NO125556B - - Google Patents

Description

Device for multiple and automatic

analyzes of liquid mixtures.

The present invention relates to a device for multiple and automatic analyzes of liquid mixture samples, each of which is made up of a mixture in selected proportions of a liquid substance to be analysed, and an addition of a reagent. The device is especially, but not exclusively, intended for on the basis of various samples, e.g. blood samples, urine samples, etc., and to measure physiological characteristics, e.g. urea content, cholesterol content, number of leukocytes per unit of volume in the blood, sugar content, etc.

There are known systems for multiple and automatic analyzes which, at the start of a circuit run, mostly comprise a so-called sampling apparatus which makes it possible to obtain a mixture

in specific proportions of the substance to be analyzed and of reagents.

It is this mixture that is called the sample. At the end of the circuit, a measuring device, in which the sample is placed, measures a physical quantity that characterizes the sample and which makes it possible to determine the quantities of the various elements that are sought in the substance to be analyzed. The measuring device most often used in multiple and automatic analysis devices is the colorimeter, which comprises a light beam source that emits radiation with a specific wavelength that passes through the sample and a photoelectric cell that is energized by the radiation that leaves the sample, and which emits an electrical voltage depending on the quantity of the desired substance in the sample.

Between these two devices, the sample is subjected to certain treatments, e.g. mixing, heating, cooling, irradiation, etc.

The facilities that are now known for automatic analysis have provided far greater possibilities than the manual methods that were previously used.

After all, these systems still entail numerous manual interventions that often give rise to serious errors. The main shortcomings of the current facilities should be briefly mentioned.

Possible identification errors:

- contamination of the samples in relation to each other,

-significant consumption of often expensive reagents,

- low rate for the measurements,

-poor adaptation to the available data processing options, as the processes to be carried out take too long for data processing devices, -low reliability for the entire facility, a piece of fibrin can stop an entire process sequence, -poor measurement reliability: for example, footbometer cells in contact with all the products, become unclear and cause significant deviations, which are expensive to determine and remove.

In the current facilities for multiple or automatic analyses,

the sample is generally placed at the exit from the sampling apparatus, in individual vessels or containers, e.g. rudder or crucible. The handling of these individual containers towards the measuring device, through the intermediate treatments, makes it necessary, when desired. to multiply or automate the analyses, to use complicated devices, e.g. plates that rotate and carry the individual containers. Moreover, the individual containers are so expensive that it is necessary to reuse them, whereby it becomes necessary to wash them. Incidentally, these containers do not make it possible to

carry out measurements, especially chlorimetric, through the walls, so that it is necessary to pour the contents into the measuring device, whereby multiple and especially automatic analyzes become difficult to carry out. Finally, the products are mixed using mechanical or magnetic stirrers that are immersed in contact with the sample, which entails the risk of contamination.

There are other facilities which are better than those mentioned above, and in which the product to be analyzed and the reagents are taken out in specific conditions in a suitable way, most often by means of a dosing pump, and fed into a rudder to measuring devices under the action of one pump. The liquid samples are separated using? gas segments. The rudder is connected to the measuring device where the samples follow one another. The rudder is generally made of plastic which is soft and transparent.

This device nevertheless has serious disadvantages. First of all, the sample flows in the same tube and this causes contamination of a sample by those that go ahead, and so that the measurement accuracy is reduced. The effect of this contamination is all the greater if capillary tubes are used to carry out the analyzes in small quantities, as the ratio between the contact surfaces and the volume of the sample thereby increases.

Another disadvantage is due to the fact that the advance speed of the sample in the rudder must be small for the flow to remain laminar,

otherwise the gas separation between two samples that follow one another will not be certain.

This limits the pace of the automatic analyses, although the relevant devices for sampling and measurement otherwise allow a fast pace of the order of magnitude of one analysis per Sec.

Another disadvantage of this facility lies in the fact that

use is limited to the presentation of liquid samples.

In a facility for automatic analyses, it is finally important, in order to avoid errors, that each sample can be marked individually during the entire passage. Carrying out the test in a rudder does not make it possible to carry out this marking.

The main purpose of the present invention is to provide a device of the type indicated above and in which the aforementioned disadvantages are avoided.

This is achieved according to the invention by means of a device whose distinctive feature is that it includes a transport bridge for moving the sample, and which is designed by a number of chambers that are closely connected and firmly interconnected, each chamber being extended by a flexible and transparent material and arranged to receive a mentioned liquid mixture sample, at least a transfer means for withdrawing a given quantity of liquid and/or reagent from a corresponding storage container and transferring this to at least one chamber on a transporter by placing the connected storage container under gas pressure, the transfer device is equipped with a single wire, which is given such a translational movement that one end of it is fed into the storage container and its other end is fed in turn into each chamber along the transport beam, whereby the end that is fed into the storage container can be placed on one or the other side of the liquid level in this container<*>, at least one device for mechanical treatment etc g heat treatment of the liquid mixture samples in the conveyor's chambers, as well as at least one measuring device of photocolorimetric type for analyzing the sample, and which is designed to be connected to a data processing device for producing the measurement results at a faster rate, while the liquid mixture samples are moved along the analysis device with the help of the conveyor.

With the aid of the analysis device of the invention, a facility for multiple analyzes is achieved, which is mainly automatic and works at a fast pace, as well as enabling processing of the measurement results in a modern data processing device. The analysis device according to the invention also makes it possible to largely eliminate all errors in the identification of the sample, and if such an error does occur, it can be detected with absolute certainty. Furthermore, suitable liquid mixtures can be prepared by adding very precisely to the taken samples. dosed amounts of small volume reagents. The device of the invention also enables the use of the relevant photometric apparatus under the best working conditions, without the risk of the transparency being reduced.

A large number of physiological data can thus be reliably measured using the analysis device of the invention.

According to a further distinctive feature of the invention, the conveyor is appropriately defined by a first and second belt of flexible and transparent material, whereby at least one of the belts

is provided with bulges in the form of deformations and bands

is liquid-tightly connected at least along the edges of the deformations for delimiting said chambers, which are formed by the protrusions, perpendicular to the direction of deformation. The tapes are also preferably equipped with perforations along the sides, for step-by-step mechanical feeding of the type used in film projectors. Furthermore, one of the conveyor belts is preferably provided with a magnetic track along the edges, which enables coded identification of the liquid that has been taken out.

In the analysis device according to the present invention

the sample is quickly advanced between the different devices by means of a film or a belt which carries a number of chambers with equal spaces between them and which consists of a flexible and transparent material. This device overcomes the disadvantages mentioned above and has the following advantages: - the handling of the samples takes place in individual containers, whereby the dangers of mutual contamination are avoided and it is possible to carry out a specific identification of each sample, - very small samples can be handled, e.g. samples that are less than 3

a cm,

-handling in deformable containers makes it possible to carry out

certain operations, especially mixing and transfer to the measuring device without the sample coming into contact with any foreign substance, - the handling of the sample takes place in a chemically inert manner in relation to the substances being transported,

- the handling of the samples in transparent containers does that

it is possible to observe them visually and to carry out colorimetric measurements or measurements with rays through the container walls, -the introduction of the samples in closed containers ensures against any evaporation, which is very important when it comes to volatile substances, -it is possible to introduce samples with hby viscosity or grbt-shaped or.powdered samples,

The movement of the sample, especially for presentation to a number of automatic analysis processes, can be easily simplified by the fact that the sample is arranged at a constant distance on a flexible carrier, similar to a cinema film, whose step-by-step presentation is well known. The speed of this step-by-step performance makes it easy to achieve a measure of one sample per Sec.

Finally, the price of the equipment used is according to

the invention so low that it is less than the costs of cleaning, so that it is not necessary to use the same equipment again, whereby any risk of contamination is avoided.

This is very important when it comes to analyzes of radioactive products.

Other properties and advantages of the device according to the invention will be apparent from the following description of a laboratory for blood analyses, and which is shown as an example,

on the attached drawings.

Fig. 1 shows the device for presenting samples.

Fig. 2 shows a cross-section along the line B-B in fig. 1.

Fig. 3 shows in perspective and broken down a device for presenting samples in a first embodiment. Fig. h shows the same device in section along the line C-C in fig. 3» Fig. 5 shows in perspective another embodiment of a device for presenting samples. Fig. 6 shows a side view of a device which is specially designed for transferring blood samples. Fig. 7 and 8 show in two sections the same device, following the lines D-D and E-E in fig. 6.

Fig. 9 shows in perspective a machine for taking samples.

Fig. 10 shows an identification card for samples.

Fig. 11 shows in perspective a detail of the identification machine shown in fig. 9. Fig. 12 schematically shows the identification station at the entrance to the central laboratory.

Fig. 12a shows part of this station on a larger scale.

Fig. 13-17 schematically shows the different phases when cutting and gluing tape or film that carries the sample.

Fig. 18 shows a synoptic view of an analysis series.

Fig. 19 shows the same row in perspective.

Fig. 20 schematically shows a machine for producing analysis film or tape. Fig. 21 shows in perspective a chamber or cavity in the analysis film. Fig. 22 clarifies the working principle for a device with withdrawal and injection pipettes in an analysis row. Fig. 23 shows in perspective a device for extraction and injection in a foil-drawn embodiment. Fig. 2h shows in perspective a device for limiting the movement of the replacement needle in this device. Fig. 25 shows a device for photocolorimetric analysis in an analysis series.

Fig. 26 shows a detail from fig. 25.

Fig. 27 shows how the cavity looks in the device shown in fig. 26. Fig. 1 shows a belt 1 which carries a number of identical containers 3 of transparent and deformable material. In the embodiment shown, the tape is formed of two films of soft, transparent '•' and heat-weldable thermoplastic material, which are superimposed,

and welded over part of the surface so that a casing is formed, the welding beams 2 being arranged so that the parts which are not welded limit a series of similar containers or capsules 3-

In the embodiment shown in fig. 1 and 2, the capsules have at least one opening h, which is preferably straight upwards to make it possible to insert a needle on a sampling device.

The welding of the two films that form the casing can be carried out so that the two films are not welded together along the upper edge at a height of a few mm, which thereby forms a groove where the needle of the sampling device engages during the movement of the casing, whereby the insertion of the needle into the containers is facilitated.

The containers can be of any shape. Their volume can be

as little as required and especially less than 1 cm^. It may

for example, but not absolutely, ensure that the volume is approximately double the sample to be taken.

In the case where the casing has a thickness which limits the deformability, slits 5 are taken out between each container.

In another embodiment, the device for presentation is extended

from two sheets of soft material that can be heat-welded, which are partially welded together, and where at least one of the sheets has indentations, the sheets not being welded together by these indentations which thereby limit the chamber.

A device, according to this principle, is shown in an exploded state in fig. 3 and comprises a first sheet 10 which is flat and made of soft heat-weldable material, and another sheet 12 which is also made of soft and heat-weldable material, for example, but not necessarily of the same material, where, e.g. e.g. during heat deformation, portions 13 are pressed in. These depressions have, for example, the shape of a parallelepiped. When the two sheets 10 and 12 are welded together, as shown in section in fig. •+, they thereby limit a chamber lh which can receive the samples in order to advance them or analyze them. in

The device according to the invention makes it possible to easily fill the chambers, as the edges for these are sufficiently wide to

could be pierced by a hypodermic needle.

The parallel pipette can be provided with a narrowing 15 and the piercing of the film by means of the filling needles then takes place through the area 15, which, after pulling out the 1 needles, can be clamped together by means of a heat clamp to thereby close the needle holes.

As shown in fig. 5, a double chamber can be obtained. One of these chambers 16, which is decorated with a top 17, is connected to the neighboring chamber 18 through a line 19 which is also formed by a depression in the film 15-

These double-chambers are used when the products are fast in

in the chamber 16 form precipitates. The line 19 is lined with a suitable porous material 20. By pressing together the chamber 16, e.g. by means of rollers, it is possible to transfer all liquid to the chamber 18 while the solid sediment remains in the chamber .16.

In another embodiment, it is possible to give the depressions that form the chamber an arbitrary shape, e.g. shape of a ball cap.

Optionally, a chamber with a larger content can also be achieved, wood

to make depressions in both sheets and weld the sheets together in places that are not deformed, while the depressions lie opposite each other.

Films of the type shown in fig. 1-5 are fbr they are formed

and are welded with perforations that make it possible to advance them in the same way as with cinema film.

Fig. 6-8 show the respective in perspective and in different sections, an embodiment of a device for presenting sampling materials which is particularly suitable for blood sampling.

This device will be referred to below as the elementary film.

The container is formed by two chambers 30 and 31 in different chambers which are connected to each other through a line 32. The first chamber is intended, for example, to receive the blood sample which is to be subjected to chemical analysis in the central laboratory, while the smallest chamber must be haematologically analysed.

Each chamber contains a specific reagent or anticoagulant, either in the form of liquid that is injected into each of the chambers for the blood collection, or in the form of thin layers of soluble solids that are placed in the chambers as they were formed.

The devices shown in fig. 3-8 is provided with a magnetic track 35 which lies parallel to the edge of the film and whose purpose will be explained below.

This track is either formed by means of a coating of magnetic ink arranged on the film, or by means of a magnetic kiebe tape glued to the film.

Otherwise, the chambers are arranged on the film so that there is sufficient space between them or between each of them and the edge of the film so that it is possible to stick a label for identification of the sample they contain.

Fig. 9 shows in perspective a machine for taking samples of

the species which, according to the invention, is arranged in each collection centre.

The elementary films of the kind shown in fig. 6 contains a certain number of double chambers, e.g. 30°g 31"The number of

such double chambers can, for example, be 25.

The take-out machine essentially comprises two coils 4-0 and 4-1, which are influenced in a known manner by means of the coils in a tape recorder, The donor coil 4-0 contains an unused elementary film 4-2. The machine contains a motor, which is not shown, for example a stepping motor, which, by advancing the film in the direction of the arrow 75, makes it possible to place the double chambers in front of an extraction means.

The patient places his arm 4-4- on a pillow 4-3. The withdrawal takes place

by means of a needle 4-5 which the officer inserts into the patient's vein, and is connected through a steering line 4-6 to a needle 4-7 which is to be inserted into one of the chambers that make up a double chamber, here the chamber 30. At the same time as the needle 4-7 is inserted into the chamber 30, another needle 4-9, which is firmly connected to the needle 4-7, is inserted into the chamber 30, as shown in the drawing, or into the flap 31, so that the double chamber comes into contact with the atmosphere and thereby the filling takes place with the help of gravity. The needle device is, on a larger scale, shown in fig. 11. The movement device for needles 4-7 and 4-9 is not

shown. It can be executed in any known manner.

The identification of each withdrawal takes place in the following way:

When the patient enters, he receives a card of the type shown in fig. 10. This card.61 has at least one tag 62 which can be torn off.

All the cards and receipts 62 bear the number of the probationer in question, here 2<4>-00 and the order number for the patient, here 9104-.'

The patient writes his civil position on card 61 and his name on at least one receipt. A copy of this card, which is required for the records in the test station, can be obtained in any known way, e.g. using blue paper, a photocopy or filling in a receipt that bears the same numbers as the card.

The card 61 is quickly inserted into a slot for the withdrawal of the blood

65 in the machine. A slot 60 which is taken out in the card makes it possible to limit the vertical stroke for this in the slot 65. This removes the end of a felter 66 which is inserted into the slot for the needles<4>-7 and 4-9. This makes it possible to take the test.

Stop now; the filling of double chambers is signalled, either by visible observation of the height in the chamber 30, or automatically by means of a feeler of a known type which is not shown and which affects a bell or a light. A member then cuts off the tag 62 and glues it to the film at the location of the chamber 31. This cutting member comprises a matrix 67 which is acted upon by means of a jack 58 which cooperates with an installation plate 69 which is pressed against the film by means of a jack 70.

The gluing takes place in any known way, e.g. by means of an adhesive layer on one of the surfaces of the tag. After. the gluing is finished, the film is quickly advanced a step so that the chamber 30 -comes opposite a device which will close the holes which have been made by means of the needles 4-7 and 4-9 during the sampling. This last device includes in particular a heating matrix 71 which is pressed by means of a jack 72 against the upper part of the

chamber to be closed.

The machines are equipped with a control device that is not shown,

and which consists of a foil for the presence of the identification receipt, and which e.g. is. a phototransistor or a magnetic reader that interacts with a magnetic tag placed on the receipt. If the foiler does not detect the presence of an identification tag, a stop will prevent the film from being advanced. In the opposite case, the motor can go ahead and advance one step, so that another double chamber is placed in front of the take-out means. The arm 66 is then quickly returned by means of a spring 73 to a position where sampling is not possible.

The order for the presentation of the film is given by the officer with help

by a button, not shown, which is accessible from the front of the machines.

When the original sample film is completely used up, in the present example when 25 samples have been taken out, the donor coil 4-0 is empty -while the receiver coil<4>-1 is full. It can then be sent to the central laboratory under appropriate conditions.

Finally, it should be noted that the machine can optionally be supplied with

a device that prevents turning in the direction of arrow 75.

The central analysis laboratory, which will be described here as an example, mainly comprises two departments, one for chemical analysis and a so-called hematology department, and a station for the identification of the samples taken from the original film and common to both departments and is connected to an electronic organizer.

The identification station is shown schematically in fig. 12 and 12a.

In the identification station, the film with the sample, which arrives

from the sample station, unwound from the donor coil 81 in the direction of the arrow 83 towards a receiver coil 82. The movement takes place step-

show, so that each double chamber is placed in turn in front of the mark 79?and the identification tag 62, which is glued to the film in the vicinity of this double chamber, is read through a magnifying device 8h by an officer who has at his disposal a keyboard machine 85. The officer writes down on the left page of a sheet 86 the information that he reads off the receipt. At the same time, the information is sent in coded form to a memory. 87. As soon as the information is placed in the memory, it is transferred so that it cannot be undone to an organizer 88. This sends the information it has received, through tele-entry, using the keyboard 85, to the right part of the sheet 86 If the information carried by one and the same line in the sheet coincides, the information concerned by the orderer is correct and the officer gives the order by means of a forward movement, e.g. key 91 so that the film is advanced one step.

During the movement of the film, the transfer of the content takes place in

the local memory to the magnetic tape 35 carried by the film, through a writing head 89 similar to that used in a conventional magnetic memory. At the same time, a verification is made of the identification signal for the double chamber which is one step in front of the double chamber 80 by reading with the help of a magnetic reading head 90 and the correct transfer to the organizer 88.

This makes a comparison with the information it has previously received from memory 87.

If the information is the same, there is certainty that it

coded information carried by the magnetic tape at the point of withdrawal is in accordance with that carried by the ticket in question. In the opposite case, an alarm device is triggered.

In fig. 12, the arrows show the different transmissions of information. The use of, a. local memory 87 is necessary because of the difference between the working pace of the officer and of the orderly.

When the donor coil is empty, the receiver coil is transferred to the next station. The operator places a new donor coil on hand and starts the device until it has an empty stock of coils

which he shall identify-.

Using this device, the sample is identified on magnetic tape, and a complete list of the samples to be analyzed is available in written form.

As described above, the -prove film comprises several double chambers, As the two chambers in a double chamber are connected to each other through a channel. Each of the chambers contains a specific anticoagulant.

When the sequence for closing the holes made with the sample needles is triggered at the blood sampling station, the connecting channel between the chambers is closed. One of them, namely the smallest, serves to deliver blood to the hematology department.

The blood contained in each small chamber in the sample film is transferred to the relevant cavity in an auxiliary film, the method and the machine then being used being described below.

When the spools for the test films are first empty or partially empty of blood contained in the small chambers, and which are intended for chemical examination, they quickly become a centrifugation station. The blood contained in the chambers is divided into a solid phase that remains at the bottom of the chamber and a liquid phase or serum that lies above the solid phase and is subjected to analysis.

The auxiliary tubes to be used in the hematology department are not centrifuged.

At the exit of the centrifugation station, the spools for the sample films quickly become a gluing station for these films. This gluing station is semi-automatic and is placed under the control of an attendant during its entire working life. At this station, several test films are assembled butt-in-butt to form a single film, a so-called large test film whose role will be explained below.

At the exit from the centrifugation devices, each reel for the sample film is placed on a table which is constantly rotating, so that the officer who is at the gluing station has easy access at any time to the reel which he is to place in place. The gluing device makes it possible to produce a continuous band from different coils that have been centrifuged.

The cutting and gluing of the films must be described in more detail

with reference to fig. 1 3—17.

Fig. 13 shows a front end of an elementary sample film with double chambers. The test film is extended so that the part 90 of soft tape provided with double chambers extends past the last chamber 91, towards the end of the film and has a completely determined length, where lA L, L denote the distance between two double chambers that follow one another. The other band 93 which forms the film extends in the same direction over a length well greater than L. Fig. 14 shows another end of an elementary sample film with double chambers, where the band 93 extends past the last small chamber 9h with a length equal to 1A L, while the band provided with double chambers extends over a length well greater than L.

The end portions of the film which extend past the end chambers with a length greater than L are not active portions of the film which serve for anchoring on the coils.

Cutting up the ends of the file, shown in fig. 15 and 16, is achieved on

such a way that the non-active parts are reduced to a length equal to 3A-L outside the respective chambers.

The gluing takes place as shown in fig. 17 in that the other end of a first elementary film is placed in contact with the first end of another elementary film, so that a continuous band is obtained where the different double chambers lie at the same distance from each other with a length L.

This method of gluing makes it possible to avoid that the large sample film exhibits interruptions in the thickness of the gluing areas.

A pasting and cutting is carried out in the same way for the auxiliary films.

A control device makes it possible to signal to the orderer in the laboratory irregularities in the identification that can sneak onto the magnetic tape.

At the same time, the inscription of a suitable signal on the magnetic tape at the location of the identification code, just opposite a defective part of the magnetic tape, will make it possible not to trigger the analysis sequence when a chamber that is not identified or poorly identified arrives at the analysis stations.

Fig. 18 shows a synoptic diagram of a line for chemical analyses.

The large sample film 120 is advanced step by step in the direction of the arrow 121.

1

It crosses, e.g. at a right angle, a film, a so-called analysis film 1:22 which includes a number of cavities which are evenly arranged. This film is created at the starting point of the actual analysis line in order to save storage space. This film is extended from two reels 123 and 121+, each of which contains a strip of purely heat-weldable material with perforations similar to those present in a cinema film;

The tape from one of these reels, here reel 124-, also has a magnetic track.

The tape that does not have a magnetic track enters, with the help of a drive device, into a device 125 where the cavity is heat-formed.

This device is in the form of a very small press, and the treatments take place as rectilinear movements back and forth. At the exit of this heat-forming device, the strip is, by means of another drive device, quickly into a thermo-welding device 126.

The band carrying the magnetic track enters at height with the drive device in the same heat welding device 126. The side holes make it possible to achieve complete synchronism for the two bands.

By means of another rectilinear movement back and forth, the two bands which are placed opposite each other in this way are consequently heat-welded. At the output of this device, the analysis film 122 is thus formed.

At the exit from the yarm welding device, analysis crosses

the film 122 the big trial film 121.

Near the crossing point there is a station 127,

the so-called transfer station, where the following operations are carried out:

- withdrawal from each chamber in the large sample film of a measured volume' of the liquid phase it contains by means of a pipette device 128', - introduction of this volume into a cavity in the analysis film by means of a probe device 129" , -transfer of the identification information carried by the part of the large test film located at the location of this chamber,

to that part of it. magnetic tapes on the analysis film located at the location of the corresponding cavity.

These transfers require step-by-step and synchronized presentation of the measurement film and the large test film.

The analysis film, whose cavities contain the measured quantities, shifts so that the cavities come to and stop a moment of

a certain number of stations for adding reagents, e.g.

131 j 133» 1355 between which are arranged mixing means for the contents of the cavities, e.g. 132, 13^? 136 of the lamellar type.

The film then arrives at a station 137 where the holes made by the needles are heat-welded. The film then enters a thermostatically controlled room 138 where the chemical reaction can take place. The residence time in this room, which is common to all the analyses, apart from the enzyme analyses, can for example be of the order of 8 minutes. The film which moves forward step by step is thus stored in a space, and each cavity stays there for the time necessary for the reaction. After exiting the room, a sudden shock is applied to an organ 14-0 to stop the reaction.

An analysis device 14-1, e.g. a photo colorimeter.

The analysis results for the contents of each cavity are, like the corresponding identification information, transferred to a central memory for numerical processing with the help of an organizer in the laboratory.

The film is then decomposed using a suitable device 1<4>-2 and the remains collected in a container 14-3.

in

Fig. 19 shows in perspective an analysis line which only includes a single station for adding reagent 127. The reference numbers used in fig. 19 'denote the corresponding elements in fig. 18.

Fig. 20 shows a preferred embodiment of a machine for processing the analysis film.

This machine essentially comprises two spools 123°g 124- which emit soft heat-weldable tapes which are provided with side holes in the same manner as a cinema film.

The tape from reel 1.24- carries a magnetic track.

The coils 123 and 124 are set in motion simultaneously by means of a stepping motor 150, on whose shaft 152 several secondary shafts are arranged, e.g. 153-156 which drives gears, e.g. 157-160.

The. tape discharged from reel 123 passes in front of a cavity hot-forming means and with a matrix, whose active elements 161 and 1:62, which are heated, are moved by means of a jack

163. The element 162 is controlled by means of fixed rods 164-

and 165. After the formation of the cavities', e.g. 168, the two bands are placed opposite each other and are heat-welded, preferably by means of a heating block 169 which cooperates with the aforementioned element 162, in which a hollow 170 corresponding to the shape of the sample chambers has been taken out. At the output of the apparatus, the analysis film 122 described above is obtained.

In the figure, it is shown schematically and for the sake of simplicity that the cavity has a parallelepiped shape. This shape is not limiting in any way, as the cavity can have any shape that suits the nature of the sample and the type of analysis.

Fig. 21 shows in perspective a portion of an ■ analysis film 174- where the cavities 175 have a shape that is particularly suitable for chemical analysis, e.g. those that are usually performed on blood samples. The cavity 175 is essentially in the form of a pocket in the shape of a ball cap, the upper part of which has a flattened part 176 for the insertion of needles. The sample which is contained in the cavity and which consists of a mixture of serum and additive, is designated 177.

The various withdrawals with specific volumes that are made either at the station where the auxiliary film is produced on the basis of the sample film or at the transfer station 127 or at the various stations for introducing reagents, are obtained with the help of a withdrawal and measuring device for samples that are made of a movable sampling pipette equipped with a height gauge and extended with a rudder through which the liquid flows under the influence of a gas under pressure.

Fig., 22 shows the working principle of the apparatus.

The apparatus comprises ice container 201 which is provided with a lid

202 through which passes a rudder 203 which is equipped with a crane

21<4>- and a shut-off valve 217, and a soft rudder 204- which is connected to a pipette 205 which can be moved under the influence of an electromagnet 206. The pipette 20.5 and the electromagnet 206 are carried underneath by a float 207 which lies above the liquid 20B which contained in the container.

The rudder 204- is extended with a rudder 215 above another container 209. Along the rudder 204- is placed a level meter 210 which consists of a radiation meter with a radiation source 211 and a cell 212. An electronic relay 213 sends current from the cell to the electromagnet.

The device works in the following way:

The substance 208 to be taken out is placed in the container 201, and the float 207 and the lid 202 are placed tightly. A container 209

who will take the test is arranged under the end of the rudder 21 5-

The rudder 203 is connected to a gas source, the pressure of which is greater than the atmospheric pressure by a value that is at least equal to the weight

of the liquid column whose height is equal to the distance between the liquid surface and the highest point on the rudder 20<4>-. Withdrawal

the pipette 205 is in the lower position, i.e. it dives down

in the liquid.

As soon as the tap 214- is opened, the gas pressure on the surface of the liquid will cause it to rise up into the pipette and into the soft and roomy-looking rudder 204-. As soon as the liquid reaches the level gauge 210, the cell is no longer energized by the radiation and through the relay 213 it affects the electromagnet 206 which lifts the pipette out of the liquid. The amount of liquid sucked in is therefore equal to the volume of the channel between the end of the pipette and the level gauge.

The gas pressure that continues to be released at the open end of the pipette drives all the liquid contained in the tube 204 towards the container 209.

As soon as the liquid plume in its entirety has passed past the meter 210,. the cell is again energized and sends, to relay 213, an order to lower the pipette. This order can be delayed to wait until the device is completely empty and the container 209 is replaced by a new container.

It is clear that several elements that are discussed in this description to show the working method can be replaced with equivalent elements.

Thus, the electromagnet 206 can be replaced with a hydraulic or pneumatic jack.

The level gauge can be of any suitable type, e.g. in the form of a photoelectric cell or radiation indicator, or cell with electrical contacts, between which the liquid to be analyzed forms the path of an electric current.

The rudder 204- is described as a soft and transparent rudder in the case where a radiation meter is bent. For a contact

meter, it is not necessary for the rudder to be transparent.

The rudder can also be rigid and made with a connection in the pipette 205 which makes it possible to move the pipette back and forth and correspondingly to the movement of the float when the liquid level drops, e.g. an elastic connection.

The arrangement of the pipette on a float has the advantage that it is easy to place and makes it possible to limit the stroke of the pipette to a few mm. Such a small stroke is important for a fast sampling rate. e.g. one withdrawal per second, which the device can easily provide. Moreover, it is easy to achieve a movement back and forth with such a small amplitude by means of an electromagnet of small strength and small volume. Pressurization of the container takes place using any gas whose pressure is above atmospheric pressure. The gas is generally compressed air. A neutral gas, eg nitrogen, can be used. The effective pressure of the gas is regulated by means of the tap 217, so that the advance speed of the liquid in the pipette and the rudder 204 can be varied. This can be an automatic pressure regulator which maintains a constant pressure in the container 201. When the pipette is withdrawn from the liquid 208, the gas pressure will drive the sample towards the container 209 and the gas contained will escape through the rudder 20<4>-until the pipette again dipped into the liquid. This gas cycle takes place at high speed and causes a good cleaning of the walls so that contamination of a sample by traces of previous samples is prevented.

Although the level gauge used may be of any known type, a level gauge utilizing the radiation of a radioactive substance has the advantage of making it possible to determine the passage of a liquid, which may even be colourless, flowing in a capillary -rbr. A level gauge with electrical contacts has the same advantage.

It is assumed that the level gauge can be moved along the rudder 204-

to vary the volume taken out.

The above description shows that one of the biggest advantages of the sampling device lies in the fact that it is suitable. .used to measure very small volumes, of the order of magnitude fractions of cm^ and with a fast rate, of the order of magnitude 1 sample per second.

Fig. 23 shows in perspective a device for extracting and injecting a measured volume of a liquid, in a preferred embodiment. This device works according to the principle described above, it can be used at the stations for adding reagents during the analysis sequence, as well as for stations for filling up serum for analysis film and auxiliary film.

The example shown in the figure concerns a device for

withdrawal of a certain amount of reagent into a cavity and introduction of this reagent into the relevant cavity in an analysis film.

The container 230 containing the reagent 231 is a container which

is closed with constant height. The container contains a float 232 which is hinged about a horizontal axis which is formed by several blades, e.g. 233. -The float serves to close a channel 234-

for the supply of reagent when the height rises above a certain upper limit

and to open if the height drops too far down. According to the principle described above, a gas under pressure is quickly introduced through a channel 235 located above the height of the reagent.

The analysis film 236 moves in the direction of the film 237 so that each cavity 238 in turn stops for a specific time just opposite the device for taking out and injecting.

This device comprises a rudder 24-0 which can be immersed in the liquid in the vessel 231 and for this purpose is permanently connected to an electromagnet 24-1. This rudder is connected through a soft channel 24-2 to an injection needle 24-3 which can penetrate into the cavity 238 in its upper part. This needle is firmly connected to a jack 24-4-. Another needle 24-5 which is fixedly connected to the jack 24-4 serves to put the interior of the cavity under atmospheric pressure. An electronic device comprises two probes 24-6 and 24-7 which serve to control the movements of the various moving parts and to ensure the introduction of a measured quantity of the reagent.

The device works in the following way:

As soon as a cavity 238 reaches the device, the electromagnet 24-1 controls the lowering of the rudder 24-0 into the liquid in the vessel 230. The pressure exerted by the gas over the liquid causes it to rise in the rudder. The probe 24-7 will. when it detects the passage of liquid, control the insertion of the needles 24-3 and 24-5 into the cavity 238. The probe 24-6, whose position can be regulated along the channel 24-2, so that it is possible to set the amount to be injected , senses the arrival of the liquid and controls the rise of the rudder 24-0 out of the liquid. The pressure prevailing in the room then drives the withdrawn amount through the needle towards the cavity which is set under atmospheric pressure. After pulling out the needles, the film is advanced one step and the following cavity enters the device.

This device can be adapted to the removal from the chamber in a large removal film of a given amount of blood and the introduction of this amount of blood into the corresponding cavity in an auxiliary film, e.g. the one shown in fig. I8cg 19.

In the device shown in perspective in fig. 2h, the chamber for a large test film replaces the chamber 30 referred to above. Moreover, the rudder 2kO is replaced by a needle whose movements are controlled so that it dips into the liquid phase in each chamber without ever coming into contact with the solid phase. An embodiment example is shown in fig. 2h. The large film 250 is forced to move step by step in the direction of the arrow 2^1 so that the large chambers, e.g. 252 arrives at and stops for a short specified time at the location of a test needle 253-This needle is firmly connected to a piston 25<*>+ which can move inside a cylinder 255. The piston is normally held in a high position by means of a pressurized gas that enters through a line 256. The separation of the height 257 that separates the liquid phase 258 from the solid phase 259 is achieved by means of an electronic device comprising several optical cells, e.g. 261, which is arranged vertically behind the film 250 and is illuminated through this by means of light sources, e.g. 262.

The cylinder is internally equipped with a rudder, e.g. 265, which makes it possible to inject compressed gas. In addition, in the upper part of the cylinder there is arranged a line 269 - which, when open, makes it possible to create a pressure that is higher than that - which is obtained through the line 256. The mentioned rudders are arranged t vertically so that they represents the height sensed in the chamber 252. The opening and closing of each rudder can be controlled by means of a sMd 266 which is influenced by means of a coil 267. A rudder is arranged for each optical cell. If a cell is energized, which means it is opposite the liquid phase, the corresponding rudder is stopped and vice versa.

The order of withdrawals is as follows:

At the moment when the chamber is stopped, the rudder 269 is opened. The piston descends to a height determined for it by the first rudder which is opened as it should. The needle 253 then dives into the serum 258. A needle 270 which is controlled by means of a jack 271 sticks into the chamber in its upper part so that it is placed under a pressure greater than atmospheric pressure. The serum then rises into the needle 253 and a certain volume is injected, as described above in relation to the cavities in the analysis film.

Fig. 25 shows a preferred embodiment of a device for photocolorimetry. analysis.

The cavities 175 in the analysis film 17<4>- stop one after the other for a short time, generally less than 1 second, in front of a photocolorimeter comprising a luminous radiation source 330, a series of filters and screens 331-33<*>+ in particular arranged for the measurement to be carried out, and a receiver cell 335 of the photoelectric type.

A device comprising a fixed plate 336 and a movable plate 337 which is moved by means of a jack 338 maintains the cavity when it stops in the optical axis of the fbtocolorimeter and thereby makes it possible to ensure a constant thickness of the liquid to be analyzed, placed in the path of the radiation.

During the stay of the cavity between the mentioned plates, the liquid, in the cavity, as shown in fig. 21-27, pass from a lower height 178 to an upper height 179• The passage of the light radiation takes place through a limited observation zone 180 in the cavity.

The movement of the film in front of the photometer is ensured by means of a mechanical drive device which is synchronized with the device used in front of the various injection heads and in the equipment to obtain the film.

The laboratory can also be equipped with enzymatic lines that make it possible to provide a development curve over time for the enzyme under consideration.

An enzymatic line differs from the line for chemical analyzes discussed above in that it comprises several photocolorimeters which are separated by means of baths where the reaction takes place in the lbpet of a specific time. The measurements made using the various photo colorimeters are sent to the data processor and processed by the latter.

The laboratory includes a hematology department, which in particular includes a department for counting blood cells and a department for hemoglobin analysis.

After the station for distribution of the withdrawals that follows

after the input identification of the coils, several film coils are arranged which are intended for hematology and which consist of coils for elementary films for the withdrawals. An adhesive station similar to the one described in the chemistry department makes it possible to ensure that a continuous film is formed.

There is then a continuous film which is identified at the exit from the hematological adhesive station.

'During the course of this film there are three different lines of analysis:

A line for counting the red blood cells, a line for counting

of the white blood cells and a line for hemoglobin analysis.

The line for counting the red blood cells makes it possible by superimposing two counting devices to achieve an average counting rate of one count per second. This count is carried out e.g. over 5,000 blood cells. The chain works in the following way: There is transfer using two extraction and injection heads that work simultaneously, from two samples from the extraction film directly to the counters.

'The input to the counters consists of a dilution device which is specially designed for this strong dilution (1/50,000).

The counter works on the basis of the diluted sample, and takes

out e.g. 0.5 cm^ resolution. The line for counting red blood cells makes it possible, with the help of a suitable device, to

state the mean volume of the bodies. It also makes it possible to calculate the hematocrib value.

The average volume x the number of red blood cells^the volume per blood cell.

The line for counting white blood cells works in exactly the same way, as the dilution is then also carried out in the counting apparatus by means of a mechanism that ensures the accuracy of a resolution of 1/500.

The pulses from each counter are utilized, both for the line for red bodies and for the line for white bodies, by means of an electronic counter, the contents of which are read in parallel by means of a data processor.

As soon as the count is finished, each counter will notify the orderer that the count has ended by means of a signal to cancel the program.

The line for the hemoglobin analyzes is a common line for chemical dosing. The combination of the hemoglobin dosage and the number of red blood cells in the data processor makes it possible to calculate the average hemoglobin density.

Optionally, the laboratory may include a department for setting up the leukocyte formula, based on the examination of color layers.

Certain cavities in the sample films cannot, during the analysis, accommodate any sample or reagent. These cavities must determine the photo-colorimeter calibration during the measurement. Other cavities may be filled with comparison solution for readjustment of the photocolorimeter scale.

The materials in the analysis film can suitably be a colored plastic that acts as an optical filter.

The multiple and automatic analysis device according to the invention has the following advantages:

- It is not possible to make a mistake during the identification.

- Contamination of the samples in relation to each other is avoided.

- Consumption of reagents is the least possible.

- The measuring speed is very high.

- The device can be easily adapted to the possibilities provided by the organizer. - The accuracy is very high as the measurements are independent of each other and of the security system used.

- Measurement reliability is very high: each measurement cavity is independent.

- The use is very cheap and the staff required is small.

- The various information obtained are independent of each other so that they can be used for diagnosis.

The invention is not limited to a device for blood analysis. -

It can be adapted to any' problem for multiple analysis. The blood samples taken are only given as examples. The devices described can be used for the analysis of different samples, and can be adapted to the needs of the expert.

Claims (1)

1. Device for multiple and automatic analyzes of liquid mixture samples, each of which is produced by a mixture in selected proportions of a liquid substance to be analyzed, <p> and an addition of reagent, characterized in that it comprises a conveyor (122) for moving the sample, and which is formed by a number of chambers (3,14, 30,175) which are tightly connected and firmly interconnected, each chamber being lined with a flexible and transparent material and arranged to receive a mentioned liquid mixture sample, at least one transfer means (127) for withdrawing a given amount of liquid and/or reagent from a corresponding supply container (208) and transferring this to at least one chamber on the conveyor belt (122) by the connected storage container is placed under gas pressure, as the transmission device is equipped with a single wire (205+20^+215)> which is given such a translational movement that one end of it is fed into the storage container and its other end is fed in turn into each chamber along the conveyor belt, whereby the end which is lowered into the storage container can be placed on one or the other side of the liquid level in this container, at least one device (132,134,136-T38) for mechanical treatment and heat treatment of the liquid mixture samples in the transport year's chambers, as well as at least one. measuring device (1.4-1 )• of photocolprimetric type for analyzing the samples, and which is designed to be connected to a data processing device for producing the measurement results at a faster rate, while the liquid mixture samples are moved along the analysis device using the conveyor. . 2.. Device as stated in claim \ t characterized by -, that the -conveyor consists of a first and/or second belt (2 and 12J of flexible and transparent material, with at least one (12) of the belts being equipped with deformations perpendicular to the belt plane, and the belts are sealingly connected at least along the edges of the deformations to form said chambers and delimiting lase. perpendicular-to the direction of deformation.- 3. Device as specified in claim 2, characterized by . that the tapes are provided with perforations along the side edges and possibly a step-by-step mechanical advance of the same kind as a cinema film. h. Device., as specified in requirements. 2, characterized in that at least one (10) of the conveyor belts is equipped with. a magnetic track (35) along one of the edges, and which enables a coded identification of the contents of each chamber and cooperates with a device (fig. 12) for identification of the withdrawn liquid mixture sample. 5- Device as stated, in claim. 2, characterized in that each chamber is mainly designed as a parallelepiped. 6. Device as specified in claim 2, characterized in that each deformation, on one of the bands together with the other band forms two mutually adjacent parallelepipeds, which thus limit two volumes and form a pair of chambers = (16-18, 30,31) which are interconnected through a channel (20,32), which enables the separation of solid particles from the liquid sample to be analyzed. 7. Device as stated in claim 1, character! s ert in that a reagent is placed in each chamber. 8. Device as specified in claim 1, characterized in that the walls of the chambers are colored to serve as an optical filter. 9-, Device as stated in claim 2, k a-, r. a k t e. r 1& e r t in that it- comprises- an- entrance s-station (fig. 9-11) for mechanical packaging of: the liquids to be analysed,. in the chambers - on a storage conveyor (120) which is identical to the aforementioned transporter for movement, the entrance station comprising a device for successive filling of the storage conveyor's chambers. O&X with the respective liquids-with the help of e-t withdrawal device (4-5+ <!> +6+ <1> +7 ); which successively connects each storage container. with a storage chamber, as well as a device (61-62) for identifying each sample, the latter device cooperating with a rocker (66)" which blocks the withdrawal device and prevents filling, of each chamber (30)" when the identification device does not is located in the middle in front of the corresponding storage chamber for the liquid, under which the supply transport fuel is advanced step by step to enable the stop of each storage chamber perpendicular to the outlet 10. Device as stated in claim 9"characterized in that the withdrawal means comprises a hollow needle (4-7)" arranged to penetrate each of the walls of the storage chambers. 11. Device, as stated in claim 10, characterized in that - the identification device (61) comprises a card with at least one separable strip (62) which is provided with identification data - for each withdrawn liquid that is to fill a storage chamber, whereby the strip is arranged in order to be separated and. is affixed to the conveyor, which is located perpendicular to the storage compartment in question, and the card is placed in a pocket (65) at the entry station, in the middle in front of the storage chamber which is to receive one of the liquids to be analysed, the said card simultaneously leading to the side of the said locking rocker (66), ; which has previously been in the movement path of the needle (4-7). 12. Device as stated in claim 1, characterized in that the means for transferring a given amount of liquid includes a means (210,24-6) for detecting the presence of the liquid, and which is arranged on the line at a certain distance from the end of the line that is lowered into the storage container, and controls the raising of this end to a position above the liquid level in the presence of liquid at the level of the discharge member, under which the gas pressure, after said line end has been raised above the liquid level, is maintained in the storage container so that the amount of liquid in the line can be driven into the transfer conveyor's chambers. 13. Device as stated in claim 12, characterized in that the gas pressure in the storage container is produced by means of a line system that opens into the container and is connected to a compressed gas source, which can be equipped with an adjustable reducing valve.. 1 <4> -. Device as stated in claim 13, characterized in that at least the end of the wire which is inserted into the chambers of the displacement conveyor is extended like a needle (2 <4> -3) of the hypodermic type, and which penetrates into the relevant chambers by sticking hole on the chamber walls, under which the needle is firmly connected to a holder that imparts translational movement. 15. Device as stated in claim 1 <4>- , characterized in that the sensing device (210) is made up of a radiation indicator, which comprises a source for optical (211) or radioactive radiation which is emitted through any transparent part of the line (204-) , as well as a theft recipient (212-213). 16. Device as specified in claim 14-, characterized in that the sensing element is made up of an electrical resistance bridge, one side of which comprises two electrodes which are inserted in the wire. 17. Device as stated in claim 14-, characterized in that it comprises an electromagnet (207)? whose anchor is firmly connected to the end of the cable which is inserted into the storage container, and whose power supply is controlled by the sensing device (210) for setting the rudder end above or below the liquid level. 18. Device as stated in claim 17, characterized in that the armature of the electromagnet is connected to a device for limiting its movement. 19. Device as stated in claim 18, characterized in that, when the storage container contains a solid phase with an overlying liquid phase, said device for restricting movement comprises a device (261,262) for monitoring the boundary layer between said phases as well as a device for regulating the movement area of the cable end. 20. Device as set forth in claim 19, characterized in that the boundary removal device comprises several vertically arranged photoelectric cells, which are illuminated by means of several light sources through the container, which is made of transparent material. 21. Device as set forth in claim 20, characterized in that the regulating body comprises a cylinder (255) with a piston (254-), which is firmly connected to a needle (253) which penetrates into a chamber on the displacement transport Sren, the cylinder comprises a number of nozzles (265) for the supply of compressed gas, and which are arranged vertically in the same way as the photoelectric cells, as well as arranged to be closed by means of solenoid valves (266), which are influenced by electromagnets (267), which in their turn is controlled by the photoelectric cells. 22.. Device as stated in claim 14-, character i' sert in that the chambers comprise a part of elastic and permeable material, so that the holes that are formed when inserting said needle are automatically connected when. the needle is withdrawn. 23. Device as stated in claim 22, characterized in that at least one member for mechanical treatment is made up of a rolling member, which consists of at least two rollers, placed on either side of the conveyor for compressing each chamber at the passage of the conveyor. 2h. Device as specified in claim 22, characterized in that at least one organ for mechanical treatment is made up of a mixer, which comprises at least two toothed wheels which cause the transfer conveyor to describe a helical path. 25. Device as specified in claim 23, characterized in that at least one element for heat treatment is made up of a thermostat-regulated chamber, in which a chemical reaction develops, said element comprising means for causing each chamber on the conveyor to stay in the thermostat-regulated chamber under an adjustable and prior specific time. 26. Device as specified in claim 25, characterized in that at least one measuring device of the photocolorimeter type comprises two parallel plates (336,337)? between which each chamber with liquid mixture samples is placed in contact at the moment of measurement, whereby at least one of the two plates can be moved perpendicularly to the conveyor under the influence of a mechanism (338), which is controlled by the conveyor's advance device. 27. Device as stated in claim 11, characterized in that the storage container for each liquid to be analyzed is made up of a storage chamber on the storage conveyor, and that it includes a device for transferring the identification located on the strip (62), the latter device being equipped with an optical device (84-) for reading the alpha number in the information on the strip, a means (85) for transferring the information in coded form to a local memory (87), a means for transferring this information in the local memory without distortion to a memory in the data processing device (88), a means (83,86) for reshaping into alpha-numeric form the coded information present in the data processing machine, as well as means (89) for transferring the coded information from the local memory (87) to a magnetic track (35) on the transfer conveyor. 28. Device as specified in claim 27, characterized in that the device for transferring identification includes means for reading the written information in the magnetic track and for comparing this information with corresponding information in the data processing device. 29. Device as specified in claim 2, characterized in that a first end of the transfer conveyor is arranged in such a way that the end part of the first belt extends past the first chamber at said first end with a length equal to a given proportion of the space between the chambers, and that the end part of the second belt extends in the same direction with an extent that is equal to the difference between the mutual distance between the chambers and the said length", the other end of the conveyor belt being arranged so that the end part of the second belt extends past the first chamber at the said other end with the same stated length, and the the end part of the first belt extends in the same direction to an extent equal to the specified difference, so that several conveyor belts can be assembled end to end without thickening in the joints.