EP3663001A1 - Pipette device with throttle position in the pipette channel - Google Patents

Abstract

Pipetting device (10) at least for dispensing dosing liquid by increasing the pressure of a working fluid, comprising a dosing liquid receiving space (38) at least partially filled with working fluid with a pipetting opening (36) as a first flow cross-section constriction, through which dosing liquid depending on the pressure of the working fluid can be dispensed from the dosing liquid receiving space (38), and a pressure changing device (40) which is designed to change the pressure of the working fluid in the dosing liquid receiving space (38), the pipetting device (10) being operationally filled with working fluid The pipetting channel (12) has a throttling point (42) as a further flow cross-sectional constriction, which is dimensioned such that a ratio of a flow resistance (R ₁) between the metering liquid receiving space (38) and the pressure change device (40) ) of the pipetting opening (36) for dispensed dosing liquid to a flow resistance (R2) of the throttle point (42) for working fluid which flows through the throttle point (42) during the dispensing of the dosing fluid, less than 0.5, preferably less than 0.3, particularly is preferably less than 0.225, the flow resistances of the respective flow cross-section constriction (36 or 42) being calculated taking into account the product from the viscosity of the medium of working fluid and metering liquid associated with the respective flow cross-section constriction (36 or 42) and the characteristic length (l < sub> Dst </sub>, l _Pof) of the assigned flow cross-section constriction (36 or 42) divided by the fourth power of the characteristic dimension (d _Dst, d <sub > Pof </sub>) of the flow cross-section of the assigned flow cross-section constriction (36 or 42).

Description

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 at least partially filled with working fluid with a pipetting opening as a first flow cross-section constriction, through which dosing liquid depending on the pressure of the working fluid from the dosing liquid. Receiving space is dispensable, and a pressure changing device which is designed to change the pressure of the working fluid in the metering liquid receiving space.

Such pipetting devices are well known in the prior art. When dispensing dosing liquid, a dosing liquid present in a dosing liquid receiving space is pushed out through a pipetting opening of the dosing liquid receiving space by increasing a pressure of a working fluid, which is also located in the dosing liquid receiving space.

Since the pipetting opening generally represents a narrowest flow cross-section when expelling the dosing liquid from the dosing liquid receiving space, the pipetting opening forms a first flow cross-sectional 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 metering liquid receiving space is filled or at least partially filled by a metering liquid inlet and then expelled from the latter by the described dispensing by means of excess pressure of the working fluid based on the ambient pressure of the liquid receiving space.

In the case of these washing heads, the metering liquid is a washing liquid which is dispensed through the pipetting opening in order to use the washing liquid to clean an object, such as a container, provided underneath. Here too, it is important to correctly measure the amount of washing liquid dispensed.

In principle, however, it should also not be ruled out that washing heads add the metering liquid, i.e. washing liquid, in addition or as an alternative to the above-mentioned inflow through known aspiration, i.e. by means of a negative pressure of the working fluid in the metering liquid receiving space through the pipetting opening into the metering liquid receiving space record, tape.

A problem with the pipetting device mentioned at the outset, in particular in its configuration as a washing head, is that the repeated expulsion of dosing liquid through the pipetting opening or on a channel which leads to the pipetting opening forms deposits which form the flow cross section of the pipetting opening or of the channel leading to the pipetting opening. This leads to changes in the dosing behavior, so that after some operating time, pipetting devices which are essentially identical in construction and which are operated with the same dosing liquid and otherwise the same operating parameters can undesirably show different dosing behavior.

It is therefore an object of the present invention to develop a pipetting device 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 The pipetting opening does not influence the dosing behavior of the pipetting device, or at least influences it less than before.

This object is achieved according to the present invention by a generic pipetting device, in which the pipetting device has a throttle point as a further flow cross-sectional constriction, which is dimensioned such that a ratio of a flow resistance, in a pipetting channel that is operationally filled with working fluid, between the dosing liquid receiving space and the pressure changing device (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 , wherein the flow resistances of the respective flow cross-sectional constriction are calculated taking into account the product of the viscosity of the medium of the working fluid associated with the respective flow cross-sectional constriction un d dosing liquid and the characteristic length of the assigned flow cross-section constriction, divided by the fourth power of the characteristic dimension of the flow cross-section of the assigned flow cross-section constriction.

With the described throttling point, a constriction in the flow cross-section is created between the pressure changing device and the metering liquid receiving space, which ensures that a pressure change caused by the pressure changing device in the working fluid does not suddenly, but only gradually continues in the metering liquid receiving space, which is surprisingly for one Insensitivity of the dispensing behavior of the pipetting device to changes, in particular changes due to deposition, of the flow cross section of the pipetting opening. Thus, pipetting devices of essentially the same construction, which are operated essentially with identical settings, can have an essentially identical dispensing behavior, although deposits of different thicknesses are present at their pipetting openings.

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 working fluid, usually a gas, flows has a significantly smaller cross-sectional opening than the pipetting opening. However, it should not be excluded that a liquid is also used as the working fluid.

The respective dynamic viscosity, which is generally designated in the literature with the formula symbol “η”, is to be used as the viscosity.

The designated characteristic length of the assigned cross-sectional constriction can be the length of the cylindrical channel in the case of cylindrical flow cross-sectional constrictions or, in the case of channels tapering to the flow cross-sectional constriction, can be the length of the channel section in which the flow cross-sectional area of the channel is based on the smallest flow cross-sectional area in the throttle point or in Pipette opening doubled. If there is no doubling of the flow cross-sectional area 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 lengths for rectangular flow cross-sections, an arithmetic mean of long and short axes, etc. for elliptical flow cross-sections. 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 use of characteristic dimensions is well known in fluid mechanics.

wobei η_Pof die dynamische Viskosität einer die Pipettieröffnung durchströmenden Dosierflüssigkeit, η_Dst eine dynamische Viskosität eines die Drosselstelle durchströmenden Arbeitsfluids, I_Pof eine charakteristische Länge der Pipettieröffnung, I_Dst eine charakteristische Länge der Drosselstelle, d_Pof eine charakteristische Abmessung des Strömungsquerschnitts der Pipettieröffnung und d_Dst eine charakteristische Abmessung des Strömungsquerschnitts der Drosselstelle ist.The ratio of the flow resistance (R ₁ ) of the pipetting opening and the flow resistance (R ₂ ) of the throttle point is preferably calculated from: $$\frac{R_1}{R_{\mathrm{2nd}}}=\frac{{\eta }_{\mathit{Pof}}\cdot l_{\mathit{Pof}}\cdot d_{\mathit{German}}^{\mathrm{4th}}}{{\eta }_{\mathit{German}}\cdot l_{\mathit{German}}\cdot d_{\mathit{Pof}}^{\mathrm{4th}}}$$

where η _{Pof is} the dynamic viscosity of a metering liquid flowing through the pipetting opening, η _{Dst is} a dynamic viscosity of a working fluid flowing through the throttling point, I _{Pof is} a characteristic length of the pipetting _opening , I _{Dst is} a characteristic length of the throttling point, d _{Pof is} a characteristic dimension of the flow cross section of the pipetting _opening and d _{Dst is} a characteristic dimension of the flow cross section of the throttle point.

The present invention preferably relates to a washing head pipetting device already mentioned at the outset, which is designed to dispense washing liquid as metering liquid in precise dosages. Such washing head pipetting devices are generally used to clean objects in sample containers, such as so-called "wells", by dispensing a precisely metered amount of washing liquid. The exact dosage of the washing liquid is of great importance to bring about a predetermined cleaning state. The general rule is that the volume flow of washing liquid is set so that the washing performance is as large as possible, but the duration of the washing process is as short as possible. In the event of incorrect pipetting of washing liquid, there can be a risk of so-called "overwashing", which can lead to undesired detachment of elements on the object to be washed and / or in the sample container.

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, washing liquid is fed to the dosing liquid receiving space of a preferred washing head pipetting device as a dosing liquid through a dosing liquid feed.

Therefore, the washing head pipetting device discussed here can have a metering liquid inlet through which the metering liquid receiving space can be at least partially filled with metering liquid, that is to say in the present application case with washing liquid. For this purpose, it can be provided that the metering liquid inlet opens into the metering liquid receiving space. The metering liquid inlet is generally provided - apart from the advantageous mouth just described - as a channel formed separately from the metering liquid receiving space.

In a further advantageous embodiment of the present invention, the washing head pipetting device can have a metering liquid pump for operating the metering liquid inlet, with which metering liquid, in particular washing liquid as metering liquid, can be conveyed along the metering liquid inlet into the metering liquid receiving space. Furthermore, in order to prevent undesired running of metering liquid from the metering liquid inlet into the metering liquid receiving space, a valve at the metering liquid inlet, in particular in a region near the mouth, can be provided, which can be opened and closed by a control device. The metering liquid pump can also be operated with this or another control device.

The above-mentioned metering liquid pump does not have to be provided, however, since the metering liquid, in particular as a washing liquid, moves from a geodetically above the mouth of the metering liquid inlet into the metering liquid receiving space gravity driven can be promoted. Then the valve mentioned above is absolutely necessary.

In order to increase the washing efficiency of a washing head pipetting device, said washing head pipetting device 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 simultaneously cleaned by the washing head pipetting device.

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 dispense essentially the same amount of metering liquid with high accuracy, even though the individual pipetting channels, be it due to manufacturing tolerances, are coupled pipetting tips it can have different geometrical shapes due to deposits of different thicknesses at the pipetting openings, be it a combination of these or other causes, so that without application of the present invention, the individual pipetting channels of a multichannel 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 metering liquid receiving space and the pressure changing device can be successfully used not only in the dispensing of metering liquids, but also in their aspiration. Here, too, the dispensing behavior may become insensitive to deposits and other changes in the flow cross section in the pipetting opening.

Therefore, the present invention relates in particular to those pipetting devices which, in addition to the above-mentioned dispensing, also for aspirating dosing liquid, in this case by reducing the Pressure of the working fluid in the metering liquid receiving space are formed. In this case, when aspirating dosing liquid, it can be aspirated into the dosing liquid receiving space depending on the pressure of the working fluid through the pipetting opening.

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 differently viscous dosing liquids, can be determined in the pipetting devices in the prior art with identical pipetting devices and essentially identical operating parameters.

It has been found that the throttle point in the pipetting channel that is recommended in the present case is fluid-mechanically suitable between the pressure changing device and the metering liquid receiving space within certain limits for evening out the metering behavior across differently viscous metering liquids. In other words: With essentially identical pipetting devices and essentially identical operating parameters, the dosing behavior of these pipetting devices is within certain limits independent of the viscosity of the dosing liquid.

However, compared to the previous case of a metering behavior that is essentially independent of changes in the pipette opening flow cross section, this requires a significant reduction in the flow cross section of the throttle point.

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 these flowing through in the dispensing of the dosing fluid Working fluid is less than 0.001, preferably less than 0.00075, particularly preferably less than 0.0005.

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.

Experiments have shown that the above-mentioned upper limits of the ratio of the flow resistances cause a dosing behavior which is essentially independent of the viscosity of the dosing liquid, if the dynamic viscosity of the dosing liquid particularly has the value of 0.004 Nsm ^-2 , preferably 0.0035 Nsm ^-2 preferably does not exceed 0.0031 Nsm ^-2 .

Working fluids can be used successfully, the dynamic viscosity of which 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.

It can also be considered to equip the throttle point with an optionally adjustable flow cross-section, for example by changing the gap width of an annular gap or with a mechanism similar to that used to adjust the orifice on mechanical cameras. The flow cross section of the throttle point can thus be adapted to the working fluid used and / or the metering liquid to be metered in each case.

For better controllability, in particular fine controllability of an aspiration or / and dispensing process, it can further be considered that the pipetting channel is adjustable between a blocking position in which a working fluid flow is prevented in the pipetting channel and an open position in which a working fluid flow is permitted in the pipetting channel Valve. The valve can initially be closed are held 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 changed up to a cross-section of zero, so that the valve described here can be implemented using an advantageously small number of components by means of the throttle point described above with a variable flow cross-section.

Furthermore, a quantity of liquid can be metered with high precision in a manner known per se by intermittently opening and closing the valve.

Since the effect of the presently discussed invention, as explained at the outset, is that a pressure change originating from the pressure change device cannot suddenly spread into the metering liquid receiving space, it is advantageous if the valve at the throttle point or fluid mechanically between the pressure change device and the throttle point is provided.

According to a structurally possible embodiment of the present invention, at least one reservoir of working fluid 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, provision can be made for a dispensing reservoir under a first system pressure and an aspiration reservoir under a second system pressure, which can optionally be connected to the pipetting channel in a pressure-transmitting manner and are separable therefrom, the first system pressure being greater than an ambient pressure of the pipetting device and the second system pressure being less than the ambient pressure.

With regard to the flow processes of the working fluid through the throttle point, it is advantageous in aspiration and dispensing processes if the system pressure is at least opposite for dispensing processes the ambient pressure of the metering liquid receiving space does not exceed an overpressure of 1.5 bar, preferably 1.2 bar, particularly preferably 1.0 bar. With higher pressure differences between the system pressure and the ambient pressure, there can be highly turbulent flows of the working fluid through the throttle point, which under certain circumstances can impair the effect of the present invention.

In principle, however, it can also be considered that the pressure change device has a discontinuously or continuously operating pump, possibly in combination with a valve arrangement, which can be arranged in the delivery path of the pump and optionally opened and closed. With regard to the always desired automation of dosing processes, it is advantageous if the pump is driven by a motor.

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 movably accommodated therein along the cylinder axis, the cylinder and piston limiting at least one working volume which can be changed by a relative movement of the piston relative to the cylinder and which is or can be brought into fluid transmission connection with the pipetting channel. The piston-cylinder arrangement represents the most common design of the pressure change device in pipetting devices. It also offers the possibility of very precise pressure control through the use of small piston areas and piston strokes that are long in relation to this.

Especially with the aforementioned piston-cylinder device as the pressure changing device, the pipetting device can also be a pipetting device which can be operated manually as intended, in which case the piston can be moved relative to the cylinder by manual operation. This operation can be done directly, i.e. by pulling it out or pushing the piston in by hand, or can be done indirectly, for example by tensioning a spring, which drives a relative movement between the piston and the cylinder after triggering. The manually operable pipetting device preferably has only exactly one pipetting channel for the most accurate dosing possible.

"Manually operated according to the intended purpose" is not intended to cover those cases which are fundamentally operated by motor or otherwise in an automated manner and can only be operated further by a manual emergency operation in the event of a power supply failure.

Particularly in the case of dosing by aspiration and dispensation, it is advantageous to meet the highest hygiene requirements if the dosing liquid receiving space and the pipetting opening are designed on a pipette tip that is separate from the pipette channel that has the throttle point and that can optionally be connected to and / or separated from it are. In contrast, outlets, so-called "washing pipes", which are provided rigidly with the pipetting device, are preferred for the aforementioned washing head pipetting device.

The present invention will be explained in more detail below with reference to the accompanying drawing, which shows a rough schematic longitudinal section through an embodiment of a pipetting device according to the invention.

In Figure 1 An embodiment of a pipetting device according to the invention, shown roughly schematically, is generally designated by 10. The pipetting device 10 comprises a pipetting channel 12, to which a pipette 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 along a longitudinal axis coinciding with the cylinder axis Z. L of the pipetting device 10 is adjustable relative to the cylinder section 16 via a piston rod 20 by a motor 22.

The motor 22 is controlled by a control unit 24, for example as a function of the detection signal of a pressure sensor 26, which detects the pressure of a working fluid, such as air, in a working chamber 28 that changes in volume due to 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 a ejector 30 which can be moved along the longitudinal axis L of the pipette device 10 relative to the cylinder section 16, has a coupling area 32 designed for coupling to the pipette channel 12, one in the in Figure 1 Example shown conical 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 possibly also by the coupling area 32 is at least partially filled, in the dosing liquid - The aspirating space can be aspirated and dispensed from it.

The assembly of cylinder 16 and piston 18 forms a pressure change device 40 for changing the pressure of working fluid in the metering liquid receiving space 38.

wobei η_Dst die dynamische Viskosität des Arbeitsfluids ist, I_Dst eine charakteristische Länge der Drosselstelle 42 in Strömungsrichtung des Arbeitsfluids bei der Dispensation von Dosierflüssigkeit ist und wobei d_Dst eine charakteristische Abmessung des Strömungsquerschnitts der Drosselstelle 42 ist, in dem in Figur 1 gezeigten Beispiel der Durchmesser der Drosselstelle 42 ist. In dem in Figur 1 gezeigten Beispiel ist die Drosselstelle 42 im Wesentlichen durch einen zylindrischen Kanal gebildet, so dass die Länge des Kanals die charakteristische Länge I_Dst der Drosselstelle 42 ist.According to the invention, a throttle point 42 is provided between the pressure changing device 40 and the metering liquid receiving space 38, which has a flow resistance R ₂ for working fluid, which is preferably calculated from $$R_{\mathrm{2nd}}=\frac{128\cdot {\eta }_{\mathit{German}}\cdot l_{\mathit{German}}}{\pi \cdot d_{\mathit{German}}^{\mathrm{4th}}}$$

where η _{Dst is} the dynamic viscosity of the working fluid, I _{Dst is} a characteristic length of the throttle point 42 in the direction of flow of the working fluid in the dispensing of dosing liquid, and wherein D _{Dst is} a characteristic dimension of the flow cross section of the throttle point 42 in which in Figure 1 Example shown is the diameter of the throttle point 42. In the in Figure 1 In the example shown, the throttle point 42 is essentially formed by a cylindrical channel, so that the length of the channel is the characteristic length I _{Dst of} the throttle point 42.

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 spread of the working fluid pressure from the working space 28 into the metering liquid receiving space 38.

The valve 44 is preferably also operable by the control device 24.

wobei η_Pof die dynamische Viskosität des die Pipettieröffnung 36 durchströmenden Mediums, also der Dosierflüssigkeit, ist, I_Pof eine charakteristische Länge eines zur Pipettieröffnung 36 führenden Auslassendes der Pipettierspitze 14 ist, und d_Pof eine charakteristische Abmessung des Strömungsquerschnitts der Pipettieröffnung 36, im vorliegenden Regelfall einer kreisförmigen Pipettieröffnung der Durchmesser der Pipettieröffnung 36 ist.The pipetting opening 36, on the other hand, has a flow resistance R ₁ during dispensing, which preferably results from $$R_1=\frac{128\cdot {\eta }_{\mathit{Pof}}\cdot l_{\mathit{Pof}}}{\pi \cdot d_{\mathit{Pof}}^{\mathrm{4th}}}$$

where η _{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, and d _{Pof is} a characteristic dimension of the flow cross section of the pipetting _opening 36, in the present case as a rule of a circular pipetting opening is the diameter of the pipetting opening 36.

At the in Figure 1 The example shown here of a pipette tip 14 tapering conically or in some other way towards the pipette opening 36 can be used to determine the characteristic length:
The characteristic length I is the length that the outlet end of the pipette tip 14 has from the pipette opening 36 to the point at which the flow cross section of the pipette tip 14 has twice the area as the pipette opening 36. Since the flow cross section in a circular shape is proportional to the square of the radius or the diameter, the length that exists between the respective flow cross-section constriction and a flow cross-section whose diameter is √2 times the diameter can be assumed as the characteristic length of an outlet area that tapers conically or otherwise to the respective flow cross-section constriction with the narrowest flow cross-section the flow cross-sectional constriction is.

It has been found that with increasing flow cross sections in the pipette tip 14 or also 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 throttling point 42 which have a flow cross-sectional area that is more than twice as large as the flow cross-sectional area of the narrowest cross-section only contribute to the respective flow resistance of the relevant flow cross-section constriction in subordinate orders of magnitude. They can therefore be neglected.

Then when the ratio of the two flow resistances at the throttle point 42 and the pipetting opening 36, taking into account the media flowing through the respective flow cross-sectional constrictions, a ratio of 0.5 based on their dynamic viscosity, 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 or / and crystallized metering liquid.

Of course, the metering behavior changes with increasing narrowing of the pipetting opening 36 from falling below a critical constriction level even in spite of the provision of the throttle point 42 in the pipetting channel 12 between the pressure changing device 40 and the metering liquid receiving space 38. However, the limit at which influences of such deposits occur of the pipetting opening 36 or in a region close to the pipetting opening 36 during dispensing, are pushed further in the direction of a cross-sectional reduction of the pipetting opening 36.

The same applies to the aspiration of dosing liquid.

If 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 within certain limits independent of the viscosity of the Dosing liquid used are made so that different viscous dosing liquids can be dosed the same with one and the same pipetting device 10 and one and the same operating parameters. This considerably simplifies the operation of pipetting devices.

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 means of a pipetting device according to the invention without changing the operating parameters.

Dosing tasks of pipetting devices can therefore be significantly simplified with the present invention.

The present invention is particularly applicable for dosing tasks which a pipetting device 10, as a so-called "washing head pipetting device", has to fulfill when it is intended to dispense washing liquid as dosing liquid in precise doses.

These washing head pipetting devices can be used to clean objects 37 in sample containers 39 or sample containers 39 alone, which are usually located under the pipetting opening 36, by dispensing a measured amount of washing liquid as a metering liquid.

For this purpose, such a washing head pipetting device 10 can have a metering liquid inlet 50 which, starting from a metering liquid supply 52, can open into the metering liquid receiving space 38 at an opening 54.

In this case, the metering liquid receiving space can advantageously be filled with metering liquid (then in the form of washing liquid) through the metering liquid inlet 50, so that in this case the metering liquid need not be aspirated through the pipetting opening 36.

The metering liquid in the metering liquid supply 52 can be conveyed into the metering liquid receiving space 38 by a pump 56, which can also be controlled by the control / regulating device 24, via the metering liquid inlet 50. In order to be able to set the delivery rate conveyed through the metering liquid inlet 50 even more precisely, a valve 58 can also be provided on the metering liquid inlet 50, which valve 58 can be opened and closed by the control device 24.

For example, by means of a suitable program in the control device, a predetermined pressure can be built up in the metering liquid supply 50 when the valve 58 is closed by operating the pump 56, whereupon the valve 58 is opened for a predetermined time and then closed again.

In order to prevent or keep dosing liquid running from the dosing liquid inlet 50 into the dosing liquid receiving space 38, the valve 58 is preferably arranged at the mouth 54 or in relation to the total length of the dosing liquid inlet close to the mouth 54. The distance of the valve 58 from the mouth 54 should preferably not exceed 5% of the total length of the metering liquid inlet 58.

The pipetting device 50, in particular as a washing head pipetting device 10, can have further pipetting channels beyond the illustrated pipetting channel 12, which are essentially identical to the illustrated pipetting channel 12, so that the pipetting device 12 shown in FIG Fig. 1 The illustrated pipetting channel 12 is described by way of example for all pipetting channels of a multi-channel pipetting device. Washing head pipetting devices can, for example, have pipetting channels 12 in a matrix arrangement of 8 × 12 = 96 pipetting channels.

In the case of a multi-channel pipetting device, the metering liquid inlets 50 to each pipetting channel 12 can then be connected to a common metering liquid supply 52 via a common pump 56.

Likewise, all piston rods 20 of the individual pipetting channels 12 can be adjusted by a common motor 22.

Nevertheless, it should not be excluded that each pipetting channel has its own motor 22, its own pump 56 and / or its own dosing liquid supply 52.

The fixing means 60 is intended to indicate that the pipetting tip 34 can be permanently coupled to the pipetting channel 12 as a washing tube and cannot be detached. The washing tube can also be formed in one piece with a tube of the pipetting channel, for example with the cylinder section 16.

1. 1. Pipettiervorrichtung (10) wenigstens zur Dispensation von Dosierflüssigkeit durch Erhöhung des Drucks eines Arbeitsfluids, umfassend:
   • einen wenigstens teilweise mit Arbeitsfluid gefüllten Dosierflüssigkeits-Aufnahmeraum (38) mit einer Pipettieröffnung (36) als einer ersten Strömungsquerschnittsverengung, durch welche hindurch Dosierflüssigkeit in Abhängigkeit vom Druck des Arbeitsfluids aus dem Dosierflüssigkeits-Aufnahmeraum (38) hinaus dispensierbar ist, und
   • eine Druckveränderungsvorrichtung (40), welche dazu ausgebildet ist, den Druck des Arbeitsfluids im Dosierflüssigkeits-Aufnahmeraum (38) zu verändern,
   dadurch gekennzeichnet, dass die Pipettiervorrichtung (10) in einem betriebsmäßig mit Arbeitsfluid gefüllten Pipettierkanal (12) fluidmechanisch zwischen dem Dosierflüssigkeits-Aufnahmeraum (38) und der Druckveränderungsvorrichtung (40) eine Drosselstelle (42) als weitere Strömungsquerschnittsverengung aufweist, welche derart dimensioniert ist, dass ein Verhältnis eines Strömungswiderstands (R₁) der Pipettieröffnung (36) für dispensierte Dosierflüssigkeit zu einem Strömungswiderstand (R₂) der Drosselstelle (42) für Arbeitsfluid, welches die Drosselstelle (42) 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 (36 bzw. 42) berechnet werden unter Berücksichtigung des Produkts aus der Viskosität des der jeweiligen Strömungsquerschnittsverengung (36 bzw. 42) zugeordneten Mediums aus Arbeitsfluid und Dosierflüssigkeit und der charakteristischen Länge (I_Dst, I_Pof) der zugeordneten Strömungsquerschnittsverengung (36 bzw. 42), geteilt durch die vierte Potenz der charakteristischen Abmessung (d_Dst, d_Pof) des Strömungsquerschnitts der zugeordneten Strömungsquerschnittsverengung (36 bzw. 42).
2. 2. Pipettiervorrichtung (10) nach Anspruch 1,
   dadurch gekennzeichnet, dass sie eine Waschkopf-Pipettiervorrichtung (10) ist, welche zur Dispensation von Waschflüssigkeit als Dosierflüssigkeit ausgebildet ist und welche einen Dosierflüssigkeits-Zulauf (50) aufweist, der vorzugsweise im Dosierflüssigkeits-Aufnahmeraum (38) mündet, so dass der Dosierflüssigkeits-Aufnahmeraum (38) durch den Dosierflüssigkeits-Zulauf (50) wenigstens teilweise mit Dossierflüssigkeit füllbar ist.
3. 3. Pipettiervorrichtung (10) nach Anspruch 1 oder 2,
   dadurch gekennzeichnet, dass sie eine Mehrzahl von im Wesentlichen parallelen Pipettierkanälen (12) aufweist, von welchen jeder Pipettierkanal (12) mit je einer Drosselstelle (42) als der weiteren Strömungsquerschnittsverengung versehen ist.
4. 4. Pipettiervorrichtung (10) nach einem der vorhergehenden Ansprüche,
   dadurch gekennzeichnet, dass sie auch zur Aspiration von Dosierflüssigkeit durch Verringerung des Drucks des Arbeitsfluids ausgebildet ist, wobei bei der Aspiration Dosierflüssigkeit in Abhängigkeit vom Druck des Arbeitsfluids durch die Pipettieröffnung (36) in den Dosierflüssigkeits-Aufnahmeraum (38) hinein aspirierbar ist, wobei das Verhältnis des Strömungswiderstands (R₁) der Pipettieröffnung (36) für dispensierte Dosierflüssigkeit zu dem Strömungswiderstand (R₂) der Drosselstelle (42) 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.
5. 5. Pipettiervorrichtung (10) nach einem der vorhergehenden Ansprüche,
   dadurch gekennzeichnet, dass die 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.
6. 6. Pipettiervorrichtung (10) nach einem der vorhergehenden Ansprüche,
   dadurch gekennzeichnet, dass die Viskosität des Arbeitsfluids den Wert von 0,00003 Nsm^-2, vorzugsweise von 0,00002 Nsm^-2, besonders bevorzugt von 0,0000175 Nsm^-2 nicht übersteigt.
7. 7. Pipettiervorrichtung (10) nach einem der vorhergehenden Ansprüche,
   dadurch gekennzeichnet, dass die Drosselstelle (42) einen wahlweise veränderbaren Strömungsquerschnitt aufweist.
8. 8. Pipettiervorrichtung (10) nach einem der vorhergehenden Ansprüche,
   dadurch gekennzeichnet, dass der Pipettierkanal (12) ein zwischen einer Sperrstellung, in welcher eine Arbeitsfluidströmung im Pipettierkanal (12) unterbunden ist, und einer Offenstellung, in welcher eine Arbeitsfluidströmung im Pipettierkanal (12) gestattet ist, verstellbares Ventil (44) aufweist.
9. 9. Pipettiervorrichtung (10) nach Anspruch 8,
   dadurch gekennzeichnet, dass das Ventil (44) an der Drosselstelle (42) oder fluidmechanisch zwischen der Druckveränderungsvorrichtung (40) und der Drosselstelle (42) vorgesehen ist.
10. 10. Pipettiervorrichtung (10) nach einem der vorhergehenden Ansprüche,
    dadurch gekennzeichnet, dass sie als die Druckveränderungsvorrichtung (40) wenigstens ein unter einem Systemdruck stehendes Reservoir an Arbeitsfluid aufweist.
11. 11. Pipettiervorrichtung (10) nach Anspruch 10,
    dadurch gekennzeichnet, 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 (12) verbindbar und von diesem trennbar sind, wobei der erste Systemdruck größer ist als ein Umgebungsdruck der Pipettiervorrichtung (10) und der zweite Systemdruck kleiner ist als der Umgebungsdruck.
12. 12. Pipettiervorrichtung (10) nach Anspruch 10 oder 11,
    dadurch gekennzeichnet, dass der Systemdruck für Dispensationsvorgänge gegenüber dem Umgebungsdruck des Dosierflüssigkeits-Aufnahmeraums (38) einen Überdruck von 1,5 bar, vorzugsweise von 1,2 bar, besonders bevorzugt von 1,0 bar nicht übersteigt.
13. 13. Pipettiervorrichtung (10) nach einem der vorhergehenden Ansprüche,
    dadurch gekennzeichnet, dass die Druckveränderungsvorrichtung (40) eine Pumpe, insbesondere motorisch angetriebene Pumpe, aufweist.
14. 14. Pipettiervorrichtung (10) nach einem der vorhergehenden Ansprüche,
    dadurch gekennzeichnet, dass die Druckveränderungsvorrichtung (40) eine Kolben-Zylinder-Vorrichtung (16, 18, 20) mit einem sich längs einer Zylinderachse (Z) erstreckenden Zylinder (16) und mit einem darin längs der Zylinderachse (Z) beweglich aufgenommenen Kolben (18) aufweist, wobei Zylinder (16) und Kolben (18) wenigstens ein Arbeitsvolumen (28) begrenzen, welches durch eine Relativbewegung des Kolbens (18) relativ zum Zylinder (16) veränderlich ist und welches mit dem Pipettierkanal (12) in Fluidübertragungsverbindung steht oder bringbar ist.
15. 15. Pipettiervorrichtung (10) nach einem der vorhergehenden Ansprüche,
    dadurch gekennzeichnet, dass der Dosierflüssigkeits-Aufnahmeraum (38) und die Pipettieröffnung (36) an einer von dem die Drosselstelle (42) aufweisenden Pipettierkanal (12) gesondert ausgebildeten, wahlweise mit diesem verbindbaren oder von diesem trennbaren Pipettierspitze (14) ausgebildet sind.

In order to take over the complete original disclosure content of the parent application in the present divisional application, on the following pages 20 to 23 the originally filed claims 1 to 15 are now repeated as part of the description.

1. A pipetting device (10) at least for dispensing dosing liquid by increasing the pressure of a working fluid, comprising:
   • an at least partially filled with working fluid dosing liquid receiving space (38) with a pipetting opening (36) as a first flow cross-section constriction through which dosing liquid can be dispensed from the dosing liquid receiving space (38) depending on the pressure of the working fluid, and
   • a pressure change device (40) which is designed to change the pressure of the working fluid in the metering liquid receiving space (38),
   characterized in that the pipetting device (10) has a throttle point (42) as a further flow cross-sectional constriction in a pipetting channel (12) that is operationally filled with working fluid between the dosing liquid receiving space (38) and the pressure changing device (40), which is dimensioned such that a ratio of a flow resistance (R ₁ ) of the pipetting opening (36) for dispensed dosing liquid to a flow resistance (R ₂ ) of the throttle point (42) for working fluid which flows through the throttle point (42) during the dispensing of the dosing fluid, less than 0.5, is preferably less than 0.3, particularly preferably less than 0.225, the flow resistances of the respective flow cross-section constriction (36 or 42) being calculated taking into account the product from the viscosity of the medium composed of working fluid and of the respective flow cross-section constriction (36 or 42) Dosing liquid and the characteristic length (I _Dst , I _Pof ) of the assigned flow _{cross-sectional constriction} (36 or 42), divided by the fourth power of the characteristic dimension (d _Dst , d _Pof ) of the flow cross-section of the assigned flow _{cross-sectional constriction} (36 or 42).
2. 2. pipetting device (10) according to claim 1,
   characterized in that it is a washing head pipetting device (10) which is designed for dispensing washing liquid as a metering liquid and which has a metering liquid inlet (50) which preferably opens into the metering liquid receiving space (38) so that the metering liquid Receiving space (38) can be at least partially filled with dosing liquid through the metering liquid inlet (50).
3. 3. pipetting device (10) according to claim 1 or 2,
   characterized in that it has a plurality of substantially parallel pipetting channels (12), of which each pipetting channel (12) is each provided with a throttle point (42) as the further narrowing of the flow cross section.
4. 4. pipetting device (10) according to any one of the preceding claims,
   characterized in that it is also designed for aspirating dosing liquid by reducing the pressure of the working fluid, wherein in the case of aspiration dosing liquid can be aspirated into the dosing liquid receiving space (38) depending on the pressure of the working fluid through the pipetting opening (36), the Ratio of the flow resistance (R ₁ ) of the pipetting opening (36) for dispensed dosing liquid to the flow resistance (R ₂ ) of the throttle point (42) for this working fluid flowing through the dispensing of the dosing fluid is less than 0.001, preferably less than 0.00075, particularly preferably less than 0.0005.
5. 5. pipetting device (10) according to any one of the preceding claims,
   characterized in that the viscosity of the dosing liquid does not exceed the value of 0.004 Nsm ^-2 , preferably 0.0035 Nsm ^-2 , particularly preferably 0.0031 Nsm ^-2 .
6. 6. pipetting device (10) according to one of the preceding claims,
   characterized in that the viscosity of the working fluid does not exceed the value of 0.00003 Nsm ^-2 , preferably 0.00002 Nsm ^-2 , particularly preferably 0.0000175 Nsm ^-2 .
7. 7. pipetting device (10) according to one of the preceding claims,
   characterized in that the throttle point (42) has an optionally variable flow cross-section.
8. 8. pipetting device (10) according to any one of the preceding claims,
   characterized in that the pipetting channel (12) has a valve (44) adjustable between a blocking position in which a working fluid flow in the pipetting channel (12) is prevented and an open position in which a working fluid flow is permitted in the pipetting channel (12).
9. 9. pipetting device (10) according to claim 8,
   characterized in that the valve (44) is provided at the throttle point (42) or fluid mechanically between the pressure changing device (40) and the throttle point (42).
10. 10. pipetting device (10) according to any one of the preceding claims,
    characterized in that as the pressure changing device (40) it has at least one reservoir of working fluid under a system pressure.
11. 11. pipetting device (10) according to claim 10,
    characterized in that a dispensing reservoir under a first system pressure and an aspiration reservoir under a second system pressure are provided, which can optionally be connected to and separated from the pipetting channel (12) in a pressure-transmitting manner, the first system pressure being greater than one Ambient pressure of the pipetting device (10) and the second system pressure is less than the ambient pressure.
12. 12. pipetting device (10) according to claim 10 or 11,
    characterized in that the system pressure for dispensing processes does not exceed an overpressure of 1.5 bar, preferably 1.2 bar, particularly preferably 1.0 bar, in relation to the ambient pressure of the metering liquid receiving space (38).
13. 13. pipetting device (10) according to one of the preceding claims,
    characterized in that the pressure changing device (40) has a pump, in particular a motor-driven pump.
14. 14. pipetting device (10) according to any one of the preceding claims,
    characterized in that the pressure changing device (40) is a piston-cylinder device (16, 18, 20) with a cylinder (16) extending along a cylinder axis (Z) and with a piston (movably received therein along the cylinder axis (Z)) 18), the cylinder (16) and piston (18) delimiting at least one working volume (28) which is variable by a relative movement of the piston (18) relative to the cylinder (16) and which is in fluid transmission connection with the pipetting channel (12) or is feasible.
15. 15. pipetting device (10) according to any one of the preceding claims,
    characterized in that the metering liquid receiving space (38) and the pipetting opening (36) are formed on a pipetting tip (14) which is separate from the pipetting channel (12) and which has the throttle point (42), can be optionally connected to or separated from it.

Claims (16)

Pipetting process comprising the steps: Provision of a metering liquid receiving space (38), which has a pipetting opening (36) as the first flow cross-section constriction, - Aspirating dosing liquid through the pipetting opening (36) into the dosing liquid receiving space (38) by lowering a pressure of a working fluid, and 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, characterized in that
the working fluid flows through a throttle point (42) as a further narrowing of the flow cross section both during aspiration and during dispensing. The pipetting method according to claim 1, wherein a ratio of the flow resistance (R1) of the pipetting opening (36) with respect to the metering liquid to the flow resistance (R2) of the throttle point (42) with respect to the working fluid is less than 0.5, in particular less than 0.3 and in particular less than Is 0.225. 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 , particularly 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 , particularly preferably the value of 0.0000175 Nsm ^-2 . The pipetting method according to any one of claims 1 to 4, wherein the working fluid is a gas. Pipetting method according to one of claims 1 to 5, wherein a liquid amount of the dosing liquid is determined by a time during which a valve upstream of the pipetting opening (36) is opened. Pipetting method according to one of claims 1 to 6, wherein the dosing liquid receiving space provided is at least partially filled with a working fluid, the lowering of the pressure of the working fluid and the increase of the pressure of the working fluid being carried out by means of a pressure change device (40) which is designed to do this To change the pressure of the working fluid in the metering liquid receiving space (38) and wherein the throttle point (42) is arranged in a pipetting channel (12) which is arranged mechanically between the metering liquid receiving space (38) and the pressure changing device (40). The pipetting method according to claim 7, wherein a liquid quantity of the dosing liquid is dosed very precisely by intermittently opening and closing a valve, the pipetting channel (12) having the valve and the valve being adjustable between a blocking position in which a working fluid flow in the pipetting channel is prevented, and an open position in which a working fluid flow is permitted in the pipetting channel. Pipetting method according to one of claims 7 or 8, wherein the pressure changing device (40) has working fluid at a system pressure. Pipetting method according to claim 9, wherein a dispensing reservoir under a first system pressure and an aspiration reservoir under a second system pressure are provided, which are selectively connected in a pressure-transmitting manner to the pipetting channel (12) to increase the pressure or to decrease the pressure of the working fluid or be separated from it, the first system pressure being greater than one Ambient pressure of the pipetting device (10) and the second system pressure is less than the ambient pressure. A method for producing a dose of a dosing liquid comprising the pipetting method according to any one of claims 1 to 10, wherein the dose is dispensed in the dispensing step. A method for producing a plurality of doses of a dosing liquid which essentially comprise the same amount of dosing liquid, each dose of the plurality of doses being produced according to the method according to claim 11 and wherein the plurality of doses comprises at least a first dose which is dispensed from a first pipetting opening and comprises a second dose which is dispensed from a second pipetting opening. The method of claim 12, 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, essentially identical pipetting devices. A method according to any one of claims 12 or 13, wherein the steps of the pipetting process are carried out at each dose of the A plurality of cans can be carried out with identical operating parameters. A method according to claim 11 for producing a first dose of a first dosing liquid with a first viscosity and a second dose of a second dosing liquid with a second viscosity, which is different from the first viscosity,
wherein the first dose is produced in a first dosing process and wherein the second dose is produced in a second dosing process and wherein the first and the second dose comprise essentially the same amount of dosing liquid,
the steps of the pipetting method according to one of claims 1 to 10 being carried out with identical operating parameters in the first and in the second dosing process. The method of claim 15, 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 metering 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.

Images