DOSING DEVICE AND METHOD OF DOSING LIQUID MEDIA

Abstract

A dosing device has a dosing tip for dispensing liquid medium and at least one pressure vessel with a pressurizing gas, in which an overpressure or a negative pressure can be set as a predefined pressure setpoint value of an internal pressure by a pressure regulator, the internal pressure set by means of the pressurizing gas acting on a first liquid medium. A bidirectional flow meter is provided to measure a quantity of the first medium that is moved by the internal pressure prevailing in the pressure vessel. Furthermore, a dosing valve is provided upstream of the dosing tip, which is adapted to enable or disable a flow of the first medium from the flow meter to the dosing tip. For precise dosing, the first medium is moved by means of a change in the predefined pressure setpoint value of the internal pressure of at least one pressure vessel, and the moved quantity of the first medium is measured by means of the flow meter.

Claims

1. A dosing device, comprising: a dosing tip for dispensing liquid medium; and at least one pressure vessel with a pressurizing gas, in which an internal pressure can be set by a pressure regulator to a predefined pressure setpoint value, which is an overpressure or a negative pressure relative to an environment of the dosing device, wherein the internal pressure is set by the pressurizing gas acting on a first liquid medium, a bidirectional flow meter that is designed to measure a quantity of the first medium that is moved by the internal pressure prevailing in the pressure vessel, and a dosing valve located upstream of the dosing tip and designed to enable or disable a flow of the first medium from the flow meter to the dosing tip.

2. The dosing device according to claim 1, wherein the predefined pressure setpoint value of the internal pressure in the pressure vessel can assume a negative pressure that moves the first medium away from the dosing tip and aspirates a second liquid medium into the dosing tip.

3. The dosing device according to claim 1, wherein a separation aid is present in the dosing tip, which consists of a separation medium aspirated into the dosing tip or a movable separating element inserted into the dosing tip.

4. The dosing device according to claim 3, wherein the separating element comprises a piston having a sealing disk that is arranged in a widened portion of the dosing tip directed away from an outlet end of the dosing tip and rests against an inner wall of the dosing tip, and a rod which projects perpendicularly from the sealing disk and protrudes into a narrower portion of the dosing tip adjoining the widened portion towards the outlet end.

5. The dosing device according to claim 1, further comprising two pressure vessels with pressurizing gas, wherein in one of the pressure vessels, the predefined pressure setpoint value of the internal pressure can be set as a negative pressure relative to the environment of the dosing device, and in the other pressure vessel, the predefined pressure setpoint value of the internal pressure can be set as an overpressure relative to the environment of the dosing device.

6. The dosing device according to claim 5, wherein a switching valve is arranged downstream of the pressure vessels and upstream of the flow meter.

7. The dosing device according to claim 5, wherein an equalizing tank is additionally provided downstream of the pressure vessels, which is adapted to be placed in fluid communication with each of the two pressure vessels and in which a part of the first medium is held.

8. The dosing device according to claim 7, wherein the pressurizing gas is exclusively present in both pressure vessels.

9. A method of dosing at least one liquid medium by a dosing device having a dosing tip for dispensing liquid medium and at least one pressure vessel with a pressurizing gas, in which an internal pressure can be set by a pressure regulator to a predefined pressure setpoint value, which is an overpressure or a negative pressure relative to an environment of the dosing device, wherein the internal pressure is set by the pressurizing gas acting on a first liquid medium, a bidirectional flow meter that is designed to measure a quantity of the first medium that is moved by the internal pressure prevailing in the pressure vessel, and a dosing valve located upstream of the dosing tip and designed to enable or disable a flow of the first medium from the flow meter to the dosing tip, the method comprising: setting the internal pressure of at least one pressure vessel to the predefined pressure setpoint value; moving the first medium within the dosing device by a pressure differential between the internal pressure and an environment of the dosing device; and measuring the moving quantity of the first medium by the flow meter, which is fluidically arranged between the dosing tip and the pressure vessel.

10. The method according to claim 9, wherein a second liquid medium is aspirated through the dosing tip and subsequently dispensed through the dosing tip.

11. The method according to claim 9, wherein the aspiration of the second medium is affected by selecting a negative pressure for the predefined pressure setpoint value of the internal pressure in at least one pressure vessel and, resulting therefrom, by a movement of first medium away from the dosing tip.

12. The method according to claim 9, wherein, prior to the aspiration of the second medium, a separation medium is aspirated through the dosing tip as a separation aid, which is located between the first and second media, or a separating element inserted in the dosing tip is moved, the separation aid preventing contact between the two media.

13. The method according to claim 9, wherein a dosing is performed by a pressure-time control, wherein before the start of a dosing process the pressure setpoint value is adjusted of the internal pressure within the pressure vessel and a quantity of the first medium moved within a switching time interval is measured.

14. The method according to claim 13, wherein at least one dosing process is provided in which only a partial quantity of the total quantity of the first medium to be moved is moved, wherein after this dosing process a deviation of the quantity moved in this dosing process from a predefined quantity to be moved is determined and the switching time interval is adapted for a subsequent dosing process.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0083] FIG. 1 shows a schematic representation of a dosing device according to a first embodiment of the invention;

[0084] FIG. 2 shows a schematic representation of a dosing device according to a second embodiment of the invention;

[0085] FIG. 3 shows a schematic representation of a dosing device according to a third embodiment of the invention;

[0086] FIGS. 4 and 5 show dosing tips for a dosing device according to the invention; and

[0087] FIGS. 6 to 8 show schematic flow diagrams for dosing methods according to the invention for implementation with a dosing device according to the invention.

DETAILED DESCRIPTION

[0088] FIG. 1 shows a dosing device 10 according to a first embodiment.

[0089] The dosing device 10 is used to precisely dose extremely small quantities of liquids (for example in the range of from 1 μl to 50 μl). To do so, the liquid is pressed out of a dosing tip 12 (see also FIGS. 4 and 5) so that it exits at an outlet end 14 of the dosing tip 12 and enters a suitable container 16, for example a sample container.

[0090] In these examples, dosing into the container 16 is performed in a contactless manner, i.e., the outlet end 14 of the dosing tip 12 touches neither the container 16 nor a medium present in this container 16.

[0091] The container 16 may be configured to be inserted into the dosing device 10, but is generally separable from the dosing device 10. In addition, in principle, the dosing tip 12 can cooperate with different containers.

[0092] Inside the dosing device 10, a first liquid medium 20 is located in a fluid conduit system 18.

[0093] Here, the first medium 20 is a liquid the properties of which are well known and which, in this example, may also be made use of as a process medium or as a flushing or cleaning solution. For example, distilled water, alcohols or particular oils come into consideration here.

[0094] The fluid conduit system 18 is composed of all of the fluid carrying components of the dosing device 10.

[0095] In this example, the fluid conduit system 18 is linear in structure, with a dosing valve 22 being arranged upstream of the dosing tip 12, the dosing valve 22 in turn being followed upstream by a flow meter 24, from which a conduit section runs to an upstream pressure vessel 26.

[0096] The dosing valve 22 is a solenoid valve here, the drive unit of which is partitioned off from the fluid-carrying areas, for example by a diaphragm, so that the first medium 20 will not come into contact with the drive components of the dosing valve 22 when it flows through the dosing valve 22.

[0097] When the dosing valve 22 is open, first medium 20 can flow through the dosing valve 22 toward the dosing tip 12 and in the opposite direction. When the dosing valve 22 is closed, the first medium 20 cannot move through the dosing valve 22.

[0098] Due to the capillary forces which act in the fluid conduits and the dosing tip 12 and which are caused by the small cross-section, a quantity of first medium 20 located between the outlet end 14 of the dosing tip 12 and the dosing valve 22 will generally not flow out of the dosing tip 12.

[0099] The flow meter 24 may be configured as desired, but it is essential that it be able to capture or register the passage of quantities of liquid e.g. smaller than 1 μl in either direction.

[0100] In the pressure vessel 26, part of the volume is filled with a pressurizing gas 28, which may be air or an inert gas, for example. The remaining volume is filled with first medium 20.

[0101] The pressure vessel 26 is in fluid communication with a pressure regulator 30, which is capable of setting the internal pressure p in the pressure vessel 26 to a predefined pressure setpoint value p.sub.S over a wide pressure range. To this end, the pressure regulator 30 is connected to a pressure source (not illustrated), for example a pump or a compressed gas accumulator.

[0102] In this example, the predefined pressure setpoint value p.sub.S of the internal pressure p can be selected to be between about 20 mbar (20 hPa), possibly 500 mbar (500 hPa), and 3 bar (3000 hPa), so that the internal pressure p can be set to any desired value within these limits. The internal pressure p can thus assume both a marked negative pressure compared to the environment of the dosing device 10 and a marked overpressure compared to the environment of the dosing device 10.

[0103] In all examples described herein, the internal pressure p in the pressure vessel 26 remains constant during a dosing process, so that the pressure differential used to move the first medium 20 also remains constant.

[0104] The pressure regulator 30 may be made use of for this purpose, for example, but it is also possible to select the volume of the pressure vessel 26 to be large enough in comparison to the volume of the conduits of the dosing device 10 for the pressure vessel 26 to provide a sufficiently large reservoir to keep the internal pressure p constant for all practical purposes for the duration of a dosing process even without readjustment.

[0105] The pressure vessel 26 and the pressure regulator 30 here are part of a pressure control unit 32, which is structurally designed, e.g., as a component of the dosing device 10.

[0106] A control unit 34 is connected to the pressure regulator 30 and can exchange data with it and provide instructions to the pressure regulator 30.

[0107] The control unit 34 may be integrated into the dosing device 10, but may also be implemented externally and be connected to the dosing device 10 wirelessly or via a data line using a suitable interface.

[0108] The flow meter 24, the dosing valve 22 and the dosing tip 12 are part of a dosing unit 36, which may form a further structural component of the dosing device 10. An interface between the pressure control unit 32 and the dosing unit 36 is implemented, for example, by an outlet of the pressure vessel 26 and an inlet of the flow meter 24.

[0109] The control unit 34 is also connected to the flow meter 24 and the dosing valve 22, and in particular receives flow measurement values from the flow meter 24 and specifies a switching time interval t.sub.I for the dosing valve 22, which determines a period of time for which the dosing valve 22 is open during the dosing process.

[0110] The dosing device 10 can be operated in several different modes.

[0111] In a first mode, first medium 20 can be delivered, i.e. dispensed, through the dosing tip 12.

[0112] To this end, an overpressure p.sub.Ü is specified for the pressure setpoint value p.sub.S and the internal pressure p in the pressure vessel 26 is set accordingly to an overpressure that is high enough to overcome the flow resistance of the fluid conduit system 18 in relation to the ambient pressure of the dosing device 10, and the dosing valve 22 is opened. The pressurizing gas 28, which is under pressure p, therefore moves the first medium 20 toward and out of the dosing tip 12.

[0113] FIG. 6 shows an example of a pressure-time controlled dosing method for the dispensing of medium, e.g. of first medium 20 (method A).

[0114] First, the pressure regulator 30 sets the internal pressure p to a predefined pressure setpoint value p.sub.S, which is transmitted by the control unit 34, for example, and which defines an overpressure p.sub.Ü in relation to the environment (steps 100 and 102).

[0115] Based on the setpoint pressure value p.sub.S (which now corresponds to the internal pressure p in the pressure vessel 26), the total quantity of medium to be dispensed and other parameters, for example the current temperature, the viscosity of the first medium 20 and its density, the control unit 34 calculates a switching time interval t.sub.I which indicates the period of time for which the dosing valve 22 is to be open in order to dispense the desired amount of medium (step 104).

[0116] Simultaneously with the opening of the dosing valve 22, the measurement of the flow rate at the flow meter 24 is started (step 106).

[0117] After the switching time interval t.sub.I has elapsed, the dosing valve 22 is closed again and the measurement data of the flow meter 24 are transmitted to the control unit 34. The control unit evaluates the measurement and determines a deviation between the quantity of first medium 20 that has flowed through as ascertained by the flow meter 24 and the predefined partial quantity to be dispensed (step 108).

[0118] If the deviation is smaller than a predefined threshold value, the dosing will be continued with the existing values for the pressure setpoint value p.sub.S and the switching time interval t.sub.I for the next dosing process.

[0119] If the deviation is above the threshold value, the switching time interval t.sub.I and/or the pressure setpoint value p.sub.S are adapted for the subsequent dosing process (step 110).

[0120] Since the deviation becomes smaller with repeated passes through this closed loop control system, in most cases the dose dispensed will have been set to the desired value after a few dosing processes. It is possible to dispose of the medium 20 dispensed in these dosing processes used for setting and only employ the medium 20 for the actual process in step 112 when the deviation is sufficiently small.

[0121] It is possible to perform a check as described above also during dispensing of the total amount.

[0122] In a further mode, a second medium 38 can be aspirated into the dosing tip 12 from an external container (for example, the container 16 in FIG. 1). This is outlined as method B in FIG. 7.

[0123] To this end, a pressure setpoint value p.sub.S that corresponds to a negative pressure p.sub.U in relation to the environment of the dosing device 10 is specified by means of the pressure regulator 30 (steps 101 and 102).

[0124] As in the example just described, the control unit 34 determines a switching time interval t.sub.I for the dosing process, which opens the dosing valve 22 until the quantity to be dosed of first medium 20 has flowed through the flow meter 24 (step 104).

[0125] In this case, the first medium 20 flows away from the dosing tip 12 and toward the pressure vessel 26 when the dosing valve 22 is opened. This produces a negative pressure at the outlet end 14 of the dosing tip 12, which sucks (aspirates) the second medium 38 into the dosing tip 12.

[0126] In this case, the first medium 20 acts purely as a system or control medium to move the second medium 38.

[0127] The remaining steps 106 to 112 are performed as described above for the dispensing process.

[0128] A dosing process takes about 10 ms, for example.

[0129] In the examples of FIGS. 6 and 7, only the switching time interval t.sub.I is adjusted, while the pressure setpoint value p.sub.S remains unchanged. But it would be possible in all cases with the same result to also or exclusively change the pressure setpoint value p.sub.S.

[0130] To prevent mixing of the first medium 20 with the second medium 38 and thus contamination of both the second medium 38 and the dosing device 10, a separation aid is used here.

[0131] In one possible variant, a separation medium 40 is aspirated as a separation aid before the second medium 38 is aspirated. The result is depicted in FIG. 4. A small amount of the separation medium 40 is present between the first medium 20 and the second medium 38 and prevents contact between the two media 20, 38.

[0132] The separation medium 40 used may be, for example, a suitable liquid that is not miscible with either of the two media 20, 38, or, due to capillary forces, simply an air bubble.

[0133] The separation medium 40 is taken up from a separate container (not shown) (or, in the case of air, from the environment) before the dosing tip 12 is brought into contact with the second medium 38.

[0134] In an alternative variant, which is illustrated in FIG. 5, a separating element 42 is accommodated in the dosing tip 12 as a separation aid and is configured here in the form of a piston which includes, at its end remote from the outlet end 14, a sealing disk 44 from which a rod 46 projects perpendicularly toward the outlet end 14, which rod 46 is not in contact with an inner wall of the dosing tip 12 and which serves as a guide for the sealing disk 44 in order to keep the latter in sealing contact with the inner wall.

[0135] In this example, the sealing disk 44 is arranged in a widened portion 45 of the dosing tip 12, while the rod 46 protrudes into a narrower portion 47.

[0136] The sealing disk 44 separates the first medium 20 from the second medium 38, with the separating element 42 shifting within the dosing tip 12 as a result of the movement of the first medium 20.

[0137] To again dispense the second medium 38 now located in the lower portion of the dosing tip 12, the method A described above and illustrated in FIG. 6 is carried out again.

[0138] It is possible to aspirate a larger quantity of second medium 38 and to dispense it again in smaller quantities, for example, to take up 25 μl into the dosing tip 12 and to dispense 1 μl each in 25 individual dosages.

[0139] A process medium that is used as a reagent, for example in a diagnostic procedure or a manufacturing method, is usually employed as the second medium 38.

[0140] Of course, different second media 38 may be aspirated and dispensed successively by the dosing device 10.

[0141] Alternatively or additionally, a flushing or cleaning solution could also be used as the second medium 38.

[0142] The first medium 20, in contrast, can either be used purely as a system or control medium for moving the second medium 38 or can also be dispensed as a process medium. Here, the first medium 20 is furthermore used as a flushing or cleaning solution, for which purpose it is discharged through the dosing tip 12 in order to remove residues therefrom.

[0143] FIG. 8 shows the flexibility of the dosing device 10 using several possible methods. It is illustrated here to dose either first medium 20 or second medium 38.

[0144] If only first medium 20 is to be dispensed, the method A according to FIG. 6 is carried out in step 124.

[0145] If second medium 38 is to be dispensed, a separation aid, either a mechanical separating element 42 or a separation medium 40, is first introduced into the dosing tip 12 (step 114). If a separation medium 40 is to be used (step 116), it is taken up into the dosing tip 12 by means of the steps of the method B in FIG. 7.

[0146] Then the required amount of second medium 38 is aspirated (step 118), which is again carried out by means of the method B in FIG. 7.

[0147] Subsequently, in step 120, the second medium 38 is dosed, i.e. dispensed, using the method A from FIG. 6.

[0148] Finally, a flushing step 122 using first medium 20 may be performed, in which the remainder of the second medium 38 is removed from the dosing tip 12 and residues are eliminated. For this purpose, the method A of FIG. 6 is carried out with first medium 20 only, without first taking up second medium 38.

[0149] Process sequences other than those shown and described here are, of course, also conceivable; these possible processes are mentioned only by way of example.

[0150] If separation medium 40 is aspirated or the dosing tip 12 is flushed with first medium 20, this can be effected with low accuracy and therefore less time required.

[0151] FIG. 2 shows a second embodiment of the dosing device 10, which is likewise suitable for carrying out all of the methods described above.

[0152] The only difference from the first embodiment is that two pressure vessels 26 are provided here, each of which cooperates with a pressure regulator 30 of its own, with the internal pressure p of one pressure vessel 26 being permanently set to an overpressure p.sub.Ü and that of the other pressure vessel 26 being permanently set to a negative pressure p.sub.U. In this way, the changeover between dispensing and aspirating can be carried out faster, since the pressure vessel 26 does not first have to be changed over from overpressure to negative pressure or vice versa. Before starting a dosing process, e.g., the internal pressure p of one of the pressure vessels 26 is set to the predefined pressure setpoint value p.sub.S, wherein in each case only the level of overpressure or negative pressure needs to be adjusted.

[0153] In this example, both pressure vessels 26 contain both pressurizing gas 28 and first medium 20.

[0154] Here, the two pressure vessels 26 are connected with the inlet of the flow meter 24 by means of a 3/2-way switching valve 48, if required by a pipe that is part of the fluid conduit system 18.

[0155] To apply the desired pressure to the fluid conduits of the dosing device 10, the switching valve 48 is placed in fluid communication with the respective pressure vessel 26 in which the pressure setpoint value p.sub.S is set.

[0156] FIG. 3 shows a third embodiment of the dosing device 10, which is likewise suitable for carrying out all of the methods described above.

[0157] In contrast to the embodiment just described, an equalizing tank 50 is arranged in the fluid conduit system 18 between the switching valve 48 and the flow meter 24 in addition to the two pressure vessels 26. The equalizing tank 50 holds both an amount of first medium 20 and pressurizing gas 28.

[0158] In this example, the two pressure vessels 26, which are connected with the equalizing tank 50 by means of the switching valve 48, contain exclusively pressurizing gas 28, but no first medium 20.

[0159] The presetting of the predefined pressure setpoint value p.sub.S is performed here by setting the internal pressure p in the equalizing tank 50 by means of the position of the switching valve 48 and the pressure values p.sub.Ü, p.sub.U in the two pressure vessels 26, with pressurizing gas 28 flowing into the equalizing tank 50 from one of the pressure vessels 26 or flowing out of the equalizing tank 50 and into one of the pressure vessels 26, depending on the pressure setpoint value p.sub.S to be set.

[0160] This value can be checked, if desired, by means of a pressure sensor (not illustrated) within the equalizing tank 50.

[0161] The pressure transferred to the first medium 20 in the fluid conduit system 18 here corresponds to the internal pressure p in the equalizing tank 50, which therefore also acts as a pressure vessel.