AT520151A1 - ANALYZER AND METHOD FOR CARRYING OUT CHEMICAL, BIOCHEMICAL AND / OR IMMUNECHEMICAL ANALYZES - Google Patents

Abstract

The invention relates to a method and a device for carrying out chemical, biochemical and / or immunochemical analyzes of liquid samples which are present in a sample store (920) of an automatic analyzer (100) with the aid of liquid reagents which are present in at least one reagent store ( 950a, 950b) of the analyzer (100), with cuvettes (201) for receiving the liquid samples and reagents, wherein a plurality of cuvettes are arranged as at least one stationary, linear cuvette array (200) in the analyzer. The analyzer has movable and stationary machine components, wherein at least two machine components are designed to be movable independently of one another along or parallel to the line of movement defined by the linear cuvette array (200) in the x direction and to access respectively different cuvettes (201) or groups of cuvettes ( 201) in freely selectable order.

Description

The invention relates to an automatic analyzer for carrying out chemical, biochemical and / or immunochemical analyzes of liquid samples which are present in a sample store of the analyzer, with the aid of liquid reagents which are present in at least one reagent store of the analyzer, and a method for automatic chemical , biochemical and / or immunochemical analysis of liquid samples.

Automated analyzers or analyzers are routinely used in, for example, clinical diagnostics, analytics, and microbiology, with the need to quickly, accurately, and reproducibly determine various properties and ingredients of liquid samples, especially with optical methods.

In the known analyzers different measuring principles are used. On the one hand, devices with a stationary detection unit, for example a stationary photometer, and a disk-shaped rotatable holder with cuvettes are used to hold the reaction mixtures of samples and reagents to be measured. The cuvettes are successively passed by the detection unit and measured. As a result, the cuvette carousel must stop each time a new sample or reagent is placed in a cuvette or the cuvette is to be washed and provided for a new test. The conceptually fixed cycle times are accompanied by a significant drop in efficiency. Further details can be found in the discussion of the state of the art (see point A).

For a better understanding of the invention, a few essential technical terms used in the subject application are further defined:

analyzer:

Apparatus for carrying out chemical, biochemical and / or immunochemical analyzes of liquid samples present in a sample store present in the analyzer with the aid of liquid reagents present in at least one reagent store present in the analyzer. χ-Γ ν and z-axis: x-axis means the horizontal longitudinal axis, y-direction the horizontally extending latitude or longitude axis, and z- the vertical height axis of the analyzer (see, for example, Figure 3). cuvette:

A cuvette in the sense of the present invention refers to a container which is closed on all sides, open at the top and thermostatable, for receiving sample and reagent liquids and the resulting reaction mixtures and serves to measure the reaction mixtures by means of photometric and / or luminescence-optical methods. A cuvette in the sense of the present invention has at least one window which is permeable to the applied optical measuring method and is arranged in a side wall of the cuvette or is entirely optically transparent. stationary cuvette array:

Designates a multiplicity of juxtaposed cuvettes, which are arranged stationary in the analyzer and are moved along none of the x, y and z axes during the usual measuring operation. linear cuvette array:

Denotes a single row of a plurality of cuvettes arranged along a straight line.

Reaaenzienaefäß:

Container for receiving reagents needed to perform the analysis.

Probenaefäß:

Vessel or container, which contains in the analyzer, the analysis sample (the sample to be analyzed), from which for the analysis of individual analytes or

Parameter multiply smaller sample quantities (aliquots) can be removed. The analysis does not take place in the vessel of the analytical sample, but after addition of the reagents in the cuvette, which serves in this sense as a reaction vessel.

Analvsenprobe:

The analytical sample (usually called only a sample or a substance sample) is the material to be analyzed that is introduced into the analyzer. This material is a liquid mixture and may, for example, be a body fluid such as e.g. Blood serum, blood plasma, urine and cerebrospinal fluid. Other mixtures are e.g. Drinking water, sewage, wine, beer and fruit juices as well as liquids from chemical and biochemical fermentation processes.

Analvt:

The analytes or analytes (also referred to as parameters) are those substances contained in an analytical sample which are to be used to make statements with an analyzer via a chemical analysis with the aid of liquid reagents, i. which are determined quantitatively, indicating the concentration.

Analysis:

The analysis or test (in the case of immunochemical analyzes also referred to as immunoassay) refers to the quantitative determinations of an analyte contained in the analytical sample with the aid of liquid reagents, which are automatically carried out with an analyzer.

pipetting:

Designates the entire system of an automatic pipetting device for liquid transfer between different vessels, which contains one or more movable pipettors including all mobile and stationary components required for their function, including supplying fluidics (hose connections, pumps, valves, containers, etc.), sensors, control and power supply includes.

pipettor:

Describes a with respect to the receptacles (cuvettes, sample vessels, reagent vessels) horizontally in at least one direction linearly movable or pivotable component of the pipette. The pipettor includes a suspension component having at least one pipetting needle, which is movable alone or together with the pipettor and lowered into a receptacle.

pipetting:

Designates a cannula or hollow needle attached to the pipettor together with its holder for sucking up samples from the sample vessels and / or for sucking up reagents from the reagent vessels and for dosed delivery of the absorbed liquids into the cuvettes.

Stationary machine component:

Automaton component which is stationary in the analyzer and during the normal measurement operation is not moved along the linear cuvette array (moved).

Mobile vending component:

Designates a machine component, which is not stationary in the analyzer and can be moved and positioned at least along the linear cuvette array during the usual measuring operation by means of a controlled drive. A) Analvsensvsteme with on turntables circular anaeordneten. movable reaction vessels / cuvettes fKarussellanordnunα,)

US Pat. No. 8,911,685 B2 (HITACHI) discloses a typical automatic analyzer for carrying out chemical and biochemical analyzes of liquid samples by means of photometric measuring methods. An essential feature of these analyzers are arranged on the peripheral circumference of a turntable reaction vessels, which also act as cuvettes, and stationary along the turntable circumference arranged device components, such as. Pipettors (sample dispenser, reagent dispenser), mixing device, optical measuring device and cuvette washing unit. The thermostating of the cuvettes can be integrated, for example, in the form of a temperature-controlled water bath in the turntable. The sample containers are placed on a sample turntable that locates reagents on a reagent turntable.

From DE 11 2009 002 702 B4 (HITACHI) a further automatic analyzer is known, whose sample container and reagent container are present in a carousel arrangement. As shown in Fig. 1 of the subject application, the analyzer comprises a sample disk A on which a number of sample containers B for receiving a sample can be mounted; a first reagent disc CI and a second reagent disc C2, on each of which a number of reagent containers Dl or D2 for receiving a first reagent or a second reagent can be arranged; and a reaction disk E on which a number of cuvettes or reaction vessels F are arranged along the circumferential direction.

Between the reaction disc E and the sample disc A, a sample dispenser G is provided which emits a sample sucked on the sample container B in the reaction vessel F. Furthermore, wipe the reaction disk E and the first reagent disc CI a first reagent dispenser Hl is provided which emits a sucked from the reagent container Dl on the first reagent disc CI reagent in the reaction vessel F. Similarly, a second reagent dispenser H2 is provided between the reaction disk E and the second reagent disk C2, which dispenses a reagent sucked from the reagent container D2 on the second reagent disk C2 into the reaction container F. The sample dispensing device G and the two reagent dispensers H1 and H2 are stationarily arranged at defined points along the circumference of the reaction disc E.

At the outer circumference of the reaction disc E, two fixed stirrers J1, J2 stirring the liquid in the reaction vessels F after discharge of the first reagent and the second reagent, a light source K for sending light through the reaction vessels F, and a vessel cleaning mechanism L for

Purify the reaction vessel F, provided in this order in the direction of rotation of the reaction disc E.

In a position opposite to the light source K, a stationary spectroscopic system M is arranged such that the reaction disk E is located therebetween. In the vicinity of the spectroscopic system, a signal processing circuit N is provided, which processes the signals from the spectroscopic system M.

The signal processing circuit N is connected to a computer (not shown). The automatic analyzer also includes a controller S which controls the operation of the analyzer.

Such analyzers are characterized in that all processes are predetermined by rigid clock cycles of the carousel and must run in predetermined time windows. Actions such as dispensing, mixing, measuring and washing can only take place if the respective cuvettes are located at the positions of the respective device components.

Thus, a sample (not anytime, but) can be dispensed into an empty cuvette only when the empty cuvette passes the position of the sample pipettor and stops the cuvette carousel at that position. A reagent can only be dispensed into a cuvette containing the sample as the cuvette passes the position of the reagent pipettor and stops the cuvette carousel at that position. The same applies to the stirring of reaction mixtures from the sample and the reagents in the cuvettes with mechanical stirring and for the optical measurement at the position of the optical measuring device.

Thus, for example, a particular cuvette can not be measured optically at any time or not repeatedly in small time intervals, since it is only necessary to wait until the cuvette in question is at the position of the optical measuring unit or past it "on the fly" during the measurement to be led.

In the case of completed reactions, it is not possible to measure directly, and in the case of kinetic measurements, the time intervals between the individual measurements are relatively large (at least one plate revolution). Upon completion of measurements, a cuvette can not be readily washed and provided for a new test disadvantageously. A cuvette can not be washed and provided for a new test until the cuvette in question is in the position of the cuvette washing station and at a fixed time or a fixed period of time from the beginning of the test to the cycle time corresponding to the conceptually fixed cycle times. at the relevant position a wash stop is (is provided). As a result, all cuvettes are "blocked" for the same amount of time, regardless of whether the measurement duration for the respective tests is short or long.

The rotationally organized carousel arrangement with moving samples, reagents and cuvettes, in particular the carousel concept with movable cuvettes and stationary automatic components, results in relatively high throughput times for the individual tests and limits the number of tests per hour on a device with one certain number of cuvettes can be performed. B) Analvsensvsteme with circular anaeordneten, stationary Reaktionsaefäßen / cuvettes

US Pat. No. 5,178,833 A (BIOSEMA) discloses an automatic analyzer with circular measuring cups and reagent vessels arranged in a circle, stationary relative to the apparatus, wherein the measuring cuvettes are arranged in an outer ring and the reagent vessels are arranged in two inner rings. In the center of the annularly arranged reagent vessels, the axis of rotation of a stationary pipettor is positioned, which is surrounded by an annular washing vessel for the lowerable pipetting needle of the pipettor. The sample vessels of the analyzer are located on a separate turntable on the periphery of the stationary cuvette rings. An optical measuring unit reaches the measuring cuvettes by means of a rotary movement about the central axis of the analyzer. The optical path leads through the liquid surface along the longitudinal axis of the individual cuvettes. The pipetting needle reaches the sample vessels, the measuring cuvettes, the reagent vessels and the washing vessel by means of rotational movements of two horizontal arms of the pipettor about a first, central axis and a further axis.

The disadvantage is that the disclosed configuration allows only an independently movable pipetting needle for sample and reagents, that the reagent storage is limited to the surface of the inner stationary rings and that the optical path passes through the surface of the reaction liquid. A particular disadvantage is that the cuvettes can not be washed, but must be replaced after use sector by sector with the outer ring. C) Analvsensvsteme with linear anaeordneten. movable reaction vessels / cuvettes

From GB 1 321 754 A, an automatic analyzer with reaction vessels / cuvettes fixed on linearly movable, continuous endless belts is known.

US 2014/0287523 A1 (ABBOTT) also discloses an analyzer with reaction vessels or cuvettes arranged linearly on bands. The linear endless belts are clamped on two pulleys, wherein in the longitudinal direction, for example, in a "pretreatment lane" and in a "primary process lane" corresponding reaction vessels are attached. By rotating the rollers, the reaction vessels or cuvettes can be moved back and forth in the direction of the tape and also bypass the rollers on the bottom. The arrangement runs on a "linear variant" of the classic carousel arrangement, in which the reaction vessels or cuvettes move on a circular path. Common to both variants, however, is that the reaction vessels or cuvettes are still moved relative to the device and driven to the processing stations (machine components). There are therefore essentially the same disadvantages as already mentioned in point A).

WO 99/046601 A1 (HITACHI) shows a linear, moveable cuvette array with stationary device components (dispensers for sample liquid and reagents, mechanical agitators, photometer and cuvette washing station).

As shown in FIG. 2 of the subject application, in WO 99/046601 A1 a plurality of cuvettes or reaction vessels 2 are arranged in a support frame or a transport strip 7 at predetermined intervals in a thermostatically controlled chamber (water bath) 1. The mixture of the cuvette in ha Its done for example by means of ultrasound. The transport bar with the reaction vessels 2 is linearly moved by means of a drive unit 8 in the direction of arrow 9. Further, in addition to the thermostatically controlled chamber 1 a

Sample pipetting unit 3a, a Reagenzzinjektionseinheit 3b, an optical measuring unit 4, a Küvettenwascheinheit 5, and a first stirring mechanism 6a and a second stirring mechanism 6b for re-stirring the contents of the reaction vessels 2 are provided. The stirring mechanism 6a or 6b can also be designed as an ultrasonic generator, which acts on the reaction vessels 2 via the water bath in the chamber 1. In this embodiment variant, the water in the thermostatically controlled chamber 1 is kept at a constant temperature at which the reactions take place and the optical measurement can be carried out.

During operation of the device, a reaction vessel 2 stops at the sample pipetting unit 3 a, which discharges the sample into the reaction vessel 2. Also, the reagent injection unit 3b discharges the reagent used for the assay into the corresponding reaction vessel 2. In addition, the first stirring mechanism 6a for mixing the reaction solution and the second stirring mechanism 6b again stir the mixture in the reaction vessel 2. The optical measurement unit 4 measures the absorption in the corresponding reaction vessel. Furthermore, the cuvette washing unit 5 discards the tested reaction solution and cleans the reaction vessel 2. After the completion of these operations, the movement of the reaction vessels 2 by the drive unit 8 is started. As the reaction vessels 2 continue to move, the sample pipetting unit 3a, the reagent injection unit 3b, and the first and second stirring mechanisms 6a, 6b are washed in a cleaning unit. A number of chemical analyzes are performed by repeating the above procedure. As can be seen from the above process, the individual components of the device must be arranged in the order named along the direction of movement 9.

A disadvantage of this concept is that the transport bar 7 necessarily requires a lot of free space for the linear movement of the reaction vessels 2 to the left or right of the stationary device components 3a, 3b, 6a, 6b and 5. Thus, the longitudinal axis of the analyzer inevitably increases by at least twice the length of the transport bar. 7

The cuvettes or reaction vessels 2 of the device according to WO 99/046601 A1 are thus moved past the stationary device components, analogously to the turntable variant described above. The system is inflexible, there are essentially the disadvantages that have already been mentioned in point A). D) Systems with circular and / or linear anaeordneten stationary Reaktionsaefäßen / cuvettes

From EP 2 309 251 A1 (SIEMENS) an automatic analyzer with stationary sample vessels or cuvettes present in a circular or linear arrangement is known, wherein the optical measuring unit is designed to be movable on a rotatable device along the sample vessels. According to one embodiment, the rotatable device, which carries the light source in the form of an LED and the photodetector in the form of a photodiode, be arranged below the receptacle of the sample vessels, whereby it is always possible to access the sample vessels by means of a gripping arm. The rotatable device may also include a plurality of LEDs of different wavelengths and a plurality of photodiodes to allow the samples to be measured at multiple wavelengths. The photodiodes can be replaced by a CCD element.

The arrangement described in EP 2 309 251 A1 is unsuitable for clinical chemistry analyzers (CC analyzers) and directed to an analyzer for hemostatic measurements (for the determination of blood coagulation). This arrangement may also be part of a multi-device system (e.g., PCR analyzer, refrigerator). The sample vessels are not reused but optionally passed to other components of a system, e.g. disposed of by means of a gripping arm or after the determination of the coagulation parameters.

In the case of coagulation measurements, only whole blood (blood plasma with the blood cells contained therein) in undiluted form is considered as a sample. In contrast, whole blood is completely unsuitable for the photometric measurements of the subject CC analyzer, since the blood cells scatter the light, and thus the measurement results would be falsified. Therefore, CC analyzers always use blood plasma or blood serum, which is also heavily diluted by the addition of reagents.

According to EP 2 309 251 A1, the vessels with the incoming samples (optionally after the addition of reagents) are used directly for the optical measurement.

With a CC analyzer, cell-free blood plasma / blood serum is always measured, which is introduced into the device by means of sample vessels, after which aliquots of the samples are transferred by means of pipettor together with reagents into separate cuvettes, which are then measured photometrically.

E) Laboratory robots and automatic pipetting and analizing devices for preparing and / or analyzing samples with stationary reaction vessels / cuvettes in 2D arrangement fMicrotiter plate

A typical analyzer for performing biochemical analyzes of liquid samples using microtiter plates is e.g. from EP 0 259 386 B1 (TECAN). The analyzer comprises a primary rack for holding a plurality of sample vessels, a cross table positionable in the xy direction next to the primary rack for holding a microtiter plate, a sample distributor arm arranged above the primary rack and the cross table, freely positionable in an upper horizontal plane and one located within the positioning area of the cross table Photometer whose beam path vertically penetrates the xy plane of the cross table.

Another example of a machine for the automatic preparation and analysis of samples in the wells of a microtiter plate is known from DE 10 2004 057 450 B4 (CYBIO).

There are a variety of machines of this type that use microtiter plates for the detection and determination of substances. Microtiter plates contain many mutually isolated wells in rows and columns (2D arrays). They are used for a wide variety of operations. The pipetting is done either manually or with high throughput screening (HTS) with the help of pipetting robots. Photometric determinations, e.g. Absorption measurements on microtiter plates in transmitted light with photometers are carried out so that the beam path traverses the well in the vertical direction through the liquid surface. For exact quantitative determinations, however, it is essential to guide the light rays through the measuring liquid via the most precisely defined and known paths and paths. Any scattering of light on particles, turbidities, entry surfaces, surfaces (for example, liquid surface, cuvette wall) leads to light losses which on the other hand falsify the measurement result.

From EP 2 410 342 A2 (HOFFMANN-LA ROCHE) a pipetting device is known, which has a pipettor with a plurality of flat, juxtaposed frame elements, which together with their pipetting needles on a main frame body in a horizontal, normal to the main frame body x Direction are movable. The pipetting device serves to transfer samples or reagents from a first row of vessels to an x-directional second row of vessels. The pipetting needles are first adjusted in y-direction to the distance of the vessels of the first row to receive sample or reagent liquid and then - adapted to dispense the sample or reagent liquid - to the distance of the second row of vessels. An independent movement of two pipetting needles in the x and y direction is not provided. Traveling modules for the y-direction and the z-direction (lifting and lowering of the pipetting needles) are arranged in flat, adjacent frame elements on the gap in order to keep the distance between the individual pipetting needles to each other low. An independent movement of the pipetting needles in the y-direction, however, is limited. For example, it is not possible to move the frame elements past one another on the transfer arm, resulting in a reciprocal restriction of the freedom of movement of the pipetting needles. Such pipetting devices find a useful application, especially in connection with microtiter plates.

From EP 1 230 553 B1 (MAXMAT) a chemical or biological analyzer is known which has a storage module for sample tubes and tubes for reagents. Furthermore, an analysis module with a reaction container in the form of a microtiter plate, as well as a movable on a rail sampling module (pipettor) is provided with two spaced apart at a fixed distance pipetting needles that work independently for automatic sampling in the z-direction and each with a retractable aspiration pipette for transferring predetermined amounts of samples and reagents from the storage module to the analysis module. In the horizontal x / y plane, the two pipetting needles can only be moved together.

The analysis module has a microtiter plate heating plate located near the bottom of the wells of the microtiter plate to convect the contents of the wells by convection. The extraction unit further includes a mixing device controlled by an electromagnet to effect alternate reciprocation of the pipetting needle when in a lowered position in a well of the microtiter plate to mix the mixture of samples and reagents.

US Pat. No. 5,897,837 A (TOA MEDICAL) discloses a pipetting apparatus suitable for sample pretreatment of an immunoassay analyzer having a first block of a pipettor movable horizontally in the x- and y-direction and equipped with two pipetting needles side by side is that can be lowered or raised independently. In this case, one of the two needles can be assigned to reagents that have other needle samples. In addition, a second block which can be moved in the x-y direction and has a lowerable pipetting needle is also present. For the needle cleaning, a stationary needle washing station must be started up. In the horizontal x- / y-plane, the two pipetting needles of the first movable block are disadvantageously only jointly movable. This has the disadvantage that the masses of the robot components of the pipettor can not be divided into the two horizontal axes x and y, so that the mass of the second pipette unit must always be accelerated for approaching positions in the y direction. Likewise, the mass of the needle washing unit including needle washing vessel must always be mitbeschleunigt in both horizontal directions. Furthermore, due to the common horizontal movement, it is not possible to simultaneously insert both needles for pipetting at different, non-adjacent positions of a row of vessels.

The object of the invention is in automatic analyzers for carrying out chemical, biochemical and / or immunochemical analyzes of liquid samples, the above - especially in connection with the predetermined by rigid clock cycles and run in predetermined time windows processes limited sample throughput of known systems - mentioned disadvantages and to propose improvements that increase the sample throughput without significantly increasing the cost of the individual analysis or the analyzer, at least maintaining the quality of the analysis. Furthermore, an improved method for automatic chemical, biochemical and / or immunochemical analysis of liquid samples is proposed.

This object is achieved by an analyzer with cuvettes for receiving the liquid samples and reagents, wherein a plurality of cuvettes is arranged as at least one stationary, linear cuvette array in the analyzer, with movable and stationary machine components, at least comprising: • along a through the linear cuvette array defined movement line in the x-direction movable executed pipettor, which is equipped with at least one pipetting needle, which is designed lowered in the z-direction in the cuvettes and in a direction of the x-direction substantially normal y-direction between the cuvettes and a mixing unit for mixing the samples and reagents in the cuvettes, an optical measuring unit which - for obtaining a measuring signal - measuring radiation emerging through a measuring window arranged laterally on the cuvette receives • a cuvette washing unit which can be moved in the x-direction for cleaning the cuvettes, • a needle washing unit for cleaning the at least one pipetting needle, and • a stationary thermostatting unit for setting a predeterminable measuring temperature in the cuvettes, wherein at least two automatic components independently of one another along or parallel to the movement line defined by the linear cuvette array can be moved in the x direction and in each case have access to different cuvettes or groups of cuvettes in a freely selectable order.

The method according to the invention for the automatic chemical, biochemical and / or immunochemical analysis of liquid samples present in a sample store of an analyzer with the aid of liquid reagents present in at least one reagent store of the analyzer for determining at least one analyte concentration in the sample comprising the following steps: - transferring a predetermined quantity of a liquid sample from a sample vessel in the sample store into a cuvette of a stationary, linear cuvette array by means of a first pipettor movable along the cuvette array; - Transferring a predetermined amount of a reagent liquid from a reagent vessel of the reagent storage in the cuvette of the stationary, linear cuvette array by means of the first pipettor or by means of a second, independent of the first movable pipettor; - mixing the liquids in the cuvette; optionally transferring a predetermined quantity of a further reagent liquid from a reagent vessel of the reagent store into the cuvette of the stationary, linear cuvette array by means of the first or the second pipettor; - if necessary, repeated mixing of the liquids in the cuvette; - photometric measurement of the contents of the cuvette by means of a movable along the cuvette array optical measuring unit and determining at least one measured value; Calculating and displaying the analyte concentration based on the determined measured value and on known or predetermined reference and calibration values; Washing and drying the cuvette by means of a cuvette washing unit movable along the cuvette array; and - providing the cuvette for subsequent analysis.

Thus, according to the invention, it is imperative that two machine components are designed to be movable independently of one another in the x-direction: the pipettor (in the simplest case a single pipettor with a single pipetting needle) and the cuvette washing unit. The mixer unit and the optical measuring unit can be stationary or movable, the Thermostatisiereinheit is mandatory stationary. It should also be noted that two different moveable machine components accessing the cuvette openings can not simultaneously access one and the same cuvette. In practice, however, it is in any case not necessary for the pipettor and cuvette washing unit, for example, to access the same cuvette "simultaneously". Furthermore, it should be noted that stationarily formed automatic components are designed so that they access any cuvette anyway, for example by virtue of the fact that each cuvette or group of cuvettes is assigned such an automatic component.

Due to the random access of the machine components, in particular the cuvette washing unit, to any cuvettes and the at least one pipettor (with at least one pipetting needle) to any sample vessels, reagent vessels and cuvettes, the throughput increases in comparison to a rotary automated machine with the same Number of cuvette considerably.

According to an advantageous embodiment of the invention, the analyzer has two independently movable in the x-direction pipettors.

Compared to the variant with a pipettor, a further increase in throughput results from the fact that the first pipettor can pipette samples into a first cuvette, while the second pipettor can simultaneously pipette reagents into a second cuvette of any desired selectivity.

According to the invention, it is further provided that at least one pipettor has two pipetting needles that can be moved independently of one another in the y-direction, parallel to one another. The two pipetting needles of a pipettor can thus pass each other independently along the same distance in the y-direction, without colliding.

In accordance with this advantageous variant, two different types of needles may also be used (e.g., for different pipetting volumes, with special coatings for different sample and reagent types, without the need for another pipettor or a needle exchange station).

A particularly advantageous variant of the invention provides that the needle washing unit is arranged on the pipettor and designed to be movable therewith.

Next throughput-enhancing is the measure that can pipette a pipetting needle, while at the same time the second is cleaned. There are also advantages with only one pipetting needle on the pipettor, since the pipettor does not always have a stationary one

Need to start needle washing unit. Since the y movement of the respective pipetting needle can take place independently of the needle washing unit carried along the pipettor, it is possible to divide the moving masses of the robotics components on the two horizontal axes so that the needle washing unit only has to be accelerated in the x direction.

The analyzer has an optical measuring unit, which according to the invention is designed as a unit which can be moved along the linear, stationary cell array.

According to the invention, the analyzer has a stationary mixer unit, for example an oscillator which acts on the cuvette array, for mixing the samples and reagents of individual groups of cuvettes, preferably of each individual cuvette. The advantage of a stationary mixer unit over a traveling one is that there is less mobile component, thus reducing the complexity of hardware and logistics of the analyzer.

The analyzer has a cuvette washing unit, which according to the invention is designed as a movable automatic component which has access to a cuvette or a group of cuvettes, preferably to two to five cuvettes arranged side by side, at the same time in each washing position.

According to the invention, the analyzer for setting a predeterminable measurement temperature on a Thermostatisiereinheit comprising heating foils which contact individual cuvettes or groups of cuvettes thermally and can be acted upon with different temperature levels.

According to the invention, the cuvettes have in a near-ground region preferably plane-parallel inlet and outlet windows, which are permeable to the inlet and outlet radiation or measuring radiation of the optical measuring unit.

Embodiments are also conceivable in which the cuvettes of the cuvette array have only one lateral outlet window in a region near the bottom, which is permeable to the emission radiation or measuring radiation of the optical measuring unit,

The invention is explained in more detail below with reference to partially schematic exemplary embodiments. Show it:

1 shows an automatic analyzer with rotary plates arranged in a circle, movable reaction vessels or cuvettes according to the prior art,

2 shows an automatic analyzer with linearly arranged, movable reaction vessels or cuvettes according to the prior art,

3 shows an automatic analyzer according to the invention for carrying out chemical, biochemical and / or immunochemical analyzes of liquid samples with a linear, stationary cuvette array in a three-dimensional overall view,

4 is a sectional view of the analyzer according to line IV-IV in Fig. 5,

5 is a simplified plan view of the analyzer of FIG. 3,

6 shows two independently movable pipettors of the automatic analyzer according to FIG. 3 in a three-dimensional view, FIG.

7 shows a movable, optical measuring unit of the automatic analyzer according to FIG. 3 in a sectional view,

8 shows a stationary mixer unit of the automatic analyzer according to FIG. 3 in a three-dimensional view, FIG.

9 shows a movable cuvette washing unit of the automatic analyzer according to FIG. 3 in a three-dimensional view, FIG.

10 is a needle washing unit of the automatic analyzer of FIG. 3 in a three-dimensional, partially cutaway view,

FIG. 11 shows a thermostating unit for the cuvettes of the automatic analyzer according to FIG. 3 in a three-dimensional, partially cutaway view, FIG.

12 shows fluidic elements of a pipetting needle of a pipettor according to FIG. 6 in a schematic illustration,

FIG. 13 shows fluidic elements of a needle washing unit according to FIG. 10 in a schematic representation, and FIG

14 shows fluidic elements of a cuvette washing unit according to FIG. 9 in a schematic representation.

Functionally identical parts are provided in the embodiment variants with the same reference numerals.

The automatic analyzers shown in FIGS. 1 and 2 relate to examples of the prior art and are described in detail in the introduction to the description (see points A) and C)).

The automatic analyzer 100 shown in FIGS. 3 to 5 is used to carry out chemical, biochemical and / or immunochemical analyzes of liquid samples. For simplicity, only those components of the analyzer 100 are shown, which are essential for the subject invention, wherein on analyzer components, such as pumps, valves, evaluation, control and drive units, not discussed in more detail.

The liquid samples are present in sample containers 921 in a sample storage 920 of the analyzer 100 and are analyzed with the aid of liquid reagents which are present in reagent containers 951 a, 951 b in two reagent storage units 950 a, 950 b of the analyzer 100.

The cuvettes 201 for receiving the liquid samples and reagents are arranged in the form of a stationary, linear cuvette array 200 in the analyzer 100 and remain in their original position during a large number of individual analyzes. The cuvette array 200 is disposed between the first reagent storage 950a and the second reagent storage 950b in the illustrated example.

The automatic analyzer 100 is equipped with movable and stationary automatic components, namely: • with two pipettors 300a, 300b movable along an axis of movement defined by the linear cuvette array 200 in the x-direction, each equipped with two pipetting needles 301al, 301a2 and 301bl, 301b2 are in the z-direction in the cuvettes 201, in the sample 920 located in the sample vessels 921 and in the reagent in the storage 950 a, 950 b located reagent vessels 951 a, 951 b are designed lowered and in a direction substantially perpendicular to the x-direction y Direction between the cuvettes 201 and the sample bearing 920 and / or the two reagent bearings 950a, 950b are designed to be movable; • with a mixer unit 400 for mixing the samples and reagents in the cuvettes 201; • with an optical measuring unit 500, which - for obtaining a measurement signal - by a laterally arranged on the cuvette 201 measuring window (202, 203) exiting measuring radiation receives (see Fig. 7); With a cuvette washing unit 600 for cleaning the cuvettes 201, which can be moved along the movement line defined by the cuvette array 200 in the x-direction, with needle washing units 700al, 700a2, 700bl, 700b2 for cleaning the pipetting needles 301al, 301a2, 301bl, 301b2 of the two Pipettors 300a, 300b; and • with a stationary thermostat unit 800 for setting a predeterminable measurement temperature in the cuvettes 201.

The pipettors 300a, 300b are fastened to the parallel rails purple, 111b by means of movable receiving elements (not shown), furthermore a corresponding rail 113 together with a movable receptacle 501 for the optical measuring unit 500 and a rail 112 together with a movable receptacle 601 for the cuvette washing unit 600 intended. The movable recordings of the pipettors 300a, 300b, and the receptacles 501 and 601 are driven, for example, by means of toothed belts and stepper motors not shown here at one end of the rails 112, 113, IIIa and 111b.

As can be seen in particular in FIG. 4, at least two-in the illustrated example several-of the automatic components are designed to be movable independently of one another along or parallel to the line of movement defined by the linear cuvette array 200 in the x-direction, and can each be directed to different cuvettes 201 or Access groups of cuvettes 201 in a freely selectable order.

In the illustrated embodiment according to FIGS. 3 to 5, the analyzer 100 has a sample storage 920, a first reagent storage 950 a and a second reagent storage 950 b. The storage areas can be completely or partially cooled.

To load the analyzer 100 with sample material, vessels 921 with analysis samples are introduced into the sample storage 920 manually or by means of robotics into predetermined positions. The analyzes desired for the individual analysis samples are input to the controller of the analyzer 100.

To charge the analyzer with reagents, reagent vessels 951a, 951b with reagents for analyzing different analytes are introduced into the two reagent stores 950a, 950b of the analyzer 100 in predetermined positions either manually or by robotics.

Vessels containing calibration fluids and reference samples can also be placed in the sample or reagent storage facilities.

In the embodiment shown, the analyzer according to FIGS. 3 to 5 has two pipettors 300a, 300b which can be moved independently of one another in the x-direction, accessing individual cuvettes 201 of the cuvette array 200 completely independently of one another and in an arbitrary order, with the exception of the same cuvette can.

The two pipettors 300a, 300b according to FIG. 6 each have a vertical tower 303a, 303b, and an arm 304a, 304b oriented horizontally in the y-direction, so that a substantially L-shaped support structure (pipettor 300a) for the two pipetting needles 301al , 301a2 or T-shaped support structure (pipettor 300b) is formed for the two pipetting needles 301bl, 301b2, which can be moved in the x-direction along the rail lila or 111b. Each pipettor thus has two pipetting needles 301al, 301a2 or 301bl, 301b2, which can be moved parallel to one another in the y-direction, with their cannulas or

Hollow needles 307 on. The pipetting needles 301al, 301a2 or 301bl, 301b2 are fastened to the left and right of the arm 304a and 304b, respectively, by means of a receptacle 305 movable in the y-direction and can thereby pass each other unhindered. Each receptacle 305 has a downwardly projecting rail section 306, at which the needle can be lowered in the z direction into the cuvettes 201 of the cuvette array 200.

The individual pipetting needles 301al, 301a2 and 301bl, 301b2 each have a needle holder 308 with a region projecting in the direction of the cuvette array 200, which carries the hollow needle 307. As a result, even if the hollow needle 307 of the pipetting needle 301b2 is aligned or lowered in alignment with the cuvette 201, sufficient clearance for the L-shaped pipettor 300a remains to be able to pass the T-shaped pipettor 300b (see FIG. 4).

In the illustrated example, therefore, the pipettor 300b or its two pipetting needles 301bl, 301b2 can only access the sample vessels 921 in the sample storage 920 and the reagent vessels 951b in the reagent storage 950b, whereas the pipettor 300a or its pipetting needles 301al 301a2 only have access to those in the reagent storage 950a has arranged reagent vessels 951a. All pipetting needles 301al, 301a2 or 301bl, 301b2 can be moved to the level of the cuvette array 200 and lowered into the individual cuvettes 201.

A substantial increase in the sample throughput can be achieved by arranging the needle washing units 700al, 700a2 or 700bl, 700b2 on the pipettor 300a or 300b, respectively, and making it movable with it. In the illustrated embodiment, each pipetting needle 301al, 301a2, 301bl, 301b2 has its own needle washing unit 700al, 700a2, 700bl, 700b2, which can be arranged, for example, respectively on the vertical tower 303a or 303b of the pipettor 300a or 300b. Thus, in each case one of the pipetting needles 301al or 301bl in the associated needle washing unit 700al or 700bl can be washed, while the respectively other pipetting needle 301a2, 301b2 dips into a cuvette 201 (see FIG. 6).

There are also simple embodiments of the analyzer conceivable that have only one pipettor. This can either be designed as an L-shaped pipettor 300a laterally movable on a sample or reagent storage and have only one movable pipetting needle 301al or have a T-shaped support structure and be designed movable between a sample and a reagent storage.

The optical measuring unit 500 illustrated in FIG. 7 is designed as a unit which can move along the linear, stationary cuvette array 200 on the rail 113 with the aid of the receptacle 501. In the example shown in FIG. 7, this consists of a light supplying unit 520 on one side of the cuvette array 200 and a spectroscopic unit 530 on the other side, which are rigidly connected to one another via the receptacle 501. The optical measuring unit 500 comprises a light source 521, for example a halogen lamp, in each case one beam path for the entrance 502 and the exit or exit door. Measuring radiation 503 with lenses 522, 523, 532 533, filters 524, deflecting mirrors 525, 531 and a spectrometer 535, which detects the spectrum of the measuring radiation or the intensity of the measuring radiation at individual predetermined wavelengths in the range of 300 to 800 nm. In the example shown in FIG. 7, the spectrometer 535 consists of a polychromator comprising an entrance slit 536, a deflecting mirror 539 and a concave diffraction grating 537, which images the spectrum of the measuring radiation 503 onto a sensor array 538, for example a photodiode array. The liquid present in the cuvette 201 is measured in transmitted light in the illustrated example, wherein the incident radiation 502 enters the cuvette 201 through a lateral entrance window 202 and exits the cuvette 201 through an opposite exit window 203.

Preferably, the optical measuring unit 500 comprises a reference detector 526 for measuring and compensating variations in the intensity of the light emitted by the light source 521. This comprises, for example, a beam splitter 528 located in the beam path for the incident radiation 502, a diaphragm 529 and a photodetector 527, for example a photodiode.

With the optical measuring unit 500 described above, various optical measurements at single and / or multiple wavelengths in the wavelength range of the ultraviolet and visible light ranges can be performed. Examples include photometric, turbidimetric, and luminometric measurements.

In the following, an optical measuring process using the example of a photometric measurement will be described. The incident radiation 502 originating from the polychromatic light source 521 passes through the reaction mixture of sample and the reagents added for the respective analysis in the cuvette 201, enters the spectroscopic unit 530 as measuring radiation 503, and is measured in the spectrometer 535 with respect to the wavelengths at the diffraction grating 537 divided and received by the sensor array 538. The individual light-receiving elements of the sensor array 538 of the spectrometer 535, for example photodiodes, and the reference photodiode 527 of the reference detector 526 emit a photocurrent corresponding to their respective measurement wavelength, which is converted by a signal processing circuit and by means of AD converter into a digital measurement. Depending on the respective analysis, an operating unit calculates individual or periodically measured digital measured values over time and at one or more wavelengths with the previously known reference and calibration values assigned to the respective analysis to a concentration value of the analyte.

For mixing the samples and reagents, a stationary mixer unit 400 is assigned to the entire cuvette array 200, preferably individual groups of cuvettes 201 (see FIGS. 3 and 4). The mixer unit 400 is designed, for example, as an oscillating transmitter acting on the cuvette array 200 according to FIG. 8 and has a base mass 491 which supports a carrier element 493 for the cuvette array 200 with spring elements, for example inclined leaf spring elements 492. An electromagnetic donor element 494 acting on magnets or ferromagnetic regions in the support member 493 may induce an arcuate reciprocation in the x-z plane into the cuvette array 200, thereby providing faster mixing of the samples and reagents at a suitable excitation frequency takes place in the cuvettes 201.

The cuvette washing unit 600 shown in FIG. 9 is designed to be movable in the x-direction via a receptacle 601 along the rail 112 (see FIG. 4). The head 602 of the unit 600 can be moved up and down in the z-direction by means of a vertically oriented rail section 603 guided in the receptacle 601 to introduce either the washing bodies 610 or the drying punches 620 into the cuvettes 201 of the cuvette array 200 , agreement

Adjustment element 604, which is guided in the head 602 and carries, for example, four drying punches 620 and washing bodies 610, can be switched by a displacement in the y-direction from the washing position into the drying position. Individual fingers 605, which carry the washing bodies 610 and drying punches 620, can be swiveled up, as indicated by arrow 691, so that only one or a few cuvettes 201 are washed simultaneously.

10 is an enlarged sectional view showing the structure of a needle washing unit indicated by the general reference numeral 700, which corresponds to the substantially identical needle washing units 700al, 700a2, 700b, 700b2 shown at different positions in FIGS. 3 to 6, and one with the reference numeral 301, which corresponds to the substantially identically constructed pipetting needles 301al, 301a2, 301bl, 301b2 shown at different positions in FIGS. 3 to 6. The hollow needle 307 of the pipetting needle 301 is introduced through a receiving opening 711 in the housing 710 of a needle washing unit 700, wherein at the same time the lumen of the hollow needle 307 is cleaned with a system liquid 712 and the outside of the needle with a rinsing liquid 714 supplied via an annular cleaning nozzle 713 from an annular chamber 715 can be. For internal and external cleaning of the hollow needle 307 by repeatedly aspirating and expelling washing solution from the lower part of the needle washing unit 700, washing solution can be introduced via a radial inlet 716, which can then be emptied via a suction opening 717.

FIG. 11 shows an enlarged detail of the linear cuvette array 200 of the analyzer 100 with the partially cut-away housing 892 and a cuvette 201 arranged therein which is contacted by a heating foil 891 of a thermostatic unit 800, whose electrical contact pins 893 are in contact with the Exit housing 892. Further electrical contact pins 894 can be provided for contacting a temperature sensor. The cuvette 201 has laterally in a near-ground region, preferably plane-parallel measuring windows, in the example shown inlet and outlet windows 202, 203 (exit window not visible), which for the incident radiation and the exit or. Measuring radiation of the optical measuring unit 500 are permeable. In the area of the inlet and outlet windows 202, 203 of the cuvette 201, the housing 892 has corresponding openings 895. The individual contact pins 893, 894 snap into corresponding contact openings which are provided in the carrier element 493 of the mixer unit 400 (see FIG. 8). At the bottom of the housing 892 latching elements 896 are formed, which engage in the mounting of the cuvette array 200 in or on the support member 493 of the mixer unit 400.

12 shows the fluidic circuit diagram of a pipetting needle 301, the hollow needle 307 of which is connected via a pressure transfer channel 712 filled with a degassed liquid to a precision piston pump 325, preferably a positive displacement pump (dilutor) driven by a stepper motor. The positive displacement pump has an additional fluid port on the side, which is connected via a solenoid valve 326 to a system liquid supply unit 320 which is provided with a rinse pump 321 from a storage vessel 322, e.g. degassed, deionized water promotes, which is a solenoid valve 323 refillable, or pressurizable.

For the detection of faults, the pressure transmission channel 712 in the vicinity of the pipetting needle 301 has a further connection to a pressure sensor 324, which is connected to an evaluation and control unit, not shown here, for example for detecting obstruction of the hollow needle 307.

Description of a Pipetting Process For the transfer of a defined amount of liquid with the pipetting needle 301, it is first moved in the horizontal direction to a first vessel, 5 pL of air (spacer) sucked into the tip of the hollow needle 307 and the pipetting needle 301 lowered in the direction of the liquid surface of the first vessel , In order to ensure a sufficient, but not too large immersion depth of the pipetting needle 301, the downward movement of the hollow needle 307 in a defined immersion depth by a signal of a liquid surface detection device (not shown), for example, with capacitive detection principle, stopped. For aspiration of a defined amount of liquid with high accuracy in the pL range, a negative pressure in the hollow needle 307 of the pipetting needle 301 is now generated by downward movement of the working piston of the displacement pump (dilutor) shown in FIG. 12, which produces the aspiration of a corresponding volume of liquid from a first vessel causes. The pipetting needle 301 is now moved together with the aspirated liquid, which is separated by a separation bubble (spacer) from the system liquid to a second vessel, the process now runs in the opposite direction and the aspirated liquid through the tip of the hollow needle 307 in the second Vessel is discharged. At least between two pipetting operations with different liquids to be pipetted, an internal and external cleaning of the pipetting needle 301 in a needle washing unit 700 always takes place (see FIG. 10).

10 shows the hollow needle 307 of the pipetting needle 301 lowered therein. The housing 710 of the needle washing unit (see FIG. 10) has a concentrically encircling annular chamber 715 in the upper area, which serves as a medium feed for a plurality of internal feeders , concentrically aligned cleaning nozzles 713, and each connected via solenoid valves to a washing liquid supplying unit 719 (for example, deionized water), and a drying air supplying unit 727.

An inlet 716 radially arranged in the middle of the height of the housing 710 of the needle washing unit 700 is likewise connected to a magnetic valve and serves exclusively for the supply of surfactant-containing washing solution from a supply unit 723.

The supply units 719 for a rinsing liquid and 723 for a washing solution each have a pump 720, 724, which promote a surfactant-containing washing solution or rinsing liquid from the respective storage containers 721, 725, each via a solenoid valve 722, 726 refillable, or under pressure settable are. The air supply unit 727 has an air pump 728 for providing compressed air and possibly a drying template (not shown).

The suction opening 717 located at the bottom of the needle washing unit 700 is connected via a solenoid valve 718 to the submerged sewage collecting unit 729 which essentially consists of a collecting tank 730 which has a connection to a vacuum pump 731 in the gas space above the liquid Solenoid valve is connected to the sump 730. The collected wastewater can be discharged via a solenoid valve 732 at the bottom of the collecting container 730 and fed to a further wastewater treatment.

Description of a needle wash pre-wash

In a typical washing process of the pipetting needle 301, it is first moved horizontally to the needle washing unit 700 and lowered into the lower holding position of the washing chamber. All wastewater arising during the cleaning of the pipetting needle 301 is sucked off via the suction opening 717 located at the bottom, collected, and if necessary after-treated. Subsequently, via the precision piston pump 325 of the pipetting needle 301 shown in FIG. 12, first of all residual amounts of the last pipetted liquid located in and on the needle tip are emptied and sucked off. Finally, the lowered pipetting needle 301 is rinsed from behind by means of the system liquid supply unit 320 shown in FIG.

In a next step, a defined volume of surfactant-containing washing solution is introduced through the inlet 716 in the housing 710 of the needle washing unit 700 (with the solenoid valve 718 closed at the suction opening 717), whereby the chamber in the lower part fills with a defined level of washing solution. The hollow needle 307 of the pipetting needle 301 is lowered so far that by immersion in the washing solution an external wetting of the needle, and by sucking the washing solution into the needle interior, an internal wetting of the hollow needle 307 can take place. Subsequently, the aspirated washing solution is ejected again, whereby the process of sucking and discharging the washing solution can be repeated several times to improve the cleaning effect.

In a final step, the contaminated washing solution is aspirated and flushed the interior of the hollow needle 307 with system liquid (eg degassed, deionized water), while the outside of the hollow needle 307 is simultaneously rinsed with flushing liquid from the delivery unit 719 by the overhead, concentrically arranged cleaning nozzles 713, wherein the tip of the hollow needle 307 is moved from the bottom up to improve the cleaning effect.

After completion of the simultaneous inner and outer irrigation, the hollow needle 307 is again moved to the lower holding position, the media supply of the cleaning nozzles 713 switched to the supply unit 727 for compressed air and the tip of the hollow needle 307 again moves from bottom to top, making adhering drops of water from the Needle surface can be removed quickly. The pipetting needle 301 can now be moved out of the needle washing unit 700, and is ready for pipetting after the aspiration of a separating air spacer (5 pL).

14 shows the fluidic circuit diagram and the longitudinal section of a finger 605 of the cuvette washing station 600 hinged to the adjusting element 604 with a washing body 610 and a drying punch 620 (see also FIG. 9), the descriptions of the providing units 630 (washing liquid), 634 (washing solution) and 638 (air), as well as the waste water collecting unit 640 can be taken from the supply units 719 (rinsing liquid), 723 (washing solution), 727 (air) and 729 (waste water) of the figure description to Fig. 13, which are functionally identical to the units shown in Fig. 14 , or are identical.

The washing body 610, as well as the drying punch 620 of the finger 605 of the cuvette washing station 600 can be successively lowered by horizontal and vertical translational movements into the cuvette 201 to be washed of a linear cuvette array, wherein after lowering into the cuvette 201 each have a circumferential gap of less than 1 mm between the inside of the cuvette 201 and the washing body or blind die remains open to allow a controlled flow of cleaning media along the inner cuvette wall.

The washing body 610 has at its upper end an elastomeric seal 611 which prevents leakage of the cleaning media between the upper cuvette rim and the bottom of the finger 605 during the washing process. Around the shaft of the rising channel 612 running in the middle of the washing body 610 for sucking off the waste water and exhaust air there is arranged an annular circulating media feed which allows flushing of the cuvette inside from top to bottom (see arrows). The washing body 610 can be supplied with surfactant-containing washing solution from the supply unit 634, flushing liquid (for example deionized water) from the supply unit 630, or compressed air from the supply unit 638 via corresponding solenoid valves, which are discharged via the pressurized waste water collecting unit 640 in which these are supplied via a solenoid valve to the under-pressurized sewage collecting unit 640. The wastewater collection unit 640 consists essentially of a collecting container 730, which in the gas space above the liquid via a connection to a

Vacuum pump 642 which is connected via a solenoid valve to the reservoir 641. The collected effluents can be discharged via a solenoid valve 643 at the bottom of the reservoir 641 and fed to a further wastewater treatment.

The dry punch 620 is made of a porous air-permeable material and internally has a non-bottomed longitudinal channel 621 which serves to supply and distribute the compressed air through the wall of the porous dry stamp 620 into the cuvette 201. The dry punch 620 does not terminate at the bottom of the finger 605 with a seal, but is slightly above in the lowered state and forms between the top of the cuvette 201 and finger bottom a circumferential air outlet gap (see horizontal arrows). The dry punch 620 may be connected to the compressed air from the delivery unit 638 via a solenoid valve.

Description of a cuvette washing process

In a step preparing the actual cleaning, the washing body 610 is lowered into the cuvette 201 to be washed and the reagents / sample mixture which is located in the cuvette 201 after the analysis are sucked off via the central riser channel 612 and fed to the wastewater collecting unit 640.

In a first cleaning step, washing solution from the preparation unit 634, rinsing liquid from the supply unit 630 and finally compressed air from the supply unit 638 are rinsed, and this cleaning sequence can be repeated several times with said media in order to improve the cleaning effect.

The washing body 610 is then lifted out of the washed but residual moisture cuvette 201, and the finger is moved in the y direction.

In a second cleaning step, the drying punch 620 is now lowered into the cuvette 201 in the z-direction and air is blown past the cuvette inside with dry compressed air from the supply unit 638 for a certain period of time, the air required for this purpose being uniform from the porous body of the drying punch 620 exit, sweeps from bottom to top on the inside of the cuvette 201, and emerges on the shaft of the Trockenstempels 620.

Examples:

The automatic analyzer according to FIGS. 3 to 5 operates, for example, as follows:

In the run-up to an analysis, i. For the determination of an analyte Ax of an analytical sample Px, the analyzer control unit gathers from the known and previously entered information all the data needed for the analysis of the analyte Ax (analysis protocol, positions of the vessels 921, 951a, 951b with the analytical sample and those for the analysis required reagents, position of a free cuvette 201 in the cuvette array 200, cuvette temperature, selection of the measurement procedure, the calibration data, the measurement and evaluation algorithms).

Example: single analysis

Phase 1

At the beginning and during the analysis, the temperature of the cuvette 201 provided for the analysis is regulated to a predetermined temperature by means of the thermostating unit 800 assigned to the cuvette 201.

From the first pipetting needle 301bl of the T-shaped pipettor 300b, a predetermined amount of a first analysis sample is taken in the sample storage 920 from a first sample vessel 921, and a predetermined amount thereof is discharged into a free cuvette 201. Following the pipetting operation, the pipetting needle 301bl is washed and provided in the first needle washing unit 700bl of the pipettor 300b.

Phase 2

From a pipetting needle 301al of the L-shaped pipettor 300a, a predetermined amount of a first reagent liquid is received in the reagent storage 950a from a first reagent vessel 951a, and a predetermined amount is pipetted into the cuvette 201. Thereafter, the two liquids are mixed in the cuvette by brief (a few seconds) switching on the mixing unit 400 associated with the cuvette. Following the pipetting operation, the pipetting needle 301al is washed and provided in a first needle washing unit 700al of the L-shaped pipettor 300a.

Phase 3

Depending on the respective analysis protocol, the second pipetting needle 301b2 of the T-shaped pipettor 300b in the reagent storage 950b receives a predetermined amount of a second reagent liquid from a reagent vessel 951b and dispenses a predetermined amount into the cuvette 201. Thereafter, the contents of the cuvette by brief (a few seconds) switching on, the cuvette 21 associated mixer unit 400 is mixed. Following the pipetting operation, the pipetting needle 301b2 is washed and provided in the second needle washing unit 700b2 of the T-shaped pipettor 300b.

Phase 4

Phase 4 begins with photometric measurements on cuvette 201, usually after completion of phase 2.

The optical measuring unit 500 periodically traverses the linear cuvette array 200 and generates a measured value when passing on the fly 202 at the entrance 202 or exit window 203 of the cuvette 201, if provided by the measurement protocol at the respective passing time. Alternatively, the optical measuring unit 500 may also stop briefly as it passes by and measure during the stop to obtain a more accurate reading. While the chemical reaction in the cuvette 201 takes place between sample and reagent, measuring points can be generated at defined time intervals. Depending on the respective analysis protocol, singular or - in the case of kinetic measurements - time-dependent measured values obtained at one or more wavelengths and with previously known reference and calibration values assigned to the respective analysis are calculated and displayed to a concentration value of the analyte.

Depending on the type of analysis and sample, the measurement process - especially in kinetic measurements - can extend over very different periods of a few seconds to the two-digit minute range.

Immediately after completion of the photometric measurement, the cuvette 201 is released for washing with the cuvette washing unit 600. The washing process by means of cuvette washing unit 600 takes place immediately after release of the cuvette, preferably together with a plurality of adjacent cuvettes 201 likewise released for washing and after "freeing" the movable cuvette washing unit 600. After washing and drying, the cuvette 201 is provided for the next analysis.

Example: multiple analyzes

Prior to performing multiple analyzes, the sample bearing 920 is manually or automatically loaded with samples Pi to Pn. The type and number of analyzes Ai to An to be performed for each sample Px are input to the controller of the analyzer 100. Optionally, the reagents bearings 950a, 950b are charged or replenished with the reagents required for the analyzes to be performed. For each PXAX analysis to be performed, the phases 1 to 4 described above are run through, each beginning with phase 1.

After the pipettor 300b in phases 1 and 3 is taken up by the analysis PXAX to be performed, phase 1 of the subsequent analyzes PxAx + i or Px + iAx can only begin after the completion of phase 1 and outside of phase 2 of the ongoing analyzes , for as many subsequent analyzes as it is "free", ie not cuvettes claimed by other analytical processes.

The concept according to the invention makes it possible, in contrast to the systems described at the outset, for a cuvette to be promptly washed and made available for a new test after the measurement has been completed, without adversely affecting the processes of the ongoing analysis processes.

Claims (10)

An automated analyzer (100) for performing chemical, biochemical and / or immunochemical analyzes of liquid samples present in a sample store (920) of the analyzer with the aid of liquid reagents contained in at least one reagent store (950a, 950b) of the Analyzer present, with cuvettes (201) for receiving the liquid samples and reagents, wherein a plurality of cuvettes (201) as at least one stationary, linear cuvette array (200) is arranged in the analyzer, with movable and stationary machine components, comprising at least: • along a line of movement defined by the linear cuvette array (200) in the x-direction movable pipettor (300a, 300b) which is equipped with at least one pipetting needle (301al, 301a2, 301bl, 301b2) in the z-direction in the cuvettes ( 201) is designed lowered and in a direction of the x-direction substantially normal y-direction between the Küv a mixing unit (400) for mixing the samples and reagents in the cuvettes (201), an optical measuring unit (500), and a sample storage unit (920) and / or the reagent storage unit (950a, 950b); , which - for obtaining a measuring signal - by a laterally arranged on the cuvette (201) measuring window (202, 203) receiving measuring radiation, • a movable in the x-direction cuvette washing unit (600) for cleaning the cuvettes (201), • a Needle washing unit (700al, 700a2, 700bl, 700b2) for cleaning the at least one pipetting needle (301al, 301a2, 301bl, 301b2), and • a stationary Thermostatisiereinheit (800) for setting a predetermined measurement temperature in the cuvettes (201), wherein at least two automatic components independently of one another along or parallel to the line of movement defined by the linear cuvette array (200) in the x-direction, and in each case access to u have different cuvettes (201) or groups of cuvettes (201) in arbitrary order. 2. Analyzer according to claim 1, characterized in that the analyzer (100) has two independently movable in the x-direction pipettors (300a, 300b). 3. Analyzer according to claim 1 or 2, characterized in that at least one pipettor (300a, 300b) has two independently, parallel to each other in the y-direction movable pipetting needles (301al, 301a2, 301bl, 301b2). 4. Analyzer according to one of claims 1 to 3, characterized in that the needle washing unit (700al, 700a2, 700bl, 700b2) is arranged on the pipettor (300a, 300b) and designed to be movable therewith. 5. Analyzer according to one of claims 1 to 4, characterized in that the optical measuring unit (500) along the linear, stationary cuvette array (200) movable spectrometer (535). 6. Analyzer according to one of claims 1 to 4, characterized in that for mixing the samples and reagents the entire cuvette array (200), preferably individual groups of cuvettes (201), a stationary mixer unit (400), for example one on the cuvette array (200 ) attacking oscillator, is assigned. 7. Analyzer according to one of claims 1 to 4, characterized in that the Küvettenwascheinheit (600) for cleaning the cuvettes (201) is designed as a movable machine component, in each washing position on a cuvette (201) or a group of cuvettes, preferably on two to five juxtaposed cuvettes (201), has access at the same time. 8. Analyzer according to one of claims 1 to 4, characterized in that the Thermostatisiereinheit (800) for setting a predetermined measurement temperature heating foils (891), the individual cuvettes (201) or groups of cuvettes (201) contact thermally and with different temperature levels can be acted upon. 9. Analyzer according to one of claims 1 to 8, characterized in that the cuvettes (201) in a near-ground region, preferably plane-parallel to each other, one (202) and exit window (203), which for the entrance and exit radiation or Measuring radiation of the optical measuring unit (500) are permeable. A method of automatically chemically, biochemically and / or immunochemically analyzing liquid samples present in a sample store (920) of an analyzer with the aid of liquid reagents present in at least one reagent store (950a, 950b) of the analyzer for detection at least one analyte concentration in the sample, characterized by the steps of: - transferring a predetermined amount of a liquid sample from a sample vessel (921) in the sample store (920) to a cuvette (201) of a stationary, linear cuvette array (200) by means of one along the cuvette array movable first pipettor (300b); Transfer of a predetermined amount of reagent liquid from a reagent vessel (951a) of the reagent storage (950a) into the cuvette (201) of the stationary, linear cuvette array (200) by means of the first pipettor (300b) or by means of a second, independent of the first transportable pipettor ( 300a); - mixing the liquids in the cuvette (201); optionally transferring a predetermined amount of another reagent liquid from a reagent vessel (951b) of the reagent storage (950b) into the cuvette (201) of the stationary, linear cuvette array (200) by means of the first or the second pipettor (300a, 300b); - if necessary, again mixing the liquids in the cuvette (201); - Photometric measurement of the contents of the cuvette (201) by means of a along the cuvette array (200) movable optical measuring unit (500); and determining at least one measured value; Calculating and displaying the analyte concentration based on the determined measured value and on known or predetermined reference and calibration values; - Washing and drying the cuvette (201) by means of a cuvette washing unit (600) movable along the cuvette array (200); and - providing the cuvette (201) for subsequent analysis.