Field of the invention

The present invention relates to a fluid drainage cannula and its method of manufacture, and in particular to a drainage cannula for use in extracorporeal membrane oxygenation (ECMO), and/or cardio-pulmonary bypass, and/or haemodialysis applications. of the invention

Any reference in this specification to prior publication (or information derived therefrom), or to any matter which is known, is not, and should not be taken as an acknowledgement or admission or any form of suggestion that the prior publication (or information derived therefrom) or known matter forms part of the common general knowledge in the field of endeavour to which this specification relates.

Conventional drainage cannulas are used in applications such as veno-arterial extracorporeal membrane oxygenation (ECMO), which is a form of mechanical circulatory and respiratory support, as well as in cardio-pulmonary bypass and haemodialysis. It is however a known issue that thrombosis is one of the most significant complications affecting ECMO patients (affecting up to 33% of ECMO patients), and adversely increasing morbidity and mortality rates particularly for patients who receive prolonged ECMO support with veno-arterial cannulation.

ECMO circuits are complex systems and thromboemboli may originate within the drainage cannula which may influence the formation of additional thromboemboli downstream in the pump and oxygenator. Probability of thrombosis occurring within the drainage cannula may be influenced by a variety of factors such as material and surface properties, the condition of the blood biochemistry, and the local flow conditions. Insertion of the cannula in the vein can affect the venous flow, which may lead to thrombosis by introducing stagnation zones (low shear) and recirculation zones. At very low shear, coagulation begins by allowing the proteins of the coagulation cascade to produce fibrin and consequently forming a red thrombus. On the other hand, high shear stresses can lead to thrombosis by activating platelets. It is therefore essential that the local flow conditions around and within the drainage cannula are understood and employed to optimise cannula design to reduce thrombosis. Conventional drainage cannulas often contain a single large tip end opening and multiple smaller side openings to reduce shear stress and maintain circulation in the event of venous collapse or hole occlusion by suction of the vessel wall. However, one major problem with conventional drainage cannula designs is the presence of pervasive stagnant flows at recirculation zones at the end opening and inlets of the side openings (this can be seen in dark blue areas denoted reference number 20 in the CFD diagram of Figure 2), which increases the risk of local coagulation or clotting of blood at or around the area of said stagnant flows. Also there appears to be limited knowledge in the field on the combined effect of various ECMO drainage cannula design parameters on flow dynamics which may lead to thrombus formation.

The applicant has determined that it would be advantageous to provide an improved drainage cannula that is suitable for use in extracorporeal membrane oxygenation, and/or cardiopulmonary bypass, and/or haemodialysis applications. The present invention seeks to at least in part alleviate the problems identified above or to provide the public with a useful choice.

Summary of the invention

According to an aspect of the present invention, there is provided a fluid drainage cannula, the cannula comprising an elongate tubular body having an annular wall which defines an internal lumen, the body extending between a distal end for insertion into a vessel of a subject and a proximal end for connection with an outlet hub; a tip portion of the body located at or about the distal end, the tip portion comprising a length of the body which includes one or more openings, to facilitate the flow of fluids between the vessel and the lumen, wherein the lumen is of non-uniform diameter along at least a portion of the length of the tip portion.

In one embodiment, the lumen is of varying diameter along the entire length of the tip portion.

In one embodiment, the lumen of the tip portion is configured such that the diameter of an intermediate segment of the tip portion is less than the diameter of one or both adjacent segment(s) located on either side of the intermediate segment. In one embodiment, the lumen of the tip portion is configured, in the longitudinal direction, with a generally parabolic sectional profile in which the smallest diameter of the lumen is located at or about an intermediate segment of the tip portion.

In one embodiment, the lumen terminates at a tip end of the tip portion and wherein the tip end comprises an opening having a diameter that is the same or smaller than the diameter of the intermediate segment of the tip portion.

In an alternative embodiment, the lumen terminates at a tip end of the tip portion and wherein the tip end comprises an opening having a diameter that is larger than the diameter of the intermediate segment of the tip portion.

In one embodiment, the wall at the tip portion of the body is configured to have a thickness that varies between about 0.2 mm and about 2 mm. In a further embodiment, the wall at the tip portion has a maximum thickness of about 1.2 mm.

In one embodiment, the tip portion comprises a plurality of side openings in the wall to facilitate the flow of fluids between the vessel and the lumen.

In one embodiment, the plurality of side openings is annularly spaced around the tip portion of the body.

In one embodiment, the plurality of side openings comprises rows of openings extending along a longitudinal length of the tip portion and/or arranged to be offset from adjacent like-rows of openings.

In one embodiment, the plurality of the side openings is configured with a diameter of between about 0.5 mm and about 5 mm, and more preferably between about 2 mm and about 3 mm.

In an alternative embodiment, the plurality of the side openings is configured with diameters varying between about 0.5 mm and about 5 mm, and more preferably between about 2 mm and about 3 mm. In one embodiment, the diameter of the plurality of the side openings varies according to the distance between each said side opening and the distal end.

In one embodiment, one or more of the plurality of side openings is configured with a diameter that varies along the wall of the body.

In one embodiment, a distance between each of the plurality of the side openings is between about 1 mm and about 40 mm, and more preferably about 3 mm.

In one embodiment, the plurality of side openings is configured to be angled from the wall towards the lumen generally in the direction of the proximal end, and preferably angled in a range of between about 15 degrees and about 90 degrees in the direction of the proximal end, and more preferably angled about 30 degrees in the direction of the proximal end.

In one embodiment, an inlet portion of one or more said plurality of side openings in the wall is configured with a curved sectional profile along a longitudinal direction of the wall.

In one embodiment, an outlet portion of one or more said plurality of side openings in the wall is configured with a curved sectional profile along a longitudinal direction of the wall.

In one embodiment, the fluid drainage cannula further comprises an additional elongate tubular body to facilitate flow of fluids therethrough, and wherein the elongate tubular body and the additional elongate tubular body are joined along their respective lengths.

In one embodiment, the additional elongate tubular body is not provided with side openings along its length and is configured with an internal lumen of uniform diameter.

In one embodiment, the fluid drainage cannula as described above is used in extracorporeal membrane oxygenation and/or cardio-pulmonary bypass applications with fluid flow rates ranged between about 0.5 and about 8 litres per minute, and more preferably between about 2 and 3 litres per minute.

In one embodiment, the fluid drainage cannula as described above is used in haemodialysis applications with fluid flow rates ranged between about 0.2 and about 0.4 litres per minute. According to another aspect of the present invention, there is provided a cannula tip when used with a fluid drainage cannula, which comprises an elongate tubular body having an annular wall which defines an internal lumen, the body extending between a distal end for insertion into a vessel of a subject and a proximal end for connection with an outlet hub, the cannula tip comprising: a tip portion of the body located at or about the distal end, the tip portion comprising a length of the body which includes one or more openings to facilitate the flow of fluids between the vessel and the lumen, wherein the lumen is of non-uniform diameter along a substantial length of the tip portion.

According to yet another aspect of the present invention, there is provided a method of enhancing flow dynamics of a drainage cannula when used in extracorporeal membrane oxygenation, and/or cardio-pulmonary bypass, and/or haemodialysis applications, the method comprises providing a fluid drainage cannula as described herein, connecting a proximal end of the cannula to an outlet hub and inserting a distal end of the cannula into a vessel of a subject.

According to a further aspect of the present invention, there is provided a method of manufacturing a cannula tip of a fluid drainage cannula as described herein, comprising the steps of: casting a volume representing desired fluid passageways of the tip portion, including the lumen (and optionally the side openings), into a solid mould; forming a substrate (such as a soft silicone or similar material) around the solid mould to create an outer mould of the tip portion; casting a volume representing fluid flow only in the lumen of the tip portion into a split solid mould; inserting the split solid mould into the outer mould to form a combined mould; and injecting and setting cannula forming material in the combined mould to form the tip portion of the cannula.

Further aspects of the present invention and further embodiments of the aspects described in the preceding paragraphs will become apparent from the following description.

While aspects of the drainage cannula will be described below for use in combination with each other in the preferred embodiments of the present invention, it is to be understood by a skilled person that some aspects of the present invention are equally suitable for use as standalone inventions that can be individually incorporated into cannulas not described herein. Throughout this specification and the claims which follow, unless the context requires otherwise, the word "comprise", and variations such as "comprises" and "comprising", will be understood to imply the inclusion of a stated integer or step or group of integers or steps but not the exclusion of any other integer or step or group of integers or steps.

The word “about” or “approximately” when used in relation to a stated reference point for a quality, level, value, number, frequency, percentage, dimension, location, size, amount, weight or length may be understood to indicate that the reference point is capable of variation, and that the term may encompass proximal qualities on either side of the reference point. In some embodiments, the word “about” may indicate that a reference point may vary by as much as 30 percent.

As used herein, the word "substantially" may be used merely to indicate an intention that the term it qualifies should not be read too literally and that the word could mean “sufficiently”, “mostly” or "near enough” for the patentee's purposes.

Brief description of the drawings

Further aspects of the present invention and further embodiments of the aspects described in the preceding paragraphs will become apparent from the following description. The invention will now be described, by way of example only, with reference to the accompanying drawings, in which:

Figure 1 is a schematic view of simplified geometry showing a conventional drainage cannula inserted into the Right Atrium via the Inferior Vena Cava;

Figure 2a shows a CFD analysis diagram relating to typical drainage fluid flow characteristics at a tip end of a conventional drainage cannula;

Figure 2b shows the related analysis chart corresponding to velocity at the tip end of the conventional drainage cannula;

Figures 3a-3b show a schematic sectional view of a drainage cannula tip portion in accordance with one embodiment of the present invention, along with a perspective view of the fluid flow inside the tip portion;

Figures 4a to 8c show cannula tip portion designs in accordance with various embodiments of the present invention, including schematic sectional views of drainage cannula tip portions, schematic sectional views of the fluid flow inside the tip portions, and corresponding CFD analysis diagrams of fluid flow inside the tip portion;

Figure 9 shows a CFD analysis diagram of the tip portion of Figure 8c when rotated approximately 90 degrees about a longitudinal axis;

Figures 10a- 10c show a cannula tip portion design in accordance with a further embodiment of the present invention, including schematic sectional views of drainage cannula tip portion, schematic sectional views of the fluid flow inside the tip portion, and CFD analysis diagram of fluid flow inside the tip portion;

Figure 11 is a schematic view of the shape and configuration of a solid mould for manufacturing the tip portion of the drainage cannula;

Figure 12 is a schematic view of a soft silicone outer mould formed around the solid mould;

Figure 13 is a schematic view of a split solid mould used with the outer mould for forming a tip portion of the drainage cannula according to an embodiment of the present invention;

Figure 14 is a schematic sectional view of a drainage cannula tip portion in accordance with another embodiment of the present invention;

Figure 15 is a schematic sectional view of a drainage cannula tip portion in accordance with a further embodiment of the present invention, showing a cannula with multiple elongate tube bodies and lumens; and

Figures 16A and 16B provide experimental data in the form of clot volume charts which show the difference in clot volume comparing the cannula of the present invention and a conventional cannula design.

Detailed description

Preferred embodiments of the present invention seek to provide an improved drainage cannula design that reduces the likelihood of stagnant flow formation at recirculation zones proximate the cannula’s side openings.

Figures 1 and 2 show the use of a conventional drainage cannula and their typical performance characteristics with respect to fluid flow dynamics inside the cannula. Figure 1 shows one end of a drainage cannula 10 being inserted into a patient such as the Right Atrium 5 via the Inferior Vena Cava 3 in simplified geometric representations of body vessels 1. The drainage cannula can be of any suitable length, with a proximal end 15 connected to an outlet hub (not shown) and a distal end 14, which is inserted into the vessels 1. A tip portion 12 of the cannula 10 is located at the distal end 14 and covers a length of the cannula 10 leading up to the end point of the cannula 10. The tip portion 12 is provided with an opening 17 at the end point, and often along with side openings 16, for draining fluid such as blood from the vessels 1 into the cannula 10, for example as part of a complex assisted circulatory system.

Figures 2a and 2b show a CFD analysis diagram and a corresponding flow velocity chart relating to typical drainage fluid flow characteristics at a tip portion 12 of a conventional drainage cannula. The colour blue in the CFD diagram indicates low fluid velocity while the green, orange and red represents increasing levels of fluid velocity. Conventional drainage cannulas show typical stagnant or relatively lower velocity flows (areas shown in blue) occurring at flow recirculation zones 20 inside the cannula near the side openings 16. It has been observed by the inventors that this stagnation is caused by flow separation at the edges of side openings 16 where sharp changes in the direction of flow occur. Changing the angle of entry of the side openings 16 could enhance flow dynamics inside the cannula by minimising flow disturbances around the side openings 16; however, this has been observed to shift stagnant flow zones to areas around the side openings 16 which increases the risk of thrombosis occurring in the side openings 16. Further, the velocity chart shows a significant tapering of fluid flow velocity at areas 22 around side openings 16 closer to the tip end of the cannula and at the centreline of the cannula tip. Higher fluid flow velocity tend to occur at areas 24 closer to the side opening 16 leading into the primary section of the cannula. These examples clearly illustrate the existence of significant fluid dynamics problems in conventional drainage cannulas and the need to address the issue of minimising stagnant flows in and around the cannula so as to reduce the likelihood of thrombosis occurring in a patient during use of the drainage cannula.

Embodiments of drainage cannula 10 designs in accordance with the present invention are shown in Figures 3 to 10, 14 and 15, in which partial sections of the cannula 10 corresponding to a length around the distal end 14 of the cannula 10 are shown for each embodiment. This length is referred to as the tip portion 12 of the cannula 10, which comprises an elongate tubular body 11 having an annular tube wall 18 within which an internal lumen 13 for fluid flow is defined. In the context of the invention, the lumen 13 is to be understood to refer to the internal cavity of the cannula structure having a sectional diameter. In the embodiments shown, the tip portion 12 and the internal lumen 13 of the body 11 terminates at the tip end, in which an opening 17 is provided for fluid flow, and a length of the body 11 having a plurality of side openings 16 provided to facilitate the fluid flow between the vessel 1 and the lumen 13 of the cannula 10.

With reference to Figures 3a and 3b, the tip portion 12 of the cannula 10 comprises an altered section of the cannula 10 within which the lumen 13 is of non-uniform or varying diameter. In particular, the lumen 13 at an intermediate/middle segment 44 of the section is gradually narrower or of less diameter than the diameter of the lumen 13 at adjacent segments of the section located on either side of the intermediate segment. This can be seen when comparing the diameter of the lumen 13 at regions 32, 31 immediately adjacent the intermediate segment of the lumen 13. It is to be appreciated that the intermediate/middle segment 44 of the present invention as described herein should not be strictly limited to an exact length-wise middle segment of the tip portion 12 of the cannula body 11. In some embodiments, the intermediate/middle segment 44 is an area that comprises a section of the lumen 13 of the smallest internal diameter in the tip portion 12 of the cannula body 11. This results in a graduated narrowed passage for fluid flow around the intermediate segment of this section of the lumen 13 and broader passageway for fluid flow at adjacent segments of the lumen 13. In other words, an inner surface of the lumen 13 at the section of the tip portion 12 is said to have a generally parabolic sectional profile 34, in the longitudinal direction (when viewing the cannula on its side as seen in the Figure). In the preferred embodiment, the altered section of the cannula 10, within which the lumen 13 is of varying diameter or where the inner surface of the lumen 13 has a parabolic profile 34, covers the length of cannula body 11 in which the plurality of side openings 16 are provided. It is to be appreciated that the present invention is not limited to embodiments in which the altered section must cover all side openings 16. In some embodiments, the opening 17 of the tip end is configured with a diameter that is larger than the diameter of the intermediate segment 44 of the tip portion 12. In other embodiments, the opening 17 of the tip end is configured with a diameter that is the same or smaller than the diameter of the intermediate segment 44 of the tip portion 12.

It has been found that the variation in the internal diameter of the lumen 13 as described above advantageously suppresses the boundary layer growth between the side openings 16 and the lumen 13, and reduces the occurrence of recirculation zones 20 for fluid flowing around the side openings 16 and the mainstream fluid passageway of the cannula through this section of the lumen 13. A perspective view of the fluid flow 40 through the tip portion 12 of the cannula 10 as configured is shown in Figure 3b, which clearly shows the shape of the fluid flow body in which an intermediate segment 44 of the flow body forms a gradually narrowing passageway connecting to broader passageways 41, 42 before and after the intermediate segment 44. Side flow volumes 46 passing through the side openings 16 are also illustrated in the perspective view.

The diameter of the lumen 13 may be altered in a number of ways. In one example, the diameter of the lumen 13 in an altered section of the tip portion 12 may be altered by varying the thickness of the annular tube wall 18. Figures 4a to 8c show embodiments of the present invention in which the maximum thickness of the tube wall 18 of the tip portion 12 varies between about 0.9 mm and about 1.5 mm. The embodiment of cannula design as shown in Figure 4a has a maximum tube wall 18 thickness of about 0.9 mm in the altered section of the tip portion 12, the cannula design shown in Figure 5a has a maximum tube wall 18 thickness of about 1.2 mm in the same section, and the cannula design shown in Figure 6a has a maximum tube wall 18 thickness of about 1.5 mm in the same section. In the examples provided, the cannula tube wall 18 has a standard thickness of about 0.5 mm. It is to be appreciated that these dimensional values are non-limiting and other tube wall 18 thickness parameters may be equally suitable for creating an effective parabolic sectional profile, including wall thicknesses that range between about 0.2 mm and about 2 mm. The exemplary embodiments provided in the Figures show a gradual change (slope) of tube wall 18 thickness across the altered section of the tip portion 12; however, it is to be appreciated that the magnitude in which the tube wall 18 thickness change across the section is not limited to the ones shown in the examples as other variations in the magnitude of the tube wall 18 thickness change (slope) may also be suitable without departing from the spirit of the invention.

For embodiments illustrated in each of Figures 4a to 6c, the effect of the altered section of the lumen 13 in the tip portion 12 on the fluid flow dynamics of the cannula 10 is shown in the form of velocity contours in the longitudinal plane in the corresponding CFD analysis diagrams. The embodiments shown in Figures 4a to 6c have increasingly greater parabolic sectional profiles (or correspondingly thicker maximum tube wall 18 thickness) in the altered section of the lumen 13. It can be seen that the formations of recirculation zones 20, 24 and stagnant flows 22 in all three embodiments shown have reduced over conventional drainage cannula designs with non-altered (e.g. parallel) lumen 13 profiles. In particular, the example shown in Figure 5a, which has an altered lumen 13 section with a maximum thickness of 1.2 mm (or an added thickness of 0.7 mm to the normal tube wall thickness) resulted in comparatively more uniform flow, and substantially shifted the recirculation zones 20 to the side openings 16, while introducing only a modest decrease in the diameter of the lumen 13 in the altered section of the tip portion 12. It can also be seen that the narrowed passageway of the lumen 13 in the altered section also appears to increase the overall flow rate of fluids in the lumen 13 of the embodiments shown in Figure 4a to 6c, including fluid flows at the tip end opening 17 as well as for the main flow stream 26.

Figures 7a to 7c show an embodiment of the drainage cannula having the additional feature in which sections 36, 37 of the lumen 13 leading into, and out of, the altered section described above of the lumen 13 with the parabolic sectional profile 34 (or of varying diameter) have been configured so that the sections 36, 37 form part of the same parabolic sectional profile 34. In other words, the parabolic sectional profile 34 of the lumen 13 extends right through to the tip end opening 17 in a smooth curvature 43 so as to allow more gradual changes in the tube wall 18 thickness of the lumen 13 and over a longer length of fluid flow in said altered section of the lumen 13. This feature advantageously reduces abrupt shape changes of fluid flow within the lumen 13, resulting in thinner boundary layers at the sides of the parabolic profile 34 of the lumen 13, and therefore further enhancing the flow dynamics of fluids in the tip portion 12 of the cannula 10.

It is to be appreciated that while a generally parabolic sectional profile 34 has been described in relation to the altered section of the lumen 13 in the drainage cannula 10 embodiments described in this specification, the invention is not limited to the parabolic configurations or a specific parabolic shape. The variation of a segment of the lumen 13 for fluid flow to achieve reduced stagnation of fluids and/or recirculation zones may also be achieved by varying the tube wall 18 thickness of the cannula body 11 or by altering the diameter of the lumen 13 so as to result in non-parabolic sectional profiles. In the examples provided, the narrowest section of the lumen 13 has been configured to be substantially at the intermediate/middle segment of the tip portion 12; however, it may be equally suitable for the narrowest section of the lumen 13 to not be substantially located at the intermediate/middle segment of the lumen 13. Dimensional values provided in the embodiments are for reference only and are not limiting on the scope of the invention. Moreover, the portion of lumen 13 of varying dimeter may in some embodiments span the entire length of the tip portion 12 of the cannula 10. In some embodiments, the tip portion 12 of the cannula 10 further comprises a plurality of side openings 16 in the tube wall 18 to facilitate the flow of fluid between the body vessel 1 and the lumen 13. The plurality of side openings 16 may be provided in a number of non-limiting configurations. Referring to Figures 3a to 7c, the plurality of side openings 16 may be annularly spaced around the tip portion 12 of the cannula 10, and may comprise rows of openings 16 extending along the longitudinal length of the tip portion 12 and/or may be arranged to be offset from adjacent like -rows of openings 16. In some configurations, the rows of side openings 16 are spaced 90 degrees apart.

The plurality of side openings 16 of the tip portion 12 can be configured with any number of suitable numbers and sizes. In one example, the plurality of side openings 16 are configured with the same diameter in the tube wall 18, and the diameter of the openings 16 may be chosen between about 0.5 mm and about 5 mm, and more preferably between about 2 mm and 3 mm. In another example, the plurality of side openings 16 on the cannula 10 may have different diameters that vary between about 0.5 mm and about 5 mm, and more preferably between about 2 mm and 3 mm. In another embodiment, the diameter of the plurality of the side openings 16 may vary according to the distance between each said side opening 16 and the distal end 14 of the cannula 10. For example, the diameter of side openings 16 in this embodiment may increase or reduce in size, relative to each other, depending on how close each side opening 16 is to the tip end of the cannula 10.

By way of a non-limiting example, the distance between each of the adjacent side openings 16 may range between about 1 mm and 40 mm along the longitudinal length of the cannula 10, and more preferably about 3 mm. In yet another embodiment, the diameter of the side opening may vary along the tube wall 18 of the cannula 10. For example, the diameter of the cavity of the opening 16 may be smaller or larger at one end of the tube wall 18 (closer to the outer surface of the cannula 10) than at an opposing end of the tube wall 18 (closer to the inner surface of the cannula).

It has been found that variations in the side openings 16 as described above may influence fluid flow dynamics inside the tip portion 12 of the lumen 13. Furthermore, the angle in which the side openings 16 are configured in the tube wall 18 relative to the lumen 13 may also influence the fluid flow dynamics inside the lumen 13. In the preferred embodiment, the plurality of side openings 16 is configured to be angled towards the lumen 13, from an outer surface of the tube wall 18, generally in the direction of the proximal end 15. More preferable, as seen in the Figures illustrating preferred embodiments, the side openings 16 are angled about 30 degrees from the tube wall 18 towards the lumen 13 in the direction of the proximal end 15. In some embodiments, the side openings 16 are angled in a range of between about 15 degrees and about 90 degrees towards the lumen 13 in the direction of the proximal end 15, though it is to be appreciated that other angle variations not specifically described herein may also be suitable for use with the cannula lumen 13 as described in the specification to improve fluid flow dynamics inside the lumen 13.

Referring to Figures 8a to 8c, there is provided an exemplary embodiment having a continuous section of lumen 13 of parabolic sectional profile through to the tip end opening 17. In addition, an inlet 38 and/or outlet 39 portion of one or more of the plurality of side openings 16 in this embodiment are provided with curved configurations which results in curved sectional profiles 48, 49 along the longitudinal direction of the tube wall 18. The curved sectional profiles advantageously reduce pressure drop of fluid flow moving into and out of the side openings 16 by reducing sharp corners or abrupt changes in the direction of fluid flow within the tip portion 12 of the cannula 10. This feature further enhances fluid flow dynamics in the cannula 10 and assists with reducing stagnant flows 22 and recirculation zones 20 in the lumen 13. Figure 9 is a view of the tip portion 12 of Figure 8c when rotated approximately 90 degrees about the longitudinal axis of the tip portion 12 to show an offset row of side openings 16. A variation of this embodiment with arrows showing the primary directions of fluid flow from the patient (distal end 14) to the machine (proximal end 15) is also shown in Figure 14.

Figures 10a to 10c illustrate the profiles of a further embodiment of the present invention wherein a partial section of the lumen 13 is provided with a reduced diameter or a parabolic sectional profile. More specifically, the internal surface of the lumen 13 is provided with an initial curvature (for example, a parabolic curve) to reduce the inner diameter around an intermediate section of the cannula before substantially straightening out to result in a small opening 17 (or inner diameter end) with the same or greater wall thickness towards the tip end section 36. In some embodiments, the straightening out of the inner surface of the lumen 13 can be flat (substantially uniform diameter) or of a gradual sloping contour. This embodiment advantageously retains a significant portion of the technical merits of the earlier described embodiments while allowing further improvements in manufacturability of the cannula using, for example, a dip moulding process, where a shaped mandrel is dipped into a suitable material and allowed to cure. This process can be repeated until a desired thickness of the wall 18 is achieved. In this manufacturing process, side opening 16 can be added after formation of the cannula tip portion 12 through conventional punching mechanisms.

It is to be noted that the drainage cannula 10 as described has been configured so that it is particularly effective for use in applications involving high fluid flow rates. Suitable applications including, but not limited to, extracorporeal membrane oxygenation and/or cardiopulmonary bypass applications, and for fluid flow rates ranged between about 0.5 and about 8 litres per minute, and more preferably between about 2 and 3 litres per minute. For haemodialysis applications, the preferable fluid flow rates range between about 0.2 and about 0.4 litres per minute.

In another configuration, the present invention may be incorporated in the form of a dual or multi-lumen cannula. One example of which is shown in Figure 15. Figure 15 illustrates a hybrid cannula having a tubular cannula body 11A with a lumen 13 of non-uniform diameter as described above, and this tubular body 11A is joined with an additional elongate tubular body 11B along their respective lengths, thereby forming a dual-lumen catheter, wherein one lumen is dedicated to blood withdrawal or drainage, and the other lumen is dedicated to blood return or infusion (as indicated by the arrows showing direction of fluid flow). In such embodiments, the drainage lumen would benefit from the improvements described herein using the cannula body 11A having a non-uniform diameter lumen 13A, whilst the infusion lumen performs acceptably using a conventionally designed cannula body 11B with a uniform diameter lumen 13B. It is noted that in the example shown, side openings are not provided in the additional tubular body 1 IB; however, it is to be understood that this example is not to be limiting and that side openings can be provided in some configurations.

It is also to be understood that in multi-lumen embodiments, the cannula walls 18 of each respective tubular body 11A, 11B separate the respective lumens 13A, 13B, thereby minimising any impact on fluid movement within the lumens 13 A, 13B of each tubular body 11A, 11B.

In-silico and ex- vivo research investigations have been conducted in respect of the cannula designs described herein. Referring to Figures 16A and 16B, which are clot volume charts from experimental data which show the difference in clot volume comparing the cannula of the present invention and a conventional cannula design. It has been found that the cannula design as described provides advantages over conventional designs including high flow velocity at the tip portion of the cannula around the cannula openings, resulting in fewer clotting formations during use and lower clotting volume.

The cannula tip portion 12 of the drainage cannula 10 all as described above (including the altered flow section of lumen 13, tip end opening 17 and side openings 16) may be formed separately and connected to a length of conventional cannula of any suitable length. Alternatively, the cannula tip portion 12 may be integrally formed with any suitable length of cannula body 11 for connection at the proximal end 15 with an outlet hub or device. In use, the proximal end 15 of the drainage cannula 10 is connected to an outlet hub as part of a medical application, and the distal end 14 of the drainage cannula 10, at which the tip portion 12 of the cannula body 11 is located, is inserted into a body vessel of a patient or subject.

The unique lumen 13 section of the cannula 10 can be manufactured in a number of suitable ways. One method to manufacture a lumen 13 section in the tip portion 12 of cannula 10 with varying diameters as described above is a three-part moulding process involving customised manufacturing technique. With reference to Figures 11 to 13, a solid mould 50 (made from a metallic material) is first created by casting a volume representing desired fluid passageways of the tip portion 12, including the lumen 13 (and optionally excluding the side openings 16). In the second step, a substrate such as a soft silicone (or suitable soft material) is formed around the solid mould 50 (as it is placed concentrically in a housing) to create an outer mould 52 of the tip portion 12. The outer mould 52 includes the shape and configuration of the side openings 16, and the use of a soft material such as silicone allows the easy removal of the solid mould 50 without causing damage to the soft outer mould 52. Next, a volume representing fluid flow only in the lumen 13 of the tip portion 12 is cast into a two-piece split solid mould so that the mould can be easily extracted in a subsequent forming step. Each of the solid moulds are machined with a smooth finish. Once the moulds 50, 52, 54 are created, the tip portion 12 of the cannula 10 can be manufactured by inserting the split solid mould 54 into the outer mould 52 to form a combined mould 56, and then injecting and cannula forming material (such as polyurethane) in the combined mould 56 to form the tip portion 12 of the cannula 10. The formed tip portion 12 of the cannula 10 can then be removed from the combined mould 56 once the forming material has been allowed to set. It will be understood that the invention disclosed and defined in this specification extends to all alternative combinations of two or more of the individual features mentioned or evident from the text or drawings. All of these different combinations constitute various alternative aspects of the invention.

In the description and drawings of this embodiment, same reference numerals are used as have been used in respect of the first embodiment, to denote and refer to corresponding features. While various embodiments of the present invention have been described above, it should be understood that they have been presented by way of example only, and not by way of limitation. It will be apparent to a person skilled in the relevant art that various changes in form and detail can be made therein without departing from the spirit and scope of the invention. Thus, the present invention should not be limited by any of the above described exemplary embodiments.