Pipetting device, pipetting robot and method for using the pipetting device

Abstract

The invention relates to a pipetting device (1) for metering a liquid (60) by means of a fluid flow. The pipetting device (1) comprises a pump (2) with a pump chamber (27) for generating the fluid flow, wherein in the pump chamber (27) a pump element (20) is arranged by means of which the pump chamber (27) is divided into a pressure chamber (21) and a suction chamber (22), and wherein the pump element (20) can be moved in the pump chamber (27) such that the fluid flow can be generated by a change in volume of the pressure chamber (21) and the suction chamber (22). The pipetting device (1) further comprises a valve (3) for controlling the fluid flow, wherein the valve (3) is fluidically connected via a first inlet (31) to the pressure chamber (21) and via a second inlet (32) to the suction chamber (22). The pipetting device (1) also comprises a connection element (6) with a fluid inlet (63) which is fluidically connected to an outlet (38) of the valve (3) such that the fluid flow generated by the pump (2) can act on the liquid (60) via the connection element (6) for metering purposes.

Description

[0001] P ipettiervorrichtunq , pipetting robot and method for using the

[0002] Pipetting device

[0003] The invention relates to a pipetting device for dosing a liquid, a pipetting robot and a method for using the pipetting device according to the preamble of the independent claims.

[0004] Pipettes are currently used for dispensing liquids. Pipettes are typically used in the medical field, with disposable plastic pipette tips used to prevent contamination. For small volumes, so-called micropipettes are used, allowing small volumes of approximately 100 nanoliters and more to be pipetted. For repetitive tasks, electronically controlled pipettes are available, which are also used in laboratory automation and robotics.

[0005] Some pipettes work according to the displacement principle, whereby a moving piston displaces or draws in air, causing a liquid to flow out of or into the pipette tip.

[0006] As an alternative to the displacement principle, there are pipettes in the state of the art that operate according to the air cushion principle. A corresponding pipetting device is known, for example, from DE10237770A1. In this case, an air column separates the liquid drawn into the pipette tip from the interior of the pipette. The movement of a pump element of the pump creates a vacuum in the pipette tip, which causes the liquid to rise into the tip. The air column moved by the pump element creates a fluid flow, which causes the liquid to move into or out of the pipette tip.

[0007] Furthermore, devices used exclusively for dispensing liquids are known in the prior art. Unlike pipettes, these devices typically have a reservoir from which the liquid is dispensed. A specific volume is repeatedly dispensed from the reservoir. A corresponding liquid dispensing device is known from US Pat. No. 7,303,728 B2. Furthermore, WO 2006005923 A1 discloses a liquid dispensing system for dispensing liquid volumes in the submillimeter range.

[0008] Resonant acoustic pumps are known from WO 2022023703 A1, in which the volume of a pumping chamber is reduced to move a fluid out of the pumping chamber. EP 1531937 A1 uses a piezoelectric pump for a pipetting device. The pump is a disc-shaped micropump with a pumping chamber and a piezoelectric diaphragm actuating element, which can be moved by applying a voltage such that the volume of the pumping chamber can be changed. For control purposes, the micropump comprises two valves with piezoelectric elements.

[0009] However, the devices described above have a complex structure and do not allow for precise, rapid and accurate intake and dispensing of liquids.

[0010] The object of the invention is therefore to provide a pipetting device for dosing liquids, a pipetting robot and a method for using the pipetting device, which avoid the disadvantageous effects known from the prior art, in particular enable precise and rapid processing of liquids and have a simple structure.

[0011] The object is achieved by a pipetting device, a pipetting robot and by a method for using the pipetting device having the features of the independent claims.

[0012] According to the invention, a pipetting device for dosing a liquid by means of a fluid flow is proposed, which comprises a pump, a valve and a connecting element.

[0013] The pump has a pumping chamber for generating the fluid flow, with a pumping element arranged in the pumping chamber, which divides the pumping chamber into a pressure chamber and a suction chamber. The pumping element is movable within the pumping chamber such that the fluid flow can be generated by changing the volume of the pressure chamber and the suction chamber.

[0014] The valve is used to control the fluid flow generated by the pump, wherein the valve is fluidly connected to the pressure chamber via a first inlet and is fluidly connected to the suction chamber via a second inlet.

[0015] The connecting element has a fluid inlet which is fluidly connected to an outlet of the valve in such a way that the fluid flow generated by the pump can act on the liquid for dosing via the connecting element.

[0016] The combination of valve and pump provides a system for precise fluid transfer, which operates primarily according to the air displacement principle. The fluid flow can be understood in particular as a gas or air flow, with the pumping chamber being an air / gas-filled space (which can particularly be disc-shaped) enclosed by a housing. The pumping element preferably separates the pressure chamber and the suction chamber from each other in a gas-tight manner.

[0017] By arranging the valve with multiple inlets to the various pump chambers, the liquid dispensing and aspiration can be precisely controlled. This arrangement also allows for rapid switching. Neither multiple pumps nor additional chambers are required. Furthermore, the use of the pump with two chambers enables a wide pipetting volume range.

[0018] In a particularly preferred embodiment, the pump is a micropump, in particular a piezoelectric micropump. A micropump can be understood as a pump of small size, which is thus particularly suitable for pipetting devices and can use an oscillating membrane as the pumping element. For this purpose, the pumping element can be a piezoelectric disk, or the pumping element can comprise a membrane and a piezoelectric actuating element for moving (oscillating) the membrane.

[0019] Moving the membrane or the piezoelectric disc causes a corresponding volume change (through a resonant standing wave) of the pressure chamber and the suction chamber, with a reduction in the volume of the suction chamber resulting in an increase in the volume of the pressure chamber, and vice versa. Piezoelectric pumps are known as so-called resonant acoustic pumps from WO2022023703. In this regard, reference is therefore made to application WO2022023703, the content of which is hereby incorporated into this application. The piezoelectric micropump can use high-amplitude acoustic resonance in disc-shaped cavities (with a high aspect ratio, i.e., the ratio of the radius of the cavity to the height of the cavity) in which radial pressure oscillations are excited.

[0020] In a particularly preferred embodiment, the pumping chamber can comprise first and second end walls which are connected to a peripheral side wall, wherein the first and second end walls each comprise an opening (pressure opening and suction opening) which contains the one-way valves. The pumping element is located between the first and second end walls and is connected to the peripheral side wall by an insulator (holding element) to define first and second cavities for receiving the fluid (i.e. pressure chamber and suction chamber), wherein each of the cavities is substantially cylindrical and has a characteristic height and a characteristic radius. The ratio of the radius to the height can be greater than about 1.2. The pumping element is configured to oscillate in an axial direction to generate radial pressure oscillations of the fluid in the first and second cavities.

[0021] In practice, the first inlet of the valve can be fluidly connected to a pressure opening of the pressure chamber via a pressure line. Furthermore, a one-way valve (i.e., one that allows flow only in one direction, in particular a check valve) can be arranged at the pressure opening. This valve is oriented such that fluid flow can only occur in the direction of the first inlet or the valve. In this case, an overpressure is generated by the pressure chamber, which leads to fluid flow toward the valve (i.e., out of the pressure chamber).

[0022] Furthermore, the second inlet can be fluidly connected to a suction opening of the suction chamber via a suction line. A one-way valve can also be arranged at the suction opening, but it is oriented such that fluid flow can only occur from the direction of the second inlet or the valve. In this case, a negative pressure is created by the suction chamber, which leads to fluid flow from the direction of the valve (i.e., into the suction chamber).

[0023] Consequently, the suction chamber can generate negative pressure (suction pressure) in the valve interior / valve chamber, and the pressure chamber can generate positive pressure in the valve interior / valve chamber. When the valve outlet opens, the positive pressure leads to a fluid flow toward the connecting element, allowing fluid to be released from the connecting element. The negative pressure leads to a fluid flow away from the connecting element, allowing fluid to be drawn into the connecting element.Preferably, however, the outlet of the valve is simply designed as an opening, so that the positive pressure when the first inlet is opened leads to a fluid flow in the direction of the connecting element, whereby liquid can be dispensed from the connecting element, and the negative pressure when the second inlet is opened leads to a fluid flow from the direction of the connecting element, whereby liquid can be taken up into the connecting element. The connecting element is preferably a pipette tip adapter, which comprises a channel extending from the fluid inlet to a fluid outlet, wherein the fluid outlet is arranged on a receiving element for receiving a pipette tip. In this way, the liquid can be taken up and dispensed via an exchangeable pipette tip, thereby avoiding cross-contamination.

[0024] The pressure chamber and the suction chamber can each comprise a compensating opening through which an interior of the pressure chamber and an interior of the suction chamber are fluidically connected to the environment. The compensating opening can thus be understood, in particular, as an opening in a housing wall surrounding the chamber through which gas can flow into or out of the chamber. Thus, during the fluid flow from the pressure chamber, gas can flow into the pressure chamber, and during the fluid flow into the suction chambers, gas can flow out of the suction chamber.

[0025] In practice, the suction line and / or the pressure line can include a bypass opening dimensioned such that a predefined minimum flow can be set independently of the pump's minimum power. The minimum flow can be adjusted because the bypass opening causes a pressure drop (in the pressure line) or a pressure increase (in the suction line), both of which depend on the size of the bypass opening.

[0026] The pipetting device may comprise a control device for controlling the valve and the pump, wherein the control device may comprise a valve controller for separately controlling the first inlet and the second inlet (and optionally the outlet). Furthermore, the control device may comprise a pump controller for controlling the movement of the pump element. Furthermore, a pressure and / or flow sensor may be provided, which is connected to the control device and arranged at the outlet and / or the connecting element for determining the pressure and / or flow.

[0027] In practice, the valve can be a three-way valve (3 / 3), in particular a piezoelectric three-way valve. The valve uses (separate / separately controllable) piezoelectric actuators for the first and second inlets, whose movement / deformation enables the flow of the fluid stream. The valve control can apply an electrical voltage to the actuators, whereby a piezoelectric material of the actuators is compressed or stretched (depending on the applied voltage). This mechanical deformation generates a movement. The movement of the piezoelectric actuator either presses a corresponding closure element against a valve seat to block the fluid flow, or moves it away from it to allow the fluid flow.Because the piezoelectric material reacts immediately to changes in electrical voltage, the valve can be opened or closed within a very short time. This enables precise control of the fluid flow and thus very precise fluid intake and discharge. Furthermore, the first inlet and the second inlet can be controlled separately and reliably, allowing the interior of the valve to be fluidically connected to either the pressure chamber or the suction chamber. This enables, in particular, a seamless transition between positive, negative, and no flow.

[0028] Any desired dosing volume of the liquid can be set through the interaction of the valve controller and the pressure / flow sensors of the control device. The flow sensor can measure air flow rates from 0.1 to 1000 pl / s, and the pressure sensor can measure air pressures from 1 to 1050 hPa. The valve can therefore be used as an automated valve, connected to sensors and the control device to control the flow based on specific conditions or parameters.

[0029] In practice, the pipetting device can be part of a robotic system. A pipetting robot can therefore comprise one or more pipetting devices, which can be moved and controlled by a movement device. The movement device can be a robotic arm. Freely programmable movement sequences enable a wide variety of tasks to be performed in a wide range of applications.

[0030] Alternatively, the pipetting device can be a handheld device (particularly battery-operated).

[0031] The invention further proposes a method for using the pipetting device, wherein the fluid flow is generated by moving the pump element within the pump chamber. Overpressure can be generated in the valve interior by opening the first inlet, and negative pressure can be generated by opening the second inlet. Thus, the fluid flow is then transferred to the liquid / can act on the liquid. Alternatively, the fluid flow can be transferred to the liquid by opening the outlet, as described above.

[0032] In practice, the sensors (pressure and flow) can be used to measure the fluid flow over time, as well as the expansion / contraction of the volume in the pipette tip and the pipette tip adapter, to determine the displaced air volume. The displaced air volume creates a pressure differential that pulls or pushes the liquid into or out of the pipette tip, which is attached to the pipette tip adapter. The air displacement volume can be determined by precisely measuring the fluid flow under constant pressure control, enabling control of the valve and thus the dispensing volume.

[0033] The pipetting device according to the invention has the following significant advantages over a manual pipette: It enables fast and precise pipetting without knowledge of the properties of the liquid being moved. It enables an unusually large pipetting volume range (replacing several standard manual pipettes). Since the pipetting mechanism is entirely driven by electrical motion, many secondary features can also be realized, such as autocalibration, drip-free control, multidispensing, and Bluetooth connectivity.

[0034] In the following, the invention is explained in more detail using exemplary embodiments with reference to the drawings.

[0035] Fig. 1 is a schematic representation of a first embodiment of a pipetting device according to the invention;

[0036] Fig. 2 is a schematic representation of a second embodiment of a pipetting device according to the invention.

[0037] Fig. 1 shows a schematic representation of a first embodiment of a pipetting device 1 for dosing a liquid 60 by means of a fluid stream.

[0038] The pipetting device 1 comprises a pump 2 with a pump chamber 27 for generating the fluid flow, wherein a pump element 20 is arranged in the pump chamber 27, by which the pump chamber 27 is divided into a pressure chamber 21 and a suction chamber 22.

[0039] The pump element 20 is movable in the pump chamber 27 such that the fluid flow can be generated by a volume change of the pressure chamber 21 and the suction chamber 22.

[0040] Furthermore, the pipetting device 1 comprises a piezoelectric three-way valve 3 for controlling the fluid flow. The three-way valve 3 (i.e., an interior space 30) is fluidly connected to a pressure opening 23 of the pressure chamber 21 via a first inlet 31 and a pressure line 33. A one-way valve 23 is arranged in the pressure opening 23 and is oriented such that the fluid flow can only flow in the direction of the three-way valve 3.

[0041] Furthermore, the three-way valve 3 (i.e. the interior space 30) is fluidly connected to a suction opening 24 of the suction chamber 22 via a second inlet 32 ​​and via a suction line 34, wherein a one-way valve 24 is arranged in the suction opening 24, which is aligned such that the fluid flow can only flow from the direction of the three-way valve 3.

[0042] In addition, the pipetting device 1 comprises a control device 4 for controlling the three-way valve 3 and the pump 2. For opening and closing the first and second inlets 32, 33, the three-way valve 3 comprises piezoelectric actuators 47, which are controlled by a valve control 45 of the control device 4.

[0043] Furthermore, the pipetting device 1 comprises a pipette tip adapter 6, which comprises a channel 62 extending from a fluid inlet 63 to a fluid outlet 64, wherein the fluid outlet 64 is arranged on a receiving element 65 for receiving a pipette tip 61. The pipette tip adapter 6 is fluidly connected to an outlet 38 of the valve 3 such that the liquid 60 can be drawn into the pipette tip 61 or ejected from the pipette tip 61 by the fluid flow generated by the pump 2.

[0044] Here, the pump 2 is designed as a piezoelectric micropump 2 with a disc-shaped pump chamber 27, wherein the pump element 20 is a membrane with a piezoelectric actuating element, which is controlled by a pump controller 43 of the control device 4. A voltage is applied to the piezoelectric actuating element to set the membrane in motion.

[0045] In addition, the control device 4 comprises a control element 41 which is connected to the pressure sensor 51 and the flow sensor 52 and a voltage regulator 42 which is connected to a power source 46.

[0046] Since the pumping chamber 27 is divided into the pressure chamber 21 and the suction chamber 22 by the pumping element 20, the pumping chamber 27 has two sections 21, 22 arranged one above the other. To achieve a high compression ratio, the pumping chamber 27 has a low height.

[0047] During an intake process, the three-way valve 3 is first actuated such that only the second inlet 32 ​​is open. The three-way valve 3 is actuated by applying an electrical voltage to the piezoelectric actuator 47.

[0048] In addition, the piezoelectric actuator of the

[0049] A voltage is applied to the pump element 20 to cause the diaphragm to deform, thereby increasing the volume of the suction chamber 22. This creates a negative pressure in the suction chamber 22, causing air to be sucked in from the suction line 34, which flows through the one-way valve 24 into the suction chamber 22.

[0050] This creates a fluid flow in the direction of the pump 2, which is transferred via the outlet 38 of the three-way valve 3 and through the channel 62 to the liquid 60, which is thus sucked into the pipette tip 61.

[0051] After the intake process is completed, the second inlet 32 ​​is closed.

[0052] During an ejection process, the three-way valve 3 is first actuated such that only the first inlet 31 is open. The three-way valve 3 is actuated by applying an electrical voltage to the piezoelectric actuator 47.

[0053] In addition, a voltage is applied to the piezoelectric actuator of the pump element 20 to cause the diaphragm to deform, thereby reducing the volume of the pressure chamber 21. This creates an overpressure in the pressure chamber 21, forcing air out of the pressure chamber 21 and flowing through the one-way valve 23 into the pressure line 33.

[0054] This creates a fluid flow in the direction of the three-way valve, which is transferred via the outlet 38 of the three-way valve 3 and through the channel 62 to the liquid 60, which is thus ejected from the pipette tip 61.

[0055] After the discharge process is completed, the first inlet 31 is closed. The pressure chamber 21 and the suction chamber 22 each comprise a compensating opening 25, 26 through which an interior of the pressure chamber 21 and an interior of the suction chamber 22 are fluidly connected to the environment, allowing air to flow in and out, respectively. The compensating openings 25, 26 are openings in a housing wall surrounding the pump chamber 27.

[0056] Continuous flow measurement by the combined flow and pressure sensor 5 allows valve 3 to be closed and pump 2 to be stopped as soon as the target volume is reached. Flow rate monitoring also supports the possibility of multiple dosing.

[0057] Fig. 2 shows a schematic representation of a second embodiment of a pipetting device 1 according to the invention. The structure of the pipetting device 1 corresponds to the structure of the embodiment of Fig. 1 , but the pipetting device 1 additionally comprises an ambient pressure sensor 44, which is used to compensate for pipetting errors due to ambient pressure changes.

[0058] Furthermore, the suction line 34 comprises a bypass opening 36 and a damping volume 39 to enable a slow and wave-free increase in pressure and flow.

[0059] The invention is not limited to the disclosed embodiments. Other variations of the disclosed embodiments may be understood and effected by those skilled in the art in practicing a claimed invention from a study of the drawings, the disclosure, and the dependent claims. In the claims, the word "comprising" does not exclude other elements or steps, and the indefinite article "a" or "an" does not exclude a plurality. The mere fact that certain measures are repeated in mutually different dependent claims does not mean that a combination of those measures cannot be advantageously used. Any reference signs in the claims should not be construed as limiting the scope.

Claims

1. A pipetting device for dosing a liquid (60) by means of a fluid flow, comprising a pump (2) with a pump chamber (27) for generating the fluid flow, wherein a pump element (20) is arranged in the pump chamber (27), by means of which pump element the pump chamber (27) is divided into a pressure chamber (21) and a suction chamber (22), and the pump element (20) is movable in the pump chamber (27) such that the fluid flow can be generated by a change in the volume of the pressure chamber (21) and the suction chamber (22); and a valve (3) for controlling the fluid flow, wherein the valve (3) is fluidly connected to the pressure chamber (21) via a first inlet (31) and is fluidly connected to the suction chamber (22) via a second inlet (32);and a connecting element (6) with a fluid inlet (63) which is fluidly connected to an outlet (38) of the valve (3) in such a way that the fluid flow generated by the pump (2) can act on the liquid (60) for dosing via the connecting element (6); 2. Pipetting device according to claim 1, wherein the first inlet (31) is fluidly connected to a pressure opening (23) of the pressure chamber (21) via a pressure line (33).

3. Pipetting device according to claim 2, wherein a one-way valve (23) is arranged at the pressure opening (23), which is oriented such that the fluid flow can only occur in the direction of the valve (3).

4. Pipetting device according to one of the preceding claims, wherein the second inlet (32) is fluidly connected to a suction opening (24) of the suction chamber (22) via a suction line (34).

5. Pipetting device according to claim 4, wherein a one-way valve (24) is arranged at the suction opening (24), which is aligned such that the fluid flow can only occur from the direction of the valve (3).

6. Pipetting device according to one of claims 2 to 5, wherein the suction line (33) and / or the pressure line (34) comprise a bypass opening (36) which is dimensioned such that a predeterminable minimum flow can be set independently of a minimum power of the pump (2).

7. Pipetting device according to claim 3 or 5, wherein the one-way valve (23, 24) is a check valve.

8. Pipetting device according to one of the preceding claims, wherein the pressure chamber (21) and the suction chamber (22) each comprise a compensating opening (25, 26) through which an interior of the pressure chamber (21) and the suction chamber (22) is fluidly connected to the environment.

9. Pipetting device according to one of the preceding claims comprising a control device (4) for controlling the valve (3) and the pump (2).

10. Pipetting device according to claim 9, wherein the control device (4) comprises a valve control (45) for separately controlling the first inlet (31) and the second inlet (32).

11. Pipetting device according to claim 9 or 10, wherein the control device (4) comprises a pump control (43) for controlling the movement of the pump element (20).

12. Pipetting device according to one of claims 9 to 11 comprising a pressure and / or flow sensor (51, 52) which is connected to the control device (4) and is arranged on the outlet (38) and / or the connecting element (6) for pressure and / or flow determination.

13. Pipetting device according to one of the preceding claims, wherein the pump (2) is a micropump (2), in particular a piezoelectric micropump (2).

14. Pipetting device according to one of the preceding claims, wherein the pumping element (20) is a piezoelectric disc or the pumping element comprises a membrane and a piezoelectric actuating element for moving the membrane.

15. Pipetting device according to one of the preceding claims, wherein the connecting element (6) is a pipette tip adapter (6) which comprises a channel (62), and the channel (62) extends from the fluid inlet (63) to a fluid outlet (64), wherein the fluid outlet (64) is arranged on a receiving element (65) for receiving a pipette tip (61).

16. Pipetting device according to one of the preceding claims, wherein the valve (3) is a three-way valve (3), in particular a piezoelectric three-way valve (3).

17. Pipetting device according to one of the preceding claims, wherein the pumping element (20) is arranged between holding elements of the pumping chamber (27).

18. A method for using a pipetting device (1) according to one of the preceding claims, comprising Generating the fluid flow by moving the pumping element (20) within the pumping chamber (27); Opening the first inlet (31) to generate an overpressure in a valve interior (30) of the valve (3) and to transfer the fluid flow to the liquid (60), or Opening the second inlet (32) to generate a negative pressure in the valve interior (30) and to transfer the fluid flow to the liquid (60).

19. The method according to claim 18, wherein the pipetting device (1) comprises a control device (4) for controlling the valve (3) and the pump (2) and a pressure and / or flow sensor (51, 52), wherein the outlet (38) of the valve (3) is controlled by a signal from the pressure and / or flow sensor (51, 52).

20. Pipetting robot comprising a pipetting device (1) according to one of claims 1-17 and a movement device for moving the pipetting device (1).

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