WO1993020612A2

WO1993020612A2 - Automatic device for the photometric analysis of liquid samples

Info

Publication number: WO1993020612A2
Application number: PCT/EP1993/000804
Authority: WO
Inventors: Hans-Jürgen KOLDE; Michael Kiehl; Wolfgang Koehne; Isabel Ramirez
Original assignee: Baxter Deutschland Gmbh
Priority date: 1992-04-02
Filing date: 1993-04-01
Publication date: 1993-10-14
Also published as: AU3950693A; DE4210963A1; WO1993020612A3

Abstract

A device (2) for the photometric analysis of liquid samples has the advantage of allowing a plurality of samples which require different processing steps (different incubation and measurement times) to be processed. It is therefore possible to carry out in a relatively short period more than twenty different types of tests with this device. A device for gripping objects (41) and a process for analysing liquid samples inside vessels by means of a device for the automatic analysis of liquid samples are disclosed. A process is disclosed for measuring samples, according to which the sample material is transferred from a sample container into a vessel, is processed and is subjected to at least one measurmenet process, then the corresponding measurement value is stored.

Description

Automatic device for the photometric analysis of liquid samples

The invention relates to a versatile device for processing samples with different incubation time requirements, capable of adding a number of intermediate and / or final (start) reagents and measuring photometric and turbidimetric variables at any time. In particular, the invention relates to a device for automatic photometric blood coagulation analysis.

Already known devices for automatic clinical laboratory analysis process a number of samples per hour using automatic sample filling, dilution of the sample and automatic addition of the reagent. The samples are filled into cuvettes, which are transported manually (one after the other) or by a transport mechanism. This transport mechanism can e.g. B. be a conveyor belt that brings the cuvettes into the incubation zones and finally to the photometer station (s) where the measurement of the desired variables takes place. These devices require rigid cycle times for the preincubation, incubation and measuring time in order to ensure synchronization between the various mechanical and electronic parts which appear in the preparation of the sample, during transport and measurement. The state of the art is "Paramax" (Baxter, device for analysis in clinical chemistry) and ΕlectralOOOc "(MLA, device for blood coagulation analysis) and" ACL300 "

Laboratory, device for blood coagulation analysis). While these devices have been used successfully, there is a need to further improve them, particularly in terms of flexibility.

The devices of the prior art more or less all have the following disadvantages:

a) The devices can run only a few different types of tests simultaneously or in quick succession, all z. B. are coagulation tests.

b) The devices have only a limited number of reagent holders. If Test B is to be run, Test A's reagents in the reagent holders must be replaced.

c) The two wavelengths for coagulation (e.g. 548 µm) and chromogenic (405 µm) tests are not available at the same time.

d) The processing of the samples follows rigid cycle times, which do not allow flexible tests with different cycle symbols to be put in between.

e) "STAT samples (emergency samples) with different test requirements are difficult to integrate into a routine process if a different test is to be carried out at any time ie the operating personnel must change the reagents and change the test variables.

f) When a new test appears on the market, it is extremely rare for the user to be able to adapt it directly to the device. The only way for the user is to make a request to the producer of the test. This procedure usually takes a long time before the user gets the hardware and / or software to perform the test.

In order to overcome the aforementioned disadvantages, it is an object of this invention to provide a device which shows flexibility and allows the user to carry out essentially any type of photometric or turbidimetric test, preferably any type of coagulation test or chromogenic test. to perform at any time. Another object of this invention is to be able to carry out any determination in the event of an emergency request without additional manipulation by the user.

The invention relates to a device for the photometric analysis of liquid samples according to claim 1. A further object of the invention is a gripping device as defined in the claims. Another object of the invention is an analysis method as defined in the corresponding claims. Another object of the invention is a method for performing measurement methods on samples as defined in the corresponding claims. The device according to the invention is capable at any time of processing a number of samples which require different working steps (different incubation times and measuring times). Therefore, it is with this device z. B. possible to perform more than twenty different types of tests in a relatively short time. For example, any coagulation test (e.g., quick test, aPTT test, etc.) or any chromogenic test can be performed in one measuring station because the two wavelengths used for this type of test are available all at once in a preferred two-channel photometer . A preferred version of the device has at least five photometer channels, preferably at least ten photometer channels. Because each sample has an individual identity in the work chain, a cuvette that requires four minutes of incubation time can be adjacent to a cuvette that only needs one minute of incubation time, without slowing down the entire sample processing method. For example, one can easily imagine that samples are measured in the measuring station in order to carry out a quick test, while in the meantime samples which are to be subjected to an aPTT test are in a cuvette template or incubation template and are waiting for in the measuring station to be transferred to the measurement. Because the device operates under computer control (personal computer), it is a further object of this invention to provide a user-friendly PC environment which allows the device and method to be adapted quickly and easily to new (future) tests.

Another Ai-tsführungsfoπn of the present invention relates to a method for performing measurement methods on samples. This. Process is defined in more detail in the claims. A plurality of measurement methods are preferably carried out with a large number of samples. So each sample can have one or more Measurement procedures to be assigned. Processing is initially based on a procedural priority list. During the implementation of the individual stages, the selection of the cuvettes and the respective processing takes place on the basis of a status priority list, regardless of the process priority.

In a preferred embodiment of the invention, the sample template is subdivided into at least two sample template inserts, one of the sample template inserts serving as an emergency insert. Doing so

In the method automatically controlled by the computer, whenever the transfer of sample material to a cuvette is to be made possible, it is first automatically determined whether one or more samples are present in the emergency insert and, if this is the case, these samples with priority, ie before the samples from the others

15 sample template inserts are placed in the cuvettes. The samples from the emergency insert also have priority over the others if they relate to methods of lower priority than those of the other samples (routine samples).

20 The described method has the advantage that a very high degree of flexibility is achieved with relatively simple means and one and the same device can be used for new measuring methods simply by the device operator changing few specifications in the software controlling the device. With the preferred batch function, in which each of the

25 drive an optimal batch size, which is currently 3, 4 or 5 in most cases. With great efficiency and speed, the loss of sample material in cuvettes (for example because an incubation time is exceeded without a measuring station being free) can be avoided.

^' 3fl In a preferred embodiment of the method, the computer controlling the method stores information for each cuvette of a cuvette holder, which preferably has a rectangular, structured grid structure for holding the cuvettes, and is preferably stored in a thermostatted ARRAY (incubation rack array). The position of the cuvette in question is also stored in the sample processing control memory (IDA) in this incubation rack array. The state of the cuvette can preferably assume one of four possibilities, namely "empty", "in progress", "garbage", ΕRROR. ”On the basis of this modification, the computer can automatically determine whether empty cuvettes in the cuvette holder for further sample material The method can then be transferred to another cuvette holder with empty cuvettes and the first cuvette holder can be disposed of and replaced by a new cuvette holder with nothing but empty cuvettes.

Show it:

Fig. 1 is an overall perspective view, partially schematic

FIG. 2 is a schematic plan view, showing the drive of the working head 40. FIG. 3 is a front view, schematically showing the drive of the

Gripping device 41 and the pipetting device 42 Fig. 4, the cannula with Hekeinrichtung

Fig. 5a in perspective, gripping and Hpettiereinrichtung on the

Working head Fig. 5b to 5e four work steps, namely:

5b the gripping device has gripped the cuvette 5c the gripping device removes the cuvette from the

Template 5d Reset the cuvette into the template

5e detaching the gripping device from the cuvette. FIG. 6 tempering device of the cuvette template

FIG. 7 heatable reagent master block in perspective view. FIG. 8 the optical measuring device in a horizontal longitudinal section

Fig. ^9a uπά 9b example of a flow diagram

The device (FIG. 1) comprises an identification device 1 which allows: a) patient identification, b) localization of the sample in a sample template and c) selection of the test methods to be carried out. The "bar-coded" patient number is read by means of a bar code scanner ("bar code scanner"). The sample identification process can also be carried out with a computer keyboard 32 alone. The position of the sample in the sample template is identified by placing the template on a platform 14 of the aforementioned device, "push buttons" making contact when a sample container is depressed. The desired test method (s) is / are then carried out using the above-mentioned device keyboards 16 or by loading a patient list through a host computer 4 which is connected to the system in combination with a conventional one bidirectional interface and the software is connected.

As soon as the (patient) sample container is identified, the sample container 20 is placed in a sample drawer 22 in the automatic analysis device 2. The device is available with various reagent templates 24a / b / c with enough space for reagents for a large number equipped by various tests. As soon as the user has checked that all reagents are in their reserved place and that there is enough liquid for washing a pipette, the device is operated under PC control 3. A special feature of this device is that it can carry the same reagent at different reagent positions, as required by the user. This prevents the compulsion to stop a run to replace an empty reagent bottle.

The main actuator of the automatic analysis device is an x-y-z driven manipulator or arm 40, which consists of a gripping device 41 and a pipetting device 42. At the start of the run, the manipulator travels to the washing station 120a or 120b, where the inside and outside of the pipette 6 are washed before entering a new sample or reagent. The manipulator then goes to the sample template selected by the user, where the pipette 6 pulls up the first sample in an amount which is defined in a work list. The manipulator then moves to the cuvette template 50a or 50b, where the sample is placed in a cuvette 5.

The exact amount of liquid, preferably plasma or reagent, which is sucked in or released by the pipette is regulated by a valve-nozzle pump unit 80, 81, 82. Using this unit, the amount of water used to wash the pipette can also be regulated. The water for washing the pipette is brought into the pipette via a flexible plastic hose 86, which is connected to the pipette at the top. As soon as all samples to be processed in one go have been distributed into the cuvettes, the manipulator "intermediate reagents", if necessary, begins to pipette. During the necessary incubation period for each sample expires (if this is the case), the manipulator can process other samples that require the same test. In addition, the device is also capable of carrying out any other type of test at this time without additional changes.

When the incubation time for a sample has expired, the manipulator 40 moves to the cuvette template and the gripping device 41 grips the cuvette 5 containing the sample and transfers it to a free position in the measuring station 60. Then the manipulator 40 moves to the starting reagent position in the reagent template 24c and sucks in the starting reagent by means of the pipette 6, which is then added to the cuvette. After the measurement (clumping time, absorption change per minute, etc.) has been carried out in the photometer, the cuvette 5 is gripped by the gripping device 41 and is preferably returned to its old position in the cuvette template. The position of the cuvette used is blocked in the work list for further use.

The device 2 has at least two cuvette template units 50a, 50b. As soon as a cuvette template with used cuvettes 5 is full, the manipulator 40 automatically uses the cuvettes of the next possible cuvette template. The cuvette tray 51 used can be thrown away while the automatic analysis device 2 continues the measuring operation, because the cuvette tray 51 is mounted on a drawer 52 which can be removed at any time during the sample processing without the device being closed to stop. This allows an immediate exchange for a new cuvette tray 51, which should preferably be preheated. By the time the cuvettes 5 are filled with liquid, they have already been brought to the desired incubation temperature. In order to avoid cleaning, the pipette 6 is washed in the washing station 120a or 120b. The cycle of placing cuvettes in the cuvette template, adding samples and reagents, transporting the cuvettes to the measuring station, etc. continues until all samples in the work list have been processed.

The driven manipulator 40 runs on a guide rail (FIGS. 1 and 2, 100), which permits right / left movement of the mampulator (X axis). This X guide rail is mounted on a second guide rail, which enables the manipulator's Y movement and forward and backward movement (Figs. 2, 102). Both guide rails are controlled by a system of drive belts, drive gears, ball bearings and deflection rollers 104, 106, 108, 110 and driven independently of one another by two motors 112a, 112b. The displacement of the drive belt 104 is controlled by means of a rotary pulse generator 112c, 112d.

Light sensors 111 determine the position of the manipulator in the device.

For each driver 114a, 114b that controls the X and Y motors, X and Y interfaces 116a, 116b provide information between a microprocessor 118 that controls the manipulator position and the X and Y motors, respectively back. 3 shows in detail a cross-sectional view of the pipetting device 42 and the gripping device 41 and which part is regulated by a microprocessor 119. The microprocessor 119 controls the movement of the gripping device up and down, opens and closes the gripping tongs and regulates the pipette position, a level sensor 132 and a heating element 134 of the pipette 6. The microprocessor 119 communicates with the PC via the Microprocessor 118. The up and down movement (Z) of the gripping device 41 is carried out by a gripper step motor 41a, which drives a crank 121, which is connected to the gripping device 41 via a connecting rod 124. At the top of the gripping device 41, a light sensor 122a transmits its Z position to the microprocessor 119.

The Z position of the pipette 6 is regulated in a similar manner by means of a stepper motor 42a and a light sensor 122b. The stepper motor 42a drives a belt drive 140, which is located on the support base 142 of the pipette 6. When the level of the liquid contained in the reagent bottles and sample containers changes, a level sensor 132 detects the surface of the liquid and passes the information on to the microprocessor 119, which regulates the Z movement of the pipette 6. Level sensor 132 is responsive to a change in capacitance when the pipette contacts the surface of a liquid. During the aspiration of liquid, the pipette 42 moves down and stops at a certain distance below the meniscus. This distance is determined by the diameter of the reagent bottles or sample tubes and by the amount of liquid to be pipetted, as specified in the work list. It is preferred that the tip of the pipette 6 is not immersed too deeply in the liquid; on the other hand, it is also expedient that the pipette 6 is immersed deep enough to suck in the desired amount of liquid without air bubbles. If 1 ml of liquid is to be aspirated from a sample tube (small diameter) or from a reagent bottle (large diameter), the level sensor 132 detects the liquid surface. In the case of the sample tube, the pipette 6 sinks lower than in the case of the reagent bottle. Fig. 3 also shows that the microprocessor 119 transmits the signal to operate a magnet 123 which controls the opening of the gripping device 41 at the moment when a cuvette 5 is to be placed. The operation of the gripping device 41 is described in more detail in FIGS. 5a to 5e.

Fig. 3 also shows the internal structure of the pipette 6, i. H. the heating device. The pipette 6 is heated to temperatures of 20-50 ° C., preferably 30-40 ° C., in particular 37 ° C., via a heating element 134. The current temperature within the pipette is determined via a thermosensitive element 136, which is connected to a temperature regulator 138. FIG. 4 shows a cross-sectional view of the pipette. The pipette 6 consists of a long stainless steel tube 43 which is covered with a material which acts as a heating element. The upper part of the stainless steel tube 43 is connected to a plastic tube 86, which in turn is connected to one end of the valve 80 of the dilutor 81.

5a is a detailed illustration of the gripping device 41 and pipetting device 42 on the manipulator 40

Rotation of a crank 121 becomes a cycle from gripping to

Set down a cuvette (Fig. 5b - 5e). A connecting rod 124 connected to the crank 121 transmits the motion to the

Gripping device 4L which slides vertically along two slide rods 125 When gripping a cuvette 5, the gripping device 41 moves down and when the gripping tongs 130 come in contact with side projections ^H 5a of the cuvette 5, the gripping tongs open in the opposite direction

Force of a spring 128. At the bottom dead center of the gripping device 41, the spring 128 can close the gripping tongs 130, hook projections 130a of the gripping tongs underside the side projections 5a of the cuvette 5. to grab. A pressure piece 131, which is loaded in the direction of the cuvette 5 by means of spring 131a, secures the gripped cuvette in the gripping tongs 130.

The settling cycle requires an additional mechanism. Figures 5b-5e show in sequence how this cycle is carried out. The first step (FIG. 5c) is the transfer (X-Y, 40) of the cuvette 5 in the desired position (possible position in the cuvette template or in the measuring station). If the gripping device 42 is exactly at the desired position, the second step is to lower the cuvette (Z) (the gripping device 42 slides along two sliding bars 125. During this time, the magnet 123 is activated and a transverse lifting bar 123a comes into it Path of movement of a head 126a of the plunger 126. The third step (FIG. 5d) takes place when the transverse rod 123a touches the head 126a of the plunger 126. As the gripping device 42 slides further down, the plunger is prevented from doing so because of the The round part of the plunger 126 presses the inner sides 130b of the gripping tongs 130 apart, opens the latter and at this moment releases the cuvette 5 (FIG. 5e) 5 has been set down, the spring 131a presses the pressure piece 131 back into its rest position, when the now open gripping device Moved upward 42, a "closer" 129 comes into contact with the upper part of the head 126a of the plunger 126, brings it back into its initial position between the rounded walls 130b of the gripping pliers 130 (see position of the plunger in FIG. 5c Step 1), wherein the spring 128 closes the gripper 130.

The device comprises various sample templates (Fig. 1, 20). Most are identical to one another with space for different sample containers or sample tubes 21. A sample template 20a has, for example a smaller number of sample tubes 21 and can be used in emergency situations (STAT template). If a template is not the current work template, this template can be removed from the test machine at any time because the templates are arranged in a drawer 22. As previously mentioned, the advantage of using multiple sample and cuvette templates is that new samples and cuvettes can be inserted into the system at any time without interrupting the process. The sample templates can be cooled to 5 - 20 ° C, preferably 10 - 15 ° C. The temperature of the templates is adjusted using a closed zululating system (not shown) which allows a liquid, preferably cold water, to circulate in metal parts below the template (not shown) and which cools the sample templates to the desired temperature. The thermostatting can also about electrical elements, preferably Peltier elements.

Two cuvette templates (FIGS. L 50a and 50b) each contain different cuvettes 5. The cuvettes 5 are lined up in a polystyrene tray (FIGS. 6, 51), which the user places in the cuvette drawer 52. The cuvette tray 51 is adapted to the cuvette drawer 52 so that the tray does not move when the gripping device grips a cuvette. In addition, the cuvette templates show a series of "rails" 54 which support the tray. The spaces between two adjacent rails 54 are shaped in this way that the cuvettes have as large a contact surface as possible with the heatable part of the drawer 52, which is heated to 25-45 ° C., preferably 30-40 ° C., more preferably 37 ° C. using a closed water system 56 Temperature setting is preferred in order to incubate the sample in the cuvettes or the still unfilled cuvettes. When all the cuvettes in the polystyrene tray have been used, the tray with the cuvettes is removed from the device by hand and thrown away.

Because the different test procedures require different reagents

5, the device contains various reagent templates (Fig. 7,

24) with conical reagent holders 25. The template opposite the

Photometer (Fig. L 24c) preferably contains starting reagents. template

24b is aligned, preferably to take up intermediate reagents, and lies between the sample and cuvette templates. Template 24a is located behind the sample templates and preferably contains "deficiency" - and

Control plasmas and preferably reagents for chromogenic tests.

In addition, reagents for preferably turbidimetric immunological tests can be stored there. The design of the device also allows other photometric or turbidimetric tests from 5 other areas of clinical laboratory operations, e.g. B. clinical chemistry.

The diameter of the reagent holder is selected so that the laboratory staff can place the original reagent bottle 23 directly in the holder (see 0 Fig. 7). Concentric rings 26 are used to adapt other bottles with different diameters to the device. So that the reagents do not heat up, the reagent templates are cooled to 5-20 ° C., preferably 10-15 ° C., preferably using the above-mentioned closed water system 5b 5. Here too, Peltier elements can preferably be used for thermostatization become. At the end of the day (or a sample run) there are still residues in the reagent bottles, so that it makes sense that the reagent template can be removed from the device by moving the screws 27a and 27b and in a refrigerator for future use can be kept. The operating personnel need not connect or disconnect pumps or wash reagent reservoirs, which of course saves labor costs and time.

The measuring station comprises a photometer with various independent optical channels. Each optical channel is constructed in the same way with no general parts or components between the channels. This design allows sample processing to continue uninterrupted in the event of a breakdown of one of the channels. Figure 8 shows in detail one of the optical channels.

The light beam emitted by the light source (halogen lamp, 220) is collected by means of a converging lens 222 and directed onto an entry slit 224 in the direction of an intermediate slit 226. The light beam then passes through an input lens 228 and is focused into the sample in the cuvette shaft 230 by means of an output slit 232. The light beam leaving the cuvette shaft is split into two beams (50% of the total transmitted light) using a beam splitter 233. The beam splitter can be made of any common material, e.g. B. fiber optics.

Each secondary light beam is directed to a filter unit which has a lower 234 and an upper filter 236. The lower filter has a transmission peak of a particular wavelength and the upper filter one at a wavelength different from the lower. In this way it is possible to carry out bichromatic measurements of samples at two different wavelengths simultaneously.

Each filtered light beam is then focused with a Sarnmell lens 238a, 238b. Finally, the focused light beam is used measured by ordinary photodetection means (photocell, 240a or 240b) and the resulting signal is amplified with a suitable amplifier 242a, 242b.

The advantage of the design mentioned above is that it is possible to take two different types of measurements, e.g. B. in two channels (z. B. turbidimetric and chromogenic measurement) because the channels preferably do not require a separate filter, like other devices of the prior art. There is no need to reserve part of the channels for one type of measurement and the rest for another type. With this feature it is possible to achieve completely random access possibilities because two wavelengths are present at the same time. Instead of using a two-wavelength photometer, it is also possible to use a "diode array photometer" which also offers the possibility of measuring at several wavelengths simultaneously.

The cuvette shaft (FIGS. 8, 230) is embedded in a metal block which can be heated to a desired temperature via a closed system 56 of circulating water. A thermosensitive element 250 detects any change in the desired temperature and a thermal resistor 252 brings the temperature to the average desired temperature.

In order to hold the cuvette 5 in the cuvette shaft 230 of the photometer, a special mechanism was devised. This mechanism consists of a pressure roller 254 which is connected to a pressure spring 256. Because all steps in sample processing require the use of the manipulator (eg pipetting of sample and reagents, transport of the cuvettes), it is preferred to rationalize the work flow with the purpose of a maximum number of samples per hour by minimizing the time when the manipulator has nothing to do.

On the other hand, the device according to the present invention is capable of executing any type of test method at any time, and since these different test types have different requirements with regard to incubation time, dilution steps, etc., a software program can be used to check the status Each sample is checked and recorded in a short period of time up to a maximum of 5 msec, preferably every 2nd msec. The advantage of such a software program is to monitor those samples whose incubation time is close to being exceeded. In this case, it is advisable to first process samples that are in critical condition (the incubation period has been exceeded). Only then should less urgent steps in the work chain, such as dilution of a sample, be carried out, which in principle is a step that is independent of time

Another purpose of such software control is to provide a quick transition between routine and emergency samples. At the time when emergency samples (STAT samples) are to be processed, it is advisable:

a) to be able to stop the processing of new samples from the "routine line" b) to be able to continue the processing of already incubating samples from the "routine line" while the emergency samples are being processed. A premature interruption of the "routine workflow" can lead to a loss of sample and reagents, which can be prevented with optimal work planning.

In addition, the software should ensure that sample processing of the interrupted "routme line" starts again exactly at the point where it was interrupted. This can be done after all STAT samples have reached a certain level of sample processing and there is now enough time to start new samples. This prevents any loss of time between the "routine" and STAT work.

At the beginning of a normal run, a waiting list containing status values is drawn up. This waiting list is preferably stored in a sample processing memory (IDA).

A simple matrix is used to compile the waiting list.

One step for optimizing the work flow is that as many samples as possible are collected in one run that require the same test type (method type). However, not all samples that require the same test type are processed at the same time, but depending on the batch size, a number of samples to be processed are combined into batches. The batch size is recorded in a work list (method list) entered into the computer, which, among other things, pipettes the - the amount of liquid, incubation time, etc., for each test type. The software program enables batches with the same Run test type 1 one below the other, for example if 25 samples require test "A" and 10 samples require test "B" and the batch size for both tests is "5", 5 batches of test "A 'run (in the example, the process priority is higher than Test "B" have one after the other, then 2 batches of test "B." The advantage of this is to save pipetting time: For example, it is more efficient that the pipette takes up a large amount of reagent and then dispenses it in different aliquots than For each sample, for example, measure the reagent and add it individually to the cuvette, for example to the plasma.

9a and 9b show an exemplary flow diagram which summarizes how state values are generated and how they increase.

The reservation of a cuvette in the cuvette template also runs via the software program. If the test type requires dilution steps of the sample, then at least two cuvettes are reserved in the cuvette template for performing this step. The software program uses the data from the work list to check whether a certain step is necessary, e.g. B. diluting a sample. If a step in a test is not necessary, the state value jumps to the next method-dependent state. If an error happens during sample processing, e.g. B. the incubation time has expired and the start response was not added immediately afterwards, the state value for this approach automatically jumps to state number 70 (FIG. 9b), i. that is, this approach is repeated from the beginning.

A general step for all tests is the addition of the start reagent

(last reagent). Between states 20 and 40 there are various critical states (not included in the flow diagram) that should be kept in mind, e.g. B. To what extent the incubation period has expired must be before the last reagent is to be added. This check is done because the cuvette should be in the measuring station before the incubation period has expired. When state 40 is reached (FIG. 9b), the cuvette is brought into the measuring station and the rest of the incubation period expires there. As soon as state 51 is reached, the start reagent is added without delay.

Another aspect of sample processing that can occur is that at a given moment there are more tests to be processed than there is free space in the measuring station. Therefore, removing the cuvette from the measuring station as soon as the measurement of a sample has been carried out (state 61) is a step that requires intensive monitoring. State 61 is therefore at the top of the following priority list. In this way it is ensured that as soon as a sample is ready for measurement, a place in the measuring station is free for it. As soon as the measured sample is removed from the measuring station, the cuvette is preferably returned to its starting position in the cuvette template. This position is then declared as "garbage" so that the cuvette used is skipped if a cuvette in the cuvette template (state 1) is to be reserved. If there is an aborted test at this time (has a status value of 70), this has a higher priority than adding a new test to the waiting list.

It is not an unusual situation that several samples have to be processed in parallel. For example, the situation can arise that one sample requires the addition of start reagent at the same time (state 51), another sample should be transported to the measuring station (state 40) and a third sample is to be transported from the measuring station to the cuvette template (state 61). Which step should be carried out first with the manipulator? Because of this, it exists a priority list. The priority list (status priority list) looks in a simplified manner as follows:

Priority list 61 51

34

08 06 05 04 .... 01

The first row contains the state with the highest priority. If more than two states are in the same row, the first state has priority over the second etc. The last row contains the group with the lowest priority.

A scanning program (loop) scans this priority list and matches it with the status values available at the moment for all tests in the waiting list. The waiting list not only reserves a place for sample processing, but also shows the current status value for each sample at any moment. If the scanning program finds a test with the state number 61, the manipulator will carry out the step which is associated with this number, ie remove a cuvette from the photometer and preferably place it in the cuvette template in the intended place and immediately again Bring a cuvette from the cuvette template with state value 40 into the photometer (rational coupling of states). If none of the samples state 61 or 5L, the program jumps to the next priority state and checks all states in the waiting list to this value, etc. If there is nothing to do with higher priority and there is enough space in the waiting list, the manipulator starts one new sample too to edit. This is done until all desired tests have been completed.

Claims

PATENT CLAIMS

1. Device (2) for the photometric analysis of liquid

Samples with the following subcomponents:

at least one sample template (20) for receiving a plurality of sample containers;

an identification device (1) for automatically identifying the sample container;

at least one reagent template (24 a, b, c) for receiving several reagent containers;

- At least one washing station (120 a, b) for one

Pipetting device (42);

at least one interchangeable cuvette template (50a, b) for holding a plurality of cuvettes;

a measuring station (60) with at least two cuvette shafts (230) for simultaneous measurement of a corresponding number of liquid samples in cuvettes; a manipulator (40), which can be positioned in three dimensions, for the automatically controlled gripping, moving, filling and depositing of cuvettes, the manipulator 5 - a gripping device (41) for gripping a cuvette and a pipetting device (42) for transferring sample liquid one of the sample containers in one or more of the cuvettes and for transferring at least one reagent from one of the reagent containers into one or more of the cuvettes 15;

the subcomponents being attached and designed in relation to one another in such a way that the entire device, the analysis process and the storage or output of the photometric data are automatically controlled from a programmable computer,

that the manipulator (40) is moved to the respective 25 sample container and to the respective reagent container,

that sample material or reagent (s) is taken up from the relevant container by means of the pipetting device (42), that the manipulator (40) is moved to the cuvette template (50 a, b) and there releases sample material into a certain cuvette in certain quantities,

that the manipulator (40) is moved to a specific cuvette and there releases reagent (s) in a specific amount,

- That the manipulator (40) to the cuvette template

(50 a, b) is moved and takes a cuvette containing certain sample material there,

that the manipulator (40) is moved with a gripped cuvette to the measuring station (60) and there introduces the cuvette into a cuvette shaft (230),

that the sample of the inserted cuvette is measured and the measurement result is displayed and / or printed out and / or saved, and

that the manipulator (40) is brought to the measuring station (60), grips the measured cuvette, the manipulator with the gripped cuvette to one

Dispensing position is brought in which the cuvette is dispensed.

2. Device according spoke 1, characterized in that at least two sample templates (20) for receiving sample Containers to enable tandem operation next to each other and / or that at least two reagent templates (24) for receiving reagent containers are arranged in the device.

3. Apparatus according to claim 1 or 2, characterized in that the identification device (1) comprises a device which recognizes a mark arranged on the sample containers.

4. Device according to one of claims 1 to 3, characterized in that the sample containers carry a code track which can be scanned by means of an optical reading device.

5. Device according to one of claims 1 to 4, characterized in that the sample template (20) and / or the reagent template (24) and / or the cuvette template (50 a, b) and / or the cuvette shafts of the measuring station (230) a certain temperature can be thermostatted, in particular by means of a closed system of circulating liquid or by means of electrical heating elements (preferably Peltier elements).

6. Device according to one of claims 1 to 5, characterized in that two cuvette templates (50 a, b) with each

Drawers (52) for receiving a tray (51) from cuvettes

, are arranged side by side and can be equipped independently of each other.

7. Device according to one of claims 1 to 6, characterized in that the measuring station (60) 5-10 independent cuvette shafts (230) for measuring 5-10 samples in cuvettes side by side.

5

8. Device according to one of claims 1 to 7, characterized in that the measuring station (60) has at least one multi-channel photometer, in particular one in which the photometric measurement is based on a bichromatic measurement 0, preferably one for bichromatic Measurement where

Light of the wavelengths 548 nm and 405 nm is used.

9. Device according to one of claims 1 to 8, characterized in that the gripping device (41) has a gripping pliers which can be actuated by a displacement of a plunger (126).

10. Device according to one of claims 1 to 9, characterized in that the gripping or settling function of the Greifein¬ direction (41) is determined by a solenoid (123). 0

11. Device according to one of claims 1 to 10, characterized in that the cuvettes have on one side a ausgebil¬ Deten projection for hooking the gripping pliers.

5 12. Device according to one of claims 1 to 11, characterized in that the Hpettiereinrichtung (42) can be heated by means of a regulated heating device (134).

13. Device according to one of claims 1 to 12, characterized in that a sensor on the warping device (42) (132) for measuring the change in capacity is arranged in the sample container and / or the reagent container.

14. Device according to one of claims 1 to 13, characterized in that sample material from a certain

Sample container is removed from the sample template (20) and transferred to a specific cuvette in the cuvette template (50), diluted there in a predetermined ratio and one or more aliquots of the diluted sample are then transferred to one or more cuvettes.

15. Device for gripping objects (41), characterized by

(1) a gripper which (a) has at least two grippers (130) which can be moved relative to one another between an open and a closed position, (b) one for the purpose of opening the grippers (130)

Settling of a previously recorded object has an actuating element (126) which is designed to be movable relative to the grippers (130) and is arranged in the device (41) in such a way that the grippers (130) move into their open position during their relative movement can be brought

(2) a drive for moving the gripping tongs (moving the tongs), possibly with a picked-up object, (3) a control part (123a) which is movably arranged in the device (41) between a neutral position and an open position such that the control part (123a) engages with the actuating element (126) in the open position in such a way stands that the actuating element (126) brings the grippers (130) into their open position during the movement of the gripping pliers.

16. The device according to claim 15, characterized in that the

Control part (123a) causes a relative movement between the grippers and the actuating element (126) in the open position during the gripper displacement, as a result of which the grippers (130) are brought into their open position and thereby release a gripped object.

17. Device according to claims 15 or 16, characterized gekenn¬ characterized in that the control part (123a) in the open position causes a relative movement of the actuating element (126) in the opposite direction 0 to Zaπgen displacement, whereby the grippers (130) are brought into their open position.

18. Device according to one of claims 15 to 17, characterized in that the actuating element (126) due to the 5 by the forceps displacement relative movement, the

Gripper (130) opens transversely to the direction of this relative movement

19. Device according to one of claims 15 to 18, marked by a closer (129) which actuates the actuating element, after this has caused the grippers (130) to open, resets during the returning pliers movement, in particular by the closer (129) engaging with the actuating element (126) in such a way that the actuating element (126) is relatively displaced in the opposite direction to the returning pliers movement is so that the grippers can return to their closed position.

20. Device according to one of claims 15 to 19, characterized in that the grippers (130) in the region in which they come into engagement with the objects to be picked up are designed so that the grippers for the purpose of picking up an object during the tongs displacement be opened by the object to be picked up pushing the grippers (130) apart.

21. Device according to one of claims 15 to 20, marked by a pretensioning device, in particular a spring, for closing the gripper (130).

22. Device according to one of claims 15 to 21, characterized in that the drive has an eccentric (121) for generating the tong displacement.

23. The device according to claim 22, characterized by a push rod (124) for implementing the rotary movement of the eccentric (121) on the device.

24. Device according to claims 22 or 23, characterized in that a rotary movement of the eccentric (121) by 360 ° each have a work cycle for gripping or a work cycle for releasing an object.

25. Device according to one of claims 15 to 24, characterized by control of the movement of the gripping tongs via position sensors by a microprocessor (119).

26. Device according to one of claims 15 to 25, characterized by a (electro) magnet (123) for actuating the

Control section (123a).

27. The apparatus of claim 25 and 26, characterized in that the electromagnet is controlled by the microprocessor.

28. Device according to one of claims 15 to 27, gekenn¬ characterized by a straight guide of the gripping tongs.

29. Device according to one of claims 15 to 28, characterized in that the gripping tongs can be positioned three-dimensionally (in three planes), the drive additionally has an x / y ring slide with which the gripping tongs can be arranged over different working positions .

30. Device according to one of claims 15 to 29, marked by a positiomer device, in particular a cube (131), which (or which) is pressed elastically onto a cuvette to be picked up, in order to prevent the grippers from moving along the cuvette

31. Method for analyzing liquid samples in cuvettes in one

Apparatus for the automatic analysis of liquid samples, characterized by the following steps automatically controlled by a computer: 5 (1) Allocation of a defined space in a cuvette template (50a, 50b) for the sample present in a cuvette in such a way that the cuvette coincides with sample located therein at the defined place,

(2) optionally diluting the sample, by adding 0 of diluent, generating a first actual value signal which corresponds to the added amount of diluent and generating a first setpoint signal corresponding to the desired amount of diluent, comparing this actual and setpoints and 5 stop dilution when a given is reached

Approximation of these actual and target values, possibly transferring one or more aliquots of the diluted sample into one or more cuvettes,

(3) if necessary, waiting for a preheating time below 0 to heat the cuvette and sample, generating a second actual value signal that corresponds to the elapsed preheating time, and generating a second target value signal that corresponds to the desired preheating time, comparing these actual and target values and 5 termination of preheating when a given approximation of these actual and target values has been reached.

(4) optionally adding one or more intermediate reagents and waiting for one or more incubation times, ό (5) moving the cuvette to a measuring station (6) Add a start reagent to the sample

(7) Carrying out the measurement

(8) Remove the cuvette from the measuring station.

32. The method according to claim 31, characterized by the generation of a temporal sequence of work signals, which define which sample is being treated and which steps the respective sample is subjected to, and corresponding execution of the processing of the samples including the movement of the cuvette as such from the station Station.

33. The method according to claim 31 or 32, characterized in that a plurality of samples are processed directly in succession by the same operation.

34. The method according to any one of claims 31 to 33, characterized in that in each case those samples are automatically processed first, the incubation time of which is possibly taking into account a predetermined tolerance

35. The method according to any one of claims 31 to 34, characterized in that the current processing of a sample is interrupted when a critical phase in the processing of another sample has been reached, in particular if the incubation time of the other sample is critical and is in progress.

36. The method according to claim 35, characterized in that the interrupted processing is then continued.

37. The method according to any one of claims 31 to 36, characterized in that the test (if appropriate automatically) is repeated if incorrect sample processing is automatically detected.

38. The method according to any one of claims 31 to 37, characterized ge indicates that the sample is brought into the measuring station before the incubation period has expired and the remaining incubation time is carried out there.

39. The method according to any one of claims 31 to 38, characterized in that several mutually independent measuring stations are used, in the cuvettes for performing analyzes are placed.

40. The method according to any one of claims 31 to 39, characterized in that the measuring station is a photometric measuring station.

41. The method according to any one of claims 31 to 40, characterized in that a device according to one of claims 1-14 is used.

42. Method for carrying out measurement methods on samples, in which sample material is transferred from a sample container into a cuvette, the sample material is subjected to processing, at least one on the processed sample material Measurement is carried out and a corresponding measurement variable is registered, characterized in that a large number of sample containers with different samples are provided in a template, that each sample can be subjected to a plurality of measurement methods and that each sample is assigned information which These measuring methods are to be carried out such that a method priority information is assigned to each individual measuring method, that sample material is transferred from the respective sample container into cuvettes one after the other in such a way that first all sample materials for which the measuring method is carried out with the highest priority are carried out then, all sample materials for which the measuring method is to be carried out with the second highest priority etc. are to be transferred to the corresponding cuvettes, so that each cuvette is assigned status information that reflects the status of the sample material The measurement procedure carried out and the next step to be carried out characterizes that the sequence of processing the cuvettes is based on a status priority list in such a way that cuvettes with status information of higher status priority are processed before cuvettes with status information of lower status priority, regardless of which procedure priority the measurement procedure has

43. The method according spoke 42, characterized in that in a computer controlling the method a. Sample identification, sample container position in the template and procedures to be carried out for each sample container of the template are stored (rack data), b. In accordance with the process priorities in order starting with the highest process priority, information about the position of the associated sample container and the relevant method is written into an FTFO memory of the computer, the rack data being stored in the FTFO memory in such a way that when the FLFO memory first information about all

Sample container positions at which the procedure with the highest priority is to be carried out, as well as information identifying the procedure, after which the corresponding information on the next lower procedure priorities is read, c. that this information from the FIFO memory is used to occupy free positions of a sample processing control memory, IDA, such that in IDA a sample identification, the position of the cuvette in the system in which the sample material is or is to be arranged, and the

Status information is stored, i. that the status information is checked automatically in the IDA and the result determines which step is carried out with which cuvette next, e. and that the corresponding new status information is written in EDA assigned to the corresponding cuvette.

44.. Method according to Claim 42 or 43, characterized in that in a computer which automatically controls the method a number of groups (BATCH size) is stored for each of the different measuring methods, and that a number of cuvettes as a group are subjected to the relevant measuring method or individual steps thereof according to the batch size.

45. The method according to any one of the preceding claims, characterized in that when the processing of the cuvettes is carried out due to the status priority after a predetermined period of time has elapsed, without the processing being a full one

Has passed through the status priority list, the processing is carried out again at the beginning of the status priority list, so that cuvettes with a status change that may have occurred in the meantime are preferably processed to higher priorities.

46. The method according to any one of claims 43 - 45, characterized gekenn¬ characterized in that the information and instructions for the individual steps of the measurement process is stored in files in the memory of a computer controlling the process.

47. The method according to any one of the preceding claims, characterized in that the samples consist essentially of liquids with human and / or animal components, in particular human body fluids, preferably blood plasma.

48. The method according to any one of the preceding claims, characterized in that the method with a device according to one of the preceding device claims is performed.

49. The method according to any one of the preceding claims, characterized in that the sample template and cuvette holding devices, which are preferably thermostatted and can hold a plurality, preferably 100 to 600 cuvettes, are arranged in one device such that a gripper arm and a pipette from A computer controls both the movement of the cuvettes and the introduction of the materials into the cuvettes, and that the movement of the pipette and gripper arm is carried out by a mechanical X / Y / Z control system, preferably both the sample container and the reagents and diluents - Containers, as well as the cuvettes, as well as measuring stations

Measuring device for the cuvettes are arranged in an X / Y grid structure.

50. The method according to any one of the preceding claims, characterized in that the measurement of the sample material with a

Multi-channel photometer, preferably a photometer with at least 5 channels.