NEUROSURGICAL DEVICE

Abstract

A neurosurgical apparatus for convection enhanced delivery of an infusate to the brain parenchyma, the apparatus comprising: a guide tube for insertion into the brain and having a proximal end, a distal end and a through-bore for passage of a cannula; wherein at least an outer layer (24) of the guide tube is of a hydrophobic material that is resiliently deformable and porous to allow passage of air. Also provided is a kit for convection enhanced delivery of an infusate to the brain parenchyma and a surgical method for convection enhanced delivery of an infusate to the brain parenchyma.

Claims

1. A neurosurgical apparatus for convection enhanced delivery of an infusate to the brain parenchyma, the apparatus comprising: a guide tube for insertion into the brain and having a proximal end, a distal end and a through-bore for passage of a cannula; wherein at least an outer layer of the guide tube is of a hydrophobic material that is resiliently deformable and porous to allow passage of air.

2. The neurosurgical apparatus of claim 1, wherein at least the outer layer of the guide tube is superhydrophobic.

3. The neurosurgical apparatus of claim 1, wherein at least the outer layer of the guide tube comprises at least one of ePTFE, silicone foam, polyurethane foam, shape memory polymer, polymers extruded as microporous hollow fibres and electrospun polymers.

4. The neurosurgical apparatus of claim 3 wherein at least the outer layer of the guide tube comprises at least one polymer extruded as microporous hollow fibres, or an electrospun polymer: wherein the polymer extruded as microporous hollow fibres, or electrospun polymer is selected from the group consisting of; PTFE (polytetrafluoroethylene), PVDF (polyvinylidene difluoride), PU (polyurethane), polypropylene, or mixtures and/or copolymers thereof.

5. The neurosurgical apparatus of claim 1, wherein the guide tube further comprises an outermost layer axially outward of the outer layer, wherein the outermost layer comprises a hydrophilic material.

6. The neurosurgical apparatus of claim 5, wherein the outermost layer comprises a mixture of hydrophilic and hydrophobic materials.

7. The neurosurgical apparatus of claim 1, wherein the outer layer or outermost layer comprises a coating and/or surface treatment configured to improve lubricity and/or to promote tissue integration, optionally wherein the coating comprises a hydrophilic material.

8. The neurosurgical apparatus of claim 1, wherein at least the outer layer of the guide tube has a Poisson's ratio of zero or less.

9. The neurosurgical apparatus of claim 1, wherein the guide tube is constructed of a non-homogeneous material and/or of a plurality of materials with different stiffnesses.

10. The neurosurgical apparatus of claim 9, wherein the guide tube is constructed of a foam having increasing density from the outside radially inwards towards the throughbore, or a region of increased density at or near the throughbore.

11. The neurosurgical apparatus of claim 9, wherein the guide tube has a laminated structure with a stiffer layer or layers at or near the throughbore.

12. The neurosurgical apparatus of claim 11, wherein the stiffer layer or layers are porous to air.

13. The neurosurgical apparatus of claim 11, wherein a stiffer layer forms the surface of the throughbore.

14. The neurosurgical apparatus of claim 11, wherein at least one of the stiffer layer or layers comprises a polymer selected from the group consisting of: polyether ether ketones (PEEK); nylons; polyurethanes; polyesters; fluoropolymers such as polytetrafluoroethylene (PTFE), polymeric perfluoroethers such as perfluoroalkoxy alkanes (PFA), polyvinylidene difluoride (PVDF), and fluorinated ethylene propylene (FEP); liquid crystal polymers (LCP); and mixtures or copolymers thereof.

15. The neurosurgical apparatus of claim 11, wherein at least one of the stiffer layer or layers has been manufactured by a process comprising at least one of: micro-perforating sheet material of a polymer film by drilling or by laser; weaving, braiding or electrospinning polymer fibres about a cylindrical former to form a tube of porous polymer sheet material; and 3D printing a polymer in a porous form.

16. The neurosurgical apparatus of claim 1, wherein the guide tube has an outer diameter between 0.75 mm to 2.5 mm.

17. The neurosurgical apparatus of claim 1, wherein the throughbore of the guide tube has a diameter of from 0.4 mm to 0.7 mm.

18. The neurosurgical apparatus of claim 1, further comprising a guide hub for securing to the skull of a patient before insertion of the guide tube and having a passage for the guide tube therethrough.

19. The neurosurgical apparatus of claim 18, wherein the guide tube has an increased diameter open proximal end for seating in a corresponding shaped seat in the guide hub passage.

20. The neurosurgical apparatus of claim 1, wherein the guide tube comprises an enlargement at the proximal end sized and shaped for securing in a burr hole in a skull.

21. The neurosurgical apparatus of claim 1, wherein the guide tube is resiliently extendible and compressible in the axial direction, at least in a proximal end portion.

22. The neurosurgical apparatus of claim 21, wherein the proximal end portion of the guide tube has a Poisson's ratio of zero or less.

23. The neurosurgical apparatus of claim 21, wherein the guide tube is of laminate construction, comprises an inner tube of a stiffer material overlaid with an outer layer of a porous resiliently deformable material; and wherein the proximal end portion is not provided with the inner tube.

24. The neurosurgical apparatus of claim 1, further comprising a cannula for insertion through the guide tube into the brain, to deliver an infusate to a target brain volume.

25. The neurosurgical apparatus of claim 24, wherein the cannula comprises a bubble vent configured to prevent gas and/or micro-organisms from entering the cannula.

26. The neurosurgical apparatus of claim 25, wherein the bubble vent comprises a first membrane and a second membrane separated by an air gap, wherein the first membrane is hydrophobic and the second membrane is hydrophilic.

27. The neurosurgical apparatus of claim 1, further comprising a probe for insertion into tissue, the probe comprising: a rod having a rounded or conical distal end provided with an axially extending, narrower diameter spike having an extreme end for dissecting tissue.

28. A cannula for insertion through a guide tube into the brain, to deliver an infusate to a target brain volume, wherein the cannula comprises a bubble vent configured to prevent gas and/or micro-organisms from entering the cannula.

29. The cannula of claim 28, wherein the bubble vent is permanently joined to and/or integrally formed with the cannula.

30. A guide tube for insertion into the brain comprising: a proximal end; a distal end; and a through-bore for passage of a cannula; wherein at least an outer layer the guide tube is of a hydrophobic material that is resiliently deformable and porous to allow passage of air.

31. A package comprising the guide tube of claim 30 and a packaging tube, wherein the guide tube is provided within the packaging tube, and the packaging tube is configured to compress the outer layer of the guide tube.

32. The package of claim 31, further comprising a stylet within the through-bore of the guide tube.

33. A probe for insertion into tissue, the probe comprising: a rod having a rounded or conical distal end provided with an axially extending, narrower diameter spike having an extreme end for dissecting tissue.

34. The probe of claim 33 having a diameter of 1.3 mm or less.

35. The probe of claim 33 34, wherein the spike is from 4 mm to 5 mm long and tapers from 0.5 mm to 0.3 mm at its extreme distal end.

36. A kit for convection enhanced delivery of an infusate to the brain parenchyma comprising: a) a guide tube for insertion into the brain and having a proximal end, a distal end and a through-bore for passage of a cannula; wherein at least an outer layer of the guide tube is of a hydrophobic material that is resiliently deformable and porous to allow passage of air; and b) a guide tube probe for passing through the throughbore of the guide tube, to assist insertion of the guide tube into the brain; c) a probe for preparing a track in the brain for a cannula; and d) a cannula for passage through the guide tube to deliver an infusate to the brain.

37. The kit of claim 36 wherein the probe c) for preparing a track for a guide tube and cannula in the brain comprises: a rod having a rounded or conical distal end provided with an axially extending, narrower diameter spike having an extreme end for dissecting tissue.

38. The kit of claim 36, further comprising a guide hub for fitting to a burr hole in the skull and connecting to the proximal end of the guide tube.

39. A surgical method for convection enhanced delivery of an infusate to the brain parenchyma, the method comprising: a) passing a guide tube into the brain parenchyma, wherein the guide tube comprises: a proximal end; a distal end; and a through-bore for passage of a cannula; wherein at least an outer layer the guide tube is of a hydrophobic material that is resiliently deformable and porous to allow passage of air; and wherein the guide tube is passed into the brain with the aid of a guide tube probe passing through the throughbore so that its distal end is at or just beyond the distal end of the guide tube; b) when the distal end of the guide tube is at its planned position, advancing the guide tube probe further along the trajectory to create a track through the brain tissue to accommodate the cannula; c) removing the guide tube probe; d) passing a cannula through the throughbore and into the brain along the track; and e) passing an infusate into the brain via the cannula.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0089] Embodiments of the invention will now be described with reference to the following schematic drawings, in which:

[0090] FIG. 1 shows a prior art neurosurgical assembly with reflux;

[0091] FIG. 1a is a magnified view of part of FIG. 1;

[0092] FIG. 2a shows a magnified view of part of a neurosurgical assembly according to the invention;

[0093] FIG. 2b shows a cross section of a guide tube as depicted in FIG. 2a;

[0094] FIGS. 3a and 3b show cross section views of shows part of a neurosurgical assembly according to the invention;

[0095] FIG. 3c shows a neurosurgical assembly in use;

[0096] FIGS. 4a and 4b show the ends of probes for creating a track in brain tissue;

[0097] FIG. 5 shows a bubble vent attached to the proximal end of the cannula;

[0098] FIG. 6 shows an exploded view of the bubble vent;

[0099] FIG. 7 shows an alternative design of bubble vent;

[0100] FIG. 8 shows an exploded view of the bubble vent of FIG. 7;

[0101] FIG. 9 shows a cross section of the bubble vent of FIGS. 7 and 8;

[0102] FIG. 10 shows a close up view of the bubble vent of FIG. 9 in use;

[0103] FIG. 11 shows a cross-section of a guide tube having an outermost layer;

[0104] FIG. 12 shows components of a kit for convention enhanced delivery of an infusate;

[0105] FIG. 13 shows an assembled neurosurgical apparatus;

[0106] FIG. 14 shows a guide tube with a perforated inner tube extending through substantially its entire length;

[0107] FIG. 15 shows a close-up view of the proximal end of an assembled neurosurgical apparatus.

DETAILED DESCRIPTION OF THE DRAWINGS

[0108] FIG. 1 shows a prior art neurosurgical assembly 1 comprising an enlarged head 2, at the proximal end of a guide tube 4 and a cannula 6 that extends from a source of infusate 8 through the guide tube 4 to a distal end 10. The enlarged head 2 is secured in a burr hole (not shown) in the skull of a patient and the distal end of the cannula 10 is positioned within brain tissue 12 so as to deliver infusate from the extreme distal end 14 of the cannula 6 into a target volume of brain tissue as suggested by dashed line ellipse 16.

[0109] However, and as indicated in FIG. 1, the infusate may reflux, finding a path of lower resistance along the outside wall of cannula 6 and guide tube 4, in an axial flow 20 that extends (magnified view FIG. 1a) from the extreme end 14 of cannula 6 up the outside of the distal end. Magnified view FIG. 1a shows the axial flow 20 along the distal ends 10 and 18 of cannula 6 and guide tube 4, resulting in loss of infusate from the region of target volume 16. The step (abrupt change in diameter) caused by the change in diameter from the cannula 6 to the, square cut, extreme end distal end 22 of the guide tube 4 can act against reflux continuing in the direction suggested by arrow R. However, the step can be overwhelmed by fluid volume and the prevention of reflux along the outside surface of the guide tube 4 can depend on the extent of sealing interaction between the guide tube 4 and brain tissue 12. That sealing interaction may not be sufficient to prevent fluid passing the step at distal end 22 of guide tube 4.

[0110] FIG. 2a shows in magnified view the distal ends 18 and 14 of the guide tube 4 and cannula 6, where the guide tube 4 is in accordance with the invention. The intended result of an infusion is to deliver infusate into the target volume 16 of brain tissue 12. In practice, successful delivery of infusate may approximate to that suggested by teardrop shape 24.

[0111] In the example of FIG. 2a the guide tube 4 is resiliently deformable, hydrophobic or superhydrophobic and porous to air. On insertion into a premade track made in brain tissue 12, the guide tube 4 has been compressed radially inwards. In place as depicted, the guide tube 4 exerts pressure radially outwards in attempting to return to its natural (uncompressed) state. This pressure (suggested by arrows P) provides at least an initial sealing interaction with the brain tissue 12. Thus, the guide tube of the invention exerts pressure along its length to aid in preventing reflux.

[0112] In addition, the porous nature of at least the outer layer of guide tube 4 can allow integration with brain tissue 12 over time, blocking the reflux path.

[0113] FIG. 2b shows the whole length of the guide tube of FIG. 2a in schematic cross section (not to scale). In this example the guide tube has an outer layer 24 of ePTFE and an inner layer 26 of porous (microperforated) PEEK. The guide tube 4 has a flared proximal end 28 for seating in a guide hub as described hereafter. Through bore 30 is for passage of a cannula to deliver infusate. When the guide tube is being inserted into the brain the throughbore 30 is fitted with a probe 32 as shown in the figure. Probe 32 incudes a step 34, a change in diameter, to correspond to and engage with flared end 28 of the guide tube 4.

[0114] The outer layer 24 is porous and superhydrophobic. Therefore, the outer layer is porous to air but not to aqueous fluids. The inner layer 26 of microperforated PEEK is relatively hydrophobic with a water contact angle between 70? and 90?. When in place or being driven into brain tissue 12, air present outside inner layer 4 or in throughbore 30 will tend to enter the body of the guide tube and vent to atmosphere as suggested by arrows V.

[0115] FIG. 3a shows an alternative guide tube to that of FIG. 2b in schematic cross section, with like parts numbered the same. In this example the lower part of outer layer 24, including the distal end 18 has been bonded to the inner layer of perforated PEEK 26 after stretching the (ePTFE) material. Consequently, the extreme distal end 36 of the outer layer 24 is under tension and deforms to a rounded bullet like shape. This may aid in avoiding trauma on insertion into brain tissue. The bullet-like shape may also be provided by cutting the end of the guide tube while inside a package, as described above.

[0116] In this example the inner perforated PEEK layer does not extend the whole length of the guide tube 4. An upper portion (proximal portion 38) of the guide tube 4 is not lined. This portion of the guide tube is resiliently extendible and compressible in the axial direction. The unlined proximal portion has a length L. This length may be relatively short, for example of the order of 1 to 1.5 cm, designed in use to span the distance from a patient's skull to the surface of the brain.

[0117] In use as described below with reference to FIGS. 3b and 3c the proximal portion 38 may be compressed on insertion into a patient to then act as a shock absorbing element, capable of accommodating relative motion between brain and skull. As the proximal portion 38 is formed of ePTFE in this example it may show a change in density but little change in diameter on stretching or compressing. Alternatively, the inner perforated layer 26 may extend over substantially the entire length of the guide tube 4, as shown in FIG. 14.

[0118] Also shown in FIG. 3a are an ePTFE washer 40 and a PEEK washer 42 to aid sealing to a seat in a guide hub (not shown in this figure). The washers 40, 42 may also help to create a fluid and gas seal between the guide hub and the guide tube 4.

[0119] FIG. 15 shows a close-up view of the proximal end of the guide tube 4 during use, when engaged with a guide hub 50, cannula 6 and cap 100. In this example, no washers are present. A fluid and gas seal between the guide tube 4 and the guide hub 50 and between the guide tube 4 and the cannula 6 is created through compression of the resiliently-deformable outer layer of the flared proximal end 28 of the guide tube 4. Compression of the outer layer of the guide tube 4 creates a proximal seal 102 with a stop 104 provided on the cannula 6. Compression of the outer layer of the guide tube 4 also creates a distal seal 108 with the guide hub 50.

[0120] FIG. 3b shows the arrangement of FIG. 3a but being inserted into the brain as suggested by arrow I. insertion is carried out with the aid of two coaxially arranged probes. A central probe 44 passes through the through bore 30 and extends below the distal portion 18 of guide tube 4. An outer probe 46 fits around central probe 44 and has a step 34 for engaging with flared guide tube end 28. Outer probe 46 also has a step 48 for engaging with the upper end of liner tube 26. When inserting the guide tube 4, as suggested by arrow I, the length L of the unlined proximal portion of guide tube 4 is shortened (compressed) as the distance between steps 34 and 48 is less than the uncompressed length L. As an alternative to the dual probe arrangement shown a single probe including both steps 34 and 48 in its outer profile and passing down through the whole length of throughbore 30 could be employed.

[0121] FIG. 3c shows the guide tube 4 of FIGS. 3a and 3b in use. The guide tube 4 is seated in place in a guide hub 50, fitted in a burr hole 52 of a patient's skull 54. The guide tube has been inserted through the pia 56 of a patient's brain tissue 12. Cannula 6 fed with infusate fluid from a source 8 passes down the guide tube throughbore with a distal end 10 extending beyond the guide tube 4. The unlined proximal portion 38 of the guide tube 4 is compressed as discussed above with respect to FIG. 3b. If the brain tissue 12 moves relative to the skull 54 the proximal portion 38 can move resiliently to accommodate the displacement, avoiding disturbance to the guide tube 4 where it is inside brain tissue 12. For example, the uncompressed length L of unlined proximal portion 38 may be 1.3 cm with the length I compressed to 1 cm on fitting in place.

[0122] FIG. 4a shows the end 58 of a hardened stainless steel probe 60. The end 58 is rounded (bullet nosed) in shape and has a projecting spike 62 in the form of a rod tapering from rounded end 58 to the extreme distal end 64 of the spike 62. An alternative end 58 with a conical shape is shown in FIG. 4b. In both examples, the extreme end 64 of the spike is itself rounded. The probes find use in dissecting tissue to form a track, for example to form a track through brain tissue prior to inserting guide tubes such as those discussed above and shown in FIGS. 1 to 3.

[0123] FIG. 5 shows a proximal end of a cannula 6 comprising a bubble vent 74 provided at the proximal end of the cannula 6. The configuration and component parts of the bubble vent 74 are described below and illustrated in FIG. 6. In summary, the bubble vent 74 mitigates the risk of bubbles entering the brain if they have come out of solution in the infusate or have been entrained in the infusate during the connection and/or disconnection of a delivery system that is used to deliver the infusate to the cannula 6, such as a dispenser, infusion line, and/or pump. The bubble vent 74 is preferably provided integrally with the cannula 6, as shown in FIG. 5, which further reduces the chance of bubbles being entrained during connection of the cannula 6 to the delivery system. The bubble vent 74 may also be configured to prevent pathogens (for example micro-organisms such as bacteria) from entering the cannula 6.

[0124] FIG. 6 illustrates an exploded view of the bubble vent 74, configured for attachment to the cannula 6 and a fluid connector of the delivery system. The bubble vent 74 includes a perforated filter guard 80, a bubble filter 82, retaining rings 83A, 83B, a retaining cap 84, a septum stopper 86 and a septum cap 88.

[0125] In the illustrated example, the bubble filter 82 is a low volume bubble filter made from expanded polytetrafluoroethylene (ePTFE), which has a super-hydrophobic, gas permeable, microporous structure configured to remove bubbles from the flowing therapeutic fluid. In the illustrated example the bubble filter 82 is effective to remove bubbles at flow rates of less than or equal to 30 ?l/min. The filter 82 is contained in the perforated filter guard 80 and in the illustrated example the bubble filter 82 is received over a hollow post 85 and is retained by a retainer ring 83A to the hollow post 85, which is positioned concentric to the filter guard 80.

[0126] In the illustrated example, the filter guard 80 is a hollow shell that includes a distribution of a plurality of perforations (small holes) 87 around the shell wall. The perforations 87 facilitate degassing the fluid as it flows through the bubble filter 82 from the delivery system to the cannula 6. The filter guard 80, as the name suggests also guards/protects the filter 82 against damage. The combination of the bubble filter 82 and the filter guard 80 facilitates dispersion of entrained air/bubbles from the dispenser fluid flow before the fluid passes into the cannula 6.

[0127] The bubble vent 74 also includes a retaining cap 84, which connects with the filter guard 80 to complete the assembly of the bubble vent 74 and to contain the bubble filter 82 within the bubble vent 74. The retaining cap 84 includes a hollow retaining post 89 and a retainer ring 83B which engage with the bubble filter 82 to ensure the bubble filter 82 is correctly positioned and retained in the filter guard 80 to ensure efficient functionality of the bubble filter 82 during use.

[0128] In the illustrated example, the retaining cap 84 includes a septum stopper 86, which provides a sealed unit until the septum 86 is pierced by a hollow needle to provide fluid connection to the cannula 6. The septum stopper 86 is retained under compression by the septum cap 88.

[0129] In the illustrated example, the retaining cap 84 and filter guard 80 are joined by a snap fit connection. However, alternative arrangements could be used to join them together, for example a threaded connection, welded connection, glued connection etc.

[0130] The bubble vent 74 incorporating the low volume bubble filter 82, reduces the risk of air being delivered e.g. to the brain with the fluid containing therapeutic agent/infusate. It will be appreciated fluid containing air/bubbles will be space occupying and therefore is capable of stretching and tearing brain tissue whilst also disrupting delivery/distribution of the therapeutic agent/infusate. The bubble vent 74 can also act to filter out pathogens, including bacteria and other microorganisms from the fluid.

[0131] FIGS. 7 to 10 show an alternative design of bubble vent 174. FIG. 7 shows the bubble vent 174 in its assembled state ready for use. Similar to the bubble vent 74, the bubble vent 174 comprises a retaining cap 84. The retaining cap 84 comprises a proximal connector 176, for example a threaded connector, for connection to a fluid connector of the delivery system.

[0132] FIG. 8 shows an exploded view of the bubble vent 174, and FIG. 9 shows a cross-sectional view. The proximal connector 176 may comprise a septum 86 to seal the proximal connector 176 until the septum 86 is pierced, for example by a hollow needle. The bubble vent 174 comprises a fluid passage 140 fluidly connecting the proximal connector 176 and the cannula 6. In this design, the bubble vent comprises a first membrane 150 and a second membrane 152. The first membrane 150 and the second membrane 152 are positioned between a distal end of the fluid passage 140 and a proximal end of the cannula 6. The first membrane 150 and the second membrane 152 may be substantially parallel to one another, and may be substantially perpendicular to an axis of the fluid passage 140. The first membrane 150 is positioned closer to the distal end of the fluid passage 140 than the second membrane 152, such that fluid entering the bubble vent 174 through the septum 86 reaches the first membrane 150 before the second membrane 152. An annular washer 153 may be positioned between the first membrane 150 and the second membrane 152 that forms a peripheral fluid seal between the membranes and the housing of the connector 174 and separates the membranes centrally to create a cylindrical gap between them. The cylindrical gap may have a diameter of between 2 mm and 6 mm but is most preferably 4 mm. The gap may separate the membranes 150 and 152 by 0.05 mm to 0.2 mm but most preferably by 0.1 mm. The first membrane 150 and the second membrane 152 may be connected to one another and to the other components of the bubble vent 174 via connection surfaces 180. The connection surfaces 180 may be joined by any suitable method, for example using ultrasonic welding or using an adhesive layer. The bubble vent 174 may comprise a support member 184 to support the distal surface of the second membrane 152 and allow liquid that has passed through the second membrane 152 to more easily reach the cannula 70.

[0133] The first membrane 150 is hydrophobic and gas permeable. A hole 154 is provided in the first membrane 150 where the fluid passage 140 meets the first membrane 150, such that fluid from the fluid passage 140 can pass through the first membrane 150 via the hole 154. The septum sealed connector 174 may comprise a support member to support the proximal surface of the first membrane 150 and annular connection surfaces to attach the membrane around its periphery and around its central hole 154 (not shown in FIG. 8). The second membrane 152 is liquid permeable and preferably hydrophilic. It is not essential that the second membrane 152 is hydrophilic, however gas venting works most efficiently using the combination of a hydrophobic and a hydrophilic membrane. Use of the hydrophobic first membrane 150 alone could result in air being drawn from the atmosphere through the first membrane 150 and into the infusate if the pressure in the line falls below atmospheric pressure. This can happen if the connector is elevated above the head by more than 10-25 cm (depending on intracranial pressure). The second membrane 152 being hydrophilic prevents air ingress into the brain even in such situations. The second membrane 152 is impermeable to gas and bacteria. No hole is provided in the second membrane 152, such that fluid from the fluid passage 140 must pass through the material of the second membrane 152 to reach the cannula 6. One or more vent holes 160 (for example, two vent holes in the example of FIG. 7) are provided in the bubble vent 174 on a proximal side of the first membrane 150. No holes are provided in the first membrane 150 where the vent holes 160 meet the first membrane 150, such that fluid from the fluid passage 140 must pass through the material of the first membrane 150 to reach the vent holes 160.

[0134] The operation of the bubble vent 174 is demonstrated in the close-up view of FIG. 10. A mixture of liquid and gas (for example an infusate to be delivered to a patient's brain via the cannula 6 with some entrained bubbles of air) enters the bubble vent 174 via the septum 86 and the fluid passage 140. The mixture passes through the first membrane 150 via the hole 154. The liquid is drawn to the hydrophilic second membrane 152, and soaks through the second membrane 152 (which is liquid permeable) into the cannula. The layer of liquid and the second membrane 152 form a barrier preventing gas from passing into the cannula 6. The gas will pass along the air gap between the first membrane 150 and the second membrane 152, and can escape through the gas-permeable first membrane 150 at the position of one of the vents 160. The hydrophobic nature of the first membrane 150 repels liquid and prevents the liquid forming a similar barrier as on the second membrane 152, thereby allowing the gas to pass out of the bubble vent 174 via the vent holes 160.

[0135] FIG. 11 shows a cross-sectional view perpendicular to the long axis in an example in which the guide tube 4 comprises an outermost layer 27 axially outward of the outer layer 24, wherein the outermost layer 27 comprises a hydrophilic material. The outermost layer 27 of hydrophilic material may contribute to improving the lubricity and/or tissue integration properties of the guide tube 4, as described above. In this example, the inner layer is formed of PEEK with perforations 25, the outer layer 24 is formed of electrospun hydrophobic polyurethane, and the outermost layer 27 is formed of hydrophilic polyurethane.

[0136] FIG. 12 shows components of a kit for convection enhanced delivery of an infusate to the brain parenchyma. The components include the guide hub 50, the guide tube 4, the cannula 6, and the threaded stop 70 which is screwed into the guide hub 50.

[0137] FIG. 13 shows the assembled neurosurgical apparatus, with the cannula 6 passed into the through-bore of the guide tube 4, and the threaded stop 70 screwed into the guide hub 50.