EP2191135A1

EP2191135A1 - Micrometering system

Info

Publication number: EP2191135A1
Application number: EP08804174A
Authority: EP
Inventors: Gernot Heuser
Original assignee: Individual
Current assignee: Individual
Priority date: 2007-09-12
Filing date: 2008-09-12
Publication date: 2010-06-02
Also published as: DE102008042071A1; WO2009034187A1

Abstract

The invention relates to a metering system 22 having at least one bidirectionally operating micropump 1 or an arrangement having at least one micropump 1 allowing a bidirectional pump operation, used for filling and emptying microtiter plates. Each micropump 1 is advantageously associated with a calibration unit.

Description

description

micro-dosing system

The invention relates to a metering system with at least one micropump, a method for operating a metering system with a calibration unit and the use of a micropump, in particular in a metering system.

There is a large number of different micropumps. Micromembrane pumps are widely used which have, for example, an electromagnetic, piezoelectric, thermal or electrostatic drive. The pump bodies are made e.g. made of silicon or plastic.

Micropumps, in particular micromembrane pumps, and their construction and operation are e.g. in DE 19719862 A1, DE 19720482 C5 and DE 10360709 A1.

There are several variants of piezoelectrically driven micromembrane pumps that work with active valves, with passive check valves or valveless.

The known micromembrane pumps are operated unidirectionally. The delivery rate differs greatly from micropump to micropump.

For filling of microtiter plates with samples or for the metering of samples in the chambers (wells or wells) of microtiter plates multiple Kolbenhubpipetten are in use. Other metering systems use conventional pumps, e.g. Peristaltic pumps, which are removed from the dosing site and the samples are supplied via hoses to the wells of the microtiter plates. As a rule, the hoses are arranged in a row. Micropumps are not used for such dosing systems so far.

The object of the invention is to provide an alternative dosing system for precise doses of a medium. Another object is to provide an alternative metering system with multiple metering devices.

The problem is solved by the subject matter of the independent claims. The metering system according to the invention contains at least one

The micropump, the micropump or micropumps of the metering system are generally arranged in the region or in the vicinity of the outlet for the medium to be metered, that is to say in the case of metering in the vicinity of the metering location. The metering system preferably contains at least one bidirectionally operating micropump. The micropump is usually part of a dosing unit. As an alternative to the bidirectionally operating micropump, two unidirectionally operating micropumps can be connected in such a way that bidirectional operation results.

The micropump is advantageously associated with at least one active intake valve and at least one active exhaust valve, or it includes at least one intake valve (input valve, valve at the input of the pump) and at least one exhaust valve (output valve, valve at the output of the pump) providing bidirectional operation allow the micropump. The micropump is thus designed for bi-directional delivery of a pumping medium (medium to be delivered, liquid and / or gas). Advantageously, the micropump is connected or equipped with a control unit. The micropump is preferably a piezoelectric micromembrane pump. The valves are preferably microvalves. The pump preferably includes piezoelectric micro-diaphragm valves.

A bidirectional promotion of the pumping medium can be alternatively to the use of a bidirectionally operable micropump by an arrangement of two counter-connected unidirectional operating micropumps, which usually have passive valves (eg check valves) realize. The desired conveying direction in the dosing unit is set and controlled by valves. This means that unidirectionally operating micropumps with opposite direction of conveyance are alternatively used with the help of valves in the line path. This variant of a bidirectionally operable dosing unit is less preferred than the use of bidirectionally operable micropumps. The invention thus relates to a metering system with one or more metering units, which are bidirectionally operable. Preferably, the metering units are independently operable in a metering system.

The basic structure of a piezoelectric micromembrane pump, but with passive valves for unidirectional operation, is described in DE 19719862 A1, to which reference is hereby made.

The micropump is hereinafter referred to as a pump.

As a pump micro diaphragm pumps are preferably used. However, it is also possible to use piston stroke pumps, gear pumps or other types of pumps available on the microscale.

To increase the delivery rate, two or more micropumps can be interconnected in a metering unit. For example, two or more micropumps are operated in parallel in a variant of the dosing unit.

The pump will be described using the example of a micro-diaphragm pump.

The pump has a base body with an input path or

Input channel and an output path or output channel. In or on the base body, a conveyor or a moving element is arranged. In the input channel is at least one input valve and in the output channel is arranged at least one output valve usually.

The main body of the pump is preferably made of one or more materials which are chemically resistant and biochemically and microbiologically inert. Such materials are e.g. suitable plastics, ceramics, glass. It is advantageous to use plastics, in particular thermoplastics such as polycarbonate, polypropylene, PET, PBT, PPS, polyphenylsulfone, polyimide, PFA.

The main body of the pump is e.g. from a top and a

Lower part constructed, for example, an upper and lower plate, the channels for the medium to be metered (pumping medium) and as a support for functional elements such as pump diaphragm and moving element (eg piezoelectric actuator). As a rule, the main body contains at least one inlet valve and at least one outlet valve. These valves are included a diaphragm pump, for example, arranged in the region of the pump diaphragm or outside the region of the pump diaphragm.

Input valve and output valve are preferably active valves. Active valves are valves that can be opened or closed by means of a control or a control signal. Such controllable or switchable valves are, for example, solenoid valves, pneumatic or hydraulic valves, e.g. Diaphragm valves.

Piezoelectric micro-diaphragm valves have a piezoactuator coupled to a valve membrane, with which a channel or a conduit path is e.g. can be closed by a valve seat. Active microvalves are e.g. in DE 19719862 A1, to which reference is hereby made.

Advantageously, input valve and output valve of a micropump are coupled. In particular, input valve and output valve form a tandem valve in which the valves are alternately opened and closed. This is achieved, for example, by a rocking mechanism on valve bodies or valve flaps. Furthermore, a coupling of the Ventiantriebes with the pump drive is advantageous. For example, The piezoelectric actuator of a piezo-membrane pump can also serve as a drive of input valve and output valve.

A bidirectional operation of the pump can also be constructed with passive micro-valves, for example by rotatably arranged check valves. That is, the pump's direction of flow can be adjusted by turning it through 180 ° of a check valve at the inlet and a check valve at the outlet of the pump. The invention thus relates to a rotatable microvalve, in particular a rotatable check valve in micro construction. Advantageously, rotatable valves can be mechanically coupled. For example, rotatable valves at the input and output of a pump may be mechanically coupled, such as via a common axis of rotation. The direction of passage at the inlet and outlet of a pump can also by replacing the check valve by a counter-rotating Check valve to be changed. For example, with a kind of slide, which carries two juxtaposed counter-rotating check valves, by changing the position of the slide, the forward direction at the input or output of the pump can be changed. Several slides can be mechanically coupled (eg slide at input and output of one pump or slide of several pumps at input or output of the pump). The rotatable valves and the slides are moved, for example, by means of an electric motor or an electromagnet, which are usually controlled.

The pump is usually self-priming. The pump is in

Generally suitable for the conveyance of liquids and gases.

The pump is preferably controlled via a feedback such that a predetermined volume (setpoint), for example in the range of 10 to 1000 microliters, preferably 20 to 500 microliters, in particular 20 to 200 microliters, with high precision, generally with a Deviation from the setpoint of less than a microliter, is dosed. This is achieved by the use of a calibration unit and a control unit, which will be explained.

The precision of the pump with calibration unit is independent in particular of the temperature, the viscosity and the surface tension of the medium to be metered.

A preferred embodiment of the dosing or the dosing unit contains at least one micro-diaphragm pump with piezoelectric drive having at least one active pump inlet valve and at least one active Pumpenauslaßventil. The dosing unit in a dosing system advantageously contains a calibration unit.

Preference is given to a metering system with a plurality of metering units, in particular a metering system for multiple, row-by-row or areal metering of samples or reagents or sample application. The dosing system is particularly advantageous for sample or reagent dosing in so-called microtiter plates, arrangements of reaction vessels, sample containers, sample vessels, tubes, with flat carriers (with or without wells for a sample or reagent house; eg sample or reagent chip) or similar dosing tasks. Very advantageous are dosing systems with a number of dosing units, which corresponds to the number of doses or dosing points. For example, the metering units of the metering system are arranged corresponding to the wells for receiving samples (wells or wells) of a microtiter plate. The metering units of the metering system form, for example, an array (arrangement of rows).

A dosing unit typically comprises a sample feed (supply line, for example hose or channel) to the pump, a pump and a dosing line or discharge line. Advantageously, the pump is equipped with a calibration unit. Typically, the calibration unit is located directly at the pump outlet and leads directly to the outlet. In an alternative design, the discharge line or output channel of the pump and calibration unit are disconnected. The calibration unit can be arranged for example in an additional, closable by a valve line at the pump outlet, which does not lead to the dosing but to a storage or waste container. It is possible to use a calibration unit for a plurality of metering units (less preferred).

The calibration unit comprises a measuring section with at least two measuring points, preferably three measuring points. At the measuring points are usually sensors. The measuring section is a section of a conduit path with precise dimensions, for example a section of a channel or a capillary. The measuring section has a defined and previously known volume. The measuring path is used to detect the velocity of a volume element of the pumping medium during operation of the pump or the determination of the delivery rate of the pump under the given conditions. In the case of a liquid as pump medium, the time at which the front of the pumping medium (end of a liquid column, meniscus of the liquid) reaches the measuring points is generally measured. This is detected for example by means of light barriers at the measuring points. For this purpose, there are windows in the line path at the measuring section or it will be Cable path with transparent walls used. Other sensors include conductivity probes, capacitance sensors or electrochemical sensors. The determined measured values are evaluated in one unit. In this case, an actual value (eg, actual value of the delivery rate per unit time) is determined, which is compared in a control unit with a predetermined desired value. The control unit regulates the power of the pump so that the setpoint is reached.

In the conduction path are advantageously one or more devices for the detection of foreign bodies in the pumping medium or bubbles in a liquid pumping media. These detection units are preferably arranged on capillaries, e.g. Photocells, light sensors or conductivity sensors. These test devices are particularly advantageously integrated in the calibration unit of a dosing unit. Advantageously, a measuring signal of the testing device is used to control or control the dosing process. For example, upon detection of foreign bodies or bubbles in a liquid to be dispensed, an alarm is triggered or a special control process is initiated at the affected dosing unit.

The surface of the conduit path and the pump, in particular the inner surface and the surfaces which come into contact with the pumping medium, is advantageously modified. Surface modification in the dosing system serves to reduce friction, improve cleanability and improve dosing. In particular in the region of the outlet opening, the surface of the conduit path for the medium to be metered (eg capillary made of plastic or glass) is modified, for example coated or surface-modified, so that a liquid bubbles off and drops are repelled at the outlet opening. This increases the precision of the dosage. The surface is rendered hydrophobic, for example by a coating, in particular a fluorosilane coating. Also advantageous is a modification of the surface by creating or applying a surface structure having liquid-repellent properties, in particular a nanostructured surface, for example a surface with so-called lotus effect. Particularly advantageous is a surface modification by combined creation of a hydrophobic and nanostructured surface.

The detachment of a liquid drop at the end of a metering operation is advantageously assisted by a shaker, vibrator or mechanical means (e.g., beater). The devices can be arranged in the area of the outgoing line or capillary. Very vorteihaft is a version that shakes the whole dosing, vibrating or vibrated. For example, a preferably controllable vibrator for a temporary use is mounted on or in the dosing.

The delivery rate of a micropump with piezo drive can be adjusted by setting suitable parameters such as frequency, amplitude and shape (sine, rectangle, triangle, etc.) of the control signal or the voltage for the pump drive. The adjustment of the delivery rate by means of a control and regulation is advantageously carried out during the metering operation.

The calibration unit is preferably arranged at the outlet of the pump.

The miniaturization of the pump (micro construction of the pump) allows the pump to be brought directly into the vicinity of the dosing and the way from the pump outlet to the output of the dosing unit can be made very small. The preferred metering with at least one metering unit with at least one micropump and immediately subsequent calibration, in particular the Meßkapillare at the output of the medium to be dispensed, allows a minimization of the path for the medium to be metered and thus a reduction of the dead volume and the total volume of the metering in the dosing system. It can thereby the required minimum amount of the metered medium and the amount for the ongoing operation of the dosage can be significantly reduced, so the yield in the dosage can be increased, which is particularly interesting in the dosage of expensive reagents. Dosing errors and hose-related errors in the Dosages that are common in conventional dosing systems with long hoses do not occur. The dosing system according to the invention is characterized by a high precision and reproducibility in the dosage.

Advantageously, several dosing units are arranged in one row or in several rows (array). This is advantageously done on a common carrier. The microstructure allows the construction of a dosing head with a large number of independent dosing units in the smallest of spaces.

The metering units and the built up from metering units

Dosing (dosing) are used very advantageous in the dosing of liquids in microtiter plates. The preferred dosing head for microtiter plates contains a dosing unit for each well of the microtiter plate.

Due to the bidirectionally operating pump (pump with reversing conveying direction), the metering units are also suitable for suction of media, in particular liquids. The dosing system can therefore be used advantageously for the filling and emptying of sample containers, in particular microtiter plates.

Pumps or pump arrangements with reversing conveying direction are advantageous in metering systems

A) to ensure a clean controlled media breakage without dripping with Preflow, b) to clean / rinse pumps and possibly hoses, c) to calibrate the flow of the pump via a capillary and d) emptying and filling microtiter plates to be able to.

The invention will be explained by way of examples in the drawing.

[0044] In the drawings:

Fig. 1a: highly simplified schematic of a piezoelectric

Micro diaphragm pump in cross section,

1 b: schematic representation of the pump of Fig. 1a during the suction of the medium (view in cross section),

1c: schematic representation of the pump of FIG. 1a during the ejection of the medium (view in cross section), FIG. 2a is a simplified schematic diagram of a piezoelectric micromembrane pump in cross section with alternative arrangement of the valves,

FIG. 2b shows a schematic representation of the pump of FIG. 2a during the aspiration of the medium (view in cross section), FIG.

2c: schematic representation of the pump of FIG. 2a during the ejection of the medium (view in cross section), FIG. 3: schematic representation of a metering unit with micropump and measuring capillary (view in cross section),

Fig. 4: schematic representation of a microvalve with slide, Fig. 5: schematic representation of a microvalve with rotatable core, Fig. 6: schematic representation of a micropump with slide, Fig. 7: schematic representation of a microvalve with valve flap, Fig. 8: schematic Illustration of a rotatable unidirectional micropump for bidirectional operation,

9 shows a schematic representation of a microvalve with a rotatable non-return valve,

10 shows a schematic representation of a metering system (metering head) with metering units with common base body and coupled valves of the metering units,

11: schematic of a dosing head in section, FIG. 12: schematic of a dosing system for microtiter plates with obliquely arranged micropumps, FIG.

Fig. 13: Schematic of a dosing system for microtiter plates with straight micropumps. The piezoelectric diaphragm pump 1 shown in FIG. 1 a has a base body or housing 2 with a housing lower part 2 b and an upper housing part 2 a, an input channel 8, an output channel 11, pump inlet valve 6 and pump outlet valve 7, a pump membrane 4 and a piezoceramic disk 3 (piezoelectric actuator). on. The micropump is similar in construction to the micropump described in DE 19720482 C5, to which reference is made, but differs in the type of valves used 6 and 7 and in the mode of operation. The illustration of the valves is greatly simplified and only symbolic. The valves are active valves (microvalves), for example micromembrane valves, in particular magnetic, pneumatic, hydraulic or preferably piezoelectrically adjustable valves. The main body 2 is usually made of one or more inert thermoplastics, such as polyphenylsulfone (PPSU). The pump diaphragm consists for example of glass, ceramic or plastic. The piezoelectric actuator 3 is fixed on the pump diaphragm 4. By deformation of the piezoelectric actuator 3, the pump diaphragm 4 is deflected, whereby an enlargement or reduction of the pump chamber volume is generated. In the position shown of piezoelectric actuator 3 and pump diaphragm 4 (fitting the base body 2), the pump chamber volume is reduced to a minimum. The channels 8, 9, 10 and 11 serve as a path for the pumping medium. Upper housing part 2a and lower housing part 2b are connected for example by gluing, welding or screwing.

The operation of the pump is shown in Fig. 1 b (suction phase) and Fig. 1c. In the suction phase (FIG. 1 b), an enlarged pump chamber volume 5 is created by curvature of the piezoactuator 3 between the upper housing part 2 a and pump diaphragm 4, the controlled inlet valve 6 being opened and the controlled output valve 7 being closed. The flow direction of the pumping medium is represented by an arrow in the input channel 8. In the ejection phase (FIG. 1 c), the curvature of the piezoactuator 3 is reduced. He moves to the top of the upper housing part 2a, whereby the pump chamber volume 5 is reduced. In this case, the controlled input valve 6 is closed and the controlled output valve 7 is opened.

By appropriate control of piezoelectric actuator 3 and the active

Valves 6 and 7, the pumping operation is carried out. The pump can bidirectionally promote the pumping medium due to the use of the active valves. This is of fundamental importance for the work of the dosing unit or dosing system. Figs. 2a-c are analogous to Figs. 1a-c and differ in the

Arrangement of the active valves 6 and 7. In Fig. 2a-c, the valves 6 and 7 next piezoelectric actuator 3 / pump diaphragm 4 are arranged in the upper housing part 2a, as well as the channels 8, 9, 10 and 11. Thus, only a simple Cover plate with possibly minor adjustments as housing base 2b needed.

Upper housing part 2a with the functional elements 3-11 could be arranged as a module one or more times on one or both sides of the lower housing part 2a, which now acts as a carrier. This enables space-saving multipump systems with one or two rows of pumps on one carrier. By combining several such carriers with rows of pumps, it is possible to realize arrays (series of rows) of pumps.

The diagram in Fig. 3 shows a simplified example of a

Dosing unit (view in cross section). The dosing unit comprises a conduit 16 (e.g., duct, tube, capillary, tube) for supplying the pumping medium to the pump 1 and a conduit 12 located at the outlet of the pump 1. In line 12 is contained as a separate part (for example capillary with measuring points 13, 14, 15 or sensors) or integrated a calibration device or calibration unit. The pumping medium exits at the line end 17. The line end 17 is preferably part of a measuring capillary or a measuring channel 12.

The preferred method for calibrating the pump 1 will be explained with reference to FIG. The calibration procedure requires a bi-directional pump. The calibration takes place during the operation of a metering unit with the pumping medium to be metered and is preferably automated. The calibration is a route with defined dimensions in a line 12, which is preferably arranged at the output of the pump 1. As a measuring path is advantageously a capillary (eg glass or plastic) used. The capillary extends advantageously over the entire or almost entire conduction path 12. In the preferred embodiment of the calibration unit, there are 3 measuring points 13, 14 and 15 at the measuring path. At the measuring points measured values are detected which indicate whether pumping medium is at the respective measuring point. To carry out the calibration, the measuring section must be emptied of the pumping medium, usually a liquid, in particular an aqueous sample with organic constituents, up to the measuring point 14. At this time, there is a gas, eg air, in the space of the line 12 from before the measuring point 14 to after the measuring point 15, usually up to the line end 17. This emptied state of the line 12 is either already (eg at the beginning with deflated dosing unit) or is achieved by means of the pump 1 and corresponding control of the valves 6, 7 by conveying the pumping medium to the measuring point 14. The actual measuring path for calibration is between the measuring points 14 and 15. After the pumping medium was brought in front of the measuring point 14 in a first step, the pump 1 is put into operation in a second step. This operating state of the pump 1 corresponds to the operation during the dosing process. After exceeding the pumping medium front of measuring point 15, the pump 1 is usually stopped. The times of passage of the pumping medium or the pumping medium front (usually a liquid meniscus in the capillary) at the measuring points 14 and 15 are detected. This is done, for example, using sensors such as photoelectric sensors, conductivity sensors or capacitance sensors. With the help of the defined inner volume of the capillary between the measuring points 14 and 15 and the detected time values, the delivery rate or the delivery volume per unit time and thus the pump delivery rate is determined by an evaluation unit which is part of a control unit, for example. This evaluation provides an actual value for the pump power. The determined actual value is compared in a control unit with a desired value in accordance with the desired metering quantity or the desired metering volume and the pump power is adjusted by the controller. (Change in the control of the piezo diaphragm pump used, for example by adaptation of frequency, amplitude and / or waveform such as sine, square, triangular shape of the voltage to supply the piezoelectric actuator the pump). Through this calibration and adaptation step, which is optionally repeated one or more times, the pump is optimally adjusted to the medium to be dosed. The pump or the precision of the pump is thus independent of the temperature, the viscosity and / or the surface tension of the pumping medium. The metering of a medium such as a liquid is done with the help of the calibration with high precision. Calibration based on bi-directional operation of the pump provides greater precision of fluid metering than with a unidirectional pump. In addition, the bidirectionality of the pump allows retraction of the pumping medium from the discharge end 17 after each metering step, whereby dripping of the pumping medium can be prevented very effectively. For this purpose, a slight withdrawal of the pumping medium from the outlet end 17 is generally sufficient. Furthermore, the pumps can be automatically cleaned by backwashing.

The calibration of the pump is particularly advantageous when several

Dosage units e.g. combined in a dosing head. The pumps are thus set or maintained during the metering operation to a uniform setpoint. This compensates for the usual deviations in the operating characteristics of the piezo actuators of the pumps.

A device or a sensor for the detection of foreign bodies or bubbles in the pumping medium is advantageously arranged in the region of the calibration unit on the line 12 or integrated in the calibration unit. Particularly advantageously, one or more measuring points 13, 14, 15 of the calibration unit are also used for the detection of foreign bodies or bubbles.

The calibration unit with at the measuring points 13, 14, 15 arranged

Sensors can thus be used not only for calibrating the flow rate of the pump 1, independent of external parameters such as temperature and independent of the properties of the pumped medium, but also for monitoring or monitoring the flow of the pumping medium. Length and lumen of the capillary preferably used in the region of the measuring section with the measuring points 13, 14, 15 are designed for the requirements of precision and delivery volume range.

The output line 12 is usually short. Typically, the length of the exit conduit 12 is less than 10 cm, typically less than 5 cm. The length depends essentially on the length of the measuring section of the calibration unit, which depends on the desired measurement accuracy.

The surfaces of the conduits 12, 16, the pump 1 and the outlet 17 which come into contact with the pumping medium are preferably surface-modified, e.g. hydrophobized and / or nanostructured (especially surface with lotus effect). This has advantages for the promotion of the pumping medium, for the cleaning of the dosing unit and the droplet detachment at the outlet opening 17 during the metering.

The detachment of liquid droplets at the outlet opening 17 is advantageously assisted by a device which causes the end of the line 12 to vibrate, leads to an abrupt rash of the line end or abuts the line end. The precision of the dosage can be increased by means of such a device.

In Fig. 4 is an example of serving as a valve shifter (slide 18 with passage openings 20, 20 ') in cross section. A movable slide 18 with one or two or more passage openings 20, 20 'serves to one or two or more lines 8, 8' (eg pump channels) to close or open, depending on the position of the slide 18. In the example shown, the Conduits 8 and 8 'in a coupled manner with the aid of the slide 18 is closed or opened. In the illustrated position of the spool 18, the passage in conduit 8 (eg, pump input port) is closed, while the passage in conduit 8 '(eg, pump exit port) is released. By moving the slider 18, the passage in the conduit 8 can be opened while the passage in the conduit 8 'is closed. The slider 18 is usually by a drive (eg electric motor or Electromagnet) adjusted. This is preferably done by means of a controller. Particularly advantageous is a coupling of the slider 18 (when used as opening and closing mechanism of the pump inlet channel and pump outlet channel) with the piezoelectric actuator of the pump 1 as a drive. This allows the valve functions at the pump inlet and pump outlet to be directly synchronized with the pumping process. This is shown using the example of FIG. 6.

Fig. 5 shows a microvalve with a rotatable core 19 with a

Through hole (cross section). The flow in the conduit paths 8, 8 'is adjusted by rotation of the rotary member 19, which has a through opening. Depending on the rotation of the rotary member 19 different parts of the line paths 8, 8 'connected to each other.

In Fig. 6, a pump 1 with slide 18 (suction) is shown. In the suction caused by curvature of the piezoelectric actuator 3 between the upper housing part 2a and pump diaphragm 4 an enlarged pump chamber volume 5, wherein at the position of the slide 18, the channels 8 and 9 are connected to the input of the pump 1 and the passage between the channels 10 and 11 at the output the pump 1 is interrupted. The flow direction of the pumping medium is represented by an arrow in the input channel 8. In the ejection phase, the slide 18 is brought into a position in which the channel 9 is closed and the channel 10 is open. Advantageously, the adjustment of the slider 18 is coupled to the deflection of the piezoelectric actuator 3. In another variant, instead of a slide, the entire, correspondingly adapted housing lower part 2b is moved to alternately close or open the pump inlet channel 8, 9 and pump outlet channel 10, 11.

In Fig. 7, an example of a valve with valve flap 21 is shown. The valve flap 21 is adjusted between the line paths 8, 8 '. Various switching states are shown in the left and right part of the figure. The valve flap 21 is e.g. Magnetically or adjusted by means of a drive.

Fig. 8 shows a simplified representation of the structure of a bidirectionally operating micropump by rotation of a unidirectional operating Micropump 1 with the passive valves 6 and 7, wherein the position of the valves with respect to the connecting lines 12 and 16 is reversed. Shown are the switching states a and b, which merge by rotation of the pump 1 by 180 ° into each other.

A sliding device as an alternative to the rotation of the pump is also possible.

In Fig. 9, a rotating device 19 is shown with integrated check valve 6 in the line 8 in the switching states a and b. The rotating device 19 is, for example, a rotary core with a passage in which a check valve 6 is arranged. By rotation of the rotary core 19 about the dashed axis of rotation by 180 °, the check valve 6 is reversed in the line 8. The rotation of the rotator 19 is e.g. with the usual drives and is usually controlled.

Fig. 10 shows as an example a metering system 22 with the pumps 1, V, 1 "and 1" '. A slider 18 is provided with through holes having check valves with changing passage direction. Depending on the position of the slide, a certain forward direction is set at the pump inputs to the supply lines 16. A rotating device 19 with check valves ensures at the pump outputs to the lines 12 for a particular forward direction.

In the example, turning device 19 and sliding device 18 are shown united. This is for explanation. In practice, the metering system 22 will only have one way of adjusting the direction of passage at the pump inlet and pump outlet.

Figures 4 to 10 illustrate that multiple valves may be coupled. They can be connected to each other in such a way that only one drive is necessary.

Since inlet and outlet valves are alternately open or closed for a pump, this can be represented by a shuttle valve which is controlled pneumatically, mechanically, electromechanically, by a separate piezoactuator or by the pump drive. The shuttle valve can be switched linearly (FIG. 4), by rotation (FIG. 5) or by folding over (FIG. 7).

The arrangement of outlet and inlet immediately next to each other is particularly favorable for the application of a shuttle valve while saving space.

Another option is the use of a passive pump

Valves whose pump body (with the valves) is rotatably mounted. As a result, the pumping direction is also reversible (FIG. 8).

Common to all valve solutions is the option, analogous to a triple or

Multi-way cock, multiple inlet and / or outlet channels interconnect.

Fig. 11 shows a metering system 22 with two metering units, each with a pump 1, the supply line 16, an active input valve 6, an active output valve 7, a control electronics 24 for valves and pump drive, power supply 25, a control line 26, a light guide 27 and 28 and a calibration unit with the measuring points 13, 14, 15 on the output line 12. As a measuring path is preferably a capillary or a part of a capillary. With an inner diameter of 0.2mm and a length of 20mm results in a test volume of 2.5μl. The delivery rate of the pump 1 results from the determined time duration, which is needed to fill the test volume. Depending on the power of the pump and the desired precision, the length of the test track or the test volume can be adjusted. Well suited is a glass capillary. Advantageously, the capillary is used as output line 12. That is, the capillary is connected directly to the pump outlet. The length of the capillary from the pump outlet to the outlet opening 17 is generally in the range of 10 to 40 mm, in particular in the range of 20 to 30 mm. In the example shown, the optical fiber 27 serve as a light transmitter and the optical fiber 28 as a receiver. A portion of the light guides 27 and 28 is arranged along the capillary or the measuring path on opposite sides of the transparent capillary. Both light guides 27, 28 carry notches or openings at the measuring points 13, 14, 15. In the Optical fiber 27 is fed, for example, white light. At the openings are advantageous filters which are transparent to different wavelengths of light (eg yellow, green, red) attached, for example, a color layer. The optical waveguide 28, which, like the transmitting optical waveguide 27, carries corresponding filters at the measuring points, serves as a receiver and is connected to a light sensor. The measuring arrangement of the calibration unit in the form of light barriers can be built in this way space saving. Alternatively, individual miniaturized light barriers can be used at the measuring points 13, 14, 15. The calibration is preferably carried out automatically, for example with the aid of a controller for the dosing unit.

An exchangeable connection plate 23 allows easy replacement of the dosing head 22. The pumps 1 e.g. have a common pump body or are arranged as individual pumps on a support. The arrows marked a and b indicate a cut surface, as shown in the following figures.

The preferred dosing head 22 is designed for 96-well microtiter plates. A dosing head for larger microtiter plates (e.g., 384, 1536, 6144 wells or wells) is readily constructable. The dosing head is suitable for all microtiter plates with fewer wells than those for which the dosing head is designed.

The dosing head integrates micropumps into a unit on the surface of a microtiter plate (eg 8.5x12.5 cm). The pumps are advantageously arranged in layers in diagonal-vertical planes (see FIG. 12). The pumps are sufficient in the version described here a width of about 13mm. The pump housings are manufactured inexpensively, for example, in injection molding technology from plastic and assembled in layers. Membranes, capillaries, optics and electrical connections are inserted in the individual levels, as far as they are not already part of the molded part. The finished dosing head housing is connected via a plug connection with the control and evaluation electronics. Supply line (s) for the pumped medium are connected via an exchangeable plate 23 with the dosing head 22, so that in the preferred Dosing head 22 either 1 to 96 different media can be dosed or promoted at the same time.

The dosing head 22 can operate each dosing unit separately with a separate medium and its own delivery volume.

The pumps 1 in the dosing head 22 are located directly above the microtiter plate 29 to be filled. The pumps 1 are ideally arranged at the same height. This can be deviated from lack of space. The dosing head 22 itself can be positioned above the microtiter plate as desired (3-axis controllable mount). It is also possible that the dosing head with the cannulas (lines 12) dips into the wells 30 of the microtiter plate 29 or moves synchronously to the filling level.

Advantageously, the dosing head 22 is used for coating microtiter plates 29. Simplified, to coat a microtiter plate 29, the cavities 29 are filled with a solution containing the chemical for a coating. After an incubation period, during which the chemical docks to the plate surface, the supernatant, the solvent, is removed. This can be realized with the dispensing head (dosing head 22) without retooling by dipping the dosing head 22 with the cannulas (lines 12) into the wells 30 after the precise dosing and sucks the solvent. The dosing head 22 is used here for filling and emptying of microtiter plates.

A complete Dispensiergerät (Dispensiermodul) carries the dosing head 22, the interface to the controller, a reading station to uniquely identify the microtiter plate, the air-conditioned master chamber with swivel table, supply of cleaning solutions and a vessel for spent rinse solution. All processes are monitored by sensors, the filling of the microtiter plate is carried out according to predetermined parameters automatically with a performance of about 2000 microtiter plates per hour (1 OOμl water per well). This is followed by automatic cleaning of the wetted parts.

Fig. 12 shows the arrangement of individual micropumps 1 over one

Microtiter plate 29. Each cavity is 30 (well) of the microtiter plate 29 associated with a micropump 1. The oblique or diagonal arrangement (relative to the edges of the microtiter plate 29) of the micropumps 1 is particularly space-saving. FIG. 13 shows a corresponding metering system with micropumps 1 arranged just in relation to the edges of the microtiter plate 29. FIGS. 12 and 13 illustrate that the metering system or the metering head with the metering units can be adapted to the dimensions of the microtiter plate and has a base surface comparable in size. The micropumps 1 are used very close to the microtiter plate 29.

Claims

claims

1. dosing system (22) with at least one bidirectionally operable micropump (1) or an arrangement with at least one micropump (1), which allows a bidirectional pumping operation, or at least one rotatable or displaceably arranged unidirectionally operating micropump (1) or with one or more Pairing oppositely connected unidirectional micropumps (1).

2. metering system (22) according to claim 1, characterized in that the metering system (22) has a plurality of independently operable metering units or at least one metering unit with a measuring arrangement for calibrating the micropump (1) or for monitoring the pumping operation or the operation of the micropump (1) or with a measuring arrangement for detecting measured values which relate to a property or a state of the pumping medium, or with a measuring arrangement for monitoring a dosing process.

3. dosing system (22) according to claim 1 or 2, characterized in that the micropump (1) at least one active inlet valve (6) and at least one active outlet valve (7) or a valve arrangement for bidirectional operation of the micropump (1) or a sliding device (18) or rotating device (19) for opening and closing of conduit paths or channels (8, 9 and 10, 11) are associated or the dosing (22) coupled valves (6, 7) at input (8) and output (11) the micropump (1) or coupled valves (6, 7) of two or more dosing units or coupled valve and micropump drives.

4. dosing system (22) according to one of claims 1 to 3, characterized in that the dosing system (22) includes a calibration unit having a defined measuring path or a defined measuring channel or a measuring path or a measuring channel with a measuring device.

5. dosing system (22) according to claim 4, characterized in that the measuring device contains at least two, preferably three or more measuring points (13, 14, 15) with at least one sensor.

6. dosing system (22) according to one of claims 1 to 5, characterized in that the metering system (22) for each micropump (1) a Meßdatenerfassungs- and -auswertungseinheit or the dosing (22) for each micropump (1) a Meßdatenerfassungsungs- and -auswertungseinheit and a central control unit.

7. dosing system (22) according to any one of claims 1 to 6, characterized in that the dosing system (22) contains arranged in one or more rows of dosing units.

8. dosing system (22) according to any one of claims 1 to 7, characterized in that the dosing system (22) comprises a dosing with vibrating, vibrating or a mechanical device for droplet detachment in the dosage.

9. A method for operating a dosing system (22) with a calibration unit, characterized by the detection of the pump characteristic by measuring the velocity of the pumping medium between two measuring points (14, 15) comprising one or more sensors in a measuring path such as a Meßkapillare or a Measuring channel and automatic adjustment of the pump power to a setpoint based on the detected and evaluated measured values at the measuring points.

10. Use of one or more micropumps (1) with at least one active inlet valve (6) and at least one active outlet valve (7) or a suitable valve arrangement for bi-directional delivery of a liquid or gaseous medium or with a device for achieving bidirectional delivery of a liquid or gaseous medium in a metering, application, coating, filling and / or emptying system for microtiter plates (29), sample or reagent vials, sample or reagent vials, flat vials for sample or reagents, vials with or without vials for specimens or reagents, chip cards or other specimen or reagent receptacles.