Neurosurgical devices

Abstract

The fluid transfer tube (6) is for insertion into biological tissue to deliver an injection fluid. The fluid transfer tube includes a proximal end, a distal end (18) for insertion into tissue, a through bore (52) configured to allow the flow of the injection fluid from the proximal end to the distal end, and a plurality of perfusion regions (54) on the outer surface of the fluid transfer tube. The perfusion regions extend from the distal end of the fluid transfer tube along the length of the fluid transfer tube. The perfusion regions are configured to allow the flow of the injection fluid along the perfusion regions from the distal end to the proximal end of the fluid transfer tube when the distal end of the fluid transfer tube is inserted into tissue. The fluid transfer tube is configured for non-traumatic insertion into tissue.

Description

Technical Field

[0001] The present invention relates to an apparatus and method for use in neurosurgical procedures. In particular, the present invention relates to an apparatus for delivering a therapeutic agent by direct injection into living tissue such as brain parenchyma, and a method of delivering a therapeutic agent.

Background Art

[0002] Treatment of nervous system diseases can be inhibited by the presence of the blood-brain barrier. The blood-brain barrier can make it difficult to develop therapeutic agents that can be delivered from the systemic circulation to a part of the central nervous system such as brain parenchyma. It may be desirable to deliver a therapeutic agent to a specific region of the brain ("brain volume" or "target volume"). In order to reduce undesirable side effects, it is desirable to obtain an appropriate concentration of the therapeutic agent in the target volume while minimizing exposure of the rest of the brain to the therapeutic agent. Also, it is desirable to ensure that the therapeutic agent is evenly distributed throughout the target volume while minimizing trauma to the tissue within the target volume.

[0003] Convection-enhanced drug delivery (CED) is a method of targeted delivery of a therapeutic agent to a specific brain volume by controlled injection of a therapeutic agent delivered in a fluid into the brain parenchyma using an extremely small cannula or tubing (often referred to in the art as a micro-catheter). The cannula has one or more ports at its distal end, allowing the infusion fluid containing the therapeutic agent to exit the catheter and enter into the target brain volume. A continuous pressure gradient must be achieved at the port to overcome the local pressure of the target brain volume and thereby allow the infusion fluid to effectively flow into the target brain volume.

[0004] Using CED presents challenges. This is because the fluid flowing from the cannula tends to be trapped directly in the area around the cannula by the surrounding tissue and by tissue sealing at the cannula end. To overcome this sealing and deliver the fluid into the tissue, it is possible to increase the pressure of the injector. However, increased pressure often causes tissue fragmentation around the cannula, leading to tissue trauma and uneven or inadequate distribution of the injector after fragmentation.

[0005] In addition, the injectable fluid is often delivered only to small, roughly spherical or pear-shaped regions extending from the cannula or into cavities within the tissue. Therefore, delivering treatment to clinically meaningful tissue volumes can be challenging. Most targets for treating CNS (central nervous system) diseases with CED require the implantation of several cannulas to achieve the desired range of injectable fluid into brain tissue. Once the desired target volume and shape are defined from MRI images, understanding the possible distribution shapes and volumes that can be achieved with the cannulas deployed determines the number and orientation of cannulas required to fill the volume. To fill elongated tissue volumes, sequential injections performed at different points along the trajectory into the brain may be required. Similarly, to fill larger, more spherical structures within the brain, multiple passes may be required. [Overview of the project]

[0006] Given the aforementioned difficulties, there remains a need for neurosurgical devices that can provide improved control over the delivery of the injectable fluid to the target volume, while reducing the likelihood of causing trauma to surrounding tissues.

[0007] According to a first embodiment, a fluid transfer tube is provided for insertion into biological tissue to deliver an injectable fluid, the fluid transfer tube comprising a proximal end, a distal end for insertion into tissue, a through bore configured to allow the flow of the injectable fluid from the proximal end to the distal end, and a plurality of recirculation regions on the outer surface of the fluid transfer tube, the recirculation regions comprising a plurality of recirculation regions extending from the distal end of the fluid transfer tube along the length of the fluid transfer tube, the recirculation regions configured to allow the flow of the injectable fluid along the recirculation regions from the distal end to the proximal end of the fluid transfer tube when the distal end of the fluid transfer tube is inserted into tissue, the fluid transfer tube is configured for non-traumatic insertion into tissue.

[0008] By providing a recirculation region extending along the fluid transfer tube, the distribution of the injectable fluid into the surrounding tissue can be controlled more precisely. Furthermore, the injectable fluid can be effectively distributed over a much larger volume simultaneously, enabling faster injection at lower fluid pressures. This can reduce the length of the procedure while also lowering the risk of damage to sensitive tissues such as the brain.

[0009] Optionally, a reflux region is provided by a change in the radius of the fluid transfer tube, which is optionally reduced in the reflux region compared to the radius of fluid transfer tubes circumferentially adjacent to the reflux region. The change in radius creates a difference in resistance to the flow of the injected fluid along the outer surface which can be used to generate the reflux region. The reduced radius in the reflux region creates a clear path for the injected fluid to follow.

[0010] The external diameter and radius of the fluid transfer tube can be arbitrarily varied to allow for non-traumatic insertion into tissue. By selecting an appropriate size and profile for the radius variation, the possibility of damage to surrounding tissue during insertion can be reduced.

[0011] The radius of the fluid transfer tube can be arbitrarily increased monotonically away from the center of the recirculation region, or arbitrarily increased strictly away from the center. Continuously increasing the radius generates a single minimum position within each recirculation region, which improves the consistency of the recirculation behavior.

[0012] Optionally, the distal end of the fluid transfer tube is configured to compress the tissue when inserted into it, with the compression by the perfusion region being lower than the compression by the outer surface of the fluid transfer tube circumferentially adjacent to the perfusion region. The lower compression of the surrounding tissue by the perfusion region means that a less effective seal is formed around the fluid transfer tube, allowing the injectable fluid to flow along that region of the tissue at a lower fluid pressure. Furthermore, the reduced tissue compression allows for greater dispersion of the injectable fluid into the tissue above the perfusion region, as intracellular space is more open within the tissue. This leads to improved dispersion of the injectable fluid into the tissue, more homogeneous distribution, and more precise control of injectable fluid distribution at lower fluid pressures.

[0013] Optionally, the perfusion region is configured to allow the injector to flow along the perfusion region rather than permeate the tissue when the distal end of the fluid transfer tube is inserted into the tissue. This ensures that the injector flows rapidly along the perfusion region, ensuring that the injector comes into contact with the tissue throughout the entire area to which it is to be delivered. This helps ensure that the injector is delivered to the target volume rather than being pushed into other nearby tissues.

[0014] The outer diameter of the fluid transfer tube is optionally 1 mm or less, optionally 0.75 mm or less, and optionally 0.5 mm or less. Tubes with these narrower diameters are less invasive and less likely to cause damage to surrounding tissues when inserted.

[0015] Optionally, the through-bore of the fluid transfer tube has a diameter of 0.4 mm or less, optionally 0.3 mm or less, or optionally 0.2 mm or less. Narrow through-bores reduce constraints on the overall size of the fluid transfer tube and allow for increased design flexibility regarding the outer surface of the fluid transfer tube.

[0016] Optionally, the minimum radius of the fluid transfer tube in the recirculation region is at least 50%, optionally at least 60%, optionally at least 70%, and optionally at least 80% of the radius of the fluid transfer tubes circumferentially adjacent to the recirculation region. This means that the change in the radius of the fluid transfer tube is not too large, thereby reducing the stress on the surrounding tissue and the possibility of damage to that tissue.

[0017] Optionally, the minimum radius of a fluid transfer tube in the recirculation region is up to 90%, optionally up to 80%, optionally up to 70%, and optionally up to 60% of the radius of a fluid transfer tube circumferentially adjacent to the recirculation region. These differences in radius in the recirculation region are large enough to clearly define the recirculation region and help ensure that the desired recirculation behavior is generated.

[0018] Optionally, the reflux region is substantially longitudinal, and optionally parallel to the longitudinal axis of the fluid transfer tube. The longitudinal region allows for rapid reflux of the injected fluid proximal to fill the intended volume.

[0019] Optionally, the reflux region extends along at least a portion of the fluid transfer tube that is configured to contact the tissue when the distal end of the fluid transfer tube is inserted into the tissue. This helps ensure that the injectable fluid is effectively dispersed throughout the target volume of tissue.

[0020] The reflux region is not optionally extended to the proximal end of the fluid transfer tube. This reduces the possibility of the injectable fluid leaking out of the body during delivery.

[0021] Optionally, multiple reflux regions include a total of at least four reflux regions, at least five reflux regions, at least six reflux regions, and at least five reflux regions. A greater number of regions helps to more uniformly distribute the injector around the fluid transfer tube and target volume. Six reflux regions have been found to have particularly good distribution of the injector around the fluid transfer tube without overcomplicating the manufacturing process.

[0022] Optionally, the reflux region includes a channel. The channel is easy to manufacture and provides a very clearly defined path for the injection fluid to reflux.

[0023] The outer diameter of the fluid transfer tube and the depth of the channel are determined at will to allow non-traumatic insertion into the tissue. An appropriate channel depth can allow for non-traumatic insertion.

[0024] The channel has a radial depth of at least 0.05 mm, at least 0.075 mm, and at least 0.1 mm. These depths provide sufficient radius reduction to propel the injectable fluid flow, while being shallow enough to allow non-traumatic insertion.

[0025] Optionally, the outer surface of the fluid transfer tube in the reflux region is concave, and / or the outer surface of the fluid transfer tube circumferentially adjacent to the reflux region is convex. A concave reflux region helps define a clear minimum radius point in the reflux region, improving the consistency of the reflux behavior. A convex profile adjacent to the reflux region provides a smooth transition from the reflux region.

[0026] Optionally, the outer surface of the fluid transfer tube at its distal end is either smoothly curved or flat at all points around the periphery of the fluid transfer tube. A smooth surface reduces the risk of the surface catching on or cutting into surrounding tissue and causing damage during insertion or use.

[0027] Optionally, the maximum curvature of the outer surface of the fluid transfer tube that is circumferentially adjacent to the reflux region is less than or equal to the maximum curvature of the outer surface of the fluid transfer tube in the reflux region. Ensuring that there is no maximum curvature in a region of larger radius adjacent to the reflux region reduces the strain on the surrounding tissue when conforming to the outer surface.

[0028] Optionally, the perimeter of the fluid transfer tube is at least 5% larger, optionally at least 10% larger, and optionally at least 15% larger than the outer perimeter of the fluid transfer tube. This increases the surface area where the infusion fluid contacts the surrounding tissue.

[0029] Optionally, the outer surface of the fluid transfer tube is substantially flat in the reflux region. A flat region is easier to manufacture and can provide a smooth profile that is less likely to cause tissue damage.

[0030] Optionally, the plurality of reflux regions includes a total of six reflux regions, and the distal end of the fluid transfer tube has a hexagonal profile. The hexagonal profile has been found to provide a good balance of reflux performance and manufacturing simplicity.

[0031] Optionally, the fluid transfer tube is configured to be inserted into the tissue through a guide tube that includes a proximal end and a distal end configured for insertion into the tissue. The guide tube enables accurate placement of the fluid transfer tube into the tissue along a desired trajectory and helps prevent the infusion fluid from leaving the target volume.

[0032] According to a second aspect, there is provided a neurosurgical device including a guide tube that includes a proximal end and a distal end configured for insertion into the tissue, and a fluid transfer tube of the first aspect configured to be inserted into the tissue through the guide tube.

[0033] Guide tubes allow for precise placement of fluid transfer tubes into tissue along the desired trajectory and help prevent the injected fluid from deviating from the target volume.

[0034] The distal end of the fluid transfer tube is optionally configured to protrude into the tissue beyond the distal end of the guide tube by a length that can be adjusted and / or fixed. This allows the size of the target volume to be adjusted for different procedures.

[0035] Optionally, the reflux region does not extend along the portion of the fluid transfer tube that is configured to be inside the guide tube when the distal end of the fluid transfer tube is inserted into the tissue. This reduces the flow of injectable fluid back into the guide tube (which may be undesirable and could increase the possibility of leakage).

[0036] Optionally, the fluid transfer tube includes a stop that engages with the proximal end of the guide tube, thereby setting the length to which the fluid transfer tube protrudes beyond the distal end of the guide tube. This allows the length of the target volume to be easily set before insertion of the guide tube and fluid transfer tube, thereby reducing the complexity of the insertion procedure. This reduces the possibility of errors by the system user.

[0037] Optionally, the difference between the outer diameter of the fluid transfer tube and the outer diameter of the distal end of the guide tube forms a step, which restricts the recirculation of the injectable fluid proximal to the step when the fluid transfer tube is inserted into the tissue through the through-bore of the guide tube. The step forms an effective seal that confines the injectable fluid to the target volume.

[0038] According to a third aspect, a kit is provided for a convection-enhanced drug delivery method of an injectable fluid into tissue, the kit comprising a fluid transfer tube, the fluid transfer tube having a proximal end, a distal end for insertion into tissue, a through bore configured to allow the flow of an injectable fluid from the proximal end to the distal end, and a plurality of reflux regions on the outer surface of the fluid transfer tube, the reflux regions extending from the distal end of the fluid transfer tube along the length of the fluid transfer tube, and a delivery probe configured to be inserted into tissue to form a fluid transfer tube track, the cross-sectional area of ​​the delivery probe being greater than the cross-sectional area of ​​the distal end of the fluid transfer tube.

[0039] A kit equipped with a suitably designed delivery probe can ensure that the dimensions of the probe and the formed track are appropriately fitted to the fluid transfer tube.

[0040] Optionally, the kit further includes a guide tube, which comprises a proximal end and a distal end configured for insertion into tissue, and a fluid transfer tube configured to be inserted into tissue through the guide tube. The guide tube allows for precise placement of the fluid transfer tube into tissue along a desired trajectory and helps prevent the injectable fluid from deviating from the target volume.

[0041] According to a fourth aspect, a method is provided for convection-enhanced drug delivery of an injectable fluid into tissue, the method comprising the steps of delivering the injectable fluid into tissue via a fluid transfer tube, wherein the step of delivering the injectable fluid includes the step of flowing the injectable fluid along a plurality of reflux regions on the outer surface of the fluid transfer tube from the distal end of the fluid transfer tube toward the proximal end of the fluid transfer tube.

[0042] By providing a recirculation region extending along the fluid transfer tube, the distribution of the injectable fluid into the surrounding tissue can be controlled more precisely. Furthermore, the injectable fluid can be effectively distributed over a much larger volume simultaneously, enabling faster injection at lower fluid pressures. This reduces the length of the procedure while also lowering the risk of damage to sensitive tissues such as the brain.

[0043] Optionally, the method further includes the steps of advancing a delivery probe into the tissue to form a fluid transfer tube track before delivering the injectable fluid, and inserting a fluid transfer tube into the tissue along the fluid transfer tube track. Using a suitably designed delivery probe makes it possible to ensure that the dimensions of the probe and the formed track are appropriately fitted to the fluid transfer tube.

[0044] The step of voluntarily inserting the fluid transfer tube is non-traumatic. This avoids damage to surrounding tissues that could lead to complications following the injection procedure.

[0045] Optionally, the cross-sectional area of ​​the distal end of the delivery probe is larger than the cross-sectional area of ​​the distal end of the fluid transfer tube. This ensures that space is provided around the fluid transfer tube to allow reflux of the injected fluid.

[0046] Optionally, the method further includes the step of inserting a guide tube into the tissue, the step of advancing a delivery probe including the step of advancing the delivery probe through the guide tube, the step of inserting a fluid transfer tube including the step of inserting a fluid transfer tube through the guide tube, the fluid transfer tube track extending from the distal end of the guide tube. Using a guide tube helps to guide the probe and fluid transfer tube along a desired trajectory.

[0047] Optionally, the method includes a step of first delivering the injector at a first flow rate, followed by a step of delivering the injector at a second flow rate, the first flow rate being lower than the second flow rate. The initial lower flow rate helps to gradually adapt the surrounding tissue to the inflow of the fluid, thereby reducing the risk of tissue disruption.

[0048] The initial flow rate is optionally set to a maximum of 1 μl / min. This has been found to be a reasonably low initial flow rate to avoid tissue disruption.

[0049] The second flow rate is optional, ranging from 3 μl / min to 7 μl / min, and optional, 3 μl / min or 5 μl / min. These flow rates allow for the delivery of a clinically effective volume of the infusion solution on a reasonable timescale.

[0050] Optionally, this method includes a step of continuously increasing the rate of delivery of the injectable solution from a first flow rate to a second flow rate, and optionally, the delivery rate is up to 0.5 μL / min 2 It is increased by only that much, and further optionally, up to a maximum of 0.2 μL / min 2 It increases only by a small amount. Continuous increases avoid gradual changes that can cause high strain on surrounding tissues.

[0051] In any aspect, the tissue may be animal tissue, may be mammalian tissue, or may be human tissue. Optionally, the tissue may be brain tissue or may be brain parenchyma. Optionally, the injectable fluid may be a therapeutic fluid. These tissues are particularly suitable for treatment using these devices and methods, because injecting therapeutic fluids using other devices or methods may be more difficult.

[0052] Herein, embodiments of the present invention will be described as non-limiting examples with reference to the accompanying drawings. [Brief explanation of the drawing]

[0053] [Figure 1] This figure shows a cross-section of a fluid transfer tube with a reflux region. [Figure 2] This diagram shows a cross-section of a fluid transfer tube having five reflux regions. [Figure 3] This is a diagram of the fluid transfer tube shown in Figure 1, which extends from the guide tube. [Figure 4] This is a diagram of the fluid transfer tube shown in Figure 2, which extends from the guide tube. [Figure 5] This figure shows a cross-section of the tube in Figure 1, demonstrating the reflux of the injected fluid. [Figure 6] This is a further figure demonstrating the reflux of the injected fluid from the tube in Figure 1. [Figure 7] This figure shows a cross-section of the tube in Figure 2, demonstrating the reflux of the injected fluid. [Figure 8] This is a further figure demonstrating the reflux of the injected fluid from the tube in Figure 2. [Figure 9] This figure shows a cross-section of an alternative design for a fluid transfer tube with a reflux region. [Figure 10] This is a diagram of the fluid transfer tube shown in Figure 9, which extends from the guide tube. [Figure 11] These are MRI images taken during the delivery of an injectable fluid using a prior art fluid transfer tube. [Figure 12] Figure 1 shows MRI images taken during the delivery of the injection fluid using the fluid transfer tube. [Figure 13] This is a diagram of a bubble vent. [Figure 14] Figure 13 is an exploded view of the bubble vent. [Figure 15] This is a diagram showing another design for a bubble vent. [Figure 16] Figure 15 is an exploded view of the bubble vent. [Figure 17] Figure 15 is a cross-sectional view of the bubble vent. [Figure 18] Figure 15 shows the operation of the bubble vent. [Figure 19] This figure shows a neurosurgical device including a fluid transfer tube. [Figure 20] This is a diagram showing the assembled neurosurgical device shown in Figure 19. [Figure 21] This figure shows a neurosurgical device including a fluid transfer tube and an integrated bubble vent. [Figure 22] This figure shows the assembled neurosurgical device shown in Figure 21. [Modes for carrying out the invention]

[0054] To address the limitations of the prior art devices described above, this disclosure provides a fluid transfer tube 6, such as the one shown in cross-section in Figure 1. The fluid transfer tube 6 is intended for insertion into biological tissue to deliver an injectable fluid. The tissue can be animal tissue, and can be mammalian tissue, such as human tissue. In particular, the tissue can be brain tissue, such as brain parenchyma. Thus, the fluid transfer tube 6 (which may also be referred to as a cannula or catheter) can be used, for example, to allow fluid transfer into or from the mammalian central nervous system, in order to provide fluid access to the mammalian central nervous system.

[0055] Primarily, the fluid transfer tube 6 is intended to provide fluid access to the human brain. In other words, the fluid transfer tube 6 is configured to allow fluid transfer to and from the mammalian brain and can also be configured to deliver the injector using convection-enhanced drug delivery methods. In particular, the fluid transfer tube 6 is used to transfer fluid to and from a target brain volume. As discussed above, the treatment of neurological diseases with therapeutic agents may be hindered by the blood-brain barrier, and therefore, treatment using the fluid transfer tube 6 is advantageous for these diseases. The injector can be a therapeutic fluid. The injector can carry any suitable therapeutic agent, inert fluid, imaging agent, or diagnostic agent that can be delivered into the tissue via a suitable biologically inert fluid.

[0056] The fluid transfer tube 6 can be configured to be inserted into tissue through a guide tube 4, which includes a proximal end and a distal end 18 configured for insertion into tissue. The fluid transfer tube 6 is passed along the through-bore of the guide tube from the proximal end of the guide tube 4 to the distal end 18 of the guide tube 4. Typically, the fluid transfer tube 6 protrudes beyond the distal end 18 of the guide tube 4, so that the distal end 10 of the fluid transfer tube 6 is positioned in the brain target volume. The guide tube 4 and the fluid transfer tube 6 can optionally be referred to as a cannula assembly, a neurosurgical cannula assembly, or a neurosurgical device, together with other components described below.

[0057] The fluid transfer tube 6 is configured to be inserted into tissue coaxial with a trajectory to a target (for example, within the brain). The trajectory can be established by image guidance and can be defined between an entry point (for example, on the skull) and the target. The target can be a specific region of the mammalian brain or a location within the mammalian brain. The distal end 10 of the fluid transfer tube 6 can be inserted into a predetermined location within the brain along the trajectory to the target.

[0058] The fluid transfer tube 6 includes a proximal end and a distal end 10 for insertion into tissue. The proximal end of the fluid transfer tube 6 can be positioned outside the brain during use (but can still be inside the skull and / or cranial cavity). The fluid transfer tube 6 can have a fluid connector at its proximal end, which is configured to connect to a fluid infusion line or directly to a syringe and infusion pump. At least the distal end 10 of the fluid transfer tube 6 can be configured to be inserted into tissue using image guidance. For example, at least the distal end 10 of the fluid transfer tube 6 can contain radiopaque material. Optionally, the fluid transfer tube 6 can contain radiopaque material along substantially its entire length.

[0059] The fluid transfer tube 6 includes a through bore 52 configured to allow the flow of the injection fluid from the proximal end to the distal end 10. The through bore of the fluid transfer tube 6 can have a diameter b of 0.4 mm or less, optionally 0.3 mm or less, optionally 0.2 mm or less. The through bore of the fluid transfer tube 6 can have a diameter b between 0.1 mm and 0.4 mm, for example, a diameter b of 0.4 mm. Optionally, the through bore of the fluid transfer tube 6 can have a diameter b between 0.10 mm and 0.15 mm, for example, a diameter b of approximately 0.127 mm (5 / 1000 inch).

[0060] The length of the fluid transfer tube 6 can be at least 100 mm. Generally, the fluid transfer tube 6 can have a length that is at least the length of the guide tube 4 to which the fluid transfer tube 6 is configured to be used.

[0061] The fluid transfer tube 6 may contain biocompatible materials. For example, the fluid transfer tube 6 may contain biocompatible plastics such as polyetheretherketone (PEEK) or polyurethane (e.g., carbothane). The fluid transfer tube 6 may be formed from rigid materials, such as fused silica, ceramics (e.g., zirconia ceramic), metals (e.g., titanium or stainless steel), or rigid biocompatible plastics (e.g., PEEK). Alternatively, the fluid transfer tube 6 may be formed from flexible materials, such as flexible biocompatible plastics. The choice of using a rigid or flexible fluid transfer tube 6 may be made based on the specific application. Optionally, the distal end 10 of the fluid transfer tube 6 may be rounded, conical, or bullet-shaped to minimize tissue trauma during insertion. However, this is not mandatory, and the distal end 10 may be cut into a square. Due to the non-traumatic insertion characteristics of the fluid transfer tube 6, for example, due to its narrow outer diameter, the fluid transfer tube 6 does not cause significant tissue damage during insertion. Therefore, the shape of the distal end 10 is not very important in reducing trauma.

[0062] To improve lubricity, reduce tissue adhesion, reduce tissue integration ability, or provide other desirable properties, at least the outer surface 56 of the fluid transfer tube 6 may include a coating. For example, the outer surface 56 may be post-treated by, for example, plasma treatment, or may have a suitable coating applied to provide it with desired properties. For example, a lubricating coating of parylene or polytetrafluoroethylene (PTFE) may be used to reduce the shear force on the tissue when the fluid transfer tube 6 is inserted into the tissue. Alternatively, a lubricating heat-shrinkable plastic tube may be applied to the outer surface of the fluid transfer tube 6. For example, the heat-shrinkable tube may be formed from PTFE, FEP, PET, or polyolefin.

[0063] As another example, a coating can be provided on the distal end 10 of the fluid transfer tube to reduce tissue adhesion or integration (e.g., a cytotoxic coating). With respect to long-term implantation of the fluid transfer tube 6, tissue may grow or adhere around the distal end 10, thereby potentially blocking the through-bore 52 and hindering the delivery of the injectable fluid. A suitable coating can prevent or reduce this effect.

[0064] The material and / or thickness of the fluid transfer tube 6 may be such that the tube can be cut by hand using a knife or sharp blade. The fluid transfer tube 6 may be cut to a desired insertion length for fixation of its proximal end (for example, in the skull) before insertion. The fluid transfer tube 6 may be cut with a sharp blade in a cutting fixture.

[0065] The fluid transfer tube 6 includes a plurality of recirculation regions 54 on its outer surface 56. The plurality of recirculation regions 54 can include at least four recirculation regions 54, optionally at least five recirculation regions 54, or optionally at least six recirculation regions 54. As shown in Figure 1, the plurality of recirculation regions can include a total of six recirculation regions 54, i.e., exactly six recirculation regions 54.

[0066] In another embodiment shown in Figure 2, the multiple recirculation regions can include a total of five recirculation regions 54, i.e., exactly five recirculation regions 54, so that the multiple recirculation regions consist of exactly five recirculation regions 54. Using five recirculation regions may be preferable because it has been found that five recirculation regions provide better distribution than four or six recirculation regions. This is due to the balance between the number of recirculation regions 54 around the fluid transfer tube 6 and the size of each individual recirculation region 54 (it can be larger in the case of five recirculation regions than in the case of six recirculation regions).

[0067] The recirculation region 54 extends from the distal end 10 of the fluid transfer tube 6 along the length of the fluid transfer tube 6. The recirculation region 54 can be substantially longitudinal. For example, the recirculation region 54 can be parallel to the longitudinal axis of the fluid transfer tube 6, as shown with respect to the six recirculation region embodiments in Figure 3 and the five recirculation region embodiments in Figure 4. However, this is not mandatory, and other configurations are possible. For example, the recirculation region 54 can extend spirally from the distal end 10 around the outer surface 56 along the length of the fluid transfer tube 6. Each recirculation region 54 forms a continuous region on the outer surface 56.

[0068] The reflux region 54 is configured to allow the flow of the injectable fluid along the reflux region 54 from the distal end 10 of the fluid transfer tube 6 to the proximal end of the fluid transfer tube 6 when the distal end 10 of the fluid transfer tube 6 is inserted into the tissue. This provides a more uniform and consistent distribution of the injectable fluid around the fluid transfer tube 6. The reflux region 54 also reduces the contact area with the tissue, thereby increasing the lubricity of the fluid transfer tube 6 and improving the ease of insertion into the tissue.

[0069] The effect of the reflux region 54 is demonstrated with respect to six embodiments of the reflux region in Figures 5 and 6, and five embodiments of the reflux region in Figures 7 and 8. The injectable fluid flows down the through bore 52 from the proximal end of the fluid transfer tube and out of the through bore 52 at the distal end 10 of the fluid transfer tube 6. The reflux region 54 provides a region of lower resistance to the fluid flow, causing the injectable fluid to flow back towards the proximal end along the interface between the outer surface 56 and the tissue around the fluid transfer tube 6. The injectable fluid can then be pushed outward into the surrounding tissue along the entire length of the reflux region 54 in contact with the tissue.

[0070] The reflux region 54 can be configured to allow the injector to flow along the reflux region 54 rather than permeate the tissue when the distal end 10 of the fluid transfer tube 6 is inserted into the tissue. Thus, the injector first flows along the outer surface 56 of the fluid transfer tube 6, as shown in Figures 6 and 8, filling the reflux region 54 before moving outward into the surrounding tissue. This means that the injector can be distributed more uniformly across the entire area of ​​the outer surface 56 that is in contact with the tissue.

[0071] As described above, the fluid transfer tube 6 can be used in combination with the guide tube 4. The guide tube 4 has a larger outer diameter than the fluid transfer tube 6. The difference between the outer diameter d of the fluid transfer tube 6 and the outer diameter of the distal end 18 of the guide tube 4 is such that a step 20 is formed. Step 20 restricts the recirculation of the injected fluid proximal to step 20 when the fluid transfer tube 6 is inserted into the tissue through the through-bore of the guide tube 4.

[0072] As the injectable fluid travels down the fluid transfer tube 6 and is delivered into the tissue through its distal end 10, the recirculating fluid travels back along the recirculation region 54 toward step 20, which is created by the change in diameter at the distal end 18 of the guide tube 4 extending from the fluid transfer tube 6. The high-pressure zone in the tissue immediately distal to step 20, which is created by the insertion of the guide tube 4, compresses the tissue interface and resists recirculation outside the target region.

[0073] A further advantage of the recirculation region 54 is that the injectable fluid can be distributed over a larger volume at lower pressures. The low resistance of the recirculation region 54 causes the injectable fluid to be distributed more easily over the outer surface 56 of the fluid transfer tube 6. In prior art devices, compression of the surrounding tissue can form a tight seal around the outer surface of the fluid transfer tube. This is especially true for devices intended for non-traumatic insertion (e.g., those with a narrow outer diameter). This means that it is necessary to increase the fluid pressure to push the injectable fluid out of the distal end into the tissue. Once the injectable fluid is discharged from the distal end 10, it cannot recirculate back over the outer surface of the device due to the effective sealing of the tissue around the outer diameter. This means that the injectable fluid tends to be pushed outward into a spherical region centered on the distal end of the device. This provides limited control over the volume to which the injectable fluid is delivered. Furthermore, higher fluid pressure creates a relatively higher risk of tissue damage, or a relatively high risk of the injected fluid being completely pushed out of the target area into other areas of the tissue.

[0074] In contrast, in this fluid transfer tube 6, the reflux region 54 provides a low-resistance path for the injected fluid to move along the outer surface of the fluid transfer tube 6 away from the distal end 10 of the fluid transfer tube 6. This means that a lower fluid pressure can be used to distribute the injected fluid. It also means that the distance between step 20 and the distal end 10 of the fluid transfer tube 6 can be used to control the volume to which the injected fluid is delivered more precisely and effectively.

[0075] The fluid transfer tube 6 is configured for non-traumatic insertion into tissue. This means that the configuration of the fluid transfer tube 6 is designed to minimize injury, trauma, or damage to the tissue when it is inserted into the tissue. For example, the configuration can be designed so that no tissue crushing or tearing occurs during insertion. Insertion of the fluid transfer tube 6 is only possible by expanding the surrounding tissue. Typically, as discussed further below, a fluid transfer tube track is formed in the tissue before insertion of the fluid transfer tube 6. Non-traumatic insertion may mean that no further injury, trauma, or damage to the tissue (e.g., tissue crushing or tearing) occurs when the fluid transfer tube 6 is inserted into the tissue along the pre-formed fluid transfer tube track.

[0076] The configuration of the fluid transfer tube 6 for non-traumatic insertion is provided by the appropriate dimensions and characteristics of the fluid transfer tube 6 and the recirculation region 54.

[0077] The variation in the outer diameter d and radius of the fluid transfer tube 6 allows for non-traumatic insertion into tissue while maintaining the recirculation area. The outer diameter d of the fluid transfer tube 6 can be selected to be small enough to minimize tissue damage when inserted. The outer diameter can be 1.0 mm or less, optionally 0.75 mm or less, and optionally 0.5 mm or less. The fluid transfer tube 6 can have an outer diameter between 0.4 mm and 0.7 mm, preferably between 0.5 mm and 0.6 mm, for example, an outer diameter of 0.5 mm. For clarification, unless otherwise specified, the “outer diameter” of the fluid transfer tube 6 is generally used to mean the outermost or maximum diameter of the fluid transfer tube 6, as indicated by length d in Figure 1.

[0078] The distal end of the fluid transfer tube 6 can be configured to compress the tissue laterally when inserted into the tissue, and the compression of the tissue by the reflux region 54 can be less than the compression of the tissue by the outer surface 56 of the fluid transfer tube 6 that is circumferentially adjacent to the reflux region 54. This reduced compression of the tissue by the reflux region 54 leads to the need for a lower fluid pressure for the injected fluid to be pushed along the reflux region 54.

[0079] The recirculation region 54 can be provided by a change in the radius of the fluid transfer tube 6. In the following, the radius of the fluid transfer tube 6 will generally be defined with respect to a specific point on the outer surface 56 of the fluid transfer tube 6, and unless otherwise specified, it will refer to the distance from the central longitudinal axis of the fluid transfer tube 6 to that point.

[0080] For example, as shown in Figure 1, the radius of the fluid transfer tube 6 can be reduced in the recirculation region 54 with respect to the radius of the fluid transfer tube 6 circumferentially adjacent to the recirculation region 54. The recirculation region 54 can include a region in which the radius of the fluid transfer tube 6 is reduced relative to the maximum radius of the fluid transfer tube 6. In Figure 1, each recirculation region 54 is in direct contact with a circumferentially adjacent recirculation region 54 on either side, and the maximum radius of the fluid transfer tube 6 is reached only at a point on the outer surface where two adjacent recirculation regions 54 meet. However, this is not generally required, and in other implementations, the recirculation regions 54 can be spaced circumferentially around the outer surface 56 of the fluid transfer tube 6. In particular, the recirculation regions 54 can be spaced uniformly around the periphery of the fluid transfer tube 6.

[0081] The cross-sectional profiles of each of the multiple reflux regions 54 can be identical. This helps to provide consistent and predictable reflux behavior around the entire fluid transfer tube 6.

[0082] The radius of the fluid transfer tube 6 can increase monotonically away from the center of the recirculation region 54 in the circumferential direction. That is, each recirculation region 54 can have its own point of minimum radius. The radius can increase strictly away from the center of the recirculation region 54.

[0083] The minimum radius of the fluid transfer tube 6 in the recirculation region can be at least 50%, optionally at least 60%, optionally at least 70%, or optionally at least 80% of the radius of the fluid transfer tube 6 circumferentially adjacent to the recirculation region 54, or the maximum radius of the fluid transfer tube 6. The minimum radius of the fluid transfer tube 6 in the recirculation region can be up to 90%, optionally up to 80%, optionally up to 70%, or optionally up to 60% of the radius of the fluid transfer tube 6 circumferentially adjacent to the recirculation region 54, or the maximum radius of the fluid transfer tube 6.

[0084] Each recirculation region 54 extends not only along the length of the fluid transfer tube 6 but also has width in the circumferential direction. The circumferential width of each recirculation region 54 can be defined as an angular width in terms of the angle stretched by the recirculation region 54 along the longitudinal axis of the fluid transfer tube 6. The angular width of each recirculation region can be at least 15 degrees, optionally at least 30 degrees, and optionally at least 45 degrees. The angular width of each recirculation region can be up to 90 degrees, optionally up to 75 degrees, and optionally up to 60 degrees. For example, the angular width of each recirculation region can be 60 degrees, as shown in Figure 1. Furthermore, the circumferential width of each recirculation region 54 can be expressed as a distance around its periphery. The width can be at least 0.1 mm, optionally at least 0.15 mm, optionally at least 0.2 mm, and optionally at least 0.25 mm.

[0085] The recirculation region 54 can extend along at least a portion of the fluid transfer tube 6 that is configured to contact tissue when the distal end 10 of the fluid transfer tube 6 is inserted into the tissue. This can be the portion of the fluid transfer tube 6 that protrudes beyond the distal end 18 of the guide tube 4 when the fluid transfer tube 6 is configured for insertion through the guide tube 4. The recirculation region 54 does not have to extend to the proximal end of the fluid transfer tube 6. The recirculation region 54 can extend at least 1 mm, optionally at least 2 mm, optionally at least 5 mm, and optionally at least 10 mm from the distal end 10 of the fluid transfer tube 6.

[0086] However, in some implementations, the reflux region 54 can extend to the proximal end of the fluid transfer tube 6 and / or along substantially the entire length of the fluid transfer tube 6. This may be preferable depending on the method of manufacturing the fluid transfer tube 6. For example, manufacturing the fluid transfer tube 6 to have a reflux region 54 along its entire length, or to have a uniform cross-section along its length, can reduce costs.

[0087] As shown in Figure 1, the reflux region 54 may include a channel. In this case, the outer diameter d of the fluid transfer tube 6 and the depth of the channel may allow for non-traumatic insertion into the tissue. The channel may have a radial depth a of at least 0.05 mm, optionally at least 0.075 mm, and optionally at least 0.1 mm.

[0088] The outer surface 56 of the fluid transfer tube 6 in the reflux region 54 can be concave, as shown in Figure 1. This defines the minimum radius in the reflux region 54, which helps to direct the flow of the injected fluid. The outer surface 56 of the fluid transfer tube 6 circumferentially adjacent to the reflux region 54 can be convex. The outer surface 56 circumferentially adjacent to the reflux region 54 can have a radius of curvature that is, among other things, within 10% of the outer diameter d of the fluid transfer tube 6, optionally within 5%, and optionally approximately half. The maximum curvature of the outer surface 56 of the fluid transfer tube 6 circumferentially adjacent to the reflux region 54 can be less than or equal to the maximum curvature of the outer surface 56 of the fluid transfer tube 6 in the reflux region 54. This prevents the fluid transfer tube 6 from having sharp tips or vanes around its periphery (which could cause tissue damage during insertion).

[0089] The outer surface 56 of the fluid transfer tube 6 at its distal end 10 can be smoothly curved or flat at all points around the periphery of the fluid transfer tube 6. This also helps prevent tissue damage during insertion. This is particularly important because the fluid transfer tube 6 may twist when it is inserted or when it is fixed at its proximal end.

[0090] The circumference of the fluid transfer tube 6 can be at least 5% larger, optionally at least 10% larger, and optionally at least 15% larger than the outer circumference of the fluid transfer tube 6. This helps to increase the surface area to which the injected fluid is distributed during use. Here, the outer circumference refers to the circumference defined by the outer diameter d of the fluid transfer tube 6, as shown by the dashed circle 58 in Figure 1.

[0091] Figures 9 and 10 show alternative designs for the fluid transfer tube 6. In this design, the outer surface 56 of the fluid transfer tube 6 is substantially flat in the recirculation region 54. Thus, the cross-section of the fluid transfer tube 6 can be a regular polygonal cross-section. In this case, the vertices of the regular polygon can be rounded to reduce the possibility of trauma to surrounding tissue. In Figure 9, the multiple recirculation regions 54 include a total of six recirculation regions 54, and the distal end 10 of the fluid transfer tube 6 has a hexagonal profile in cross-section.

[0092] Figures 11 and 12 are MRI images taken during the injection procedure to demonstrate the effectiveness of the fluid transfer tube 6. In both cases, the fluid transfer tube 6, 206 is inserted into the brain tissue along the guide tube 4.

[0093] Figure 11 shows the left putamen of a non-human primate after injecting 150 μl of an injector containing an MRI contrast agent (gadoteridol) using a prior art fluid delivery tube 206 lacking a perfusion region 54. The injector was delivered at 1 μl / min for 10 minutes, 2 μl / min for 5 minutes, and then at 3 μl / min for 43 minutes and 20 seconds. The bright white areas indicate where the injector entered the tissue surrounding the distal end 10 of the fluid delivery tube 6. As can be seen, the injector is escaping from the target volume of the 3 mm cylinder shown in red. Instead, the injector forms an irregular spherical distribution roughly centered on the distal end of the tube 206. The injector travels much further in the direction toward the bottom of the image than in the opposite direction toward the top of the image. This is likely due to leakage of the injector from the target brain structure into the surrounding white matter (which has lower resistance to fluid flow). This loss of containment makes it impossible to deliver the injectable fluid accurately. This is because any further increase in fluid pressure would cause the injectable fluid to continue leaking into the surrounding tissue rather than refluxing through the tube to fill the target volume.

[0094] Figure 12 shows injection into a shell using the fluid transfer tube 6 of this disclosure, according to the design shown in Figure 1. In this case, a bright white area of ​​the injected fluid can be seen extending proximal from the distal end 10 of the fluid transfer tube 6 to the step in which the distal end of the guide tube is positioned. The injected fluid takes on a clearly defined, regular cylindrical shape around the distal end 10 of the fluid transfer tube 6, where the fluid transfer tube 6 protrudes beyond the end of the guide tube 4. This demonstrates how the reflux region 54 enables more consistently controlled injected fluid delivery.

[0095] It is important that air is not delivered into the brain through the fluid transfer tube 6, and to reduce this risk, the fluid transfer tube 6 may include a bubble vent 74. The bubble vent 74 is preferably provided at the proximal end of the fluid transfer tube 6, as shown in Figure 13. The configuration and component parts of the bubble vent 74 are described below and illustrated in Figure 14. The bubble vent 74 is configured to prevent gas from entering the fluid transfer tube 6. The bubble vent 74 reduces the risk of bubbles entering the brain if bubbles escape from the solution in the infusion or become mixed into the infusion during connection and / or disconnection of the delivery system (e.g., dispenser, infusion line, and / or pump) used to deliver the infusion fluid to the fluid transfer tube 6. Bubbles injected into brain tissue can tear the tissue and disrupt the distribution of the therapeutic fluid / infusion. The bubble vent 74 can be permanently bonded to and / or formed integrally with the fluid transfer tube 6, which further reduces the possibility of bubbles being introduced during connection of the fluid transfer tube to the delivery system. The bubble vent 74 is preferably supplied integrally with the cannula 6, as shown in Figure 13. Figure 14 illustrates an exploded view of the bubble vent 74 configured for attachment to the cannula 6 and the 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. The bubble vent 74 may include a low-volume bubble filter 82 (for example, made from stretched polytetrafluoroethylene (ePTFE)). The bubble filter 82 may have a hydrophobic (optionally, superhydrophobic), gas-permeable, microporous structure configured to remove bubbles from the flowing therapeutic fluid / injection solution. The bubble filter 82 may be effective in removing bubbles at flow rates of 30 μl / min or less.The bubble vent 74 may further include a filter guard 80. In the illustrated example, the bubble filter 82 is effective in removing bubbles at flow rates of 30 μl / min or less. The filter 82 is contained within a perforated filter guard 80, and in the illustrated example, the bubble filter 82 is received on a hollow post 85 and held in place on the hollow post 85 by a retainer ring 83A, and the hollow post 85 is positioned concentrically on the filter guard 80.

[0096] The filter guard 80 may include a hollow shell, which includes a distribution of multiple perforations 87 (small holes) around the shell wall, which facilitates the degassing of the fluid / injection as it flows through the bubble vent 74 into the fluid transfer tube 6. The filter guard 80 can also guard / protect the bubble filter 82 against damage. The combination of the bubble filter 82 and the filter guard 80 facilitates the dispersion of air / bubbles mixed in from the fluid flow before the fluid enters the fluid transfer tube 6.

[0097] The bubble vent 74 may include a retaining cap 84, which connects to the filter guard 80, completing the assembly of the bubble vent 74 and containing the bubble filter 82. The retaining cap 84 may include a hollow retaining post 89 and retainer ring 83B, which engage with the bubble filter 82, ensuring that the bubble filter 82 is properly positioned and held within the filter guard 80, and ensuring the efficient function of the bubble filter 82 during use. The retaining cap 84 may include a septum stopper 86, which provides a sealed unit until the septum 86 is punctured by a hollow needle to provide a fluid connection to the fluid transfer tube 6. The septum stopper 86 may be held under compression by a septum cap 88. The retaining cap 84 and the filter guard 80 may be joined by a snap-fit ​​connection. However, alternative arrangements can also be used to join them together (for example, screw connections, welded connections, glued connections, etc.).

[0098] The bubble vent 74, incorporating the bubble filter 82, reduces the risk of air being delivered to, for example, the brain, along with the fluid containing the therapeutic agent / injection. It is recognized that fluid containing air / bubbles would occupy space and therefore could stretch and tear brain tissue, while also disrupting the delivery / distribution of the therapeutic agent / injection.

[0099] Figures 15 to 18 show alternative designs for the bubble vent 174. The bubble vent 174 is configured to prevent gas from entering the fluid transfer tube 6. The bubble vent 174 can also be configured, either additionally or alternatively, to prevent pathogens (e.g., microorganisms such as bacteria) from entering the fluid transfer tube 6. This reduces the risk of intracranial infection caused by the treatment.

[0100] Figure 15 shows the bubble vent 174 in its assembled state, ready for use. Similar to the bubble vent 74, the bubble vent 174 includes a retaining cap 84. The retaining cap 84 includes a proximal connector 176 (e.g., a screw-type connector) for connection to the fluid connector of the delivery system.

[0101] Figure 16 shows an exploded view of the bubble vent 174, and Figure 17 shows a cross-sectional view. The proximal connector 176 may include a septum 86 for sealing the proximal connector 176 until the septum 86 is punctured, for example, by a hollow needle. The bubble vent 174 includes a fluid passage 140 that fluidly connects the proximal connector 176 and the fluid transfer tube 6. In this design, the bubble vent includes a first membrane 150 and a second membrane 152. The first membrane 150 and the second membrane 152 are positioned between the distal end of the fluid passage 140 and the proximal end of the fluid transfer tube 6. The first membrane 150 and the second membrane 152 may be substantially parallel to each other and substantially perpendicular to the 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, so that the fluid entering the bubble vent 174 through the septum 86 reaches the first membrane 150 before the second membrane 152. An annular washer 153 can be positioned between the first membrane 150 and the second membrane 152, forming a peripheral fluid seal between the membranes and the housing of the connector 174, separating the membranes in the center and creating a cylindrical gap between them. The cylindrical gap can have a diameter between 2 mm and 6 mm, but is most preferably 4 mm. The gap can separate the membranes 150 and 152 by only 0.05 mm to 0.2 mm, most preferably 0.1 mm. The first membrane 150 and the second membrane 152 can be connected to each other and to other components of the bubble vent 174 via a connecting surface 180. The connecting surface 180 can be joined by any suitable method (for example, using ultrasonic welding or using an adhesive layer). The bubble vent 174 may include a support member 184 for supporting the distal surface of the second membrane 152 and for allowing the liquid that has passed through the second membrane 152 to be easily reached by the cannula 6.

[0102] The first membrane 150 is hydrophobic and gas permeable. A pore 154 is provided within the first membrane 150 where the fluid passage 140 meets the first membrane 150, allowing fluid from the fluid passage 140 to pass through the first membrane 150 via the pore 154. The septum-sealed connector 174 may include a support member for supporting the proximal surface of the first membrane 150 and an annular connecting surface for attaching the membrane around its periphery and at the central pore 154 (not shown in Figure 16). The second membrane 152 is liquid permeable and preferably hydrophilic. While it is not essential for the second membrane 152 to be hydrophilic, gas venting works most efficiently using a combination of hydrophobic and hydrophilic membranes. Using the hydrophobic first membrane 150 alone may result in air being drawn from the atmosphere through the first membrane 150 into the injection fluid when the pressure in the line is below atmospheric pressure. This can occur if the connector is lifted above the head by more than 10-25 cm (depending on intracranial pressure). The hydrophilic nature of the second membrane 152 prevents air from entering the brain even in such situations. The second membrane 152 is impermeable to gases and bacteria. No vents are provided within the second membrane 152, and the fluid from the fluid passage 140 must pass through the material of the second membrane 152 to reach the fluid transfer tube 6. One or more vent holes 160 (for example, two vent holes in the example of Figure 16) are provided within the bubble vent 174 proximal to the first membrane 150. No vents are provided within the first membrane 150 where the vent holes 160 meet the first membrane 150, and the fluid from the fluid passage 140 must pass through the material of the first membrane 150 to reach the vent holes 160.

[0103] The operation of the bubble vent 174 is demonstrated in the close-up view of Figure 18. A mixture of liquid and gas (for example, an infusion fluid to be delivered to the patient's brain via the fluid transfer tube 6, with some mixed air bubbles) enters the bubble vent 174 via the septum 86 and fluid passage 140. The mixture passes through the first membrane 150 via the pore 154. The liquid is attracted to the hydrophilic second membrane 152 and permeates into the second membrane 152 (which is liquid permeable) and enters the cannula. The layer of liquid and the second membrane 152 form a barrier that prevents gas from entering the fluid transfer tube 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 one of the locations of the vent 160. The hydrophobic nature of the first membrane 150 repels liquids, preventing them from forming a barrier similar to that on the second membrane 152, thereby allowing gases to pass through the vent holes 160 and out of the bubble vent 174.

[0104] The fluid transfer tube 6 can be provided as part of a neurosurgical apparatus (for example, the neurosurgical apparatus shown in Figure 19), which also includes a guide tube 4. The guide tube 4 includes a proximal end and a distal end 18. The distal end 18 is configured for insertion into tissue. The guide tube 4 can be configured for insertion into tissue using image guidance. For example, at least the distal end 18 of the guide tube 4 can include a radiopaque material. The guide tube 4 includes a through bore 30 for the passage of the fluid transfer tube 6. The guide tube 4 (or the cannula assembly if the fluid transfer tube 6 is inserted into the guide tube 4 before insertion into tissue) is preferably passed down a prefabricated track into the tissue. As the guide tube 4 enters the track, the track is gently expanded to a larger diameter than the guide tube 4. The fluid transfer tube 6 is then inserted into the tissue through the through bore of the guide tube 4.

[0105] The distal end 10 of the fluid transfer tube 6 can be configured to protrude into the tissue beyond the distal end 18 of the guide tube 4 by a length that can be adjusted and / or fixed. The fluid transfer tube 6 can be positioned so that its distal end 10 is at least aligned with or protrudes beyond the distal end 18 of the guide tube 4 when it is inserted through the through-bore of the guide tube 4 before its insertion into the tissue. The guide tube 4 can be inserted into brain tissue with the fluid transfer tube 6 protruding beyond its distal end 18 by a predetermined length, so that when the distal end 18 of the guide tube 4 reaches the target region, the distal end 10 of the fluid transfer tube 6 also reaches its planned target. Alternatively, after insertion of the guide tube 4, the distal end 10 of the fluid transfer tube 6 can be advanced through the tissue of a selected target.

[0106] When used for fluid access to the brain, the guide tube 4 can be inserted through a trepanation hole in the skull where the guide hub 50 is already fitted. The guide hub 50 is for fixation to the patient's skull before insertion of the guide tube 4 into the brain. A separate guide hub can be provided as part of a neurosurgical apparatus including the guide tube 4 and the fluid transfer tube 6 and / or other components. The guide hub 50 has a passage for the guide tube 4 through it. The guide hub 50 provides a fixed reference point in the skull from which the orientation and length of the probe, guide tube 4, and fluid transfer tube 6 can be directed. The proximal end of the guide tube 4 can be fixed to the guide hub 50 by, for example, a fitting with a bore through it (e.g., a screw fitting). The interposition of a deformable washer (e.g., a silicone washer) between the distal end of the screw fitting and the guide tube 4 allows for radial compression and sealing around the fluid transfer tube 6. Furthermore, this makes it possible to fix the position of the fluid transfer tube 6 relative to the guide hub 50 (and thereby relative to the skull). When compressed around the fluid transfer tube 6, such a washer can also create a fluid seal between the fluid transfer tube 6 and the guide tube 4.

[0107] The fluid transfer tube 6 (particularly the proximal end of the fluid transfer tube 6) may include a stop 70 that engages with the proximal end of the guide tube 4, thereby setting the length by which the fluid transfer tube 6 protrudes beyond the distal end of the guide tube 4. The stop 70 may also be configured to engage with the proximal end of the guide tube 4 and form a fluid seal between the fluid transfer tube 6 and the guide tube 4. This seals a potential leakage route for fluid that might otherwise flow out of the tissue from between the through-bore of the guide tube 4 and the fluid transfer tube 6. The seal also closes a potential entry route for bacteria into the tissue. The fluid seal may also be formed by compression of a deformable washer (e.g., a silicone washer) or by compression of the elastically deformable outer layer of the guide tube 4.

[0108] The position of the stop 70 along the length of the fluid transfer tube 6 may be adjustable. This allows the length of the fluid transfer tube 6 that protrudes beyond the distal end 18 of the guide tube 4 to be adjusted. Alternatively, the stop 70 may be fixed to the fluid transfer tube 6, and the insertion depth of the fluid transfer tube 6 may be adjusted by cutting it to the desired length relative to the stop 70 using a knife. The stop 70 may be a screw-type stop that screws into complementary threads in the bore of the guide hub.

[0109] The stop 70 can be overmolded onto the fluid transfer tube 6. The stop 70 can include an indentation or castellation on its proximal surface, which is configured to receive and hold the fluid transfer tube 6. The fluid transfer tube 6 can be bent and press-fitted into the indentation, holding its proximal portion at a predetermined angle to the portion inserted into the tissue. This can help orient the fluid transfer tube 6 outward from the tissue.

[0110] For example, if the reflux region 54 extends to the proximal end of the fluid transfer tube 6 and / or extends along substantially the entire length of the fluid transfer tube 6, the reflux region 54 can extend along a portion of the fluid transfer tube 6 proximal to the stop 70. In this case, the sleeve 68 can be provided over a portion of the fluid transfer tube 6 proximal to the stop 70, that is, over a portion of the fluid transfer tube configured to be outside the tissue when the distal end 10 of the fluid transfer tube 6 is inserted into the tissue.

[0111] The function of the sleeve 68 can be to protect the fluid transfer tube 6 or to help keep the fluid transfer tube 6 within the indentation or castellation of the stop 70. The sleeve 68 can be fixed to the fluid transfer tube 6 as part of the attachment of the stop 70 to the fluid transfer tube 6. For example, the sleeve 68 can be placed on top of the fluid transfer tube 6 before the stop 70 is attached to the fluid transfer tube 6. The distal end of the sleeve 68 can be fixed inside the stop 70, for example, during the overmolding of the stop. The sleeve 68 can include a plastic material. The sleeve 68 can be attached to the fluid transfer tube 6 by heat shrinking.

[0112] The reflux region 54 does not have to extend along the portion of the fluid transfer tube 6 configured to be inside the guide tube 4 when the distal end 10 of the fluid transfer tube 6 is inserted into the tissue. Therefore, only the length of the fluid transfer tube 6 configured to protrude into the tissue beyond the distal end 18 of the guide tube 4 can include the reflux region 54. This reduces the possibility of the injectable fluid traveling back inside the guide tube 4 toward the proximal end of the guide tube 4 (which could cause undesirable fluid loss or increase the possibility of leakage outside the target region).

[0113] The guide tube 4 can be a rigid guide tube inserted into a predetermined location within the tissue along a trajectory established by image guidance. The rigid guide tube is typically used in conjunction with a rigid fluid transfer tube 6. The rigid guide tube includes rigid materials such as ceramics, metals (e.g., titanium or stainless steel), or rigid plastic materials (e.g., PEEK). The proximal end of the rigid guide tube is typically guided and held by a stereoguide or robotic guide during use.

[0114] Convection-enhanced drug delivery techniques can be used for both acute (short-term) and chronic (longer-term or repeated) delivery of treatment to tissues. For example, gene therapy can be performed in a single treatment session, while treatments for other reasons, such as chemotherapy, may require repeated infusions into the brain (chronic treatment regimens).

[0115] When the guide tube 4 is rigid, it can be inserted directly into the tissue without the need to form a track in the tissue beforehand. The rigid guide tube 4 and the corresponding rigid fluid transfer tube 6 may be particularly suitable for acute treatment, in which the guide tube 4 is inserted into the brain to perform a specific procedure and then removed when the procedure is complete.

[0116] When a rigid guide tube 4 is used, the fluid transfer tube 6 can be inserted into the through-bore 30 of the guide tube 4 before the guide tube 4 is inserted into the tissue, so that the guide tube 4 and the fluid transfer tube 6 are inserted into the tissue as a single unit (cannula assembly). In this case, during use, the fluid transfer tube 6 is primed with fluid before insertion of the cannula assembly into the tissue. This prevents air from being trapped inside the fluid transfer tube 6 (the air will then be pushed into the tissue as the fluid is passed through the fluid transfer tube 6). The fluid transfer tube 6 can be positioned and held within the through-bore of the guide tube by a releaseable compression seal at the proximal end of the guide tube 4. The compression seal can interact with a depth control stop 70 (if present) above the fluid transfer tube 6. The fluid transfer tube 6 can also be rigid. For example, the fluid transfer tube 6 may contain or be formed from a rigid material such as fused silica, metal (e.g., titanium or stainless steel), or a rigid biocompatible plastic (e.g., polyetheretherketone (PEEK)).

[0117] Alternatively, the guide tube 4 can be a cuttable or flexible guide tube, which is cut to a predetermined length, with its distal end inserted into a predetermined location in the tissue by image guidance, and its proximal end fixed in the skull during use. The material and / or thickness of the guide tube 4 can be such that it can be cut by hand using a knife or sharp blade. When the guide tube 4 is flexible, the fluid transfer tube 6 can also be flexible. For example, the fluid transfer tube 6 can contain a flexible material or be made from a flexible material. This allows the fluid transfer tube 6 to move and maintain its intended position in the target even when tissue movement occurs.

[0118] Exemplary neurosurgical devices are shown in Figures 19 and 20. The neurosurgical devices in Figures 19 and 20 include a fluid transfer tube 6, a guide tube 4, a guide hub 50, and a stop 70. Figure 19 shows the components of the device separately, while Figure 20 shows the assembled components as they will be during use.

[0119] Further exemplary neurosurgical devices are shown in Figures 21 and 22. The neurosurgical devices of Figures 21 and 22 are substantially similar to those of Figures 19 and 20, but also include a bubble vent 74 provided integrally with the proximal portion of the fluid transfer tube 6. Figure 21 shows the components of the device separately, and Figure 22 shows the assembled components as they will be during use.

[0120] In contrast to holding the guide tube 4 by a stereoguide during the delivery of the injectable fluid (where only a single target injection can be achieved at a time), the use of embodiments with bone fixation using a guide hub 50 facilitates simultaneous injection through several implanted devices. This significantly reduces procedure time and patient risk. Fixing the proximal end of the guide tube 4 to the skull (or to the guide hub 50 fixed to the skull) provides a relatively safe placement for long-term or chronic treatment. Thus, this type of guide tube 4 can be left in place for extended periods of time for use when chronic or chronic intermittent injections are required.

[0121] In some situations, for example when using a rigid guide tube 4, the fluid transfer tube 6 and guide tube 4 can be assembled together and delivered together into the tissue. In other situations, for example when using a guide tube 4 fixed to the skull (e.g., as shown in Figures 19 and 20), the distal end 10 of the fluid transfer tube 4 can be passed through the through-bore of the guide tube 4 after insertion of the guide tube 4 into the tissue, passing through the proximal end of the guide tube 4 and through to the distal end 18 to be delivered to the target. While the fluid transfer tube 6 passes through the through-bore of the guide tube 4, a column of air inside the guide tube 4 is pushed distally by a piston-like action. This can lead to tearing of the tissue in the target area. To mitigate this, the guide tube 4 can be configured to vent gas from the through-bore of the guide tube 4 to the proximal end of the guide tube 4, preferably through the inner surface of the through-bore. Venting air from the guide tube 4 to the atmosphere can be stopped when the fluid transfer tube 6 is fully inserted into the guide tube 4. At this point, the fluid transfer tube 6 can engage with the proximal end of the guide tube 4, for example, via a stop 70 or an intervening washer, to create a seal.

[0122] Furthermore, the fluid transfer tube 6 can be provided as part of a kit for a convection-enhanced drug delivery method for injecting fluid into tissue. The kit includes the fluid transfer tube 6, which includes a proximal end, a distal end 10 for insertion into tissue, a through bore 52 configured to allow the flow of injecting fluid from the proximal end to the distal end 10, and a plurality of reflux regions 54 on the outer surface 56 of the fluid transfer tube 6. The kit can also include a guide tube 4 and / or a guide hub 50.

[0123] The kit further includes a delivery probe configured to be inserted into tissue to form a fluid transfer tube track. The delivery probe can be a track-forming probe.

[0124] The delivery probe can be configured to be inserted into the through-bore of the guide tube 4. The guide tube 4 can be inserted into the tissue when mounted on the delivery probe, or it can be inserted into the guide tube 4 after it has already been inserted. Once the distal end 18 of the guide tube 4 is positioned at its predetermined target location in the tissue, the delivery probe can be advanced further along the same trajectory as the guide tube 4. The distal end of the delivery probe can be advanced until it reaches a planned location for the fluid transfer tube 6, thereby forming a track for the fluid transfer tube 6. The delivery probe is then withdrawn, leaving the guide tube 4 in place and a distal track for accommodating the fluid transfer tube 6. The distal end of the delivery probe can be configured to incise the tissue to assist in forming the fluid transfer tube track.

[0125] The cross-sectional area of ​​the delivery probe is larger than the cross-sectional area of ​​the distal end 10 of the fluid transfer tube 6. This means that when the fluid transfer tube 6 is inserted, the tissue will not be significantly compressed where it comes into contact with the fluid transfer tube 6. This reduces sealing around the fluid transfer tube 6 and allows the injected fluid to reflux more easily along the reflux region 54.

[0126] The delivery probe may include a rod having a rounded or conical distal end. The rod may be provided with a spike extending axially from the distal end of the rod to provide tissue-cutting capability at the distal end of the delivery probe. The spike may have a narrower diameter than the rod. The spike may be provided with a rounded extreme distal end. The spike may be tapered from the point where the spike abuts the rod at the rounded distal end of the rod to the extreme distal end of the spike. The spike may have a maximum diameter that is at most the diameter of the fluid transfer tube 6 (preferably smaller than the diameter of the fluid transfer tube 6). When in use, the spike at the distal end of the delivery probe may cut through tissue with reduced trauma when it is inserted, thereby generating a track with minimal tissue trauma.

[0127] The outer diameter of the distal end of the delivery probe can be approximately equal to the outer diameter of the fluid transfer tube 6. In this case, the reduction in the cross-sectional area of ​​the delivery probe relative to the fluid transfer tube 6 is due to the reduction in cross-sectional area caused by the presence of the reflux region 54. Furthermore, this choice of outer diameter means that the surrounding tissue can be slightly compressed circumferentially adjacent to the reflux region 54, resulting in a small sealing effect in these areas. This helps ensure that the injectable fluid flows first along the reflux region 54 rather than diffusing into the surrounding tissue.

[0128] The delivery probe can be fabricated from rigid materials such as hardened stainless steel or tungsten carbide. The delivery probe may have a coating to increase its lubricity, such as PTFE or parylene. The profile of the delivery probe is designed to pass through tissue to the target precisely and with minimal trauma, so that the subsequent insertion of the fluid transfer tube is relatively non-traumatic. It is also designed to form a track through gentle tissue expansion, allowing for the creation of a tissue seal rather than tissue fragmentation.

[0129] Each of the guide tube 4, the delivery probe, and the fluid transfer tube 6 may, if necessary, include any of the features described herein in relation to other embodiments.

[0130] A surgical procedure utilizing the fluid transfer tube 6 described herein is described below.

[0131] A method of enhancing convection of an injectable fluid into tissue involves delivering the injectable fluid into the tissue via a fluid transfer tube 6. Delivering the injectable fluid involves flowing the injectable fluid from the distal end 10 of the fluid transfer tube 6 toward the proximal end of the fluid transfer tube 6 along a plurality of reflux regions 54 on the outer surface 56 of the fluid transfer tube 6. The reflux regions 54 can be configured in relation to the fluid transfer tube 6 as described above.

[0132] This method may further include advancing a delivery probe into the tissue to form a fluid transfer tube track before delivering the injectable fluid, and inserting the fluid transfer tube 6 into the tissue along the fluid transfer tube track. The cross-sectional area of ​​the distal end of the delivery probe is greater than the cross-sectional area of ​​the distal end of the fluid transfer tube.

[0133] The insertion of the fluid transfer tube 6 can be non-traumatic. This can be achieved by the appropriate selection of the configuration and dimensions of the fluid transfer tube 6 and the recirculation region 54, as described above.

[0134] This method may further include inserting a guide tube 4 into the tissue, and advancing the delivery probe may include advancing the delivery probe through the guide tube 4. A fluid transfer tube track may extend from the distal end of the guide tube 4, and insertion of the fluid transfer tube 6 may include inserting the fluid transfer tube 6 through the guide tube 4.

[0135] This method may further include providing positive pressure of the injectable fluid within the fluid transfer tube 6 during insertion of the fluid transfer tube 6. This helps prevent coring of brain tissue by the fluid transfer tube 6 and also prevents air ingress that may occur if the fluid transfer tube 6 is inserted while gas-filled. However, this is not mandatory, and alternatively, the fluid transfer tube 6 can be primed or filled with the injectable fluid at neutral pressure before insertion of the fluid transfer tube 6. While positive pressure can reduce coring in some situations, it also means that additional injectable fluid is delivered during insertion of the fluid transfer tube 6 and before the distal end 10 of the fluid transfer tube 6 reaches the target region. This may be undesirable in some situations.

[0136] This method may include delivering the injector at a first flow rate and then at a second flow rate, where the first flow rate is lower than the second. The purpose of using a lower flow rate initially is to gradually open the interstitial space between cells in the tissue, allowing fluid flow into the tissue without disrupting it. This prevents the formation of fragments, which, if formed, tend to propagate as the injection progresses. The first flow rate can be up to 1 μl / min. The second flow rate can be between 3 μl / min and 7 μl / min, and optionally, the second flow rate can be 3 μl / min or 5 μl / min.

[0137] This method may include continuously and / or smoothly increasing the rate of delivery of the injector from a first flow rate to a second flow rate. The delivery rate can be up to 0.5 μL / min. 2 It can be increased by as much as 0.2 μL / min, and further optionally, up to a maximum of 0.2 μL / min. 2 It is possible to increase it by that amount.

[0138] Furthermore, the details of this method can be explained by the following numbered clauses.

[0139] M1. A method for enhancing the convection of an injectable fluid into a tissue, the method comprising the step of delivering the injectable fluid into the tissue via a fluid transfer tube, the step of delivering the injectable fluid comprising the step of flowing the injectable fluid along a plurality of reflux regions on the outer surface of the fluid transfer tube from the distal end of the fluid transfer tube toward the proximal end of the fluid transfer tube.

[0140] M2. The method according to clause M1, further comprising the steps of advancing a delivery probe into the tissue to form a fluid transfer tube track before delivering the injectable fluid, and inserting a fluid transfer tube into the tissue along the fluid transfer tube track.

[0141] M3. The method according to clause M2, wherein the step of inserting the fluid transfer tube is non-traumatic.

[0142] M4. The method according to clause M2 or M3, wherein the cross-sectional area of ​​the distal end of the delivery probe is greater than the cross-sectional area of ​​the distal end of the fluid transfer tube.

[0143] M5. The method according to any one of the clauses M1 to M4, further comprising the step of inserting a guide tube into tissue, the step of advancing a delivery probe comprising the step of advancing a delivery probe through the guide tube, the fluid transfer tube track extending from the distal end of the guide tube, and the step of inserting a fluid transfer tube comprising the step of inserting a fluid transfer tube through the guide tube.

[0144] M6. The method according to any one of the clauses M1 to M5, comprising the steps of first delivering an injection fluid at a first flow rate and then delivering an injection fluid at a second flow rate, wherein the first flow rate is lower than the second flow rate.

[0145] M7. The method according to clause M6, wherein the first flow rate is a maximum of 1 μl / min.

[0146] M8. The method according to clause M6 or M7, wherein the second flow rate is between 3 μl / min and 7 μl / min, and optionally the second flow rate is 3 μl / min or 5 μl / min.

[0147] M9. This method includes a step of continuously increasing the rate of delivery of the injector from a first flow rate to a second flow rate, and optionally, the delivery rate is up to 0.5 μL / min. 2 It is increased by only that much, and further optionally, up to a maximum of 0.2 μL / min 2 The method described in any one of the clauses M6 through M8, which is increased by only one of them.

[0148] M10. The method described in any one of the clauses M1 to M9, wherein the tissue is animal tissue, optionally mammalian tissue, optionally human tissue.

[0149] M11. The method described in any one of the clauses M1 to M10, wherein the tissue is brain tissue, and optionally brain parenchyma.

[0150] M12. The method according to any one of the clauses M1 to M11, wherein the injectable fluid is a therapeutic fluid. [Explanation of Symbols]

[0151] 4 Guide Tubes 6. Fluid transfer tube 10 Distal end 18 Distal end 20 steps 50 Guide Hubs 52 Penetrating Bore 54 Reflux Region 56 Outer surface 58 circular 68 sleeves 70 Stop 74 Bubble Vent 80 Filter Guard 82 Bubble Filter 83A, 83B Retaining Rings 84 Retaining Caps 85 Hollow Post 86 Septum Stopper 87 Perforation 88 Septum Cap 89 Hollow retaining post 140 Fluid passage 150 First membrane 152 The second membrane 153 Washer 154 Hole 160 Vent hole section 174 Bubble Vent 176 Proximal connector 180 connection surface 184 Support Member 206 Fluid transfer tubes, fluid delivery tubes a. Radial depth b. Diameter of the through bore d Outer diameter of the fluid transfer tube 6

Claims

1. A fluid transfer tube for insertion into biological tissue to deliver an injection fluid, The proximal end and A distal end for insertion into the aforementioned tissue, A through bore is configured to allow the flow of the injection fluid from the proximal end to the distal end, A plurality of recirculation regions on the outer surface of the fluid transfer tube, wherein the recirculation regions extend from the distal end of the fluid transfer tube along the length of the fluid transfer tube and Includes, The reflux region is configured to allow the flow of the injected fluid along the reflux region from the distal end to the proximal end of the fluid transfer tube when the distal end of the fluid transfer tube is inserted into the tissue. The fluid transfer tube is configured for non-traumatic insertion into the tissue.

2. The fluid transfer tube according to claim 1, wherein the recirculation region is provided by a change in the radius of the fluid transfer tube, and optionally, the radius of the fluid transfer tube is reduced in the recirculation region with respect to the radius of the fluid transfer tube circumferentially adjacent to the recirculation region.

3. The fluid transfer tube according to claim 2, wherein the outer diameter of the fluid transfer tube and the change in the radius of the fluid transfer tube allow for non-traumatic insertion into the tissue.

4. The fluid transfer tube according to claim 2 or 3, wherein the radius of the fluid transfer tube increases monotonically away from the center of the recirculation region in the circumferential direction, and optionally, the radius increases strictly away from the center.

5. The distal end of the fluid transfer tube is configured to compress the tissue when inserted into it. The fluid transfer tube according to any one of claims 1 to 4, wherein the compression of the tissue by the reflux region is lower than the compression of the tissue by the outer surface of the fluid transfer tube that is circumferentially adjacent to the reflux region.

6. The fluid transfer tube according to any one of claims 1 to 5, wherein the reflux region is configured to allow the flow of the injected fluid along the reflux region rather than the injecting fluid to penetrate the tissue when the distal end of the fluid transfer tube is inserted into the tissue.

7. The fluid transfer tube according to any one of claims 1 to 6, wherein the outer diameter of the fluid transfer tube is 1 mm or less, optionally 0.75 mm or less, and optionally 0.5 mm or less.

8. The fluid transfer tube according to any one of claims 1 to 7, wherein the through bore of the fluid transfer tube has a diameter of 0.4 mm or less, optionally 0.3 mm or less, optionally 0.2 mm or less.

9. The minimum radius of the fluid transfer tube in the reflux region is at least 50%, optionally at least 60%, optionally at least 70%, optionally at least 80% of the radius of the fluid transfer tubes circumferentially adjacent to the reflux region, and / or The fluid transfer tube according to any one of claims 1 to 8, wherein the minimum radius of the fluid transfer tube in the recirculation region is, at most 90%, optionally at most 80%, optionally at most 70%, and optionally at most 60% of the radius of the fluid transfer tubes circumferentially adjacent to the recirculation region.

10. The fluid transfer tube according to any one of claims 1 to 9, wherein the recirculation region is substantially longitudinal, and the recirculation region is optionally parallel to the longitudinal axis of the fluid transfer tube.

11. The reflux region extends along at least a portion of the fluid transfer tube that is configured to contact the tissue when the distal end of the fluid transfer tube is inserted into the tissue, and / or The fluid transfer tube according to any one of claims 1 to 10, wherein the reflux region does not extend to the proximal end of the fluid transfer tube.

12. The fluid transfer tube according to any one of claims 1 to 11, wherein the plurality of recirculation regions include a total of at least four recirculation regions, optionally at least five recirculation regions, optionally at least six recirculation regions, and optionally five recirculation regions.

13. The fluid transfer tube according to any one of claims 1 to 12, wherein the reflux region includes a channel.

14. The fluid transfer tube according to claim 13, wherein the outer diameter of the fluid transfer tube and the depth of the channel allow for the non-traumatic insertion into the tissue.

15. The fluid transfer tube according to claim 13 or 14, wherein the channel has a radial depth of at least 0.05 mm, optionally at least 0.075 mm, and optionally at least 0.1 mm.

16. The outer surface of the fluid transfer tube in the reflux region is concave, and / or The outer surface of the fluid transfer tube adjacent to the reflux region in the circumferential direction is convex, and / or The fluid transfer tube according to any one of claims 1 to 15, wherein the outer surface of the fluid transfer tube at the distal end is smoothly curved or flat at all points around the periphery of the fluid transfer tube.

17. The fluid transfer tube according to any one of claims 1 to 16, wherein the maximum curvature of the outer surface of the fluid transfer tube circumferentially adjacent to the reflux region is less than or equal to the maximum curvature of the outer surface of the fluid transfer tube in the reflux region.

18. The fluid transfer tube according to any one of claims 1 to 17, wherein the circumference of the fluid transfer tube is at least 5% larger than the outer circumference of the fluid transfer tube, optionally at least 10% larger, and optionally at least 15% larger.

19. The fluid transfer tube according to any one of claims 1 to 12, wherein the outer surface of the fluid transfer tube is substantially flat in the reflux region.

20. The fluid transfer tube according to claim 19, wherein the plurality of recirculation regions comprise a total of six recirculation regions, and the distal end of the fluid transfer tube has a hexagonal profile.

21. The fluid transfer tube according to any one of claims 1 to 20, wherein the fluid transfer tube is configured to be inserted into the tissue through a guide tube which includes a proximal end and a distal end configured for insertion into the tissue.

22. A guide tube comprising a proximal end and a distal end configured for insertion into tissue, The fluid transfer tube of claim 21 and Neurosurgical devices, including [specific type of device].

23. The fluid transfer tube according to claim 21, or the neurosurgical device according to claim 22, wherein the distal end of the fluid transfer tube is configured to protrude into the tissue beyond the distal end of the guide tube by a length that can be adjusted and / or fixed.

24. The fluid transfer tube according to claim 21, or the neurosurgical device according to claim 22 or 23, wherein the recirculation region does not extend along a portion of the fluid transfer tube configured to be within the guide tube when the distal end of the fluid transfer tube is inserted into the tissue.

25. The fluid transfer tube according to claim 21, or the neurosurgical device according to any one of claims 22 to 24, wherein the fluid transfer tube includes a stop, the stop engaging with the proximal end of the guide tube, thereby setting a length by which the fluid transfer tube protrudes beyond the distal end of the guide tube.

26. The difference between the outer diameter of the fluid transfer tube and the outer diameter of the distal end of the guide tube forms a step, the step restricts the recirculation of the injected fluid proximal to the step when the fluid transfer tube is inserted into the tissue through the through bore of the guide tube, the fluid transfer tube according to claim 21, or the neurosurgical device according to any one of claims 22 to 25.

27. A kit for enhancing convection of drug delivery solutions into tissues, A fluid transfer tube comprising a proximal end, a distal end for insertion into the tissue, a through bore configured to allow the flow of the injection fluid from the proximal end to the distal end, and a plurality of reflux regions on the outer surface of the fluid transfer tube, the reflux regions extending from the distal end of the fluid transfer tube along the length of the fluid transfer tube, A delivery probe configured to be inserted into the tissue to form a fluid transfer tube track Includes, The kit wherein the cross-sectional area of ​​the delivery probe is greater than the cross-sectional area of ​​the distal end of the fluid transfer tube.

28. The kit further includes a guide tube, the guide tube comprising a proximal end and a distal end configured for insertion into tissue, The kit according to claim 27, wherein the fluid transfer tube is configured to be inserted into the tissue through the guide tube.

29. The fluid transfer tube according to any one of claims 1 to 26, or the kit according to claim 27 or 28, wherein the tissue is animal tissue, optionally mammalian tissue, optionally human tissue, and / or the tissue is brain tissue, optionally brain parenchyma.

30. The fluid transfer tube according to any one of claims 1 to 26 or 29, or the kit according to claim 27, 28, or 29, wherein the injected fluid is a therapeutic fluid.

31. A method for enhancing convection of a fluid injected into tissue and for drug delivery, A step of delivering the injection fluid into the tissue via a fluid transfer tube, the step of delivering the injection fluid comprising flowing the injection fluid along a plurality of reflux regions on the outer surface of the fluid transfer tube from the distal end of the fluid transfer tube toward the proximal end of the fluid transfer tube, Methods that include...

32. The above method, before delivering the injection solution, The steps include advancing the delivery probe into the tissue to form a fluid transfer tube track, The steps include inserting the fluid transfer tube into the tissue along the fluid transfer tube track, The method according to claim 31, further comprising:

33. The method according to claim 32, wherein the step of inserting the fluid transfer tube is non-traumatic.

34. The method according to claim 32 or 33, wherein the cross-sectional area of ​​the distal end of the delivery probe is greater than the cross-sectional area of ​​the distal end of the fluid transfer tube.

35. The method further includes the step of inserting a guide tube into the tissue, The step of advancing the delivery probe includes the step of advancing the delivery probe through the guide tube, The fluid transfer tube track extends from the distal end of the guide tube, The method according to any one of claims 31 to 34, wherein the step of inserting the fluid transfer tube includes the step of inserting the fluid transfer tube through the guide tube.

36. The method according to any one of claims 31 to 35, comprising the steps of first delivering the injection fluid at a first flow rate and then delivering the injection fluid at a second flow rate, wherein the first flow rate is lower than the second flow rate.

37. The method according to claim 36, wherein the first flow rate is a maximum of 1 μl / min.

38. The method according to claim 36 or 37, wherein the second flow rate is between 3 μl / min and 7 μl / min, and optionally the second flow rate is 3 μl / min or 5 μl / min.

39. The method includes the step of continuously increasing the rate of delivery of the injection solution from the first flow rate to the second flow rate, wherein the rate of delivery is optionally up to 0.5 μL / min ２ It is increased by only that much, and further optionally, up to a maximum of 0.2 μL / min ２ The method according to any one of claims 36 to 38, wherein the amount is increased by only that amount.

40. The method according to any one of claims 31 to 39, wherein the tissue is animal tissue, optionally mammalian tissue, optionally human tissue.

41. The method according to any one of claims 31 to 40, wherein the tissue is brain tissue, and optionally brain parenchyma.

42. The method according to any one of claims 31 to 41, wherein the injected fluid is a therapeutic fluid.

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