EP2481481A1 - Adjustment method for microtiter plate washing machines - Google Patents

Abstract

Adjusting microplate washing device (1) comprising at least one receiver (2) for receiving a microplate (3) containing a well-array (4), a washing head (5) with washing cannulas, a working plane, a reference plane, a sensor device, and a controller, comprises (a) converging the receiver and the washing head until the lowermost ends of the washing cannulas contacts at least one surface that defines the reference plane, detecting a signal of the sensor device and thus determining a relative elevation value, and determining active elevation position of the lowermost ends of the washing cannulas. Adjusting microplate washing device (1) comprising at least one receiver (2) for receiving a microplate (3) containing a well-array (4), a washing head (5) with washing cannulas that are arranged in an array corresponding to at least one portion of the well array of the microplate, a working plane defined by the washing cannulas with their lowermost ends, a reference plane, a sensor device, and a controller that is operatively connected with the sensor device, comprises (a) converging the receiver and the washing head by moving the receiver and/or the washing head until the lowermost ends of the washing cannulas contacts at least one surface that defines the reference plane; detecting a signal of the sensor device using the controller and thus determining a relative elevation value, where the signal indicates the contacting of the surface with the lowermost ends of the washing cannulas or is usable for determining the position of the surface defining the reference plane; and determining an active elevation position of the lowermost ends of the washing cannulas with respect to an inner surface of the well bottom of the microplate, based on the relative elevation value, during the operation of the microplate washing device. The working plane and the reference plane are arranged parallel to each other. An independent claim is also included for using the microplate washing device for adjusting the microplate washing device, which comprises the receiver, the washing head, the working plane, the sensor device, the controller that is operatively connected with the sensor device, which processes the signals of the sensor device and controls the movements of the receiver and/or the washing head, and the reference plane, comprising converging the receiver and the washing head by moving the receiver and/or the washing head until the lowermost ends of the washing cannulas contact inner surfaces of the well bottoms of the microplate located in the receiver, detecting the contacting of the inner surfaces of the well bottoms with the lowermost ends of the washing cannulas by the sensor device and the controller, conducting the microplate washing device by controller, for moving the receiver and/or the washing head such that the lowermost ends of the washing cannulas are brought in an active elevation position with respect to the inner surface of the well bottoms of the microplate.

Description

The invention relates to a setting method for microplate washing devices. Microplate washers have been known for some time and are used to treat multiwell plates in which, for example, immunoassays (such as enzyme-linked immunosorbent assay) are performed. Such experiments include the addition and also the removal of liquid reagents in the wells of the microplates. Some components of these fluids enter into chemical bonds with the walls of the wells and / or other components, therefore it is often necessary to remove the unbound components from the wells, i. wash out. This washout is usually done by means of wash tubes, i. by introducing washing liquid into the wells via so-called dispenser cannulas and by aspirating the washing liquid from the wells via so-called aspiration cannulas.

Such microplate washing devices comprise at least one receptacle for receiving a microplate and a washing head with washing cannulas. In this case, a microplate comprises a wells array (compare standard microplates according to the standard ANSI_SBS 1-2004) and the washing cannulas of the washing head are arranged in an array corresponding to at least part of the well array of this microplate. Because multiple wells are to be washed simultaneously, and preferably simultaneously, it is important that the bottom ends of the wash cannula define a working plane that is very close to the bottom of the microplate wells without the wash tubs of the wash head contacting those bottoms of the microplate well. In order for the washing cannulas to be able to assume such a position in the wells, it has proved useful to arrange the working plane defined by the washing cannulas with their lowest ends and a reference plane (for example the inner surfaces of the corrugated bottoms) parallel to one another.

The present invention assumes that this parallel arrangement of working plane and reference plane has already been completed. This is also the case in already known processes, so that in a first phase, in processes known from the prior art, the receptacle and the washing head, by moving the receptacle, the washing head or both, approximate each other until the bottommost ends of the washing cannulas touch at least one surface defining the reference plane. A particular difficulty arises in optically controlling these motions when opaque microplates (e.g., black microplates for fluorescence measurements or white microplates for luminescence measurements) are used in this adjustment operation such that the washpipes are to contact the inner surfaces of the wells of the wells of that microplate. This first phase is quite tricky because of the limited visual control and, in particular, the skill of the person making the adjustment.

For well-known and repeatedly used microplates, it has proven useful to create a so-called disk library in which all important parameters and geometric features of already known microplates are stored. For example, for the 24-well microplates, the center distance between two adjacent wells is 18 mm, for 96-well microplates 9 mm and for 384-well microplates 4.5 mm. The inner surfaces of the flat corrugated sheets of preferred microplates are each located at a distance, called "well bottom elevation", over the footprint of these microplates as follows: Table 1 Greiner 96 well flat bottom Wells and flat bottom (Art. No. 655 101) = transparent microplate with 96 3.7 mm 96 Greiner Micro-Assay-Plate transparent bottom (Item No. 655 096) = black microplate with 3.5 mm Greiner 384 Well flat bottom 384 wells and flat bottom (Art. No. 781 = 101) transparent microplate with 2.9 mm 384 Greiner Micro-Assay-Plate transparent bottom (Item No. 781 096) = black microplate with 2.9 mm.

These data were taken from the Greiner Microplate Dimensions Guide (Revision July 2007, 073 027) (see also www.gbo.com/bioscience).

The storage of such disk library data in the software or firmware of microplate washers has proven particularly useful. However, if less common plate formats are used whose mass can not be retrieved from the disk library, an optically controlled adjustment must be made in the manner just mentioned, which is quite difficult and therefore particularly time-consuming, especially in the case of opaque microplates.

It is therefore an object of the present invention to propose an alternative adjustment method for using any microplate formats and types of microplates in microplate washers that at least substantially eliminates the disadvantages known from the prior art.

This object is achieved by the method defined in the independent claim 1 by using a microplate washing device described in the introduction, which additionally comprises a sensor device and a control operatively connected to this sensor device. In this case, the controller detects a signal of this sensor device and thus determines a relative altitude value. This signal indicates contact of the surface with the bottommost ends of the wash cannulas or is useful for determining the position of that surface. Based on this relative height value, an active elevation of the bottommost ends of the wash cannulas with respect to an inner surface of the well bottoms of a microplate is determined during operation of the microplate washer.

Preferably, the surface defining the reference plane is selected from the group consisting of inner surfaces of the bottoms of the wells of a microplate, a reference surface of an adjustment plate, a surface of an insert plate, and a footprint of the receptacle for receiving a microplate. Preferred embodiments and further inventive features emerge from the dependent claims.

• Das Einstellen der aktiven Höhenlage der Waschkanülen für das Arbeiten mit opaken Mikroplatten kann spätestens nach dem Einlegen der Mikroplatte in die Aufnahme des Mikroplatten-Waschgeräts automatisch erfolgen.
• Das Einstellen der aktiven Höhenlage der Waschkanülen für das Arbeiten mit bislang unbekannten, opaken Mikroplatten erfolgt objektiver und zuverlässiger als von Hand mit optischer Kontrolle, weil es unabhängig von der subjektiven Wahrnehmung eines Operateurs erfolgt.
• Das Einstellen der aktiven Höhenlage der Waschkanülen für das Arbeiten mit bislang unbekannten, opaken Mikroplatten benötigt trotz erhöhter Reproduzierbarkeit weniger Zeit.

Compared to prior art adjustment methods for using any microplate formats in microplate washers the method according to the invention comprises the following advantages:

• The setting of the active height position of the washing cannulas for working with opaque microplates can take place automatically at the latest after the insertion of the microplate into the receptacle of the microplate washer.
• The setting of the active height of the washing cannulas for working with hitherto unknown, opaque microplates is more objective and reliable than by hand with optical control, because it is independent of the subjective perception of an operator.
• Adjusting the active height of the washing cannulas for working with hitherto unknown, opaque microplates requires less time despite increased reproducibility.

Fig. 1

einen schematischen Vertikalschnitt durch ein Mikroplatten-Waschgerät mit einem Waschkopf und einer in die entsprechende Aufnahme eingesetzten Mikroplatte;

Fig. 2

Detailschnitte, welche die wesentlichsten Höhenpositionen darstellen, dabei zeigt:
Fig. 2A einen Vertikalschnitt durch die Mikroplatten-Aufnahme mit einer Mikroplatte und einer Waschkanüle in Arbeitsposition;
Fig. 2B einen Vertikalschnitt durch eine in die Mikroplatten-Aufnahme eingelegte Einstellplatte, deren Oberfläche die Innenoberflächen der Böden der Mikroplattenwells simuliert, wobei die Sensorvorrichtung einen Fühler umfasst, der um den Arbeitsabstand über die Waschkanülen hinaus ragt;
Fig. 2C einen Vertikalschnitt durch eine in die Mikroplatten-Aufnahme eingelegte Einstellplatte, deren Oberfläche die Innenoberflächen der Böden der Mikroplattenwells simuliert, wobei die Sensorvorrichtung einen Fühler umfassen kann, dessen vorderstes Ende in der Arbeitsebene liegt; und
Fig. 2D einen Vertikalschnitt durch eine in die Mikroplatten-Aufnahme eingelegte Einstellplatte, deren Oberfläche die Arbeitsebene der Waschkanülen in den Mikroplattenwells simuliert, wobei die Sensorvorrichtung einen Fühler umfassen kann, dessen vorderstes Ende in der Arbeitsebene liegt;

Fig. 3

Detailschnitte, welche die wesentlichsten Höhenpositionen darstellen, dabei zeigt:
Fig. 3A einen Vertikalschnitt durch die Mikroplatten-Aufnahme mit einer Mikroplatte und einer Waschkanüle in Arbeitsposition;
Fig. 3B einen Vertikalschnitt durch eine in die Mikroplatten-Aufnahme eingelegte Einlegeplatte, wobei die Sensorvorrichtung einen Fühler umfassen kann, dessen vorderstes Ende in der Arbeitsebene liegt;
Fig. 3C einen Vertikalschnitt durch die Mikroplatten-Aufnahme, wobei die Sensorvorrichtung einen Fühler umfassen kann, dessen vorderstes Ende in der Arbeitsebene liegt; und
Fig. 3D einen Vertikalschnitt durch eine in die Mikroplatten-Aufnahme eingelegte Mikroplatte, wobei die Oberflächen der Wellböden die die Bezugsebene definierende Oberfläche darstellen;

Fig. 4

einen schematischen Vertikalschnitt durch ein Mikroplatten-Waschgerät mit einem Waschkopf aber ohne eingesetzte Mikroplatte;

Fig. 5

eine 3D-Darstellung entsprechend einem Teil von Fig. 4, mit einer Sensorvorrichtung, die eine Lichtschranke umfasst;

Fig. 6

ein Weg/Weg-Diagramm zum Ermitteln des vorbestimmten Korrekturbetrags, der beim Ermitteln der aktiven Höhenlage der untersten Enden der Waschkanülen gemäss der zweiten Ausführungsform des erfindungsgemässen Einstellverfahrens in Betracht gezogen werden muss (vorzugsweise durch den Hersteller des Mikroplatten-Waschgeräts);

Fig. 7

ein Signal/Weg-Diagramm beim Ermitteln des vorbestimmten Korrekturbetrags in Fig. 6;

Fig. 8

ein Weg-Diagramm zum Ermitteln der aktiven Höhenlage der untersten Enden der Waschkanülen in Bezug auf eine Innenoberfläche der Wellböden einer Mikroplatte beim Betrieb des Mikroplatten-Waschgeräts (vorzugsweise durch den Anwender des Mikroplatten-Waschgeräts);

Fig. 9

ein Signal/Weg-Diagramm beim Ermitteln der aktiven Höhenlage in Fig. 8.

The method according to the invention will be explained in more detail with reference to schematic drawings, which illustrate exemplary embodiments and are not intended to limit the scope of the invention. Showing:

Fig. 1

a schematic vertical section through a microplate washer with a washing head and a microplate inserted into the corresponding receptacle;

Fig. 2

Detail sections, which represent the most significant height positions, showing:
Fig. 2A a vertical section through the microplate receptacle with a microplate and a washing cannula in working position;
Fig. 2B a vertical section through an inserted in the microplate receptacle adjustment plate, the surface of which simulates the inner surfaces of the bottoms of the Mikroplattenwells, the sensor device comprises a sensor which projects beyond the working distance on the washing cannulas;
Fig. 2C a vertical section through an inserted into the microplate receptacle adjustment plate whose surface the Simulating internal surfaces of the bottoms of the microplate wells, which sensor device may include a probe whose foremost end is in the working plane; and
Fig. 2D a vertical section through an inserted in the microplate receptacle adjustment plate, the surface of which simulates the working level of the washing cannulas in the Mikroplattenwells, the sensor device may include a sensor whose foremost end is located in the working plane;

Fig. 3

Detail sections, which represent the most significant height positions, showing:
Fig. 3A a vertical section through the microplate receptacle with a microplate and a washing cannula in working position;
Fig. 3B a vertical section through an insert plate inserted into the microplate receptacle, wherein the sensor device may comprise a sensor whose foremost end lies in the working plane;
Fig. 3C a vertical section through the microplate receptacle, wherein the sensor device may include a sensor whose front end is located in the working plane; and
Fig. 3D a vertical section through a microplate inserted into the microplate receptacle, wherein the surfaces of the corrugated floors represent the surface defining the reference plane;

Fig. 4

a schematic vertical section through a microplate washer with a washing head but without inserted microplate;

Fig. 5

a 3D representation corresponding to a part of Fig. 4 with a sensor device comprising a light barrier;

Fig. 6

a path / path diagram for determining the predetermined correction amount, the in determining the active altitude of the lowest Ends of the washing cannulas according to the second embodiment of the adjusting method according to the invention must be considered (preferably by the manufacturer of the microplate washer);

Fig. 7

a signal / path diagram in determining the predetermined correction amount in Fig. 6 ;

Fig. 8

a path diagram for determining the active elevation of the bottommost ends of the washing cannulas with respect to an inner surface of the well plates of a microplate during operation of the microplate washer (preferably by the user of the microplate washer);

Fig. 9

a signal / path diagram when determining the active altitude in Fig. 8 ,

The FIG. 1 shows a schematic vertical section through a microplate washer 1 with a washing head 5 and inserted into the corresponding receptacle 2 microplate 3. The wells array 4 of the microplate is only hinted at here. The washing head 5 is equipped with washing cannulas 6; These washing cannulas 6 are arranged in an array which corresponds to at least part of the well array 4 of this microplate 3. Shown here is a linear array with six dual cannulas that can be submerged in six adjacent wells of a microplate. The longer cannulas 6 are the aspirating cannulas for aspirating fluid from the wells, and the shorter cannulas 6 'are the dispenser cannulas for introducing fluid into the wells.

With their lowermost ends, the washing cannulas 6 define a working plane 7 that is aligned parallel to a reference plane 8 on this exemplary device. This parallel arrangement of working plane 7 and reference plane 8 is important because so all the washing cannulas 6 of a washing head 5 can be arranged with their lowest ends in an active altitude 14, in which they the same distance from the inner surfaces 15 of the bottoms of the Wells used Take microplate 3. Minimizing this distance between the aspiration cannulas and the corrugated floors, the so-called working distance 22, allows the most extensive aspiration of liquid from the wells, which is particularly advantageous when performing ELISA experiments (ie so-called "enzyme-linked immunosorbent assays"). The working distance 22 is preferably 0.1 to 0.5 mm and especially preferably 0.2 to 0.3 mm. If you want to work with adherent cells or with magnetic beads, then a larger working distance is usually selected 22, which is usually not as critical as in ELISA experiments. If an experiment requires a certain working distance 22, the required value can be included in the software or firmware of the microplate washer 1 concerned; this working distance 22 can be called up as needed during operation of the microplate washing device 1.

In a first phase of the microplate washing apparatus setting process, the receptacle 2 and / or a washing head 5 preferably attached to a washing head carrier 9 are moved towards one another until the bottommost ends of the washing cannulas 6 (in this case the aspirating cannulas) at least define the reference plane 8 Touch surface 10. Thus, either the receptacle 2 alone or the washing head 5 alone or the receptacle 2 and the washing head 5 are moved together, so that a mutual approach takes place.

This surface 10 defining the reference plane 8 may be provided by any stable plane parallel to the bottommost ends of the washing cannulas 6 of a washing head 5 and also parallel to the inner surfaces 15 of the bottoms of the wells of the microplate 3 used. The surface 10 defining the reference plane 8 is preferably selected from the group, which inner surfaces 15 of the bottoms of the wells of a microplate 3, a reference surface 16 of an adjustment plate 17, a surface 18 of an insert plate 19 and a support surface 20 of the receptacle 2 for receiving a microplate 3 includes. However, it is also possible for a bottom closed microplate 3, which is to be used in the microplate washing device 1, to insert vice versa into the receptacle 2, so that the turned-up bottom of the microplate forms the surface 8 defining the reference plane 8. Likewise, the surface of a microplate lid can serve as the reference surface 8 defining surface 10, wherein the microplate lid is placed on an inserted into the receptacle 2 microplate 3. The topmost surface a microplate 3 can also serve as the surface 10 defining the reference plane 8, the microplate 3 being inserted into the receptacle 2.

To carry out the method according to the invention, the microplate washing device 1 comprises a sensor device 11 and a controller 12 operatively connected to this sensor device. The sensor device 11 preferably comprises a touch sensor which is selected from the group comprising electro-mechanical pushbuttons and electrical contacts. Especially preferably, the sensor device 11 comprises a non-contact sensor which is selected from the group comprising capacitive proximity switches, Hall sensors and light barriers.

According to the invention, the controller 12 detects a signal of this sensor device 11 and thus determines a relative altitude value 13. This sensor signal indicates contact of the surface 10 (which defines the reference plane 8) with the lowermost ends of the washing cannulas 6. Alternatively, this sensor signal is usable to determine the position of this surface 10 (which defines the reference plane 8).

In both cases, with the controller 12 based on this relative height value 13, an active altitude 14 of the bottommost ends of the washing cannulas 6 with respect to an inner surface 15 of the well bottoms of a microplate is determined during operation of the microplate washer 1.

The method according to the invention is particularly suitable for determining the active height position 14 of the lowest ends of the washing cannulas 6 for the operation of the microplate washing device in the case of microplates 3 with flat bottoms (cf., for example, Table 1). With appropriate positioning of the washing cannulas 6 relative to the respective microplate 3, the inventive method, however, also for microplates with round or U-bottoms (eg Greiner Art. No. 650 207), microplates with pointed or V-floors (eg Greiner Art. No. 651 209) or any other type of microplate.

The relative height value 13 (cf. Fig. 6 ) can be determined by different methods. Preferably, for a high-resolution measuring device for Detecting the position used in linear displacements relative to a known reference point. A measuring probe of the type HEIDENHAIN ST 1288 (DR JOHANNES HEIDENHAIN GmbH, 83301 Traunreut, Germany) was used with an accuracy of +/- 1 μm. The relative altitude value 13 is then calculated from the distance traveled with respect to the known level of the reference point; is preferably measured directly on the washing head 5 or at the back (see. Fig. 4 ).

The height adjustment of the washing head 5 is preferably carried out by means of a motor-driven drive spindle 32 (see. 4 and 5 ). The drive spindle 32 used is made of 303 stainless steel and has a diameter of 5.54 mm and a pitch of 4.86 mm. To drive this drive spindle 32, a stepper motor from HAYDON (type E43H4Q-05) without gear ratio (HAYDON KERK, Waterbury, CT 06705, USA) is used. With this linear motor, according to the data sheet, the motor axis and thus also the drive spindle 32 rotate by an angle increment of 1.8 ° per full step. Preferably, the drive spindle 32 is an extension of the motor axis. With the drive spindle 32 used, the motor 31 generates a height adjustment of the washing head 5 of 0.0243 mm (= 24.3 μm) per full step or of 4.86 mm per 200 full steps, ie per axis revolution. In a preferred, special control of the stepping motor (as this is known to any person skilled in the art and is supported in this case by the motor driver) of the motor 31 is moved in quarter steps, so that one rotation of the motor shaft and the drive spindle requires 800 quarter steps. The resolution thus achieved in the movement of the washing head 5 in the direction of the vertical Z-axis is thereby preferably 6.075 μm per single quarter step.

According to a first embodiment of the adjustment method according to the invention, a washing head 5 is used in which at least one of the washing cannulas 6 or a sensor 21 (additionally inserted or attached) is at least partially electrically conductive. These at least one washing cannula 6 or this sensor 21 are electrically connected to the controller. The reference surface 16 of the adjustment plate 17, the surface 18 of an insert plate 19 or the base 20 of the receptacle 2 for receiving a microplate 3 are also at least partially electrically conductive and electrically connected to the controller 12. The control applies an electrical voltage via the two connections to the at least one washing cannula 6 or this sensor 21 and to the surface 10 defining the reference plane 8. If now the reference plane 8 defining surface 10 (ie the reference surface 16, the surface 18 or the base 20) with the lowest end of the at least one washing cannula 6 or the probe 21 is touched, an electrical contact is made and the circuit is closed; this signal is detected by the controller 12.

The FIG. 2 shows detail sections, which represent the most significant height positions. In Fig. 2A is a vertical section through the microplate receptacle 2 with an inserted microplate 3 and a washing cannula 6 shown in working position. Well visible (but not to scale), the working distance 22 is shown here, which is 0.2 mm in this particularly preferred case. Here, therefore, the active altitude 14 of the lowest ends of the washing cannulas 6 during operation of the microplate washing device 1 is shown with inserted microplate. The most uniform possible setting of this active altitude 14 for the lowest ends of all washing cannulas 6 of a washing head 5 is the aim of the present inventive method.

In Fig. 2B a vertical section through an inserted into the microplate holder 2 adjustment plate 17 is shown. The surface of the adjustment plate 17 is formed as a reference surface 16 and corresponds here just the inner surfaces 15 of the bottoms of the microplate wells (see. Fig. 2A ). In this case, the washing head 5 comprises an electrically conductive sensor 21 of the sensor device 12, wherein the foremost end of the sensor 21 protrudes beyond the lowest ends of the washing cannulas 6 by the working distance 22. The sensor 21 thus protrudes by a measure beyond the washing cannulas 6, which corresponds to the working distance 22 of the lowest ends of the washing cannulas 6 during operation of the microplate washing device 1.

In Fig. 2C is a vertical section through an inserted into the microplate holder 2 adjustment plate 17 is shown. The surface of the adjustment plate 17 is formed as a reference surface 16 and corresponds here just the inner surfaces 15 of the bottoms of the microplate wells (see. Fig. 2A ). In this case, the washing head 5 may comprise an electrically conductive sensor 21 of the sensor device 12, wherein the foremost end of the sensor 21 is located in the working plane 7 of the washing cannulas 6. The washing head 5 is shown here interrupted, this indicates the optional use of the electrically conductive probe 21; If at least one of the washing cannulas 6 is at least partially electrically conductive, this sensor 21 can be dispensed with.

In Fig. 2D is a vertical section through an inserted into the microplate receptacle 2, special adjustment plate 17 'shown. The surface of this adjustment plate 17 'simulates the working plane 7 (ie the active height position 14) of the washing cannulas 6 in the microplate wells. Also in this case, the washing head 5 may comprise an electrically conductive sensor 21 of the sensor device 12, wherein the foremost end of the sensor 21 is located in the working plane 7 of the washing cannulas 6. The washing head 5 is shown here interrupted, this indicates the optional use of the electrically conductive probe 21; If at least one of the washing cannulas 6 is at least partially electrically conductive, this sensor 21 can be dispensed with.

According to a first variant of the first embodiment of the method according to the invention, the reference surface 16 'of the adjustment plate 17' is the surface 10 defining the reference plane 8 (cf. Fig. 2D ). In this case, the washing head 5 may comprise an electrically conductive sensor 21 of the sensor device 12, wherein the foremost end of the sensor 21 preferably lies in the working plane 7 of the washing cannulas 6. Here, the reference plane 8 coincides with the active altitude 14. Therefore, the controller 12 sets the active altitude 14 to be determined of the bottommost ends of the washing cannulas 6 for operation of the microplate washer 1 with the relative height value 13 of the bottommost ends of the washing cannulas 6 or probe 21 upon touching the surface 10 defining the reference plane 8 ,

According to a second variant of the first embodiment of the method according to the invention, the reference surface 16 of the adjustment plate 17 is the surface 10 defining the reference plane 8 (cf. Fig. 2C ). Also in this case, the washing head 5 may comprise an electrically conductive sensor 21 of the sensor device 12, wherein the foremost end of the sensor 21 is preferably located in the working plane 7 of the washing cannulas 6. Here the reference plane 8 does not coincide with the active altitude 14. The controller 12 therefore determines the active altitude 14 the lowermost ends of the washing cannulas 6 for the operation of the microplate washing device 1 in that with the relative height value 13 of the lowermost ends of the washing cannulas 6 or the probe 21 when touching the reference plane 8 defining surface 10, a working distance 22 is charged.

According to a third variant of the first embodiment of the method according to the invention, the reference surface 16 of the adjustment plate 17 is the surface 10 defining the reference plane 8 (cf. Fig. 2B ). In this case, the washing head 5 comprises an electrically conductive sensor 21 of the sensor device 12, wherein the foremost end of the sensor 21 is located at the working distance 22 below the working plane 7 of the washing cannulas 6. Here, the reference plane 8 coincides with the inner surfaces 15 of the bottoms of the microplate wells. The controller 12 therefore determines the active elevation 14 of the lowermost ends of the wash cannulas 6 for operation of the microplate washer 1 in that the relative height value 13 of the foremost end of the probe 21 when touching the surface 10 defining the reference plane 8 with the active elevation 14 the lowest ends of the washing cannulas 6 for the operation of the microplate washer 1 is equated.

The FIG. 3 shows detail sections, which represent the most significant height positions. In Fig. 3A is a vertical section through the microplate receptacle 2 with an attached microplate 3 and a washing cannula 6 shown in working position. Well visible (but also not to scale), the working distance 22 is shown here, which is 0.15 mm in this particularly preferred case. Here, therefore, the active altitude 14 of the lowest ends of the washing cannulas 6 during operation of the microplate washing device 1 is shown with inserted microplate. The most uniform possible setting of this active altitude 14 for the lowest ends of all washing cannulas 6 of a washing head 5 is the aim of the present inventive method.

In Fig. 3B a vertical section through an inserted into the microplate holder 2 insert plate 19 is shown. The surface 18 of the insert plate 19 is formed as a reference surface 16 and does not correspond to the inner surfaces 15 of the bottoms of the Mikroplattenwells (see. Fig. 3A ). This surface 18 may define a level that coincides with another altitude clearly defined by the microplate 3 agree. However, it is also conceivable that this surface 18 of the insert plate 19 defines a level that does not coincide with any height position uniquely defined by the microplate 3. In this case, the washing head 5 may comprise an electrically conductive sensor 21 of the sensor device 12, wherein the foremost end of the sensor 21 is located in the working plane 7 of the washing cannulas 6. The washing head 5 is shown here interrupted, this indicates the optional use of the electrically conductive probe 21; If at least one of the washing cannulas 6 is at least partially electrically conductive, this sensor 21 can be dispensed with.

Fig. 3C shows a vertical section through the microplate receptacle 2. The footprint 20 of the receptacle 2 for a microplate 3 is here the surface defining the reference plane 8 10. Also in this case, the washing head 5 may comprise an electrically conductive probe 21 of the sensor device 12, wherein the Foremost end of the probe 21 in the working plane 7 of the washing cannulas 6 is located. The washing head 5 is shown here interrupted, this indicates the optional use of the electrically conductive probe 21; If at least one of the washing cannulas 6 is at least partially electrically conductive, this sensor 21 can be dispensed with.

In Fig. 3D a vertical section through a microplate 3 inserted into the microplate receptacle 2 is shown. In this case, the washing head 5 does not comprise an electrically conductive sensor 21 of the sensor device 12. The sensor device 12 rather comprises a non-contact sensor which is installed in the microplate washing device 1 (US Pat. see. Fig. 4 ).

According to a fourth variant of the first embodiment of the method according to the invention, the surface 18 of the insert plate 19 is the surface 10 defining the reference plane 8 (cf. Fig. 3B ). In this case, the washing head 5 may comprise an electrically conductive sensor 21 of the sensor device 12, wherein the foremost end of the sensor 21 preferably lies in the working plane 7 of the washing cannulas 6. Here the reference plane 8 does not coincide with the active altitude 14. The controller 12 therefore determines the active altitude 14 of the lowermost ends of the washing cannulas 6 for the operation of the microplate washer 1 in that with the relative height value 13 of the bottommost ends of the washing cannulas 6 or of the probe 21 when touching the surface 8 defining the reference plane 8 a microplate typical height 23 and a working distance 22 are calculated.

According to a fifth variant of the first embodiment of the method according to the invention, the base 20 of the receptacle 2 for receiving a microplate 3 is the surface 10 defining the reference plane 8 (cf. Fig. 3C ). In this case, the washing head 5 may comprise an electrically conductive sensor 21 of the sensor device 12, wherein the foremost end of the sensor 21 preferably lies in the working plane 7 of the washing cannulas 6. Here the reference plane 8 does not coincide with the active altitude 14. Therefore, the controller 12 determines the active elevation 14 of the lowermost ends of the washing cannulas 6 for the operation of the microplate washer 1 in that with the relative height value 13 of the lowermost ends of the washing cannulas 6 or the probe 21 upon touching the surface 10 defining the reference plane 8 a micro-plate representing height 24 and a working distance 22 are charged.

Deviating from the FIGS. 2B, 2C and 2D and FIGS. 3B and 3C, in which the level of the lower end of the probe 21 differs by a maximum of the working distance 22 from the level of the lower ends of the washing cannulas 5, this difference in level can also be significantly greater. In addition, the lower end of the probe 21 may be above the level of the lower ends of the washing cannulas 6. Thus, an adjustment plate 17 can be inserted into the receptacle 2, which has a specific survey for the sensor, which would even extend beyond an inserted microplate. Such a survey (which may also be located on the edge of the microplate holder 2) is detected by the sensor 21 with particular certainty and prevents the sensor 21 and an inserted microplate 3 from touching or even damaging each other.

The FIG. 4 shows a schematic vertical section through a microplate washer 1 with a washing head 5 (here six pairs of washing cannulae, so six Aspirierkanülen 6 and six Dispenskananülen 6 'has) but without inserted into the designated receptacle 2 microplate 3. The washing cannulas 6,6' of the Wash head 5 are arranged here in a linear array, the at least one Part of the wells array of this microplate 3 corresponds. Preferably, eight aspirating needles 6 and eight dispensing cannulas 6 'are used, so that just one column of a 96-well microplate can be processed simultaneously; For this purpose, a longer aspirating cannula 6 and a shorter dispenser cannula 6 'are each lowered into each of the eight wells of a column of a 96-well microplate. It can also be provided to equip the washing head with a non-linear array of washing cannulas, for example with a 4 × 4 array, a 2 × 8 array or an 8 × 12 array, the latter being a so-called 96-well washing head equivalent. Larger arrays of, for example, 12 × 16 (192-well head) or 16 × 24 (384-head) washing cannulas or pairs of washing cannulae are also conceivable.

• einer ganzen Reihe von 12 Wells bei um 90° gedrehten 96-er Mikroplatten,
• einer ganzen Kolonne von 16 Wells bei 384-er Mikroplatten, oder
• einer ganzen Reihe von 24 Wells bei um 90° gedrehten 384-er Mikroplatten.

In addition to the already described, strip-shaped washing heads with a substantially linear arrangement of 8 pairs of washing cannulae, washing heads of microplate washing devices with a substantially linear arrangement of 12, 16 or 24 pairs of washing cannulae can also be set with the method according to the invention. Such washing heads are suitable for washing, for example:

• a whole series of 12 wells with 90-degree rotated 96-well microplates,
• a whole column of 16 wells on 384 microplates, or
• a full set of 24 wells with 90 ° rotated 384 microplates.

The probe 40 is here on top of the washing head 5, so that the effective movement of the washing head 5 is measured and read on a separate display 41 and / or can be stored in the controller 12 of the microplate washer 1.

The washing head 5 is shown here adjustable in height, but it can also be designed as stuck in the washing operation of the device. In any case, during the performance of the adjustment method according to a second embodiment of the adjustment method according to the invention, the washing head 5 is vertically movable so far that the setting method described below according to the second embodiment can be carried out. The microplate holder 2 may be fixed or height-adjustable. Any height adjustment of the washing head 5 and / or the microplate holder 2 is preferably carried out in the vertical Z direction of a Cartesian coordinate system. It can also be provided be to move the micro-plate holder 2 in the horizontal X-direction of this Cartesian coordinate system, as is known for example from the microplate washer, the current applicant offers under the trade name Power Washer 384 ^™ . In any case, the microplate washer 1 is designed so that the receptacle 2 with the microplate 3 and a washing head 5 can be approximated to one another such that the washing cannulas 6, 6 'can be placed in the wells of this microplate 3.

It is also important that a working plane 7 defined by the washing cannulas 6 with their lowest ends and a reference plane 8 are arranged parallel to one another. If these two planes 7, 8 are not parallel to one another, then the washing cannulas 6 of a linear array (ie in strip arrangement) could still be arranged at the same height if the tilting axis of one of the two planes 7, 8 is parallel to the bottommost ends of the washing cannulas 6 runs. However, if a non-linear (or 2-dimensional) array of, for example, 8 × 12 washing cannulas 6 or pairs of washing cannulas is used, then not all washing cannulas 6 can be arranged at the same working distance 22 to the inner surfaces 15 of the well bottoms of a microplate 3.

Since it is essential for the reproducible performance of delicate experiments that the geometric conditions in all involved wells of a microplate are as equal as possible, a uniform working distance 22 of all Aspirierkanülen 6 is sought from the inner surfaces 15 of the well plates of a microplate 3.

Starting from the parallel arrangement of the working plane 7 and the reference plane 8, the receptacle 2 and / or a washing head 5, preferably attached to a washing head carrier 9, are moved towards one another in a first phase of the setting process according to the invention until the bottommost ends of the washing cannulas 6 at least one touching the reference plane 8 defining surface 10.

In the Fig. 4 there is shown a light barrier 25 (OPTEK, type OPB460N 11, OPTEK Technology Inc., Carrollton, Texas 75006, USA) rigidly connected to the washing head 5. This light barrier 25 belongs to the sensor device 11 and serves to detect the contact of a surface 10 defining the reference plane 8. For carrying out the method according to the invention, the microplate washing device 1 comprises a sensor device 11 and a controller 12 operatively connected to this sensor device. The controller 12 detects a signal from this sensor device 11 which indicates the contact of the surface 10 with the bottommost ends of the washing cannulas 6 ( see the first embodiment of the method according to the invention already described) or can be used for its determination (compare the second embodiment of the method according to the invention described below).

In both embodiments of the method according to the invention, with the controller 12 based on the relative height value 13, an active altitude 14 of the bottommost ends of the washing cannulas 6 with respect to an inner surface 15 of the well bottoms of a microplate is determined during operation of the microplate washer 1.

The FIG. 5 shows a 3D representation corresponding to a part of Fig. 4 , with a sensor device 11, which comprises a light barrier 25. On a support device 37 of the microplate washer 1, a linear guide 30 is fixed, which preferably runs exactly in the Z direction of a Cartesian coordinate system. A linear guide of the type MN12 from SCHNEEBERGER (SCHNEEBERGER Holding AG, 4914 Roggwil, Switzerland) was used. Along this linear guide 30 movable at least one connecting piece 36 is arranged, on which the washing head carrier 9 is rigidly secured. The washing head 5 is not shown here, only a part of the washing head carrier 9 used here is visible. The double arrows indicate the height-adjustable parts.

At a connecting piece 36, a sling 35 is attached and thus rigidly connected to the washing head carrier 9. This connection between the connector 36 and sling 35 is preferably made by means of two screws 39, wherein in the Fig. 5 only one of these screws 39 is visible. The sling bar 35 has at least one slot 33, but preferably two slots 33, each with an end stop. The motor 31 drives a drive spindle 32, which in turn acts on a lifting flange 26 which is guided non-rotatably, so that upon rotation of the drive spindle 32, depending on the selected direction of rotation, the lifting flange 26 is lowered or raised. Attached to the rotary flange 26 are at least one, preferably but two beams 27 which support the wash head carrier 9 over the sling bar 35. As shown, these two beams 27 are movable in the slots 33 of the sling 35 in the Z direction. The two bars 27 and the two slots 33 are preferably coordinated so that when lifting the beam 27 with the lifting flange 26 both beams 27 simultaneously act on the respective end stops of the slots 33. Thus, the washing head carrier 9 is raised as soon as the two beams 27 act on the respective end stops of the slots 33 and the lifting flange 26 is moved up in the Z direction.

The situation is different when, when the lifting flange 26 moves downwards, the washing head carrier 9 rests against an obstacle, because, for example, the washing cannulas 6 with their lowest ends stand up on a surface 10 defining the feed 8. In this case, only the lifting flange 26 moves downwards: The two bars 27 separate from the respective end stops of the slots 33 and move with the lifting flange 26 down. But because the photocell 25 is fixedly fixed to the sling 36 (for example, with two screws 39 ', see. Fig. 5 ), and because the sling bar is firmly connected to the washing head carrier 9 (for example, with two screws 39, see. Fig. 5 ), the light barrier 25 with the sling 36 and the washing head support 9 stops. In this sole down moving the beam 27 and the one bar 27 is moved out of the light barrier 25, which had 34 interrupted the light beam. As soon as this bar 27 releases the light beam 34 (ie no longer interrupts), a corresponding signal of the light barrier 25 is detected and processed by the controller 12.

Because the geometry of the drive spindle 32 and the gear ratio of an optional transmission (not shown) are known and because the number of angular increments of the motor 31 are continuously recorded by the controller, a correction amount 28 corresponding to the height difference that the beam 27 can determine between the release of the end stop "of his" slot 33 and the release of the light beam 34 of the light barrier 25 must cover. This correction amount 28 is typical and unchangeable for each device, it can be determined once by the manufacturer of a particular microplate washer 1 (see. Fig. 6 ) and then stored as a known parameter in the firmware of this particular microplate washer 1.

Preferably, the sling bar 35 includes a fixedly connected thereto tab 38. At this tab 38, all electrical lines between the photocell 25 and the controller 12 are attached.

• I. Der Hebeflansch 26 des Mikroplatten-Waschgeräts 1 und der Waschkopf 5 werden zusammen gesenkt bis der Waschkopf 5 beim Punkt II ansteht und sich nicht mehr weiter senkt. Dieses Absenken erfolgt mittels des Motors 31 und der Antriebsspindel 32. Während des Absenkens folgt der HEIDENHAIN Messtaster dieser Bewegung des Waschkopfs 5.
• II. Der Punkt II wird mit dem HEIDENHAIN Messtaster ermittelt. Der Punkt II entspricht dem im erfindungsgemäss Verfahren verwendeten relativen Höhenwert 13, der selbst dem Höhenwert Z_H1 des Hebeflanschs 26 entspricht.
• III. Der Hebeflansch 26 des Mikroplatten-Waschgeräts 1 wird alleine weiter gesenkt bis die Lichtschranke 25 in Punkt IV meldet, dass der Lichtstrahl durch den Balken 27 nicht mehr unterbrochen ist. Dieses Absenken erfolgt vorzugsweise z.B. in Viertelschritten des Schrittmotors 31, wobei jeder Viertelschritt des Schrittmotors dem Absenken des Hebeflanschs 26 z.B. um 6.075 µm entspricht.
• IV. Die Anzahl der Viertelschritte des Schrittmotors 31, die es braucht, um den Hebeflanschs 26 vom Punkt II auf den Punkt IV abzusenken wird erfasst und mit 6.075 µm multipliziert, wodurch der Höhenwert Z_H2 des Hebeflanschs 26 erhalten wird.
• V. Die Differenz der beiden Höhenwerten Z_H1 und Z_H2 des Hebeflanschs 26 entspricht dem gesuchten Korrekturbetrag 28, der damit für dieses Mikroplatten-Waschgerät 1 vorbestimmt ist.
• VI. Der für jedes Mikroplatten-Waschgerät 1 individuell vorbestimmte Korrekturbetrag 28 wird in die Firmware des betreffenden Mikroplatten-Waschgeräts 1 aufgenommen und ist im Betrieb des Mikroplatten-Waschgeräts 1 nach Bedarf abrufbar.

The FIG. 6 FIG. 12 shows a path / path diagram for determining the predetermined correction amount 28 to be taken into consideration when determining the active altitude 14 of the bottommost ends of the washing cannulas 6 according to the second embodiment of the adjustment method according to the invention. In the Fig. 6 On the first axis, the effective movement (Z _H ) of the lifting flange 26 in the direction of the Z axis and on the second axis, the externally measured (eg with the HEIDENHAIN probe) movement (Z _M ) of the washing head 5 of the microplate washer 1 applied , The correction amount 28 is essentially determined by the geometry of the light barrier 25 and of the beam 27 engaging in this light barrier 25. This correction amount 28 is determined by the manufacturer of the microplate washer 1 by default as follows:

• I. The lifting flange 26 of the microplate washer 1 and the washing head 5 are lowered together until the washing head 5 is present at point II and no longer lowers. This lowering takes place by means of the motor 31 and the drive spindle 32. During the lowering, the HEIDENHAIN probe follows this movement of the washing head 5.
• II. Point II is determined with the HEIDENHAIN probe. Point II corresponds to the relative height value 13 used in the method according to the invention, which itself corresponds to the height value Z _H 1 of the lifting flange 26.
• III. The lifting flange 26 of the microplate washing device 1 is lowered further alone until the light barrier 25 reports in point IV that the light beam is no longer interrupted by the bar 27. This lowering preferably takes place, for example, in quarter steps of the stepping motor 31, with each quarter step of the stepping motor corresponding to the lowering of the lifting flange 26, for example by 6.075 μm.
• IV. The number of quarter steps of the stepping motor 31 needed to lower the lift flange 26 from the point II to the point IV is detected and multiplied by 6,075 μm, thereby obtaining the height value Z _H 2 of the lift flange 26.
• V. The difference between the two height values Z _H 1 and Z _H 2 of the lifting flange 26 corresponds to the sought correction amount 28, which is thus predetermined for this microplate washing device 1.
• VI. The individually predetermined correction amount 28 for each microplate washer 1 is incorporated into the firmware of the respective microplate washer 1 and is retrievable as needed during operation of the microplate washer 1.

The FIG. 7 shows a signal / path diagram in determining the predetermined correction amount 28 in FIG Fig. 6 , In the Fig. 7 is on the first axis, the effective movement (Z _H ) of the lifting flange 26 of the microplate washer 1 in the Z-axis direction and plotted on the second axis, the signal of the photocell 25. The diagram shows that the signal of the light barrier 25 changes from 0 to 1 at the height value Z _H 2 of the lifting flange 26. This is done in phase III of the standard procedure performed by the manufacturer of the microplate washer 1 for determining the correction amount 28.

1. A. Der Hebeflansch 26 des Mikroplatten-Waschgeräts 1 und der Waschkopf 5 werden (zumindest teilweise) gemeinsam abgesenkt bis die Lichtschranke 25 in Punkt B meldet, dass der Lichtstrahl durch den Balken 27 nicht mehr unterbrochen ist. Dieses Absenken erfolgt vorzugsweise z.B. in Viertelschritten des Schrittmotors 31, wobei jeder Viertelschritt des Schrittmotors dem Absenken des Hebeflanschs 26 z.B. um 6.075 µm entspricht.
2. B. In Punkt B, der dem Höhenwert Z_H2 des Hebeflanschs 26 entspricht, wird die Abwärtsbewegung des Hebeflanschs 26 gestoppt.
3. C. Der Hebeflansch 26 des Mikroplatten-Waschgeräts 1 und der Waschkopf 5 werden (zumindest teilweise) gemeinsam angehoben um einen Wert, der sich zusammensetzt aus dem vorbestimmten Korrekturbetrag 28 und dem verlangten Arbeitsabstand 22. Dieses Anheben erfolgt vorzugsweise z.B. in Viertelschritten des Schrittmotors 31, wobei jeder Viertelschritt des Schrittmotors dem Anheben des Hebeflanschs 26 um 6.075 µm entspricht.

The FIG. 8 1 shows a path diagram for determining the active height position 14 of the bottommost ends of the washing cannulas 6 with respect to an inner surface 15 of the well bottoms of a microplate 3 during operation of the microplate washer 1. This process is carried out by the user using the microplate washer 1 is working. The user proceeds as follows:

1. A. The lifting flange 26 of the microplate washer 1 and the washing head 5 are (at least partially) lowered together until the light barrier 25 in point B reports that the light beam is no longer interrupted by the beam 27. This lowering preferably takes place, for example, in quarter steps of the stepping motor 31, with each quarter step of the stepping motor corresponding to the lowering of the lifting flange 26, for example by 6.075 μm.
2. B. In point B, which corresponds to the height value Z _H 2 of the lifting flange 26, the downward movement of the lifting flange 26 is stopped.
3. C. The lifting flange 26 of the microplate washer 1 and the washing head 5 are raised together (at least partially) by a value which is composed of the predetermined correction amount 28 and the required working distance 22. This lifting preferably takes place, for example, in quarter steps of the stepping motor 31, wherein each quarter step of the stepping motor corresponds to raising the lifting flange 26 by 6.075 μm.

Preferably, this determination of the active height position 14 of the lowermost ends of the washing cannulas 6 with respect to an inner surface 15 of the well bottoms of a microplate 3 during operation of the microplate washer 1 automatically, so that the user only has to trigger the process. This triggering is preferably carried out by activating a dedicated switch. This switch is designed, for example, as a virtual switch (for example on a PC monitor or a graphical user interface [GUI]), as a key on a PC keyboard or as an electrical pushbutton or switch.

The FIG. 9 shows a signal / path diagram in determining the active altitude 14 of the lowermost ends of the washing cannulas 6 in Fig. 8 , In the Fig. 9 is on the first axis, the effective movement (Z _H ) of the lifting flange 26 of the microplate washer 1 in the Z-axis direction and plotted on the second axis, the signal of the photocell 25. The diagram shows that the signal of the light barrier 25 at the height value Z _H 2 (corresponds to the point B in FIG Fig. 8 ) of the lifting flange 26 changes from 0 to 1. This is done at the end of phase A of the standard procedure performed by the user of the microplate washer 1 to determine the active elevation 14 of the bottommost ends of the wash tubules 6 with respect to the inner surface 15 of the well bottoms of a microplate used.

It is advantageous to let the user of the microplate washer determine the time of this setting himself, because the user first selects one for the microplate washer Use provided microplate 3 in the receptacle 2 of the microplate washer 1 must insert. This is especially the case when the microplate washer 1 must be set to a previously never used microplate 3. Preferably, after the adjustment process has been completed on the microplate washing device 1, the currently set distance between the lowermost ends of the washing cannulas 6 (ie the working plane 7) and the standing surface 20 of the microplate 3 (ie the surface of the microplate holder 2) is displayed in mm.

Preferably, the user may place the determined value, which is composed of the predetermined correction amount 28 and the required working distance 22, together with the type of microplate used to determine this value in the disk library of the microplate washer 1.

If this microplate 3 is a microplate previously processed with the present microplate washer 1, the user may dispense with the adjustment process and set the required value composed of the predetermined correction amount 28 and the required working distance 22 together with the corresponding microplate type of retrieve the disk library.

However, the motor 31 may also be used as a DC motor for driving the drive spindle 32. In this case, the DC motor is equipped with a decoder (for example, a slotted disk 42 and a light barrier 43) which detects angular increments so that, similarly to the stepping motor, the drive spindle 32 moves in angular increments or detects movement thereof at least in angular increments can. Important for the exact movement of the washing head 5 is the one hand, the translation of the motor used and on the other hand, the pitch or pitch of the drive spindle 32. Again, it is preferred that the drive spindle 32 is an extension of the motor axis. In particular, the reproducibility of the movements of the washing head 5 should be noted.

According to the second embodiment of the method according to the invention, a microplate washing device 1 is used (by the manufacturer or by the user) which comprises a light barrier 25 which is rigidly connected to the washing head 5 (see. 4 and 5 ). In addition, the microplate washing device 1 comprises a lifting flange 26 which is rigidly connected to a beam 27 supporting the washing head carrier 9.

During one of the first phase (see I in Fig. 6 ), second phase (see III in Fig. 6 ) of the adjustment method according to the invention, the light barrier 25 and the beam 27 are moved away from each other (preferably by the manufacturer) until a light beam 34 of the light barrier 25 interrupted by the beam 27 during the first phase is no longer interrupted.

During a first phase (see A in Fig. 8 ) of the inventive adjustment method (preferably by the user) the light barrier 25 and the beam 27 are moved away from each other until a interrupted by the beam 27 light beam 34 of the light barrier 25 is no longer interrupted.

Furthermore, in the course of the adjustment process according to the invention with the controller 12, the relative height value 13 of the bottommost ends of the washing cannulas 6 when touching the reference plane 8 (preferably from the manufacturer of the microplate washing device) can be determined by the constant travel of the lifting flange 26 the beam 27 during the second phase (see III in Fig. 6 ), determined as a predetermined correction amount 28 and is calculated with a determined at the end of the second phase height position 29 of the lifting flange 26.

For carrying out the adjustment method according to the invention, preferably the inner surfaces 15 of the bottoms of the wells of a microplate 3 serve as the surfaces 10 defining the reference plane 8 (cf. Fig. 3D ). In this case, the washing head 5 does not comprise an electrically conductive sensor 21 of the sensor device 12. Moreover, the reference plane 8 does not coincide with the active height position 14 of the bottommost ends of the washing cannulas 6. Therefore, the controller 12 determines the active altitude 14 of the lowermost ends of the washing cannulas 6 for the operation of the microplate washer 1 in that a working distance 22 is offset with the relative height value 13 of the bottommost ends of the washing cannulas 6 when the surface 10 defining the reference plane 8 is touched becomes. In this case, however, it is not just touching to determine the relative altitude value 13 serves; it must also be in the context of the Fig. 6 described procedure for determining the correction amount 28 are considered. Accordingly, for determining the active altitude 14 of the lowermost ends of the washing cannulas 6 according to the second embodiment of the adjusting method of the present invention, the predetermined correction amount 28 and the working distance 22 are taken into consideration.

The controller 12 finally determines the active altitude 14 of the lowermost ends of the washing cannulas 6 for the operation of the microplate washer 1, characterized in that the determined at the end of the second phase height position 29 of the lifting flange 26, a predetermined correction amount 28 and a working distance 22 are charged.

• eine Aufnahme 2 zum Aufnehmen einer Mikroplatte 3, wobei die Mikroplatte 3 ein Wells-Array 4 umfasst;
• einen Waschkopf 5 mit Waschkanülen 6, wobei die Waschkanülen 6 in einem Array entsprechend zumindest einem Teil des Wells-Arrays 4 dieser Mikroplatte 3 angeordnet sind und mit ihren untersten Enden eine Arbeitsebene 7 definieren; und
• eine Sensorvorrichtung 11 sowie eine mit dieser Sensorvorrichtung wirkverbundene Steuerung 12, welche die Signale dieser Sensorvorrichtung 11 verarbeitet und die Bewegungen der Aufnahme 2 und/oder des Waschkopfs 5 steuert.

An inventive use of a microplate washer 1 relates to the setting of the same. Use is made of a microplate washing device 1, which comprises at least:

• a receptacle 2 for receiving a microplate 3, the microplate 3 comprising a well array 4;
• a washing head 5 with washing cannulas 6, wherein the washing cannulas 6 are arranged in an array corresponding to at least part of the well array 4 of this microplate 3 and define with their lowest ends a working plane 7; and
• a sensor device 11 and a control device 12 operatively connected to this sensor device, which processes the signals of this sensor device 11 and controls the movements of the receptacle 2 and / or the washing head 5.

It is assumed that the working plane 7 defined by the washing cannulas 6 with their lowest ends and a reference plane 8 are arranged parallel to one another.

1. (a) die Aufnahme 2 und der Waschkopf 5, durch Bewegen der Aufnahme 2, des Waschkopfs 5 oder beider, einander angenähert werden, bis die untersten Enden der Waschkanülen 6 Innenoberflächen 15 der Wellböden einer in der Aufnahme 2 befindlichen Mikroplatte 3 berühren;
2. (b) dieses Berühren der Innenoberflächen 15 der Wellböden mit den untersten Enden der Waschkanülen 6 mit der Sensorvorrichtung 11 und der Steuerung 12 erfasst wird; und
3. (c) die Steuerung das Mikroplatten-Waschgerät veranlasst, die Aufnahme 2 und/oder den Waschkopf 5 so zu bewegen, dass die untersten Enden der Waschkanülen 6 in eine aktive Höhenlage 14 in Bezug auf die Innenoberfläche 15 der Wellböden der Mikroplatte 3 gebracht werden.

The use according to the invention of this microplate washing device 1 is characterized in that:

1. (a) the receptacle 2 and the washing head 5, by moving the receptacle 2, the washing head 5 or both, are approximated to each other, until the bottom Ends of the washing cannulas 6 contact inner surfaces 15 of the well bottoms of a microplate 3 located in the receptacle 2;
2. (b) detecting said contacting of the inner surfaces 15 of the corrugated bottoms with the lowermost ends of the washing cannulas 6 with the sensor device 11 and the controller 12; and
3. (c) the controller causes the microplate washer to move the receptacle 2 and / or the wash head 5 so that the lowermost ends of the wash tubules 6 are brought into an active elevation 14 with respect to the inner surface 15 of the well bottoms of the microplate 3.

Particularly preferred is a use of the microplate washer at which the bottom ends of the washing cannulas 6 in operation of the microplate washer 1 in its determined in step (c) active altitude 14 by a working distance 22 from the inner surfaces 15 of the corrugated floors in step (a ) are set and entered by a user, or by the controller 12, a stored value for the working distance 22 is retrieved and automatically included in determining the active altitude 14.

Although not all references in the figures have been discussed in every case, they always refer to the same technical features.

LIST OF REFERENCE NUMBERS

1

Microplate washer

2

admission

3

microplate

4

Wells array

5

washing head

6.6 '

Washing cannula (n)

6

Aspirierkanüle

6 '

Dispenserkanüle

7

working level

8th

reference plane

9

Washing head carrier

10

Surface defining the reference plane

11

sensor device

12

control

13

relative altitude

14

active altitude

15

Inner surface (s) of the bottoms of the wells of a microplate

16.16 '

Reference area of 17,17 '

17.17 '

adjustment

18

Surface of 19

19

insert plate

20

Floor space of 2

21

sensor

22

working distance

23

Microplate-typical height

24

Microplate representing height

25

photocell

26

lift flange

27

the washing head carrier supporting beams

28

predetermined correction amount

29

ascertained height position of 26

30

linear guide

31

engine

32

drive spindle

33

slot

34

Beam of 25

35

slingBar

36

joint

37

carrying device

38

flap

39

screw

40

probe

41

Display of 40

42

slotted disc

43

photocell

Claims (18)

Setting procedure for microplate washing devices,
wherein a microplate washer (1) is used, which comprises at least: A receptacle (2) for receiving a microplate (3), the microplate (3) comprising a well array (4); and A washing head (5) with washing cannulas (6), wherein the washing cannulas (6) are arranged in an array corresponding to at least part of the well array (4) of this microplate (3); wherein a working plane (7) defined by the washing cannulas (6) with their lowest ends and a reference plane (8) are arranged parallel to each other;
and wherein, in a first phase of this process, the receptacle (2) and the washing head (5) are brought closer to each other by moving the receptacle (2), the washing head (5) or both until the lowest ends of the washing needles (6) at least a surface (10) defining the reference plane (8), characterized in that the microplate washer (1) comprises a sensor device (11) and a controller (12) operatively connected to this sensor device, wherein a signal is transmitted to the controller (12) this sensor device (11) is detected and thus a relative height value (13) is determined, this signal indicating that the surface (10) is in contact with the lowest ends of the washing cannulas (6) or can be used to determine the position of this surface (10), and based on said relative height value (13), an active elevation (14) of the lowermost ends of the washing cannulas (6) with respect to an inner surface (15) of the well bottoms of a microplate in operation of the microplate washer (1) is determined. Adjusting method according to claim 1, characterized in that the surface (10) defining the reference plane (8) is selected from the group which inner surfaces (15) of the bottoms of the wells of a microplate (3), a reference surface (16) of an adjustment plate (17 ), a surface (18) of an insert plate (19) and a standing surface (20) of the receptacle (2) for receiving a microplate (3), the washing head (5) being optionally attached to a washing head support (9). Adjustment method according to claim 1 or 2, characterized in that the sensor device (11) comprises a touch sensor which is selected from the group comprising electro-mechanical buttons and electrical contacts. Setting method according to claim 1 or 2, characterized in that the sensor device (11) comprises a non-contact sensor which is selected from the group comprising capacitive proximity switches, Hall sensors and light barriers. Adjusting method according to claim 2, characterized in that at least one of the washing cannulas (6) or a sensor (21) and the reference surface (16) of the adjusting plate (17), the surface (18) of an insert plate (19) or the standing surface (20) the receptacle (2) for receiving a microplate (3) are each at least partially electrically conductive, so that when touching the surface (10) defining the reference plane (8) with the lowermost end of the at least one washing cannula (6) or of the probe ( 21) an electrical contact is made. Adjusting method according to claim 5, characterized in that the sensor (21) ends in the same working plane (7) as the washing cannulas (6). Adjusting method according to claim 5, characterized in that the sensor (21) projects beyond the washing cannulas (6) by a distance corresponding to a working distance (22) of the lowest ends of the washing cannulas (6) during operation of the microplate washing device (1). Adjustment method according to claim 5 or 6, characterized in that the reference surface (16) of the adjustment plate (17 ') is the surface (10) defining the reference plane (8), and in that the controller (12) is the active height position (14) of the lowest Ends of the washing cannulas (6) for the operation of the microplate washing device (1) with the relative height value (13) of the lowest ends of the washing cannulas (6) or of the probe (21) when touching the surface (10) defining the reference plane (8) equates. Adjusting method according to claim 5 or 6, characterized in that the reference surface (16) of the adjustment plate (17) is the surface (10) defining the reference plane (8), and in that the controller (12) determines the active elevation (14) of the lowest ends of the Washing cannulas (6) for the operation of the microplate washing device (1) determined by the fact that with the relative height value (13) of the lowest ends of the washing cannulas (6) or of the sensor (21) when touching the surface defining the reference plane (8) ( 10) a working distance (22) is charged. Adjusting method according to claim 5 or 7, characterized in that the reference surface (16) of the adjustment plate (17) is the surface (10) defining the reference plane (8), and in that the controller (12) determines the active elevation (14) of the lowest ends of the Washing cannulas (6) for the operation of the microplate washer (1) with the relative height value (13) of the lowest end of the sensor (21) upon touching the surface (10) defining the reference plane (8). Adjusting method according to claim 5 or 6, characterized in that the surface (18) of the insert plate (19) is the reference plane (8) defining surface (10), and that the controller (12) the active altitude (14) of the lowest ends of Washing cannulas (6) for the operation of the microplate washing device (1) determined by the fact that with the relative height value (13) of the lowest ends of the washing cannulas (6) or of the sensor (21) when touching the surface defining the reference plane (8) ( 10) a microplate typical height (23) and a working distance (22) are charged. Adjustment method according to claim 5 or 6, characterized in that the standing surface (20) of the receptacle (2) for receiving a microplate (3) is the surface (10) defining the reference plane (8), and in that the control (12) is the active one Altitude (14) of the lowermost ends of the washing cannulas (6) for the operation of the microplate washer (1) determined by the relative height value (13) of the lowest ends of the washing cannulas (6) or the sensor (21) when touching the the reference plane (8) defining surface (10) representing a microplate height measurement (24) and a working distance (22) are charged. Adjustment method according to claim 1 or 2, characterized in that the microplate washing device (1) comprises a light barrier (25) which is rigidly connected to the washing head (5), and that the microplate washing device (1) has a lifting flange (26). which is rigidly connected to a beam (27) supporting the washing head support (9), wherein during a second phase following the first phase the light barrier (25) and the beam (27) are moved away from one another until one during the the first phase by the beam (27) interrupted light beam (34) of the light barrier (25) is no longer interrupted. Adjusting method according to claim 13, characterized in that the controller (12) determines the relative height value (13) of the bottommost ends of the washing cannulas (6) upon contact with the reference plane (8) by providing a constant path which the lifting flange (26) communicates with the beam (27) covers during the second phase, is calculated as a predetermined correction amount (28) with a determined at the end of the second phase height position (29) of the lifting flange (26). Adjusting method according to claim 14, characterized in that the inner surfaces (15) of the bottoms of the wells of a microplate (3) are surfaces (10) defining the reference plane (8), and in that the control (12) is the active elevation (14) of the lowest Ends of the washing cannulas (6) for the operation of the microplate washer (1) determined by the working height (13) of the lowest ends of the washing cannulas (6) when touching the reference plane (8) a working distance (22) is charged. Adjusting method according to claim 13, characterized in that the inner surfaces (15) of the bottoms of the wells of a microplate (3) are surfaces (10) defining the reference plane (8), and in that the control (12) is the active elevation (14) of the lowest Ends of the washing cannulas (6) for the operation of the microplate washer (1) determined by a constant path which the lifting flange (26) traverses with the bar (27) for releasing the light barrier (25) as a predetermined correction amount (28 ) and a working distance (22) with a determined height position (29) of the lifting flange (26) are charged. Use of a microplate washer (1) for adjusting the same, the microplate washer comprising at least: A receptacle (2) for receiving a microplate (3), the microplate (3) comprising a well array (4); A washing head (5) with washing cannulas (6), wherein the washing cannulas (6) are arranged in an array corresponding to at least part of the well array (4) of this microplate (3) and define a working plane (7) with their lowest ends ; and A sensor device (11) and a controller (12) operatively connected to this sensor device, which processes the signals of this sensor device (11) and controls the movements of the receptacle (2) and / or the washing head (5);
wherein the working plane (7) defined by the washing cannulas (6) with their lowest ends and a reference plane (8) are arranged parallel to one another, and wherein the use of this microplate washing device (1) is characterized in that : (a) approximating the receptacle (2) and the washing head (5) by moving the receptacle (2), the washing head (5) or both, until the bottommost ends of the washing cannulas (6) have inner surfaces (15) of the well bottoms touching a microplate (3) located in the receptacle (2); (b) detecting said contacting of the inner surfaces (15) of the corrugated bottoms with the lowermost ends of the washing cannulas (6) with the sensor device (11) and the controller (12); and (c) the controller causes the microplate washer to move the receptacle (2) and / or the wash head (5) such that the lowermost ends of the wash tubules (6) are in an active elevation (14) relative to the inner surface (14). 15) of the well bottoms of the microplate (3) are brought. Use according to claim 17, characterized in that the lowest ends of the washing cannulas (6) in operation of the microplate washing device (1) in its determined in step (c) active altitude (14) by a working distance (22) from the inner surfaces (15 ) of the well bottoms of the microplate (3) used in step (a) are removed, the working distance (22) being set and input by a user, or a stored value for the working distance (22) retrieved by the controller (12) and automatically calculated when determining the active altitude (14).

Images