EP3663001B1 - Pipetting method with throttle position in the pipette channel - Google Patents
Pipetting method with throttle position in the pipette channel Download PDFInfo
- Publication number
- EP3663001B1 EP3663001B1 EP20152812.2A EP20152812A EP3663001B1 EP 3663001 B1 EP3663001 B1 EP 3663001B1 EP 20152812 A EP20152812 A EP 20152812A EP 3663001 B1 EP3663001 B1 EP 3663001B1
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- EP
- European Patent Office
- Prior art keywords
- pipetting
- dosing liquid
- dosing
- working fluid
- pressure
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- 239000007788 liquid Substances 0.000 claims description 154
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- 230000003247 decreasing effect Effects 0.000 claims 1
- 238000005406 washing Methods 0.000 description 37
- 230000001105 regulatory effect Effects 0.000 description 5
- 230000008878 coupling Effects 0.000 description 3
- 238000010168 coupling process Methods 0.000 description 3
- 238000005859 coupling reaction Methods 0.000 description 3
- 238000004140 cleaning Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 238000004891 communication Methods 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
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- 238000003825 pressing Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
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Classifications
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/02—Burettes; Pipettes
- B01L3/021—Pipettes, i.e. with only one conduit for withdrawing and redistributing liquids
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/14—Process control and prevention of errors
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/14—Process control and prevention of errors
- B01L2200/148—Specific details about calibrations
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/14—Means for pressure control
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2400/00—Moving or stopping fluids
- B01L2400/04—Moving fluids with specific forces or mechanical means
- B01L2400/0475—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure
- B01L2400/0487—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure fluid pressure, pneumatics
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2400/00—Moving or stopping fluids
- B01L2400/06—Valves, specific forms thereof
Definitions
- the present invention relates to a pipetting device at least for dispensing dosing liquid by increasing the pressure of a working fluid, comprising a dosing liquid receiving space which is at least partially filled with working fluid and has a pipetting opening as a first flow cross-section constriction, through which dosing liquid flows out of the dosing liquid chamber as a function of the pressure of the working fluid.
- Receiving space can also be dispensed, and a pressure changing device which is designed to change the pressure of the working fluid in the dosing liquid receiving space.
- the pipetting opening generally represents a narrowest flow cross-section when the dosing liquid is expelled from the dosing-liquid receiving space, the pipetting opening forms a first flow cross-section constriction of the pipetting device discussed here.
- Pipetting devices of the type mentioned at the outset are used, for example, as washing heads, in which the dosing liquid receiving space is filled or at least partially filled by a dosing liquid feed and then expelled from the latter by the described dispensing by means of excess pressure of the working fluid relative to the ambient pressure of the liquid receiving space.
- the dosing liquid is a washing liquid which is dispensed through the pipetting opening in order to clean an object provided underneath, for example a container, with the washing liquid.
- the washing liquid is a washing liquid which is dispensed through the pipetting opening in order to clean an object provided underneath, for example a container, with the washing liquid.
- washing heads in addition to or as an alternative to the aforementioned inflow, by aspiration known per se, i.e. by means of a negative pressure of the working fluid in the dosing liquid receiving space, through the pipetting opening and into the dosing liquid receiving space record, tape.
- aspiration known per se i.e. by means of a negative pressure of the working fluid in the dosing liquid receiving space, through the pipetting opening and into the dosing liquid receiving space record, tape.
- this object is achieved by a pipetting method in which the pipetting device has a throttle point as a further flow cross-section constriction in a pipetting channel that is operationally filled with working fluid, fluid-mechanically between the dosing liquid receiving space and the pressure-changing device, which is dimensioned in such a way that a ratio of a flow resistance ( R 1 ) of the pipetting opening for dispensed dosing liquid to a flow resistance (R 2 ) of the throttle point for working fluid, which flows through the throttle point when dispensing the dosing fluid, is less than 0.5, preferably less than 0.3, particularly preferably less than 0.225, the flow resistances of the respective flow cross-section constriction being calculated taking into account the product of the viscosity of the medium of working fluid and dosing liquid associated with the respective flow cross-section constriction t and the characteristic length of the associated flow area restriction divided by the fourth power of the characteristic dimension of the flow area of the associated flow area restriction.
- the ratio of the flow resistances mentioned which is decisive for the functioning of the solution presented here, means that the throttle point through which the working fluid, usually a gas, flows has a significantly smaller cross-sectional opening than the pipetting opening.
- a liquid is also used as the working fluid.
- the viscosity to be used is the respective dynamic viscosity, which is generally denoted in the literature by the symbol “ ⁇ ”.
- the designated characteristic length of the associated cross-sectional constriction can be the length of the cylindrical duct or, in the case of ducts tapering conically towards the flow cross-sectional constriction, it can be the length of the duct section in which the flow cross-sectional area of the duct, starting from the smallest flow cross-sectional area in the throttle point or in the Pipette opening doubled. If the flow cross-sectional area does not double over the maximum ascertainable length of the channel, the entire length of the channel can be used as the characteristic length.
- the characteristic dimension of the flow cross-section can be the diameter for circular flow cross-sections, an edge length for square flow cross-sections, an arithmetic mean of long and short edge length for rectangular flow cross-sections, an arithmetic mean of long and short axis for elliptical flow cross-sections, etc. If the flow cross section changes over the length of the flow cross section constriction, the smallest flow cross section occurring in the flow cross section constriction should be used.
- the present invention preferably relates to a washing head pipetting device already mentioned at the outset, which is designed to deliver washing liquid as dosing liquid in precise doses.
- washing-head pipetting devices are generally used to clean objects held in sample containers, such as so-called "wells", by dispensing a precisely metered quantity of washing liquid.
- the precise dosing of the washing liquid is of great importance in order to bring about a predetermined cleaning state.
- the volume flow of washing liquid is set in such a way that the washing performance is as great as possible, but the duration of the washing process is as short as possible. If washing liquid is pipetted incorrectly, there may be a risk of so-called “overwashing”, which can lead to elements being undesirably dissolved on the object to be washed and/or in the sample container.
- washing head pipetting device aspirates the washing liquid as dosing liquid via the pipetting opening into the dosing liquid receiving space, for reasons of simpler handling the dosing liquid receiving space of a preferred washing head pipetting device is supplied with washing liquid as dosing liquid through a dosing liquid inlet.
- the washing head pipetting device discussed here can therefore have a dosing liquid inlet through which the dosing liquid receiving space can be at least partially filled with dosing liquid, ie with washing liquid in the present application.
- the dosing liquid feed opens into the dosing liquid receiving space.
- the dosing liquid inlet is generally provided as a channel formed separately from the dosing liquid receiving space.
- the washing head pipetting device can have a dosing liquid pump in a further advantageous embodiment of the present invention, with which dosing liquid, in particular washing liquid as dosing liquid, can be conveyed along the dosing liquid feed into the dosing liquid receiving space.
- a valve can be provided on the dosing liquid feed, in particular in an area close to the mouth, which can be opened and closed by a control device.
- the dosing liquid pump can also be operated with this or another control device.
- the dosing liquid pump mentioned above does not have to be provided, since the dosing liquid, in particular as washing liquid, is pumped from a geodetic over the mouth of the dosing liquid inlet into the dosing liquid receiving space gravity can be promoted. Then, however, the valve mentioned above is absolutely necessary.
- a washing head pipetting device In order to increase the washing efficiency of a washing head pipetting device, it can have a plurality of pipetting channels which are provided essentially parallel to one another, so that a plurality of objects corresponding to the plurality of pipetting channels can be subjected to cleaning by the washing head pipetting device at the same time.
- the present invention is particularly advantageous in the case of a multi-channel pipetting device, since the invention can ensure that each pipetting channel can deliver essentially the same amount of dosing liquid with a high level of accuracy, although the individual pipetting channels, be it due to manufacturing tolerances coupled to pipetting tips it can have different geometric shapes due to different levels of deposits on the pipetting openings, be it a combination of these or other causes, so that without the present invention being used, the individual pipetting channels of a multi-channel pipetting head would deliver different pipetting results with the same operating parameters of the pipetting device.
- the principle of throttling the working fluid flow between the dosing liquid receiving space and the pressure-changing device can be used successfully not only in the dispensing of dosing liquids, but also in their aspiration.
- the dosing behavior can be insensitive to deposits and other flow cross-section changes in the pipette opening.
- the present invention relates in particular to those pipetting devices which, in addition to the above-mentioned dispensing, are also used to aspirate metering liquid, in this case by reducing the Pressure of the working fluid in the dosing liquid receiving space are formed.
- dosing liquid when dosing liquid is aspirated, it can be aspirated through the pipetting opening into the dosing liquid receiving space as a function of the pressure of the working fluid.
- the throttle point recommended here in the pipetting channel is fluid-mechanically between the pressure-changing device and the dosing liquid receiving space, within certain limits, also suitable for equalizing the dosing behavior across dosing liquids with different viscosities.
- the dosing behavior of these pipetting devices is independent of the viscosity of the dosing liquid within certain limits.
- Working fluids can be used successfully here whose dynamic viscosity does not exceed the value of 0.00003 Nsm -2 , preferably 0.00002 Nsm -2 , particularly preferably 0.0000175 Nsm -2 .
- the dynamic viscosity is meant.
- the throttle point can also be considered to equip the throttle point with a flow cross section that can be changed as desired, for example by changing the gap width of an annular gap or with a mechanism similar to that used to adjust the aperture on mechanical cameras.
- the flow cross section of the throttle point can thus be adapted to the working fluid used in each case and/or the dosing liquid to be metered in each case.
- the pipetting channel can be adjusted between a blocked position, in which a working fluid flow in the pipetting channel is prevented, and an open position, in which a working fluid flow in the pipetting channel is permitted valve.
- the valve can initially be closed be maintained until the working fluid has been brought to a desired pressure in an area at least close to the pressure-changing device.
- the throttle point can be variable down to a cross section of zero, so that the valve described here can be implemented using an advantageously small number of components through the throttle point described above with a variable flow cross section.
- a quantity of liquid can be metered with high precision in a manner known per se by intermittently opening and closing the valve.
- At least one reservoir of working fluid that is under a system pressure can be provided as the pressure-changing device. More precisely, in order to carry out both aspiration and dispensing processes on one and the same pipetting channel, a dispensing reservoir under a first system pressure and an aspiration reservoir under a second system pressure can be provided, which can optionally be connected to the pipetting channel in a pressure-transmitting manner and are separable therefrom, wherein the first system pressure is greater than an ambient pressure of the pipetting device and the second system pressure is smaller than the ambient pressure.
- the ambient pressure of the dosing liquid receiving space does not exceed an overpressure of 1.5 bar, preferably 1.2 bar, particularly preferably 1.0 bar.
- an overpressure of 1.5 bar preferably 1.2 bar, particularly preferably 1.0 bar.
- Higher pressure differences between the system pressure and the ambient pressure can lead to highly turbulent flows of the working fluid through the throttling point, which under certain circumstances can impair the effect of the present invention.
- the pressure-changing device has a discontinuously or continuously operating pump, optionally in interaction with a valve arrangement that is arranged in the conveying path of the pump and can be selectively opened and closed.
- a valve arrangement that is arranged in the conveying path of the pump and can be selectively opened and closed.
- the pressure changing device has a piston-cylinder device with a cylinder extending along a cylinder axis and with a piston accommodated therein so that it can move along the cylinder axis, with the cylinder and piston delimiting at least one working volume , which can be changed relative to the cylinder by a relative movement of the piston and which is or can be brought into fluid communication with the pipetting channel.
- the piston-cylinder arrangement represents the most common design of the pressure-changing device in pipetting devices. It also offers the possibility of very precise pressure control through the use of small piston areas and relatively long piston strokes.
- the pipetting device can also be a manually actuated pipetting device as intended, in which case the piston in particular can then be moved relative to the cylinder by manual actuation.
- This actuation can be immediate, ie by pulling it out or pressing in the piston by hand, or can take place indirectly, for example by tensioning a spring which drives a relative movement between the piston and the cylinder after it has been triggered.
- the manually operable pipetting device preferably has only exactly one pipetting channel for the most precise possible dosing.
- Manually operable as intended is not intended to cover cases that are generally operated by a motor or otherwise automatically and can only continue to be operated by manual emergency actuation in the event of a power supply failure.
- the dosing liquid receiving space and the pipette opening are formed on a pipette tip that is separate from the pipette channel that has the throttle point and can be optionally connected to and/or separated from this pipette tip are.
- outlets provided rigidly with the pipetting device so-called “washing tubes”, are preferred for the aforementioned washing head pipetting device.
- FIG 1 an embodiment of a pipetting device according to the invention shown in a roughly schematic manner is generally denoted by 10 .
- the pipetting device 10 comprises a pipetting channel 12 to which a pipetting tip 14 is detachably coupled in a manner known per se.
- the pipetting channel 12 has a cylinder section 16 in which a piston 18 can be moved along a longitudinal axis which coincides with the cylinder axis Z L of the pipetting device 10 can be adjusted relative to the cylinder section 16 via a piston rod 20 by a motor 22 .
- the motor 22 is controlled by a control/regulating unit 24, for example as a function of the detection signal from a pressure sensor 26, which detects the pressure of a working fluid, such as air, in a working chamber 28 whose volume is variable as a result of the movement of the piston 18.
- a control/regulating unit 24 for example as a function of the detection signal from a pressure sensor 26, which detects the pressure of a working fluid, such as air, in a working chamber 28 whose volume is variable as a result of the movement of the piston 18.
- the pipette tip 14 which can be detached from the pipette channel 12 in a manner known per se by means of an ejector 30 that is movable along the longitudinal axis L of the pipette device 10 relative to the cylinder section 16, has a coupling region 32 designed for coupling to the pipette channel 12, a figure 1 example shown, has a conically extending wall area 34 and a pipetting opening 36, through which a dosing liquid, depending on the pressure of a working fluid with which a dosing liquid receiving space 38 surrounded by the wall area 34 and optionally also by the coupling area 32 is at least partially filled, into the dosing liquid -Receiving space can be aspirated and dispensed from this.
- the assembly of cylinder 16 and piston 18 forms a pressure changing device 40 for changing the pressure of the working fluid in the dosing liquid receiving space 38.
- the throttle point 42 can also have a valve 44 with which the throttle point 42 can be completely closed in order to interrupt a pressure propagation of the working fluid pressure from the working chamber 28 into the dosing liquid receiving chamber 38 .
- the valve 44 can preferably also be actuated by the control/regulating device 24 .
- ⁇ Pof is the dynamic viscosity of the medium flowing through the pipetting opening 36, i.e. the dosing liquid
- I Pof is a characteristic length of an outlet end of the pipetting tip 14 leading to the pipetting opening 36
- d Pof is a characteristic dimension of the flow cross section of the pipetting opening 36, in the present standard case a circular pipetting opening is the diameter of the pipetting opening 36 .
- the characteristic length I is the length that the exit end of the pipette tip 14 has, starting from the pipette opening 36 to the point at which the flow cross section of the pipette tip 14 has twice the surface area of the pipette opening 36.
- the characteristic length of an outlet area that tapers conically or in some other way towards the respective flow cross-section constriction with the narrowest flow cross-section can be assumed to be the length that exists between the respective flow cross-section constriction and a flow cross-section whose diameter is ⁇ 2 times the diameter of the flow cross-section constriction.
- the ratio of the two flow resistances at the throttle point 42 and the pipette opening 36 is a ratio of 0.5, preferably does not exceed 0.3, particularly preferably 0.225
- the dispensing behavior of the pipette tip 14, which can also be rigidly connected to the pipette channel 12 is largely independent of changes in the flow cross section, for example due to deposits of dried and/or crystallized dosing liquid.
- the dosing behavior changes with increasing narrowing of the pipetting opening 36 from below a critical degree of narrowing, even despite the provision of the throttle point 42 in the pipetting channel 12 fluid-mechanically between the pressure varying device 40 and the dosing liquid receiving space 38.
- the limit from which the influences of such deposits can of the pipetting opening 36 or in a region close to the pipetting opening 36 during dispensing, can be pushed further in the direction of a reduction in the cross-section of the pipetting opening 36 .
- the aspiration and dispensing behavior of the pipetting device can even be independent of the viscosity within certain limits used dosing liquid are made, so that with one and the same pipetting device 10 and one and the same operating parameters different viscous dosing liquids can be dosed the same. This considerably simplifies the operation of pipetting devices.
- the present invention can be used in particular for dosing tasks which a pipetting device 10 has to fulfill as a so-called “washing-head pipetting device” if this washing liquid is to be dispensed in precise doses as dosing liquid.
- washing head pipetting devices can be used to clean objects 37 in sample containers 39 or sample containers 39 alone, which are usually located below the pipetting opening 36, in a defined manner by dispensing a measured amount of washing liquid as dosing liquid.
- such a washing head pipetting device 10 can have a dosing liquid inlet 50 which, starting from a dosing liquid reservoir 52 , can open out at an orifice 54 into the dosing liquid receiving space 38 .
- the dosing liquid receiving space can advantageously be filled with dosing liquid (then in the form of washing liquid) through the dosing liquid inlet 50 so that the dosing liquid does not have to be aspirated through the pipetting opening 36 in this case.
- the dosing liquid in the dosing liquid reservoir 52 can be conveyed by a pump 56, which can also be controlled by the control/regulating device 24, via the dosing liquid inlet 50 into the dosing liquid receiving space 38.
- a valve 58 can also be provided on the dosing liquid inlet 50 which can be opened and closed by the control/regulating device 24 .
- a suitable program in the control/regulating device can initially build up a predetermined pressure in the dosing liquid inlet 50 by operating the pump 56 with the valve 58 closed, whereupon the valve 58 is opened for a predetermined time and then closed again.
- the valve 58 is preferably arranged at the orifice 54 or, in relation to the total length of the dosing liquid feed, close to the orifice 54.
- the distance of the valve 58 from the orifice 54 should preferably not exceed 5% of the total length of the dosing liquid feed 58 .
- the pipetting device 50 in particular as a washing-head pipetting device 10, can have further pipetting channels in addition to the pipetting channel 12 shown, which are configured essentially identically to the pipetting channel 12 shown, so that the pipetting channel shown in 1 illustrated pipetting channel 12 is described as an example for all pipetting channels of a multi-channel pipetting device.
- the dosing liquid feeds 50 to each pipetting channel 12 can then be connected to a common dosing liquid reservoir 52 via a common pump 56 .
- all piston rods 20 of the individual pipetting channels 12 can be adjusted by a common motor 22 .
- each pipetting channel has its own motor 22, its own pump 56 and/or its own supply of dosing liquid 52.
- the fixing means 60 is intended to indicate that the pipette tip 34 can be coupled to the pipette channel 12 as a washing tube permanently and not detachably.
- the washing tube can also be designed in one piece with a tube of the pipetting channel, for example with the cylinder section 16.
Description
Die vorliegende Erfindung betrifft eine Pipettiervorrichtung wenigstens zur Dispensation von Dosierflüssigkeit durch Erhöhung des Drucks eines Arbeitsfluids, umfassend einen wenigstens teilweise mit Arbeitsfluid gefüllten Dosierflüssigkeits-Aufnahmeraum mit einer Pipettieröffnung als einer ersten Strömungsquerschnittsverengung, durch welche hindurch Dosierflüssigkeit in Abhängigkeit vom Druck des Arbeitsfluids aus dem Dosierflüssigkeits-Aufnahmeraum hinaus dispensierbar ist, und eine Druckveränderungsvorrichtung, welche dazu ausgebildet ist, den Druck des Arbeitsfluids im Dosierflüssigkeits-Aufnahmeraum zu verändern.The present invention relates to a pipetting device at least for dispensing dosing liquid by increasing the pressure of a working fluid, comprising a dosing liquid receiving space which is at least partially filled with working fluid and has a pipetting opening as a first flow cross-section constriction, through which dosing liquid flows out of the dosing liquid chamber as a function of the pressure of the working fluid. Receiving space can also be dispensed, and a pressure changing device which is designed to change the pressure of the working fluid in the dosing liquid receiving space.
Derartige Pipettiervorrichtungen sind im Stand der Technik hinreichend bekannt. Bei der Dispensation von Dosierflüssigkeit wird in an sich bekannter Weise eine in einem Dosierflüssigkeits-Aufnahmeraum vorhandene Dosierflüssigkeit durch Erhöhung eines Drucks eines Arbeitsfluids, welches sich ebenfalls in dem Dosierflüssigkeits-Aufnahmeraum befindet, durch eine Pipettieröffnung des Dosierflüssigkeits-Aufnahmeraums ausgeschoben.Such pipetting devices are well known in the prior art. When dosing liquid is dispensed, a dosing liquid present in a dosing liquid accommodating space is pushed out through a pipetting opening of the dosing liquid accommodating space by increasing the pressure of a working fluid which is also located in the dosing liquid accommodating space.
Da die Pipettieröffnung in der Regel einen engsten Strömungsquerschnitt beim Austreiben der Dosierflüssigkeit aus dem Dosierflüssigkeits-Aufnahmeraum darstellt, bildet die Pipettieröffnung eine erste Strömungsquerschnittsverengung der vorliegend diskutierten Pipettiervorrichtung.Since the pipetting opening generally represents a narrowest flow cross-section when the dosing liquid is expelled from the dosing-liquid receiving space, the pipetting opening forms a first flow cross-section constriction of the pipetting device discussed here.
Pipettiervorrichtungen der eingangs genannten Art werden beispielsweise als Waschköpfe verwendet, bei welchen der Dosierflüssigkeits-Aufnahmeraum durch einen Dosierflüssigkeits-Zulauf gefüllt oder wenigstens teilweise gefüllt und anschließend durch die beschriebene Dispensation mittels Überdruck des Arbeitsfluids bezogen auf den Umgebungsdruck des Flüssigkeits-Aufnahmeraums aus letzterem ausgetrieben wird.Pipetting devices of the type mentioned at the outset are used, for example, as washing heads, in which the dosing liquid receiving space is filled or at least partially filled by a dosing liquid feed and then expelled from the latter by the described dispensing by means of excess pressure of the working fluid relative to the ambient pressure of the liquid receiving space.
Bei diesen Waschköpfen ist die Dosierflüssigkeit eine Waschflüssigkeit, welche durch die Pipettieröffnung hindurch abgegeben wird, um einen darunter vorgesehenen Gegenstand, etwa einen Behälter, mit der Waschflüssigkeit zu reinigen. Auch hierbei kommt es auf eine korrekte Bemessung der abgegebenen Menge an Waschflüssigkeit an.In the case of these washing heads, the dosing liquid is a washing liquid which is dispensed through the pipetting opening in order to clean an object provided underneath, for example a container, with the washing liquid. Here, too, it is a question of correctly measuring the amount of washing liquid that is dispensed.
Grundsätzlich soll jedoch auch nicht ausgeschlossen sein, dass Waschköpfe die Dosierflüssigkeit, also etwa Waschflüssigkeit, zusätzlich oder alternativ zu dem zuvor genannten Zulauf durch an sich bekannte Aspiration, also mittels eines Unterdrucks des Arbeitsfluids im Dosierflüssigkeits-Aufnahmeraum durch die Pipettieröffnung hindurch in den Dosierflüssigkeits-Aufnahmeraum aufnehmen. Aus dem Stand der Technik bekannte Systeme werden in
Ein Problem der eingangs genannten Pipettiervorrichtung, insbesondere in ihrer Ausgestaltung als Waschkopf, liegt darin, dass sich durch das wiederholte Austreiben von Dosierflüssigkeit durch die Pipettieröffnung an dieser oder an einem Kanal, welcher zur Pipettieröffnung führt, Ablagerungen bilden, welche den Strömungsquerschnitt der Pipettieröffnung bzw. des zur Pipettieröffnung führenden Kanals verändern. Hierdurch kommt es zu Veränderungen im Dosierverhalten, so dass nach einiger Betriebszeit im Wesentlichen baugleiche Pipettiervorrichtungen, welche mit der gleichen Dosierflüssigkeit und ansonsten gleichen Betriebsparametern betrieben werden, unerwünschterweise unterschiedliches Dosierverhalten zeigen können.One problem with the pipetting device mentioned at the outset, particularly when it is designed as a washing head, is that deposits form on the pipetting opening or on a channel leading to the pipetting opening due to the repeated expulsion of dosing liquid through the pipetting opening, which deposits reduce the flow cross-section of the pipetting opening or of the channel leading to the pipette opening. This leads to changes in the dosing behavior, so that after a certain period of operation, pipetting devices that are essentially identical in construction and are operated with the same dosing liquid and otherwise the same operating parameters can undesirably exhibit different dosing behavior.
Es ist daher Aufgabe der vorliegenden Erfindung, eine Pipettierverfahren der eingangs genannten Art derart weiterzubilden, dass ihr Dosierverhalten unempfindlicher gegen Veränderungen des Strömungsquerschnitts der Pipettieröffnung bzw. des zur Pipettieröffnung führenden Kanals des Dosierflüssigkeits-Aufnahmeraums gemacht wird, so dass mögliche oder sogar wahrscheinliche Ablagerungen an der Pipettieröffnung das Dosierverhalten der Pipiettiervorrichtung nicht oder zumindest in geringerer Weise als bisher beeinflussen.It is therefore the object of the present invention to develop a pipetting method of the type mentioned at the outset in such a way that its dosing behavior is made less sensitive to changes in the flow cross section of the pipetting opening or the channel of the dosing liquid receiving space leading to the pipetting opening, so that possible or even probable deposits on the Pipetting not affect the dosing behavior of the pipetting device, or at least to a lesser extent than before.
Diese Aufgabe wird gemäß der vorliegenden Erfindung gelöst durch ein Pipettierverfahren, bei welcher die Pipettiervorrichtung in einem betriebsmäßig mit Arbeitsfluid gefüllten Pipettierkanal fluidmechanisch zwischen dem Dosierflüssigkeits-Aufnahmeraum und der Druckveränderungsvorrichtung eine Drosselstelle als weitere Strömungsquerschnittsverengung aufweist, welche derart dimensioniert ist, dass ein Verhältnis eines Strömungswiderstands (R1) der Pipettieröffnung für dispensierte Dosierflüssigkeit zu einem Strömungswiderstand (R2) der Drosselstelle für Arbeitsfluid, welches die Drosselstelle bei der Dispensation des Dosierfluids durchströmt, kleiner als 0,5, vorzugsweise kleiner als 0,3, besonders bevorzugt kleiner als 0,225 ist, wobei die Strömungswiderstände der jeweiligen Strömungsquerschnittsverengung berechnet werden unter Berücksichtigung des Produkts aus der Viskosität des der jeweiligen Strömungsquerschnittsverengung zugeordneten Mediums aus Arbeitsfluid und Dosierflüssigkeit und der charakteristischen Länge der zugeordneten Strömungsquerschnittsverengung, geteilt durch die vierte Potenz der charakteristischen Abmessung des Strömungsquerschnitts der zugeordneten Strömungsquerschnittsverengung.According to the present invention, this object is achieved by a pipetting method in which the pipetting device has a throttle point as a further flow cross-section constriction in a pipetting channel that is operationally filled with working fluid, fluid-mechanically between the dosing liquid receiving space and the pressure-changing device, which is dimensioned in such a way that a ratio of a flow resistance ( R 1 ) of the pipetting opening for dispensed dosing liquid to a flow resistance (R 2 ) of the throttle point for working fluid, which flows through the throttle point when dispensing the dosing fluid, is less than 0.5, preferably less than 0.3, particularly preferably less than 0.225, the flow resistances of the respective flow cross-section constriction being calculated taking into account the product of the viscosity of the medium of working fluid and dosing liquid associated with the respective flow cross-section constriction t and the characteristic length of the associated flow area restriction divided by the fourth power of the characteristic dimension of the flow area of the associated flow area restriction.
Mit der beschriebenen Drosselstelle wird zwischen der Druckveränderungsvorrichtung und dem Dosierflüssigkeits-Aufnahmeraum eine Engstelle im Strömungsquerschnitt geschaffen, welche dafür sorgt, dass eine durch die Druckveränderungsvorrichtung bewirkte Druckänderung im Arbeitsfluid sich nicht schlagartig, sondern nur allmählich in den Dosierflüssigkeits-Aufnahmeraum fortsetzt, was überraschenderweise für eine Unempfindlichkeit des Dispensationsverhaltens der Pipettiervorrichtung gegenüber Änderungen, insbesondere ablagerungsbedingte Änderungen, des Strömungsquerschnitts der Pipettieröffnung sorgt. Somit können im Wesentlichen baugleiche Pipettiervorrichtungen, welche im Wesentlichen mit identischen Einstellungen betrieben werden, ein im Wesentlichen identisches Dispensationsverhalten aufweisen, obwohl an ihren Pipettieröffnungen unterschiedlich starke Ablagerungen vorhanden sind.With the throttle point described, a constriction is created in the flow cross-section between the pressure-changing device and the dosing-liquid receiving space, which ensures that a pressure change in the working fluid caused by the pressure-changing device does not suddenly, but only gradually, continues into the dosing-liquid receiving space, which is surprising for a Insensitivity of the dispensing behavior of the pipetting device to changes, in particular changes caused by deposits, of the flow cross-section of the pipetting opening. Thus, pipette devices that are essentially structurally identical and are operated with essentially identical settings can have essentially identical dispensing behavior, although deposits of different thicknesses are present at their pipette openings.
Das Verhältnis der genannten Strömungswiderstände, welches für das Funktionieren der hier vorgestellten Lösung maßgeblich ist, führt dazu, dass die mit Arbeitsfluid, in der Regel einem Gas, durchströmte Drosselstelle eine deutlich kleinere Querschnittsöffnung aufweist als die Pipettieröffnung. Es soll jedoch nicht ausgeschlossen sein, dass auch eine Flüssigkeit als Arbeitsfluid verwendet wird.The ratio of the flow resistances mentioned, which is decisive for the functioning of the solution presented here, means that the throttle point through which the working fluid, usually a gas, flows has a significantly smaller cross-sectional opening than the pipetting opening. However, it should not be ruled out that a liquid is also used as the working fluid.
Als Viskosität ist dabei die jeweilige dynamische Viskosität heranzuziehen, welche in der Literatur in der Regel mit dem Formelzeichen "η" bezeichnet ist.The viscosity to be used is the respective dynamic viscosity, which is generally denoted in the literature by the symbol “η”.
Die bezeichnete charakteristische Länge der zugeordneten Querschnittsverengung kann bei zylindrischen Strömungsquerschnittsverengungen die Länge des zylindrischen Kanals sein oder kann bei konisch auf die Strömungsquerschnittsverengung zulaufenden Kanälen die Länge des Kanalabschnitts sein, in welchem sich die Strömungsquerschnittsfläche des Kanals ausgehend von der kleinsten Strömungsquerschnittsfläche in der Drosselstelle oder in der Pipettieröffnung verdoppelt. Findet über die maximal feststellbare Länge des Kanals keine Verdopplung der Strömungsquerschnittsfläche statt, so kann die gesamte Länge des Kanals als charakteristische Länge herangezogen werden.In the case of cylindrical flow cross-section constrictions, the designated characteristic length of the associated cross-sectional constriction can be the length of the cylindrical duct or, in the case of ducts tapering conically towards the flow cross-sectional constriction, it can be the length of the duct section in which the flow cross-sectional area of the duct, starting from the smallest flow cross-sectional area in the throttle point or in the Pipette opening doubled. If the flow cross-sectional area does not double over the maximum ascertainable length of the channel, the entire length of the channel can be used as the characteristic length.
Als charakteristische Abmessung des Strömungsquerschnitts kann bei kreisförmigen Strömungsquerschnitten der Durchmesser, bei quadratischen Strömungsquerschnitten eine Kantenlänge, bei rechteckigen Strömungsquerschnitten ein arithmetischer Mittelwert aus langer und kurzer Kantenlänge, bei elliptischen Strömungsquerschnitten ein arithmetischer Mittelwert aus langer und kurzer Achse usw. herangezogen werden. Sofern sich der Strömungsquerschnitt über die Länge der Strömungsquerschnittsverengung ändert, sollte der kleinste in der Strömungsquerschnittsverengung auftretende Strömungsquerschnitt herangezogen werden.The characteristic dimension of the flow cross-section can be the diameter for circular flow cross-sections, an edge length for square flow cross-sections, an arithmetic mean of long and short edge length for rectangular flow cross-sections, an arithmetic mean of long and short axis for elliptical flow cross-sections, etc. If the flow cross section changes over the length of the flow cross section constriction, the smallest flow cross section occurring in the flow cross section constriction should be used.
Die Verwendung charakteristischer Abmessungen ist in der Strömungsmechanik ausreichend bekannt.The use of characteristic dimensions is well known in fluid mechanics.
Vorzugsweise wird das Verhältnis des Strömungswiderstands (R1) der Pipettieröffnung und des Strömungswiderstands (R2) der Drosselstelle berechnet aus:
Bevorzugt betrifft die vorliegende Erfindung eine eingangs bereits erwähnte Waschkopf-Pipettiervorrichtung, welche dazu ausgebildet ist, Waschflüssigkeit als Dosierflüssigkeit in genauen Dosierungen abzugeben. Derartige Waschkopf-Pipettiervorrichtungen dienen in der Regel dazu, in Probenbehältern, etwa so genannte "Wells", aufgenommene Objekte durch Abgabe einer genau dosierten Menge an Waschflüssigkeit zu reinigen. Dabei ist zur Herbeiführung eines vorbestimmten Reinigungszustands die genaue Dosierung der Waschflüssigkeit von großer Wichtigkeit. Allgemein gilt, dass der Volumenstrom an Waschflüssigkeit so eingestellt wird, dass die Waschleistung möglichst groß, die Zeitdauer des Waschvorgangs jedoch möglichst kurz ist. Bei fehlerhafter Pipettierung von Waschflüssigkeit kann die Gefahr einer so genannten "Überwaschung" bestehen, welche dazu führen kann, dass am zu waschendem Objekt oder/und im Probenbehälter unerwünschterweise Elemente gelöst werden.The present invention preferably relates to a washing head pipetting device already mentioned at the outset, which is designed to deliver washing liquid as dosing liquid in precise doses. Such washing-head pipetting devices are generally used to clean objects held in sample containers, such as so-called "wells", by dispensing a precisely metered quantity of washing liquid. The precise dosing of the washing liquid is of great importance in order to bring about a predetermined cleaning state. In general, the volume flow of washing liquid is set in such a way that the washing performance is as great as possible, but the duration of the washing process is as short as possible. If washing liquid is pipetted incorrectly, there may be a risk of so-called “overwashing”, which can lead to elements being undesirably dissolved on the object to be washed and/or in the sample container.
Obwohl nicht ausgeschlossen sein soll, dass eine derartige Waschkopf-Pipettiervorrichtung die Waschflüssigkeit als Dosierflüsigkeit über die Pipettieröffnung in den Dosierflüssigkeits-Aufnahmeraum aspiriert, wird aus Gründen einfacherer Handhabung dem Dosierflüssigkeits-Aufnahmeraum einer bevorzugten Waschkopf-Pipettiervorrichtung Waschflüssigkeit als Dosierflüssigkeit durch einen Dosierflüssigkeits-Zulauf zugeführt.Although it should not be ruled out that such a washing head pipetting device aspirates the washing liquid as dosing liquid via the pipetting opening into the dosing liquid receiving space, for reasons of simpler handling the dosing liquid receiving space of a preferred washing head pipetting device is supplied with washing liquid as dosing liquid through a dosing liquid inlet.
Deshalb kann also die hier diskutierte Waschkopf-Pipettiervorrichtung einen Dosierflüssigkeits-Zulauf aufweisen, durch welchen der Dosierflüssigkeits-Aufnahmeraum mit Dosierflüssigkeit, also im vorliegenden Anwendungsfall mit Waschflüssigkeit, wenigstens teilweise füllbar ist. Hierzu kann vorgesehen sein, dass der Dosierflüssigkeits-Zulauf in den Dosierflüssigkeits-Aufnahmeraum mündet. Der Dosierflüssigkeits-Zulauf ist in der Regel - abgesehen von der eben beschriebenen vorteilhaften Mündung - als gesondert von Dosierflüssigkeits-Aufnahmeraum ausgebildeter Kanal vorgesehen.The washing head pipetting device discussed here can therefore have a dosing liquid inlet through which the dosing liquid receiving space can be at least partially filled with dosing liquid, ie with washing liquid in the present application. For this purpose it can be provided that the dosing liquid feed opens into the dosing liquid receiving space. Apart from the advantageous orifice just described, the dosing liquid inlet is generally provided as a channel formed separately from the dosing liquid receiving space.
Zum Betrieb des Dosierflüssigkeits-Zulaufs kann die Waschkopf-Pipettiervorrichtung in einer weiteren vorteilhaften Ausgestaltung der vorliegenden Erfindung eine Dosierflüssigkeitspumpe aufweisen, mit welcher Dosierflüssigkeit, insbesondere Waschflüssigkeit als Dosierflüssigkeit, längs des Dosierflüssigkeits-Zulaufs in den Dosierflüssigkeits-Aufnahmeraum förderbar ist. Weiterhin kann zur Verhinderung eines unerwünschten Nachlaufens von Dosierflüssigkeit aus dem Dosierflüssigkeits-Zulauf in den Dosierflüssigkeits-Aufnahmeraum ein Ventil an Dosierflüssigkeits-Zulauf, insbesondere in einem mündungsnahen Bereich, vorgesehen sein, welches durch eine Steuereinrichtung geöffnet und geschlossen werden kann. Mit dieser oder einer anderen Steuereinrichtung kann im Übrigen auch die Dosierflüssigkeitspumpe betrieben werden.To operate the dosing liquid feed, the washing head pipetting device can have a dosing liquid pump in a further advantageous embodiment of the present invention, with which dosing liquid, in particular washing liquid as dosing liquid, can be conveyed along the dosing liquid feed into the dosing liquid receiving space. Furthermore, to prevent an undesired afterflow of dosing liquid from the dosing liquid feed into the dosing liquid receiving space, a valve can be provided on the dosing liquid feed, in particular in an area close to the mouth, which can be opened and closed by a control device. The dosing liquid pump can also be operated with this or another control device.
Die oben erwähnte Dosierflüssigkeitspumpe muss jedoch nicht vorgesehen sein, da die Dosierflüssigkeit, insbesondere als Waschflüssigkeit, von einem geodätisch über der Mündung des Dosierflüssigkeits-Zulaufs in den Dosierflüssigkeits-Aufnahmeraum schwerkraftgetrieben gefördert werden kann. Dann ist allerdings das oben erwähnte Ventil unbedingt notwendig.However, the dosing liquid pump mentioned above does not have to be provided, since the dosing liquid, in particular as washing liquid, is pumped from a geodetic over the mouth of the dosing liquid inlet into the dosing liquid receiving space gravity can be promoted. Then, however, the valve mentioned above is absolutely necessary.
Um die Wascheffizienz einer Waschkopf-Pipettiervorrichtung zu erhöhen, kann diese eine Mehrzahl von Pipettierkanälen aufweisen, welche im Wesentlichen parallel zueinander vorgesehen sind, so dass eine der Mehrzahl von Pipettierkanälen entsprechende Mehrzahl von Objekten gleichzeitig einer Reinigung durch die Waschkopf-Pipettiervorrichtugn unterzogen werden kann.In order to increase the washing efficiency of a washing head pipetting device, it can have a plurality of pipetting channels which are provided essentially parallel to one another, so that a plurality of objects corresponding to the plurality of pipetting channels can be subjected to cleaning by the washing head pipetting device at the same time.
Gerade bei einer Mehrkanal-Pipettiervorrichtung ist die vorliegende Erfindung von großem Vorteil, da die Erfindung dafür sorgen kann, dass jeder Pipettierkanal im Wesentlichen die gleiche Menge an Dosierflüssigkeit mit hoher Genauigkeit abgeben kann, obwohl die einzelnen Pipettierkanäle, sei es durch Fertigungstoleranzen angekoppelter Pipettierspitzen, sei es durch unterschiedlich starke Ablagerungen an den Pipettieröffnungen, sei es eine Kombination dieser oder anderer Ursachen, unterschiedliche geometrische Frmen aufweisen können, so dass ohne Anwendung der vorliegenden Erfindung die einzelnen Pipettierkanäle eines Mehrkanal-Pipettierkopfs bei gleichen Betriebsparametern der Pipettiervorrichtung unterschiedliche Pipettierergebnisse liefern würden.The present invention is particularly advantageous in the case of a multi-channel pipetting device, since the invention can ensure that each pipetting channel can deliver essentially the same amount of dosing liquid with a high level of accuracy, although the individual pipetting channels, be it due to manufacturing tolerances coupled to pipetting tips it can have different geometric shapes due to different levels of deposits on the pipetting openings, be it a combination of these or other causes, so that without the present invention being used, the individual pipetting channels of a multi-channel pipetting head would deliver different pipetting results with the same operating parameters of the pipetting device.
Das Prinzip der Drosselung der Arbeitsfluidströmung zwischen Dosierflüssigkeits-Aufnahmeraum und Druckveränderungsvorrichtung kann nicht nur bei der Dispensation von Dosierflüssigkeiten, sondern auch bei deren Aspiration mit Erfolg angewendet werden. Auch hier kann es zu einer Unempfindlichkeit des Dosierverhaltens gegenüber Ablagerungen und sonstigen Strömungsquerschnittsveränderungen in der Pipettieröffnung kommen.The principle of throttling the working fluid flow between the dosing liquid receiving space and the pressure-changing device can be used successfully not only in the dispensing of dosing liquids, but also in their aspiration. Here, too, the dosing behavior can be insensitive to deposits and other flow cross-section changes in the pipette opening.
Deshalb betrifft die vorliegende Erfindung insbesondere auch solche Pipettiervorrichtungen, welche außer zur obengenannten Dispensation auch zur Aspiration von Dosierflüssigkeit, in diesem Falle durch Verringerung des Drucks des Arbeitsfluids im Dosierflüssigkeits-Aufnahmeraum, ausgebildet sind. In diesem Falle ist bei der Aspiration von Dosierflüssigkeit diese in Abhängigkeit vom Druck des Arbeitsfluids durch die Pipettieröffnung in den Dosierflüssigkeits-Aufnahmeraum hinein aspirierbar.Therefore, the present invention relates in particular to those pipetting devices which, in addition to the above-mentioned dispensing, are also used to aspirate metering liquid, in this case by reducing the Pressure of the working fluid in the dosing liquid receiving space are formed. In this case, when dosing liquid is aspirated, it can be aspirated through the pipetting opening into the dosing liquid receiving space as a function of the pressure of the working fluid.
Im Falle von Dosiervorgängen, also der Aspiration und der Dispensation von Dosierflüssigkeit, sind bei den Pipettiervorrichtungen im Stand der Technik bei baugleichen Pipettiervorrichtungen und im Wesentlichen identischen Betriebsparametern Unterschiede im Dosierverhalten für unterschiedliche Dosierflüssigkeiten, insbesondere für unterschiedlich viskose Dosierflüssigkeiten feststellbar.In the case of dosing processes, i.e. the aspiration and dispensing of dosing liquid, differences in the dosing behavior for different dosing liquids, in particular for dosing liquids with different viscosities, can be observed in the pipetting devices of the prior art with identical pipetting devices and essentially identical operating parameters.
Es hat sich dabei herausgestellt, dass die vorliegend empfohlene Drosselstelle im Pipettierkanal fluidmechanisch zwischen der Druckveränderungsvorrichtung und dem Dosierflüssigkeits-Aufnahmeraum in gewissen Grenzen auch zur Vergleichmäßigung des Dosierverhaltens über unterschiedlich viskose Dosierflüssigkeiten hinweg geeignet ist. Mit anderen Worten: Bei im Wesentlichen baugleichen Pipettiervorrichtungen und im Wesentlichen gleichen Betriebsparametern ist das Dosierverhalten dieser Pipettiervorrichtungen in gewissen Grenzen unabhängig von der Viskosität der Dosierflüssigkeit.It has been found that the throttle point recommended here in the pipetting channel is fluid-mechanically between the pressure-changing device and the dosing liquid receiving space, within certain limits, also suitable for equalizing the dosing behavior across dosing liquids with different viscosities. In other words: With pipetting devices that are essentially structurally identical and operating parameters are essentially the same, the dosing behavior of these pipetting devices is independent of the viscosity of the dosing liquid within certain limits.
Hierzu bedarf es allerdings, verglichen mit dem vorherigen Fall eines im Wesentlichen von Veränderungen des Pipettieröffnungs-Strömungsquerschnitts unabhängigen Dosierverhalten, einer deutlichen Reduzierung des Strömungsquerschnitts der Drosselstelle.However, compared to the previous case of a dosing behavior that is essentially independent of changes in the flow cross section of the pipette opening, this requires a significant reduction in the flow cross section of the throttle point.
Versuche haben gezeigt, dass das Dosierverhalten im Wesentlichen gleicher Pipettiervorrichtungen bei im Wesentlichen gleichen Betriebsparametern dann im Wesentlichen unabhängig von der Viskosität der Dosierflüssigkeit ist, wenn das Verhältnis des Strömungswiderstands (R1) der Pipettieröffnung für dispensierte Dosierflüssigkeit zu dem Strömungswiderstand (R2) der Drosselstelle für diese bei der Dispensation des Dosierfluids durchströmendes Arbeitsfluid kleiner als 0,001, vorzugsweise kleiner als 0,00075, besonders bevorzugt kleiner als 0,0005 ist.Experiments have shown that the dosing behavior of essentially the same pipetting devices with essentially the same operating parameters is essentially independent of the viscosity of the dosing liquid if the ratio of the flow resistance (R 1 ) of the pipetting opening for dispensed dosing liquid to the flow resistance (R 2 ) of the throttle point for this flowing through during the dispensing of the dosing fluid Working fluid is less than 0.001, preferably less than 0.00075, more preferably less than 0.0005.
Wiederum gilt die Unabhängigkeit des Dosierverhaltens von der Viskosität sowohl für das Dispensations- wie auch das Aspirationsverhalten. Es wird lediglich die Dispensation als Bezugsvorgang herangezogen.Again, the independence of the dosing behavior from the viscosity applies to both the dispensing and the aspiration behavior. Only the dispensation is used as a reference process.
Versuche haben gezeigt, dass die oben genannten Obergrenzen des Verhältnisses der Strömungswiderstände dann ein von der Viskosität der Dosierflüssigkeit im Wesentlichen unabhängiges Dosierverhalten bewirken, wenn die dynamische Viskosität der Dosierflüssigkeit den Wert von 0,004 Nsm-2, vorzugsweise von 0,0035 Nsm-2, besonders bevorzugt von 0,0031 Nsm-2 nicht übersteigt.Experiments have shown that the above upper limits of the ratio of the flow resistances cause a metering behavior that is essentially independent of the viscosity of the metering liquid if the dynamic viscosity of the metering liquid is 0.004 Nsm -2 , preferably 0.0035 Nsm -2 , particularly preferably not exceeding 0.0031 Nsm -2 .
Dabei können Arbeitsfluide mit Erfolg verwendet werden, deren dynamische Viskosität den Wert von 0,00003 Nsm-2, vorzugsweise von 0,00002 Nsm-2, besonders bevorzugt von 0,0000175 Nsm-2 nicht übersteigt. Dabei ist wiederum die dynamische Viskosität gemeint.Working fluids can be used successfully here whose dynamic viscosity does not exceed the value of 0.00003 Nsm -2 , preferably 0.00002 Nsm -2 , particularly preferably 0.0000175 Nsm -2 . Here again the dynamic viscosity is meant.
Weiter kann daran gedacht sein, die Drosselstelle mit einem wahlweise veränderbaren Strömungsquerschnitt auszurüsten, etwa durch Veränderung der Spaltweite eines Ringspalts oder mit einem Mechanismus, ähnlich jenem, wie er zur Verstellung der Blende an mechanischen Fotoapparaten verwendet wird. Damit kann der Strömungsquerschnitt der Drosselstelle an das jeweils verwendete Arbeitsfluid oder/und die jeweils zu dosierende Dosierflüssigkeit angepasst werden.It can also be considered to equip the throttle point with a flow cross section that can be changed as desired, for example by changing the gap width of an annular gap or with a mechanism similar to that used to adjust the aperture on mechanical cameras. The flow cross section of the throttle point can thus be adapted to the working fluid used in each case and/or the dosing liquid to be metered in each case.
Zur besseren Steuerbarkeit, insbesondere Feinsteuerbarkeit eines Aspirations- oder/und Dispensationsvorgangs kann weiter daran gedacht sein, dass der Pipettierkanal ein zwischen einer Sperrstellung, in welcher eine Arbeitsfluidströmung im Pipettierkanal unterbunden ist, und einer Offenstellung, in welcher eine Arbeitsfluidströmung im Pipettierkanal gestattet ist, verstellbares Ventil aufweist. Dabei kann das Ventil zunächst geschlossen gehalten werden, bis in einem zumindest nahe der Druckveränderungsvorrichtung gelegenen Bereich das Arbeitsfluid auf einen gewünschten Druck gebracht wurde. Insbesondere kann die Drosselstelle bis zu einem Querschnitt von Null veränderbar sein, so dass das hier beschriebene Ventil unter Verwendung einer vorteilhaft geringen Anzahl an Bauteilen durch die oben beschriebene Drosselstelle mit veränderbarem Strömungsquerschnitt realisiert sein kann.For better controllability, in particular fine controllability of an aspiration and/or dispensing process, it can also be considered that the pipetting channel can be adjusted between a blocked position, in which a working fluid flow in the pipetting channel is prevented, and an open position, in which a working fluid flow in the pipetting channel is permitted valve. The valve can initially be closed be maintained until the working fluid has been brought to a desired pressure in an area at least close to the pressure-changing device. In particular, the throttle point can be variable down to a cross section of zero, so that the valve described here can be implemented using an advantageously small number of components through the throttle point described above with a variable flow cross section.
Weiter kann in an sich bekannter Weise durch intermittierendes Öffnen und Schließen des Ventils eine Flüssigkeitsmenge hochgenau dosiert werden.Furthermore, a quantity of liquid can be metered with high precision in a manner known per se by intermittently opening and closing the valve.
Da die Wirkung der vorliegend diskutierten Erfindung, wie eingangs dargelegt wurde, darin liegt, dass sich eine von der Druckveränderungsvorrichtung ausgehende Druckveränderung nicht schlagartig in den Dosierflüssigkeits-Aufnahmeraum ausbreiten kann, ist es vorteilhaft, wenn auch das Ventil an der Drosselstelle oder fluidmechanisch zwischen der Druckveränderungsvorrichtung und der Drosselstelle vorgesehen ist.Since the effect of the presently discussed invention, as explained at the beginning, is that a pressure change emanating from the pressure-changing device cannot suddenly propagate into the dosing liquid receiving space, it is advantageous if the valve at the throttle point or fluid-mechanically between the pressure-changing device and the throttle point is provided.
Gemäß einer konstruktiv möglichen Ausgestaltung der vorliegenden Erfindung kann als die Druckveränderungsvorrichtung wenigstens ein unter einem Systemdruck stehendes Reservoir an Arbeitsfluid vorgesehen sein. Genauer kann zur Durchführung sowohl von Aspirations- wie auch von Dispensationsvorgängen an ein und demselben Pipettierkanal vorgesehen sein, dass ein unter einem ersten Systemdruck stehendes Dispensations-Reservoir und ein unter einem zweiten Systemdruck stehendes Aspirations-Reservoir vorgesehen sind, welche wahlweise druckübertragend mit dem Pipettierkanal verbindbar und von diesem trennbar sind, wobei der erste Systemdruck größer ist als ein Umgebungsdruck der Pipettiervorrichtung und der zweite Systemdruck kleiner ist als der Umgebungsdruck.According to a structurally possible embodiment of the present invention, at least one reservoir of working fluid that is under a system pressure can be provided as the pressure-changing device. More precisely, in order to carry out both aspiration and dispensing processes on one and the same pipetting channel, a dispensing reservoir under a first system pressure and an aspiration reservoir under a second system pressure can be provided, which can optionally be connected to the pipetting channel in a pressure-transmitting manner and are separable therefrom, wherein the first system pressure is greater than an ambient pressure of the pipetting device and the second system pressure is smaller than the ambient pressure.
Im Hinblick auf die Strömungsvorgänge des Arbeitsfluids durch die Drosselstelle hindurch ist es bei Aspirations- und Dispensationsvorgängen vorteilhaft, wenn der Systemdruck zumindest für Dispensationsvorgänge gegenüber dem Umgebungsdruck des Dosierflüssigkeits-Aufnahmeraums einen Überdruck von 1,5 bar, vorzugsweise von 1,2 bar, besonders bevorzugt von 1,0 bar, nicht übersteigt. Bei höheren Druckunterschieden zwischen dem Systemdruck und dem Umgebungsdruck kann es zu stark turbulenten Strömungen des Arbeitsfluids durch die Drosselstelle kommen, was die Wirkung der vorliegenden Erfindung unter Umständen beeinträchtigen kann.With regard to the flow processes of the working fluid through the throttle point, it is advantageous for aspiration and dispensing processes if the system pressure is opposite, at least for dispensing processes the ambient pressure of the dosing liquid receiving space does not exceed an overpressure of 1.5 bar, preferably 1.2 bar, particularly preferably 1.0 bar. Higher pressure differences between the system pressure and the ambient pressure can lead to highly turbulent flows of the working fluid through the throttling point, which under certain circumstances can impair the effect of the present invention.
Grundsätzlich kann jedoch auch daran gedacht sein, dass die Druckveränderungsvorrichtung eine diskontinuierlich oder kontinuierlich arbeitende Pumpe aufweist, gegebenenfalls im Zusammenspiel mit einer Ventilanordnung, die im Förderweg der Pumpe angeordnet und wahlweise geöffnet und geschlossen werden kann. Im Hinblick auf eine stets gewünschte Automatisierung von Dosierungsvorgängen ist es vorteilhaft, wenn die Pumpe motorisch angetrieben ist.In principle, however, it can also be considered that the pressure-changing device has a discontinuously or continuously operating pump, optionally in interaction with a valve arrangement that is arranged in the conveying path of the pump and can be selectively opened and closed. With regard to the automation of dosing processes that is always desired, it is advantageous if the pump is motor-driven.
Ebenso kann gemäß einer weiteren vorteilhaften Ausgestaltung der Pipettiervorrichtung daran gedacht sein, dass die Druckveränderungsvorrichtung eine Kolben-Zylinder-Vorrichtung mit einem sich längs einer Zylinderachse erstreckenden Zylinder und mit einem darin längs der Zylinderachse beweglich aufgenommenen Kolben aufweist, wobei Zylinder und Kolben wenigstens ein Arbeitsvolumen begrenzen, welches durch eine Relativbewegung des Kolbens relativ zum Zylinder veränderlich ist und welches mit dem Pipettierkanal in Fluidübertragungsverbindung steht oder bringbar ist. Die Kolben-Zylinder-Anordnung stellt die gebräuchlichste Ausgestaltung der Druckveränderungsvorrichtung in Pipettiervorrichtungen dar. Sie bietet überdies die Möglichkeit einer sehr genauen Drucksteuerung durch die Verwendung kleiner Kolbenflächen und im Verhältnis dazu langer Kolbenhübe.Likewise, according to a further advantageous embodiment of the pipetting device, it can be considered that the pressure changing device has a piston-cylinder device with a cylinder extending along a cylinder axis and with a piston accommodated therein so that it can move along the cylinder axis, with the cylinder and piston delimiting at least one working volume , which can be changed relative to the cylinder by a relative movement of the piston and which is or can be brought into fluid communication with the pipetting channel. The piston-cylinder arrangement represents the most common design of the pressure-changing device in pipetting devices. It also offers the possibility of very precise pressure control through the use of small piston areas and relatively long piston strokes.
Gerade mit der zuvor genannten Kolben-Zylinder-Vorrichtung als der Druckveränderungsvorrichtung kann die Pipettiervorrichtung auch eine bestimmungsgemäß manuell betätigbare Pipettiervorrichtung sein, wobei dann insbesondere der Kolben durch manuelle Betätigung relativ zum Zylinder bewegbar ist. Diese Betätigung kann unmittelbar, also durch Herausziehen oder Eindrücken des Kolbens mit der Hand, oder kann mittelbar, etwa durch Spannen einer Feder, welche nach einem Auslösen eine Relativbewegung zwischen Kolben und Zylinder antreibt, erfolgen. Bevorzugt weist die manuell betätigbare Pipettiervorrichtung zur möglichst genauen Dosierung nur genau einen Pipettierkanal auf.Especially with the aforementioned piston-cylinder device as the pressure-changing device, the pipetting device can also be a manually actuated pipetting device as intended, in which case the piston in particular can then be moved relative to the cylinder by manual actuation. This actuation can be immediate, ie by pulling it out or pressing in the piston by hand, or can take place indirectly, for example by tensioning a spring which drives a relative movement between the piston and the cylinder after it has been triggered. The manually operable pipetting device preferably has only exactly one pipetting channel for the most precise possible dosing.
Mit "bestimmungsgemäß manuell betätigbar" sollen solche Fälle nicht erfasst sein, welche grundsätzlich motorisch oder sonstwie automatisiert betätigt sind und nur für den Ausfall einer Energieversorgung durch eine manuelle Notbetätigung weiter betrieben werden können."Manually operable as intended" is not intended to cover cases that are generally operated by a motor or otherwise automatically and can only continue to be operated by manual emergency actuation in the event of a power supply failure.
Gerade für Fälle einer Dosierung durch Aspiration und Dispensation ist es zur Erfüllung höchster Ansprüche an Hygiene vorteilhaft, wenn der Dosierflüssigkeits-Aufnahmeraum und die Pipettieröffnung an einer von dem die Drosselstelle aufweisenden Pipettierkanal gesondert ausgebildeten, wahlweise mit diesem verbindbaren oder/und von diesem trennbaren Pipettierspitze ausgebildet sind. Dagegen sind für die zuvor genannte Waschkopf-Pipettiervorrichtung starr mit der Pipettiervorrichtung vorgesehene Auslässe, so genannte "Waschrohre", bevorzugt.Especially in cases of dosing by aspiration and dispensing, it is advantageous in order to meet the highest standards of hygiene if the dosing liquid receiving space and the pipette opening are formed on a pipette tip that is separate from the pipette channel that has the throttle point and can be optionally connected to and/or separated from this pipette tip are. On the other hand, outlets provided rigidly with the pipetting device, so-called "washing tubes", are preferred for the aforementioned washing head pipetting device.
Die vorliegende Erfindung wird nachfolgend anhand der beiliegenden Zeichnung näher erläutert werden, welche einen grobschematischen Längsschnitt durch eine erfindungsgemäße Ausführungsform einer Pipettiervorrichtung zeigt.The present invention will be explained in more detail below with reference to the accompanying drawing, which shows a roughly schematic longitudinal section through an embodiment of a pipetting device according to the invention.
In
Der Pipettierkanal 12 weist einen Zylinderabschnitt 16 auf, in welchem ein Kolben 18 längs einer mit der Zylinderachse Z zusammenfallenden Längsachse L der Pipettiervorrichtung 10 über eine Kolbenstange 20 durch einen Motor 22 relativ zum Zylinderabschnitt 16 verstellbar ist.The
Der Motor 22 wird durch eine Steuer/Regeleinheit 24 angesteuert, beispielsweise in Abhängigkeit vom Erfassungsignal eines Drucksensors 26, welcher den Druck eines Arbeitsfluids, etwa Luft, in einer durch die Bewegung des Kolbens 18 volumenveränderlichen Arbeitskammer 28 erfasst.The
Die Pipettierspitze 14, welche durch einen längs der Längsachse L der Pipettiervorrichtung 10 relativ zum Zylinderabschnitt 16 beweglichen Abwerfer 30 in an sich bekannter Weise vom Pipettierkanal 12 lösbar ist, weist einen zur Kopplung mit dem Pipettierkanal 12 ausgebildeten Kopplungsbereich 32, einen in dem in
Die Baugruppe aus Zylinder 16 und Kolben 18 bildet eine Druckveränderungsvorrichtung 40 zur Veränderung des Drucks von Arbeitsfluid im Dosierflüssigkeits-Aufnahmeraum 38.The assembly of cylinder 16 and
Erfindungsgemäß ist zwischen der Druckveränderungsvorrichtung 40 und dem Dosierflüssigkeits-Aufnahmeraum 38 eine Drosselstelle 42 vorgesehen, welche einen Strömungswiderstand R2 für Arbeitsfluid aufweist, welcher sich vorzugsweise berechnet aus
Die Drosselstelle 42 kann darüber hinaus ein Ventil 44 aufweisen, mit welchem die Drosselstelle 42 vollständig abschließbar ist, um eine Druckausbreitung des Arbeitsfluiddrucks vom Arbeitsraum 28 in den Dosierflüssigkeits-Aufnahmeraum 38 zu unterbrechen.The throttle point 42 can also have a
Das Ventil 44 ist vorzugsweise ebenfalls durch die Steuer/Regeleinrichtung 24 betätigbar.The
Die Pipettieröffnung 36 weist dagegen beim Dispensieren einen Strömungswiderstand R1 auf, welcher sich vorzugsweise ergibt aus
Bei dem in
Die charakteristische Länge I ist jene Länge, die das Austrittsende der Pipettierspitze 14 ausgehend von der Pipettieröffnung 36 bis zu jener Stelle aufweist, an welcher der Strömungsquerschnitt der Pipettierspitze 14 den doppelten Flächenbetrag aufweist wie die Pipettieröffnung 36. Da der Strömungsquerschnitt bei kreisförmiger Gestalt proportional zum Quadrat des Radius bzw. des Durchmessers ist, kann als charakteristische Länge eines sich konisch oder sonstwie zur jeweiligen Strömungsquerschnittsverengung mit engstem Strömungsquerschnitt hin verjüngenden Austrittsbereichs jene Länge angenommen werden, die zwischen der jeweiligen Strömungsquerschnittsverengung und einem Strömungsquerschnitt besteht, dessen Durchmesser das √2-fache des Durchmessers der Strömungsquerschnittsverengung beträgt.At the in
The characteristic length I is the length that the exit end of the pipette tip 14 has, starting from the pipette opening 36 to the point at which the flow cross section of the pipette tip 14 has twice the surface area of the pipette opening 36. Since the flow cross section in a circular shape is proportional to the square of the radius or diameter, the characteristic length of an outlet area that tapers conically or in some other way towards the respective flow cross-section constriction with the narrowest flow cross-section can be assumed to be the length that exists between the respective flow cross-section constriction and a flow cross-section whose diameter is √2 times the diameter of the flow cross-section constriction.
Es hat sich nämlich herausgestellt, dass mit größer werdenden Strömungsquerschnitten in der Pipettierspitze 14 oder auch in der Drosselstelle 42 jene Bereiche mit deutlich größerem Strömungsquerschnitt als der engste Strömungsquerschnitt kaum zum Strömungswiderstand der jeweiligen Austrittsöffnung beitragen. Mit anderen Worten: Jene Bereiche der Pipettierspitze 14 oder der Drosselstelle 42, welche eine Strömungsquerschnittsfläche aufweisen, die mehr als doppelt so groß wie die Strömungsquerschnittsfläche des engsten Querschnitts ist, tragen nur noch in untergeordneten Größenordnungen zum jeweiligen Strömungswiderstand der betreffenden Strömungsquerschnittsverengung bei. Sie können daher vernachlässigt werden.It has been found that with increasing flow cross-sections in the pipette tip 14 or in the throttle point 42, those areas with a significantly larger flow cross-section than the narrowest flow cross-section hardly contribute to the flow resistance of the respective outlet opening. In other words: Those areas of the pipette tip 14 or the throttle point 42 that have a flow cross-sectional area that is more than twice the flow cross-sectional area of the narrowest cross-section only contribute to the respective flow resistance of the relevant flow cross-section constriction to a minor extent. They can therefore be neglected.
Dann, wenn das Verhältnis der beiden Strömungswiderstände an der Drosselstelle 42 und der Pipettieröffnung 36 unter Berücksichtigung der die jeweiligen Strömungsquerschnittsverengungen durchströmenden Medien anhand von deren dynamischer Viskosität ein Verhältnis von 0,5, vorzugsweise 0,3, besonders bevorzugt 0,225, nicht übersteigt, ist das Dispensationsverhalten der Pipettierspitze 14, welche auch starr mit dem Pipettierkanal 12 verbunden sein kann, weitgehend unabhängig von Veränderungen des Strömungsquerschnitts etwa durch Ablagerungen von getrockneter oder/und auskristallisierter Dosierflüssigkeit.If the ratio of the two flow resistances at the throttle point 42 and the pipette opening 36, taking into account the media flowing through the respective flow cross-section constrictions based on their dynamic viscosity, is a ratio of 0.5, preferably does not exceed 0.3, particularly preferably 0.225, the dispensing behavior of the pipette tip 14, which can also be rigidly connected to the
Selbstverständlich ändert sich das Dosierverhalten mit zunehmender Verengung der Pipettieröffnung 36 ab Unterschreiten eines kritischen Verengungsgrads auch trotz des Vorsehens der Drosselstelle 42 im Pipettierkanal 12 fluidmechanisch zwischen der Druckveränderungsvorrichtung 40 und dem Dosierflüssigkeits-Aufnahmeraum 38. Jedoch kann die Grenze, ab welcher sich Einflüsse derartiger Ablagerungen an der Pipettieröffnung 36 oder in einem der Pipettieröffnung 36 nahen Bereich beim Dispensieren bemerkbar machen, weiter in Richtung einer Querschnittsverkleinerung der Pipettieröffnung 36 hinausgeschoben werden.Of course, the dosing behavior changes with increasing narrowing of the pipetting opening 36 from below a critical degree of narrowing, even despite the provision of the throttle point 42 in the
Entsprechendes gilt für die Aspiration von Dosierflüssigkeit.The same applies to the aspiration of dosing liquid.
Dann, wenn das Verhältnis der Strömungsquerschnitte R2 zu R1 kleiner als 0,001, vorzugsweise kleiner als 0,00075 und besonders bevorzugt kleiner als 0,0005, ist, kann das Aspirations- und Dispensationsverhalten der Pipettiervorrichtung sogar in gewissen Grenzen unabhängig von der Viskosität der verwendeten Dosierflüssigkeit gemacht werden, so dass mit ein und derselben Pipettiervorrichtung 10 und ein und denselben Betriebsparametern unterschiedlich viskose Dosierflüssigkeiten gleich dosiert werden können. Dies vereinfacht den Betrieb von Pipettiervorrichtungen erheblich.Then, when the ratio of the flow cross sections R 2 to R 1 is less than 0.001, preferably less than 0.00075 and particularly preferably less than 0.0005, the aspiration and dispensing behavior of the pipetting device can even be independent of the viscosity within certain limits used dosing liquid are made, so that with one and the
Versuche haben gezeigt, dass Dosierflüssigkeiten mit einer dynamischen Viskosität von bis zu 0,004 Nsm-2, vorzugsweise von 0,0035 Nsm-2 und besonders bevorzugst von 0,0031 Nsm-2 durch eine erfindungsgemäße Pipettiervorrichtung ohne Änderung der Betriebsparameter dosierbar sind. Mit der vorliegenden Erfindung können daher Dosieraufgaben von Pipettiervorrichtungen deutlich vereinfacht werden.Tests have shown that dosing liquids with a dynamic viscosity of up to 0.004 Nsm -2 , preferably 0.0035 Nsm -2 and particularly preferably 0.0031 Nsm -2 can be dosed by a pipetting device according to the invention without changing the operating parameters. Metering tasks of pipetting devices can therefore be significantly simplified with the present invention.
Die vorliegende Erfindung ist insbesondere für Dosieraufgaben anwendbar, welche eine Pipettiervorrichtung 10 als so genannte "Waschkopf-Pipettiervorrichtung" zu erfüllen hat, wenn dieser Waschflüssigkeit als Dosierflüssigkeit in genauen Dosen ausgeben soll.The present invention can be used in particular for dosing tasks which a
Diese Waschkopf-Pipettiervorrichtungen können dazu benutzt werden, Objekte 37 in Probebehältern 39 oder Probebehälter 39 allein, die sich in der Regel unter der Pipettieröffnung 36 befinden, durch Ausgeben einer abgemessenen Menge an Waschflüssigkeit als Dosierflüssigkeit definiert zu reinigen.These washing head pipetting devices can be used to clean
Eine derartige Waschkopf-Pipettiervorrichtung 10 kann hierzu einen Dosierflüssigkeitszulauf 50 aufweisen, welcher von einem Dosierflüssigkeitsvorrat 52 ausgehend bei einer Mündungsöffnung 54 in den Dosierflüssigkeits-Aufnahmeraum 38 münden kann.For this purpose, such a washing
In diesem Falle ist der Dosierflüssigkeits-Aufnahmeraum vorteilhaft durch den Dosierflüssigkeits-Zulauf 50 mit Dosierflüssigkeit (dann in Form von Waschflüssigkeit) füllbar, so dass die Dosierflüssigkeit in diesem Falle nicht durch die Pipettieröffnung 36 aspiriert zu werden braucht.In this case, the dosing liquid receiving space can advantageously be filled with dosing liquid (then in the form of washing liquid) through the
Die Dosierflüssigkeit im Dosierflüssigkeitsvorrat 52 kann durch eine Pumpe 56, welche ebenfalls durch die Steuer-/Regeleinrichtung 24 ansteuerbar sein kann, über den Dosierflüssigkeits-Zulauf 50 in den Dosierflüssigkeits-Aufnahmeraum 38 förderbar sein. Um die durch den Dosierflüssigkeits-Zulauf 50 geförderte Fördermenge noch genauer einstellen zu können, kann überdies am Dosierflüssigkeits-Zulauf 50 ein Ventil 58 vorgesehen sein, welches durch die Steuer-/Regelvorrichtung 24 geöffnet und geschlossen werden kann.The dosing liquid in the dosing liquid reservoir 52 can be conveyed by a
So kann beispielsweise durch ein geeignetes Programm in der Steuer-/Regeleinrichtung zunächst bei geschlossenem Ventil 58 durch Betrieb der Pumpe 56 ein vorbestimmter Druck im Dosierflüssigkeits-Zulauf 50 aufgebaut werden, woraufhin das Ventil 58 für eine vorbestimmte Zeit geöffnet und dann wieder geschlossen wird.For example, a suitable program in the control/regulating device can initially build up a predetermined pressure in the
Um ein Nachlaufen von Dosierflüssigkeit aus dem Dosierflüssigkeits-Zulauf 50 in den Dosierflüssigkeits-Aufnahmeraum 38 zu verhindern oder möglichst gering zu halten, ist das Ventil 58 vorzugsweise an der Mündung 54 oder im Verhältnis zur Gesamtlänge des Dosierflüssigkeits-Zulaufs nahe bei der Mündung 54 angeordnet. Die Entfernung des Ventils 58 von der Mündung 54 sollte vorzugsweise 5 % der Gesamtlänge des Dosierflüssigkeits-Zulaufs 58 nicht überschreiten.In order to prevent or minimize the overflow of dosing liquid from the
Die Pipettiervorrichtung 50, insbesondere als Waschkopf-Pipettiervorrichtung 10, kann über den dargestellten Pipettierkanal 12 hinaus weitere Pipettierkanäle aufweisen, welche im Wesentlichen identisch zu dem dargestellten Pipettierkanal 12 ausgestaltet sind, so dass der in
Bei einer Mehrkanal-Pipettiervorrichtung können dann die Dosierflüssigkeits-Zuläufe 50 zu jedem Pipettierkanal 12 über eine gemeinsame Pumpe 56 mit einem gemeinsamen Dosierflüssigkeitsvorrat 52 verbunden sein.In the case of a multi-channel pipetting device, the dosing liquid feeds 50 to each pipetting
Ebenso können alle Kolbenstangen 20 der einzelnen Pipettierkanäle 12 durch einen gemeinsamen Motor 22 verstellbar sein.Likewise, all piston rods 20 of the
Gleichwohl soll nicht ausgeschlossen sein, dass jeder Pipettierkanal seinen eigenen Motor 22, seine eigene Pumpe 56 oder/und seinen eigenen Dosierflüssigkeitsvorrat 52 aufweist.Nevertheless, it should not be ruled out that each pipetting channel has its
Mit dem Fixiermittel 60 soll angedeutet sein, dass die Pipettierspitze 34 als Waschrohr dauerhaft und eben nicht lösbar mit dem Pipettierkanal 12 gekoppelt sein kann. Das Waschrohr kann auch einstückig mit einem Rohr des Pipettierkanals ausgebildet sein, etwa mit dem Zylinderabschnitt 16.The fixing means 60 is intended to indicate that the
Claims (14)
- Pipetting method, comprising the steps of:- providing a dosing liquid receiving space (38) having a pipetting opening (36) as a first flow cross-sectional constriction, wherein the provided dosing liquid receiving space is at least partially filled with a working fluid, and- aspirating dosing liquid through the pipetting opening (36) into the dosing liquid receiving space (38) by reducing a pressure of the working fluid by means of a pressure changing device (40), which is designed to change the pressure of the working fluid in the dosing liquid receiving space (38), and wherein a throttle point (42) is arranged in a pipetting channel (12) arranged fluid-mechanically between the dosing liquid receiving space (38) and the pressure changing device (40), wherein the working fluid flows through the throttle point (42) as a further flow cross-sectional constriction during aspiration,characterized in that
the pipetting channel (12) has a valve adjustable between a closed position, in which a working fluid flow in the pipetting channel is prevented, and an open position, in which a working fluid flow in the pipetting channel is permitted, in that a liquid quantity of the dosing liquid is determined by a time during which the valve is opened, and in that a ratio of the flow resistance (R1) of the pipetting opening (36) with respect to the dosing liquid to the flow resistance (R2) of the throttle point (42) with respect to the working fluid is less than 0.5, in particular is less than 0.3 and in particular is less than 0.225. - Pipetting method according to claim 1, further comprising dispensing at least a portion of the aspirated dosing liquid through the pipetting opening (36) out of the dosing liquid receiving space (38) by increasing the pressure of the working fluid by means of the pressure changing device (40),
wherein the working fluid flows through the throttle point (42) as a further flow cross-sectional constriction during both aspiration and dispensing. - Pipetting method according to one of claims 1 or 2, wherein the viscosity of the dosing liquid does not exceed the value of 0.004 Nsm-2, preferably does not exceed the value of 0.0035 Nsm-2, more preferably does not exceed the value of 0.0031 Nsm-2.
- Pipetting method according to one of claims 1 to 3, wherein the viscosity of the working fluid does not exceed the value of 0.00003 Nsm-2, preferably the value of 0.00002 Nsm-2, more preferably the value of 0.0000175 Nsm-2.
- Pipetting method according to one of claims 1 to 4, wherein the working fluid is a gas.
- Pipetting method according to claim 5, wherein a liquid amount of the dosing liquid is dispensed with high accuracy by intermittently opening and closing the valve.
- Pipetting method according to one of claims 5 or 6, wherein the pressure changing device (40) comprises working fluid under a system pressure.
- Pipetting method according to claim 7, wherein a dispensing reservoir under a first system pressure and an aspiration reservoir under a second system pressure are provided, which, in a selective pressure-transmitting manner, are connected to or disconnected from the pipetting channel (12) for increasing the pressure or for decreasing the pressure of the working fluid, wherein the first system pressure is greater than an ambient pressure of the pipetting device (10) and the second system pressure is less than the ambient pressure.
- Method for preparing a dose of a dosing liquid comprising the pipetting method according to one of claims 2 to 8 and comprising the step of dispensing according to claim 2, wherein in the step of dispensing the dose is dispensed.
- Method for preparing a plurality of doses of a dosing liquid, which substantially comprise the same amount of dosing liquid between them, wherein each dose of the plurality of doses is each prepared according to the method according to claim 9, and wherein the plurality of doses comprises at least a first dose dispensed from a first pipetting opening and a second dose dispensed from a second pipetting opening.
- Method according to claim 10, wherein the first and second pipetting openings are formed on a first and a second pipetting tip of a multi-channel pipetting head, or wherein the first and second pipetting openings are formed on two different, substantially identical pipetting devices.
- Method according to one of claims 10 or 11, wherein the steps of the pipetting method are performed on each dose of the plurality of doses with identical operating parameters.
- Method according to claim 9 for preparing a first dose of a first dosing liquid having a first viscosity and a second dose of a second dosing liquid having a second viscosity different from the first viscosity,wherein the first dose is prepared in a first dosing process and wherein the second dose is prepared in a second dosing process, and wherein the first and second doses comprise substantially the same amount of dosing liquid,wherein in the first and second dosing processes the steps of the pipetting method according to one of claims 1 to 8 are performed with identical operating parameters.
- Method according to claim 13, wherein a first ratio of the flow resistance (R1) of the pipetting opening (36) with respect to the first dosing liquid to the flow resistance (R2) of the throttle point (42) with respect to the working fluid and a second ratio of the flow resistance (R1) of the pipetting opening (36) with respect to the second dosing liquid to the flow resistance (R2) of the throttle point (42) with respect to the working fluid is less than 0.001, preferably less than 0.00075, and more preferably less than 0.0005.
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DE102010038414A DE102010038414A1 (en) | 2010-07-26 | 2010-07-26 | Pipetting device with throttle point in the pipetting channel |
EP11172869.7A EP2412439B1 (en) | 2010-07-26 | 2011-07-06 | Pipette device with throttle position in the pipette channel |
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EP11172869.7A Division EP2412439B1 (en) | 2010-07-26 | 2011-07-06 | Pipette device with throttle position in the pipette channel |
EP11172869.7A Division-Into EP2412439B1 (en) | 2010-07-26 | 2011-07-06 | Pipette device with throttle position in the pipette channel |
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EP20152812.2A Active EP3663001B1 (en) | 2010-07-26 | 2011-07-06 | Pipetting method with throttle position in the pipette channel |
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EP (2) | EP2412439B1 (en) |
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---|---|---|---|---|
EP2569642B1 (en) | 2010-05-14 | 2022-08-10 | Tecan Trading AG | Pipetting arrangement and method of controlling a pipetting arrangement or of producing liquid product doses |
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EP3485974B1 (en) * | 2017-11-17 | 2021-09-15 | Eppendorf AG | Microdosing device for dosing minute fluid samples |
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JP2513359B2 (en) * | 1990-11-30 | 1996-07-03 | 株式会社島津製作所 | Micro pipette device |
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DE102008058213A1 (en) * | 2008-11-19 | 2010-05-20 | B. Braun Melsungen Ag | Anesthesia syringe with a longitudinally displaceable feed piston and check valve with passage and reverse direction and use of an O-ring as a check valve |
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US8715574B2 (en) * | 2009-06-19 | 2014-05-06 | Abbott Laboratories | System for managing inventory of bulk liquids |
-
2010
- 2010-07-26 DE DE102010038414A patent/DE102010038414A1/en not_active Withdrawn
-
2011
- 2011-07-06 EP EP11172869.7A patent/EP2412439B1/en active Active
- 2011-07-06 EP EP20152812.2A patent/EP3663001B1/en active Active
- 2011-07-25 JP JP2011161908A patent/JP2012068231A/en active Pending
- 2011-07-26 US US13/190,686 patent/US8656792B2/en active Active
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2017
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US8656792B2 (en) | 2014-02-25 |
JP6463386B2 (en) | 2019-01-30 |
JP2012068231A (en) | 2012-04-05 |
JP2017070950A (en) | 2017-04-13 |
EP2412439B1 (en) | 2020-03-04 |
DE102010038414A1 (en) | 2012-01-26 |
EP3663001A1 (en) | 2020-06-10 |
EP2412439A1 (en) | 2012-02-01 |
US20120017704A1 (en) | 2012-01-26 |
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