Rotor for a centrifuge and centrifuge comprising such a rotor

Abstract

Rotor for a centrifuge, said rotor having a receiving area for receiving reaction vessels (4), wherein the rotor (1) comprises a plurality of receiving areas (3) that are at different distances from a rotation axis (12) of the rotor.

Description

[0001] 23 / 01 / 2026

[0002] International patent application

[0003] BlueCatBio GmbH

[0004] P392518WO

[0005] Rotor for a centrifuge and centrifuge with such a rotor

[0006] The present invention relates to a method and a centrifuge for introducing a target substance, in particular living cells, into a retention area of ​​at least one reaction vessel, or a centrifuge for centrifuging a reaction vessel unit, and a method for emptying reaction vessels, or a method for centrifuging and a centrifuge suitable for this purpose, or a rotor for a centrifuge, and a centrifuge with such a rotor.

[0007] It is known to concentrate a target substance, particularly living cells, in a liquid solution at the bottom of a reaction vessel by centrifugation. Centrifuges can be used that generate a centrifugal acceleration of approximately 300–800 g, which is typically applied for several minutes (e.g., 3–8 minutes). This causes the cells to collect at the bottom of the reaction vessel and clump together slightly, allowing the remaining liquid in the reaction vessel to be separated from these cell clumps, e.g., by aspiration with a pipette. Methods are also known in which centrifugal accelerations of several thousand g are generated and / or the duration of centrifugation exceeds 15 minutes.

[0008] WO 2023 / 110944 A1 discloses a method for introducing a target substance into a retention area of ​​a reaction vessel. This method utilizes a reaction vessel unit comprising at least one reaction vessel with a receiving chamber for a liquid. The receiving chamber includes a retention area with a surface texture and / or shape such that, due to an adhesive force between the liquid and the retention area, and cohesion within the liquid, the retention area exerts a stronger holding effect on the liquid compared to the surrounding area. This allows a predetermined small quantity of liquid to be retained at or within the retention area when the remaining liquid is removed from the receiving chamber by centrifugation.The retention area can be formed by a surface structure that increases the adhesion to the liquid, in particular by a suitable coating. The retention area can also be formed by a capillary cavity.

[0009] In this process, the target substance contained in the liquid can be concentrated in the retention area by centrifugation.

[0010] After concentrating the target substance in the retention area, the remaining liquid can be centrifuged out of the reaction vessel, leaving only the liquid located in or on the retention area in the reaction vessel.

[0011] US 2008 / 0003640 A1 discloses a double-sided microtiter plate with cylindrical wells that can retain fluid due to surface tension, capillary action, or suitable treatment, coating, or texturing of the walls.

[0012] US 2011 / 0278304 A1 shows suspended vessels in microtiter plates that can serve as a natural barrier.

[0013] US 8,602,958 B1 discloses a microtiter plate in which, during centrifugation, the outwardly directed reaction vessels release their liquid and the reaction vessels are emptied accordingly.

[0014] US 2021 / 138485 A1 and US 11,117,142 B2 disclose centrifugation devices for cleaning a reaction vessel assembly. With these centrifugation devices, the reaction vessels are positioned with their openings facing away from the axis of rotation, so that during centrifugation, the liquid contained in the reaction vessels is ejected. It has been shown that this method removes the liquid from the reaction vessels completely and achieves a high degree of purity. Reaction vessels cleaned in this way can be reused for biological reactions in which a single molecule, especially a strand of DNA or RNA, may represent an intolerable contaminant. Ejecting liquid from the reaction vessels by centrifugation can also be referred to as "washing by centrifugation," and such a washing process can be performed with or without the addition of a washing solution.

[0015] WO 2015 / 018878 A2 describes a centrifuge for cleaning reaction vessels, in which the contents of the reaction vessels are extracted. This centrifuge has a loading mechanism located at the rear of a rotor chamber. This loading mechanism can draw a reaction vessel unit into or out of the rotor chamber by means of a flexible metal belt, whereby the free end of the flexible metal belt can be moved completely through the rotor chamber from the rear of the rotor chamber to move the reaction vessel unit accordingly.

[0016] WO 2023 / 148272 A1 discloses a draining device that can be used in a centrifuge for cleaning reaction vessel units. The draining device has a drain plate that can be positioned in the centrifuge opposite the openings of the reaction vessels of a reaction vessel unit such that the surface of the drain plate is inclined in the direction of the axis of rotation of the centrifuge, so that during centrifugation, liquid escaping from the reaction vessels due to centrifugal acceleration is collected by the drain plate and discharged laterally.

[0017] WO 2017 / 146542 A1 describes a centrifuge comprising a first rotor and a second rotor within a single housing. The two rotors can be driven independently. The first rotor is positioned further inward than the second rotor, but both rotors share the same axis of rotation. The receiving areas for reaction vessels are arranged at the same distance from the axis of rotation within each rotor, but at different distances between the two rotors.

[0018] US patent 2016 / 0250608 A1 discloses a mixing device, which can also be configured as a centrifuge. The mixing device has a head that can be coupled to the centrifuge and includes a holding body with horizontal channels for each test tube. The channels are arranged at varying distances from the axis of rotation.

[0019] WO 2023 / 110944 A1 shows a rotor with two diametrically opposed recording areas. The two recording areas are equidistant from the axis of rotation.

[0020] From DE 102017 112 553 A1 a centrifuge is known with which a liquid phase can be separated from solids.

[0021] US Patent 2015 / 0174591 A1 describes the use of a centrifuge to remove red blood cells from whole blood and retain platelets and other factors in a reduced plasma volume. Platelet-rich plasma (PRP) and / or platelet-poor plasma (PPP) can be rapidly obtained and are immediately ready for injection into the host.

[0022] One object of the invention is to further develop the method or centrifuge described above in such a way that a target substance, in particular living cells, can be introduced into a retention area of ​​a reaction vessel by centrifugation with high efficiency and quality. This object is achieved by the subject matter of the independent claims. Advantageous embodiments are specified in the respective dependent claims.

[0023] As explained earlier, conventional methods involve centrifuging a target substance, particularly live cells, in a liquid solution for several minutes until the cells form a clump or pellet at the bottom of the reaction vessel. The liquid can then be easily separated from the cell clump by aspiration with a pipette. This allows the cells to be exposed to different solutions. This method is primarily used to wash cells, i.e., to remove foreign contaminants. Cells purified in this way are often examined using flow cytometry. In this process, the cells are individually passed through a counter tube, where they are optically excited to emit fluorescence radiation, which is then detected and analyzed.Although clumping significantly simplifies the separation of cells from the liquid, it can be a disadvantage in subsequent processes, especially when the cells need to be examined individually, as is the case, for example, in flow cytometry. The cells then have to be separated from the clump, which is not trivial and can also lead to cell damage.

[0024] The invention is based on the finding that centrifuging a target substance, particularly living cells, with a centrifugal acceleration of approximately 300-800 g for several minutes (e.g., 3-6 minutes) leads to such strong clumping of the cells that, after reintroduction of a solution, the target substance or the cells can no longer dissolve completely and are only available to a small extent for subsequent process steps. Furthermore, the cells are stressed by the prolonged centrifugal force, which affects the biological outcome of the experiment, e.g., by activating signal transduction pathways.

[0025] The inventors also recognized that prolonged centrifugal force can damage some of the cells.

[0026] The inventors conducted extensive series of experiments, initially focusing on methods with lower centrifugal acceleration, as they assumed this would cause minimal cell damage. Centrifugal accelerations of 20-100 g were tested for varying centrifugation durations. The results were better than with conventional centrifugal methods, but not entirely satisfactory, as either an insufficient number of cells were concentrated in the retention area, or they tended to clump together, or they were damaged. The inventors realized that, unlike conventional centrifugation methods, high centrifugal accelerations in the range of, for example, 300-800 g were not harmful to the target substances being centrifuged, especially living cells, provided the cells were in solution. Therefore, the inventors concluded that the centrifugation should not be performed for too long.

[0027] In the inventive method for introducing a target substance, in particular living cells, into a retention area of ​​at least one reaction vessel, a reaction vessel is used in which the retention area is located in the region of the bottom of the reaction vessel. A sample comprising a target substance in a liquid solution is centrifuged such that the target substance concentrates in the retention area. The method is characterized in that a predetermined centrifugal acceleration a is applied to the target substance during centrifugation, and a maximum settling time of the target substance is estimated based on at least the centrifugal acceleration and the viscosity of the liquid solution, wherein the centrifugation is not performed for more than ten times the maximum settling time and the centrifugal acceleration a is at least 100 g.

[0028] Since the centrifugation process always involves accelerating and decelerating the rotor, it is advantageous for the centrifugation duration to be longer than the estimated settling time. The shorter the acceleration and deceleration phases, the smaller the time difference can be compared to the estimated settling time.

[0029] The invention is further based on the understanding that the particles of the target substance, in particular the cells, are not damaged during centrifugation as long as they remain in the solution of the sample. Only when the target substance has reached the bottom of the reaction vessel or has formed a clump of several particles of the target substance can the centrifugal force exerted by the centrifuge completely or partially damage the cell. Since the duration of the centrifugation is limited to ten times the maximum settling time, the risk of damage to or unacceptable clumping of the cells to be concentrated is low.

[0030] A centrifugation duration ten times the maximum settling time is significantly shorter than the conventional centrifugation duration of a few minutes. During such a centrifugation time, the particles, especially cells, concentrate in the retention area without clumping together. They are then available individually for subsequent processing. For flow cytometric analysis, it is necessary that the cells are available and analyzed individually. Even two adjacent cells (duplets) are often excluded from further analysis. The centrifugal acceleration applied during centrifugation is preferably at least 100 g and particularly at least 250 g, where g is the acceleration due to gravity of 9.81 m / s². 2Preferably, the centrifugal acceleration is at least 500 g or at least 600 g, and can even be a multiple of 600 g. To minimize the overall duration of the centrifugation process, it is ideal if the centrifuge used can accelerate and decelerate as quickly as possible. Preferably, the centrifuge reaches a centrifugal acceleration of 1000 g in less than 3 seconds, or at least in less than 5 seconds, and decelerates just as quickly. The time spent accelerating and decelerating also contributes to the settling time, which is particularly significant for commercially available benchtop centrifuges that require 20-30 seconds to accelerate to 600 g and must be taken into account when calculating t.

[0031] Preferably, the centrifugation time should not exceed 5, 2.5, 1.5, or 1.2 times the maximum settling time. Experience has shown that centrifuging for slightly longer than the estimated maximum settling time is sufficient. Longer centrifugation does not significantly increase the amount of target substance or cells in the retention area. However, excessively long centrifugation times lead to cell clumping and can damage the cells.

[0032] The descent time is preferably estimated using the following formula:

[0033]

[0034] where

[0035] t is the maximum settling time for a particle to settle from a radius Ri to a radius Rf,

[0036] D is the diameter of the target substance particles

[0037] ] the fluid dynamic viscosity of the liquid solution [Pa s],

[0038] Rf is the target radius [m]

[0039] Ri is the initial radius [m]

[0040] p P the specific weight of the particles [kg / m³] 3 ],

[0041] pf is the specific gravity of the liquid solution [kg / m³]. 3 ]

[0042] ei) Angular velocity [rad / s] If the particles have different diameters, then preferably the minimum diameter of the particles is used, as this determines the maximum settling time. However, if the particle diameter should extend over a larger range and the majority of the particles should lie within a relatively narrow range, then it may also be appropriate to use the mean or median of the particle diameters.

[0043] The target radius Rf is the radius extending from the axis of rotation to the radially outer edge of the retention area. The initial radius Ri is the radius extending from the rotor's axis of rotation to the surface of the sample in reaction vessel 4. The difference between the target radius Rf and the initial radius Ri is the distance a particle in the solution must travel to reach the retention area from the solution surface, assuming the particle moves in a straight line along the radius.

[0044] This formula allows for a very precise estimation of the settling time of particles in a liquid solution when these particles are located in a reaction vessel that has essentially vertical side walls opposite a bottom wall, so that the particles in the liquid solution can move in a straight line towards the bottom wall during centrifugation.

[0045] At least one reaction vessel can have a conical shape, and the maximum settling time can then be estimated based on the shape of the vessel, taking into account a recoil effect of the target substance particles against a conical section of the vessel. During centrifugation, the target substance particles are moved against the walls of the conical section of the reaction vessel, which are inclined relative to the vessel's longitudinal axis, and are reflected by them. The particles thus collide elastically with the vessel wall and are deflected back into the receiving chamber of the vessel filled with the liquid solution. This increases the distance traveled by the individual particles as they settle towards the retention area, thereby extending the settling time accordingly.

[0046] Such a corrected descent time can be estimated using the following formulas:

[0047]

[0048] where RÜ is the radius from the axis of rotation to the top of the fill level in the reaction vessel and Rfi is the radius from the axis of rotation to the top of the funnel in the reaction vessel, !

[0049] sln(90° - / 7 - A)' (4)

[0050] where Ri2 is the radius from the axis of rotation to the top edge of the funnel in the reaction vessel, Rf2 is the radius of the axis of rotation to the bottom edge of the funnel in the reaction vessel, and β is the angle of deviation of the centrifugal acceleration vector.

[0051] from the longitudinal axis of the reaction vessel, and

[0052] A the angle between the longitudinal axis of the reaction vessel and the wall

[0053] of the reaction vessel in the conical area of ​​the reaction vessel.

[0054] The first term of this formula (4) for the funnel corresponds to that of the formula (1) explained above or to formula (3). The second term is a correction term that describes the extension of the distance traveled.

[0055] The first term of formula (4), or formulas (1) and (3), is exact only if the particle moves in a straight line from the top of the liquid, parallel to the longitudinal axis of the reaction vessel. In practice, however, some particles are inherently located closer to the retention area and therefore have a shorter distance to travel. Furthermore, the centrifugal force is not aligned parallel to the longitudinal axis in all reaction vessels, as explained in more detail below. This results in variations in the actual time the particles take to reach the retention area. These variations are small, but therefore determining the maximum settling time is an estimate. However, this estimate, even though it contains inaccuracies, is sufficient to significantly improve the quality of the target substance in the retention area compared to conventional methods.

[0056] A deviation of the centrifugal acceleration vector from the longitudinal axis of the reaction vessel occurs when the respective reaction vessel is positioned with its longitudinal axis obliquely relative to the radius of the rotor extending through it. This is the case when a reaction vessel unit is used that comprises multiple reaction vessels, where the reaction vessels are arranged with their respective longitudinal axes parallel to each other and in a single plane, with multiple reaction vessels distributed along the rotor in the direction of rotation. In such a case, the rotor has a radius perpendicular to the plane of the reaction vessel unit. This radius is referred to as the rotor radius. However, there are other radii on the rotor that pass through the reaction vessels and are not located within the region of the rotor radius. These other radii form an angle with the rotor radius.The further the reaction vessels are from the rotor radius, the greater the inclination of the longitudinal axis of the respective reaction vessel relative to the radius extending through the respective reaction vessel. Accordingly, the deviation of the centrifugal acceleration vector from the longitudinal axis of the reaction vessel is also greater the further the reaction vessel is from the rotor radius.

[0057] The reaction vessels can be rotationally symmetrical, featuring a rotationally symmetrical conical section that opens into the retention area. However, reaction vessels can also be non-rotationally symmetrical, for example, with a retention area that is elongated with two short and two long sides. In such a shaped retention area, the wall section of the reaction vessels adjacent to the short sides is significantly steeper than the wall section adjacent to the long sides. With this type of reaction vessel design, the wall length Sw, the length of the wall in the shallowly inclined section, is used to estimate the maximum settling time, since the majority of the target substance particles enter the retention area along this wall.

[0058] Tests have shown that this correction value provides a very good estimate of the maximum settling time. However, it does not account for collisions between individual particles of the target substance. It is assumed that these collisions lead to a further, slight increase in the maximum settling time. Therefore, it is advisable to perform centrifugation for slightly longer than the estimated maximum settling time.

[0059] The conical section of the reaction vessel can have an angle A of at least 25° or at least 30° with respect to the longitudinal axis of the reaction vessel. The angle should preferably not exceed 70° and, in particular, not exceed 50°. With an inclination of more than 50°, there is a risk that, when using a reaction vessel unit in which the reaction vessels are arranged far from the rotor radius, the deviation of the centrifugal acceleration from the longitudinal axis of the reaction vessel could create a situation where the centrifugal acceleration is approximately perpendicular to the wall of the reaction vessel or even forms an angle of more than 90° between the centrifugal acceleration and the wall region located radially outside the point of impact of the particles or the vector of the centrifugal acceleration on the wall.In such a situation, the reflection of the target substance particles off the inclined wall would cause them to be reflected radially outwards, thus moving them away from the center of the rotor. The particles would therefore also be moved away from the containment area, which is obviously undesirable. This effect is greater the smaller the rotor. Therefore, such shallow wall sections should be avoided in rotors with a small radius.

[0060] Steep wall sections have the advantage that the number of reflections from the target substance particles on the inclined wall is low, which in turn leads to a short settling time. On the other hand, the steeper the walls of the respective reaction vessel, the smaller the volume for a given height. It should be noted that for most applications, the height of reaction vessel units I cannot be arbitrarily high, as the plates must be compatible with other steps in a workflow. At the same time, it is advantageous to maximize the filling volume for a given height. With steep walls, this results in the shape of a slim, short tube with a small volume. An inclination A of approximately 35° of the inclined walls relative to the longitudinal axis of the respective reaction vessel has proven to be a good compromise.

[0061] The retention area is preferably designed as a capillary cavity. A capillary cavity is a region of the reaction vessel where the walls are so closely spaced that a liquid is held within the cavity by capillary action. In a capillary cavity, there is a large surface area between the liquid and the cavity, resulting in a correspondingly high adhesive force due to interfacial tension. Furthermore, cohesion within the liquid, due to surface tension, holds the liquid molecules together so tightly that they are not carried away when the rest of the receiving space is emptied. The capillary action thus arises according to the specific adhesive and cohesive forces.In particular, during the centrifugation of the liquid, the liquid volume in the receiving chamber of the reaction vessel above the capillary cavity will separate from the liquid volume within the capillary cavity, and atmospheric air will flow into the receiving chamber. This creates an interface at the opening of the capillary cavity, and the surface tension at this interface significantly contributes to the holding effect. The capillary cavity can be designed as a depression in the bottom or side wall of the receiving chamber. The opening of the capillary cavity is preferably located in the center of the bottom wall. However, it can also be positioned off-center.

[0062] The capillary cavity preferably has a volume of not less than 1 pl and / or not more than 50 pl or not more than 20 pl or not more than 10 pl.

[0063] The capillary cavity preferably has a diameter of at least 0.75 mm, and particularly at least 1 mm, at its opening into the rest of the reaction vessel. Such a large opening of the capillary cavity is advantageous so that dispensing can still be carried out easily in step 3 and so that an aspiration needle of a flow cytometer can fit into the capillary cavity to allow for the withdrawal of any residual volume.

[0064] On the other hand, it is preferred that the diameter of the capillary cavity opening is no more than 3 mm and, in particular, no more than 2 mm. Specifically, the capillary cavity has no larger diameter in any cross-section perpendicular to the longitudinal axis of the respective reaction vessel. This ensures that the capillary force with which a liquid is held in the capillary cavity is high.

[0065] At least one reaction vessel can be part of a reaction vessel unit, where the reaction vessel unit comprises several reaction vessels arranged in a single plane. Such reaction vessel units are most commonly found in the form of standardized microtiter plates with, for example, 96, 384, or 1536 reaction vessels. These microtiter plates are defined by the ANSI SLAS 4-2004 (R2012) standard.

[0066] Centrifugation is preferably carried out using a centrifuge with a radius of at least 7 cm, and in particular at least 9 cm. The larger the radius, the smaller the deviations in the direction of centrifugal acceleration from the longitudinal axis of the reaction vessels when the reaction vessels are located far from the rotor radius. It has been shown that, in practice, at least for standardized microtiter plates, a centrifuge radius of no more than 20 cm, and in particular no more than 15 cm, and especially no more than 12 cm, is sufficient to keep this deviation low.

[0067] According to another aspect, a centrifuge is provided which includes a rotor with a shaft and a receiving area for receiving reaction vessels, wherein this centrifuge is characterized by a control device which is designed to carry out a procedure as described above.

[0068] According to another aspect, a centrifuge is provided for centrifuging a reaction vessel unit with several reaction vessels arranged in a flat surface, wherein the centrifuge comprises a rotor with a shaft and a receiving area for receiving the reaction vessels. This centrifuge is characterized by a quality factor not greater than 0.7, where the quality factor Qf is calculated by the following formula:

[0069]

[0070] where

[0071] I the moment of inertia of the rotor,

[0072] MR the mass of the rotor and

[0073] R is the radius of the rotor. Unless otherwise specified, the rotor radius RR is the radius from the axis of rotation to the receiving area of ​​the rotor, specifically at the plane or surface on which the reaction vessel unit rests when the rotor is not rotating, provided the reaction vessels are arranged with their openings facing radially outwards for emptying. As explained in more detail below, the rotor can also have multiple receiving areas in radially different positions. In such a rotor with multiple radially separated receiving areas, the radius R of the rotor is the radius of the outermost receiving area.

[0074] The quality factor QF should be as small as possible, less than 0.7, less than 0.6, less than 0.5, and especially less than 0.4. This ensures a high tolerance with respect to uneven loading of the reaction vessels 4.

[0075] According to another aspect, the centrifuge for centrifuging a reaction vessel unit with several reaction vessels arranged in a flat plane can include a rotor with a shaft and a receiving area for receiving the reaction vessels. This centrifuge is characterized by the fact that the shaft has at least 70% of the rotor's weight, with the maximum radius Rw of the shaft not exceeding 30% of the rotor's maximum radius RRM. The maximum radius Rw of the shaft is the radius from the axis of rotation to the shaft's circumference. The maximum radius RRM of the rotor is the radius from the axis of rotation to the rotor's circumference. The shaft can have at least 80% or even at least 90% of the rotor's weight. The maximum radius of the shaft Rw can also be no greater than 25%, 20%, or 15% of the rotor's maximum radius RRM, respectively.

[0076] A centrifuge designed according to the two aspects mentioned above allows for significantly different loads on the two rotor halves without imbalance affecting the centrifuge's operation at high speeds. This design therefore offers considerably greater tolerance in determining the counterweight for a given load. Fewer counterweights are also required. Furthermore, the rotor load can vary more during operation without requiring adjustments to the counterweight. This significantly simplifies workflow planning and reduces the potential for errors.

[0077] This can be used in centrifuges with rotation axes arranged parallel or perpendicular to the sand surface of the centrifuge. The shaft can be made at least partially of tungsten and / or lead or a suitable alloy. This concentrates the weight of the rotor onto the shaft. The remaining components of the rotor are then preferably made of a lightweight material, such as aluminum or an aluminum alloy, or plastic.

[0078] The rotor can have a radius RR of at least 70 mm and, in particular, at least 85 mm.

[0079] The rotor's receiving area is preferably rectangular with two longitudinal sides and two transverse sides, the longitudinal sides being arranged parallel to the axis of rotation. This minimizes the dispersion of centrifugal forces in the different reaction vessels.

[0080] The shaft can extend over a longer area than the rest of the rotor. This makes it possible to concentrate a lot of mass in the area of ​​the shaft.

[0081] Preferably, the receiving area and / or connecting elements between the shaft and the receiving area are made of aluminium or plastic.

[0082] The centrifuge can have a motor capable of generating a rotor torque of at least approximately 300 mNm. The torque can be at least 400 mNm, 500 mNm, 600 mNm, 750 mNm, 900 mNm, and, in particular, at least 1 Nm. Such a high torque allows for very rapid rotor acceleration, which is especially advantageous for emptying the reaction vessels using a discharge device described in more detail below.

[0083] The shaft can have a rotor rod and several annular shaft bodies through which the rotor rod extends.

[0084] The rotor can have several approximately flat rotor laminations arranged transversely to the rotor shaft and each fixed between two shaft bodies. This is a very simple rotor design, which also makes it relatively easy to concentrate the rotor's weight, especially in the area of ​​the shaft, and to design the area of ​​the rotor away from the axis of rotation to be very lightweight.

[0085] The shaft bodies can be made of tungsten and / or lead or a suitable alloy to concentrate weight in the center of the rotor. According to another aspect, a method for emptying reaction vessels by centrifugation is provided, wherein the reaction vessels are arranged with their openings directed radially outwards in a centrifuge, and a discharge device is arranged adjacent to and radially outside the reaction vessels on the rotor of the centrifuge for axially discharging liquids contained in the reaction vessels. The centrifuge is designed according to one of the aspects described above.

[0086] According to a further aspect, a method for centrifuging reaction vessels is provided, wherein the reaction vessels are centrifuged using a centrifuge comprising a rotor with a shaft and two receiving areas for receiving reaction vessels, the receiving areas being diametrically opposed on the rotor around a rotational axis. In one of the two receiving areas, the reaction vessels are arranged with their openings directed radially outwards, and a discharge or collection device is arranged adjacent to and radially outside the reaction vessels on the rotor of the centrifuge for collecting or axially discharging liquids contained in the reaction vessels. Further reaction vessels are arranged in the other receiving area with their openings directed radially inwards in order to centrifuge a sample or liquid contained therein.

[0087] In this method, a centrifuge is preferably used which has an upper loading opening and a lower loading opening, so that one of the receiving areas can be loaded in both a maximally upper and a maximally lower position, and a loading and unloading device is used which is height-adjustable such that the centrifuge can be loaded and unloaded with the loading and unloading device through both the upper and the lower loading opening.

[0088] In this process, reaction vessels can be emptied simultaneously in a centrifuge by centrifugation, while the contents of other reaction vessels are centrifuged in the conventional manner. Since the liquid is either discharged in a controlled manner using a drain device or collected in a controlled manner using a collection device when emptying the reaction vessels, this liquid is not distributed within the centrifuge housing and therefore cannot contaminate the contents of the other reaction vessels.

[0089] By providing two loading ports diametrically opposite the axis of rotation, two independent reaction vessel units can be added to or removed from the centrifuge at a predetermined rotor position. In this rotor position, the two receiving areas are aligned with their respective loading ports, preferably located in their uppermost and lowermost positions (6 o'clock and 12 o'clock positions). Emptying by centrifugation and conventional centrifugation can also be performed sequentially.

[0090] The collection device can comprise a porous material, in particular porous cellulose material, which absorbs the liquid discharged from the reaction vessels by capillary action, so that the collection device can be removed from the centrifuge after centrifugation without leaving any liquid residue in the centrifuge. The draining device is, of course, preferred, because with such a draining device several reaction vessel units can be emptied successively without having to replace the draining device. Naturally, the draining device can also be replaced between individual emptying processes.

[0091] In an alternative embodiment serving the same purpose of simultaneously centrifuging two reaction vessel units, one or more lids can be provided instead of a drain or collection device to seal the reaction vessels containing the sample to be centrifuged. This also ensures that the sample being centrifuged is not contaminated. However, in this embodiment, if neither a drain nor a collection device is provided, the liquid to be emptied can spread within the centrifuge housing. This liquid should then be removed using appropriate methods. The lid can be made of a rigid material, particularly rigid plastic. Alternatively, the lid can be made of a flexible material, such as a film welded onto the reaction vessel(s).

[0092] The drainage device preferably has a drainage plate which is arranged in the centrifuge opposite the openings of the reaction vessels in such a way that the surface of the drainage plate is inclined in the axial direction of the rotor and that, during centrifugation, liquid escaping from the reaction vessels due to centrifugal acceleration is collected by the drainage plate and drained in the axial direction.

[0093] According to another aspect, a centrifuge for centrifuging reaction vessels is provided, comprising a rotor with a shaft and two receiving areas for receiving reaction vessels, wherein the receiving areas on the rotor are diametrically opposed around a rotational axis, and the centrifuge has an upper loading opening and a lower loading opening, such that one of the receiving areas can be loaded in either a maximally upper or a maximally lower position. This centrifuge is characterized by either the provision of a loading and unloading device that is height-adjustable such that the centrifuge can be loaded and unloaded through both the upper and the lower loading opening, or by the provision of two loading and unloading devices, each for loading and unloading through one of the upper or lower loading openings.

[0094] One of the two receiving areas can be designed to receive the reaction vessels with their openings facing radially outwards, together with a discharge device or a collection device, which can be arranged adjacent to and radially outside the reaction vessels on the rotor of the centrifuge for collecting or axially discharging liquids contained in the reaction vessels, and

[0095] The other of the two receiving areas can be designed to receive further reaction vessels with their openings directed radially inwards in order to centrifuge a sample contained therein.

[0096] Such a centrifuge may be equipped with a control device designed to perform one of the procedures described above.

[0097] Another aspect is the rotor for a centrifuge with a receiving area for reaction vessels. The rotor is characterized by having several receiving areas, each designed to receive a plate-shaped reaction vessel unit containing multiple reaction vessels and situated at different distances from the rotor's axis of rotation.

[0098] Since multiple receiving areas are provided in radially different positions, different centrifugal accelerations can be exerted on the contents of the reaction vessels with such a rotor at the same rotational speed. It is also possible to arrange several reaction vessel units simultaneously in different radial positions within the rotor. Preferably, several receiving areas can be combined so that reaction vessels or reaction vessel units of different heights can be arranged within the rotor. Reaction vessel units of different heights can also be accommodated, with their radially outer surfaces always being approximately equidistant from the axis of rotation and, for example, aligned with a discharge device.

[0099] The receiving areas are preferably designed such that the plate-shaped reaction vessel units can be inserted into the rotor by sliding them in a direction parallel to the axis of rotation. For this purpose, the receiving areas can be defined by retaining elements running parallel to the axis of rotation, e.g., in the form of strips or retaining ribs, onto which the reaction vessel units can be placed directly or indirectly with an additional base plate. The rotor preferably has a horizontal axis of rotation. In conjunction with the receiving areas, which are designed for insertion in a direction parallel to the axis of rotation, it is possible to insert the reaction vessel units horizontally and, in particular, with reaction vessels open at the top.

[0100] The plate-shaped reaction vessel units are preferably microtiter plates. Microtiter plates are defined by the ANSI SLAS 4-2004 (R2012) standard.

[0101] Such a rotor enables novel centrifugation methods. For example, it is possible to transfer liquids from one reaction vessel unit to another. The reaction vessel units are arranged in the rotor with their openings facing each other. The centrifugation process begins with the reaction vessel unit initially containing the liquid positioned below the other reaction vessel unit. The centrifugation process ends with the reaction vessel unit into which the liquid is centrifuged being located below the other reaction vessel unit. In other words, the centrifugation process begins at the 12 o'clock position and ends at the 6 o'clock position.

[0102] The multiple receiving areas can be arranged on one side of the rotor relative to the axis of rotation, or on both sides of the rotor relative to the axis of rotation. The rotor can have at least two opposing receiving surfaces, on which retaining elements are provided at different distances from the axis of rotation. A base plate or a reaction vessel unit can be directly and detachably attached to each of these retaining elements, thus limiting one of the receiving areas in or against the radial direction. The retaining elements can be retaining ribs projecting into the interior. Alternatively, the retaining elements can be formed, for example, as grooves into which the base plates are inserted with their edge region.

[0103] With such a rotor, highly flexible mounting areas can be created in different radial positions. Furthermore, base plates are only provided where needed. This allows for significant weight savings in the radially outer area of ​​the rotor, which keeps the rotor's moment of inertia low. Additionally, mounting areas of varying heights can be created.

[0104] Preferably, there are special bottom plates for emptying (= evacuating) the reaction vessels, for centrifuging the contents of the reaction vessels, and bottom plates that serve as counterweight plates. A locking device or a coupling for securing at least one of the bottom plates to the rotor can be provided. A locking device can be very simple, consisting of a corresponding locking projection and a corresponding locking groove. The locking projection can be located on the rotor and the locking groove on the bottom plate, or vice versa. Instead of a locking device, a coupling, such as a magnetic coupling, can also be provided between the rotor and the bottom plate.

[0105] According to another aspect, a centrifuge is provided with a rotor having a shaft and a receiving area for receiving at least one reaction vessel, wherein the centrifuge is characterized by having a rotor designed according to the rotor described above.

[0106] The centrifuge can have an upper loading port and a lower loading port, so that at least one of the receiving areas can be loaded in both its maximum upper (12 o'clock position) and its maximum lower (6 o'clock position) position in the centrifuge.

[0107] The centrifuge can have a loading and unloading device that is height-adjustable in such a way that the receiving areas, which are spaced radially differently from the axis of rotation, can be loaded and unloaded, and in particular that the loading and unloading device can be used to load and unload both through the upper and the lower loading opening.

[0108] For all the aspects explained above, the centrifuge, or the centrifuge used here, has rectangular receiving areas with two longitudinal sides and two transverse sides, the longitudinal sides preferably being arranged parallel to the rotor's axis of rotation. This minimizes the dispersion of centrifugal forces in the individual reaction vessels.

[0109] Furthermore, in all aspects explained above, the rotor's axis of rotation can be arranged parallel to the centrifuge's base, so that the axis of rotation is horizontal during operation. This allows the centrifuge to be loaded and unloaded by horizontally sliding the reaction vessel unit. This makes it very easy to integrate the centrifuge into existing laboratory systems, with the processes being fully automated.

[0110] Furthermore, the centrifuge can be equipped with a dispensing device having one, and preferably several, dispensing nozzles, in accordance with all the aspects explained above. The dispensing device is preferably located in the area above the upper loading opening, and the dispensing nozzles are directed downwards. However, the dispensing nozzles do not need to be aligned exactly vertically, but can also be arranged at an angle to the vertical so that liquid can be directed against the wall of the individual reaction vessels.

[0111] Another aspect concerns a reaction vessel unit with at least one reaction vessel having a bottom section and surrounding side walls that define a funnel section adjacent to the bottom section and an upper section, wherein an opening is formed in the upper section and a retention section is located in the bottom section, and the funnel section has walls that are inclined relative to a longitudinal axis of the reaction vessel at an angle A of preferably at least 30° and / or preferably a maximum of 40°. The retention section can be designed as a capillary cavity. The side walls in the upper section preferably run parallel to the longitudinal axis.

[0112] The individual aspects can be implemented separately. However, they can also be applied in any combination with each other.

[0113] The invention is explained in more detail using the drawings as an example. The drawings show:

[0114] Figure 1 is a roughly schematic, non-scale cross-sectional representation of a rotor to illustrate different technical problems and effects with a reaction vessel unit.

[0115] Figure 2 shows a section of the reaction vessel unit from Figure 1 in the area of ​​a single reaction vessel in a sectional view.

[0116] Figure 3 shows an embodiment of a centrifuge with an open housing.

[0117] in perspective view,

[0118] Figure 4 shows the rotor together with a discharge channel of the centrifuge from Figure 3.

[0119] in perspective view looking from the front at the rotor,

[0120] Figure 5 shows the rotor and the discharge duct from Figure 4 in a sectional view.

[0121] in perspective view,

[0122] Figure 6 shows the rotor and the discharge channel from Figure 4 in a cross-sectional view,

[0123] Figure 7 shows the rotor and the discharge channel from Figure 4 in a front view; Figure 8 shows a table that includes certain parameters of different configurations of the embodiment and of comparative examples.

[0124] Figure 9 shows the embodiment of the centrifuge from Figure 3 with the housing open.

[0125] in perspective view looking towards the back,

[0126] Figure 10a-d shows a floor plate for evacuation in perspective view and side view.

[0127] Front view and top view,

[0128] Figure 11 shows a base plate for centrifuging in perspective view,

[0129] Figure 12 shows a counterweight plate in perspective view,

[0130] Figure 13 shows a rotor in front view together with a base plate,

[0131] a reaction vessel unit, a drainage device, and

[0132] a counterweight plate in a front view,

[0133] Figure 14a shows the rotor from Figure 13 in a sectional view along the section line AA in Figure 13, viewed from above.

[0134] Figure 14b shows a corner area of ​​the rotor's receiving area from Figure 14a

[0135] in enlarged view,

[0136] Figure 15a shows the rotor from Figure 13 in a sectional view along the section line BB in Figure 13, viewed from above.

[0137] Figure 15 shows an enlarged view of a corner area of ​​the rotor's receiving area.

[0138] Figures 16a-c show a diagram of the centrifugal acceleration over time for a conventional swing-out centrifuge (a), (b) and for the centrifuge according to the embodiment described above (c), and

[0139] Figure 17 shows the centrifuge from Fig. 3 with closed housing and in a front view.

[0140] Figures 1 and 2 are rough schematic and not-to-scale representations of a rotor 1 and a reaction vessel unit 2 to illustrate technical problems and effects upon which the various aspects of the methods according to the invention for introducing a target substance into a retention area of ​​at least one reaction vessel 4 and suitable centrifuges are based. The rotor 1 has at least one receiving area 3 for receiving a reaction vessel unit 2. The reaction vessel unit 2 is designed as a so-called microtiter plate, i.e., it has several reaction vessels 4, which in the present embodiment are each identical. However, as explained below, it is also possible for the reaction vessels 4 of a reaction vessel unit 2 to be designed differently.

[0141] The reaction vessels 4 each have a bottom region 5 and an opening 6 opposite the bottom region 5 (Figure 2). The openings 6 of the multiple reaction vessels 4 of the reaction vessel unit 2 are arranged in a plane 16a.

[0142] Since such a reaction vessel unit 2, when not centrifuged, is generally arranged so that the openings 6 point upwards and the bottom area 5 points downwards, "top" in relation to the reaction vessels 4 and the reaction vessel unit 2 means the area of ​​the openings 6 and "bottom" means the area of ​​the bottom areas 5. The reaction vessels 4 are connected to each other at the top by an upper connecting wall 7.

[0143] Each reaction vessel 4 has a longitudinal axis 8, which is located in the center of the respective reaction vessel 4 and extends from the bottom region 5 to the opening 6. The longitudinal axis 8 is perpendicular to the plane 16a in which the openings 6 of the several reaction vessels 4 of the reaction vessel unit 2 are arranged.

[0144] The reaction vessels 4 have an upper section 9, the walls of which run parallel to the longitudinal axis 8. These walls are also referred to as vertical walls 9. A funnel section 10, which tapers conically downwards, adjoins the upper section 9 downwards. At the lower section, or bottom section 5, of the reaction vessels 4, the funnel section 10 transitions into a capillary cavity 11. This cavity is so small that any liquid contained within it, particularly an aqueous solution, is held in place by capillary forces such that even if the reaction vessel 4 is turned upside down, the liquid does not leak out of the capillary cavity 11. The capillary cavity 11 thus forms a retention chamber.

[0145] In the embodiment shown in Figure 2, the retention area is formed by the capillary cavity 11. In principle, it is also possible to form a retention area simply by providing a coating in the bottom region 5 of the reaction vessel 4 such that a specific quantity of liquid is retained, so that when the reaction vessel 4 is emptied, a predetermined quantity or volume of liquid is retained by the retention area. The basic structure of such reaction vessels 4 with an upper region 9 with vertical walls, a funnel section 10, and a retention area, in particular a capillary cavity 11, is known from WO 2023 / 110944 A1, which is why reference is made to it here.

[0146] Such a reaction vessel unit with such reaction vessels is primarily used for washing cells, which is carried out in the following three steps:

[0147] Step 1

[0148] The cells are located in an aqueous solution in reaction vessel 4 and are centrifuged downwards. For this process, the corresponding reaction vessel 4 is positioned with its opening pointing towards a rotation axis 12 of the centrifuge, so that during centrifugation the cells in the liquid solution are driven radially outwards and thus into the retention area or the capillary cavity 11. The cells therefore collect in the capillary cavity 11.

[0149] Step 2

[0150] The reaction vessel 4 is inserted into a centrifuge with its opening 6 pointing radially outwards, so that during centrifugation the aqueous solution contained in the reaction vessel 4 is ejected. Only the aqueous solution containing the cells, located in the retention area and especially in the capillary cavity 11, remains in the reaction vessel 4. This process is referred to as "centrifugation out".

[0151] Step 3

[0152] The cells are flushed out of the retention area, in particular the capillary cavity 11. This can be done, for example, with a dispensing device that directs a liquid jet precisely into the capillary cavity 11. The liquid jet preferably has a cross-sectional area smaller than the upward-facing opening of the capillary cavity 11. This can be done automatically with a so-called liquid handler, which includes a dispensing device, or manually. This step is called "resuspension".

[0153] The fundamental goal is to retain as many cells as possible from those initially introduced into the solution within the retention area, making them available again after resuspension. Losses occur when not all cells are drawn into or concentrated within the retention area during centrifugation, or when cells clump together so strongly that they can no longer be individually released into solution during resuspension. The primary objective is to minimize these losses. However, various conflicting effects come into play. For example, a very long centrifugation period can result in a large number of cells collected in the retention area, but it can also lead to a high degree of clumping. The reaction vessels 4 can be circular in plan view and thus rotationally symmetrical.They can also have the shape of a polygon in plan view, in particular a quadrilateral or a square. The reaction vessels 4 can also have the shape of a rectangle with two longer and two shorter sides in plan view. In such a configuration of the reaction vessels 4, the retention area or the capillary cavity 11 is elongated in plan view, with the inclined walls in the funnel section 10, or walls inclined relative to the longitudinal axis 8, bordering the longitudinal direction of the capillary cavity 11.

[0154] The inclined walls in the funnel section 10 have an angle of inclination A relative to the longitudinal axis 8 of the reaction vessel 4 (Figure 2).

[0155] The rotor 1 has a shaft 13, at the center of which is the axis of rotation 12. The rotor body 14 is attached to the shaft 13. At least one of the receiving areas 3 is formed at the radially outer end of the rotor body, and preferably two receiving areas 3 are arranged symmetrically around the shaft 13 or axis of rotation 12, each for receiving a reaction vessel unit 2. In Figure 1, the rotor body 14 is represented schematically by a line and a rectangle, each representing one of the two receiving areas 3. Since the rotor body 14 must withstand considerable centrifugal forces and securely hold the reaction vessel units 2 and / or corresponding counterweights during centrifugation, the rotor body 14 must be designed with high strength, particularly in the radial direction. The actual design of the rotor body 14 therefore deviates considerably from the linear shape shown in Figure 1.

[0156] A rotor radius 15 extends from the shaft 13 or the axis of rotation 12 to each of the receiving areas 3. The rotor radius 15 is perpendicular to the plane 16a of the reaction vessel unit 2 or perpendicular to a plane 16b of the receiving area 3. The plane 16b forms the support of the receiving area 3 against which the reaction vessel unit is pressed during centrifugation. The support can be defined by a flat element or, for example, by just two strips that support the reaction vessel unit at its edges. Depending on whether the contents of the reaction vessels 4 are to be emptied or centrifuged, the reaction vessel unit rests on a plane 16c (radially inside the receiving area 3) or on a plane 16b (radially outside the receiving area 3) (Fig. 1).The rotor radius 15 extends to the receiving area 3, i.e., the plane 16c, on which the reaction vessel unit 2 rests when inserted into the receiving area 3 of the non-rotating rotor 1 for emptying the reaction vessels 4.

[0157] The receiving area 3 is arranged symmetrically to the rotor radius, such that the rotor radius 15 intersects the reaction vessel unit 2, which is located in the receiving area 3, at its center. As can be easily seen from Figure 1, the reaction vessels 4 are at different distances from the rotor radius 15, both in and against the direction of rotation 17. This is particularly true when the reaction vessel unit 2 is a flat unit with several reaction vessels 4 distributed in the plane, as is the case with microtiter plates. Since microtiter plates typically have a large number of reaction vessels 4 arranged in a regular grid in columns and rows, it is not possible to arrange all reaction vessels 4 along a line parallel to the axis of rotation 12. This is only possible with a linear arrangement of reaction vessels.

[0158] For clarity, Figure 1 shows the reaction vessels 4, which are arranged offset from each other in the direction of rotation 17 and are numbered 4 / 1 to 4 / 6. Reaction vessels 4 / 1 and 4 / 6 are located at the outer edges of the reaction vessel unit 2 and the receiving area 3 in the direction of rotation 17, whereas reaction vessels 4 / 3 and 4 / 4 are located in the immediate vicinity of the rotor radius 15 and thus in the center of the receiving area 3. The further the reaction vessels 4 are from the center or the rotor radius 15, the greater their distance from the axis of rotation 12. Accordingly, the centrifugal force exerted on the liquid in the outer reaction vessels 4 / 1 and 4 / 6 is greater than that exerted on the liquid in the more internally located reaction vessels 4 / 2 to 4 / 5. The extension of the reaction vessel unit 2 in the direction of rotation 17 thus leads to different centrifugal forces in the different reaction vessels 4 / 1 - 4 / 6.

[0159] The centrifugal force exerted in the individual reaction vessels 4 differs not only in its magnitude but also in its direction. In reaction vessels 4 / 3 and 4 / 4, which are located in the immediate vicinity of the rotor radius 15 and thus of the center of the receiving area 3, the direction of the centrifugal force deviates only slightly from the longitudinal extent of the rotor radius 15. Here, the direction of the centrifugal force is essentially almost perpendicular to the plane 16a of the reaction vessel unit 2.

[0160] Figure 1 shows a radius 18 extending from the axis of rotation 12 and passing through the interior of the reaction vessel 4 / 6, which is positioned at its outer edge opposite to the direction of rotation 17 of the receiving area 3. The centrifugal force Fz acting on the liquid in the reaction vessel 4 / 6 is directed along the longitudinal extent of this radius 18 (Figures 1, 2). This radius 18 forms an angle β with the longitudinal axis 8 of the reaction vessel 4 / 6. The angle β also forms between the radius 18 and the rotor radius 15. This means that the further the reaction vessels 4 are from the center of the receiving area 3 or from the rotor radius 15 in the direction of rotation 17, the greater the inclination of the centrifugal force Fz relative to the longitudinal axis 8 of the respective reaction vessel 4.

[0161] These differences in centrifugal forces in the individual reaction vessels 4, both in magnitude and direction, are referred to as the dispersion of centrifugal forces. The dispersion of centrifugal force is stronger the further the reaction vessel unit 2 extends in the direction of rotation 17 in the rotor 1. Since most reaction vessel units 2 are standardized microtiter plates, or at least correspond to the external dimensions of standardized microtiter plates for ease of handling, there is little opportunity in practice to change the size of the reaction vessel units 2. These reaction vessel units 2, which have the basic shape of a microtiter plate, are rectangular in plan view with two longer longitudinal sides (127.76 mm according to ANSI SLAS 4-2004 (R2012)) and two shorter transverse sides (85.48 mm according to ANSI SLAS 4-2004 (R2012)).To minimize the dispersion of the centrifugal force, it is recommended to design the rotor 1 with the receiving area 3 such that the reaction vessel units 2 are arranged with their two longitudinal sides parallel to the axis of rotation 12, so that the reaction vessel unit 2 extends in the rotor 1 in the direction of rotation 17 only with its shorter transverse sides. For reasons of balance, it is also advantageous to design the receiving area 3 symmetrically with respect to the rotor radius 15, i.e., that the reaction vessel unit 2 extends equally in the direction of rotation 17 and against the direction of rotation 17 from the rotor radius 15 (Figure 1).

[0162] To minimize the dispersion of the centrifugal force, it is advantageous to make the radius 18 of the rotor 1 as large as possible. It has been found that a rotor radius 15 of at least 7 cm, preferably at least 8 cm, and particularly at least 9 cm is advantageous, wherein the rotor radius 15 is measured from the axis of rotation 12 to the plane 16a of the reaction vessel unit 2, in which the openings 6 of the reaction vessels 4 are arranged. These radius lengths will be discussed in more detail below.

[0163] Furthermore, it is advantageous to make the shaft 13 as heavy as possible and the rotor body 14 as light as possible. This allows the ratio of the moment of inertia to the weight of the rotor 1 to be kept low. A low moment of inertia allows for rapid acceleration of the rotor 1 at low torque. A high weight of the rotor 1 means that uneven loads in the reaction vessels 4, which can cause imbalance, result in less significant imbalance. The heavier a rotor is, the more uneven the load distribution in the individual reaction vessels can be. A heavy shaft, in which the weight is concentrated directly around the axis of rotation 12 of the rotor 1, results in a high weight for the rotor 1 but contributes only slightly to the moment of inertia of the rotor 1. The moment of inertia of the rotor 1 should be as small as possible to allow for rapid acceleration or deceleration of the rotor 1 at predetermined torque.

[0164] A quality factor that describes this as a function of the radius 18 of rotor 1 can be calculated using the following formula:

[0165]

[0166] where

[0167] I the moment of inertia of the rotor,

[0168] MR the mass of the rotor and

[0169] R is the radius of the rotor.

[0170] It has been shown that this quality factor QF should be as small as possible below 0.7 or below 0.6 or below 0.5 and especially below 0.4 in order to allow a high tolerance with regard to uneven loading of the reaction vessels 4.

[0171] A first embodiment of a centrifuge is explained in more detail below (Figures 3 to 7).

[0172] The centrifuge 19 has a rotor 1, a housing 20, a loading and unloading device 21 and a drive unit 22.

[0173] In the present embodiment, the housing 20 is cuboid in shape with an approximately flat front wall 23 and an approximately flat rear wall 24. Instead of a cuboid housing 20, a housing in another shape, for example a circular cylinder, can also be provided.

[0174] The front wall 23 has an upper loading opening 25 and a lower loading opening 26 through which a reaction vessel unit 2 can be inserted into or removed from the centrifuge 19. The upper and lower loading openings 25, 26 can each be automatically closed by means of a flap, which in the present embodiment is designed as sliding doors 27 (Figure 17).

[0175] The rotor 1 comprises a shaft 13 and a rotor body 14 (Figure 4). In the present embodiment, the shaft 13 is formed from an elongated rod 28 with several annular shaft bodies 29 enclosing the rod 28. The rod 28 and the shaft bodies 29 are preferably made of steel or a tungsten alloy (Figures 5, 6).

[0176] In the present embodiment, the rotor body 14 is formed from several thin-walled rotor laminations 30. Each rotor lamination 30 has an annular central section 31 with a central opening through which the rotor rod 28 extends. Two retaining sections 33 are integrally formed on each central section 31 via two connecting webs 32. The retaining sections 33 form two elongated webs that run parallel to each other. The rotor laminations 30 are axially symmetrical about a central axis and point-symmetrical about the center point of the central section 31. Two mounting strips 34 are attached to each of the retaining sections 33, extending in the axial direction 35 of the shaft 13 (Fig. 6).The receiving strips 34 are each arranged on the radially inner side of the holding sections 33 such that a pair of receiving strips 34 are arranged on the opposite holding sections 33 with their receiving surfaces 36 (which are explained in more detail below) facing each other.

[0177] The mounting strips 34 are rigidly connected to the rotor laminations 30, for example by means of rivets, soldering, or welding. The rotor body 14, formed from the rotor laminations 30 and the mounting strips 34, consists only of thin-walled sheets and is therefore very light. Preferably, the rotor laminations 30 and the mounting strips 34 are made of an aluminum alloy.

[0178] The rotor body 14 is arranged on the rotor rod 28 such that the rotor rod 28 extends through the central opening of the central sections 31 of the individual rotor laminations 30, with a shaft 29 located between each rotor lamination 30, which maintains a distance between the rotor laminations 30. Thus, in the longitudinal or axial direction 35 of the rod 28, a rotor lamination 30 and a shaft 29 are always arranged consecutively, forming a corresponding stack. The rod 28 has threaded sections to which the stack of rotor laminations 30 and shaft 29 is secured at its ends by means of a nut 37, so that the rotor body 14 is fixed to the rod 28. Of course, the rotor body 14 can also be fastened to the shaft 13 by other means.For example, a positive-locking connection can be formed between the shaft 13 and the rotor body 14, or they can be joined by a material bond, for example by soldering or welding. As will be explained in more detail below, an advantage of this design of the rotor 1 is that the rotor body 14 is very light, whereas the shaft 13 is heavy.

[0179] In the present embodiment, the receiving strips 34 are formed from several sections 38, each extending between two adjacent rotor laminations 30 or arranged on the outside of the end rotor laminations 30. Each of the individual sections 38 of the receiving strips 34 has two through-holes 39 through which a connecting pin 40 extends, so that all sections 38 of a receiving strip 34 and the corresponding rotor laminations 30 are connected to each other (Figure 4).

[0180] On the mounting rails 34 or their sections 38, projecting retaining ribs 41 are arranged on the inwardly facing side surface. The retaining ribs 41 of each mounting rail 34 are arranged in several rows and run parallel to the axial direction 35 of the centrifuge 19. These retaining ribs 41 serve to hold a base plate 42 or directly a reaction vessel unit 2, as explained in more detail below. The retaining ribs 41 can be supported by a base plate 42 radially inwards and radially outwards.

[0181] The retaining sections 33 of the rotor laminations 30 are each formed at their free ends with an inwardly projecting projection 43, which each form a support 43 for an approximately plate-shaped discharge device 44. Such a discharge device is known from WO 2023 / 148272A1 and from the unpublished international patent application PCT / EP2024 / 071916.

[0182] The rotor 1 according to the present embodiment is formed from several identical rotor laminations 30. These can be manufactured simply and cost-effectively. The shaft bodies 29 have the same shape but can be made of different materials, thus giving the rotor 1 a different mass. The rotor 1 is therefore modular, consisting of several uniform, essentially identical parts. The modular design allows for both cost-effective manufacturing of the rotor 1 and adaptation of the rotor 1 to different requirements. The rotor laminations 30 can also be referred to as rotor clamps, which clamp the deflector 44 and / or base plates 42 at the edge to hold them against the centrifugal force in the rotor 1. The present embodiment has four rotor laminations 30. This rotor 1 is designed for centrifugal accelerations up to 1000 g.For higher centrifugal accelerations, it may be advantageous to provide more or thicker rotor laminations 30. If more rotor laminations 30 are arranged in the rotor 1, the corresponding rotor bodies 29 must be made correspondingly shorter. Rotors 1 of different weights can also be easily produced by exchanging the corresponding shaft bodies 29 made of different materials, as explained in more detail below.

[0183] These rotors 1 are therefore very cost-effective to manufacture, can be configured in different ways and are thus easily adaptable to different applications.

[0184] The centrifuge 19 can have a dispensing device 62 with several dispensing nozzles 63 (Figure 17). The dispensing nozzles 63 are arranged with their openings pointing downwards. Preferably, the dispensing nozzles 63 are arranged obliquely relative to a vertical, so that they can introduce a liquid jet obliquely into a reaction vessel 4 of the reaction vessel unit 2. This allows the liquid jet to be directed against a wall of the reaction vessel 4. In conjunction with the height adjustment device 60, the distance between the reaction vessel unit 2 or the opening 6 of the reaction vessels 4 of the reaction vessel unit 2 and the respective dispensing nozzles 63 can be kept approximately constant. This makes it possible to reliably fill reaction vessel units 2 of different heights with liquid using the dispensing device 62.The discharge device 44 has a discharge plate 45 which can be arranged in the centrifuge 19 opposite the openings 6 of the reaction vessels 4 such that the surface of the discharge plate 45 is inclined in the axial direction 35 of the centrifuge 19, so that during centrifugation, liquid escaping from the reaction vessels 4 due to centrifugal acceleration is collected by the discharge plate 45 and discharged laterally, i.e., in the axial direction 35 (Figure 6). Radially external reinforcing struts 46 are formed on the discharge plate 45, which extend transversely to the axial direction 35. The discharge plate 45 has lamellae 47 on its radially inner surface, which extend in the axial direction 35. The lamellae 47 primarily serve to control the drainage of the liquid collected by the drainage plate 45 in the axial direction 35 and prevent the liquid from flowing towards the edge of the drainage plate 45 in the opposite direction of rotation.Furthermore, the lamellae 47 and the reinforcing struts 46 serve to mechanically reinforce the drain plate 45, as this plate is subject to considerable centrifugal force during centrifugation and must withstand it. Additionally, during centrifugation, the reaction vessel unit 3 is pressed against the drain device 44, so that the corresponding forces must be transferred to the drain device 44, and in particular to its drain plate 45, and dissipated to the rotor 1. Therefore, a rigid design of the drain device 44 is advantageous.

[0185] The draining device 44 has one or more draining openings on the front side where the draining plate 45 is furthest away from the reaction vessel unit 2 or the axis of rotation 12, each of which is formed by a nozzle 48 that projects a short distance in the axial direction 35.

[0186] In the area of ​​the rear wall 24 of the housing 20 of the centrifuge 19, an annular discharge channel 49 is formed, which has a circular, circumferential annular opening 50 through which the nozzle 48 extends. In the present embodiment, the discharge channel 49 is formed from three parts: a discharge channel base body 51, which has an approximately U-shaped cross-section (Figure 6), wherein the open side of the discharge channel base body 51 is arranged in the axial direction 35 towards the rotor 1, which is covered by a radially outer ring cover element 52 and a radially inner ring cover element 53 such that an annular opening 50 is formed between the two ring cover elements 52, 53.

[0187] A drain 54 is formed on the lower part of the drainage channel base body 51, through which liquid located in the drainage channel 49 can drain away due to gravity.

[0188] The drive unit 22 of the centrifuge 19 is connected to the shaft 13 to rotate it and thus the rotor 1. The drive unit 22 comprises an electric motor, in particular a servo motor. The servo motor is equipped with an encoder that measures the motor's rotational position, which is then transmitted to a central control unit. This rotational position corresponds to the rotational position of the rotor 1. The rotational speed and acceleration of the rotor 1 can also be derived from the rotational position and controlled accordingly. The servo motor has a torque of at least 200 mNm (millinewton meters), and in particular at least 300 mNm, or at least 500 mNm, and preferably at least 750 mNm, which is applied directly to the rotor 1. In the present embodiment, a motor with a torque of approximately 1000 mNm, i.e., 1 Nm of torque, is used, which is transmitted to the shaft 13 without any reduction gearing.A reduction or transmission gearbox can be provided between the motor and shaft 13. However, it must be noted that in addition to high torque, high rotational speeds of the rotor 1 must also be generated. For example, if a centrifugal acceleration of 1000 g at a radius of 10 cm is desired, a rotational speed of approximately 3000 RPM is required. If this centrifugal acceleration is to be achieved within 5 seconds, a drive torque of at least 1000 mNm (= 1 Nm) may be necessary, depending on the load.

[0189] The loading and unloading device 21 is arranged outside the housing 20 adjacent to the front wall 23. It has a horizontal, flat receiving area represented by a transport fork 56. Similar to a forklift, the transport fork 56 serves to receive a base plate 42 of the rotor 1 and a reaction vessel unit 2 located thereon, or to receive a reaction vessel unit 2 without a separate base plate.

[0190] The loading and unloading device 21 has a sliding device 57 for moving the transport fork 56 with a base plate 42 into or out of the rotor 1 together with a reaction vessel unit 2, or with only a reaction vessel unit 2. For this purpose, the sliding device 57 has a linear motion mechanism, which is, for example, formed by a slide 58 attached to a section of a belt (not shown) that is tensioned around two pulleys, one of which is driven by a motor to move the belt and thus the slide 58. The transport fork 56 is attached to the slide 58. The slide 58 is equipped with a height adjustment device to adjust the height of the transport fork 56 accordingly.The height adjustment device can, for example, be designed using a motor-driven threaded spindle that engages with a thread connected to the transport fork 56, so that turning the threaded spindle raises or lowers the transport fork 56. The drive unit for the threaded spindle can be a stepper motor, so that the number of steps provides a signal from which the height of the transport fork 56, and thus the height of the loading and unloading device 21, can be derived. However, any other linear drive mechanism can also be used to adjust the height of the loading and unloading device 21. If very precise positioning of the loading and unloading device 21 is desired, it may be advantageous to provide a separate measuring device for detecting the vertical position of the transport fork 56 or the loading and unloading device 21.Such a measuring device can, for example, be a length scale provided on the front wall 23, which is detected by means of an optical sensor arranged on the loading and unloading device 21, in particular on the carriage 58. The length scale can, for example, be formed by a predetermined barcode on the surface of the front wall 23.

[0191] The combination of a loading and unloading device 21 with a height adjustment device, in conjunction with a rotor 1 that can be loaded with a reaction vessel unit 2 at different radii, allows for free selection between different radii. The rotor 1 described above, with retaining ribs 41 at varying distances from the axis of rotation 12, permits loading the rotor 1 with reaction vessel units 2 arranged at different radii within the rotor 1. This is advantageous, for example, when emptying reaction vessel units 2 of varying heights, as these units can preferably be inserted into the rotor 1 with their upper surface with minimal clearance below the discharge device 44. This is possible if the base section or base plate 42, which supports the reaction vessel unit 2, can be arranged at different radii on the rotor 1.These different radii, on which the base plates 42 or the base area of ​​the reaction vessel units 2 can be arranged, not only serve to compensate for different heights of reaction vessel units 2 during emptying, but also allow for special applications in which, for example, a stack of reaction vessel units 2 is arranged in the rotor 1. For instance, processes are being developed in which a first reaction vessel unit 2 is arranged in the rotor 1 with its openings 6 pointing radially outwards, and a second reaction vessel unit 2 is provided radially outside the first reaction vessel unit 2. The second reaction vessel unit 2 has corresponding reaction vessels 4 to the first reaction vessel unit 2, but these vessels have openings pointing radially inwards. The reaction vessels 4 of the second reaction vessel unit 2 contain materials that hold a specific liquid or...Specific quantities of liquid can be retained, such as by nonwovens or similar materials. In such a process, predetermined quantities of liquid can be automatically transferred from one reaction vessel unit 2 to another. With a suitable choice of the receiving material in the radially outer reaction vessel unit 2, it is also possible to separate different liquid components from each other, so that only a specific liquid component remains in the radially outer reaction vessel unit 2.

[0192] Such a centrifuge 19, which allows radially different positions of the reaction vessel units 2, enables new applications and processes. This is particularly advantageous when the axis of rotation 12 is horizontally oriented, as in the present embodiment, since the reaction vessel units 2 can then be inserted "upright," i.e., with their openings 6 facing upwards, into the centrifuge 19 or the rotor 1. Such loading can also be easily automated using the loading and unloading device 21 described above. With this centrifuge 19, new processes can thus be carried out fully automatically.

[0193] In the embodiment shown in Figure 3, the height adjustment device is designed such that the transport fork 56 can be positioned at different heights in the area of ​​the lower loading opening 26. It is also possible to provide a height adjustment device that can position the transport fork 56 at different heights in the area of ​​the upper loading opening 25, or one that has a greater stroke so that the transport fork 56 can be arranged in both the area of ​​the lower loading opening 26 and the area of ​​the upper loading opening 25.

[0194] The loading and unloading device 21, equipped with such a height adjustment mechanism, in combination with the upper loading opening 25 and the lower loading opening 26, enables the rotor 1 to be loaded with a reaction vessel unit 2, wherein the reaction vessels 4 are each arranged with their openings 6 facing upwards, allowing for both loading for emptying the reaction vessels 4 and loading for centrifuging the contents of the reaction vessels 4. To empty the reaction vessels 4, the reaction vessel unit 2 is fed to the rotor through the upper loading opening 25, which is located above the axis of rotation 12 of the rotor 1.The lower loading opening 26 is arranged below the axis of rotation 12 of the rotor 1, so that a reaction vessel unit 2, which is fed to the rotor 1 through the lower loading opening 26, points with its openings 6 towards the axis of rotation 12, so that liquid in the reaction vessels 4 is not ejected but centrifuged.

[0195] The height adjustment device can also be designed with such a large stroke that the transport fork 56 can be raised or lowered over the housing 20 of the centrifuge 19. A storage device for reaction vessel units 2 and / or counterweights for the rotor 1 can be provided on the top or bottom of the centrifuge 19. Such a storage device is also referred to as a plate hotel. It can have several vertically arranged compartments, one above the other, for receiving a single plate (= reaction vessel unit 2 or counterweight). However, such a plate hotel can also be designed from one or more rotatable disks, each with several receiving areas for a single plate.

[0196] The loading and unloading device 21 described above has a transport fork 56 for moving a base plate 42 or a reaction vessel unit 2. Such a transport fork 56 is very advantageous because the fork 56 has two fork tines 61, the distance between which can be adjusted. This allows the fork 56 to be adapted to different configurations of a rotor 1. Instead of a transport fork 56, a corresponding transport plate can also be provided, which is dimensioned so that it can be inserted into the centrifuge 19 between the receiving rails 34.

[0197] In principle, the loading and unloading device 21 can also be designed differently. For example, it can have a balcony similar to conventional centrifuges, but this balcony is height-adjustable and equipped with a slide so that a base plate 42 or reaction vessel unit 2 located on the balcony can be pushed into or pulled out of the rotor 1. With such a design of the loading and unloading device 21, it is advantageous to provide a coupling on the slide that can form a detachable connection with the base plate 42 or the reaction vessel unit 2. This coupling can be a magnetic coupling or a mechanical coupling. However, it is necessary that means for releasing the coupling be provided when the base plate 42 or the reaction vessel unit 2 is inserted into the rotor 1 and is to remain there.A magnetic coupling uses a suitable electromagnet, which is controlled accordingly. A mechanical coupling can be equipped with an electrically controlled actuator to release the coupling. However, when using a magnetic coupling, an actuating mechanism can also be provided in the rotor 1. This mechanism engages a stop against the base plate 42 or the reaction vessel unit 2 to prevent the base plate 42 or the reaction vessel unit 2 from being pulled out of the rotor 1. This prevents the magnetic coupling from disengaging automatically when the slide with the magnetic coupling is retracted. The stop can then be retracted before the rotor 1 is rotated.

[0198] In conventional centrifuges, the rotor was always designed to be as light as possible to minimize the moment of inertia. This allows for rapid acceleration and deceleration of the rotor. Since the present centrifuge 19 is intended to centrifuge reaction vessel units 2, each containing multiple reaction vessels 4, and these individual reaction vessels 4 are not always uniformly filled, significant imbalances can arise at the desired centrifugal accelerations simply due to the varying fill levels of the reaction vessels 4. Therefore, the initial idea was to weigh the reaction vessel unit 2 before loading the centrifuge 19 and then compensate for the imbalance using corresponding counterweights on the opposite side of the rotor 1. While this is technically feasible, it is very time-consuming and would significantly slow down the automated handling of the reaction vessel units 2.

[0199] Therefore, a new approach was taken, and the shaft 13 was designed with a high weight, while the rest of the rotor body 14 is comparatively light. In a first embodiment, the shaft rod 28 is made of steel. The shaft bodies 29, on the other hand, can be made of plastic, steel, or tungsten. If the shaft body is made of tungsten, this also means that it can be made of a tungsten alloy. In the present embodiment, the shaft bodies 29 are ring bodies with an outer radius of 31 mm, an inner radius of 10 mm, and a length of 27 mm. If the shaft bodies 29 are made of plastic, they are light and essentially function only as spacers between the rotor laminations 30. If, on the other hand, the shaft bodies 29 are made of steel, they weigh approximately 0.6 kg, and if made of tungsten, they weigh approximately 1.3 kg.Such wave bodies 29 can also be referred to as ballast rings. Since this concentrates the weight of the rotor 1 around the area of ​​the axis of rotation 12, the rotor 1 does become heavier due to such ballast rings, but the moment of inertia increases only slightly because of the small distance of the ballast from the axis of rotation 12.

[0200] There are different embodiments of the base plate 42. A distinction is made between a base plate 42 / 1 for evacuating reaction vessels (Figure 10a-10d), a base plate 42 / 2 for centrifugation (Figure 11) and a base plate 42 / 3 (Figure 12), which forms a counterweight plate for balancing the rotor 1.

[0201] The base plate 42 / 1 for evacuating reaction vessels has a rectangular, flat base wall 55 with a central recess 59. The rectangular base wall 42 / 1, as shown in plan view (Figure 10d), has two long sides and two shorter end faces. Along each of the shorter end faces, a raised rib 60 is formed on the base wall 55, projecting upwards and extending over the respective corners of the base plate 42 / 1. Thus, two U-shaped ribs 60 are provided in plan view, defining an area in which a reaction vessel unit 2 can be positioned on the base plate 42 / 1. The inner surfaces of the ribs 60 are arranged such that a standardized reaction vessel unit 2 can be positioned on the base plate 42 / 1 with minimal play and held securely in place.

[0202] The edge webs 60 have a vertical locking groove 64 on their outer surface in the area of ​​the longitudinal sides of the base plate 42 / 1 adjacent to each corner of the base plate 42 / 1.

[0203] The receiving areas 3 of the rotor 1, delimited by receiving ribs 34, for receiving a reaction vessel unit 2, have vertical, inwardly projecting locking projections 65 at the corresponding positions (Figures 14a, 14b). When the base plate 42 / 1 is inserted into the rotor 1, a locking connection is thus established between the base plate 42 / 1 and the rotor 1, thereby positioning the base plate 42 / 1, and thus also the reaction vessel unit 2 located on it, precisely in the rotor 1. The base plate 42 / 1, together with a reaction vessel unit 2, is arranged in the rotor 1 adjacent to a discharge device 44 such that, during centrifugation, the reaction vessel unit 2 is pressed against a circumferential edge region of the discharge device 44, so that both are sealed against each other and the liquid contained in the reaction vessels 4 is ejected and discharged in a controlled manner via the discharge device 44 to the discharge channel 49.

[0204] The base plate 42 / 2 (Figure 11) for centrifugation is designed similarly to the base plate 42 / 1 for evacuation and differs from it primarily in that the rim 60 extends completely around the base plate 42 / 2. This makes the base plate 42 / 2 for centrifugation heavier than the base plate 42 / 1 for evacuation. However, it is also stiffer due to the circumferential rim 60, which is advantageous during centrifugation because the base plate transfers the centrifugal forces exerted by the reaction vessel assembly to the rest of the rotor 1.

[0205] The base plate 42 / 2 has on each of its longitudinal sides a narrow guide web 66 projecting outwards in the plane of the base wall 55, which in turn is formed with locking grooves 64 adjacent to the corner areas of the base plate 42 / 2.

[0206] The locking projections 65 each extend in a vertical direction, i.e. perpendicular to the axis of rotation 12 between two adjacent support bars 41.

[0207] The base plate 42 / 3, which is designed as a counterweight plate, has the same shape as the base plate 42 / 2 for centrifugation and thus corresponding locking grooves 64 and is additionally provided with a weight plate 68, which gives the counterweight plate a predetermined weight.

[0208] In the same way as the base plates 42, the discharge device 44 is provided with locking grooves 67 into which the locking projections 65 can engage in a locking manner (Figure 15a, 15b).

[0209] Through these locking actions of the drainage device 44 and the base plates 42 / 1 for evacuating the reaction vessel units 2, the drainage device 44 and the base plates 42 / 1 and thus also the corresponding reaction vessel unit 2 are precisely aligned with each other.

[0210] The transport fork 56 has an upwardly projecting projection 69 on each of its fork tines 61 in the region of the rear end. These projections 69 serve, on the one hand, to push the base plate 42 or the discharge device 44 against the locking resistance when a base plate 42 or the discharge device 44 is inserted, in order to bring about the locking engagement of the locking projections 65 with the locking grooves 64, 67. In this process, the projections 69 press against the edge of the base plate 42.

[0211] When removing the base plates 42, the transport fork 56 is inserted into the centrifuge 19 or the rotor 1 at a distance below the base plate 42 and then raised so that the two projections 69 are located in the area of ​​the recess 59 of the corresponding base plate 42. When the transport fork 56 retracts, the projections 69 engage with the rear edge of the recess 59 of the respective base plate 42, so that sufficient tensile force can be exerted on the base plate 42 to release the locking connection between the base plate 42 and the rotor 1 and to remove the base plate 42 from the rotor 1. The discharge device 44 can be pulled out of the rotor 1 in the same way.

[0212] Figure 8 shows a table listing parameters of different configurations of the centrifuge described above and of two comparison centrifuges V1 and V2.

[0213] This table shows the radius R according to which the reaction vessel unit 2 is arranged with its upper edge in the rotor 1. The two comparison centrifuges (V1 , V2) were manufactured by the applicant for internal comparison tests.

[0214] The different configurations of the embodiment differ in the number of ballast rings (0, 4 or 6), which can also be made of steel or tungsten.

[0215] The table contains the number n of ballast rings of the different configurations, the material from which the ballast rings are made, and the weight m of the rotor 1 without load.

[0216] Furthermore, this table lists the moment of inertia I of the unloaded rotor.

[0217] The table lists the minimum and maximum rotor loads in grams. The load comprises the weight of a reaction vessel unit, with or without contents, and typically a counterweight inserted into the second receiving area 3 of the rotor 1. For example, a load of 50 g means that the rotor is loaded with a very light, thin reaction vessel unit with a small amount of contents, weighing approximately 20–30 g, and a corresponding counterweight of approximately 25 g inserted on the diametrically opposite side of the rotor. Experience has shown that a load of 50 g is a typical minimum load for such a rotor. The total load weight is usually in the range of 200–500 g, again distributed between the reaction vessel unit with its contents and the counterweight.In practice, it has been found that the maximum payload is approximately 800 g, with the weight distributed between the reaction vessel unit and its contents, as well as the corresponding counterweight. The interchangeable base plates 42 are assigned to the payload. / For the minimum and maximum payloads, the total weight OIG of the rotor, the total moment of inertia IG of the rotor, and the maximum possible mass deviation Am_per are listed.

[0218] When determining the maximum possible mass deviation Am_per ("per" for Permitted), it is taken into account that the rotor 1 is point-symmetric about the axis of rotation, so that the centers of mass of the two rotor halves are approximately the same distance r from the center of rotation. The maximum possible mass deviation Am_per is determined at a centrifugal acceleration of 575g. This is the case when, in the symmetrical rotor 1, a counterweight of mass m1 is located in one rotor half at a distance r from the center of mass of the counterweight to the axis, and the center of mass of the payload m2 in the other rotor half is at the same distance r from the axis; then:

[0219] Am = m2 - m1 (5)

[0220] The maximum possible mass deviation Am_per can be empirically determined for each centrifuge. For this purpose, the centrifuge is loaded with a counterweight mass m1 in one rotor half and the payload m2 in the other. In each test run, the centrifuge is accelerated to the same rotational speed OJ. Starting from a balanced state (m1 = m2), the mass of the payload m2 is increased slightly in each test run. Beyond a certain deviation Am, such strong vibrations are exerted on the centrifuge that further increases in the payload m2 are no longer possible, and the centrifuge does not remain stationary. This Am is the maximum permissible deviation Am_per. The table lists the values ​​for Am_per for a centrifugal acceleration of 575 g.

[0221] A permissible imbalance U for each centrifuge per (U: imbalance; per: permitted) can be expressed as:

[0222] Uper = Am_per xr (6)

[0223] Each centrifuge can be assigned a quality factor G based on the maximum permissible imbalance U. per assigned according to the following formula:

[0224]

[0225] If one substitutes the imbalance U in this formula per According to the above formula (4) then the following results:

[0226]

[0227] which can be resolved to Am_per:

[0228] >

[0229]

[0230] The quality factor can therefore be used to calculate the maximum possible mass deviation for a given radius r of a centrifuge.

[0231] Formula (8) shows that the larger the mass of the rotor m, the greater the maximum possible mass deviation Am_per can be. In other words, the larger the mass of the rotor, the greater the maximum possible mass deviation Am_per. Therefore, to achieve the largest possible Am_per, the rotor would need to be as heavy as possible.

[0232] Increasing the rotor weight generally also leads to an increase in the rotor's moment of inertia (I). This is true if the rotor's weight is uniformly distributed along its radius. However, the moment of inertia (I) should be kept low because, as explained above, the rotor is to be accelerated to high speeds, which, with a high moment of inertia, requires a correspondingly high torque and therefore a correspondingly powerful motor. High torque resulting from a large rotor mass is therefore disadvantageous.

[0233] The table lists a quality value Q, which is calculated using the following formula:

[0234]

[0235] where

[0236] I the moment of inertia of the rotor,

[0237] ITIG the total mass of the rotor and

[0238] r is the radius at which the reaction vessel unit is located.

[0239] The table in Fig. 8 shows that if the quality factor Q is greater than 0.65, the permissible mass deviation is less than 30 g, and the smaller the quality factor, the greater the permissible mass deviation. Conversely, if the quality factor Q is less than 0.5, less than 0.4, or less than 0.3, the permissible mass deviation is significantly larger. While there is no direct proportionality between the quality factor and the mass deviation, the table demonstrates that concentrating the mass in the region of the rotor 1's axis of rotation makes the centrifuge 19 considerably more tolerant of uneven loading. This is a significant advantage, especially for high-speed centrifuges with a rotational speed of at least 1000 RPM.Therefore, it is advantageous that the quality factor Q of rotor 1 is not greater than 0.6, in particular not greater than 0.5 and especially not greater than 0.3 and most preferably not greater than 0.25.

[0240] Regarding this quality factor Q, it is important to note that the radius r and the moment of inertia I are two quantities that are fundamentally linked, since the larger the radius r of the rotor 1, the greater the moment of inertia I, assuming the weight of the rotor 1 is uniformly distributed along the radius. In the present embodiment, however, a centrifuge with a relatively large radius (approx. 100 mm) is used, where the moment of inertia I is small, but the mass of the rotor 1 is large.

[0241] The preferred configurations of rotor 1 listed in the table above exhibit a moment of inertia with loading IG in the range of approximately 13 Mg*mm. 2 up to about 25 mg*mm 2 on.

[0242] If the centrifuge 19 is to be used to empty the reaction vessels by means of the discharge device 44 described above, then it is advantageous for the centrifugal acceleration after the first full rotation from standstill to be as close to 3g as possible, and preferably as close to 6g as possible. This assumes that the drive unit 22, as is typical for electric motors, applies a constant torque to the rotor 1, resulting in a constant or uniform acceleration. Such rapid acceleration of the centrifuge prevents the liquid to be discharged from dripping back from the discharge device 44 into one of the reaction vessels 4.In principle, it would be acceptable for individual liquid droplets to drip back from the discharge device 44 onto the reaction vessel unit 2, since they would then be removed from the reaction vessel unit and discharged again via the discharge device 44 upon further acceleration of the rotor 1. However, if the liquid to be removed contains molecules where a single molecule already constitutes contamination, as is sometimes the case in biological processes, then it may be advantageous to prevent backflow from the discharge device 44 altogether.

[0243] For the above-mentioned configurations of rotor 1, with a radius of 100 mm and an acceleration due to gravity g of 9.8 1 m / s², the following results: 2 that to achieve a centrifugal acceleration of 3 g, an angular acceleration of 23.4 rad / s is required. 2 and an angular acceleration of 46.8 rad / s² from 6 g 2The necessary torques M for achieving a centrifugal acceleration of 3 g or 6 g after one revolution are listed in the last two rows of the table in Figure 8. To achieve a centrifugal acceleration of 3 g after one revolution, a torque of at least approximately 300 mNm is required, although torques of more than 400 mNm or 500 mNm may be required depending on the configuration and loading conditions. Conversely, to achieve a centrifugal acceleration of 6 g after one revolution, a torque of at least approximately 600 mNm is required, and depending on the configuration and loading conditions, at least 750 mNm, at least 900 mNm, and particularly at least 1000 mNm may be necessary. The centrifuge 19 is therefore preferably equipped with a motor capable of exerting such a torque on the rotor 1.

[0244] Figure 16a shows a typical centrifugal acceleration profile over time, as achievable with a conventional swing-out centrifuge. The acceleration and deceleration phases each last approximately 20–30 seconds. Centrifugation can then be performed at a centrifugal acceleration of approximately 300 g for several minutes (usually about 3–7 minutes). Applying such a centrifugal acceleration profile to the cell washing procedure described above would result in the concentration of both the cells and, compared to cells, smaller debris within the retention area of ​​the reaction vessels. Debris has a diameter approximately 0.1 times that of the cells (typically about 10 pm).

[0245] Figure 16b shows a centrifugal acceleration profile that the applicant performed on a conventional centrifuge for comparison purposes. The maximum centrifugal acceleration was significantly increased. This approximately triangular profile exhibits a long acceleration phase, resulting in a maximum centrifugal acceleration of approximately 600–800 g. Once this acceleration is reached, the centrifuge is decelerated accordingly. This reduces the overall centrifugation time.

[0246] This results in less debris being concentrated in the retention area, as the debris, due to its small size and low weight, moves much more slowly towards the retention area during centrifugation than the cells.

[0247] With the centrifuge according to the embodiment described above, the desired centrifugal acceleration can be achieved much more quickly, so that the acceleration and deceleration phases until the desired centrifugal acceleration is reached are significantly shorter. The desired centrifugal acceleration of, for example, 500–800 g can then be maintained for a predetermined period. As a result, primarily only the cells are concentrated in the retention area, and the debris, which moves much more slowly, does not reach the retention area during the considerably shorter centrifugation time. The short centrifugation with high centrifugal acceleration thus achieves a very strong separation between cells and debris. This is a significant advantage of the centrifuge according to the embodiment described above. [Reference numeral list]

[0248] 1 Rotor 35 Axial direction

[0249] 2 reaction vessel unit 40 36 absorption area

[0250] 3 Recording area 37 Mother

[0251] 4 Reaction vessel 38 Sections of the mounting rail 5 Bottom area 39 Through hole

[0252] 6 Opening 40 Connecting pin

[0253] 7 Connecting wall 45 41 Support bridge

[0254] 8 Longitudinal axis 42 Base plate

[0255] 9 upper area / vertical wall 43 abutments

[0256] 10 Funnel section 44 Drainage device

[0257] 11 Capillary cavity 45 Drain plate

[0258] 12 Rotation axis 50 46 Reinforcing strut

[0259] 13 wave 47 lamella

[0260] 14 rotor bodies 48 nozzles

[0261] 15 Rotor radius 49 Drainage channel

[0262] 16a Level 50 Ring opening

[0263] Level 16b

[0264]

[0265] 51 Drainage channel base body

[0266] 16c Level 52 radial outer ring cover element 17 Direction of rotation 53 radial inner ring cover element 18 Radius 54 Expiry

[0267] 19 Centrifuge 55 Bottom wall

[0268] 20 housings 60 56 transport fork

[0269] 21 Loading and unloading device 57 Shifting device

[0270] 22 Drive unit 58 Slides

[0271] 23 Front wall 59 Recess

[0272] 24 Back wall 60 Edge rib

[0273] 25 upper loading opening 65 61 fork tines

[0274] 26 lower loading opening 62 dispensing device

[0275] 27 sliding doors, 63 dispensing nozzles

[0276] 28 Rotor rod 64 Detent groove

[0277] 29 wave bodies 65 detent projections

[0278] 30 Rotor plate

[0279]

[0280] 66 Guide bridge

[0281] 31 Central section 67 Locking groove

[0282] 32 Connecting bridge 68 Weight plate

[0283] 33 Stopping section 69 Lead

[0284] 34 Recording bar

Claims

23 / 01 / 2026 International patent application BlueCatBio GmbH P392518WO Claims 1. Rotor for a centrifuge with a receiving area (3) for receiving reaction vessels (4), characterized by that the rotor (1) has several receiving areas (3) which are each designed to receive a plate-shaped reaction vessel unit comprising several reaction vessels and are at different distances from a rotational axis (12) of the rotor.

2. Rotor according to claim 1 , characterized by that several of the receiving areas (3) are arranged on one side of the rotor (1) with respect to the axis of rotation (12).

3. Rotor according to claim 1 or 2, characterized by that several of the receiving areas (3) are arranged on both sides of the rotor (1) with respect to the axis of rotation (12).

4. Rotor according to one of claims 1 to 3, characterized by that the receiving areas (3) are rectangular with two longitudinal sides and two transverse sides, wherein the longitudinal sides are arranged parallel to the axis of rotation (12) of the rotor (1).

5. Rotor according to one of claims 1 to 4, characterized by that the rotor (1) has at least two opposing receiving surfaces (36) on which retaining elements (41) are provided at different distances from the axis of rotation (12), with which a base plate (42) can each be detachably arranged, so that one of the receiving areas (3) is thereby limited in or against the radial direction.

6. Rotor according to claim 5, characterized by that a locking device (64, 65) or a coupling is provided for fixing at least one of the base plates (42) in the rotor (1).

7. Rotor according to any one of claims 1 to 6, characterized by that the rotor has a horizontal axis of rotation (3).

8. Centrifuge comprising a rotor (1) with a shaft (13) and a receiving area (3) for receiving at least one reaction vessel (4), characterized by that the rotor is designed according to one of claims 1 to 5.

9. Centrifuge according to claim 8, characterized by that the centrifuge (19) has an upper loading opening (25) and a lower loading opening (26) so that at least one of the receiving areas (3) can be loaded in both its maximum upper and its maximum lower position in the centrifuge (19).

10. Centrifuge according to claim 8 or 9, characterized by that the centrifuge (19) has a loading and unloading device (21) which is adjustable in height in such a way that the receiving areas (3) which are spaced radially apart from the axis of rotation (12) can be loaded and unloaded and in particular can be loaded and unloaded with the loading and unloading device (21) both through the upper and the lower loading opening (25, 26).

11. Centrifuge according to one of claims 8 to 10, characterized by that the axis of rotation (12) of the rotor (1) is arranged parallel to a base surface of the centrifuge (19), so that the axis of rotation (12) is arranged horizontally during operation.

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