WO2005033671A1

WO2005033671A1 - Method and device for in vitro simulation of an in vivo fluid flow

Info

Publication number: WO2005033671A1
Application number: PCT/NL2003/000684
Authority: WO
Inventors: Willem Van Oeveren
Original assignee: Haemoprobe B.V.
Priority date: 2003-10-08
Filing date: 2003-10-08
Publication date: 2005-04-14
Also published as: AU2003304491A1

Abstract

A method for simulating in vivo flow conditions. A fluid is positioned in a fluid channel (3) in a fluid holder (2). Thereafter a fluid flow which may have a pulsatile character is generated. The generating of the fluid flow, comprises swinging the fluid holder (2) from a first position into a second position different from the first position. Thereby, an acceleration force is exerted on the fluid and a fluid flow is generated. Thereafter, the fluid holder (2) is swung back from the second position in a direction towards the first position, whereby a decelerating force is exerted on the fluid and the fluid flow is stopped.

Description

Title: Method and device for in vitro simulation of an in vivo fluid flow.

FIELD AND BACKGROUND OF THE INVENTION The invention relates to a method for in vitro simulation of an in vivo fluid flow in an animal body. The invention also relates to a medical test, a method for testing a medical device or compound, a method for growing living material in vitro, a method for pumping a fluid, a method for growing a living tissue in vitro, a flow simulator device and a fluid processing device arranged for processing an organic fluid. In vitro tests using living material requires conditions which resemble the in vivo conditions inside the living, e.g. animal, body itself as good as possible. Testing of implant devices, such as heart valves, in blood, for example, requires an in vitro simulation of the blood flow through the implant device which corresponds as much as possible to the blood flow in vivo. In the art, apparatuses for in vitro testing of compounds or devices in a blood flow are known comprising a tubular loop which can be filled with blood and in which an implant device can be positioned. The tubular loop is connected to a mechanical pump which thus can provide a blood flow. By alternately switching the pump on and off, the pulsated flow of blood in vivo is simulated. However, a disadvantage of this known apparatus is that the in vitro conditions do not simulate the in vivo conditions in a realistic manner. More in particular, the operation of the mechanical pump damages cells, e.g. red blood cells and platelets, in the blood. This damage gives rise to unwanted and unrealistic effects, such as the clotting of blood. From Chandler AB, "In vitro trombotic coagulation of blood: a method for producing a thrombus", Lab Invest 1958; 7:110-116, a method for in vitro testing of blood is known. The in- vitro model is the Candler loop, which consists of a closed tubing partly filled with air, which circulates the device constantly through the air-liquid interface. However, a drawback of this prior art method is that artifacts are induced due to the major forces applied to blood elements and protein denaturation on the air-liquid interface. An apparatus and method for in vitro testing of medical devices in blood is known from K. Munch et al, "Use of simple and complex in vitro models for multiparameter characterization of human blood-material/device interactions", J. Biomater. Sci. Polymer Edn, Vol. 11, No. 11, pp. 1147-1163 (2000). The apparatus comprises a tubing arranged in a number of valved loops. The loops are filled with blood. The loops are then rotated with a computer controlled micro-stepper motor which generates a sigmoid acceleration ramp followed by a short pause. Each loop contains a ball-and cage check valve which together with the rotational acceleration establishes a pulsatile circular flow in the loops. The apparatus known from this Munch publication does not have a mechanical pump and therefore reduces the damage to the cells in the blood caused by the pumping. However, the method described in the Munch publication has several drawbacks. For example, although the step motor causes a flow which increases and decreases, the flow inside the loop does not stop immediately. Hence, the flow in the loops does not provide a realistic simulation of the flow in vivo. Therefore, the check valves are required to obtain a blood flow with a sufficient pulsatile character. Still, even with the check valves the blood flow does not have a sufficient pulsatile character as the check valves do not close immediately because of the continuing fluid flow. Also, the check valves contain moving parts which are subject to wear and tear. Hence, the lifetime of the apparatus is limited. Furthermore, the check valves are relatively expensive and complicated to implement. A further draw-back is that the loop circuits described in the Munch publication were designed to test blood activation by the tubing material. The loop system is not suitable to house heart valves or other non-linear shaped medical devices that do not fit into the tubing. Moreover, the system is designed to be immersed in buffer solution while the system is filled with blood and operated, in order to prevent air entering the system. This means that oxygenation of the blood inside the test system is not possible. The experimental time is therefore limited to one hour at 37°C and a few hours at lower temperature, due to the oxygen demand of living blood cells.

SUMMARY OF THE INVENTION It is a goal of the invention to provide a method for in vitro simulation of an in vivo fluid flow in an animal body which can provide a flow with a pulsatile character. In order to achieve this goal, a method according to claim 1 is provided. Such a method provides a flow which can be provided with a pulsatile character because an acceleration force is exerted on the fluid by swinging the fluid holder from the first position into the second position and a decelerating force is exerted on the fluid by swinging said fluid holder back from the second position in the direction of the first position. Hence, a fluid flow is generated by the acceleration force and the fluid flow is then actively stopped, which may be performed abruptly. Hence, the flow can be provided with a pulsatile character which resembles the in vivo blood flow. A further advantage is that a check valve is not required to obtain a flow with a pulsatile character. Hence, less moving parts may be used and the lifetime of the mechanical parts used in the method is increased. Furthermore, properties of the simulated flow, such as for example the flow rate, the duration of a flow pulse otherwise or, can be adjusted in a simple manner by adjusting properties of the swinging of the fluid holder. The invention further provides a method for testing a medical device or compound according to claim 15. With such a method, a medical device or a compound, such as for example a drug or otherwise, can be tested in vitro with a realistic simulation of an in vivo fluid flow. Thus, the results of the testing can be used to provide a more accurate prediction of the performance of the medical device or compound in vitro. Also, a method for pumping a fluid according to claim 20 is provided. Also a meothod for growing living material in vitro according to claim 22 is provided. With such a method, living material is grown with characteristics suitable for implant in fluid vessels inside the animal body, because the characteristics of the living material at least partially depend on the conditions during growth and these conditions resemble the in vivo conditions accurately. The invention provides a flow simulator device according to claim 24. Such a device can be used to simulate an in vivo fluid flow in an animal body which can provide a flow with a pulsatile character A fluid processing device according to claim 25 is also provided. In such a fluid processing device, the fluid can be pumped in a manner which resembles the in vivo flow. Thus, unnatural effects caused by the pumping are prevented. Specific embodiments of the invention are set forth in the dependent claims. Further details, aspects and embodiments of the invention will be described, by way of example only, with reference to the attached drawings.

BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 schematically shows a partially cut-away perspective view of an example of an embodiment of a flow simulator device according to the invention. FIG. 2 schematically shows a perspective view of parts of an example of a fluid holder suitable for the example of FIG. 1. FIG.3 schematically show a top view of an example of the body of a fluid holder suitable for the example of FIG. 3. FIG. 4 schematically shows a cross-section of the example of FIG. 3 along the line IV-IV in FIG. 3. FIG. 5 schematically shows an example of a medical device in which a flow simulator according to the present invention is used as a pump. DETAILED DESCRIPTION The example of a flow simulator device 1 shown in FIG. 1 comprises a fluid holder 2 with a fluid channel 3. The fluid channel 2 is a closed loop channel, which in this example has an annular (circular) shape. In the example of FIG. 1, the fluid holder 2 is fixated on a rotatable cylinder 4. The rotatable cylinder 4 can be rotated around its longitudinal axis in a clockwise and an anti-clockwise direction, as is indicated with the arrow 5. The rotatable cylinder 4 extends through a passage in a housing 6. Inside the housing 6 an electromotor 7, known per se, is present which drives the rotation of the rotatable cylinder 4. The electromotor 7 can rotate the rotatable cylinder 4 alternately in a clockwise direction and an anti-clockwise direction or vice versa. The operation of the electromotor 7 is controlled by a control device 8 communicatively connected to the electromotor. The control device 8 may for example control the rotational direction of the rotor of the electromotor by applying a suitable control voltage. Such control is known per se and for the sake of brevity is not elaborated on in further detail. In use, the fluid channel 3 is filled with a fluid to perform an in vitro simulation of a fluid flow in vivo, i.e. inside a living animal body, such as the flow of blood near a heart valve in the human body or otherwise. After bringing the fluid in the fluid channel 3 a fluid flow is generated by swinging the fluid holder back and forth, e.g. in the example of FIG.1 by alternately rotating the fluid holder 2 by means of the rotatable cylinder 4 and electromotor 7 from a first position into a second position, e.g. clockwise, and rotating the fluid holder 2 from the second position back in the direction of the first position, e.g. anti-clockwise, as is indicated in FIG. 1 with the arrow 5. The swinging, e.g. rotation, of the fluid holder 2 from the first position into the second position causes a fluid flow in the direction of rotation due to the frictional force(s) exerted by the wall of the fluid channel 3 on the fluid. The swinging of the fluid holder 2 from the second position in the direction of the first position, stops the fluid flow because frictional force(s) are then exerted on the fluid by the fluid channel walls in a direction opposite to the fluid flow. Hence, the device 1 can generate a fluid flow without the necessity of moving parts, such as check valves or pumping means. Furthermore, the swinging back and forth provides a flow which has a pulsatile character, e.g. which accelerates and stops relatively abrupt. The device 1 therefore provides a fluid flow which has a good resemblance with fluid flows in vivo, such as blood flow or urine flow. Also, no mechanical pump is used and therefore adverse effects on the fluid cause by mechanical pumping is prevented, such as if for example blood is used as a fluid hemolysis (i.e. the breakdown of red blood cells). In the example of FIG. 1, the fluid channel is rotated around an, imaginary, rotation axis which extends inside the area encircled by the fluid channel 3, and more in particular the rotation axis extends through the middle of the circle defined by the annular fluid channel. Thus, the fluid in each part of the fluid thus receives the same acceleration and an uniform fluid flow is obtained. However, it is likewise possible to swing the fluid holder such that a non-uniform fluid flow is obtained. For example by rotating an annular circular fluid channel around a rotation access outside the middle or by providing a non-circular shaped, e.g. elliptical or otherwise, fluid channel. To increase the resemblance between the simulated fluid flow and the in vivo fluid flow, the swinging from the first position to the second position may be performed taking a longer time period than the back swinging from the second position in the direction of the first position or the back swinging may take a longer time than the swinging. The acceleration of the fluid flow will then be different from the deceleration. The flow of blood in the human body, for example, typically exhibits cycle of a fast acceleration, followed by an even faster deceleration and a period in which the flow is stopped. Thus, in the example of FIG. 1, to accurately simulate a blood flow in vivo, the fluid holder may be swung from the first position into the second position in certain time and be swung back in a shorter time, followed by a pause in which the fluid holder is not moved. Depending on the specific implementation, the number of rotations per time, and/or the displacement per rotation and/or the acceleration can be set to a suitable value For example, via the adjustable power supply and/or gear position inside the apparatus. It is found that an acceleration at or below 4.75 m/sec2 at a rate of 60 beats per minutes is suitable. Also found was that an acceleration at 60 beat per minutes may be at or above 2.41 m/sec2. Experiments at 30 beats per minutes showed good results at or above 1.87 m/sec2. In between these commonly used highest and lowest positions different acceleration values can be obtained. These different acceleration values can be adjusted stepwise, or can be controlled via computer software and the invention is not limited to these ranges. Likewise, the flow of urine discharged from the bladder typically exhibits a fast increase, followed by a more or less steady state and a decrease. Thus, to simulate the flow of urine discharged from the bladder, the fluid holder may for example first be rotated in a clockwise direction with a fast acceleration continued with a clockwise constant rotation velocity and then be rotated anti-clockwise. The swinging back and forth may be entirely opposite movements, e.g. the holder may be brought back into its original position, i. e. the first position, or may be brought into a third position during the swinging back, which third position lies between the first and second position. In the latter case, the holder will be swung back into its first position after a number of swinging cycles. The swing frequency may have any value suitable for the specific implementation. For example, to simulate a blood flow a suitable swing frequency lies above 1/3 Hz and can be below 4 Hz, i.e. 20-240 beats per minute, such as between 0.4 and 1 Hz. For the simulation of blood flow in a common conditions, the swing frequency may for example be in the range of 30-220 per minute. Experiments performed by the applicant show that even a swing frequency in the range of 24-60 beats per minute provides a flow which has a good resemblance with the human blood flow in vivo. The device 1 may also be provided with an adjustable frequency to provide a varying frequency, for example, in order to simulate the blood flow in a moving animal, which has a varying heart beat rate depending on the exertion. The fluid holder 2 in the example of FIG. 1 may for example be implemented as shown in FIG. 2. The example of FIG. 2 comprises a body 21 provided with a recess which defines a fluid channel 3. The fluid channel is open at a top side and can be closed off from the outside environment, for example by means of a closing 22 which can be placed on the top side. The fluid channel 3 can thus be sealed off to prevent, for example, clotting of blood due to interaction with air. To further prevent gas-fluid interfaces which may affect the fluid, the fluid channel 3 can be entirely filled with the fluid. When used for the simulation of a blood flow, the walls of the fluid channel 3 which are in contact with the fluid can be made of a blood compatible material, such as a polycarbonate, polypropylene, polytetrafluoroethylene or otherwise, to prevent clotting or other adverse interactions of the walls of the fluid channel with the blood as well. The example of FIG. 2 is especially suited for testing devices which are to be positioned in a fluid flow inside an animal body, such as invasive diagnostic devices or implant devices. It should be noted that such medical devices are known per se and for the sake of brevity are not described in further detail. The example of FIG. 2 is especially suited for testing heart valves known per se as well. The example of fig. 2 can be used as an ISO 10993-4 test-selection system for determining haemocompatibility of a device positioned in the fluid channel, for example. To fixate the position of the heart valve or another device, the wall of the fluid channel 3 is provided with slot shaped recesses, from hereon referred to as slots 31. Plates 23 with openings can be positioned perpendicular to the flow direction in the slots 31. Between the plates 23, the heart valve or another device can be placed, which is thus fixated in position in a similar fashion as a diapositive is positioned in a slide. In the example of FIG. 2, Luer locks 24 mouth into the fluid channel 3 and form passages, e.g. a fluid inlet and a fluid outlet, between the fluid channel 3 and the outside of the fluid holder 2. Via the luer locks 24 a fluid can be supplied into and discharged from the fluid channel 3. The body 21 further has a passage 25 extending with its longitudinal direction transverse through the plane in which the annular fluid channel 3 lies. The inside of the passage 25 has substantially the same shape as the rotatable cylinder 4 in FIG. 1. Thus, the passage 25 has a cylindrical shape with a cut-off side in order to couple the movement of the cylinder 4 to the body 21. The cylinder 4 may extend through the passage 25 beyond the body 21 to allow two or more fluid holders 2 to be mounted on top of each other and be rotated together by a single rotation device. To that end, components 221-224 mountable on top of the body 2 are provided with a passage for the rotatable cylinder 4 as well in the example of FIG. 2. In the example of FIG. 2, the fluid channel 3 has an annular loop shape. The fluid channel 3 is open on one side and can be covered with a closing 22. The closing comprises a semi-permeable membrane 221 which in a mounted position is in contact with the inside of the fluid channel 3. In this example, in the mounted position the semi-permeable membrane forms a part of the walls of the fluid channel 3, more specific the semi-permeable membrane constitutes the top-wall of the fluid channel. In this example, gasses, such as oxygen and carbon-oxides can pass through the semi-permeable membrane 221. Thus, in the example of FIG. 2 the fluid in the fluid channel 3 can exchanges gasses with the outside environment and thereby, for example, a blood flow can be simulated for a longer period of time, typically a couple of days, without degrading effects on the blood. The outside environment may for example be the open air, but it is likewise possible to position the device 1 in a closed-off, conditioned, environment. Such a conditioned environment or space may for example contain a medium, for example fluid or a gas, with which the fluid is to exchange matter with, such as for example a drug which is to be released slowly in the fluid. On the side of the semi-permeable membrane 221 facing away from the fluid channel 3, a grate 222 is positioned. The grate 222 has grate openings 2221,2222 which constitute defined areas in which the fluid channel 3 is allowed to be in contact with an environment outside the fluid channel 3 via the semi-permeable membrane 221. The semi-permeable membrane 221 and the grate 222 can be fixated on the body 21 by means of screw covers 223,224. A first screw cover 223 can engage on a, not shown, screw thread on a flange 251 which extends in circumferential direction around the passage 25. A second screw cover 224 outside of the body 21 can engage on a, not shown, screw thread on the radial outside edge of the body 21. In case two or more fluid holders are positioned on top of each other, the screw covers 223,224 also serve to provide a distance between the fluid holders. Thereby, the exchange between the fluid channel inside and the outside via the semi-permeable membrane 221 is maintained even with two or more fluid holders mounted on top of each other. To facilitate the alignment of the semi-permeable membrane 221 and grate 222, the body 21 is provided with a nib 211 which can extend through a first grate opening 2221 such that a second grate opening 2222 is positioned at a suitable place. In the example of fig. 2, the second grate opening is positioned near a position of a medical device, e.g. heart valve, to be tested. The nib. 211 also provides a provisional fixation which at least to some extend prevents displacement of the semi-permeable membrane 221 and the grate 222 when screwing the screw covers 223,224. The fluid channel 3 of the example shown in FIGs. 3 and 4 has a circular cross-section. The fluid channel 3 has locally a shape which resembles the shape of a fluid vessel in an animal body, e.g. near the slots 31. More specific, in that area the fluid channel 3 resembles the shape of a ventricle of the human heart. To that end, the fluid channel 3 has a chamber 32. Additionally, the parts 33 of the fluid channel 3 connected to the chamber 32 have an eliptical, egg-shaped cross-section. The walls of the chamber 32 are provided with slots 31 for positioning plates between which a heart valve can be positioned in a manner similar as in the example of FIG. 2. As is shown in FIGs. 3 and 4, the chamber 32 has a rectangular shape with rounded corners. The chamber 32 has a width which is larger than the radius of the circular cross-section. Thus, the fluid channel 3 has locally a shape which resembles a heart ventricle provided with an artificial heart valve. A suitable value of the width of the chamber is found to be in the order of 3 cm. However, the chamber 32 may likewise be provided with a different shape depending on the specific fluid vessel to be resembled, such as for example a cylindrical shape, a ball shape or otherwise. A method or device according to the invention may be used in any suitable application to simulate in vitro a fluid flow in vivo. For example, a method or device may be used for in vitro test of medical devices to be inserted in a fluid vessel of an animal. For example, an invasive diagnostic device or an implant device may be tested with a method or device according to the invention. In general, an invasive diagnostic device is insertable in the animal body, for collecting data about the animal, such as, for example, a catheter, a sensor or otherwise. In general, an implant device is implantable in the animal body and performing one or more functions of organs of the animal, such as, known per se, for example heart valves, stents, artificial blood vessels, annuloplasty ring, vena cava filters or otherwise. Increasingly, new developments to repair or replace body parts or organs are focussed on cultured host cells growing onto a matrix to replicate damaged tissue. Since cells adapt their phenotype to the conditions during growth, a fluid flow is required during growth which simulates the fluid flow in vivo. Thus, a method or flow simulator device according to the invention may be used, for example, as a 'bioreactor', to cultivate or grow living material, such as for example tissue engineering. The living material, for example a cell culture, may then be positioned in the fluid flow and provided nutrition for said living material. For example for growing heart valves, blood vessels or other vascular components, a part of the fluid channels may be provided with a shape resembling the vascular component and the cells may be grown in the part with the vascular component shape. Likewise, a method for simulating a fluid flow or a flow simulator device according to the invention may be used to test in vitro the effect of a chemical compound, e.g. a drug, on the fluid or a device positioned in the fluid channel. For example, the response of blood to the drug or the effect of this response on the performance of a heart valve, can be tested with a flow simulator device or method according to the invention. Typical drugs to be tested are inhibiters or activators of thrombocytes (also referred to as platelets), coagulation (also referred to as clotting), leukocytes (including, but not limited to, PMN

(polymorphonoclear leucocytes), monocytes, macrophages and granulocytes), and the complement system. Also, the effectiveness of a drug on cell growth during circulation can be tested with a method or flow simulator device according to the invention, because with a method or flow simulator device according to the invention the response to in flow conditions is simulated more accurately and the effect of the drug may differ to a large degree between flow or static conditions. Likewise, the cytotoxicity of a drug with respect to cells in the fluid or otherwise may be tested. A flow simulator device or method according to the invention may also be used for pumping a fluid through a medical device which lies outside the fluid channel. In that case, the flow simulator device or method is used for pumping a fluid through the medical device. FIG. 5 schematically shows a medical device, e.g. a dialysis apparatus 10, connected to a flow simulator device 1 which is used as a pumping device. The flow simulator device 1 is supposed to be implemented as in the example of FIG. 2. However, the flow simulator device 1 may likewise be implemented in a different manner. The locks of the body 21 are connected to a pump side inlet 110 and a pump side outlet 111 of the dialysis apparatus 10. The locks 24 thus function as a pump inlet 242 and a pump outlet 241 respectively. The dialysis device 10 is further connected to blood vessels in the body 11 of a human via drips 114 connected to a outside inlet 112 and a outside outlet 113 of the dialysis apparatus 10. The outside inlet 112 is connected to the pump side outlet 111 via filtering means, known per se, which remove waste products from the blood passing the filtering means. The pump side inlet 110 is connected to the outside outlet 113, via not shown means. The flow simulator device 1 pumps blood from the pump inlet 241 to the pump outlet 242. Thus, blood is sucked from the body 11 into the dialysis apparatus 10 via the outside inlet 112. The blood passes the filtering means and the, now cleaned, blood enters the flow simulator device 1 via the pump side outlet 111. The cleaned blood is pumped to the pump outlet 241 and back into the body 11 via the pump side inlet 111 dialysis apparatus 10 and outside outlet 113. In the example of FIG. 5, a dialysis apparatus is connected to the flow simulator device according to the invention. However, it is likewise possible to pump a fluid from an animal body into other apparatuses, such as for example, a heart lung machine, an apparatus for blood transfusion or otherwise. It should be noted that the above-mentioned examples illustrate rather than limit the invention, and that those skilled in the art will be able to design alternatives. It should be apparent, for example, that a different type of motor may be used in the mentioned example to provide a swing of the fluid holder. Likewise the fluid channel may be implemented in a different type of fluid holder and may for example be a channel in a closed loop tubing. Likewise, the fluid may be of any type suitable for the specific application and may for example be a organic fluid. Such an organic fluid may for example be a fluid containing hving material, such as blood or lymph cells. The organic fluid may likewise not contain living material but compounds suitable for growing or cultivating living material, such as a growth medium. The organic fluid may for example comprise blood, urine, lymph, saliva, growth medium or otherwise. In the claims, any reference signs placed between parentheses shall not be construed as limiting the claim. The word 'comprising' does not exclude the presence of other elements or steps than those listed in a claim. The word 'a' is used as meaning 'at least one'. The mere fact that certain measures are recited in mutually different claims does not indicate that a combination of these measures cannot be used to advantage.

Claims

1. A method for in vitro simulation of an in vivo fluid flow in an animal body, comprising: positioning a fluid in a fluid channel in a fluid holder; and generating a fluid flow, said generating comprising: swinging said fluid holder from a first position into a second position different from the first position; and swinging said fluid holder back from said second position in a direction towards said first position.

2. A method as claimed in claim 1, wherein said swinging said fluid holder from said first position into said second position different from the first position comprises: rotating said fluid holder in a first rotational direction and said swinging said fluid holder from said second position back into said first position comprises: rotating said fluid holder in a second rotational direction opposite to said first rotational direction.

3. A method as claimed in claim 2, wherein the fluid channel is a closed loop shaped channel and wherein the fluid holder is rotated around a rotation axis which extends in a direction through the fluid holder substantially transverse to an area surrounded by the closed loop shaped channel.

4. A method as claimed in claim 3, wherein the closed loop shaped channel has a substantially annular shape.

5. A method as claimed in any one of the preceding claims, wherein said swinging said fluid holder from the first position into the second position takes a longer time period than said swinging said fluid holder from said second position back into said first position.

6. A method as claimed in any one of the preceding claims, wherein in said swinging said fluid holder back from said second position the fluid holder is brought back into said first position.

7. A method as claimed in any one of the preceding claims, wherein said swinging is performed with a frequency between 0.3 Hz and 5 Hz.

8. A method as claimed in any one of the preceding claims, wherein said fluid channel at least locally has a shape which resembles the shape of a fluid vessel in an animal body.

9. A method as claimed in claim 8, wherein the chamber has a shape which resembles a ventricle of the heart.

10. A method as claimed in any one of the preceding claims, wherein said positioning a fluid comprises: preventing gas-fluid interfaces comprising: fining the fluid channel substantially entirely with the fluid.

11. A method as claimed in any one of the preceding claims, wherein the fluid channel has a wall which at least partially is made of a blood compatible material.

12. A method as claimed in any one of the preceding claims, wherein the fluid channel has a wall which is at least partially made of a semi-permeable membrane, said semi-permeable membrane allowing an exchange between the fluid in the chamber and a space outside the fluid channel.

13. A method as claimed in claim 21, wherein the semi-permeable membrane allows an exchange of at least one gas, such as oxygen or carbon dioxide, between the fluid and said space.

14. A method as claimed in any one of the preceding claims, wherein the fluid comprises an organic fluid, such as an organic fluid in the group consisting of blood, urine, lymph, saliva, and growth medium.

15. A testing method for in vitro testing a device or compound to be used in vivo, comprising positioning a device and/or a compound in a fluid channel of a fluid holder, in vitro simulating a fluid flow in vivo by performing a method as claimed in any one of the preceding claims; and determining at least one property of at least one of the device, the compound or the fluid.

16. A method as claimed in claim 15, wherein said device is constructed to be inserted in a fluid flow in an animal body.

17. A method as claimed in claim 16, wherein said device comprises an implant device, such as one of the group consisting of: heart valves, stents, artificial blood vessels, annuloplasty rings, vena cave filters.

18. A method as claimed any one of claims 15-17, comprising a method as claimed in claim 8 and wherein the device comprises a heart valve and the fluid channel has a chamber in which the heart valve is positioned.

19. A method as claimed in any one of claims 15-18, wherein the device comprises an invasive diagnostic device, such as a catheter or a sensor.

20. A method for pumping a fluid, comprising : providing a fluid inlet in a fluid channel in a fluid holder, connecting the fluid inlet to a fluid supply providing a fluid outlet in the fluid channel; connecting the fluid outlet to a fluid discharge; and performing a method as claimed in any one of claims 1-14.

21. A method as claimed in claim 20, wherein at least one of the fluid inlet and the fluid outlet is connected to an animal body.

22. A method as claimed in claim 20 or 21, wherein at least one of the fluid inlet and the fluid outlet is connected to a fluid processing device, such as a dialysis apparatus.

23. An method for growing a living tissue in vitro, comprising a method as claimed in any one of claims 1-14 and further comprising: positioning living material in said fluid flow and providing nutrition for said living material.

24. A flow simulator device for in vitro simulation of a fluid flow in an animal body, comprising: a fluid holder with a fluid channel; a swinging device arranged for swinging said fluid holder from a first position into a second position different from the first position; and swinging said fluid holder back from said second position in a direction towards said first position..

25. A fluid processing device arranged for processing a fluid, comprising an outside fluid inlet and an outside fluid outlet; a fluid processing device connected to said outside fluid inlet and said outside fluid outlet; a pump side fluid inlet and a pump side fluid outlet, said pump side fluid inlet and outlet being connected to the outside fluid inlet and outlet in such a way that fluid at least once passes the fluid processing device when flowing between the outside fluid and the outside fluid outlet; and a flow simulator device as claimed in claim 24 connected with its fluid channel to the pump side fluid inlet and the pump side fluid outlet.