Extracorporeal blood circulation

Abstract

The invention relates to a method and a corresponding device, by means of which device an extracorporeal, pulsatile blood circulation with purely laminar flow is generated. Without additional shear load caused by the device itself. For this purpose, closed annular channels (12) completely filled with blood (2) are rotated in their main plane. A pulsatile blood flow always in the same direction comes about because the constant rotation of the annular channel (12) is quickly stopped. A laminar blood flow arises relative to the channel and comes to a standstill again. By interruption of the annular channel (12) by means of a blocking device (30), the blood (2) remains at rest relative to the channel even when rotation is started again. The blocking device (30) is not opened again until constant rotation has been reached, and the process is then repeated cyclically. The combination of annular channel (12) and blocking device (30) in one part allows the test setup to be considerably reduced in size. A plurality of samples having a small blood volume can then be tested in parallel by means thereof. When the blood circuit is divided into a movable hose loop (6) having stationary, open hose ends (61) (62) and into an external connection (63) thereto, the device operates as a blood pump.

Description

[0001] Extracorporeal blood circulation

[0002] The innovation concerns a method and a corresponding device with which extracorporeal blood circulation is generated in order, for example, to test the compatibility of foreign materials with blood, i.e. their hemocompatibility.

[0003] These tests are used in medical research as well as in the development and approval of medical devices.

[0004] The state of the art is described in the following documents: 1

[0005] SARODE, DN, Roy, S.: In Vitro models for thrombogenicity testing of blood recirculating medical devices. In: Expert review of medical devices,

[0006] 2019, 16 years, No. 7, pp. 1-29. DOI: 10.1080 / 17434440.2019.1627199

[0007] 2

[0008] ENGELS, G.E., Blok, S.L.J., Van Oeveren, W..: In vitro blood flow model with physiologocal wall shear stress for hemocompatibility testing - An example of coronary stent testing. In: Biointerphases,

[0009] 2016, 11. Jg., Nr.3, S. 031004-1-031004-8. DOI: 10.1116 / 1.4958979

[0010] 3

[0011] VAN OEVEREN, W. Tielliu, I.F., de Hart, J,: Comparison of modified chandler, roller pump, and ball valve circulation models for in vitro testing in high blood flow conditions: Application in thrombogenicity testing of different materials for vascular applications. In: International journal of biomaterials,

[0012] 2012, S. 1 -8. DOI: 10.1155 / 2012 / 673163

[0013] 4

[0014] Online-Enyklopädie „Wikipedia“, Artikel zum Begriff „Check-Valve“ https: / / en.wikipedia.org / wiki / check_valve (aufgerufen am 14.07.2023)

[0015] 5 CYBULSKI, 0., Jakiela, S., Garstecki, P.: Whole Teflon valves for handling droplet. In: Lab on a chip,

[0016] 2016, 16. Jg., Nr.12, S. 2198-2210 DOI: 10.1039 / c6lc00375c

[0017] 6

[0018] BAERT,E.J., et al.: A new dynamic model for in vitro evaluation of intravascular devices. The International journal of artificial organs,

[0019] 2019, 42 Jg., Nr. 1 , S.42-48 DOI: 10.1177 / 0391398818806158

[0020] 7

[0021] SLEE, J.B., et al.: The use oft the ex vivo Chandler Loop Apparatus to assess the biocompatibility of modified polymeric blööd conduits.

[0022] In: JoVe (Journal of Visualized Experiments),

[0023] 2014, Nr. 90 , S. 1-8 DOI: 10.3791 / 51871

[0024] 8

[0025] THORARINSDOTTIR, H., et al.: Blood compatibility of widely used central venous catheters; an experimental study, In: Scientific Reports

[0026] 2022, 12 years, No. 1, pp. 1-10 DOI: 10.1038 / s41598-022-12564-z

[0027] In dynamic blood compatibility tests, the test materials to be examined are exposed to an artificially generated flow of human or animal whole blood. The extent of the changes in the blood then allows conclusions to be drawn about the blood compatibility of the material sample. Various aspects (hemolysis, thrombosis, coagulation, platelet activation, hematology, complement system) are always examined simultaneously.

[0028] The tests must be precisely reproducible to ensure comparable results, and the test setup itself should alter the blood as little as possible. Blood is very sensitive to shear stress during flow. The decisive factor is the peak stress, not the average stress.

[0029] The known experimental setups for hemocompatibility testing each have very specific limitations and disadvantages in this regard. The following experimental setups are commonly used:

[0030] 1

[0031] Blood circulates in closed tubing rings, driven by peristaltic or roller pumps.

[0032] Disadvantages: The shear stress on the blood at the pinch point is significant and unquantifiable. Operating the pump requires highly elastic, but highly damaging, silicone tubing.

[0033] 2

[0034] Tube rings partially filled with blood (Chandler loops) that are rotated upright.

[0035] Disadvantages: The film of blood adhering to the inner wall of the tube is in extensive contact with the air bubble. The U-shaped blood column has deflection zones at each end with turbulent flow and unquantifiable shear stress.

[0036] 3

[0037] Tubing rings completely filled with blood are alternately rotated and counter-rotated by a fixed amount. This creates a pulsating blood flow.

[0038] Disadvantage: The blood changes its direction toward the tube after each pulse. Variants with a check valve, which prevents backflow, cause unacceptable blood damage to the valve.

[0039] 4

[0040] Communicating tubing is pressurized with a protective gas at varying pressures. The blood column oscillates in the U-shaped tubing in rhythm with the pressure changes.

[0041] Disadvantages: The blood flow changes direction relative to the tube.

[0042] The U-shaped blood column, like the Chandler loop, has two deflection zones at its ends, with turbulent flow and unquantifiable shear stress. Disadvantages

[0043] All known experimental setups cause an additional, unquantifiable shear stress on the blood during operation.

[0044] The blood is therefore changed by the experimental setup itself.

[0045] Task

[0046] The task was therefore to find an in-vitro experimental setup that would avoid this disadvantage and realize a pulsating, extracorporeal blood circulation that would not subject the blood to any additional shear stress and also keep the flow direction constant.

[0047] Solution

[0048] The object of the invention is achieved by the method and device according to the invention. A cyclically repeated, always unidirectional rotational acceleration induces a pulsating, laminar blood flow in the same direction in tubing rings completely filled with blood. The blood flow is controlled by a check valve designed for optimal flow and only changes its state when the blood is stationary. No turbulence occurs when the valve is closed or opened, and none occurs during unimpeded flow.

[0049] Advantage

[0050] The blood flow is pulsatile, but always purely laminar and in the same direction. The blood is not subjected to any additional shear stress.

[0051] The shear stress is determined exclusively by known parameters, which can be modified and quantified. The highly compact design allows for a large number of small-volume blood samples to be examined simultaneously.

[0052] The method according to the invention generates a pulsating, extracorporeal

[0053] Blood circulation in a consistent flow direction using a closed, completely blood-filled annular channel rotated in its main plane by a drive. The procedure involves the following steps:

[0054] - Switching the ring channel between two states with constant rotation at different speeds;

[0055] - Blocking or opening the ring channel, only when the blood is at rest relative to the ring channel.

[0056] The device according to the invention serves to generate pulsating, extracorporeal blood circulation in a consistently consistent flow direction using a closed, completely blood-filled annular channel rotated in its main plane by a drive. The annular channel is configured to alternate between at least two states with constant rotation at different speeds.

[0057] According to a first, independent aspect of the invention, the device comprises at least one blocking device configured to completely interrupt or open the blood flow in the annular channel. The blocking device is configured to change the state of the blocking device only when the blood is at rest relative to the annular channel. The blocking device comprises two slides that are rotatably movable relative to one another, have a common axis of rotation, and have a common, rotationally symmetrical sealing surface. Furthermore, the annular channel is divided, preferably approximately in half, the halves of which each form a part with a slider of the blocking device. The blocking device has openings approximately perpendicular to the sealing surface.

[0058] Furthermore, the device can have a plurality of annular channels, each having a half and a slide forming a part. The blocking device can be detachably coupled to the drive. In addition to the blocking and passage positions, the blocking device can have a further position for completely filling the annular channel. According to a second, independent aspect of the invention, the device has, instead of the blocking device, a blocking valve configured to completely block and open the blood flow in the tubing ring. The blocking valve is also configured to change its state only when the blood is at rest relative to the tubing ring. The blocking valve consists of two valve slides that are rotatably movable relative to one another.The valve slides share a common rotational axis, a common, rotationally symmetrical sealing surface, and each have flow holes approximately perpendicular to the common sealing surface and with the same cross-section as the hose. The device also features a shut-off valve drive located in the center of the hose ring.

[0059] The check valve can also be detachably coupled to its drive. The rotating device can be configured to rotate several complete hose ring check valve units simultaneously. In addition to the blocking and passage positions, the check valve can also have an additional position for completely filling the hose ring.

[0060] According to a third, independent aspect, the device comprises a hose loop movable in its main plane with stationary hose ends, an external connection of the open hose ends, and a stationary check valve configured to completely block or open the blood flow in the circulatory system. The hose loop is configured to be rotated by a drive in alternating directions around a central position between the stationary hose ends. The check valve is configured to change its state only when the blood is at rest relative to the hose loop. When the check valve is open, the angular velocity of the rotating hose loop always increases or decreases. Further details or advantageous developments can be found in the drawings, the description, and the patent claims. The innovation is illustrated by the following figures:

[0061] Fig.1 Schematic section through a hose ring 1 in the plane of rotation with open check valve 3;

[0062] Fig.2 Schematic section through a hose ring 1 in the

[0063] Rotation plane with closed shut-off valve 3;

[0064] Fig.3 Diagram showing the angular velocity w of the hose ring 1 with two alternating constant velocities (w1 >0, CÜ2=0), the switching position (open / switching is shown hatched / closed) of the shut-off valve 3 and the volume flow Q of the blood 2 in the hose ring 1 along a common time axis t;

[0065] Fig.4 diagram according to Fig.3, wherein the hose ring 1 is moved with two alternating constant rotational speeds of different rotational directions (w1 >0, w2<0) in the rotation plane;

[0066] Fig.5 Isometric view of a compact arrangement of the

[0067] Components with disconnected hose ring 1 / check valve 3 unit;

[0068] Fig.6 Isometric view of a compact arrangement of the

[0069] Components with coupled hose ring 1 / check valve 3 unit;

[0070] Fig.7 Partially transparent, isometric illustration of the locking device with integrated, uninterrupted ring channel 12;

[0071] Fig.8 Partially transparent, isometric illustration of the locking device with integrated, interrupted ring channel 12;

[0072] Fig.9 Sectional view through a locking device with integrated annular channel 12 and flat sealing surface 33 in the plane of rotation;

[0073] Fig.10 Sectional view through a locking device with integrated annular channel 12 and cylindrical sealing surface 33 in the plane of rotation;

[0074] Fig.11 Sectional view through a locking device with integrated annular channel 12 and conical sealing surface 33 transverse to the plane of rotation;

[0075] Fig.12 Schematic longitudinal section through two concentrically rotatable valve slides 31, 32 with integrated, uninterrupted annular channel 12;

[0076] Fig.13 Schematic longitudinal section through two concentrically rotatable valve slides 31, 32 with integrated, interrupted annular channel 12;

[0077] Fig.14 Schematic view of the device as a blood pump, with an external connection to a utility circuit 63. Embodiments

[0078] A polymer tube is formed into a tube ring 1, completely filled with blood 2, and releasably sealed. The tube joint is designed as a check valve 3. The check valve 3 is fully open and allows blood 2 to flow through it without disruption.

[0079] The tubing ring 1 is rotated at a constant speed in its main plane. The blood 2 is at rest relative to the tubing ring 1.

[0080] If the rotation of the tubing ring is stopped, a force acting in the direction of rotation, caused by the change in rotation speed, acts on the blood. This causes a laminar flow of blood 2 relative to the tubing ring 1.

[0081] This laminar flow steadily decreases and comes to a standstill. A flow pulse of blood 2 develops relative to the tubing ring 1. The check valve 3 is then completely closed.

[0082] When closing, no turbulence occurs in the still blood 2.

[0083] If the stationary tubing ring is accelerated back to its original rotation, no flow of blood 2 occurs because the circuit is interrupted by the check valve 3. The blood 2 remains at rest relative to the tubing ring 1.

[0084] The accelerated rotation returns to a constant rotation.

[0085] If the shut-off valve 3 is now also fully opened again, no turbulence will occur in the still blood.

[0086] When this process is repeated cyclically, the blood 2 moves in a pulse-like manner and without turbulence in the hose ring 1, always in the same direction.

[0087] The flow direction of blood 2 is not determined by the direction of rotation of the tubing ring 1, but rather by whether the angular velocity w of the tubing ring 1 increases or decreases when the valve is open. A constant direction of the flowing blood 2 relative to the tubing ring 1 can therefore be achieved both with a constant direction of rotation (see Fig. 3) and with alternating directions of rotation (see Fig. 4). With alternating directions of rotation, the movement of the tubing ring 1 can oscillate around a central position.

[0088] The sum of the forces acting on the blood 2 in the closed tubing ring 1 during a change in velocity, causing the flow, does not depend on the location of the center of rotation. The center of rotation can be freely chosen on the rotation plane. It can be located centrically or eccentrically to the tubing ring 1 at any distance.

[0089] To ensure that blood 2 can flow smoothly through the open check valve 3, it is advantageous to design it as a slide valve. The check valve 3 then has no dead volume when closed.

[0090] Two valve slides 31, 32 each have a common sealing surface 33 and a bore perpendicular to it, which corresponds to the outer diameter of the hose ring 1. In each case one end of the hose ring 1 fits tightly into a bore in the check valve 3. The check valve 3 therefore also fulfills the function of closing the hose ring 1. If the bores are aligned, the blood 2 in the hose ring 1 can flow unhindered through the check valve 3. If the valve slides 31, 32 are moved against each other so that the bores do not overlap, the flow is blocked. The bores can preferably be designed as stepped bores. In this case, the smaller diameter on the side of the sealing surface corresponds to the inner diameter of the hose ring 1. The valve slides 31, 32 have a common axis of rotation 34. The centers of the bores then lie on a common circular line.

[0091] The valve slides 31, 32 are moved relative to one another by a drive of the check valve 4. A compact design and good handling are achieved when the drive of the check valve 4 is arranged in the center of the hose ring 1. The drive of the check valve 4 is connected to the rotating device 5 of the hose rings 1 by a synchronization device. To facilitate handling of the complete hose rings 1 closed with the check valve 3, the connection from the check valve 3 to its drive 4 can be designed to be mechanically detachable. The complete rings can then be handled separately for filling the hose rings 1 or for withdrawing the blood 2 after the end of the test procedure.

[0092] To facilitate the complete filling of the tube rings 1 with blood 2, the valve slides 31, 32 can be rotated into a further filling position in addition to the two basic positions of complete closure or opening. The ends of the tube ring 1 are then each directly connected to a filling opening and a vent opening. The open tube ring 1 then behaves like communicating tubes. For filling, the filling opening and the vent opening must be located at the highest point of the tube system.

[0093] The rotating device 5 is designed so that the rotation parameters (speed, acceleration, and cycle duration) are adjustable and reproducible. The upper speed range is limited by the centrifugal effect, which initiates separation into the blood components.

[0094] The rotating device 5 can be designed so that several hose rings 1 can be rotated simultaneously in order to carry out tests in parallel.

[0095] The axis of rotation can basically be oriented vertically, horizontally or at any angle in between.

[0096] With the rotation axis of the rotating device 5 aligned horizontally, it can also be used for tests with Chandler loops. This makes it possible to conduct comparative measurements to quantify design-related interference in the Chandler loop, such as air entrapment. Against this background, it is sensible to provide two different operating modes for the rotating device 5, one of which is for standard Chandler loop tests.

[0097] Blood compatibility tests are particularly meaningful when comparative tests are conducted using blood from a single donor. This requires test setups that utilize the smallest possible blood volume, i.e., ring channels 12 or tubular rings 1 with low filling volumes.

[0098] A variant of the device described for this purpose combines an annular channel 12 with the check valve 3.

[0099] A half-segment of the annular channel 12 is incorporated into each of the two valve slides 31 and 32. At the common sealing surface 33, the corresponding cross-sections of the annular channel segments meet seamlessly and almost perpendicularly. In this state, blood 2 can flow through the annular channel 12 unhindered.

[0100] If the valve slides 31, 32 rotate against each other around the common axis of rotation 34, an offset occurs at the transition cross-sections of the annular channel 12, up to a complete interruption.

[0101] Based on the combination of check valve 3 and ring channel 12 into one part, a variety of designs are possible.

[0102] An advantageous possibility is to combine a large number of these check valve ring channel combinations for parallel tests and to switch them through a common drive 4.

[0103] The generation of a pulsating blood flow of the type described can also be used as a blood pump.

[0104] It is sufficient if only a portion of the hose ring 1 is moved. The rest of the hose ring 1 can remain stationary. For this purpose, the hose is not closed into a ring at the joint, but forms an open hose loop 6 with an inlet 61 and an outlet 62.

[0105] The check valve 3 is located at one of the hose ends 61 or 62. The hose ends 61, 62 with the check valve 3 are stationary.

[0106] They can then be closed externally to form a useful circuit 63 and completely filled with blood 2.

[0107] The hose loop 6 is movable in the loop plane and can be rotated by a drive 5.

[0108] The mobility of the hose loop 6 corresponds, within the limits of the stationary hose ends 61, 62, to that of the freely rotating hose ring 1. The behavior of the blood 2 due to the acceleration of the rotation and the transition to a constant rotation as well as the switching of the shut-off valve 3 exclusively in the absence of blood flow is also identical.

[0109] The stationary hose ends 61, 62 require the hose loop 6 to swing around a central position with reversal of the direction of rotation as shown in Fig.4.

[0110] When the shut-off valve 3 is open, the angular velocity of the rotating hose loop 6 must always increase or decrease.

[0111] Then the flow direction of blood 2 remains constant.

[0112] The innovation concerns a method and a corresponding device with which an extracorporeal, pulsating blood circulation with purely laminar flow is generated.

[0113] Without additional shear stress from the device itself.

[0114] For this purpose, closed annular channels 12, completely filled with blood 2, are rotated in their main plane. A pulsating blood flow in the same direction is achieved by rapidly stopping the constant rotation of the annular channel 12. A laminar blood flow is created relative to the channel, which then stops again. By interrupting the annular channel 12 with a blocking device 30, the blood 2 remains at rest relative to the channel even when the channel is rotated again. The blocking device 30 is only opened again after a constant rotation has been achieved, and the process is then repeated cyclically.

[0115] The combination of the annular channel 12 and the blocking device 30 in one piece allows for a significant reduction in the size of the test setup. A large number of samples with low blood volumes can then be tested in parallel.

[0116] When the blood circuit is divided into a movable hose loop 6 with stationary, open hose ends 61, 62 and an external connection 63 thereto, the device operates as a blood pump.

[0117] List of reference symbols

[0118] 1 hose ring

[0119] 12 ring canal

[0120] 2 Blood

[0121] 3 shut-off valve

[0122] 31 Valve spool A

[0123] 32 Valve spool B

[0124] 33 Sealing surface

[0125] 34 Axis of rotation of the slide

[0126] 4 Actuator of the shut-off valve

[0127] 5 Rotating device

[0128] 6 hose loop

[0129] 61 Hose end A

[0130] 62 Hose end B

[0131] 63 External connection to a utility circuit

Claims

Patent claims 1 . Method for generating a pulsating, extracorporeal Blood circulation in a consistently constant flow direction, with the aid of a closed annular channel (12) which is completely filled with blood (2) and rotated in its main plane by a drive (5), the annular channel (12) alternating between at least two states with constant rotation at different speeds, with at least one blocking device which can completely interrupt or open the blood flow in the annular channel (12), which only changes its state when the blood (2) is at rest relative to the annular channel (12), characterized in that a) the blocking device consists of two slides (31) (32) which are rotatably movable relative to one another, with a common rotation axis (34), with a common, rotationally symmetrical sealing surface (33) b) the annular channel (12) is divided approximately in half, the halves of which form one part with each slide (31) or (32), with openings approximately perpendicular to the sealing surface (33) 2. Method according to claim 1, characterized in that several ring channels (12), each with one half forming a part with a slide (31) or (32).

3. Method according to claim 1 or 2, characterized in that the locking device is detachably coupled to its drive (4).

4. Device according to one of claims 1 to 3, characterized in that the locking device is arranged next to the positions of the Blocking and the passage has another position for completely filling the annular channel (12).

5. Device for generating a pulsating, extracorporeal blood circulation in always the same flow direction by means of a closed hose ring (1) which is completely filled with blood (2) and rotated in its main plane by a drive (5), wherein the hose ring (1) changes between at least two states with constant rotation at different speeds, with a check valve (3) which can completely block or open the blood flow in the hose ring (1), which only changes its state when the blood (2) is at rest relative to the hose ring (1), characterized in that a) the check valve (3) consists of two valve slides (31) (32) which are rotatably movable relative to one another, with a common axis of rotation (34), with a common,rotationally symmetrical sealing surface (33) with flow holes approximately perpendicular to the common sealing surface (33) in the same cross-section as the hose b) with a drive of the check valve (4) which is arranged in the center of the hose ring (1).

6. Device according to claim 5, characterized in that the shut-off valve (3) is detachably coupled to its drive (4).

7. Device according to claim 5 or 6, characterized in that the rotating device (5) can rotate several complete hose ring (1) - shut-off valve (3) units simultaneously.

8. Device according to one of claims 5 to 7, characterized in that the shut-off valve (3) has, in addition to the positions of the blocking and the passage, a further position for completely filling the hose ring (1).

9. Device for generating a pulsating, extracorporeal blood circulation in a constantly identical flow direction in a closed circuit completely filled with blood (2), comprising a hose loop (6) which is movable in its main plane and has stationary hose ends (61) (62), an external connection (63) of the open hose ends and a stationary shut-off valve (3) which can completely shut off or open the blood flow in the circuit, characterized in that a) the hose loop (6), rotated in alternating directions by a drive (5) around a central position between the stationary hose ends (61) (62) b) the shut-off valve (3) only changes its state when the blood (2) is at rest relative to the hose loop (6), c) when the shut-off valve (3) is open, the angular speed of the rotating hose loop (6) always increases or always decreases.

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