GB2560014A

GB2560014A - Pipetting system

Info

Publication number: GB2560014A
Application number: GB1703098.2A
Authority: GB
Inventors: Zver Martin
Original assignee: Stratec Biomedical AG
Current assignee: Stratec Biomedical AG
Priority date: 2017-02-27
Filing date: 2017-02-27
Publication date: 2018-08-29
Also published as: GB201703098D0

Abstract

A rinsing unit 60 for a pipetting system 10 comprises a rinsing liquid container 63, a rinsing pump 62 and a pressure tank 61. Rinsing liquid 64 is pumped from the container 63 into the pressure tank 61. Valves 41, 43 may be opened to allow pressurized rinsing liquid to flush a pipetting pump chamber 23, a pipetting tube 31 and pipetting needle 32, and/or to flow to a wash station with a nozzle 66 which creates a rinsing jet for rising the external surface of the pipette. The pipetting system may comprise a sensing unit comprising a capacitive sensor, apressure sensor and an optical sensor. The pipetting needle unit and the pipetting pump 20 are partially integrated into a rack (35, fig. 2a). Several pipetting systems may be arranged into a multiple pipetting needle arrangement, connected to a single rinsing unit 60. The pipetting needle may comprise an inner lining heating wire of a co-extrusion of FEP covered with an electrically conductive material. The pressure tank may be an air cushion.

Description

(54) Title of the Invention: Pipetting system

Abstract Title: Pressurised rinsing of a pipetting system (57) A rinsing unit 60 for a pipetting system 10 comprises a rinsing liquid container 63, a rinsing pump 62 and a pressure tank 61. Rinsing liquid 64 is pumped from the container 63 into the pressure tank 61. Valves 41,43 may be opened to allow pressurized rinsing liquid to flush a pipetting pump chamber 23, a pipetting tube 31 and pipetting needle 32, and/or to flow to a wash station with a nozzle 66 which creates a rinsing jet for rising the external surface of the pipette. The pipetting system may comprise a sensing unit comprising a capacitive sensor, apressure sensor and an optical sensor. The pipetting needle unit and the pipetting pump 20 are partially integrated into a rack (35, fig. 2a). Several pipetting systems may be arranged into a multiple pipetting needle arrangement, connected to a single rinsing unit 60. The pipetting needle may comprise an inner lining heating wire of a co-extrusion of FEP covered with an electrically conductive material. The pressure tank may be an air cushion.

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PIPETTING SYSTEM

Description

Field of the invention [0001] The invention relates to a pipetting system for the handling of liquids, and to a method for maintaining a pipetting system and for handling of liquids.

Background of the invention [0002] Automated analyser systems for use in clinical diagnostics and life sciences are produced by a number of companies. For example, the Stratec Biomedical AG, Birkenfeld, Germany, produces several devices for specimen handling and detection for use in automated analyser systems and other laboratory instrumentation.

[0003] Preparation and analysis of samples is part of everyday practice in laboratory or clinical work. The formerly manual practice is increasingly becoming automatized and parallelized, thus achieving higher efficiency and precision in the preparation and analysis of samples. Automated analyzer systems allow for reaching a higher throughput of samples.

[0004] Pipetting systems employing pipetting needles, often made from steel, or disposable tips attached to a pipetting tube are known in the art. During uptake of a liquid in the case of steel needles, the liquid enters the steel needle as well as a pipetting tube. The pipetting tube connects the steel needle to a pipetting pump. The liquid enters the disposable tip only, in the case of a disposable tip. A steel needle must be rinsed together with the pipetting tube before being reused, whereas the disposable tip may be disposed after use. The steel needle may need to be replaced if the steel needle is damaged or heavily worn. The replacement of the steel needle together with the pipetting tube often requires effort as both need to be replaced together.

[0005] Rinsing pumps are used for rinsing both the steel needle and the pipetting tube. Such pumps are often diaphragm pumps, which produce an oscillatory pressure and thus an oscillatory volumetric flow of the rinsing liquid. Therefore, pressure build-up and the flow of the rinsing liquid require a comparatively large amount of time, which can reduce throughput of the pipetting system.

[0006] The steel needles are often guided by a guide in a vertical direction and they are connected via the pipetting tube to the pipetting pump, which is usually placed at the rear side of a pipetting system. The pipetting tube is often of a length of approximately 2 to 3 meters. When the steel needle is lowered, or lifted by the guide, to or from a liquid container for uptake or release of the liquid, the pipetting tubes move and/or are bent. The moving and/or bending of the pipetting tubes causes the liquid therein to oscillate or to periodically move back and forth, resulting potentially in erroneous pipetting results.

[0007] A long pipetting tube results further in a higher dead volume between the pipetting pump and the pipetting needle, which has to be taken into account to obtain correct pipetting results. A pipetting tube of a length of 2 to 3 meters can easily result in the dead volume being more than 3 milliliters. The long pipetting tube can also lead to losses of liquids due to friction from movement of the liquid in the pipetting tube and due to bending of the pipetting tube.

[0008] Modular design of the pipetting systems enables the construction of pipetting systems employing a plurality of pipetting needles placed near to one another. Conventional multiple pipetting needle arrangements bear a risk of entanglement of the plurality of pipetting tubes, which connect the plurality of pipetting needles with at least one pipetting pump placed at the rear side of the pipetting system. As the pipetting tubes are often connected to the pipetting needles in an arc shape across the pipetting system to the upper end of the pipetting needles, such multiple pipetting needle arrangements tend to have a large height.

[0009] Heating of pipetting needles is performed to heat up cold fluids before releasing them into a reaction vessel to enable chemical reactions or prevent delaying of chemical reactions. It is state of the art to use heated stainless steel needles wrapped with heating wire covered with shrink tubing or similar material.

[0010] US 20080019878 also published as DE 10 2006 034 245 B4 discloses a positioning device for positioning pipettes in three dimensions. A pump and the pipette connected to the pump are accommodated into a sliding carriage of the positioning device. The pipettes of this patent have disposable tips.

[0011] DE 10 2007 003 040 B4 discloses a device for optical detection of at least one phase transition between at least two media. The device comprises a pipetting needle and a waveguide guiding light. The optical path of the light crosses the pipetting needle. The pipetting needle is not integrated into a vertically displaceable carriage for lowering the pipetting needle towards a liquid. The device has no rinsing unit for rinsing of the steel needle.

[0012] EP 2 359 932 Al discloses a positive displacement pump comprising a pump and a pressure sensor in fluid connection with a pump chamber of the pump via a pressure channel. EP 2 359 932 Al does not disclose a rinse system.

[0013] US5474744 discloses an automatic pipetting device with cleaning mechanism. The device comprises only one pipetting needle having a tip end and an open end and a metering syringe having an outlet. The device also comprises a mechanism for cleaning the pipetting needle with a cleaning fluid when the pipetting needle is positioned in a cleaning position. The mechanism comprises a plunger pump, a second tube having a first end and a second end, a first valve, a second valve, and a third tube having a first end and a second end, the second end of the tubing immersed in a cleaning fluid. The second end of the first tube is in fluid communication with both the outlet of the metering syringe and the first valve. The first end of the second tube is in fluid communication with the first valve. The second end of the second tube is in fluid communication with both the plunger pump and the second valve. The first end of the third tube is in fluid communication with the second valve. The mechanism for cleaning the pipetting needle is operated to activate the plunger pump and for opening and closing the first valve and the second valve, so as to establish a predetermined pressure of cleaning fluid in the second tube while the first and second valves are closed and subsequently to force the cleaning fluid through the pipetting needle while the first valve is open and the second valve is closed. No pressure tank or air cushion and no rinse system to clean the external surface of the pipette are disclosed.

[0014] US 20010027269 discloses a liquid sampler which comprises a metering pump including a cylinder having opposite end openings and a cylindrical cavity, a piston inserted in the cavity from one of the openings of the cylinder, and a driving source for reciprocally and linearly moving the piston; and a pipette directly connected to the other opening of the cylinder. For cleaning, the pipette is inserted into a cleaning vessel. The cleaning liquid is discharged from the pipette and, at the same time, supplied from the lower supply port of the cleaning vessel. Thus, the interior and exterior of the pipette are cleaned. The liquid within the cleaning vessel is drained from the drain port thereby to be collected in the drain tank, so that the surface of the cleaning liquid in the cleaning vessel is maintained substantially at a constant level. The pipetting unit is not washed under a rinsing nozzle by a liquid jet, but cleaned by inserting it into a cleaning vessel. In addition, no pressure tank or air cushion is used.

[0015] US 20060127281 discloses a pipetting apparatus with integrated liquid level and/or gas bubble detection. It does not disclose a rinsing system.

[0016] EP 2330426 discloses a function for checking whether components of an automatic analyzer properly operate. A pressure sensor is installed in a sample path. A pressure waveform obtained during a washing water discharge operation is used to check the opening/closing of a solenoid valve and the other operations of a dispensing mechanism. The nozzle is washed after a sample and a reagent are suctioned and discharged because the nozzle will be used to dispense a different sample and a different reagent. External washing and internal washing are performed for nozzle washing purposes. In external washing, the nozzle is washed by pouring a washing solution onto the outer surface of the nozzle. In internal washing the interior of the nozzle is washed by allowing the nozzle to discharge the washing solution. Upon completion of dispensing, the sample probe moves to a washing position. A water supply pump then causes washing water in a water supply tank to flow at high pressure and wash the sample probe. EP 2330426 does not disclose a pressure tank or air cushion. Furthermore, the document does not disclose a pressurized rinse system to clean the external surface of the pipetting needle.

Summary of the invention [0017] The instant disclosure provides a pipetting system comprising at least one pipetting needle fluidly connected in series to a pressure tank, which is fluidly connected with a rinsing pump which is fluidly connected with a rinsing liquid container.

[0018] In a further aspect, the pressure tank can be further fluidly connected to at least one wash station with integrated rinsing nozzle.

[0019] The wash station with integrated rinsing nozzle may be used to produce a rinsing liquid jet that cleans the pipetting needle under a defined angle.

[0020] In a further aspect, the pipetting system may comprise a pipetting tube, a rinsing tube, and a pipetting pump comprising a pipetting pump chamber and a piston, wherein the pipetting needle is fluidly connected to the pipetting tube, the pipetting pump, the rinsing tube, the pressure tank, the rinsing pump and the rinsing liquid container.

[0021] The pipetting system may further comorise a light source optically connected to an input side of the waveguide and a sensing unit for monitoring the handling of liquids, the sensing unit comprising at least one capacitive sensor in electrical connection with the pipetting needle, a pressure sensor being in fluid connection with the pipetting pump, and an optical sensor in optical connection with an output side of a waveguide guiding light through an inner portion of the pipetting needle.

[0022] It is further envisages that the pipetting system may encompass a pipettor valve, wherein the pressure tank is fluidly connected to the pipetting pump over the pipettor valve, which is controlled by a controller, wherein the controller receives signals transmitted by the capacitive sensor, the pressure sensor, and the optical sensor.

[0023] A pipetting tube may be part of a pipetting system according to the instant disclosure, wherein the pipetting tube and the pipetting pump chamber are integrated into a rack and fluidly connected to one another by a disconnectable fluid interface, the rack being adapted for positioning the pipetting needle in a vertical direction. The disconnectable fluid interface may comprise a bayonet coupling.

[0024] The pipetting system may further comprises a pressure accumulator to bridge start times of the rinsing pump.

[0025] The pipetting system may further comprise at least two pipetting needles each fluidly connected to a pipetting tube, a pipetting pump, a rinsing tube and a pressure tank fluidly connected to a rinsing pump and a rinsing liquid container.

[0026] The pipetting needles may all be connected to the same pressure tank. Further, wherein a pipetting needle, a pipetting tube and a pipetting pump may form a unit, wherein the units are arranged in a grid pattern to one another.

[0027] In a further aspect, the pressure tank may comprise a membrane which separates fluid and air.

[0028] The pipetting system may further comprise a control loop to create a constant pressure in the system.

[0029] It is intended that the pipetting needle may be made from steel. The pipetting needle may further comprise an inner lining heating wire to heat up system liquid.

[0030] The pipetting needle, the pipetting tube, the rinsing tube, the pressure tank and/or the rinsing liquid container may comprise an inner lining heating wire to heat up a system liquid. The inner lining heating wire is a co-extrusion made of FEP covered with an electrical conductive material.

[0031] The pressure tank may be an air cushion.

[0032] Another aspect of the invention is a method for cleaning internal and/or external surface of a pipetting needle of a pipetting system with an integrated pressurized rinse system, comprising the steps of pumping a rinsing liquid from a rinsing liquid container over a rinsing tube into a pressure tank with a rinsing pump; opening at least one valve to allow the rinsing liquid to flush the pipetting pump chamber, the pipetting tube and the pipetting needle and/or the wash station with integrated rinsing nozzle, wherein the wash station with integrated rinsing nozzle creates a rinsing liquid jet.

[0033] In a further aspect, the method encompasses the step of heating up a system liquid.

Brief description of the figures [0034] The invention will now be described based on the drawings. It will be understood that the embodiments and aspects of the invention described herein are only examples and do not limit the protective scope of the claims in any way. The invention is defined by the claims and their equivalents. It will be understood that features of one aspect or embodiment of the invention can be combined with a feature of a different aspect or aspects and/or embodiments of the invention. It shows:

[0035] Fig. 1 [0036] Fig. lb [0037] Fig lc [0038] Fig. 2a [0039] Fig. 2b

Scheme of a pipetting system.

Scheme of a pipetting system in a multiple pipetting needle arrangement.

Scheme of a pipetting system in a multiple pipetting needle arrangement further comprising a wash station with rinsing nozzle for external wash.

Pipetting unit and sensing unit according to one aspect of the invention, wherein the pipetting unit is partially integrated into a rack, and a pipetting needle and the sensing unit are attached to the rack. Pipetting unit of Fig. 2a from a different angle and without rack.

[0040] Fig. 3a [0041] Fig. 3b [0042] Fig. 4a [0043] Fig. 4b

Rinsing pump and a pressure tank for rinsing a pipetting unit of a pipetting system, according to one aspect of the invention.

Rinsing pump and a pressure tank of Fig. 3a from a different angle. Pipetting needle unit according to one aspect of the invention. Pipetting needle unit of Fig. 4a from a different angle.

Detailed description of the invention [0044] A rinsing liquid within the meaning of the instant invention comprises but is not limited to aqueous solutions and other liquids comprising detergents, and/or organic solvents.

[0045] Within the meaning of the instant invention, a reaction mixture or liquid comprises, without being limited to, at least one sample, buffer, reagent, probe and/or beads. A sample may be liquid or solid and stem from a patient for example or may be a probe coming from a binding reaction. Buffers might be without limitation dissolving, washing, neutralizing, stabilizing and/or a reaction buffers necessary for performing a chemical reaction. The reagents might be selected from the group comprising but not limited to: solvents, enzymes, primers, nucleotides, adenosine triphosphates, and dyes. The probe might be selected from the group comprising but not limited to: DNA and/or RNA probes comprising a quencher and/or a reporter and antibodies possibly linked to a reporter molecule.

[0046] A system liquid within the meaning of the instant invention might be any liquid comprised in the pipetting system.

[0047] According to the instant invention, a reaction vessel comprises the cavity of a well, microplate, multi-well plate or a tube.

[0048] Fig. 1 shows a pipetting system 10. The pipetting system 10 comprises a pipetting needle unit 30 and a pipetting pump 20. The pipetting needle unit 30 and the pipetting pump 20 constitute a pipetting unit 20, 30. The pipetting system 10 further comprises a sensing unit 50, and a rinsing unit 60. The same reference numerals will be used to indicate the same elements on the different figures.

[0049] The pipetting pump 20 comprises a pipetting pump motor 21, a piston 22, and a pipetting pump chamber 23. The pipetting needle unit 30 comprises a pipetting needle 32 and a pipetting tube 31, fluidly connected to one another at a pipetting needle end of the pipetting tube 31. The pipetting pump chamber 23 is connected to a pipetting needle 32 via the pipetting tube 31. The pipetting pump 20 is thus fluidly connected to the pipetting needle unit 30. The pipetting needle 32 has an opening 33 through which a liquid may be released or aspirated.

[0050] The pipetting needle 32 may be made of steel or other conducting materials. The pipetting needle 32 is otherwise electrically insulated from the rest of the pipetting system 10. The pipetting pump motor 21 drives the piston and may have an initializing sensor and a positioning control. Furthermore, the driving current of the pipetting pump motor 21 may be monitored, e.g. thereby detecting when the piston abuts against an abutment. The pipetting pump 20 may be alternatively a gear pump, a peristaltic pump or a bellows pump.

[0051] In another aspect, the pipetting needle 32 may comprise a pipetting line and a disposable tip adapted for attachment to the line.

[0052] Figs. 4a and 4b show the pipetting needle unit 30 in more detail. The pipetting needle unit further comprises a disconnectable fluid interface 34 disposed at a pipetting pump end of the pipetting tube 31 and adapted for fluidly connecting the pipetting tube 31 with the pipetting pump chamber 23. The disconnectable fluid interface 34 may comprise a bayonet coupling for connecting to the pipetting pump chamber 23.

[0053] The disconnectable fluid interface 34 may further comprise a sealing surface (not shown) for sealing a fluid connection between the pipetting tube 31 and the pipetting pump chamber 23. In this case, a terminal portion of the pipetting pump chamber 23, constituting a counterpart of the disconnectable fluid interface 34 used for forming the fluid connection, is pressed against the sealing surface of the disconnectable fluid interface 34. The fluid connection is sealed by locking the disconnectable fluid interface 34 and the terminal portion in the pressed state by means of a lock, e.g. a snap closing, a clamp, a clip, and the like. Other types of the disconnectable fluid interface 34 are conceivable.

[0054] Providing the pipetting needle 32 in conjunction with the pipetting tube 31 within the pipetting needle unit 30 enables easy and fast replacing of the pipetting needle 32. Whereas pipetting systems known in the art often require tedious coupling of the pipetting tube 31 and the pipetting needle 32 upon a replacement of the pipetting needle 32, this disclosure provides a way of replacing the pipetting needle 32 by replacing the entire pipetting needle unit 30.

[0055] The pipetting needle unit 30 and the pipetting pump 20 are arranged substantially vertically and are partially integrated into a rack 35, as shown in Figs. 2a and 2b. The sensing unit 50 is connected to the rack 35. The pipetting pump motor 21, arranged at an upper end of the rack 35, is operatively connected to the pipetting pump chamber 23 via the piston 22, the pipetting pump chamber 23 and piston 22 being accommodated within the rack 35. After fluidly connecting the pipetting tube 31 to an accessible terminal portion of the pipetting pump chamber 23, the pipetting tube 31 is pushed into and received by the rack 35, such that the pipetting needle 32 is located at a lower end of the rack 35.

[0056] Fig. 2a also shows a rinsing tube housing 55, which contains a rinsing tube 65 (not shown in Fig. 2a, as inside the rinsing tube housing 55).

[0057] The pipetting needle unit 30 and the pipetting pump 20 in conjunction with the rack 35 are commonly displaceable in a vertical direction (marked as z-direction by double-headed arrow (2) on Fig. 2b). By commonly displacing the pipetting pump 20 and the pipetting needle unit 30, the fluid connection between the pipetting needle unit 30 and the pipetting pump 20 remains constant during an operation of the pipetting systems 10. Thus, during the common displacement the fluid connection is not deformed, stretched, twisted or bent, and/or portions and parts of the fluid connection remain stationary with respect to one another. Thereby, wear of the fluid connection, such as of the pipetting tube 31, is reduced. Furthermore, there is no risk of changing a volume of the pipetting tube 31 due to deformation of the pipetting tube 31 by changing a distance between the pipetting pump 20 and the pipetting needle unit 30.

[0058] Fig 2b shows the pipetting pump 20, the pipetting needle unit 30 and sensing unit 50. The pipetting tube 31 is arranged in a substantially helical shape and has little volume. The pipetting tube 31 could also be arranged in other forms, such as a spiral shape.

[0059] The integration of the pipetting pump chamber 23, the piston 22 and pipetting tube 31 into the rack 35 reduces the distance between the pipetting pump chamber 23 and the pipetting needle 32. The distance to be covered by the pipetting tube 31 and the overall volume of the liquid accommodated by the pipetting tube 31, i.e. the dead volume between the pipetting pump 20 and the pipetting needle 32, are thereby reduced. The pipetting needle unit 30 may, for example, have a volume of up to 1 milliliter. The dead volume between the pipetting pump 20 and the pipetting needle 32 is small to enable precision of the handling of the liquid by the pipetting system 10. Furthermore, there is no movement of the pipetting tube 31 that would otherwise result in oscillation of liquid within the pipetting tube 31.

[0060] The vertical arrangement of the pipetting pump 20 and the pipetting needle 32 with the help of the rack 35 also reduces the overall height of the pipetting system 10. In prior art pipetting systems, the pipetting pump 20 often is placed at the rear side of the pipetting system 10, thus necessitating the connection of the pipetting pump 20 at the rear side with the pipetting needle 32 at the front side. The connection between the pipetting pump 20 and the pipetting needle 32 by the pipetting tube 31 of the prior art is often in the form of an arc arranged upwards in a vertical direction from the rear side and then down towards the pipetting needle 32. In order to have sufficient vertical displacement of the pipetting needle 32, the pipetting tube 31 does not form the shortest possible arc, which has the least height. The overall height of the conventional pipetting system 10 is increased and the overall volume of the pipetting tube 31 is also increased, which results in a larger dead volume. Furthermore, movement of the pipetting needle 32 with respect to the pipetting pump 20 of the prior art, which often is arranged in a stationary manner, results in movement of the pipetting tube 31 and, consequently, of the liquid within the pipetting tube 31.

Such movement include, for example, oscillations and can impair precision of pipetting results.

[0061] The overall height of the pipetting system 10 is therefore reduced with respect to prior art pipetting systems by vertically arranging the pipetting pump 20 and the pipetting needle 32, and by placing the pipetting tube 31 within the rack 35.

[0062] The sensing unit 50 comprises a pressure sensor (schematically shown as 50p) for sensing the pressure within the pipetting pump 20 and the pipetting needle unit 30, a capacitive sensor (schematically shown as 50c) for the sensing the capacitance of the pipetting needle 32, and an optical sensor (schematically shown as 50o) for receiving optical signals passed along a waveguide (shown schematically as 50w) and substantially horizontally through the pipetting needle 32. In one aspect of the disclosure, a flow sensor replaces the pressure sensor.

[0063] The pressure sensor 50p measures a difference of a pressure between a reference vacuum and a pressure inside of the pipetting system 10. The pressure sensor 50p is suitable for monitoring the functioning of the pipetting pump 20. The pressure sensor 50p can thus monitor the system for admissible pressure ranges, for system leakages, or blockages within the pipetting system 10 or at an opening 33 of the pipetting needle 32. The pressure sensor 50p is also suitable for liquid level detection and for monitoring a handling of the liquid. When the pipetting needle 32 is driven to approach a surface of the liquid in a container, pressure changes within the pipetting system 10 may occur. Such pressure changes can be more easily detectable when, in addition to the approaching of the surface of the liquid by the pipetting needle 32, the pipetting pump 20 is driven to pump air out through the opening 33 of the pipetting needle 32. Thereby, the presence of the liquid may be detected. Furthermore, an uptake or a release of the liquid produces a different pressure signal when the liquid comprises bubbles or several phases, or the pipetting needle 32 is blocked by e.g. coagulations. The handling of the liquid can be monitored by analysis of the pressure signal received from the pressure sensor 50p during the pipetting and rinsing process.

[0064] The capacitive sensor 50c detects a change in the capacitance of the pipetting needle 32. Changes in capacitance of the pipetting needle 32 occur when the pipetting needle 32 conies in contact with a surface of the liquid. By measuring the changes in capacitance, the capacitive sensor 50c is suitable for liquid level detection.

[0065] The optical sensor 50a receives a light signal from an output of the waveguide (shown schematically as 50w), such as, but not limited to, an optical fiber, a slab waveguide, strip waveguide, rib waveguide, or rectangular waveguide. The light travels along a first portion of the waveguide 50w, then traverses an inner portion of the pipetting needle 32 in a substantially horizontal direction at a location as close as possible towards the opening 33 of the pipetting needle 32 before entering a second portion of the waveguide 50w. By receiving the light signal, the optical sensor 50o can detect phase transitions, e.g. transitions between air and the liquid, or can differentiate between a gas or the liquid. The optical sensor 50o uses the principle of total reflection to carry out the measurements.

[0066] The sensing unit 50 further comprises a digital signal processor 52 for receiving and processing signals from the pressure sensor 50p, the capacitive sensor 50c, and/or the optical sensor 50o. The result of the processing of the signals is transmitted to a controller 51. The controller 51 may transmit a message to a user and halt an operation of the pipetting system 10 upon detection of predetermined patterns in the results of the processing of the signals.

[0067] The digital signal processor 52 processes signals from the several sensors 50p, 50c and 50o. The quality of the monitoring of the handling of the liquid is increased, as the sensing unit 50 becomes more versatile with the several sensors sensing properties pertaining to the handling of the liquid.

[0068] On the one hand, the several sensors 50p, 50c, 50o might measure the same property of the handling of the liquid and thus corroborate the result. For example, the pressure sensor 50p as well as the capacitive sensor 50c can measure the presence of the liquid (liquid level detection). If the signals from both sensors 50p and 50c agree, the result with respect to the presence of the liquid is more reliable. On the other hand, one of the several sensors 50p, 50c 50o might measure a certain property of the handling of the liquid exclusively or better than another one of the several sensors. The optical sensor 50o is, for example, much better suited for the detection of bubbles in the liquid than the capacitive sensor 50c or the pressure sensor 50p.

[0069] The rinsing unit 60 is generally arranged on a rear side of the pipetting system 10 and comprises a rinsing pump 62 (also shown in Figs. 3a and 3b), a rinsing tube 65, and a pressure tank 61 (also shown in Figs. 3a and 3b). The rinsing unit 60 is connected to the pipetting pump 20 and the pipetting needle unit 30 via the rinsing tube 65 and a pipetting valve 41 and/or a rinsing valve 42 mounted onto a manifold for distributing rinsing solution to pipettor. In case of multiple needle arrangement, for each pipetting unit a rinsing valve 42 is used (not shown in Fig. 3). Figure 3a shows washing valves 43 mounted onto a manifold. The pipetting valve 41 may be controlled by the controller 51 or by a user. The rinsing valve may also be controlled by a controller or a user. The pipetting valve 41 and/or the rinsing valve 42 barometrically separate the pipetting pump 20 and the pipetting needle unit 30 from the rinsing unit 60. Thus, when the pipetting valve 41 and/or rinsing valve 42 are closed, the pipetting pump 20 exclusively controls pressure changes and thus volumetric flow within the pipetting pump chamber 23, the pipetting tube 31, and the pipetting needle 32. When the pipetting valve 41 and/or rinsing valve 42 are open, the rinsing unit 60 may flush and rinse the pipetting pump chamber 23, the pipetting tube 31, and the pipetting needle 32 with a rinsing liquid 64.

[0070] In one aspect of the invention, the rinsing unit further comprises a wash station with integrated rinsing nozzle 66, fluidly connected to the pressure tank via rinsing tube 65 and washing valve 43. Each wash station with rinsing nozzle is connected to a washing valve 43. When washing valve 43 is open, the rinsing liquid 64 may flush through the wash station with integrated rinsing nozzle 66 and rinse the external surface of the pipetting needle under a resulting jet of rinsing liquid.

[0071] In another aspect of the invention, the rinsing pump 62 is a diaphragm pump. The rinsing pump 62 pumps the rinsing liquid 64 in the rinsing liquid container 63 through the rinsing tube 65 into the pressure tank 61, when the pipetting valves 41 and/or rinsing valves 42 are closed. The pressure tank 61 fills up with the rinsing liquid 64 to a certain height depending on an output pressure or the rinsing pump 62, thereby storing potential energy, which yields a corresponding pressure at the pipetting valves 41, rinsing valve 42 and/or washing valve 43. The pressure tank may comprise a membrane 68 which separates the fluid and the air [0072] Thus, when the corresponding valve or valves are open the rinsing liquid 64 is passed via the rinsing tube 65 and flushes and rinses the pipetting pump chamber 23, the pipetting tube 31, and the internal surface of the pipetting needle 32 and/or the rinsing nozzle and the external surface of the pipetting needle. The cleaning is performed at a wash station, which is a container or tank with or without integrated rinsing nozzle and a drain connected to a waste. The wash station is arranged within the range oft he pipettor.

[0073] A pressure tank 61 provides a fast and efficient rinsing of the pipetting pump chamber 23, the pipetting tube 31, and the internal and external surface of the pipetting needle 32, requiring less time for a rinsing process. The pressure tank 61 furthermore provides a continuous pressure during a rinsing process. The fast rinsing can, for example, prevent blockage of the pipetting needle 32 and/or pipetting tube 33 by coagulation when the liquid comprises blood. The fast rinsing is also useful when non-contaminating liquids are handled that are easily solvable in the rinsing liquid 64. In this case, replacement of the pipetting needle 32 and the pipetting tube 31 can be spared, thus eliminating one extra step in a handling of the liquid.

[0074] The pipetting needle 32 and the pipetting tube 31 constitute a replaceable part (indicated by the dotted frame in Fig. la). Replacement of the pipetting needle 32 and the pipetting tube 31 is useful when contaminating liquids are handled, which requires decontamination of the pipetting needle 32 and the pipetting tube 31 after a handling of the liquid. The present invention offers fast and easy replacement of the pipetting needle 32 and the pipetting tube 31.

[0075] The pipetting system 10 provides both the rinsing of the pipetting needles 32 and the pipetting tube 31, and a replacement thereof. A user can choose whether s/he rinses and/or replaces the pipetting needle 32 and the pipetting tube 31. The rinsing of the pipetting needle 32 and the pipetting tube 31 before a replacement thereof is useful because it results in easier cleaning of the pipetting needle 32 and the pipetting tube 31. Furthermore, damaging, e.g. bending or deforming, or malfunction by coagulations of the pipetting needle 32 can occur, in which cases replacement of the pipetting needle 32 is useful.

[0076] The rack 35 is adapted for arrangement of several ones of the rack 35 in a gridlike fashion because the rack 35 confines the pipetting tube 31, the pipetting pump chamber 23 and the piston 22 to a certain space within the rack 35. Thereby, several ones of a pipetting system 10 may be arranged in close proximity alongside one another into a multiple pipetting needle arrangement. Such a multiple pipetting needle arrangement may be set up without any two of the pipetting tube 32 risking interference and/or entanglement with one another. In such a multiple pipetting needle arrangement, any two adjacent ones of the pipetting systems may be spaced apart in a grid pattern by several millimeters, by for example, but not limited to, 9 millimeters or 18 millimeters.

[0077] In a multiple pipetting needle arrangement, several ones of the pipetting system 10 may be connected to a single one of the rinsing unit 60 for rinsing the several ones of the pipetting needles 32, the several ones of the pipetting tube 31, and the several ones of the pipetting pump chamber 23. The pressure tank 61 provides sufficient and immediate pressure for fast rinsing in a multiple pipetting needle arrangement. The invention therefore further allows the use of a single rinsing pump instead of needing one pump per needle.

[0078] In a multiple pipetting needle arrangement, the pressure tank 61 may be fluidly connected to a rinsing valve 42 via the rinsing tube 65 (Figure lb).

[0079] Additionally, several ones of the pipetting systems 10 may be connected to a single one of the controller 51. Alternatively, any one of the controller 51of the several ones of the pipetting system 10 may be connected to an additional controller, the additional controller communicating with any one of the controller 51.

[0080] Multiple pipetting needle arrangements are useful for highly parallelized and/or high-throughput technologies.

[0081] In one aspect of the invention, at least one component of the rinsing unit can be heated to heat up the rinsing liquid. The heating of the rinsing liquid has the positive effect that it avoids cooling down of the pipetting system when the pipetting needle is cleaned, therefore circumventing delays of a chemical reaction due to cooling down of the reaction mixture. In addition, heating of the rinsing liquid might facilitate and improve cleaning.

[0082] Needles that can be heated known from the state of the art have several disadvantages: they are expensive and produced in a time consuming production process, they necessitate an electrical connection of the heating-wire, the heating tube cover and the electrical connection of the wire can easily be damaged for example when piercing a vessel cap or diving into a hole, the gap between needle and the heating wire cover causes an increased risk of cross contamination as this gap is difficult to clean, the liquid in the tube above the needle is not heated, the air between needle and heating wire downgrades the heating performance in the case of needles comprising a heating wire inside the needle.

[0083] In another aspect of the invention, the pipetting needle and/or the tubing can be heated after cleaning of the pipetting needle cooled the pipetting system down. Therefore, the empty pipetting needle and/or tubing can be heated up before aspirating a liquid, or a liquid comprised in the pipetting needle and/or the tubing can be heated up before releasing it into a reaction vessel, to circumvent delays of a chemical reaction due to cooling down of the reaction mixture.

[0084] According to the present invention, heating of the pipetting needle and/or the tubing is performed by an inner lining heating wire, wherein the inner lining heating wire is a co-extrusion made of ferrophosphorus (FEP), Polytetrafluorethylene (PTFE) or any comparable material covered with an electrical conductive material. The heating wire is heated up by applying an outer induction field created by an induction coil. In one embodiment, the field is applied when the z-axis of the pipetting needle unit is at the top most position and enables heating during x-y movement. Depending on the position of the induction coil it is possible to heat up the heating wire inside the pipetting needle and/or the tubing or parts of the tubing as for example the pipetting tube.

[0085] In another aspect of the invention, the pipetting needle, made of steel for example, is heated directly by applying and induction field.

Reference Numerals pipetting system pipetting pump pipetting pump motor piston pipetting pump chamber pipetting needle unit pipetting tube pipetting needle opening disconnectable fluid interface rack valves pipettor valve rinsing valve washing valve sensing unit

50c capacitive sensor

50o optical sensor

50p pressure sensor

50w waveguide controller digital signal processor rinsing tube housing rinsing unit pressure tank rinsing pump rinsing liquid container rinsing liquid rinsing tube wash station with integrated rinsing nozzle pressure accumulator membrane

Claims

Claims

1.
2.

10
3.
4.

20 5.

6.

A pipetting system (10) comprising at least one pipetting needle (32) fluidly connected in series to a pressure tank (61), which is fluidly connected with a rinsing pump (62) which is fluidly connected with a rinsing liquid container (63).

The pipetting system (10) of claim 1, wherein the pressure tank (61) is further fluidly connected to at least one wash station with integrated rinsing nozzle (66).

The pipetting system (10) of claim 2, wherein the wash station with integrated rinsing nozzle (66) creates a rinsing liquid jet that cleans the pipetting needle (32) under a defined angle

The pipetting system (10) of any one of claims 1 to 4, further comprising a pipetting tube (31), a rinsing tube (65), and a pipetting pump (20) comprising a pipetting pump chamber (23) and a piston (22), wherein the pipetting needle (32) is fluidly connected to the pipetting tube (31), the pipetting pump (20), the rinsing tube (65), the pressure tank (61), the rinsing pump (62) and the rinsing liquid container (63).

The pipetting system (10) of claim 5, further comprising a light source optically connected to an input side of the waveguide and a sensing unit (50) for monitoring the handling of liquids, the sensing unit (50) comprising at least one capacitive sensor (50c) in electrical connection with the pipetting needle (32), a pressure sensor (50b) being in fluid connection with the pipetting pump (20), and an optical sensor (50o) in optical connection with an output side of a waveguide guiding light through an inner portion of the pipetting needle (32).

The pipetting system (10) of claim 6, further comprising a pipettor valve (41), wherein the pressure tank (61) is fluidly connected to the pipetting pump (20) over the pipettor valve (41), which is controlled by a controller (51), wherein the controller receives signals transmitted by the capacitive sensor (50c), the pressure sensor (50p), and the optical sensor (50o).

7. The pipetting system (10) of any one of claims 5 to 7, wherein the pipetting tube (31) and the pipetting pump chamber (23) are integrated into a rack (35) and fluidly connected to one another by a disconnectable fluid interface (34), the rack (35) be5 ing adapted for positioning the pipetting needle (32) in a vertical direction.

8. The pipetting system (10) of claim 8, wherein the disconnectable fluid interface (34) comprises a bayonet coupling.

10 9. The pipetting system (10) of any one of claims 1 to 9, wherein the pipetting system further comprises a pressure accumulator (67) to bridge start times of the rinsing pump (62).

10. The pipetting system (10) of any one of claims 1 to 10, comprising at least two pi15 petting needles (32) each fluidly connected to a pipetting tube (31), a pipetting pump (20), a rinsing tube (65) and a pressure tank (61) fluidly connected to a rinsing pump (62) and a rinsing liquid container (63).

11. The pipetting system (10) of claim 11, wherein the pipetting needles (32) are all

20 connected to the same pressure tank (61).

12. The pipetting system (10) of claim 11 or 12, wherein a pipetting needle (32), a pipetting tube (31) and a pipetting pump (20) form a unit, and wherein the units are arranged in a grid pattern to one another.

13. The pipetting system (10) of any one of claims 1 to 13, wherein the pressure tank comprises a membrane (68) which separates fluid and air.

14. The pipetting system (10) of any one of claims 1 to 14, wherein the pipetting sys30 tern (10) further comprises a control loop to create a constant pressure in the system.

15. The pipetting system (10) of any one of claims 2 to 15, wherein the pipetting needle (32) is made from steel.

16. The pipetting system (10) of any one of claims 1 to 16, wherein the pipetting needle
5 (32) comprises an inner lining heating wire to heat up system liquid.

17. The pipetting system (10) of any one of claims 5 to 16, wherein the pipetting needle (32), the pipetting tube (31), the rinsing tube (65), the pressure tank (61) and/or the rinsing liquid container (63) comprise an inner lining heating wire to heat up a sys10 tern liquid.

18. The pipetting system (10) of claim 17 or 18, wherein the inner lining heating wire is a co-extrusion made of FEP covered with an electrical conductive material.

15 19. The pipetting system (10) of any one of claims 1 to 29, wherein the pressure tank (61) is an air cushion.

20. A method for cleaning internal and/or external surface of a pipetting needle (32) of a pipetting system (10) with an integrated pressurized rinse system, comprising the

20 steps of pumping a rinsing liquid (64) from a rinsing liquid container (63) over a rinsing tube (65) into a pressure tank (61) with a rinsing pump (62); opening at least one valve to allow the rinsing liquid to flush the pipetting pump chamber (23), the pipetting tube (31) and the pipetting needle (32) and/or the wash station with integrated rinsing nozzle (66), wherein the wash station with integrated rinsing nozzle

25 (66) creates a rinsing liquid jet.

21. The method of claim 21, further comprising the step of heating up a system liquid.

Intellectual

Property

Office

Application No: GB1703098.2 Examiner: Stephen Jennings