CUVET AND MEASURING METHODS

Description

[0001] The invention relates to a cuvette suitable for stirring a liquid. The cuvette has an interior space for holding the liquid. A guide rail for a ball is formed in the interior space, wherein the guide rail is formed by two projections that project from opposite walls of the cuvette into the interior space. The invention also relates to a related method.

[0002] A liquid in a cuvette can be stirred by moving a ball within the liquid. The guide rail inside the cuvette allows a defined path to be defined along which the ball moves during stirring.

[0003] US Patent No. 4,918,984 A describes a method and device for determining the time of a change in the physical state of a liquid medium, wherein a ferromagnetic sphere at the bottom of a liquid-filled beaker is excited to periodic movements under the effect of an external magnetic field. EP 1 681 564 A1 describes a device for measuring the coagulation behavior of body fluids with a magnetically attractable sphere that is movable on a plane inclined to the horizontal within the cuvette.

[0004] For certain applications, it is desirable to achieve a high fill level in the cuvette with a small amount of liquid. This is the case, for example, when conducting an analysis that requires light to pass through the liquid. Cuvettes with a guide rail usually have a comparatively large cross-section. Therefore, a larger amount of liquid is required to reach a certain fill level.

[0005] The invention is based on the object of providing a cuvette suitable for stirring a liquid, in which a large filling height is achieved with a small amount of liquid. Based on the cited prior art, this object is achieved by the features of claim 1. Advantageous embodiments are specified in the subclaims.

[0006] According to the invention, the guide rail has a straight section and is deflected upwards at both ends.

[0007] By forming the guide rail with projections that protrude from opposite walls of the cuvette into the interior, it is possible to keep the cuvette narrow. The sphere can thus be guided along the guide rail along a defined path, even though the distance between the opposite walls is barely larger than the diameter of the sphere.

[0008] The guide rail has a section where it extends in a straight line. The guide rail is deflected upwards at both ends. This upward deflection prevents the ball from hitting the end wall of the cuvette, which would otherwise exert high local pressure on the liquid.

[0009] The invention is based on the discovery that effective mixing of the liquid is possible by moving the ball along a straight section and then deflecting it upwards. The liquid can be pushed outward by the ball, move upwards there, and then return to the center in an upper region of the liquid. The described stirring movements result in complete and even mixing of the liquid.

[0010] As the ball rolls along the bottom of the cuvette, the liquid is subjected to considerable pressure. This is undesirable for sensitive liquids. Therefore, the guide rail is preferably positioned so that the ball rolling along the guide rail does not touch the bottom of the cuvette. For the most complete and even mixing of the liquid, it is advantageous if the ball is only a short distance from the bottom of the chamber.

[0011] In a preferred embodiment, the cuvette is therefore designed such that an imaginary first circle, oriented perpendicular to the guide rail and adjacent to the floor of the interior and two opposite side walls of the interior, intersects the two projections. More preferably, a smaller, concentric imaginary second circle does not intersect the projections. The diameter of the second circle is at least 50%, preferably at least 60%, more preferably at least 80% of the diameter of the first circle.

[0012] Where the ball rests on the guide rail, considerable pressure can act on the liquid. To minimize the impact on the liquid, the guide rail is preferably designed so that the contact area between the guide rail and the ball is small. In particular, the projection can be designed so that, viewed in cross-section, it has a convex shape in the contact area. The projection can extend in a closed shape from the contact area to the bottom of the cuvette. This avoids undercuts under which the liquid can penetrate.

[0013] The two projections can be aligned parallel to each other, resulting in a guide rail of constant width. The guide rail has a section in which it extends parallel to the bottom of the cuvette. The transition between a substantially horizontal section of the guide rail and the upwardly deflected section is preferably rounded, so that the ball is decelerated gently.

[0014] The side walls of the cuvette can be essentially parallel to one another. The side walls are the walls on which the projections of the guide rail are formed. Essentially parallel means that the side walls are aligned parallel to one another in the horizontal dimension, while a slight upward widening is permissible in the vertical dimension. It is possible for the side walls to be aligned parallel to one another in the vertical dimension as well. Tests have shown that it is beneficial for the mixing process if the side surfaces diverge slightly towards the top. For example, the side surfaces can enclose an angle of between 0.2° and 5°, preferably between 0.5° and 2° in the vertical dimension. All directions refer to the state in which the cuvette is standing upright on its base surface on a horizontal surface.

[0015] For optical measurements in which a light beam passes through the two side surfaces and the liquid arranged in the interior, it is advantageous if the path of the light beam through the cuvette is short. The distance between the outside of the first side wall and the outside of the second side wall is preferably less than 8 mm, more preferably less than 6 mm, more preferably less than 5 mm. The wall thickness of the cuvette in the region of the side wall is preferably less than 1.5 mm, more preferably less than 1.2 mm, more preferably less than 0.9 mm. Parallel to the side surface, the interior of the cuvette can extend, for example, over 8 mm to 15 mm. The interior of the cuvette can have a height between 20 mm and 30 mm.

[0016] To minimize the influence of the light passing through the side wall, the side wall can have a flat section. The flat section preferably extends over at least 50%, more preferably over at least 60%, more preferably over at least 80% of the total area spanned by the cuvette in the plane of the side walls.

[0017] To enable optical measurements, the cuvette is preferably made of a transparent material, preferably a transparent plastic. For example, the cuvette can be made of polystyrene. The cuvette can be manufactured as a one-piece injection-molded part.

[0018] The invention further relates to an arrangement comprising a plurality of such cuvettes. The cuvettes can be arranged one behind the other in the longitudinal direction defined by the side walls. The cuvette arrangement can be provided with a longitudinally aligned guide device so that the arrangement can be positioned along the guide device such that a light beam can pass through a specific cuvette in a fixed position. The guide device can comprise a rib, preferably two ribs, extending in the longitudinal direction of the cuvette arrangement. The ribs can be formed on the bottom of the cuvette arrangement. The arrangement of cuvettes can be manufactured as a single-piece injection-molded part.

[0019] The invention also relates to a system comprising a cuvette and a sphere. The sphere is preferably made of a magnetic material so that it can be moved along the guide rail by a magnet arranged outside the cuvette to mix the liquid. For example, the sphere can be made of stainless steel.

[0020] The diameter of the sphere is preferably dimensioned such that the distance between the sphere and the bottom of the cuvette differs from the distance between the sphere and the side wall of the cuvette by no more than 50%, preferably by no more than 20%, more preferably by no more than 10% when the sphere rests on the guide rail in the middle of the cuvette. In a preferred embodiment, the two distances are equal. The guide rail of the cuvette can be designed such that the respective distances remain constant when the ball moves along the guide rail. The distance between the sphere and the bottom of the cuvette is preferably less than 50%, more preferably less than 20%, more preferably less than 10% than the diameter of the sphere. In an arrangement comprising a plurality of cuvettes, one such sphere is preferably provided for each of the cuvettes.

[0021] The invention further relates to a system comprising a measuring device and such a cuvette. A filling element of the measuring device is designed to introduce a quantity of liquid into the cuvette. The measuring device also comprises a drive for the ball, which is designed to set the ball in motion to mix a liquid contained in the cuvette. The drive can drive the ball in such a way that the ball's movement is redirected upward at the end of the straight section of the track.

[0022] The drive can also be designed to bring the ball into a defined state when the cuvette is filled.

[0023] A defined position of the ball during filling of the cuvette is desirable because there is a risk of air bubbles forming when the liquid first hits the ball upon entering the cuvette. To avoid this, the ball can be positioned so that the liquid exiting the filling element does not hit the ball, but directly hits the bottom of the cuvette. The drive can be designed to move the ball into such a position and hold it there. This is preferably an off-center position in the cuvette, and more preferably a position at one end of the guide rail.

[0024] Alternatively, the drive can keep the ball moving while the liquid is poured into the cuvette. Any air bubbles that form are then immediately destroyed by the movement of the ball. The phrase "the ball is brought into a defined state by the drive" encompasses both the first variant, in which the ball is brought into a fixed position where it is not impacted by the liquid, and the second variant, in which the ball is kept moving during filling.

[0025] Such a system has independent inventive content, even without the cuvette being equipped with a guide rail.

[0026] In a preferred embodiment, the drive comprises a magnet that moves in a circular path. The ball can only follow the movement of the magnet in the direction specified by the guide rail. The circular movement of the magnet is thus converted into a linear movement of the ball. This makes it possible to drive the ball, for example, with a simple stepper motor. A measuring device with such a drive has independent inventive content, even without the ball being brought into a defined state during filling and without the guide rail being formed by projections in the side wall of the cuvette. The inventive concept can be realized with any type of linear guide rail.

[0027] The circular path on which the magnet moves can be arranged in the horizontal plane. The diameter of the circular path preferably corresponds substantially to the diameter of the cuvette in the longitudinal direction. The movement of the ball preferably extends over at least 50%, preferably at least 60%, more preferably at least 80% of the length of the guide rail. The rotational speed can be between 0.1 revolutions / second and 17 revolutions / second, preferably between 0.2 revolutions / second and 10 revolutions / second. The drive is preferably designed to move the magnet along a corresponding circular path to mix the liquid. The drive can also be used to stir the liquid.

[0028] The measuring device may comprise a measuring channel extending from a light source through the cuvette arranged in a suitable position to a light sensor.

[0029] The measuring device can also comprise a controller that is designed to control the functions of the measuring device in a suitable manner. In particular, the controller can be designed to control the interaction between the filling element and the drive. To this end, the drive can first be controlled so that it brings the ball into the defined state. Subsequently, the filling element can be controlled so that a specific amount of liquid falls into the cuvette. After filling, the sphere is preferably completely immersed in the liquid; more preferably, the fill level in the cuvette is at least twice as high as the diameter of the sphere. This makes it possible to arrange the measuring channel, which extends through the liquid, above the sphere so that the measuring process remains unaffected by any movement of the sphere.The filling volume of the liquid can be, for example, between 100 µl and 200 µl, preferably less than 180 µl.

[0030] The measuring device may further comprise a feed unit configured to feed a ball to the cuvette. A sensor may be provided to check for the presence of the ball. The measuring device may comprise a heater to heat the liquid in the cuvette. In particular, the heater may be configured to heat the liquid to a temperature between 35°C and 40°C. The heater may be configured such that the heating of the liquid quantity extends over a period of between 1 minute and 3 minutes.

[0031] The measuring device can comprise a plurality of measuring stations so that several samples can be examined simultaneously. Preferably, each measuring station comprises a drive and a measuring channel. A cuvette arrangement can be used in which several cuvettes are connected to one another such that each measuring channel extends through a cuvette. If the distance between the measuring channels is twice the distance between two adjacent cuvettes in the cuvette arrangement, two measuring runs can be carried out with the cuvette arrangement. In the first measuring run, every second cuvette is examined. The cuvette arrangement is then shifted by the length of one cuvette so that the measuring channels extend through the adjacent cannula that was unused in the first measuring run.

[0032] The measuring device can be used in particular to investigate the platelet reaction in whole blood or blood plasma. The procedure is as follows. First, a cuvette is inserted into the measuring device and a sphere is placed into the cuvette. The cuvette is positioned so that the drive can act on the sphere. The sphere is brought into a defined state. The whole blood or blood plasma is introduced into the cuvette. The blood or blood plasma is heated. During heating, the sphere preferably remains stationary. A reagent is added. The sphere is set in motion by the drive to mix the liquid in the cuvette. The light passing through the liquid is measured.

[0033] During the measurement, it is usually found that the turbidity decreases over the measurement period due to agglomeration of the platelets, meaning that increasing amounts of light can pass through the liquid. The course of the light intensity over time can be recorded. A measurement can, for example, extend over a period of between 10 and 15 minutes. Conclusions about the condition of the blood or blood plasma can be drawn from the recording. The measuring device preferably has five measuring stations so that a patient's blood can be tested using five different reagents simultaneously. If an arrangement of ten cuvettes is used, the test in question can be carried out successively for two different patients using the same cuvette arrangement.

[0034] The platelets in the blood or blood plasma react sensitively to deviations in the measurement process. The measuring device is therefore preferably set up so that the entire measurement process is fully automated to avoid deviations due to human intervention. For this purpose, the measuring device can have a holder into which the sample is inserted. The sample is preferably not moved for a certain period of time so that the blood or blood plasma can settle. The holder can then be slowly swirled once or several times to gently mix the whole blood. Swirling is preferably not necessary for blood plasma. A needle can be inserted into the sample to withdraw a specific amount of the liquid. The liquid can then be introduced into the cuvette to be examined according to the described process.Here it is particularly important for reproducibility that the ball moves on the guide rail, because this keeps the area in which high local pressure is exerted by the ball small. Furthermore, the uniform distance between the ball and the sides and bottom of the cuvette is important, as this ensures that the shear in the liquid that occurs during mixing is as uniform as possible. Furthermore, the inventive shape of the cuvette means that measurements are possible with a very small amount of liquid of around 150 µl. In contrast, conventional measurements require around 300 µl to 400 µl of liquid. Especially with samples from children, this amount of liquid is often not available.

[0035] The invention also relates to a method for examining a liquid, in particular blood or blood plasma, in which light is passed through a quantity of the liquid arranged in a cuvette, and the light passing through the liquid is recorded. The method can be carried out using a cuvette according to the invention and / or a measuring device according to the invention. The method can be further developed with features described in connection with the cuvette according to the invention and / or in connection with the measuring device according to the invention.

[0036] The invention is described below by way of example with reference to advantageous embodiments in the accompanying drawings. They show: Fig. 1: various views of a cuvette arrangement according to the invention; Fig. 2a: an enlarged sectional view of parts of a cuvette from Fig. 1 ; Fig. 2b: an enlarged sectional view of the cuvette from Fig. 2a with a ball; Fig. 3: a schematic representation of a measuring device according to the invention in a side view and a top view; Fig. 4: a schematic representation of a measuring device according to the invention for performing an optical measurement on the liquid; and Fig. 5: a side view of the measuring device from Fig. 4 .

[0037] A cuvette 14 according to the invention is arranged as part of a cuvette arrangement 15 according to the invention in the Figuren 1a und 1c in plan view and in the Figuren 1b und 1d shown as a sectional view. A cuvette 14 comprises an interior 18 enclosed by a cuvette housing 17, which is in contact with the environment via an inlet 19. Extending through a lower region of the interior 18 is a guide rail 20, which is connected to the cuvette housing 17.

[0038] In this embodiment, the guide rail 20 is curved upwards at both ends and follows the contour of the cuvette housing 17. Furthermore, the interior space 18 is slightly widened from bottom to top. Furthermore, the cuvette housing 17 has a guide device 25 on a lower outer side, which extends over all cuvettes 14 of a cuvette arrangement 15.

[0039] In an enlarged view in Fig. 2 the lower part of a cuvette 14 according to the invention is shown. As in Fig. 2a As shown, the guide rail 20 extends within the interior space 18 along a lower side of the cuvette housing 17 and continues along a rounded edge and another side of the cuvette housing 17. In Fig. 2b A ball 22 with a defined diameter is arranged in the interior 18 such that the ball 22 rests on the guide rail 20. Apart from the illustrated support points (contact area) on the guide rail 20, the ball 22 is not in contact with the cuvette housing 17. The distance between the lowest point of the ball 22 and the cuvette housing 17 is identical to the distance between the lateralmost points of the ball 22 and the side wall of the cuvette housing 17.

[0040] The curvature at the ends of the guide rail 20 ensures that the ball 22 cannot run into the end wall of the cuvette. When the ball 22 moves at high speed along the guide rail 20, it can run up the ends and is thus decelerated before it comes into contact with the cuvette housing 17.

[0041] In Fig. 2b It can be seen that an imaginary first circle, whose diameter is slightly larger than the diameter of the ball 22, intersects the two projections 12, 13 of the guide rail 20. In contrast, an imaginary second circle, which is slightly smaller than the ball 22, does not intersect the two projections.

[0042] Fig. 3 shows a cuvette assembly 15 consisting of ten cuvettes 14, with the guide rails 20 of the individual cuvettes 14 arranged in a row. A ball 22 is arranged in every second cuvette 14. The position of the balls 22 is determined by the magnets 27 arranged outside the cuvette housings 17, which interact with the ferromagnetic balls 22.

[0043] The magnetic interaction makes it possible to hold the ball 22 in a defined state, for example, at one end of the guide rail 20. Such a defined state of the ball 22 is particularly advantageous when introducing a liquid into the interior 18 (not shown) using a filling element (not shown). This prevents a pipetting jet from directly impinging on the ball 22, which would otherwise cause unnecessary turbulence in the liquid. Furthermore, it is possible for the ball 22 to be in a defined state by moving slowly or at a constant speed along the guide rail 20, as explained in connection with the method according to the invention.

[0044] The method according to the invention for stirring a liquid in a cuvette can be understood by means of the illustrated states of the balls 22 and the magnets 27. In the upper part of the Fig. 3 is the cuvette assembly 15, with balls 22 and magnets 27 shown from the side, while the same condition in the lower part of the Fig. 3 seen from a bird's eye view. In this embodiment, the magnet 27 is shown in the form of a cylinder, which has a rectangular cross-section when viewed from the side and a circular cross-section when viewed from above.

[0045] During one full rotation according to the method according to the invention, the magnet 27 moves once along a circular path, while the ball 22 moves back and forth along the guide rail 20. If the states in this exemplary representation are viewed from left to right, the ball 22 is initially arranged on the right side of the guide rail 20, while the magnet 27 is placed directly below the ball 22 under the right side of the guide rail 20. If the magnet 27 moves clockwise along a quarter of a circular path, the ferromagnetic ball 22 rolls to the center of the guide rail 20 and further to the left edge of the guide rail 20 when the magnet 27 has covered the second quarter of the circular path. The return path occurs analogously until both the magnet 27 and the ferromagnetic ball 22 have reached their starting positions again.

[0046] The magnet 27 can be driven stepwise by a stepper motor (not shown), and the ball 22 can be partially or completely immersed in a sample (not shown). The repeated movement of the ferromagnetic ball 22 then creates a pumping effect in the sample, ensuring that the sample is efficiently mixed.

[0047] In Fig. 4 and 5 A machine according to the invention for determining the turbidity of a liquid is shown, which is designed to carry out the method according to the invention and is filled with a cuvette arrangement 15 according to the invention. The cuvette arrangement 15 has, as in Fig. 3 shown, in every second cuvette there is a ball 22. The arrangement of the balls 22 and the alignment of the magnets 27 located underneath is identical to the example from Fig. 3 The guide device 25 of the cuvette assembly 15 interacts with the machine such that the cuvette assembly can be displaced horizontally and aligned according to the magnets 27. In addition, in this embodiment, five stepper motors 28 arranged in a row, which can be controlled separately, form part of the machine according to the invention. The stepper motors 28 are each designed to move a magnet 27 along a circular path. This enables simultaneous stirring in five cuvettes.

[0048] The machine according to the invention enables the turbidity of a sample to be determined fully automatically during stirring or after stirring has been completed. For this purpose, a measuring channel 30 is provided, which extends through the cuvette 14. The measuring channel 30 is preferably arranged so that it extends centrally and at a height at which the interior space 18 is completely filled with a sample. During the measurement, the ball 22 should be arranged or moved in a range that does not obscure the measuring channel 30.

[0049] In Fig. 5A side sectional view of the machine according to the invention for determining the turbidity of a liquid is shown. The measuring channel 30 extends between a light source 31 and a photodetector 32 in such a way that the light passes through the cuvette 14 in a region above the sphere 22. Light emitted by the light source 31 passes through the cuvette housing 17 into the interior 18 of the cuvette 14, transmits through the sample, and exits the cuvette 14 again through the cuvette housing 17, where it is finally recorded by a photodetector 32.

[0050] The interior space 18 should have a small expansion in the area of ​​the measuring channel 30 so that the light is not completely absorbed by the sample. In the area of ​​the measuring channel 30, the cuvette housing 17 should not exceed a wall thickness of 2 mm to avoid distorting the measurement results. Furthermore, the measuring channel 30 should be sufficiently large to cover a representative area of ​​the sample.

[0051] The machine according to the invention enables the turbidity of a sample or of various samples to be measured simultaneously in five measuring channels 30. Following the measurement, the cuvette assembly 15 can be shifted horizontally, for example, by one cuvette position, to align the five previously unused cuvettes 14 with the stepper motors 28 and measuring channels 30 and to repeat the stirring according to the method according to the invention and the turbidity measurement.

Claims

1. Cuvette for stirring a liquid, comprising an inner space (18) for receiving the liquid, and comprising a running rail (20), formed in the inner space (18), for a ball (22), wherein the running rail (20) is formed by two projections (12, 13) which project into the inner space (18) from opposite side walls (10, 11) of the cuvette (14), characterized in that the running rail (20) has a rectilinear portion extending parallel to the base of the cuvette and is deflected upwards at both ends.

2. Cuvette according to Claim 1, characterized in that an imaginary first circle, which is aligned perpendicularly with respect to the running rail (20) and which touches the bottom of the inner space (18) and the side walls (10, 11) of the inner space (18), intersects the two projections (12, 13), while a smaller, concentric imaginary second circle does not intersect the projections (12, 13), wherein the diameter of the second circle is at least 50%, preferably at least 60%, more preferably at least 80%, of the diameter of the first circle.

3. Cuvette according to Claim 1 or 2, characterized in that a contact region exists between the running rail (20) and the ball (22) when the ball (22) rests on the running rail (20), wherein the projection (12, 13) is designed such that, when viewed in cross section, it has a convex shape in the contact region.

4. Cuvette according to one of Claims 1 to 3, characterized in that the side walls (10, 11) of the cuvette (14) are substantially parallel to one another.

5. Cuvette according to one of Claims 1 to 3, characterized in that the side walls (10, 11) of the cuvette (14) include an angle of between 0.2° and 5°, preferably of between 0.5° and 2°, in the vertical dimension.

6. Cuvette according to one of Claims 1 to 5, characterized in that the distance between the outer side of the first side wall (10) and the outer side of the second side wall (11) is less than 8 mm, preferably less than 6 mm, more preferably less than 5 mm.

7. System composed of a cuvette (14) according to one of Claims 1 to 6 and of a ball (22), characterized in that the ball (22) bearing on the running rail (20) is spaced apart from the bottom surface of the cuvette (14) by a distance which differs by no more than 50%, preferably by no more than 20%, more preferably by no more than 10%, from the distance from the side wall (10, 11).

8. System composed of a measuring device and of a cuvette (14) according to one of Claims 1 to 6, characterized in that the measuring device comprises the following elements: a. a filling element which is configured to introduce a quantity of liquid into the cuvette (14); b. a drive (28) for a ball (22) arranged in the cuvette (14), wherein the drive (28) is configured to bring the ball (22) into a defined state when the filling element fills the cuvette (14), wherein the ball (22) in the defined state is moved to a position so that a liquid exiting the filling element does not impact the ball (22) but impacts directly the base of the cuvette (14), wherein the drive (28) is configured in such a way that it moves the ball (22) and keeps the latter in such a position.

9. System composed of a measuring device and of a cuvette (14) according to one of Claims 1 to 6, characterized in that the measuring device comprises the following elements: a. a filling element which is configured to introduce a quantity of liquid into the cuvette (14); b. a drive (28) for a ball (22) arranged in the cuvette (14), wherein the drive (28) is configured to bring the ball (22) into a defined state when the filling element fills the cuvette (14), wherein the drive (28) is designed to keep the ball (22) in motion in the defined state while a liquid is being filled into the cuvette (14).

10. System according to Claim 8 or 9, characterized in that the drive (28) comprises a magnet moved on a circular path.

11. System according to one of Claims 8 to 10, characterized in that the measuring device comprises a measuring channel which extends from a light source (31) to a light sensor (32) and which extends through the cuvette (14) above the ball (22) resting on the running rail (20).

12. System according to one of Claims 8 to 11, characterized in that the measuring device comprises a plurality of measuring stations, wherein each measuring station has a measuring channel (31, 32) and a drive (28).

13. Method for examining a liquid, in which a light beam is guided through the liquid arranged in a cuvette and the transmitted part of the light is measured, characterized in that the cuvette (14) is designed according to one of Claims 1 to 6.