FI91041C - A method of mixing a batch of liquid in a vessel for analysis - Google Patents

Description

91041 and 5

Method for mixing a batch of liquid in a vessel for analysis - Fårfarande for blandning av en våtskesats i eet kårl f6r analys

The invention relates to a method for mixing a batch of liquid in a container. The method is especially intended for mixing liquid samples in measuring waters to be analyzed with automatic clinical chemistry analyzers.

The components of the liquid batch to be mixed in the cuvette are typically dispensed with a dispensing needle flexibly connected to an automatic microsyringe. The dosing takes place in such a way that the sample and the diluent or reagent and possibly air bubbles are sucked into the dosing needle with a syringe to separate them from each other. The tip of the dosing needle is placed in a cuvette into which the sample with diluent or reagents is emptied. Thereafter, the dispensed components and any reagents previously present in the ky-20 water are mixed together. The mixing is performed mechanically, e.g. by moving the dosing needle in a high cuvette using a separate mixer or by performing the mixing with ultrasound. After mixing, the cuvette is transferred to incubation, 25 measurements, etc. for further processing.

Said known liquid batch mixing methods are all more or less slow and cumbersome. The use of a separate mechanical stirrer is laborious and constitutes a step of more than 30 in the preparation of the liquid batch for analysis. The tip of the dosing needle, on the other hand, is inefficient as a mechanical stirrer due to its narrowness.

The object of the present invention is to provide a solution with which the batch of liquid to be analyzed can be mixed more efficiently from the enclosure without the need for any separate, mobile stirrer in the vessel. In the method according to the invention, the mixing takes place with a needle comprising a flow channel 2 with at least one suction and discharge opening at the end, holding the opening in the container below the liquid surface and performing the mixing in reciprocating movements. sprayed from the flow channel back into the vessel.

The method is characterized in that in the mixing carried out for the analysis of a batch of liquid, a needle is used, the flow channel of which has a narrowing extending substantially to the opening at which it reaches, according to which the flow resistance of the channel 10 increases at least tenfold. a converging and then turbulently disintegrating liquid flow, and that the reciprocating mixing movements are performed such that the moving liquid volume is at most about 15 to 20% of the total volume of the liquid batch to be mixed.

According to the invention, the batch of liquid is mixed with a needle for analysis, which can also be used for dispensing the components of the liquid batch into a container. However, in the analyzes so far, unlike the procedure used so far, the needle does not need to be moved, but the mixing is based solely on the movements of the liquid produced by the needle. Conventional dosing, in which the liquid contained in the straight, constant-diameter dosing needle is sprayed at once into the container, is generally not sufficient to cause said mixing of the liquid in the container, whereas in the invention, this orifice at the end of its flow channel and thereafter 30 is sprayed under pressure substantially linearly away from said orifice, and in particular according to the vena contracta -ϊίπι virtaδη of the flow to be sprayed into the vessel due to the turbulence generated in the liquid. In addition, the mixing of the liquid can be influenced by the location of the needle suction and discharge opening 35 or openings, which will be described in more detail below.

É! 91041 3

A preferred embodiment of the invention is characterized in that the mixing is combined with the simultaneous dispensing of liquid by the needle, wherein the amounts of liquid drawn from the container into the needle are on average less than the amounts of liquid sprayed from the 5 needles into the container. That is, the liquid to be dispensed is discharged into the container in small portions during the dispensing and mixing process. Such a procedure is faster than performing the dosing and mixing separately, and has the additional advantage that the liquid to be dispensed continuously flushes the flow channel inside the needle and prevents its contamination.

Of course, it is also possible for the needle to be dispensed first, in which the liquid to be dispensed is discharged from the needle into the container 15, after which the liquid in the container is mixed with said reciprocating mixing movements. In this case, the amount of liquid sucked into the needle and injected back into the container can be kept constant throughout the mixing operation.

20

According to the invention, the amount of liquid to be reciprocated in the mixing of the liquid batch according to the invention can be about 0.1-5%, most preferably about 0.1-2% of the total volume of the liquid batch to be mixed. The volume of the 25 liquid batches processed by the clinical analyzers ranges from 1 to 1000 μΐ, and the typical volume of liquid to be agitated in mixing is of the order of 1 μΐ. If liquid dosing is combined with the mixture, the amount of liquid to be dispensed can be e.g. about 10% of the total volume of the liquid batch.

30

In mixing, the frequency of the reciprocating mixing movements can be between about 5-200 Hz, preferably between 10-100 Hz, depending on e.g. the softness of the material of the cored lead connected to the needle or the air possibly contained in the lead.

35 For example, a frequency of 50 Hz can be obtained simply by a rectified mains voltage.

4

The duration of the mixing according to the invention can be about 0.1-2 s, preferably about 0.2-1 s. If the mixing lasts e.g. 0.5 s, this means a liquid suction and spraying step at a frequency of 50 Hz. . By known methods, the time taken for mixing is typically 2-4 s, in addition to which the time taken for dosing must be calculated. As mentioned above, within the time spent mixing the invention, it is also possible to administer a dosage that maximizes the time savings achieved by the invention.

10

The reciprocating mixing movements required by the invention are preferably effected by repeated compressions on the line of elastic material extending the needle, as a result of which the volume of the line changes. Compression pie-15 reduces the volume of the lead and forces the liquid to discharge from the needle into the container. Correspondingly, the cessation of compression increases the volume of the line, which causes suction from the container to the flow channel of the needle. Repeated compressions can be achieved, for example, by passing the line between the piston of the solenoid valve 20 and the fixed surface opposite it and by moving the piston back and forth by means of a spring force and an electric force applied by an electric current. Alternatively, repetitive compression can be provided by a fork formed by two piezoelectric crystals with the wire located between ceramic, metal-coated plates bending against each other.

The narrowing inside the flow channel of the needle used according to the invention, which provides said vena 30 contracta appearance in the flow to be sprayed into the vessel, is preferably conical, so that its conical angle can vary between about 15-60 °.

Said vena contracta appearance, on which the mixture according to the invention is essentially based, can be produced by a needle whose flow channel terminates in a straight line in the discharge opening at the tip of the needle, provided that the channel has a narrowing along which the flow resistance strongly increases.

II

91041 5 vaa. However, from the point of view of mixing, the needle is even more efficient, in which the flow channel ends before the tip of the needle in one or more discharge openings directed sideways from the longitudinal axis of the needle. The liquid flows are then directed to the sides of the needle towards the side walls of the container and from them further towards the bottom of the container. The result is the quenching of the kinetic energy contained in the liquid flows into the turbulence and flow of the currents generated in the cuvette.

10

The invention will now be described in detail by way of example with reference to the accompanying drawings, in which Figure 1 shows a suction step 15 of a liquid batch mixture according to the invention in which liquid is sucked from a vessel into a needle flow channel 4 show the suction-20 and discharge steps of the mixing according to the invention, in which the needle used differs from that shown in Figures 1 and 2, and Figure 5 shows the reciprocating mixing movements by repeated compressions on the tube extension of the needle.

25

The mixing of the liquid batch 1 according to Figures 1 and 2 takes place in a vessel 2 formed by a cuvette to be used in automatic analyzers. The mixing takes place by means of a needle 3 comprising a tubular shaft 4, a flow channel 5 inside the shaft 30 and a suction and discharge opening 6 at the tip of the needle at the tip of the needle. 7, along the length of which the diameter of the channel decreases e.g. η. 1 mm to 35 less than 0.5 mm.

According to Figures 1 and 2, the mixing takes place in reciprocating movements, in which the needle 3, the tip 6 of which is below the liquid surface 8 in the cuvette 6, is alternately sucked liquid from the cuvette into the flow channel 5 inside the needle. In this case, the linear velocity of the liquid jet flowing into the cuvette at the average distance of the liquid to be mixed is a multiple of the velocity of the liquid flowing into the needle at the same point. The amount of liquid to be reciprocated is typically of the order of 1 μΐ, which is suitably 0.1-5% of the total volume of the liquid batch 1 to be mixed in the cuvette, although it may be larger. According to the arrows in Fig. 1, the liquid is sucked from the approaching suction and discharge opening 6 approximately evenly from different sides of the opening. In the discharge step according to Fig. 2, on the other hand, the liquid jet 9 advances far from the opening 6 towards the bottom 15 10 of the cuvette, from where it rotates back towards the liquid surface 8 according to the arrows, causing mixing of the liquid batch 1 over its entire volume. This mixing is substantially promoted by the venous contraction effect provided by the conical constriction 7 of the flow channel 5, according to which the liquid jet 9 discharged from the opening 6 20 first converges and then spreads and begins to disintegrate into turbulence at the edges of the jet.

According to Figures 1 and 2, the cuvette 2 can be mixed in any way with a pre-metered batch of liquid 1.

However, the same needle 3 can be used for dosing, with which the liquid batch 1 is then mixed according to the invention. It is further possible that the liquid is dispensed into the cuvette 2 and the mixing takes place simultaneously. The liquid 30 to be dispensed is then in the flow channel 5 of the needle 3, and in each case a slightly larger amount of liquid is sprayed from the needle into the cuvette 2 than is drawn from the cuvette into the needle. In this case, the needle 3 is emptied of the liquid to be dispensed during simultaneous dosing and recirculation.

As an example of the simultaneous mixing and dosing according to the invention, the following can be shown: The cuvette contained 90 μΐ of liquid which had been boiled 100 times in excess protein to test the mixing. 10 μΐ of a second liquid corresponding to the consistency of the water was dispensed here with a needle with a diameter of 0.25 mm between the two suction and discharge openings. The duration of the procedure was 1 s and the frequency of the frontal movements was 50 Hz, whereby the procedure comprised 50 consecutive suction and spraying steps. In each suction step, the amount of liquid drawn into the needle was 1 μΐ and in each spraying step, the amount of liquid discharged from the needle into the cuvette was 1.2 μΐ. The linear flow velocity of the jets of liquid discharged into the cuvette was about 5 m / s measured in air, when the stirring turbulence inside the liquid did not allow the measurement. The linear flow velocity of the suction phase, measured microscopically using microparticles, is less than 0.01 m / s. The mixing was optically complete at the end of dosing when the needle was shaken. at the speed of the shaking method, mixing was not complete even with a mixing time of 5 seconds after dosing.

The successive, repeated suction and discharge steps of the mixing of the liquid batch 1 in the cuvette 2 shown in Figures 3 and 4 generally correspond to what has been described above. The difference, however, is the needle 3 used for mixing, in which the conically tapering flow channel 5 ends before the needle tip 11 in two suction and discharge openings 6 which are directed obliquely from the longitudinal direction of the needle. The tip 11 of the needle 3 is sharply tapered and closed.

In the suction step seen in Fig. 3, the needle 3 sucks liquid from the openings 6 into the flow channel 5 inside the needle in substantially the same way as the needle according to Figs. 1 and 2.

In the discharge step according to Fig. 4, the jets of liquid are directed from the openings 6 initially towards the side walls 12 of the cuvette 2, from which they turn towards the bottom 10 of the cuvette and the other towards each other. At the same time, the jets disintegrate according to the aforementioned vena contracta-il-35 mi6n, which contributes to the effectively mixing turbulence of the liquid generated in the entire liquid volume l. The mixing is even stronger than in the case shown in Fig. 2, which has the further advantage that the liquid jets directed to the sides of the needle 3 hold the liquid 1 to be mixed better without the risk of splashing in the cuvette.

Figure 5 shows a needle 3 filled with a stirrable liquid 1 in a cuvette 2, which is connected to a feed formed by a flexible rubber hose or a flexible plastic or metal tube 13. The hose 13 is guided by two metal-coated ceramic plates 14. -10 between this piezo crystal. The repeated pressures exerted on the hose 13 by these flexible plates 14 alternately reduce and expand the volume of the hose so that the needle 3, as the hose expands, draws liquid from the cuvette 2 and, as the hose contracts, sprays the liquid back into the cuvette.

The plates 14 are most preferably slightly skewed relative to each other so that the compression closes the hose 13 starting from the end of the compression farthest from the cuvette 2. This ensures that the spraying is directed towards the cuvette 2 in each case.

20

Corresponding reciprocating movements of the liquid could also be effected by means of a solenoid valve by placing a fixed response of the hose 13 and alternately the magnetic force generated by the spring force and the electric force alternately in different directions between the piston 25 of the load.

It will be clear to a person skilled in the art that the various embodiments of the invention are not limited to the above examples but may vary within the scope of the appended claims.

Claims (9)

91041 9 A method for mixing a batch of liquid (1) in a vessel (2), the method comprising mixing with a needle (3) comprising a flow passage (5) having at least one suction and discharge opening (6) at the end, holding the opening in the vessel below the liquid surface (8) and by mixing in a reciprocating motion, the liquid being alternately sucked from the vessel into the flow channel in the needle and alternately sprayed from the flow channel back into the vessel, characterized in that the mixture is analyzed by a needle (3), the flow channel (5) of which has a constriction (7) extending substantially up to the opening (6) at its end, along the length of which the flow resistance of the channel increases at least tenfold, whereby turbulent decomposition fluid flow (9), and that the reciprocating mixing movements are performed in such a way that the moving n the amount of barrier is at most about 20% of the total volume of the batch of liquid to be mixed. 20 A method according to claim 1, characterized in that the mixing is combined with the needle (3) for simultaneous dosing of liquid, wherein the amounts of liquid drawn from the container (2) into the needle are on average less than the amounts of liquid sprayed from the 25 needles into the container. A method according to claim 1, characterized in that the needle (3) is first dispensed, in which the liquid to be dispensed is discharged from the needle into the container (2), after which the liquid (1) in the container is mixed with said reciprocating mixing movements. Method according to one of the preceding claims, characterized in that the amount of liquid to be reciprocated during mixing is about 0.1-5% of the total volume of the liquid batch (1) to be mixed. 10 Method according to one of the preceding claims, characterized in that the frequency of the reciprocating mixing movements is about 5 to 200 Hz, preferably about 50 Hz. Method according to one of the preceding claims, characterized in that the duration of the mixing is about 0.1 to 2 s, preferably about 0.5 s. Method according to one of the preceding claims, characterized in that the reciprocating mixing movements are effected by repeated compressions on the line (13) of flexible material extending the needle (3), as a result of which the volume of the line changes. Method according to one of the preceding claims, characterized in that the flow channel (5) of the needle (3) tapers conically at an angle of approximately 15-60 ° towards the opening (6) at the end of the channel. Method according to one of the preceding claims, characterized in that the discharge fluid flow is directed in the needle (3) before the openings (6) towards the sides of the needle located at its tip (11) towards the side walls (12) of the container (2). ti 91041 11