NO127720B - - Google Patents

Description

Treatment device for liquid sample solution.

The present invention relates to a system for examining liquid samples at hospitals and laboratories, however small. quantities of unprocessed liquids are processed by e.g. to be spiked with different reagents and then examined, and the invention relates more particularly to improvements in processing apparatus for such systems.

The invention will be described in more detail below with regard to blood testing, but it is obvious that it is not limited to this. Clinical examinations which are carried out routinely in hospital laboratories have become increasingly important in the diagnosis and treatment of diseases, and they are also used to a large extent in connection with treatments for the prevention of diseases. A large number of samples must therefore be processed daily in most laboratories. In the past, so-called "automatic chemistry" devices have been used, with the help of which a majority of investigations have been able to be carried out by a majority of samples in a more or less continuously acting sequence.

In the many different ways in which a majority of samples have been handled, many have included a "flow-through system" as opposed to a "rate system". The immediately obvious difficulty with the flow-through systems is the identification of the sample, the problem of mixing different samples as well as the difficulties connected with the structurally and functionally complicated and expensive devices.

In order to be able to handle samples in a natural way, with the "batch system" you manage to use a simpler apparatus than with the "flow-through systems". The invention brings advantages, which seem to make the "rate method" more accepted by medium-sized and small hospitals and laboratories, but it is likely that larger institutions can also benefit from the invention. On the other hand, the opposite need not be the case, since the small institutions do not have the financial opportunity to take advantage of the great advantages associated with the more complicated and expensive flow-through devices.

With the "rate system", a good identification of the sample can be achieved. The processing of the sample can be closely monitored during the course of the examination. and the necessary equipment for processing the sample containers is relatively simple. Furthermore, with the batch method, one can use the automatic or semi-automatic addition devices, which the laboratory already possesses with only a minor, if at all, necessary change, or the devices can be easily modified for adaptation to a fast system without having to give up from some of the benefits.

According to the invention, a method has been provided to solve the problem of handling many different samples. according to which a capillary tube is used for. collection and/or

baking container ice of the raw liquid sample. The raw fluid extract, which in the following description is derived from blood, is introduced into one - six in one .. of the capillary tube, which is ;outf o-rmeit: with!;e,ri-:noyåkåd fort, internal, diametrical bore, so that the length of the blood column in this section of the tube gives a linear value, which corresponds to a given volume. When one unprocessed liquid sample is used, the glass is scratched, the capillary scar is broken between two appropriate points and the tube is broken so that the soil is broken at these points. This can be done manually or automatically, and the final products form a piece of the capillary tube _with eh, precisely measured amount of raw liquid contained therein. The whole tube piece is placed -in a container containing as large an amount of solvent or reagent as is necessary for the test to be carried out, and the container is shaken so that the blood is diluted and mixed. according to the invention, consists of one or more containers for the sample solution mounted on a holder arranged to guide the container in a treatment path, where each container is guided into position until several stations for different types of. treatment of the sample solution and containing one; injection device which is arranged to inject a reagent into the container, one at a time. the a-v containers are provided with readable characters for identification of the special type of reagent that is intended to be injected into the resp. container., and a reading device is provided for in dependence

.of every single legible character to be able to produce a signal

.'for transfer to - a device .to be able to stop the container in question in the correct position in relation to the reagent injector and to provide an injection of the correct type of reagent into the container, and. the device is characterized according to the invention by the fact that each container is cup-shaped and has a central cavity, in the middle of which is mounted a hollow cylinder which forms a hollow cylinder inside, and one liquid channel connects between the bottom of the cylinder and the bottom of the cavity through a capsule that contains the raw liquid sample, and which is arranged to be able to be broken off into a piece, of predetermined length containing a given volume of the sample liquid, arranged to be placed in the central cylinder, the reagent injector being arranged to could • spray reagent into the capillary tube and push the reagent through the capillary tube, wash this and mix the resulting solution while the capillary tube is placed in the center cylinder.

Other features of the device, according to the invention, appear from the following description and the following patent claims.

The invention will now be described in more detail with reference to the drawings, where: fig. 1 shows in perspective a sample container according to the invention,

fig. 2 is a plan view of the container according to fig. 1,

fig. 3 is a vertical, central cross-section along the line III III in fig..1,

fig. h is a horizontal cross-section along the line IV - IV' in fig. 3,

fig. 5 is a section through a piece of a capillary tube, showing how a certain amount of crude liquid can be contained therein,

fig. 6 is a vertical cross-section similar to that according to fig. 3, which cross-section shows a simplified embodiment of a sample container, and in which a piece of a capillary tube is inserted into the hollow column, and where a connection from a source of reagent is connected to the column to enable an injection of liquid into this and through the capillary scar provide a correctly diluted liquid sample,

fig. 7 is a fragmentary vertical section through a modified embodiment of a sample container and shows the manner in which a connecting sleeve can be provided for connection with the upper end

of the hollow soyle,

Fig. 8 is likewise a fragmentary section essentially along the line. VIII - VIII in fig. 6,

fig. 9 is a plan view of a modified embodiment of a sample container, showing the container without the soil mounted therein to thereby show details at the bottom of the recess,

fig. 10 is a fragmentary vertical section along line 10-ID in fig. 9, but in this case the soyle is placed in place, and in the inner cavity of the soyle a section of the capillary tube is also shown,

fig. 11 is a schematic, perspective view showing a holder provided with a sample container, and the figure also shows the procedure for inserting the capillary rib pieces into the holder's hollow column; and

fig. 12 shows, in schematic section, a holder provided with a sample container in connection with filling reagents through the syringes and those in the soil resp. cavities occurring capillary scar br.

In fig. 1 shows a container or cup 20, which is made of some suitable plastic material, which is indifferent to the liquids it is intended to contain. The container is intended for one-time use, and therefore any cheap material can be used for its manufacture. The container is provided with a central recess 22 with a lower end 2h, which can be considered to form the bottom of the recess even if it is provided with means for. to feed liquid down below this level. In the embodiment shown, the walls of the recess are conically designed, but other forms of the recess can be used as required. The container's bottom 26 is flat to enable its mounting on a table or a flat surface, as will be seen below. Two parts are connected to the container 20, one of which 28 is provided with a channel 30 with a rectangular cross-section, while the other forms a fastening member 32 provided with a channel 3^ with inwardly directed flanges 36, in which an identification card 38 or the like can be placed. The identification card 38 is indicated by dotted lines in fig. 1 and somewhat schematically in fig. 12, although it is not necessary to have knowledge of the card's details in order to understand the present invention. It is sufficient to state that the identification card 38, which is held in frictional engagement with the channel 3^? is provided with an index or fixing device in the form of a perforation, which cooperates with a pin MO attached to the container, and that the card is significantly longer than the vertical height of the container 20, so that the identification card, when the container is mounted on a surface M2, as as shown in fig. 12, extends downwards below this surface h- 2. This is also marked in fig. 1.

The purpose of the channel .30 is to enable attachment of the container to one of the posts M-t-, which is shown in fig. 12, so that the container together with several other containers is fixed and placed in the correct position for a consecutive treatment or examination.

A shallow recess Mo is arranged in the center of the bottom 2h of the recess 22. A rectangular, transverse bridge M3 connects the recess M6 with the bottom of the recess 2*+ at its upper end and is so deep that it extends down below the bottom of the recess M5. In the recess M6, a central column 50 is inserted, which is provided with holes, so that it forms a channel 52 for receiving a capillary tube as this will be explained in more detail below. It appears that the bridge M3 directly communicates with the channel 52, so that liquid fed into the channel 52 can be directed into the recess 22. In reality, the liquid will be forced from the channel into the recess 22.

Soylen 50 can be made of some suitable inert material such as e.g. glass, plastic or similar. Preferably, the soil can be produced from a piece of some commercially available plasterboard, which is preferably sufficiently rigid to be able to be pressed into the recess M6.

No capillary tube is shown in figures 1 - 55, but it should be noted that the inner diameter of the channel 52 must be slightly larger than the outer diameter of the capillary tube used, so that it can easily be fed into the channel. In the same way, the recess Mo' and the bottom 1+8 must be shaped in such a way that the lower end of a capillary tube piece, which is lined all the way down to the bottom of the soil 50, does not axially cooperate with any surface in such a way that the tube the piece's through channel is completely blocked. There must be a small clearance between the capillary tube piece and the inner surface of the channel 52.

In fig. 5 shows a capillary piece 5^, which has been cut to a specific length, so that it will contain a known volume amount of raw sample liquid 56 in its through bore. In fig. 6 shows a simplified embodiment of the sample container, denoted 20', but otherwise the same reference designations are used as for the container 20 described above. The only difference is that it is not shown equipped with projections 28 and 32, nor are any recesses indicated of the type designated by 58 in fig. 1, and which is a result of using a conventional technique for economical stuffing of containers. The bottom of the container 20' is denoted by 26, and the column 50 is fixed in the recess <1>+6, so that its channel 52 is connected to the channel 1+8, so that a connection is established for feeding liquid from the channel 52 to the recess 22.

Since in this case there is no fastening means 32, other handling and identification means can be used, such as e.g. magnetic organs. A coating of magnetic material is symbolically shown with the designation 60, which material is arranged to be able to receive identification information, and a track 62 can be used for together with an appropriate gap or projection, e.g. that in fig. 11 showed projections 6>+, to attach the containers 20' in the event that a plurality of containers are to be handled automatically, e.g. mounted on a conveyor or similar. The principle purpose of fig. 6 is to explain the manner in which the soil serves to receive a capillary piece and cooperate with an injection means.

It can be assumed that a capillary scar piece 56 is fast into the channel

52 in the soil 50 either in a container 20 of that in fig. 1 shown or in a container 20' of the type shown in fig. 6. The dilution required by the examination can now be carried out. The Subsbkel identification appears either from the identification card 38 or is placed on the magnetic surface 60 in the form of readable characters. A flexible line 66 leads from a source of reagent, such as a bottle of an appropriate diluent, which has been specially prepared for the examination to be carried out. A coupling 68 is connected to the line 66, and a head 70, which fits rigidly over the upper end of the soil 50, is threaded on, so that liquid fed through the line 66 can be forced through the channel 52 and push the raw liquid 56 out of the capillary tube 5^ cavity and into the recess 22 for the container 20 or 20'. In this way, an accurately measured volume of diluent can be pressed into the container, and to ensure that complete dilution and mixing takes place, a quantity of gas, e.g. air, after the liquid has left the reagent source, is forced through line 66. This serves to blow all the liquid out of the capillary tube, and if air blowing then continues, the air will bubble through the liquids in recess 22 and mix them. Since the dimensions of the various organs are very small, not only the pressure of the liquid but also the pressure of the gas must be of such a magnitude that the desired functions are carried out, but not so high that liquid can be blown out of the container. An ordinary container is smaller than about 25 mm hby and approx. 17 mm in diameter, measured on the inner diameter of the container at its upper end, while the bottom of the conically designed recess at level 2h is approx. 9.5 mm. With such a design of the recess, you can easily handle liquid quantities of approx.

2 to 3 ml.

A gasket can be used to provide a good seal between the coupling 68 and the free end of the spool 50, and this gasket can be designed as a small O-ring 72 placed in a suitable groove in the inner surface of the coupling head 70.

The coupling 68 may be incorporated in a piston, extending from the reagent source, which is provided with a measuring means and some other automatic means for injecting reagent or diluent, which will be further explained below.

The device for introducing liquid into the container after the capillary root cross-section is placed in the channel 52, and as shown in Fig. 6, does not require any special shape of the central column 50. It can be produced by a simple, cut-off section of a commercially available plastic tube which is inserted into the socket h6. The container is stbpt in one piece, either in the simple form as the container 20' in fig. 6 has or in the more complicated form that the container 20 in fig. 1 - k have, each of which is provided with the relevant selection 1+6. The piece of plastic must be so rigid that it can be pressed into the socket, and so that it is held firmly without the need to glue it in place. A glass rbr can also be inserted in the same way. It is probably most appropriate to stuff the soil 50 and the container 20 in one piece, if the current stuffing technology had not required such complicated stuffing forms. At present, stuffing in one piece is not economically justifiable.

In fig. 7 shows a modified embodiment of the soil. In this case, the nozzle 50' differs from the previously described designs in that it is designed with an extended nozzle 51. However, in fig. 7 shown container 20" to be identical to the other two described embodiments. The extended nozzle forms an extended introduction guide 535 which is arranged to be able to receive a conically designed male coupling 70' arranged at the end of the line 66, which leads the diluent to the container 20". The input slot 53 controls the coupling 70' to. plant in the soil 50'. This arrangement is advantageous due to the fact that no packing is needed here to prevent leakage. The tapered fit can be made by grinding or some other suitable method to ensure complete contact. Another advantage of the extended nozzle 51 is that it enables a simpler introduction of the capillary tube piece into the column 50'. In other words, it also serves as a control in this case. For the case that one handles a large number of containers and has to insert the capillary tube pieces in each of these, the introducing end of the soil, designed as a guide, enables this to be easily carried out mechanically, which will be explained below.

In the containers 20 and 20', the well KS is designed as a side branch to the outlet K6, but it is placed deeper than the outlet, so that liquid can pass freely from the channel 52 into the well k8. The dimensions have been chosen so that the bottom surface h7 of the outlet

k- 6 is crossed by the bridge only over a small part, whereby sufficient water is obtained for the lower end of the bilge, despite the fact that a liquid channel is always present. In fig. 8 shows a section along the dotted line in fig. 6. Here you can see the lower end of the syringe 50, the channel 52, the bottom end of the capillary tube piece $ K and an opening 56', which indicates the channel through the capillary tube 5<*>+, which is normally filled with some form of untreated liquid such as previously mentioned blood. From this figure it appears that the bottom of the capillary tube piece 5<*>+ has good support without the hole 56' being blocked in any way whatsoever, and liquid can therefore easily flow into the tube 56 and from there further into in recess 22.

If a given pressure is applied to the reagent which is introduced into the capillary tube 5^, all of this pressure is relieved at the bridge 8 by the devices described so far. If the capacity for liquid flow through is increased in the well K8, it is less likely that liquid will be pushed out of the container. Preferably, one uses a device of the type shown in fig. 9 and 10. In this case, the radial fbtter 80 are stuck at the bottom of the recess of a container such as e.g. the container 20, 20' or 20". The upper surface of these feet is arranged in a plane, which in the previously described devices should be defined as the bottom level 2h in the recess 22, while in this case the bottom of the quadrant-shaped holes 82 will in practice form the bottom of the container bottom, since the quadrant-shaped bottoms have a significantly larger area than the upper surfaces of the fbttes 80.

The feet 80 are not fashioned in the center of the container, but instead are shortened so as to form a central, generally square surface 8<*>+, which freely communicates with the holes 82. The radial inner tips of the feet 80 are provided with steps at 86, to form a seat for the bottom of the cylinder, corresponding to the socket >+6 in the embodiments described above. In this case, the lower, axial end of the spool 50 rests against four points. This is not shown in fig. 9 but on the other hand in fig. 10. The feet 80 are so long that the steps 86 extend radially inward a sufficient distance to provide support for the axial lower end of the capillary tube 5 as it is inserted into and pushed down to the bottom of the channel 52 without stopping at the capillary bore. .. In fig'. 10 shows the liquid flow channels from the capillary tube's 5<*>+ "hole into the wells 82 - and from there into the recess 22. It appears that - the liquid pressure is reduced in each of the wells 82, by the liquid dividing into four strbm- more, which also results in better mixing. When air is then injected, this produces bubbles in four different positions, which likewise further increases the mixing effect. It is less likely that with this embodiment you will get any splashing of liquid.

If one then turns attention to fig. 11. one sees there a plurality of containers 20' mounted on a conveyor or a belt 90 provided with a fixing device of the type described, which e.g. takes 6h on the conveyor, which cooperates with track 62 in the containers. The means shown with the reference designation '92' can be produced by some form of positioning means or holder which can be used instead of or next to the fixing means. The purpose of fig. 11 is to show how a plurality of capillary pieces 5<*>+ of appropriate length (and possibly containing a predetermined amount of liquid) can be fed into the flushes of a plurality of containers, which pass past a reagent injector . The introduction device for the capillary tube is denoted in the drawing by 9^?°g and it feeds one capillary tube piece at a time into the flushes of the passing containers. The introduction station is correctly fixed with regard to the passing conveyor 90 and the containers standing on the conveyor. These stand for so long at this station that they have time to receive their resp. pipe pieces because they are moved further. An arrangement of that in fig. 7 is of great advantage in this case, since it controls the insertion of the capillary strips, and therefore the transporter's 90 movement pattern with regard to the insertion station and the insertion device 9'+ need not be so accurate.

It should also be noted that a certain number of containers can be supplied with raw pieces containing raw samples from the same test source to be subjected to different examinations, or

each rudder section can originate from different sample sources. It is important that the identification of the sample source with the container containing the raw sample from resp. source, is secured.

In fig. 12 shows an embodiment of a treatment device for liquid samples, in which the sample containers 20 are of the same type as shown in fig. 1 - and. where each container is attached to a post M+, which in turn is attached to a holder 96. Each container is provided with an identification card 385 which extends down below its holder, so that it can be partially displaced relative to and into a pressure apparatus for or after the examination. The identification information is thus noted on the cards in the form of characters, which can be read by both humans and machines.

In practice, a holder 96 is provided with samples from the same or from many different sample sources, but in any case the containers are easily identifiable both with regard to the sample source and the type of analysis to be carried out. The holder is mounted in a device, which displaces this in relation to a plurality of stations, where each station is provided with means for supplying different reagents. It is necessary that the correct reagent is introduced into each sample container in accordance with the examination to be carried out. The apparatus according to the invention is designed to ensure such a result.

At the three stations schematically shown in fig. 12, illustrated

of the three cylinders 100, 101 and 102, it is intended that three different reagents are to be injected into those of the containers which are to be supplied with precisely this reagent. Each cylinder can be part of a injection device for a liquid reagent, which does not differ particularly from the previously known constructions found in bottle filling machines, but which is activated in accordance with the described system. The filling devices are connected to sources not shown in the drawings for reagents of various kinds, and they are provided with a rubber connection, which, on impact, is pushed down to rest against the free end of the flush, which, when the container is correctly positioned, is

itself immediately under the coupling. In fig. 12, the connecting links 68 are shown located at the lower ends of the reciprocating pistons 103. The middle piston is pushed down, while the two outer pistons are in their retracted positions •

By the one in fig. 12 device shown, each station, in addition to the injection device for the reagent liquid, is also provided with a reader 10, which is arranged to be able to read the characters affixed to the identification card 38. Each reader is designed to be able to respond to the type of inquiry that requires the reagent, which can be introduced at precisely this station. Thus, if the identification card is not provided with the special characters to which the reader is responsible, nothing happens at the station, regardless of whether the holder 96 moves or stands still. When a question mark produces a response in the reader, the holder is stopped with the container fixed at the station controlled by the reader in question. A trigger or push-off device is then actuated, which is capable of the same signal, whereby the reagent liquid injector is actuated to fill the container, by the piston pushing down the coupling connection 68 to the column 50 and forcing liquid through the channel 52 in the column thereby to provide a proper dilution of the subdilution test in the container. After the liquid has been rapidly drawn in, the plunger retracts the connecting link 68, and the holder is then free to move further. The holders can be arranged to move past a single or a plurality of stations. The effective identification of the samples and the sample sources makes it unnecessary to place the containers in any particular order in the holder 96.

Claims (9)

1. Treatment device for liquid sample dissolution consisting of one or more containers (20) for the sample solution mounted on a holder (e.g. 90) arranged to guide the containers (20) in a treatment path, where each container (20) is guided into position until several stations for different types of treatment of the sample solution and containing an injection device (e.g. 100) arranged to inject a reagent into the container, each of the containers (20) being provided with legible signs for identifying the particular type of reagent which is intended to be sprbytes into resp. container (20), and a reading device (104) is arranged to, depending on each individual readable character, be able to generate a signal for transfer to a device to be able to stop the relevant container (20) in the -correct position in relation to the agent - the injector (100) and to provide an injection of the right kind of reagent into the container (20), characterized in that each container (20) is cup-shaped and has a central cavity (22), in the middle of which is mounted a hollow soyle (50) forming a hollow cylinder (52), and a liquid channel (43) runs between the bottom of the cylinder (52) and the bottom of the cavity (22) and a capillary tube (54) which contains the raw liquid sample (56") and which is arranged to be broken off into a piece of predetermined length containing a given volume of the sample liquid (56), arranged to be placed in the central cylinder (52), the reagent injector (100) being arranged to be able to spray reagent into the capillary tube piece (54) and push the reagent through the capillary tube piece (54), wash this and mix the resulting reading while the capillary tube piece (54) is placed in the center cylinder (52). 2. Apparatus as stated in claim 1, characterized in that the hollow column (50) is mounted in a holder (46) arranged in the bottom (24) of the cavity (22). 3. Apparatus as stated in claim 2, characterized in that the holder for the soil (50) consists of a recess (.46) in the bottom of the container (20) and the liquid channel between the soil (50) and the hollow pipe rim (22) is formed by a bridge (48) connecting the outlet (46). with the hollow rim (22). 4. Apparatus as specified in claim 3, characterized in that the bottom of the burner (48) is at a level that is lower than that of the outlet (46). and the bottom of the sink (50). 5- Apparatus as stated in any of the claims 2-4, characterized in that the cavity (22) of the container (20) is cylindrical about a vertical axis and the soil (50) connects coaxially with the cavity (22) and extends a considerable distance centrally upwards through the center of the cavity (22). 6. Apparatus as stated in claim 5, characterized in that the cavity (22) of the container (20) is shaped like an upright, truncated cone. 7. Apparatus as stated in any of claims 2-6, characterized in that the bottom (24) of the cavity (22) is designed with a number of radial ribs (80) which together define a largely circular holder (86) for the soil (50) arranged so that the bottom of the soyle (50) lies above the bottom of the cavity (22), and where the feet (80) delimit segment-shaped boards (82) which form channels between the cavity (22) and the cylindrical space (52) of the soyle (50). 8. Apparatus as specified in any of claims 2-7, characterized in that the soil. (50') is designed with an extended upper end (51) which forms a guide inside the cylindrical cavity (52). 9. Apparatus as specified in any of the preceding claims, characterized in that the capillary tube piece (54) is open at both ends and designed with a diameter that is somewhat smaller than the diameter of the cylinder space (52), to enable easy insertion of the capillary tube piece into this room.