component under rotation into the first opening of the guide section, through the guide section inner lumen and into the first opening of the body.

12. The method according to claim 11 , wherein at least a portion of the guide section inner lumen is straight between the proximal end of the guide section and the distal end of the guide section.

13. The method according to claim 11 or 12, wherein the guide section is tubular in shape.

14. The method according to any preceding claim, wherein the device further comprises an insertion tip coupled to a distal end of the body.

15. The method according to any of claims 11 to 13, for the in situ formation of a helical coil at a target location, wherein the target location is a tissue of a patient, the method further comprising: inserting the device into the body of the patient and positioning the second opening of the body adjacent said target location; advancing the coil-forming component under rotation into the first opening of the guide tube, through the inner lumen of the guide tube and out of the second opening of the guide tube, into the first opening of the body, through the inner lumen and out of the second opening of the body; and wherein the forming of a helical coil from the coil-forming component forms a helical coil at the target location.

16. The method according to claim 15, wherein the coil-forming component comprises a frangible or detachable portion at a predetermined position, and wherein the method further comprises detaching the helical coil once formed.

17. A method of administering therapy into the tissue of a patient in a helical pattern, comprising the in situ formation of a helical coil according to claim 15 or 16 and further comprising the administration of therapeutics to the patient via the helical coil.

18. The method according to claim 17, wherein the coil-forming component comprises a tube, and wherein the method further comprises withdrawing the helical coil from the target location while administering therapeutics through the tube.

19. The method according to claim 18, wherein the method further comprises applying rotation to the coil-forming component during withdrawal of the helical coil from the target location, preferably wherein the rotation is equal in magnitude and opposite in direction to the rotation applied when forming the helical coil.

20. A method according to claim 17, wherein the coil-forming component comprises a metal tube or a solid metal wire, and wherein the method further comprises administering electrotherapy by passing an electric current through the helical coil.

21. Cells for use in a method of treating disease, wherein said cells are administered to the tissue of a patient using the method according to claim 18 or 19.

22. A device for the formation of a helical coil, said device comprising: a body, said body comprising: a first opening; a second opening; and an inner lumen extending from the first opening to the second opening and wherein the inner lumen follows a portion of a helical path between the first opening and the second opening of the body; wherein the device is configured to receive a coil-forming component at the first opening of the body, and the advancement of the coil-forming component through the inner lumen and out of the second opening of the body results in the formation of a helical coil.

23. The device of claim 22, wherein the portion of a helical path is less than an eighth-turn of a helix, or quarter-turn of a helix, or a half-turn of a helix.

24. The device of claim 23, wherein the helix has a diameter of 1 to 50 mm, 20 to 50 mm, 5 to 25 mm, 10 to 25 mm, 2 to 10 mm, or 6 to 8 mm, and / or wherein the helix has a pitch of 1 to 50 mm, 20 to 50 mm, 5 to 25 mm, 10 to 25 mm, 2 to 10 mm, or 6 to 8 mm.

25. The device of any of claims 22 to 24, wherein the helical coil is formed with a consistent pitch and diameter along its length.

26. The device of any of claims 22 to 25, wherein the portion of the helical path terminates at the second opening of the body.

27. The device of any of claims 22 to 26, wherein the first opening is at a proximal end of the body and the second opening is in the region of a distal end of the body, optionally, wherein the body is a cylindrical shape, and wherein the first opening is located at a base of the cylinder and the second opening is located on the curved surface of the cylinder.

28. The device of any of claims 22 to 27, further comprising a guide section, said guide section comprising: a first opening at a proximal end of the guide section; a second opening at a distal end of the guide section; and a guide section inner lumen extending from the first opening to the second opening; wherein the distal end of the guide section is coupled to a proximal end of the body, such that the second opening of the guide section is coupled to the first opening of the body, and the guide section inner lumen is continuous with the inner lumen of the body.

29. The device of claim 28, wherein at least a portion of the guide section inner lumen is straight between the proximal end of the guide section and the distal end of the guide section.

30. The device of claim 28 or 29, wherein the guide section is tubular in shape.31 . The device of any of claims 22 to 30, further comprising an insertion tip coupled to a distal end of the body.

32. The device of any of claims 22 to 31 , wherein the coil-forming component comprises a solid wire.

33. The device of claim 32, wherein the solid wire has a diameter of 0.001 mm to 10 mm, 0.05 mm to 2 mm, 0.8 to 1 .2 mm, or 4 to 6 mm.

34. The device of any of claims 22 to 31 , wherein the coil-forming component comprises a tube, optionally, wherein the tube further comprises; a removable core; and / or one or more apertures in a wall of the tube.

35. The device of any of claims 22 to 34, wherein the coil-forming component comprises a material having a low yield strain, preferably the coil-forming component comprises a metal selected from one or more of stainless steel, aluminium alloy, titanium, platinum, copper and metallic alloys, preferably titanium.

36. The device of claim 34, wherein the coil-forming component comprises a plastic tube and a removable core, said removable core comprising a metal having a low yield strain.

37. The device of claim 34 to 36, wherein the tube has an outer diameter of 0.001 to 10 mm, 0.05 mm to 2 mm, 0.8 to 1 .2 mm, or 4 to 6 mm and / or the tube has an inner diameter of 0.0005 mm to 5mm, 0.05 to 0.6 mm, 1 to 2 mm, 0.6 to 2.7 mm or 4 to 5 mm.

38. The device of any of claims 32 to 37, wherein the coil-forming component further comprises a drug-impregnated coating, preferably wherein the coating is biodegradable.

39. A kit comprising the device of any of claims 22 to 38 and said coil-forming component.

40. A method for the formation of a helical coil using the kit of claim 39, said method comprising: advancing a coil-forming component into the first opening of the body, through the inner lumen and out of the second opening of the body; and forming a helical coil from the coil-forming component.41 . The method according to claim 40, for the in situ formation of a helical coil at a target location, wherein the target location is a tissue of a patient and wherein the device comprises a guide tube according to claim 30, said method further comprising: inserting the device into the body of the patient and positioning the second opening of the body adjacent said target location; advancing the coil-forming component into the first opening of the guide tube, through the inner lumen of the guide tube and out of the second opening of the guide tube, into the first opening of the body; and wherein the forming of a helical coil from the coilforming component forms a helical coil at the target location.

42. The method according to claim 40 or 41 , wherein the coil-forming component comprises a frangible or detachable portion at a predetermined position, and wherein the method further comprises detaching the helical coil once formed.

43. A method of administering therapy into the tissue of a patient in a helical pattern, comprising the in situ formation of a helical coil according to claim 41 or 42 and further comprising the administration of therapeutics to the patient via the helical coil.

44. The method according to claim 43, wherein the coil-forming component comprises a tube, and wherein the method further comprises withdrawing the helical coil from the target location while administering therapeutics through the tube.

45. A method according to claim 43, wherein the coil-forming component comprises a metal tube or a solid metal wire, and wherein the method further comprises administering electrotherapy by passing an electric current through the helical coil.

46. Cells for use in a method of treating disease, wherein said cells are administered to the tissue of a patient using the method according to claim 44.

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