WO2010149168A1

WO2010149168A1 - Expandable diffuser

Info

Publication number: WO2010149168A1
Application number: PCT/DK2010/050158
Authority: WO
Inventors: Morten Ølgaard JENSEN; Simon Ørts GADGAARD; Andreas Baun HØST; Nikolai Dettling Madsen; Mogens Rasmussen
Original assignee: Ingeniørhøjskolen I Århus
Priority date: 2009-06-25
Filing date: 2010-06-23
Publication date: 2010-12-29

Abstract

The invention relates to diffuser adapted for converting kinetic energy of a flowing fluid into pressure energy to reduce the flow velocity of said fluid. The diffuser comprises a diffuser body comprising a proximal end, a distal end. The diffuser also comprises a frame fabricated in a first frame material that is capable of changing from a pre-stimulus state to a post-stimulus state in response to a stimulus, whereby the diffuser changes from a first geometry to a second geometry.

Description

Expandable diffuser

This invention relates to a diffuser for reducing the flow velocity of a fluid passing through a confinement, such as a tubular structure, and the use of such a diffuser as part of e.g. a cannula, and the use of such a cannula.

When a fluid is forced through a narrow lumen, the resulting high flow rates produce jet stream flow, high local velocities, turbulence, cavitation and a significant pressure drop over the flow direction in the lumen.

In several medical procedures, large volumes of fluid, such as a patient's blood, are pumped into the patient's cardiovascular system over a relative short period of time. This is the case in e.g. open heart surgery, where a lung machine provides the flow of blood through the patient, or in relation to a dialysis treatment, where a large volume of the patient's blood is circulated outside the body through an external filter to remove wastes and water, before entering the patient's cardiovascular system again. In such applications, cannulas having a relatively narrow lumen are often used to connect the cardiovascular system to the appropriate equipment.

When entering the cardiovascular system, a high blood flow velocity may due to the abovementioned effects cause haemolysis, activation and destruction of thrombocytes, and thromboembolic complications in general.

One example of a cannula is the aortic cannula used as the interface between the physiological blood circuit of a patient and the mechanical blood circuit in a lung machine. The jet from the aortic cannula may damage the interior aortic wall or dislodge atheromatous plaques and atheroemboli and cause arterial dissections, disturb flow into nearby vessels and is claimed to be a major cause of perioperative stroke

In order to reduce the duration of a dialysis treatment, a large flow velocity is often used, which can be felt by the patient, and the procedure presents in addition to the abovementioned problems a significant discomfort and stress to the patient. The negative effects of being connected to a machine for circulating a fluid into a patient^'s cardiovascular system, such as the lung machine and the dialysis equipment mentioned above, can be mitigated by increasing the exit diameter of the cannula used in relation to these systems. This can be realized by positioning a diffuser at the distal end of the cannula.

A diffuser converts kinetic energy to pressure energy. When a fluid passes through the diffuser from a distal end having a relatively smaller area to a distal end having a relatively larger area, the velocity of the fluid decreases and the pressure energy increases, i.e. the pressure gradient and the energy loss declines. For a cannula, such as an aortic cannula or a cannula for dialysis treatment, this is a very desirable conversion since the problems relating to the high flow velocity and turbulence are reduced accordingly. A diffuser may be a pipe section, where the cross-sectional area increases in the flow direction, resulting in a decrease in the flow velocity.

EP 1 453 566 B1 describes an aorta cannula, wherein the distal end is capable of taking different forms. During insertion, the cannula is folded to take the smallest outer diameter. When inserted and having blood flowing through the cannula, the end part positioned inside the blood vessel changes shape to taper expanding towards the distal end. The change of shape is determined by the balance between the pressures provided by the flow of blood through the cannula and the flow in the aorta of blood, which have not passed through the cannula. The end part of the cannula becomes deformable at operating temperature.

US 2008/0114339 describes a blood pump having a cannula with an expandable portion composed by a nitinol skeleton with the diameter at both ends of the expandable portion being fixed

US 2003/0120223 describes a cannula wherein a middle portion has a circumference which is smaller than the circumference of the distal and proximal ends of the cannula.

WO 2009/142904 describes a catheter assembly having a conical diffuser tip in order to reduce the recoil force of the catheter. A diffuser tip of a dehydrated polymer changes from one shape to a conical shape when reacting with water.

The inventors of the present application have realized that a diffuser with a fixed diameter at the distal end is not the optimal solution since this will enhance the size of the tissue region that is stressed by the perfusion, and that an expandable diffuser is preferred over a diffuser with a fixed geometry.

Accordingly, one objective of the present invention is provided by a diffuser adapted for converting kinetic energy of a flowing fluid into pressure energy to reduce the flow velocity of said fluid, said diffuser comprising a diffuser body comprising a proximal end, a distal end, and a lumen extending along a longitudinal axis between said proximal and distal ends. The diffuser body comprises a frame extending longitudinally at least along a part of said diffuser body, said frame comprising at least a first frame material. The frame is capable of changing from a pre-stimulus frame configuration to a post- stimulus frame configuration when said first frame material changes from a pre-stimulus state to a post-stimulus state in response a stimulus. The change from said pre-stimulus frame configuration to said post-stimulus frame configuration being such that said diffuser changes from a first geometry to a second geometry, where in said first geometry, the lumen circumference at said proximal end defines an area Ai,_p and the lumen circumference at said distal end defines an area Ai,_d, and where in said second geometry, the lumen circumference at said proximal end defines an area A₂,_p and the lumen circumference at said distal end defines an area A₂,d,

The frame may be substantially rigid in said post-stimulus frame configuration.

One object of the present invention is to provide a cannula capable of being inserted into a patient under treatment at a point of insertion, said cannula comprising a cannula main portion and the diffuser as described herein, where the proximal end of the diffuser is arranged in relation to a distal end of the cannula main portion.

One object of the invention is to provide a method for pumping blood into the cardiovascular system of a patient, comprising arranging a cannula as described herein in relation to said cardiovascular system so that at least said distal end of said diffuser is positioned inside a blood vessel, such as a vein or an artery, such as the aortic artery. The diffuser is then allowed to respond to a stimulus so that said diffuser takes the shape according to said second geometry and blood is pumped into said cardiovascular system. The diffuser may be mechanically confined during the perfusion into said vessel, and then be released from said confinement when the cannula is positioned correctly in relation to said vessel. The method may further comprise exposing said diffuser to a stimulus provided by an external source, such as an external heat source and/or electrical current and/or electrical voltage source.

A cannula capable of providing a reduction in the flow velocity of a fluid may be used in relation to a large variety of medical treatments where a fluid must be introduced/reintroduced into a patients body, such as in respect to open heart surgery, where the blood it ventilated by a extra-corporal lung machine. Especially in pediatric surgery, a reduction of the flow velocity of blood being reintroduced into the vascular system can enhance the chance of a positive outcome of the operation.

A cannula comprising the diffuser according the present invention also provides in improvement over prior art cannulas when applied e.g. in systems for rapid blood transfusions.

The diffuser and the cannula according to the present invention may be used in relation to medical applications where body fluids, such as blood are to be introduced into the body of a patient. The patient may be human or animal.

In the context of the present application, the phrase substantially rigid refers to the case where the diffuser remains substantially unaffected by a flow of a fluid through the diffuser and/or a flow of a fluid around the diffuser. There is hence only a small change in the circumference at the distal end of the diffuser and/or in the circumference along the diffuser in response to these flows when the frame is in the post-stimulus configuration.

The rigidity of the frame in said post-stimulus configuration may result in a resistance towards an increase and/or decrease in the diffuser circumference in response to a difference between an internal pressure from a fluid flowing through the diffuser and an external pressure from a fluid flowing outside the diffuser

The rigidity of the frame in said post-stimulus configuration may be such that the radial stress applied by a largest difference between the internal pressure and the external pressure at some point along the longitudinal axis of the diffuser leads to a relative change in the diffuser circumference anywhere along the longitudinal axis which is less than 30%, such as less than 25%, such as less than 20%, such as less than 15%, such as less than 10%, such as less than 5%, such as less than 2%, such as less than 1 %, when the pressure difference is less than about 500 mmHg, such as less than about 300 mmHg, such as less than about 200 mmHg, such as less than about 150 mmHg, such as less than about 100 mmHg, such as less than about 50 mmHg.

The rigidity of the frame in said post-stimulus configuration may result in a resistance towards an increase of the diffuser circumference in response to the maximum internal pressure at a position along the diffuser being higher than the external pressure, i.e. there is an internal overpressure at least along a part of the longitudinal axis of the diffuser.

The rigidity of the frame in said post-stimulus configuration may result in a resistance towards a decrease of the diffuser circumference in response to a pressure difference caused by the external pressure being higher than the internal pressure, i.e. there is an external overpressure at least along a part of the longitudinal axis of the diffuser.

The resistance towards an increase or decrease of the diffuser circumference in the second geometry may be such that a relative change in the diffuser circumference anywhere along the longitudinal axis is less than 30%, such as less than 25%, such as less than 20%, such as less than 15%, such as less than 10%, such as less than 5%, such as less than 2%, such as less than 1 %, when the pressure difference is less than about 500 mmHg, such as less than about 300 mmHg, such as less than about 200 mmHg, such as less than about 150 mnnHg, such as less than about 100 mmHg, such as less than about 50 mnnHg.

The change in the diffuser circumference may be measured relative to the circumference of the diffuser when the internal and external pressures applied to the diffuser are substantially cancelling each other.

The internal pressure may be larger than the external pressure along a part of the diffuser's length, i.e. its dimension along the longitudinal axis of the diffuser, or along the entire length.

The internal pressure may be smaller than the external pressure along a part of the diffuser's length, i.e. its dimension along the longitudinal axis of the diffuser, or along the entire length.

In one embodiment, the circumference of the lumen is defined by an inner surface of the diffuser.

In one embodiment, the first and/or second geometry is such that the proximal end of the diffuser is substantially arranged in a plane perpendicular to said longitudinal axis. The lumen circumference at the proximal end may be such that its tangent lines at a major part of the circumference are substantially perpendicular to the longitudinal axis of the diffuser. The circumference of the lumen at the proximal end may define a substantially circular shape in the plane perpendicular to said longitudinal axis.

The diffuser may comprise a longitudinal asymmetric design, wherein the diffuser at least in the second geometry comprises a section extending further along the longitudinal axis than another section. Such a design may be adapted to change the velocity profile of a fluid entering the proximal end of the diffuser, such as to reduce the asymmetry of the velocity profile in a plane at the distal end relative to the asymmetry of the velocity profile of the fluid in a parallel plane at the distal end. Both planes may be perpendicular to the longitudinal axis. In a diffuser comprising a longitudinal asymmetric design, the lumen circumference at the distal end of the first geometry and/or of the second geometry may be such that its tangential lines along a portion of the lumen circumference are non-perpendicular to the longitudinal axis of the diffuser, i.e. the tangent lines of a portion of the lumen circumference have angles relative to the longitudinal axis that are below about 90°. The smallest angle, α_mιn, between the longitudinal axis and a tangent line of the lumen circumference at the distal end may be below about 89°, such as below about 87°, such as below about 85°, such as below about 80°, such as below about 75°, such as below about 70°, such as below about 65°, such as below about 60°, such as below about 55°, such as below about 45°, such as below about 35°, such as below about 30°. α_mιn may be above about 10°, such as above about 15°, such as above about 20°, such as above about 25°.

The geometry of the diffuser may be described using cylindrical coordinates, wherein a point in space is described by the radial distance (distance of point from the longitudinal axis), the angular coordinate and the longitudinal position of the point.

Unless it is arranged parallel to a tangent line of the diffuser, a longitudinal section of the diffuser will comprise a first and a second portion of the diffuser.

The length or lengths of the first and second portions of the longitudinal section of the diffuser may be defined as the length or lengths of the first and second portions along the longitudinal axis, i.e. the lengths of the projection of the particular portion onto the longitudinal axis.

In one embodiment, the first and the second portions have substantially identical lengths in any longitudinal section of the diffuser.

In one embodiment, the length of the first portion differs from the length of the second portion at least in one longitudinal section of the diffuser. In one embodiment, the length of the first portion is larger than the length of the second portion. The first portion may be the longest portion of the diffuser having the maximum length and the second portion may be the shortest portion of the diffuser having the minimum length. The ratio between the length of the first portion and the length of the second portion may be in the range of about 1.02 to about 5, such as in the range of about 1.05 to about 3, such as in the range of about 1.10 to about 2, such as in the range of about 1.15 to about 1.8, such as in the range of about 1.20 to about 1.6.

The first portion having the longest length and the second portion having the shortest length may be portions that terminate at parts of the distal end lumen circumference where the tangent line of the lumen circumference is perpendicular to the longitudinal axis. Between a first portion having the longest length and a second portion having the shortest length of the diffuser, the tangent line is non-perpendicular to the longitudinal axis, and the length of the portions arranged in between changes between the longest and shortest length.

The length of portions of the diffuser may be measured relative to a plane at the proximal end, where this plane may be arranged perpendicular to the longitudinal axis of the diffuser, i.e. the length of the diffuser at one angular coordinate may be measured from said plane to the circumference at the distal end of the diffuser.

The lateral surface length of the diffuser may also be used to describe the longitudinal dimensions of the diffuser. When described using cylindrical coordinates, the lateral surface length at a given angular coordinate may be the length of the lateral surface of the diffuser along a straight line extending at a constant angular coordinate from the apex of the diffuser through the circumference of the distal end of the diffuser. The straight line may be substantially parallel to the lateral surface of the diffuser. The lateral surface of a solid is the face or surface of the solid on its sides. That is, any face or surface that is not a base. The lateral surface is the surface of the diffuser arranged between the proximal and distal ends.

In the context of the present invention, the phrase apex of the diffuser refers to the apex of a structure comprising the shape of the diffuser, such that the shape of the diffuser may be described by the structure having the apex sliced off. In a diffuser having the shape of a conical frustum, the apex of the diffuser is the apex of the original cone from which the conical frustum was defined by slicing off the apex.

In one embodiment, the lateral surface length is substantially the same for all angular coordinates in the first and/or second geometry, and the diffuser may comprise a longitudinal symmetric design.

The lateral surface length of the diffuser at a given angular coordinate may be measured relative to a plane at the proximal end, where this plane may be arranged perpendicular to the longitudinal axis of the diffuser, i.e. the lateral surface length of the diffuser at one angular coordinate may be measured from said plane to the circumference at the distal end of the diffuser.

In one embodiment, the lateral surface length has a minimum value at a first angular coordinate and a maximum value at a second angular coordinate. The ratio between the maximum and minimum lateral surface length and the minimum lateral surface length may be in the range of about 1.02 to about 5, such as in the range of about 1.05 to about 3, such as in the range of about 1.10 to about 2, such as in the range of about 1.15 to about 1.8, such as in the range of about 1.20 to about 1.6.

The maximum and minimum lateral surface lengths may be found along the straight lines, where the tangent line of the lumen circumference of the distal end is perpendicular to the longitudinal axis. In-between the straight lines corresponding to the maximum and minimum lateral surface lengths, the tangent line is non-perpendicular to the longitudinal axis, and the lateral surface length along the straight lines arranged in between changes between the maximum and minimum lateral surface lengths.

In one embodiment, the areas Ai,_p and A₂,_p are determined from the area enclosed by the lumen circumference in a plane arranged perpendicular to the longitudinal axis at the proximal end of the diffuser. Said plane may be arranged at the outermost position of the longitudinal axis at which the circumference still encloses the longitudinal axis. In one embodiment, the areas Ai,_p and A₂,_p are substantially identical, such as when both are determined from a cannula main body in relation to which the proximal end is arranged.

If a part of or if the entire lumen circumference at the proximal end is arranged with an angle to the longitudinal axis, the areas Ai,_p and A₂,_p may be determined from the circumference of the diffuser in a plane perpendicular to the longitudinal axis, said plane being arranged at the proximal end.

If a part of or if the entire lumen circumference at the distal end is arranged with an angle to the longitudinal axis, the areas Ai,_d and A₂,d may be determined from the circumference of the diffuser in a plane perpendicular to the longitudinal axis, said plane being arranged at the distal end.

In the context of the present invention, the phrase "on the other side of the diffuser" refers to e.g. two points that are arranged with a angular coordinate between each other of more than about 90°, such as more than about 105°, such as more than about 120°, such as more than about 135°, such as more than about 150°, such as substantially 180°. The points may be arranged at different radial and/or longitudinal positions.

In one embodiment, the first geometry is such that the distal end of the diffuser is substantially arranged in a plane perpendicular to said longitudinal axis

The circumference of the distal end of the diffuser in its second geometry may surround a distal base of the diffuser. The circumference of the proximal end of the diffuser in its second geometry may surround a proximal base of the diffuser. The proximal and distal bases being the openings in the diffuser at the proximal and distal ends, respectively.

The distal base may be substantially planar and be arranged substantially perpendicular to the longitudinal axis of the diffuser.

In one embodiment, the distal base is substantially planar and arranged at an angle, θdb, relative to the longitudinal axis of the diffuser. θdb may be below about 89°, such as below about 87°, such as below about 85°, such as below about 80°, such as below about 75°, such as below about 70°, such as below about 65°, such as below about 60°, such as below about 55°, such as below about 45°, such as below about 35°, such as below about 30°. θdb may be above about 10°, such as above about 15°, such as above about 20°, such as above about 25°.

The distal base may also comprise two or more regions that are arranged at an angle relative to each other. In one embodiment, the distal base is a curved surface.

In one embodiment, the second geometry is such that the distal end of the diffuser is substantially arranged in a plane perpendicular to said longitudinal axis and the distal base of said second geometry may be substantially located in said plane. The circumference of the lumen at the distal end may define a substantially circular shape in this plane, i.e. the distal base may be substantially circular.

The areas Ai,_d and A₂,d may be determined from the areas enclosed by the lumen circumference in a plane arranged perpendicular to the longitudinal axis at the distal end of the diffuser. If a part of or the entire lumen circumference at the distal end is non-perpendicular to the longitudinal axis, the areas Ai,_p and A₂,_p may be determined from the circumference of the diffuser in a plane perpendicular to the longitudinal axis. Said plane may be arranged at the outermost position of the longitudinal axis at which the circumference in said plane still encloses the longitudinal axis

In one embodiment, the first and/or second geometry of the diffuser is such that the distal end of the diffuser is substantially arranged in a plane arranged with an angle, θd, relative to the longitudinal axis of the diffuser, where θd may be below about 89°, such as below about 87°, such as below about 85°, such as below about 80°, such as below about 75°, such as below about 70°, such as below about 65°, such as below about 60°, such as below about 55°, such as below about 45°, such as below about 35°, such as below about 30°. θ_d may be above about 2°, such as above about 5°, such as above about 10°, such as above about 15°, such as above about 20°, such as above about 25°. The circumference of the lumen at the distal end arranged in said plane may define a substantially elliptical shape in this plane.

The diffuser may be part of a tube structure or be connected to a tube structure comprising a proximal tube end and a distal tube end in such a way that the proximal end of the diffuser is brought into direct or indirect contact with a distal tube end. The tube structure may comprise sections that are substantially straight along the longitudinal axis of that section, and sections that have a bend. When the diffuser is part of a cannula it may be connected to the tube structure of the cannula main portion in such a way that the proximal end of the diffuser is brought into direct or indirect contact with the distal end of the cannula main portion.

In one embodiment, the cannula main portion comprises a bend and a diffuser with a longitudinal asymmetric design, where the diffuser is arranged with the maximum lateral surface length along the outside of the bend.

When a fluid flows through straight or bended sections of a tube structure, not all fluid particles travel along the tube structure at the same flow velocity. The velocity profile describes the cross sectional variation in the flow velocity of the fluid particles. For substantially straight tube structure, the shape of the velocity profile across any given cross section of the tube structure depends upon whether the flow is laminar or turbulent. If the flow in a tube structure is laminar, the distribution of the velocity along the longitudinal axis at a given cross section will have its maximum velocity at the center of the tube. This may in particular be the case for tube structures that in cross section are substantially centro-symmetric.

When connected to the distal end of a tube structure, the axial configuration of the tube structure may determine the velocity profile of the fluid entering the proximal end of the diffuser. In the context of the present application the phrase "axial configuration of a tube structure" refers to the shape of the lateral surface of the tube structure from one end to another and any changes in the direction of the lateral surface caused by e.g. bends, such as from the proximal end to the distal end of the tube structure. The tube structure may e.g. comprise a substantially straight section and the axial configuration is hence substantially straight. The tube structure may comprise one or more straight sections and one or more bends at which the tube structure changes direction, so that the axial configuration of the tube structure is more complex than in the case of a substantially straight tube structure. The axial configuration of the tube structure may determine the velocity profile of the fluid if a bend in the tube structure has resulted in a cross sectional asymmetric velocity profile of the fluid. When the tube structure comprises a cannula main portion where the proximal end of the diffuser is connected to the distal end of the cannula main portion, the axial configuration of the cannula main portion may determine the velocity profile of the fluid, which enters the diffuser at its proximal end.

In one embodiment, the diffuser is arranged to reduce the magnitude and exposure time of turbulent shear stress applied to the cardiovascular system of a patient when blood is introduced into the cardiovascular system, whereby problems relating to turbulent stress induced activation and damage of the elements of the blood are reduced.

In one embodiment, the second geometry of the diffuser comprises a section arranged substantially along the lateral surface of an oblique frustum. In this case the longitudinal axis may coincide with a line connecting the center of the proximal base and the center of the distal base.

The center of a base of the diffuser may be determined from the circumscribed circle of the base, and the circumcenter, i.e. the center of the circumscribed circle, is defined as the center of the base. .

The distal base of the diffuser in the second geometry may comprise a section which is arranged in a plane that is oblique to the longitudinal axis of the diffuser, such as in the case of a obliquely terminated distal end of a conical frustum wherein the lateral surface of the conical frustum extends further at a first angular coordinate than at a second angular coordinate. The first and second angular coordinates may be such that the second angular coordinate corresponds to a position on the other side of the diffuser relative to the position with the first angular coordinate.

The flow direction of a fluid in a given cross section of the diffuser may be calculated from the sum of all flow vectors at the cross section.

The flow direction may be substantially parallel to the longitudinal axis of the diffuser

In tubular structures with cross sectional symmetric designs, such as cylindrical or a conical frustum, the flow direction of a fluid flowing with an equilibrated velocity profile, may be substantially parallel to the longitudinal axis of the tubular structure. In the context of the present application, the phrase equilibrated velocity profile refers to the situation where a tubular structure has been sufficiently straight for a sufficient length, so that any offset in the velocity profile caused by e.g. a bend has been cancelled. The equilibrated velocity profile is the velocity profile seen in a straight tube.

In one embodiment, the flow direction of the fluid passing through the diffuser is such that the fluid flows from the proximal end to the distal end of the diffuser.

For some applications it may be preferred that the cannula main portion has a bend in the vicinity of the diffuser, and the velocity profile of the fluid entering the diffuser may be asymmetric. In a cannula main portion having e.g. a substantially cylindrically cross sectional shape and a bend having an inside and an outside, the velocity profile after the bend may be shifted towards the outside of the bend at least over a length of the cannula main portion. As the fluid flows through the bend, it accelerates around the outside of the bend and slows down near the inside of the bend. The velocity profile thus may be distorted with a high velocity zone occurring near the outside of the bend. The fluid entering the proximal end of a diffuser connected to such a cannula main portion may thus have an asymmetric velocity profile.

An aorta cannula may have a bend close to the diffuser due to the limited space available. A diffuser comprising a longitudinally asymmetric design may be applied to at least partially compensate for an asymmetric velocity profile of the fluid entering the proximal end of the diffuser.

In this context, the phrase longitudinally asymmetric design refers to the situation, wherein the distal end of the diffuser extends further from the proximal end in a longer part than in a shorter part arranged opposite to said longitudinal axis. A diffuser comprising a longitudinally asymmetric design comprises a region, wherein a cross sectional view of the diffuser comprises a semi-circle or another structure which only partially surrounds the longitudinal axis of the diffuser.

The longitudinal asymmetric design may be advantageous both in the first and the second geometry of the diffuser. In the second geometry a diffuser comprising a longitudinal asymmetric design may at least partially compensate for a cross sectional asymmetric velocity profile as described above. In relation to applications, wherein the diffuser is the distal part of a device, which is to be introduced into a given system, such as a cannula which is inserted into a patient at a point of entry, a longitudinal asymmetric design may provide a sharper tip (smaller size) at the diffuser's distal end in its first geometry, whereby a more gentle and easy entry into the system is provided.

The shaper tip of the asymmetric design of the diffuser in its first geometry may be arranged so that the reduction of the flow velocity of the fluid exiting the distal end of the diffuser is substantially maintained compared to a symmetric diffuser having a length identical to the longer part of the asymmetric diffuser. In one embodiment, the asymmetric diffuser is arranged with the longer part arranged close to where the flow velocity is high, such as close to the portion of the diffuser arranged relative to the outside of a bend.

When the distal end of the diffuser extends further from the proximal end in a longer part than in a shorter part arranged opposite to said longitudinal axis, the ratio between the length of the longer part, L|_Ong, and the length of the shorter part, L_short, may be in the range of about 1.05 to about 5, such as in the range of about 1.10 to about 4, such as in the range of about 1.15 to about 3, such as in the range of about 1.2 to about 2.5, such as in the range of about 1.5 to about 2.3.

The asymmetry length, L_asym, defined as the difference between the length of the longer part, L|_Ong, and the length of the shorter part, L_short, may be in the range of about 0.5 mm to about 100 mm, such as in the range of about 1 mm to 75 about mm, such as in the range of about 2 mm to about 50 mm, such as in the range of about 4 mm to about 40 mm, such as in the range of about 6 mm to about 30 mm, such as in the range of about 10 mm to about 25 mm, such as in the range of about 15 mm to about 23 mm.

A diffuser comprising a longitudinal asymmetric design may be arranged in relation to a cannula main portion comprising a bend so that the longer part of the diffuser is arranged along the outside of the bend.

The longer part and the shorter part may be integral parts of the diffuser such as when the diffuser comprises a substantially coherent structure arranged in relation to said frame. The frame and/or said coherent structure may comprise an asymmetric design.

In one embodiment of the longitudinal asymmetric design of the diffuser it has the shape of a conical frustum, where a cross sectional cut has been made at the wider end of the conical frustum, i.e. the distal end in the second geometry, said cross section being arranged with an angle relative to said longitudinal axis.

In a diffuser comprising a longitudinal asymmetric design, the length of the diffuser may be defined as the longer part of the diffuser or the shorter part of the diffuser as measured from a cross sectional plane arranged perpendicular to the longitudinal axis at the proximal end of the diffuser.

The first frame material may comprise a shape memory material that is capable of "remembering" its original shape, so that it after being deformed to a temporary shape can be returned to the original shape again by applying said stimulus. The shape memory material may change from the pre-stimulus state to the post-stimulus state in response to said stimulus.

In one embodiment, the stimulus is heat and the shape memory material may be deformed from an original shape to a temporary shape while kept at a temperature below a transformation temperature interval. When heated to a temperature above the transformation temperature interval, the shape memory material may return to its un-deformed original shape.

In one embodiment, the first frame material comprises a shape memory alloy, also known as a smart metal, memory alloy, or muscle wire. A reversible, solid phase transformation known as Martensitic transformation is the force behind some shape memory alloys. The alloy material may form a crystal structure, which is capable of undergoing a change from one form of crystal structure to another.

The shape memory alloy may comprise an alloy selected from the group of a nickel-titanium alloys, such as nitinol with about 55% Ni, Ag-Cd with about 44 atomic % to about 49 atomic % Cd, Au-Cd with about 46.5 atomic % Cd to about 50 atomic % Cd, Cu-Al-Ni with about 14 to about 14.5 weight % Al and about 3 to about 4.5 weight % Ni; Cu-Sn about 15 atomic % Sn; Cu-Zn with about 38.5 to 41.5 weight % Zn; Cu-Zn-Si; Cu-Zn-Al; Cu-Zn-Sn; Fe-Pt with about 25 atomic % Pt; Mn-Cu with about 5 to about 35 atomic % Cu; Fe-Mn-Si; Pt alloys; Co-Ni-Al; Co-Ni-Ga; Ni-Fe-Ga; Ti-Pd in various concentrations; Cu- Zn-Al-Ni, Cu-Al-Ni; or Co-Cr-Ni-Mo, such as Phynox.

In one embodiment, the first frame material is such that a change from said pre-stimulus state to said post-stimulus state occurs gradually with increasing temperature over a transformation temperature interval. The corresponding change from said first frame configuration to the second frame configuration may accordingly also occur gradually with the gradual shift between the states of the first material.

In the context of the present invention, the phrase "effective transition temperature" refers to the temperature at which a gradually introduced change of a material property, such as the phase of a nitinol material, has reached a transition level wherein the frame configuration have reacted to the change in the material property, and the frame has changed from the pre-stimulus configuration to a intermediate configuration. The change from the pre- stimulus configuration to the intermediate configuration may be such that the circumference of the frame at a given position along the diffuser is increased from the pre-stimulus configuration to the intermediate configuration by a factor of at least 1.03, such as at least 1.05, such as at least 1.08, such as at least 1.1 , such as at least 1.12, such as at least 1.15, such as at least 1.2, such as at least 1.25, such as at least 1.33, such as at least 1.4, such as at least 1.5, such as at least 1.6, such as at least 1.75, such as at least 2, such as at least 3. The position may be at substantially any longitudinal position of the diffuser, such as at the distal end of the diffuser or at a midway point between the proximal and distal ends of the diffuser.

The change of the shape of the frame is completed when the temperature has reached the upper limit of the transformation temperature interval.

In one embodiment, the first frame material of said diffuser comprises nitinol material. The first frame material in said pre-stimulus state may then comprise nitinol in its Martensitic phase, and said first frame material in said post- stimulus state may comprise nitinol in its Austenite phase. The change from the Martensitic phase to the Austenite phase with increasing temperature may occur gradually over a transformation temperature interval.

The change from the first frame configuration to the second frame configuration may accordingly occur gradually with increasing temperature as the nitinol material gradually changes its phase from the Martensitic phase to the Austenite phase.

When Nitinol is deformed at a temperature below the transformation temperature interval it maintains that shape until the gradual change of phase from the Martensitic phase to the Austenite phase results in a change of shape At temperatures above its transformation temperature interval, Nitinol is able to withstand a partial deformation when a load is applied and still return substantially to its original shape when the load is removed.

In one embodiment, the frame material is made of nitinol, said material property is the phase, and the transition level relates to the situation herein the change from Martensitic to Austenite phase is more than 25%, such as more than about 35 %, such as more than about 45 %, such as more than about 55 %, such as more than about 65 %, such as more than about 75 %.

Nitinol is typically composed of approximately 50 to 55.6% nickel by weight. Nitinol wire can be heated with electricity thus realizing an electrical actuator.

In one embodiment, said first frame material comprises a polymer material. The polymer material may comprise a shape memory polymer. The polymer material may be electrically controllable, such as an Electroactive Polymer.

Electroactive Polymers or EAPs are polymers whose shape is modified when a voltage is applied to them. They can be used as actuators or sensors. As actuators, they are characterized by being able to undergo a large amount of deformation while sustaining large forces. Due to the similarities with biological tissues in terms of achievable stress and force, they are often called artificial muscles, and have the potential for application in the field of robotics, where large linear movement is often needed. EAP can have several configurations, but are generally divided in two principal classes:

• Dielectric EAPs, in which actuation is caused by electrostatic forces between two electrodes which squeeze the polymer. This kind of EAP is characterized by a large actuation voltage (several thousand volts), but very low electrical power consumption. Dielectric EAPs require no power to keep the actuator at a given position. Examples are electrosthctive polymers and dielectric elastomers.

• Ionic EAPs, in which actuation is caused by the displacement of ions inside the polymer. Only a few volts are needed for actuation, but the ionic flow implies a higher electrical power needed for actuation, and energy is needed to keep the actuator at a given position. Examples of ionic EAPS are conductive polymers, ionic polymer-metal composites (IPMCs), and responsive gels. Yet another example is a Bucky gel actuator, which is a polymer-supported layer of polyelectrolyte material consisting of an ionic liquid sandwiched between two electrode layers consisting of a gel of ionic liquid containing single-wall carbon nanotubes.

When the first frame material is in its pre-stimulus state with its initial frame configuration, the frame may be capable of being reversibly deformed by a mechanical pressure from the initial frame configuration to a deformed frame configuration with the first material in a temporary shape. In one embodiment, the deformed frame configuration is substantially stable unless further mechanical pressure or said stimulus is applied. The pre-stimulus frame configuration may comprise the deformed frame configuration, and the change of shape of the diffuser when going from the first to the second geometry may be governed by the return of the frame from the pre-stimulus frame configuration to a configuration, wherein the mechanically introduced deformation of the initial frame configuration is cancelled due to the shape memory properties of the first frame material.

In one embodiment, the post-stimulus frame configuration is substantially identical to the initial frame configuration before the mechanical pressure deforms it. This may for instance be the case when the frame is formed by a shape memory material, such as Nitinol.

In one embodiment, the post-stimulus frame configuration is defined by shaping the diffuser at a temperature above said transformation temperature interval. This may for instance be the case when the frame is formed by a shape memory material, such as Nitinol.

The first geometry and the second geometry of the diffuser may be such that A2,d > Ai,d. This corresponds to an expansion of the distal end of the diffuser in response to the applied stimulus. This expansion provides the reduction of the flow velocity at the distal end compared to the flow velocity at the proximal end.

When a fluid passes through an expanding structure, an initially laminar flow may become turbulent if large changes in the circumference occur over short distances. In relation to flowing blood into the blood system of a patient, this may cause the abovementioned problems including emboli, and turbulence should be avoided or kept at a minimum level. In a monotonously expanding structure, there is a maximum angle between the flow direction and the inner wall of the structure inside which a fluid flowing through the structure can expand while substantially maintaining a laminar flow. When the angle between the flow direction and the inner wall of the structure is larger than 7.5° the flowing fluid may separate from the inner wall causing turbulent flows to occur. In one embodiment, the increase in the lumen circumference towards the distal end of the diffuser in its second geometry does not anywhere along the diffuser correspond to said frame having a gradient relative to said longitudinal axis that exceeds 6°.

In one embodiment, the diffuser in said second geometry has a circumference of said lumen which at least along a section of the diffuser increases with a substantially constant gradient from said proximal end towards said distal end. In the context of the present application the phrase substantially constant gradient refers to the situation, wherein the frame expands substantially monotonically with only small variations in the local angle between the flow direction and the frame along the entire length of the diffuser. In this context, at small variation in the local angle corresponds to having variations below about 15% of the local angle, such as below about 12% of the local angle, such as below about 10%, of the local angle such as below about 8% of the local angle, such as below about 5% of the local angle, such as below about 2% of the local angle, such as below about 1 % of the local angle. In one embodiment, the local angle between the flow direction and the frame is below 6° along the entire length of the diffuser.

In one embodiment, the diffuser comprises at its proximal end an overlap section adapted to overlap the distal end of a cannula main portion, having a substantially constant outer diameter. The length of the overlap section may be in the range of about 1 to about 40 mm, such as in the range of about 2 mm to about 30 mm, such as in the range of about 3 mm to about 20 mm, such as in the range of about 4 mm to about 10 mm. The frame may comprise a section that extends into the overlap section of the diffuser. This section may be substantially identical in the pre-stimulus and post-stimulus configurations of the frame.

A frame comprising an overlap section that is substantially identical in the pre- stimulus and post-stimulus configurations of the frame, and an expanding section, wherein the area of the distal base increases when the frame changes to the post-stimulus configuration may be realized in nitinol material by shaping only the expanding section during a thermal cycling to define the memory effect of the frame.

The first geometry of the diffuser may take different forms. In one embodiment, the first geometry is substantially cylindrical with the circumference of said lumen at said proximal and distal ends being such that Ai,_d is substantially equal to Ai,_p, The first geometry may have a slightly narrowing circumference when going towards said distal end. In one embodiment, the first geometry is formed as a substantially conical frustum with Ai,_d < Ai,_p. When the diffuser has this shape, the introduction of the diffuser into e.g. a patients body is less stressful for the patient than in the case where said diffuser has a Ai,_d that is either equal to or larger than Ai,_p. The ratio between the areas at the proximal and distal ends of said diffuser in its first geometry may be such that the Ai,d/Ai,_p, is in the range of about 0.05 to about 0.95, such as in the range of about 0.1 to about 0.9, in range of about 0.15 to about 0.8, in the range of about 0.2 to about 0.7, in the range of about 0.2 to about 0.5.

The ratio between the areas at the proximal and distal ends of said diffuser in its first geometry may be such that the Ai,d/Ai,_p, is smaller than about 0.95, such as smaller than about 0.9, such as smaller than about 0.8, such as smaller than about 0.7, such as smaller than about 0.6, such as smaller than about 0.5, such as smaller than about 0.4, such as smaller than about 0.3, such as smaller than about 0.2, such as smaller than about 0.1. In one embodiment, the diffuser in its second geometry takes the form of a substantially a conical frustum with A₂,d> A₂,_p.The ratio A2,d/A₂,_p may be in the range of about 1.1 to about 100, such as in the range of about 1.2 to about 75, in the range of about 1.3 to about 50, in the range of about 1.5 to about 25, in the range of about 1.8 to 10, in the range of about 2 to about 5.

The opening angle of a conical frustum shaped second geometry may be in the range of about 3 degrees to about 18 degrees, such as in the range of about 4 degrees to about 15 degrees, such as in the range of about 5 degrees to about 12 degrees, such as in the range of about 7 degrees to about 11 degrees. The opening angle may be about 9 degrees.

In the context of the present invention, the term opening angle, Θ_Cf, of a conical frustum having a distal base radius, Rb, a proximal base radius, R_t, and a Length L_Cf is given by

Θ_cf = 2 tan-^{i rRb "Rt}

Lcf J

In one embodiment the gradient of the increase in the lumen circumference towards said distal end of said second geometry has different values along the diffuser and an average value, gAv- The maximum local relative deviation from the average value may be in the range of about 0.01 to about 1 , such as in the range of about 0.05 to about 0.5, such as in the range of about 0.1 to about 0.3, such as in the range of about 0.15 to about 0.25. maximum local relative deviation from the average value may be in the range of about 0.01 gAv to about 1g_Av, such as in the range of about 0.05 g_Av to about 0.5 gAv, such as in the range of about 0.1 g_Av to about 0.3 gAv, such as in the range of about 0.15 gAv to about 0.25 g_Av

The stimulus that activates the frame to change from said pre-stimulus to said post-stimulus configuration may comprise a stimulus selected from the group of a heat transfer, electrical current, voltage, acoustic waves, light, pressure, magnetic attraction, magnetic repulsion, electrical attraction, electric repulsion, and chemical stimulus In one embodiment, said stimulus comprises a heat transfer and the frame changes from said pre-stimulus frame configuration to said post-stimulus frame configuration in response to a change from a first temperature in a first temperature interval to a second temperature in a second temperature interval.

In one embodiment, the diffuser further comprises a substantially impermeable material covering at least a part of said frame. In one embodiment, the entire frame is covered by said impermeable material. The substantially impermeable material may prevent the covered part of the diffuser frame from coming into direct contact with an object in which the diffuser is placed, such as the blood or tissue of a patient. The substantially impermeable material may delay the transport if fluids, such as the blood of a patient, from an object to the covered part of the diffuser frame. The transport may be delayed by at least a factor of about 1.5, such as about 2, such as about 3, such as about 4, such as about 5, such as about 7, such as about 10, such as about 20, such as about 40, such as about 70, such as about 100, such as about 200, such as about 500, such as about 1000.

The substantially impermeable material may be arranged in a layer surrounding said frame, with the thickness of said layer being in the range of about 10 μm to about 2000 μm, such as in the range of about 10 μm to about 1000 μm, such as in the range of about 10 μm to about 500 μm, such as in the range of about 20 μm to about 250 μm, in the range of about 30 μm to about 100 μm, in the range of about 40 μm to about 75 μm.

The substantially impermeable material may be a layer arranged to surround said frame, with the thickness of said layer being in the range of about 10 μm to about 2000 μm, such as in the range of about 10 μm to about 100 μm, such as in the range of about 10 μm to about 500 μm, such as in the range of about 20 μm to about 250 μm, in the range of about 30 μm to about 100 μm, in the range of about 40 μm to about 75 μm. The layer may be arranged so that in the first geometry, surplus layer material is available at least along a portion of said diffuser so that in said second geometry, the thickness of said layer is not reduced along this portion due to e.g. stretching of the layer material in response to the change from said first to said second diffuser geometry. In one embodiment, this portion comprises at least the distal end of said diffuser.

The substantially impermeable material may be an elastomer. In one embodiment, the substantially impermeable material comprises a biocompatible material, such as Polytetrafluoroethylene (PTFE), expanded Polytetrafluoroethylene (ePTFE) and/or Polyethylene terephthalate (PETP) in at least one thin film or in woven fibers.

In the context of this patent, the phrase "biocompatible material" refers to material that are not producing a toxic, injurious, or immunological response in living tissue.

In one embodiment the diffuser is provided with an anti-coagulation agent such as a heparin coating to mitigate the coagulation of blood in response to the presence of the diffuser in a blood vessel.

In one embodiment, the stimulus is provided to the first frame material through the inclusion of a contact material that is in thermal and/or electrical contact with at least a part of said frame. The contact material may be a wire interleaved with at least a part of said frame. The wire may be a resistive wire which is capable of heating said first frame material when an electrical current is drawn through the wire. The wire may also be arranged to apply a voltage drop over said first frame material, such as a wire which is capable of applying a voltage drop over a frame comprising an electroactive polymer material.

The frame may further comprise at least a second frame material. The second frame material may change from its pre-stimulus state to its post-stimulus state at a different magnitude or value of said stimulus. In one embodiment, the frame comprises a first material and a second material which changes from their pre-stimulus states to their post-stimulus states at different temperatures, thus allowing for a two-step process, where the expansion of the diffuser occurs in a first step at one temperature and in a second step at a different temperature. The response of the second frame material to the stimulus may be different from the response of the first frame material to the stimulus. In one embodiment, the response of the first material and the response of the second material counteract each other. In one embodiment, a response of the first material and a response of the second material combine to provide a combined response. The combined response may comprise an increase in the circumference at the distal end and a change of the overall shape of the diffuser.

Different approaches can be applied alone or in combination when fabricating the frame according to the present invention. In one embodiment, the frame comprises wires of said first frame material. The wires may then be braided to realize the frame according to the present invention. Accordingly, in one embodiment, the diffuser comprises a frame with nitinol based self- expandable braided wire-structures.

The first frame material may be arranged in several ways within said frame. In one embodiment, the frame material is arranged in a lattice of diamond shaped sections with solid contact between the sections at the corners of neighboring sections of the lattice. In this arrangement, the frame may be stable towards internal pressures and it allows for a large flexibility in relation to radial compression.

In one embodiment, the frame comprises a plurality of laminar arranged sections of said first frame material. In one embodiment, the diffuser comprises a plurality of annular shaped sections of said first frame material. In one embodiment, the frame comprises sections of said first frame material arranged in a zig zag manner.

In one embodiment, the arrangement of the first frame material in the frame of the first geometry varies along the longitudinal axis. For a frame with a lattice which maintains its overall pattern along the longitudinal axis, the size of the individual parts in this pattern, such as cells in a lattice, may change. The size may e.g. increase towards the distal end. Such an arrangement may provide a more efficient expansion of the distal of the diffuser end when going from said first to said second geometry. In one embodiment, the size of the cells of a lattice increases by a factor in the range of about 1.1 to about 4, such as in the range of about 1.25 to about 3, such as in the range of about 1.5 to about 2.5, such as in the range of about 1.75 to about 2.25. In a frame with the frame material being arranged in a lattice of diamond shaped sections, the diagonal arranged along the longitudinal axis may increase towards the distal end.

The thickness of the layer of frame material, such as the radial extension of the material frame may be substantially constant along the longitudinal axis. In one embodiment, this thickness is in the range of about 0.01 mm to about 5 mm, such as in the range of about 0.02 mm to about 2 mm, such as in the range of about 0.05 mm to about 1.5 mm, such as in the range of about 0.1 mm to about 1 mm, such as in the range of about 0.2 mm to about 0.8 mm, such as in the range of about 0.3 mm to about 0.7 mm, such as in the range of about 0.4 mm to about 0.5 mm.

The thickness of the layer of frame material, such as the radial extension of the material frame may vary along the longitudinal axis.

In one embodiment, this thickness of the layer of frame material at the proximal end of the diffuser in the first geometry is in the range of about 0.01 mm to about 5 mm, such as in the range of about 0.02 mm to about 2 mm, such as in the range of about 0.05 mm to about 1.5 mm, such as in the range of about 0.1 mm to about 1 mm, such as in the range of about 0.2 mm to about 0.8 mm, such as in the range of about 0.3 mm to about 0.7 mm, such as in the range of about 0.4 mm to about 0.5 mm.

In one embodiment, this thickness of the layer of frame material at the distal end of the diffuser in the first geometry is in the range of about 0.01 mm to about 5 mm, such as in the range of about 0.02 mm to about 2 mm, such as in the range of about 0.05 mm to about 1.5 mm, such as in the range of about 0.1 mm to about 1 mm, such as in the range of about 0.2 mm to about 0.8 mm, such as in the range of about 0.3 mm to about 0.7 mm, such as in the range of about 0.4 mm to about 0.5 mm.

In one embodiment, this thickness of the layer of frame material at the distal end of the diffuser in the second geometry is in the range of about 0.01 mm to about 5 mm, such as in the range of about 0.02 mm to about 2 mm, such as in the range of about 0.05 mm to about 1.5 mm, such as in the range of about 0.1 mm to about 1 mm, such as in the range of about 0.2 mm to about 0.8 mm, such as in the range of about 0.3 mm to about 0.7 mm, such as in the range of about 0.4 mm to about 0.5 mm.

The width of the individual portions of the lattice of frame material, such as the annular extension of the material in a strut of a lattice, may be constant or may vary along the longitudinal axis. In one embodiment, this width measured at the proximal end of the frame, i.e. at the proximal end of the diffuser, in the pre-stimulus configuration is in the range of about 0.1 mm to about 1 mm, such as in the range of about 0.2 mm to about 0.8 mm, such as in the range of about 0.3 mm to about 0.6 mm, such as in the range of about 0.4 mm to about 0.5 mm. In one embodiment, this width is in the range of about 0.1 mm to about 1 mm, such as in the range of about 0.2 mm to about 0.8 mm, such as in the range of about 0.3 mm to about 0.6 mm, such as in the range of about 0.4 mm to about 0.5 mm at the distal end of the frame, i.e. at the distal end of the diffuser, in the post-stimulus configuration

The length of the individual portions of the lattice of frame material, such as the longitudinal extension of the material in a strut of a lattice, may be constant or may vary along the longitudinal axis. In one embodiment, this length measured at the proximal end of the frame, i.e. at the proximal end of the diffuser, in the pre-stimulus configuration is in the range of about 1 mm to about 10 mm, such as in the range of about 2 mm to about 8 mm, such as in the range of about 3 mm to about 6 mm, such as in the range of about 4 mm to about 5 mm. In one embodiment, this length is in the range of is in the range of about 1 mm to about 10 mm, such as in the range of about 2 mm to about 8 mm, such as in the range of about 3 mm to about 6 mm, such as in the range of about 4 mm to about 5 mm at the distal end of the frame, i.e. at the distal end of the diffuser, in the post-stimulus configuration.

In the diffuser second geometry, the circumference at said distal end of said diffuser body may substantially circular. The frame may be such that the frame material is arranged in substantially the same pattern before and after the response to said stimulus. In one embodiment, the frame comprises a lattice of diamond shaped sections. When the first frame material changes from a pre-stimulus configuration to a post-stimulus configuration, the diamond shaped sections are deformed whereby the frame is changed . However, the lattice may still comprise diamond shaped sections and the frame material is then arranged in substantially the same pattern before and after the response to said stimulus.

The frame material may also be such that it can be heated or cooled when an electrical current is drawn through the frame. In one embodiment, said first frame material is conducting and is arranged so that a current is forced to pass through substantially the whole of said frame. In one embodiment, the first frame material is arranged in a conducting pattern wherein the conducting path defined by said first frame material from a current entry point to a current exit point comprises substantially the whole of said frame, such as at least 50% of said first frame material comprised within said frame, such as at least 60% of said first frame material comprised within said frame, such as at least 70% of said first frame material comprised within said frame, such as at least 80% of said first frame material comprised within said frame, such as at least 90% of said first frame material comprised within said frame, such as at least 95% of said first frame material comprised within said frame.

I one embodiment, the frame may take the form of a meander pattern with the longer sections of the pattern being arranged with a substantially constant angular coordinate.

In one embodiment, the frame and the first frame material is adapted to respond to a change in the temperature from room temperature to the body temperature of a patient. The first temperature interval may span from about 1 °C to about 25 ⁰C, while the second temperature interval spans from about 25 ⁰C to about 42 ⁰C, or the first temperature interval may span from about 1⁰C to about 22 ⁰C, and while the second temperature interval spans from about 22 ⁰C to about 42 ⁰C. The second temperature may correspond to the body temperature of a patient under treatment, and the stimulus may comprise the heat transfer from the patient's body to said diffuser

In one embodiment, said stimulus comprises a heat transfer and the frame changes from said pre-stimulus frame configuration to said post-stimulus frame configuration in response to a change from a first temperature below an effective transition temperature of said first frame material to a second temperature above said effective transition temperature. In one embodiment, the effective transition temperature of the first frame material is within the range of about 20 ⁰C to about 37 ⁰C, such as in the range of about 22 ⁰C to about 35 ⁰C, such as in the range of about 25 ⁰C to about 32 ⁰C, such as in the range of about 27 ⁰C to about 30 ⁰C.

In one embodiment, the first frame material is super-elastic and effective transition temperature of said first frame material is below about 20 ⁰C, such as below about 15 ⁰C, such as below about 10 ⁰C.

In one embodiment, the first frame material is super-elastic and the second temperature interval comprises room temperature. In one embodiment, the lower boundary of the second temperature interval is below room temperature, such as below about 10 ⁰C, such as below about 15 ⁰C,

Superelasticity, or sometimes referred to as Pseudoelasticity, is an elastic (impermanent) response to relatively high stress caused by a phase transformation between the austenitic and martensitic phases of a crystal. It is exhibited in shape-memory alloys. Pseudoelasticity is from the reversible motion of domain boundaries during the phase transformation, rather than just bond stretching or the introduction of defects in the crystal lattice. If the domain boundaries do become pinned, they may be reversed through heating. Thus, a pseudoelastic material may return to its previous shape after the removal of even relatively high applied strains.

When mechanically loaded, a superelastic alloy deforms reversibly to very high strains by the creation of a stress-induced phase. When the load is removed, the new phase becomes unstable and the material regains its original shape. No change in temperature is needed for the superelastic alloy to recover its initial shape.

In one embodiment, the frame and the first frame material is adapted to respond to heat transfer from an external heat source. The effective transition temperature of the frame may be more than about 28 ⁰C, such as more than about 32 ⁰C, such as more than about 35 ⁰C, such as more than about 38 ⁰C, such as more than about 40 ⁰C. The effective transition temperature may be less than about 45 ⁰C, such as less than about 55 ⁰C. The upper limit for the effective transition temperature is limited by the onset of e.g. tissue damage in response to the heating. In one embodiment, the frame material is thermally isolated from the tissue of the patient, and higher temperatures can be applied to the frame material from the external heat source without damaging the tissue surrounding the diffuser or the blood flowing through and/or outside it.

In one embodiment, the cannula according to the present invention is adapted to be used as an aortic cannula, wherein said fluid is blood and said impermeable material comprises a blood impermeable material.

In the first geometry, the area, Ai_,p, defined by the diffuser lumen circumference at the proximal end is in the range of about 1 mm² to 80 mm², such as in the range of about 10 mm² to 70 mm², such as in the range of about 20 mm² to 60 mm², such as in the range of about 25 mm² to 50 mm², and wherein the area, Ai,_d, defined by the diffuser lumen circumference at the distal end is in the range of about 1 mm² to 80 mm², such as in the range of about 10 mm² to 70 mm², such as in the range of about 20 mm² to 60 mm², such as in the range of about 25 mm² to 50 mm².

In the second geometry, the area, A₂,_p, defined by the diffuser lumen circumference at the proximal end is in the range of about 1 mm² to 80 mm², such as in the range of about 10 mm² to 70 mm², such as in the range of about 20 mm² to 60 mm², such as in the range of about 25 mm² to 50 mm², and wherein the area, A₂,d, defined by the diffuser lumen circumference at the distal end is in the range of about 10 mm² to 200 mm², such as in the range of about 20 mm² to 150 mm², such as in the range of about 50 mm² to 125 mm², such as in the range of about 25 mm² to 100 mm². In one embodiment, A₂,_p is about 49 mm² and A₂,d is about 100 mm².

The length of the diffuser may vary depending on the field of application and other parameters relating to the form of the diffuser, such as the areas defined by the circumferences at the proximal and distal ends. In principle the diffuser length may vary from a few millimeters, such as 2 millimeters, to several meters, such as 2 meters, depending on the field of application.

When applied in relation to an aortic cannula, the length of said diffuser body may be in the range of about 10 mm to about 50 mm, such as in the range of about 12 mm to about 35 mm, such as in the range of about 15 mm to about 25 mm

The diffuser may also be used in relation to pediatric surgery, and in one embodiment, the cannula according to the present invention is adapted to be a pediatric aortic cannula, wherein Ai,_p and A₂,_p are in the range of about 1 mm² to about 35 mm², such as in the range of about 3 mm² to about 25 mm², Ai,d is in the range of about 1 mm² to 25 mm², and A₂,d is in the range of about 4 mm² to 300 mm², such as in the range of about 5 mm² to about 200 mm², such as in the range of about 5 mm² to about 100 mm², and wherein the length of the diffuser body is in the range of about 10 mm to 30 mm.

The diffuser is able to provide a reduction of the local flow velocity at the distal end compared to the flow velocity at the proximal end. This reduction makes the diffuser suitable for providing rapid blood transfusion without inflicting major damage to the blood vessel caused by the problems described earlier herein. Hence, in one embodiment, the cannula according to the present invention is adapted to provide non-turbulent flow of fluids at high flow velocities, wherein Ai,_p and A_{2 p} are in the range of about 0.5 mm² to about 35 mm², such as in the range of about 1 mm² to about 25 mm², Ai,_d is in the range of about 0.5 mm² to 25 mm², and A_{2 d} is in the range of about 4 mm² to 300 mm², such as in the range of about 5 mm² to about 200 mm², such as in the range of about 5 mm² to about 100 mm², and wherein the length of the diffuser body is in the range of about 10 mm to 30 mm. Due to the reduction of the flow velocity at the distal end of the diffuser, a cannula comprising a diffuser according to the present invention may also be used in relation to patients suffering from severe arteriosclerosis (porcelain Aorta).

The cannula according to the present invention may be used in relation to dialysis treatment. In one embodiment, Ai,_p and A₂,_p are in the range of about 0.5 mm² to about 35 mm², such as in the range of about 1 mm² to about 25 mm², Ai,d is in the range of about 0.5 mm² to 25 mm², and A₂,d is in the range of about 4 mm² to 300 mm², such as in the range of about 5 mm² to about 200 mm², such as in the range of about 5 mm² to about 100 mm², and the length of the diffuser body is in the range of about 10 mm to 30 mm.

The cannula according to the present invention may be part of a system for introducing and/or reintroducing fluids into a patient's body. Such a system may comprise a cannula as described herein and a flow system for controlling and transporting said fluids to and from said patient's body. The system may further comprise a stimulus generating device for providing said stimulus to said frame to activating the change of said diffuser from said first to second geometry. The stimulus generating device may be selected from the group of an external heat transfer source, a cooling element, an electrical current supplier, an acoustic wave generator, a high power light source, a compressor.

In one embodiment, the system comprises a mechanical confinement element adapted to at least partly confine a diffuser. In this embodiment, said frame is in said pre-stimulus frame configuration and removing said mechanical confinement corresponds to applying said stimulus to the diffuser. The mechanical confinement element may comprise a semi-rigid hollow element, such as a substantially tubular or ring shaped element.

In one embodiment, the mechanical confinement element comprises a wire at least partially integrated in said frame.

The frame of the diffuser may be fabricated using different techniques or combinations of these techniques. In one embodiment the frame is fabricated by arranging wires comprising said first frame material in a braided frame pattern. In one embodiment the frame is fabricated by laser cutting the frame from a sheet of said first frame material. The first frame material may be Nitinol or another shape memory alloy and the laser used for the cutting must be sufficiently powerful to provide an evaporation of the first frame material.

The diffuser may be arranged in relation to a cannula main portion using techniques know to the person skilled in the art. In one embodiment, the diffuser is attached to the cannula main portion by gluing the proximal end of said diffuser to the exit port of a cannula main portion, herein also referred to as the distal end of the cannula main portion. The proximal end of the diffuser may be arranged to overlap the distal end of the cannula.

In one embodiment, the inner diameter of the cannula main portion is arranged to increase towards the distal end of the cannula main portion at least over section in the vicinity of the distal end. The gradient of the increase in the inner circumference diameter of the cannula main portion may be substantially identical the gradient of the increase in the circumference diameter of the diffuser, thereby providing a smooth transition from cannula main portion to said diffuser. The length of the section of the cannula main portion in which the inner diameter increases may be in the range of about 1 mm to about 50 mm, such as in the range of about 2 mm to about 25 mm, such as in the range of about 4 mm to about 20 mm such as in the range of about 6 mm to about 15 mm such as in the range of about 8 mm to about 12 mm

The diffuser may be cooled to below room temperature prior to the perfusion in order to counteract a premature change from said first to second geometry.

The diffuser may also be applied in relation to situations where a liquid must be provided to a target area that is difficult to access with a catheter having a large outer diameter. One object of the invention is hence to provide a catheter for supplying a liquid to a target area, said catheter comprising a diffuser comprising a diffuser body comprising a proximal end, a distal end, and a lumen extending along a longitudinal axis between said proximal and distal ends. The diffuser body comprises a frame extending longitudinally at least along a part of said diffuser body, said frame comprising at least a first frame material. The frame is capable of changing from said pre-stimulus frame configuration to a post-stimulus frame configuration when said first frame material changes from a pre-stimulus state to a post-stimulus state in response a stimulus. The change from said pre-stimulus frame configuration to said post-stimulus frame configuration being such that said diffuser changes from a first geometry to a second geometry, where in said first geometry, the lumen circumference at said proximal end defines an area Ai,_p and the lumen circumference at said distal end defines an area Ai,_d, and where in said second geometry, the lumen circumference at said proximal end defines an area A₂,_p and the lumen circumference at said distal end defines an area A₂,d. The frame is substantially rigid in said post-stimulus frame configuration.

The frame may be coated with a material which changes the response time of the frame to the stimulus. The thickness of this material may be constant along the longitudinal axis of the diffuser. The thickness of this material may change along the longitudinal axis of the diffuser.

In one embodiment, the material comprises a thermally insulating material, which delays a thermal activation of the frame for instance in response to the body temperature of said patient. The thermally insulating material may be such that coating delays the heating of the first frame material to a temperature above the transformation temperature interval of the first frame material, whereby the user is allowed sufficient time to place e.g. a cannula comprising the diffuser in e.g. aorta of a patient. The thermally insulating material may have a thermal conductivity in the range of about 0.001 Js^"1 K^"1 m^" ¹to about 0.5 Js^"1K^"1rn^"1t, such as in the range of about 0.01 Js^"1 K^"1 m^"1 to about 0.4 Js^"1 K^"1 m^"1, such as in the range of about 0.05 Js^"1 K^"1 m^"1 to about 0.3 Js^" ¹K^"1m^"1, such as in the range of about 0.08 Js^"1 K^"1 m^"1 to about 0.2 Js^"1 K^"1 m^"1, such as in the range of about 0.10 Js^"1K^"1m^"1 to about 0.25 Js^"1K^"1m^"1.

The thermally insulating material may have a thermal conductivity that is below about 0.5 Js^"1K^"1rn^"1t, such as below about 0.4 Js^"1 K^"1 m^"1, such as about 0.3 Js^"1 K^"1 m^"1, such as in about 0.25 Js^"1 K^"1 m^"1, such as below about 0.20 Js^"1K^"1m^"1, such as below about 0.1 Js^"1K^"1m^"1.

The delay of the coated frame's response to the stimulus compared to the un- coated frame may be more than about 1 second, such as more than about 1 ,5 seconds, such as more than about 2 seconds, such as more than about 3seconds, such as more than about 5 seconds, such as more than about 7,5 seconds, such as more than about 10seconds, such as more than about 15 seconds, such as more than about 20 seconds, such as more than about 30 seconds, such as more than about 60 seconds, such as more than about 120 seconds. The delay may be less than about 1200 seconds, such as less than about 900 seconds, such as less than about 600 seconds, such as less than about 300 seconds.

The material arranged change the response time of the frame may be arranged in a substantially homogeneous layer with a thickness of said layer being in the range of about 10 μm to about 1000 μm, such as in the range of about 10 μm to about 500 μm, such as in the range of about 20 μm to about 250 μm, in the range of about 30 μm to about 100 μm, in the range of about 40 μm to about 75 μm.

In one embodiment, the frame material comprises an electrically insulating material which delays an electrically activation of the frame for instance in response to a current provided from an external current supply. The insulating material may also provide protection to the surrounding tissue towards damage from the current

When an external source is used to control the change from said first to second geometry, the external source may also be used to soften the expanded frame so that the cannula can be removed from the patient with a minimum stress for the patient.

The diffuser may also be used as an expandable guide of fluids or gasses, where the increase in the lumen circumference at the distal end provides a larger area for collecting said fluid or gas. In this embodiment, the flow direction is from the distal to the proximal end. BRIEF DESCRIPTION OF DRAWINGS

The invention will be explained more fully below in connection with a preferred embodiment and with reference to the drawings in which:

FIG. 1 shows a diffuser in an initial frame configuration, a pre-stimulus deformed frame configuration and a post-stimulus frame configuration,

FIG. 2 shows a graph of kinetic energy of a fluid which is converted into pressure energy.

FIG. 3 shows a configuration of the diffuser

FIG. 4 shows a diffuser from side view with angle and dimensions marked

FIG. 5 shows a lattice of diamond shaped sections manufactured by laser- cutting

FIG. 6 shows a frame configuration which is covered by a biocompatible material

FIG. 7 shows a diffuser assembled in an aortic cannula arrangement

FIG. 8 shows a braided frame pattern made from individual wires

FIG. 9 shows a frame configuration with said first frame material arranged in a zig-zag manner

FIG. 10 shows picture of a frame arranged with the proximal end connected to a cannula tube. The frame having temperature of 20⁰C and being in the pre- stimulus configuration.

FIG. 11 shows the device of Fig. 10 with camera facing distal end of frame.

FIG. 12 shows the device of Fig. 10 with the temperature being raised to 27°C.

FIG. 13 shows the device of Fig. 10 with camera facing distal end of frame. The temperature of the frame is raised to 28.5°C. FIG. 14 shows the device of Fig. 10 with camera facing distal end of frame. The temperature of the frame is raised to 32°C

FIG. 15 shows the device of Fig. 10 with camera facing distal end of frame. The temperature of the frame is raised to 34°C.

FIG. 16 shows a series of images taken when a frame in the pre-stimulus configuration is immersed into a water bath having a temperature of 34 ⁰C.

Fig. 17 shows a pattern for laser cutting a diffuser frame from a nitinol tube.

Figure 18 show a flow velocity plot for a diffuser arranged close to a bend. The diffuser having a symmetric termination at the distal end, where the distal end circumference is arranged in a plane that is perpendicular to the longitudinal axis of the diffuser

Figure 19 show a flow velocity plot for a diffuser arranged close to a bend. The diffuser having a symmetric termination at the distal end, where the distal end circumference is arranged in a plane that is non-perpendicular to the longitudinal axis of the diffuser

The figures are schematic and may be simplified for clarity. Throughout, the same reference numerals are used for identical or corresponding parts.

Further scope of applicability of the present invention will become apparent from the detailed description given hereinafter. However, it should be understood that the detailed description and specific examples, while indicating preferred embodiments of the invention, are given by way of illustration only, since various changes and modifications within the spirit and scope of the invention will become apparent to those skilled in the art from this detailed description.

The invention is defined by the features of the independent claim(s). Preferred embodiments are defined in the dependent claims. Any reference numerals in the claims are intended to be non-limiting for their scope. Some preferred embodiments have been shown in the foregoing, but it should be stressed that the invention is not limited to these, but may be embodied in other ways within the subject-matter defined in the following claims.

A prototype of a diffuser according to the present invention was manufactured in a shape memory alloy. The first frame material was selected to have its transformation temperature interval such that the diffuser took advantage of the difference in body temperature and room temperature. When the distal end of the diffuser was inserted in aorta of a pig, the shape recovery was "activated" by body heat from the pig which caused the frame to change from said pre-stimulus to said post-stimulus configuration, whereby the diffuser changed from said first to said second geometry. The diffuser is illustrated in Figure 1. In its second geometry 13 its shape is that of a conical frustum with a diameter growing from 7 mm at the proximal end 15 to 12 mm at the distal end 16. The opening angle is 9° of the conical frustum and the length of the diffuser 1 , 5, 9, 13 is in around 20 mm. In the pre-stimulus configuration at room temperature, the diffuser in its first geometry 5, 9 is either substantially cylindrical shaped 5, where said lumen 6 has substantially identical diameters at the proximal 7 and distal 8 ends, or shaped as a conical frustum 9, where said lumen 10 has a diameter at the distal end 12 which is less than the diameter at the proximal end 11. In the initial frame configuration 1 , the lumen 2 expands along the flow direction from a diameter at the proximal end 3, which is smaller than the diameter at the distal end 4. When mechanical pressure is applied, the diffuser can be reversible deformed to the first geometry 5, 9. The mechanical pressure may be applied with the fingers of the user.

Fig. 2 shows a plot 21 , which illustrates how kinetic energy, represented in the graph as flow velocity 22, of a fluid is converted into pressure energy in the diffuser. The flow velocity is reduced to one third of its value at the distal end of the diffuser compared to the value at the proximal end. Simultaneously, the pressure provided by the fluid is only increased by a few percent.

FIG. 3 shows a configuration of the frame 31 , wherein the first frame material is arranged in a diamond shaped lattice. The number of cells in the lattice along the circumference of the frame is constant, and the expansion from the proximal end 15 towards the distal 16 end is provided by an expansion of the individual cells. As seen in Fig. 3, a lattice cell 35 at the distal end 16 is larger than a lattice cell 34 at the proximal end 15.

FIG. 4 shows a diffuser from side view with angle and dimensions marked. The diffuser 1 is shaped as a conical frustum and comprises a frame 31 that extends longitudinally at least along a part of the diffuser 13. The opening angle 45 of the conical frustum, the longitudinal axis 46 of the diffuser, and the length 47 of the diffuser are also indicated

A prototype in nitinol was manufactured by laser cutting. The prototype consisted of a diamond shaped frame as seen in Fig. 5. The frame was covered with a graft material 61 as seen in Fig. 6. The graft material was a 50 μm thick film of ePTFE, melted between the struts in the frame. Figure 7 shows an arrangement, where the diffuser frame 31 was attached to the distal end 25 of a commercial available end hole aortic cannula 24 by pins. When an operation on a patient is completed, the configuration of the frame will allow the diffuser to be removed by compressing the diamond cells.

Another prototype of the frame 31 was fabricated by braiding the frame pattern from individual wires 82 of the first frame material, in this case nitinol wire, as seen in Fig. 8.

FIG. 9 shows yet another prototype of the diffuser 91 comprising a frame configuration wherein nitinol first frame material was arranged in a zig-zag manner.

A pattern 171 for the laser cutting of a lattice is illustrated in Figure 17, wherein it is seen that the pattern is defined in one end of the tube (the distal end of diffuser) while no lattice is cut into the other end 172 (proximal end of the diffuser). By comparing cells 174 and 175 in the lattice it is seen that the size of the rhombic cells of the diamond lattice increases towards the end 173 that corresponds to the distal end of the diffuser. Figures 10 to 16 show the design and behaviour of a nitinol based diffuser frame according to the present invention. The diffuser frame was realized from a 25 mm long nitinol tube, wherein a 20 mm long lattice of diamond shaped cells was formed by laser cutting. The tube had an inner diameter of 8.7 mm and the thickness of the frame material (i.e. the radial thickness) was 0.7 mm. The lattice extended around the whole of the diffuser circumference in the 20 mm long lattice region.

The nitinol material was in the Austenite phase for temperatures between 20⁰C and 34°C (the transformation temperatures interval) and in the Martensitic phase for temperatures below 10⁰C according to the supplier Admedes Schuessler GmbH.

The frame was mounted on a cannula having an inner diameter of 8mm and an outer diameter of approximately 8.7 mm. The frame overlaps the distal end cannula main portion for a length of 5 millimeters where no cells are defined.

A thermal cycling procedure was applied to define the memory effect of the nitinol frame. The frame temperature was cycled between a lower temperature, at which the nitinol is in its Martensitic phase, and a higher temperature, where the nitinol is in the Austenite phase. Different shapes were imposed to the frame at the different temperatures by applying a mechanical pressure to the frame.

When the frame was cooled to a lower temperature of 5°C it was shaped so that the lumen circumference had a smaller diameter at the distal end than at the proximal end, corresponding to the first geometry of the diffuser, where Aid < Ai_p. The frame is subsequently heated to a higher temperature above the transformation temperature interval, and the frame is shaped so that the frame circumference has a larger diameter at the distal end than at the proximal end, which then corresponds to the second geometry of the diffuser with A_2cι > A_2p.

When this treatment was applied to the nitinol frame it subsequently could be shaped to the pre-stimulus frame configuration while being in the Martinsitic phase and when heated to above the transformation temperature interval during use in relation to e.g. a surgical procedure, it changed to the post- stimulus frame configuration. The part of the frame which had been shaped during the thermal cycling procedure (i.e. the part extending beyond the cannula main portion) is referred to as the trained lattice structure.

When heated from e.g. room temperature to a temperature near 34°C, the frame changes from its pre-stimulus configuration to the post-stimulus configuration, corresponding to a change of the diffuser from its first to second geometry

In the second geometry, the part of the frame extending beyond the cannula has the shape of a conical frustum with an opening angle of 9° and an inner diameter of 8.7 mm at the proximal end.

The effective transition temperature of of the nitinol material was about 28.5°C and a change from the pre-stimulus frame configuration to the post-stimulus frame configuration occurs gradually when increasing the temperature from 28.5°C to 34°C. At temperatures below 28.5°C the shape of the frame corresponds to the first geometry of the diffuser having Ai_d < Ai_p.

Figure 10 shows the frame 1 being arranged on a cannula main portion 25 with a PVC fitting 26 arranged to keep the diffuser in position. The temperature of the frame is 20⁰C and the frame is in the pre-stimulus configuration corresponding to the first geometry of a diffuser. As can be seen in Fig. 10, the frame comprises a lattice of diamond shaped cells, where the longitudinal dimension of these cells increase towards the distal end. The lattice does not extend all the way to the proximal end and a section is left untreated by the laser. This section is arranged to overlap the cannula main body over 5 mm.

The shape of the frame was monitored at different temperatures while mounted on the cannula main portion. The frame was inserted into a water bath having an equilibrated temperature and its response to the temperature was monitored. The results are listed in table 1

Table 1

Figures 11 and 13-15 show the gradual change of the frame configuration in response to an increase in the temperature of the bath. The images of Figures 11 and 13-15 all depict the frame from the distal end. In Fig 11 , where the temperature of the frame is still below effective transition temperature and the shape of the frame is still according to the pre-stimulus configuration. When heated to a temperature above effective transition temperature the frame progressively changes to the post-stimulus configuration as seen in Figures 13-15, so that it ends up being substantially unfolded at 34°C (Figure 15).

The dependence of the time required to change from the pre-stimulus frame configuration to the post-stimulus frame configuration was tested at different temperatures of the bath and the results are listed in table 2

Table 2

These times were obtained when the frame was not covered with a material arranged to delay the response to the heat provided by the bath. If the diffuser was covered with one layer of a low density Polyethylen (LDPE) film (sold under the name "Vita Wrap"), the time required for change to second geometry was increased to 25 seconds.

The cannula with the diffuser was tested on a pig to investigate the change from the first to the second frame configuration in real life. Initially the frame material was not covered by a material which could delay the frame's response to the heat from the pig. In the un-coated assembly, the change from first to second configuration was substantially instantaneous when the diffuser was brought into contact with the pig, and the diffuser changed to the second geometry before it was possible to position it in aorta. Subsequently the diffuser was covered with one or more layers of a low density Polyethylen (LDPE) film, in order to delay the response to the heat provided by the heat of the pig's blood. When the frame was covered with 4 layers of the LDPE film, the response time to the blood temperature was in the order of 25 seconds which was sufficiently long time to allow the user to place the cannula tip with the diffuser in the aorta before the diffuser had changed to the second geometry. A lower number of layers may provide a sufficiently long delay but the thickness of the LDPE film and its robustness posed a potential problem in that holes in the film potentially could allow the warm blood to reach the frame material.

Figure 16 shows the lowering of the diffuser frame according to Figs. 10-15 into a heated water bath having a temperature of 34 ⁰C, causing a heat induced change of the nitinol material to its Austenite phase. The heat hence being the stimulus, which introduce a change from the pre-stimulus configuration of the frame corresponding to the first geometry wherein Ai_d < Ai_p to the post-stimulus configuration of the frame corresponding to the second geometry of the diffuser with A_2d > A_2p. In Fig 16a, the frame has not yet been brought into contact with the water, and the frame is still shaped such that Aid < Ai_p. In Fig 16 b and 16c the frame is beginning to change to the post stimulus configuration, which it has reached in fig, 16d, wherein A_2cι > A_2p. The time span from Fig. 16a to Fig. 16d is 0,576 s.

Figures 18 and 19 show flow simulated velocity plots for two different designs of the diffuser when water is pumped into a tubular structure 100 (idealization of aorta) though a cannula main body 101 at a rate of 5 L/min and a water temperature of 20⁰C. In both Figures, the diffuser is arranged close to a bend and the flow velocity is significantly higher in the part of the diffuser arranged along the outside of the bend. In Figure 18, the diffuser 102 comprises a symmetric termination at the distal end, where the distal end circumference is arranged in a plane that is perpendicular to the longitudinal axis of the diffuser. In Figure 19, the diffuser 104 comprises a longer part and the diffuser is arranged such that the longer part is arranged along the outside of the bend. The maximum flow velocity experienced at the circumference of the tube at positions 103, 105 is clearly reduced when the diffuser 102 of Figure 18 is adapted to have the longer part of the diffuser 104 of Figure 19.

Claims

1. A diffuser adapted for converting kinetic energy of a flowing fluid into pressure energy to reduce the flow velocity of said fluid, said diffuser comprising a diffuser body comprising a proximal end, a distal end, and a lumen extending along a longitudinal axis between said proximal and distal ends,

said diffuser body comprising a frame extending longitudinally at least along a part of said diffuser body, said frame comprising at least a first frame material,

said frame being capable of changing from a pre-stimulus frame configuration to a post-stimulus frame configuration when said first frame material changes from a pre-stimulus state to a post-stimulus state in response a stimulus,

the change from said pre-stimulus frame configuration to said post- stimulus frame configuration being such that said diffuser changes from a first geometry to a second geometry, where

in said first geometry, the lumen circumference at said proximal end defines an area Ai,_p and the lumen circumference at said distal end defines an area Ai,_d, and where in said second geometry, the lumen circumference at said proximal end defines an area A₂,_p and the lumen circumference at said distal end defines an area A₂,d,

2. The diffuser according to claim 1 , wherein said first frame material comprises a shape memory material that change from said pre-stimulus state to said post-stimulus state in response to said stimulus.

3. The diffuser according to claim 1 or 2, wherein said frame is capable of being reversible deformed from an initial frame configuration to a deformed configuration by a mechanical pressure, wherein said deformation is substantially stable unless further mechanical pressure or said stimulus is applied.

4. The diffuser according to claim 3, wherein said pre-stimulus frame configuration comprises said deformed configuration.

5. The diffuser according to any of the previous claims, wherein said first geometry and said second geometry are such that A₂,d > Ai,_d.

6. The diffuser according to any of the previous claims, wherein said diffuser in said second geometry has a circumference of said lumen which at least along a section of the diffuser increases with a substantially constant gradient from said proximal end towards said distal end.

7. The diffuser according to any of claims 2 to 6, wherein said shape memory material comprises a shape memory alloy selected from the group of a nickel-titanium alloy, such as nitinol with about 55% Ni, Ag-Cd with about 44 atomic % to about 49 atomic % Cd, Au-Cd with about 46.5 atomic % Cd to about 50 atomic % Cd, Cu-Al-Ni with about 14 to about 14.5 weight % Al and about 3 to about 4.5 weight % Ni; Cu-Sn about 15 atomic % Sn; Cu-Zn with about 38.5 to 41.5 weight % Zn; Cu-Zn-Si; Cu-Zn-Al; Cu-Zn-Sn;

Fe-Pt with about 25 atomic % Pt; Mn-Cu with about 5 to about 35 atomic % Cu; Fe-Mn-Si; Pt alloys; Co-Ni-Al; Co-Ni-Ga; Ni-Fe-Ga; Ti-Pd in various concentrations; Cu-Zn-Al-Ni, Cu-Al-Ni; or Co-Cr-Ni-Mo, such as Phynox.

8. The diffuser according to 7, where said first frame material in said pre- stimulus state comprises nitinol in its Martensitic phase, and said first frame material in said post-stimulus state comprises nitinol in its Austenite phase.

9. The diffuser according to any of the previous claims, wherein said first frame material comprises a polymer material, such as an electroactive polymer and/or a shape memory polymer.

10. The diffuser according to any of the previous claims, the diffuser comprising a longitudinal asymmetric design wherein the length of the lateral surface of said diffuser body has a minimum value at a first angular coordinate and a maximum value at a second angular coordinate of said diffuser.

11.The diffuser according to claim 10, wherein the ratio between the maximum lateral surface length and the minimum lateral surface length is in the range of about 1.02 to about 5, such as in the range of about 1.05 to about 3, such as in the range of about 1.10 to about 2, such as in the range of about 1.15 to about 1.8, such as in the range of about 1.20 to about 1.6.

12. The diffuser according to any of the previous claims, wherein said first geometry is substantially cylindrical and Ai,_d is substantially equal to Ai,_p.

13. The diffuser according to any of the previous claims, wherein said first geometry substantially is a conical frustum with Ai,_d < Ai,_p.

14. The diffuser according to claim 13, wherein the ratio Ai_,d/Ai_,P is in the range of about 0.05 to about 0.95, such as in the range of about 0.1 to about 0.9, in range of about 0.15 to about 0.8, in the range of about 0.2 to about 0.7, in the range of about 0.2 to about 0.5.

15. The diffuser according to any of the previous claims, wherein said second geometry is substantially a conical frustum with A₂,d> A₂,_p.

16. The diffuser according to any of the previous claims, wherein the ratio A₂,d /A₂,p is in the range of about 1.1 to about 100, such as in the range of about 1.2 to about 75, in the range of about 1.3 to about 50, in the range of about 1.5 to about 25, in the range of about 1.8 to 10, in the range of about 2 to about 5.

17. The diffuser according to claim 15 or 16, wherein the opening angle of said conical frustum is in the range of about 3 degrees to about 18 degrees, such as in the range of about 4 degrees to about 15 degrees, such as in the range of about 5 degrees to about 12 degrees, such as in the range of about 7 degrees to about 11 degrees.

18. The diffuser according to claim 17, wherein the opening angle of said conical frustum is about 9 degrees.

19. The diffuser according to any of the previous claims, wherein said stimulus comprises a stimulus selected from the group of a heat transfer, electrical current, voltage, acoustic waves, light, pressure, magnetic attraction, magnetic repulsion, electrical attraction, electric repulsion, and chemical stimulus.

20. The diffuser according to claim 19, wherein said stimulus comprises a heat transfer and wherein said frame changes from said pre-stimulus frame configuration to said post-stimulus frame configuration in response to change from a first temperature below an effective transition temperature to a second temperature above said effective transition temperature.

21.The diffuser according to any of the previous claims further comprising a substantially impermeable material at least partially covering said frame.

22. The diffuser according to claim 21 , wherein said substantially impermeable material is arranged in a layer surrounding said diffuser, the thickness of said layer being in the range of about 10 μm to about 2000 μm, such as in the range of about 10 μm to about 1000 μm, such as in the range of about 10 μm to about 500 μm such as in the range of about 20 μm to about 250 μm, in the range of about 30 μm to about 100 μm, in the range of about 40 μm to about 75 μm.

23. The diffuser according to claim 21 or 22, wherein said substantially impermeable material comprises a thermally insulating material with a thermal conductivity in the range of about 0.001 Js^"1K^"1rn^"1to about 0.5 Js^" ¹K^"1rn^"1t, such as in the range of about 0.01 Js^"1 K^"1 m^"1 to about 0.4 Js^"1 K^" ¹ITi^"1, such as in the range of about 0.05 Js^"1 K^"1 m^"1 to about 0.3 Js^"1 K^"1 m^"1, such as in the range of about 0.08 Js^"1 K^"1 m^"1 to about 0.2 Js^"1 K^"1 m^"1 , such as in the range of about 0.10 Js^"1 K^"1 m^"1 to about 0.25 Js^"1 K^"1 m^"1.

24. The diffuser according to any of claims 21 to 23, wherein said substantially impermeable material comprises a biocompatible material, such as an elastomer, Polytetrafluoroethylene (PTFE), expanded Polytetrafluoroethylene (ePTFE) and/or Polyethylene terephthalate (PETP) in at least one thin film or in a sheet of woven fibers.

25. The diffuser according to any of the previous claims, further comprising a contact material that is in thermal and/or electrical contact with at least a part of said frame.

26. The diffuser according to claim 25, wherein said contact material is a wire interleaved with at least a part of said frame.

27. The diffuser according to claim 26, wherein said wire is a resistive wire capable of heating said first frame material when an electrical current is drawn through the wire and/or a wire arranged to apply a voltage drop over said first frame material.

28. The diffuser according to any of claims 8 to 27, wherein said frame comprises self-expandable braided wire-structures comprising nitinol material.

29. The diffuser according to any of the previous claims, wherein said frame comprises a lattice of diamond shaped sections of said first frame material.

30. The diffuser according to any of the previous claims, wherein said frame comprises a plurality of laminar arranged sections of said first frame material.

31.The diffuser according to any of the previous claims, wherein said frame comprises a plurality of annular shaped sections of said first frame material.

32. The diffuser according to any of the previous claims, wherein said frame comprises sections of said first frame material arranged in a zig zag manner.

33. The diffuser according to any of the previous claims, wherein in said second geometry, the circumference at said distal end of said diffuser body is substantially circular.

34. The diffuser according to any of the previous claims, wherein said frame material is arranged in substantially the same or in different patterns before and after the response to said stimulus.

35. The diffuser according to any of the previous claims, wherein said frame is substantially rigid in said post-stimulus frame configuration, such that the radial stress applied by a largest difference between the internal pressure and the external pressure at some point along the longitudinal axis of the diffuser leads to a relative change in the diffuser circumference anywhere along the longitudinal axis which is less than 30%, such as less than 25%, such as less than 20%, such as less than 15%, such as less than 10%, such as less than 5%, such as less than 2%, such as less than 1 %, when the pressure difference is less than about 500 mmHg, such as less than about 300 mmHg, such as less than about 200 mmHg, such as less than about 150 mmHg, such as less than about 100 mmHg, such as less than about 50 mmHg.

36. The diffuser according to any of the previous claims, where said frame further comprises at least a second frame material wherein said second frame material changes from its pre-stimulus state to its post-stimulus state at a different magnitude or value of said stimulus and/or wherein the response of said second frame material to said stimulus differs from the response of said first frame material to said stimulus.

37. The diffuser according to any of the previous claims, wherein said first frame material is conducting and is arranged in a conducting pattern, wherein the conducting path defined by said first frame material from a current entry point to a current exit point comprises substantially the whole of said frame, such as at least 50% of said first frame material comprised within said frame, such as at least 60% of said first frame material comprised within said frame, such as at least 70% of said first frame material comprised within said frame, such as at least 80% of said first frame material comprised within said frame, such as at least 90% of said first frame material comprised within said frame, such as at least 95% of said first frame material comprised within said frame.

38. The diffuser according to claim 37, wherein said first frame material is arranged in a meander path with each of the longer sections of the path being arranged with a substantially constant angular coordinate

39.A cannula adapted for insertion into a patient under treatment at a point of insertion, said cannula comprising a cannula main portion and the diffuser according to any of claims 1 to 38, where the proximal end of the diffuser is arranged in relation to a distal end of the cannula main portion.

40. The cannula according to claim 39, wherein said effective transition temperature of the diffuser is in the range of about 20⁰C to about 37 ⁰C, such as in the range of about 22°C to about 35 ⁰C, such as in the range of about 25 ⁰C to about 32 ⁰C.

41.The cannula according to claim 39 or 40, wherein said diffuser comprises a longitudinal asymmetric design.

42. The cannula according to claim 41 , wherein said cannula main portion comprises a bend and the diffuser is arranged with the maximum lateral surface length along the outside of the bend.

43. The cannula according to any of claims 39 to 42, wherein said stimulus comprises the heat transfer from the patient's body to said diffuser.

44. The cannula according to claim 39, wherein said effective transition temperature is below room temperature, such as below about 15 ⁰C, such as below about 10 ⁰C, and wherein said first frame material is super- elastic.

45. The cannula according to claim 39, wherein said effective transition temperature is above 28 ⁰C, such as above 32 ⁰C, such as above 35 ⁰C, such as above 42 ⁰C, such as above 45 ⁰C.

46. The cannula according to claim 45, wherein said effective transition temperature is below 45 ⁰C, such as below 55 ⁰C.

47.An aortic cannula comprising the cannula according to any of claims 39 to 46, wherein said fluid is blood and said impermeable material comprises a blood impermeable material.

48. The aortic cannula according to claim 47, wherein A₂,_p is in the range of about 1 mm² to 80 mm², such as in the range of about 10 mm² to 70 mm², such as in the range of about 20 mm² to 60 mm², such as in the range of about 25 mm² to 50 mm², and wherein A₂,d is in the range of about 10 mm² to 200 mm², such as in the range of about 20 mm² to 150 mm², such as in the range of about 50 mm² to 125 mm², such as in the range of about 25 mm² to 100 mm².

49. The aortic cannula according to claim 48, wherein A₂,_p is about 49 mm² and A₂,d is about 100 mm².

50. The aortic cannula according to any of claims 47 to 49, wherein Ai,_p is in the range of about 1 mm² to 80 mm², such as in the range of about 10 mm² to 70 mm², such as in the range of about 20 mm² to 60 mm², such as in the range of about 25 mm² to 50 mm², and wherein Ai,_d is in the range of about 1 mm² to 80 mm², such as in the range of about 10 mm² to 70 mm², such as in the range of about 20 mm² to 60 mm², such as in the range of about 25 mm² to 50 mm².

51.The aortic cannula according to any of claims 47 to 50, wherein the length of said diffuser body is in the range of about 10 mm to about 50 mm, such as in the range of about 12 mm to about 35 mm, such as in the range of about 15 mm to about 25 mm.

52.A pediatric aortic cannula comprising the cannula according to any of claims 39 to 46, wherein Ai,_p and A_{2 p} are in the range of about 1 mm² to about 35 mm², such as in the range of about 3 mm² to about 25 mm², Ai,_d is in the range of about 1 mm² to 25 mm², A_{2 d} is in the range of about 4 mm² to 300 mm², such as in the range of about 5 mm² to about 200 mm², such as in the range of about 5 mm² to about 100 mm², and wherein the length of the diffuser body is in the range of about 10 mm to 30 mm.

53.A cannula adapted to provide a rapid blood transfusion comprising the cannula according to any of claims 39 to 46, wherein Ai,_p and A₂,_p are in the range of about 0.5 mm² to about 35 mm², such as in the range of about 1 mm² to about 25 mm², Ai,_d is in the range of about 0.5 mm² to 25 mm², and A₂,d is in the range of about 4 mm² to 300 mm², such as in the range of about 5 mm² to about 200 mm², such as in the range of about 5 mm² to about 100 mm², and wherein the length of the diffuser body is in the range of about 10 mm to 30 mm.

54.A cannula adapted to use in relation to severe arteriosclerosis (porcelain Aorta) comprising the cannula according to any of claims 39 to 46.

55. A dialysis cannula comprising the cannula according to any of claims 39 to 46, wherein Ai,_p and A₂,_p are in the range of about 0.5 mm² to about 35 mm², such as in the range of about 1 mm² to about 25 mm², Ai,_d is in the range of about 0.5 mm² to 25 mm², and A₂,d is in the range of about 4 mm² to 300 mm², such as in the range of about 5 mm² to about 200 mm², such as in the range of about 5 mm² to about 100 mm², and the length of the diffuser body is in the range of about 10 mm to 30 mm.

56.A system for introducing and/or reintroducing fluids into a patient's body, said system comprising:

a cannula according to any of claims 39 to 54; and

a flow system for controlling and transporting said fluids to and from said patient's body.

57. The system according to claim 56 further comprising a stimulus generating device for providing said stimulus to said frame to activating the change of said diffuser from said first to second geometry.

58. The system according to claim 57 wherein said stimulus generating device is selected from the group of an external heat transfer source, a cooling element, an electrical current supplier, an acoustic wave generator, a high power light source, a compressor.

59. The system according to any of claims 56 to 58, further comprising a mechanical confinement element adapted to at least partly confine a diffuser, wherein said frame is in said pre-stimulus frame configuration and wherein applying said stimulus comprises removing said mechanical confinement.

60. The system according to claim 59, wherein said mechanical confinement element comprises a semi-rigid hollow element.

61.The system according to claim 59 or 60, wherein said mechanical confinement element comprises a substantially tubular or ring shaped element.

62. The system according to claim 59 wherein said mechanical confinement element comprises a wire at least partially integrated in said frame.

63. A method for fabricating the diffuser according to any of claims 1 to 38, comprising laser cutting a sheet of said first frame material into a frame pattern.

64. A method for fabricating the diffuser according to any of claims 1 to 38 comprising arranging wires comprising said first frame material in a braided frame pattern.

65. A method of pumping blood into the cardiovascular system of a patient, comprising

arranging a cannula according to any of claims 47 to 54 in relation to said cardiovascular system so that at least said distal end of said diffuser is positioned inside a blood vessel, such as a vein or an artery, such as the aortic artery;

allowing said diffuser to respond to a stimulus so that said diffuser takes the shape according to said second geometry; and

pumping blood into said cardiovascular system.

66. The method according to claim 65, wherein said cannula comprises the diffuser of any of claims 1 to 38, said diffuser being mechanically confined during the perfusion into said vessel, and wherein said diffuser is released from said confinement when the cannula is positioned correctly in relation to said vessel.

67. The method according to claim 66 wherein said diffuser is cooled to below room temperature prior to the perfusion in order to counteract a premature change from said first to second geometry.

68. A catheter for supplying a liquid to a target area, said catheter comprising a diffuser comprising a diffuser body comprising a proximal end, a distal end, and a lumen extending along a longitudinal axis between said proximal and distal ends,

said frame being capable of changing from said pre-stimulus frame configuration to a post-stimulus frame configuration when said first frame material changes from a pre-stimulus state to a post-stimulus state in response a stimulus,

in said first geometry, the lumen circumference at said proximal end defines an area Ai,_p and the lumen circumference at said distal end defines an area Ai,_d, and where in said second geometry, the lumen circumference at said proximal end defines an area A₂,_p and the lumen circumference at said distal end defines an area A₂,d, wherein

said frame is substantially rigid in said post-stimulus frame configuration.

69. The catheter according to claim 68 further comprising the features according to any of claims 2 to 38.