WO1993020612A2 - Dispositif automatique pour l'analyse photometrique d'echantillons liquides - Google Patents

Dispositif automatique pour l'analyse photometrique d'echantillons liquides Download PDF

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Publication number
WO1993020612A2
WO1993020612A2 PCT/EP1993/000804 EP9300804W WO9320612A2 WO 1993020612 A2 WO1993020612 A2 WO 1993020612A2 EP 9300804 W EP9300804 W EP 9300804W WO 9320612 A2 WO9320612 A2 WO 9320612A2
Authority
WO
WIPO (PCT)
Prior art keywords
sample
cuvette
cuvettes
template
samples
Prior art date
Application number
PCT/EP1993/000804
Other languages
German (de)
English (en)
Other versions
WO1993020612A3 (fr
Inventor
Hans-Jürgen KOLDE
Michael Kiehl
Wolfgang Koehne
Isabel Ramirez
Original Assignee
Baxter Deutschland Gmbh
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Baxter Deutschland Gmbh filed Critical Baxter Deutschland Gmbh
Publication of WO1993020612A2 publication Critical patent/WO1993020612A2/fr
Publication of WO1993020612A3 publication Critical patent/WO1993020612A3/fr

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Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/508—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above
    • B01L3/5085—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above for multiple samples, e.g. microtitration plates
    • B01L3/50851—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above for multiple samples, e.g. microtitration plates specially adapted for heating or cooling samples
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/25—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
    • G01N21/251—Colorimeters; Construction thereof
    • G01N21/253—Colorimeters; Construction thereof for batch operation, i.e. multisample apparatus
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/00584—Control arrangements for automatic analysers
    • G01N35/0092—Scheduling
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/00584—Control arrangements for automatic analysers
    • G01N35/0092—Scheduling
    • G01N35/0095—Scheduling introducing urgent samples with priority, e.g. Short Turn Around Time Samples [STATS]
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/0099—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor comprising robots or similar manipulators
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N2035/00346—Heating or cooling arrangements
    • G01N2035/00356—Holding samples at elevated temperature (incubation)
    • G01N2035/00376—Conductive heating, e.g. heated plates
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N2035/00346—Heating or cooling arrangements
    • G01N2035/00425—Heating or cooling means associated with pipettes or the like, e.g. for supplying sample/reagent at given temperature
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/00584—Control arrangements for automatic analysers
    • G01N35/0092—Scheduling
    • G01N2035/0093—Scheduling random access not determined by physical position
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/02—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations
    • G01N35/04—Details of the conveyor system
    • G01N2035/0496—Other details
    • G01N2035/0498—Drawers used as storage or dispensing means for vessels or cuvettes
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/25—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
    • G01N21/31—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry
    • G01N21/314—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry with comparison of measurements at specific and non-specific wavelengths
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/02—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations
    • G01N35/028—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations having reaction cells in the form of microtitration plates
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N35/1081—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices characterised by the means for relatively moving the transfer device and the containers in an horizontal plane
    • G01N35/109—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices characterised by the means for relatively moving the transfer device and the containers in an horizontal plane with two horizontal degrees of freedom

Definitions

  • 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.
  • the invention relates to a device for automatic photometric blood coagulation analysis.
  • the devices can run only a few different types of tests simultaneously or in quick succession, all z. B. are coagulation tests.
  • Test B If Test B is to be run, Test A's reagents in the reagent holders must be replaced.
  • 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.
  • any coagulation test e.g., quick test, aPTT test, etc.
  • 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.
  • Another Ai-ts Operationssfo ⁇ n 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.
  • 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
  • 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).
  • 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.
  • the preferred batch function in which each of the
  • 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.
  • IDA sample processing control memory
  • 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.
  • 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
  • the gripping device has gripped the cuvette 5c the gripping device removes the cuvette from the
  • Template 5d Reset the cuvette into the template
  • 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
  • the device 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • the device is also capable of carrying out any other type of test at this time without additional changes.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • FIGS. 5a to 5e 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
  • 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
  • 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.
  • 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.
  • STAT template emergency situations
  • 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 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.
  • 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.
  • the device contains various reagent templates (Fig. 7,
  • 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
  • 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.
  • 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.
  • 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.
  • 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:
  • 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.
  • 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.
  • 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.
  • 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.

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Abstract

Le dispositif (2) d'analyse photométrique de prélèvements liquides présente l'avantage de permettre de traiter un certain nombre de prélèvements requérant différents phases de travail (différents temps d'incubation et de mesure). Ce dispositif permet de ce fait de procéder à plus de vingt différentes sortes de tests en relativement peu de temps. L'invention fait également état d'un dispositif de préhension des objets (41) et d'un procédé d'analyse des prélèvements liquides dans les cuvettes d'un dispositif d'analyse automatique de prélèvements liquides. L'invention décrit également une méthode de mesure des prélèvements selon laquelle la substance à analyser est transféré d'un récipient d'échantillons dans une cuvette, pour y subir un traitement et être soumise à une mesure au moins, et selon laquelle une grandeur mesurée correspondante est enregistrée.
PCT/EP1993/000804 1992-04-02 1993-04-01 Dispositif automatique pour l'analyse photometrique d'echantillons liquides WO1993020612A2 (fr)

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DEP4210963.9 1992-04-02
DE19924210963 DE4210963A1 (de) 1992-04-02 1992-04-02 Automatische Vorrichtung zur photometrischen Analyse von flüssigen Proben

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EP0563891A2 (fr) * 1992-04-03 1993-10-06 Toa Medical Electronics Co., Ltd. Appareil automatique d'analyse immunochimique
EP0569215A2 (fr) * 1992-05-04 1993-11-10 Wallac Oy Appareil d'analyse chimique clinique
WO1994014074A1 (fr) * 1992-12-04 1994-06-23 Eurogenetics N.V. Procede et dispositif automatise pour la realisation de tests immunologiques
WO1997019339A1 (fr) * 1995-11-17 1997-05-29 Nederlandse Organisatie Voor Toegepast-Natuurwetenschappelijk Onderzoek Tno Dispositif de mesure photometrique et support conçu pour un tel dispositif
DE19854919A1 (de) * 1998-11-27 2000-06-15 Luigs & Neumann Feinmechanik U Arbeitsplatz für mikrobiologische Untersuchungen
DE10006846A1 (de) * 2000-02-16 2001-09-06 Macherey Nagel Gmbh & Co Hg Verfahren zur photometrischen CSB-Messung sowie Küvette für photometrische Messungen
DE10133857C2 (de) * 2000-07-13 2003-06-12 Suzuki Motor Co Probenanalyseeinrichtung
WO2004003569A2 (fr) * 2002-06-28 2004-01-08 Institut Pasteur Plate-forme robotisee de culture cellulaires en batteries de reacteurs miniaturises, equipe d'un systeme de mesure en temps reel d’une propriete optique
US6678577B1 (en) 1997-05-16 2004-01-13 Vertex Pharmaceuticals Incorporated Systems and methods for rapidly identifying useful chemicals in liquid samples
WO2004098764A2 (fr) 2003-04-30 2004-11-18 Aurora Discovery, Inc. Plaque multi-puits pour stockage a densite elevee et plate-forme de dosage
US6823041B2 (en) 2001-09-07 2004-11-23 Bruker Axs Gmbh Grasping system for automated exchange of elongated samples in an X-ray analysis apparatus
US6826253B2 (en) 2001-09-07 2004-11-30 Bruker Axs Gmbh X-ray analysis apparatus
WO2005012329A2 (fr) 2003-07-29 2005-02-10 Invitrogen Corporation Dosages de kinase et de phosphatase
CN103364574A (zh) * 2013-08-06 2013-10-23 济南华天恒达科技有限公司 全自动白带分析仪
CN108732135A (zh) * 2017-11-20 2018-11-02 重庆中元汇吉生物技术有限公司 一种血液细胞及蛋白分析装置
CN110412302A (zh) * 2019-07-30 2019-11-05 香港大德昌龙生物科技有限公司 单人份化学分析装置及其分析样品的方法
CN110849701A (zh) * 2019-11-04 2020-02-28 山东见微生物科技有限公司 样本处理设备
CN111157751A (zh) * 2020-01-03 2020-05-15 香港大德昌龙生物科技有限公司 一种试剂盒装置以及试剂盒装载装置
CN112698046A (zh) * 2015-06-22 2021-04-23 深圳迈瑞生物医疗电子股份有限公司 样本分析装置及其控制方法
WO2021135366A1 (fr) * 2019-12-31 2021-07-08 科美诊断技术股份有限公司 Procédé d'agencement d'éléments de test d'échantillons et appareil

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DE19549559C2 (de) * 1994-09-21 2000-10-12 Hitachi Ltd Gerät zum Analysieren des menschlichen Blutes oder Urins
JP3228645B2 (ja) * 1994-09-21 2001-11-12 株式会社日立製作所 免疫分析装置
DE29720432U1 (de) * 1997-11-19 1999-03-25 Mwg Biotech Gmbh Roboter
JP3426540B2 (ja) * 1999-07-12 2003-07-14 理学電機工業株式会社 試料交換機を有する分析システム
DE10018876A1 (de) * 2000-04-14 2001-10-25 Mettler Toledo Gmbh Analysenvorrichtung und Analysiereinrichtung
US7198924B2 (en) 2000-12-11 2007-04-03 Invitrogen Corporation Methods and compositions for synthesis of nucleic acid molecules using multiple recognition sites
WO2002066991A2 (fr) * 2001-02-16 2002-08-29 Aventis Pharmaceuticals Inc. Dosage de matrice semi-solide automatise et appareil de traitement de liquides pour ce dernier
JP3740428B2 (ja) * 2002-03-29 2006-02-01 アロカ株式会社 検体前処理システム
JP3985665B2 (ja) 2002-11-18 2007-10-03 日立工機株式会社 自動分注装置
EP1697534B1 (fr) 2003-12-01 2010-06-02 Life Technologies Corporation Molecule d'acide nucleique contenant des sites de recombinaison et leurs procedes d'utilisation
US20080020469A1 (en) 2006-07-20 2008-01-24 Lawrence Barnes Method for scheduling samples in a combinational clinical analyzer
US20080020467A1 (en) * 2006-07-20 2008-01-24 Lawrence Barnes Fluid metering in a metering zone
EP2078961B1 (fr) * 2008-01-08 2020-04-08 Liconic Ag Dispositif de manipulation d'échantillons de laboratoire
EP2172780A1 (fr) 2008-10-01 2010-04-07 Bayer Technology Services GmbH Appareil pour effectuer automatiquement des analyses
DE102010037084A1 (de) * 2010-08-20 2012-02-23 LCTech GmbH Probenaufbereitungssystem sowie ein Verfahren zur Bearbeitung einer Probe
CN108802416A (zh) * 2017-05-05 2018-11-13 北京普利生仪器有限公司 样本分析仪的加样装置及样本分析仪
CN108061708A (zh) * 2017-12-14 2018-05-22 青岛顺昕电子科技有限公司 尿素含量分析系统及其控制系统、控制方法

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Cited By (31)

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Publication number Priority date Publication date Assignee Title
EP0563891A3 (en) * 1992-04-03 1995-05-10 Toa Medical Electronics Automated immunochemical analyzer
EP0563891A2 (fr) * 1992-04-03 1993-10-06 Toa Medical Electronics Co., Ltd. Appareil automatique d'analyse immunochimique
EP0569215A2 (fr) * 1992-05-04 1993-11-10 Wallac Oy Appareil d'analyse chimique clinique
EP0569215A3 (fr) * 1992-05-04 1995-05-24 Wallac Oy Appareil d'analyse chimique clinique.
WO1994014074A1 (fr) * 1992-12-04 1994-06-23 Eurogenetics N.V. Procede et dispositif automatise pour la realisation de tests immunologiques
US6239875B1 (en) * 1995-11-17 2001-05-29 Nederlandse Organisatie Voor Toegepast-Natuurwetenschappelijk Photometric measuring system and a holder for such a system
WO1997019339A1 (fr) * 1995-11-17 1997-05-29 Nederlandse Organisatie Voor Toegepast-Natuurwetenschappelijk Onderzoek Tno Dispositif de mesure photometrique et support conçu pour un tel dispositif
US6678577B1 (en) 1997-05-16 2004-01-13 Vertex Pharmaceuticals Incorporated Systems and methods for rapidly identifying useful chemicals in liquid samples
US7105132B2 (en) 1997-05-16 2006-09-12 Aurora Discovery, Inc. Liquid chemical distribution method and apparatus
US6685884B2 (en) 1997-05-16 2004-02-03 Vertex Pharmaceuticals, Inc. Methods for rapidly identifying useful chemicals in liquid sample
US6890485B1 (en) 1997-05-16 2005-05-10 Aurora Discovery, Inc. High throughput chemical handling system
DE19854919A1 (de) * 1998-11-27 2000-06-15 Luigs & Neumann Feinmechanik U Arbeitsplatz für mikrobiologische Untersuchungen
DE10006846A1 (de) * 2000-02-16 2001-09-06 Macherey Nagel Gmbh & Co Hg Verfahren zur photometrischen CSB-Messung sowie Küvette für photometrische Messungen
DE10006846C2 (de) * 2000-02-16 2002-03-07 Macherey Nagel Gmbh & Co Hg Verfahren zur photometrischen CSB-Messung
DE10133857C2 (de) * 2000-07-13 2003-06-12 Suzuki Motor Co Probenanalyseeinrichtung
US6826253B2 (en) 2001-09-07 2004-11-30 Bruker Axs Gmbh X-ray analysis apparatus
US6823041B2 (en) 2001-09-07 2004-11-23 Bruker Axs Gmbh Grasping system for automated exchange of elongated samples in an X-ray analysis apparatus
WO2004003569A3 (fr) * 2002-06-28 2004-04-15 Pasteur Institut Plate-forme robotisee de culture cellulaires en batteries de reacteurs miniaturises, equipe d'un systeme de mesure en temps reel d’une propriete optique
WO2004003569A2 (fr) * 2002-06-28 2004-01-08 Institut Pasteur Plate-forme robotisee de culture cellulaires en batteries de reacteurs miniaturises, equipe d'un systeme de mesure en temps reel d’une propriete optique
US8652829B2 (en) 2002-06-28 2014-02-18 Institut Pasteur Robotized platform for cell cultures in miniature reactor batteries, equipped with a system for real time measurement of cellular turbidity or other optical properties
WO2004098764A2 (fr) 2003-04-30 2004-11-18 Aurora Discovery, Inc. Plaque multi-puits pour stockage a densite elevee et plate-forme de dosage
WO2005012329A2 (fr) 2003-07-29 2005-02-10 Invitrogen Corporation Dosages de kinase et de phosphatase
CN103364574A (zh) * 2013-08-06 2013-10-23 济南华天恒达科技有限公司 全自动白带分析仪
CN112698046A (zh) * 2015-06-22 2021-04-23 深圳迈瑞生物医疗电子股份有限公司 样本分析装置及其控制方法
CN112698046B (zh) * 2015-06-22 2024-01-30 深圳迈瑞生物医疗电子股份有限公司 样本分析装置及其控制方法
CN108732135A (zh) * 2017-11-20 2018-11-02 重庆中元汇吉生物技术有限公司 一种血液细胞及蛋白分析装置
CN110412302A (zh) * 2019-07-30 2019-11-05 香港大德昌龙生物科技有限公司 单人份化学分析装置及其分析样品的方法
CN110849701A (zh) * 2019-11-04 2020-02-28 山东见微生物科技有限公司 样本处理设备
CN110849701B (zh) * 2019-11-04 2023-02-28 山东见微生物科技有限公司 样本处理设备
WO2021135366A1 (fr) * 2019-12-31 2021-07-08 科美诊断技术股份有限公司 Procédé d'agencement d'éléments de test d'échantillons et appareil
CN111157751A (zh) * 2020-01-03 2020-05-15 香港大德昌龙生物科技有限公司 一种试剂盒装置以及试剂盒装载装置

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