WO2018015544A1

WO2018015544A1 - Pipetting device, fluid processing system and method for operating a fluid processing system

Info

Publication number: WO2018015544A1
Application number: PCT/EP2017/068495
Authority: WO
Inventors: Philipp Ott
Original assignee: Tecan Trading Ag
Priority date: 2016-07-22
Filing date: 2017-07-21
Publication date: 2018-01-25
Also published as: WO2018015543A1; WO2018015419A1; WO2018015545A1

Abstract

The invention relates to a pipetting device having tube (1), which has an opening (3) at one end for suctioning or discharging a sample fluid, and which can be operatively connected to a pressure generation means at the other end, wherein a first electrode (5) is formed on the pipetting device, which forms a measuring capacitor together with a second electrode (4') formed by at least one part of the sample fluid (4') that can be received in the tube (1), which measuring capacitor is operatively connected to a measuring unit (CAP), and which measuring unit is designed to determine a volume of the suctioned or discharged sample fluid (4') according to the capacity of the measuring capacitor, as well as comprising a first electrical contact (9') which is designed to create an electrical connection with the working fluid (7), wherein the first electrical contact (9') can be electrically connected to the measuring unit (CAP) via a low-resistance converter circuit (WS). The invention further relates to a fluid processing system having a pipetting device of this type.

Description

PIPETTING DEVICE, LIQUID PROCESSING SYSTEM AND METHOD FOR OPERATING A LIQUID PROCESSING SYSTEM

RELATED APPLICATIONS

The present application claims the priority of Swiss patent application CH 00950/16 with filing date July 22, 2016, the content of which is hereby incorporated into the present application

Patent application is included, the priority of

Swiss Patent Application CH 00159/17 with filing date 10 February 2017, the content of which is hereby incorporated into the present patent application, and the priority of Swiss Patent Application CH 00523/17 with

Filing date April 19, 2017, the content of which is hereby also included in the present patent application.

TECHNICAL FIELD OF THE INVENTION

The present invention relates to the technical field of liquid processing systems, and more particularly relates to a pipetting apparatus for aspirating and dispensing liquid volumes, such as liquid samples, for automated laboratory equipment. Furthermore, a Liquid processing system comprising a

Pipetting device and a measuring unit proposed. Furthermore, methods for operating a

Proposed liquid processing system in an open and closed loop.

BACKGROUND OF THE INVENTION

When in medical, chemical, analytical or pharmaceutical laboratories large quantities of samples too

Today, mostly automated laboratory systems or systems are used, which ensure rapid and reliable processing of each individual sample

enable. Such laboratory systems are often called

Fluid handling systems designed to handle fluid volumes, and suitable to perform certain operations with these samples, such as

For example, optical measurements, pipetting, washing, centrifuging, incubating and filtering. Such

Liquid processing systems include in particular

Pipettor both for sucking and dispensing

Liquids or dispensers exclusively for dispensing liquids. Most laboratory applications require very precise pipetting operations around one

to obtain satisfactory analytical accuracy. Consequently, an accurate knowledge of the processed

Sample volumes or liquid volumes of crucial importance. In the Swiss patent application CH 00950/16 with filing date July 22, 2016, a method which provides an accurate determination of a processed (ie aspirated or

dispensed) liquid volume during pipetting, as well as a pipetting device, which uses this method for a precise determination of the processed sample quantities or liquid volumes,

proposed.

In previously known systems, this is usually determined indirectly, for example by the sample with a

known suction power is absorbed during a certain time. The problem with these indirect

Method of volume determination is that not

it can be ensured that the desired amount of sample was actually taken in (respectively given), as (for example) air instead of the

Sample liquid is sucked or no liquid is taken up, because the pipette tip is clogged. Similarly, the volume absorbed effectively depends on the viscosity and surface tension of the sample.

Other parameters such as Variations in the diameter of the opening of disposable pipette tips also affect the volume of sample effectively taken up.

Known method of capacitive

Liquid level detection (so-called "capacitive liquid level detection", cLLD) can be used to determine the level difference between the immersion in and the Determine exhalation from a sample fluid. From the level difference and the cross-sectional area of the vessel, the volume taken or delivered can be calculated. However, these methods are too imprecise for small volumes and large cross-sectional areas. They are therefore only suitable for large volumes. In addition, mechanical tolerances of the height adjustment of the capacitive sensors falsify the measurement of the level difference. Parasitic capacities can cause an inaccurate

Determination of the processed sample quantities or

Be liquid volumes.

There is a need for means, which i.a. a simple and precise determination of the processed sample volumes or liquid volumes in automated

Pipetting allow and thus a high

ensure analytical accuracy of the examinations or operations performed.

SUMMARY OF THE INVENTION

It is an object of the present invention

Provide pipetting, with the help of a simple and accurate determination of the processed

Sample volumes or liquid volumes is made possible, with interference in the determination are substantially eliminated. This object is achieved according to the invention fulfilled by the set in claim 1 pipetting device.

It is also an object of the present invention to provide a liquid processing system with the proposed one

Equip pipetting device to provide a suitable for laboratory systems or facilities. This object is achieved by the

Liquid processing system according to claim 12 solved.

Specific inventive embodiments are given in the dependent claims.

A pipetting device according to the invention comprises a tube, wherein a fluid space of the tube is at least partially filled with a working fluid which is at a first end of the tube with a pressure generating means

is operatively connectable, adapted for aspirating or dispensing a sample liquid via an opening provided at a second end of the tube, wherein the working fluid and the sample liquid from each other via an air gap

are electrically insulated, wherein at the pipetting a first electrode is formed, which together with a second electrode, which is formed by at least a portion of the sample liquid accommodated in the tube, a measuring capacitor, which with a

Measuring unit is operatively connected, which is formed, depending on the capacity of the measuring capacitor, a volume determine the sucked or dispensed sample liquid, further comprising a first electrical

Contact, which of the first electrode and second

Electrode is electrically insulated and is adapted to an electrical connection with the working fluid

wherein the first electrical contact via a low-impedance converter circuit electrically to the

Measuring unit is connectable.

The present invention allows the sample liquid to be used as one of the two electrodes of a measuring capacitor. In other words, the sample liquid acts as a "liquid electrode." Depending on the amount of the

Pipetting device sucked respectively dispensed sample liquid changes the capacity of this

Measuring capacitor (i.e., it becomes larger respectively

smaller), whereby by means of the measuring unit directly the

Volume of aspirated or dispensed

Sample fluid can be accurately determined. The

Sample liquid should have a certain conductivity. The tube itself acts as a dielectric between the two electrodes. By a corresponding design of the tube, inside which the

Sample liquid is located as a second electrode, and e.g. on the outer surface of the first electrode

is applied, even very small volumes can be determined with high accuracy. The two electrodes of the measuring capacitor can have any shape. There is only a relationship between The capacitance of the measuring capacitor depending on the sample volume can be determined.

Further details are given in the Swiss patent application CH 00950/16 with filing date July 22, 2016, the contents of which are incorporated herein.

A metallic first electrical contact on the

Bottom of the tube is electrically connected to the sample liquid. A second electrical contact at the top of the tube communicates electrically with the working fluid and can apply the working fluid to a guard potential. The air gap between the two columns of the sample liquid and the working fluid acts as an electrical insulator. The invention allows only the column of the sample liquid than for the

Measuring capacitor relevant electrode can act.

It should be noted that the term sample volume is not just the volume of liquid analysis samples

but also volumes of reagents, dilution solutions such as buffer solutions, solvents or suspensions with particles or cells.

In an embodiment variant of the pipetting device, the low-resistance converter circuit is designed for

Reducing parasitic capacitances caused by the working fluid. In a further embodiment of the

Pipetting device is the low-impedance converter circuit with a high-impedance input and a low-impedance

Provided exit.

In a further embodiment, the

The pipetting device further comprises a second electrical contact, which is electrically insulated from the first electrode and is adapted to establish an electrical connection with the sample liquid during aspiration or dispensing of the sample liquid, so that at least a portion of the sample liquid, which is located in the tube, the second Forming electrode of the measuring capacitor, wherein the first electrode is electrically connected to the measuring unit.

In a further embodiment of the

Pipetting device is the tube through the first

Electrode partly or completely sheathed.

In a further embodiment of the

Pipetting device consists of the tube at least in

Area of the opening of an electrically conductive material and forms the second electrical contact, or alternatively the tube is made of an electrically non-conductive material, which is provided as a dielectric of the measuring capacitor. In a further embodiment of the

Pipettiervorrichtung is the second electrical contact via a capacitive coupling via the sample liquid producible, which is located in a sample container, sucked from the sample liquid or in the

Sample liquid can be dispensed.

In a further embodiment of the

Pipetting the second electrical contact via a third switching element to the measuring unit, the low-resistance converter circuit or ground connectable.

In a further embodiment of the

Pipetting the first electrical contact and the first electrode via a respective first switching element and second switching element with the measuring unit, the low-resistance converter circuit or ground connectable, wherein by switching the respective couplings between the first electrical contact, the first electrode and the second electrical contact with each of the measuring unit, the low-resistance converter circuit or mass physical effects, which can adversely affect the measurement results, are substantially eliminated.

In a further embodiment of the

Pipetting device is the second electrical contact in a state isolated from ground and with the Connected measuring unit, in which the second electrical contact and the sample liquid are spaced from each other or the second electrical contact not in the

Sample liquid is immersed.

In a further embodiment of the

Pipetting device, the second electrical contact in a state connected to ground and separated from the measuring unit, in which the second electrical contact and the sample liquid communicate with each other and the second electrical contact in the sample liquid

is immersed.

According to another aspect of the present invention, a fluid processing system comprises a

proposed pipetting with a measuring unit, which is formed, depending on the capacitance of the measuring capacitor, a volume of the sucked or

to determine determined sample liquid, and a low-resistance converter circuit, wherein the first electrical contact, which is adapted to establish an electrical connection with the working fluid, and the

Measuring unit via the low-impedance converter circuit

electrically connected to each other.

In one embodiment, this includes

Liquid processing system further

Pressure generating means, wherein the pressure generating means with a regulator is connected, which is designed to be in a closed loop based on the determined by the measuring unit volume of the sucked or

delivered sample liquid and a predetermined target volume of the sucked or delivered

Sample liquid, a pressure for the suction or

Delivered the sample liquid to the working fluid

create.

In a further embodiment, this includes

Liquid processing system further comprises a motorized transport unit, such as a robot arm, on which the pipetting device is arranged, wherein the controller is additionally adapted to send signals to the transport unit to move the pipetting device so that the opening of the tube is precisely positioned, in particular in a sample container filled with the sample liquid, such as a

Sample tube or a microplate.

In a further embodiment, this includes

Fluid processing system also a third

Switching element, which electrically connects the second electrical contact with the measuring unit or separates thereof.

In a further embodiment of the

Fluid processing system is the third Switching element adapted to electrically connect the second electrical contact with ground or isolate against it.

In a further embodiment of the

Fluid processing system isolates the third

Switching the second electrical contact in a state to ground in which the second electrical contact and the sample liquid are spaced from each other and the second electrical contact not in the

Sample liquid is immersed.

In a further embodiment of the

Fluid processing system connects the third

Switching the second electrical contact in a state of ground, in which the second electrical

Contact and the sample liquid communicate with each other or the second electrical contact in the

Sample liquid is immersed.

According to another aspect of the present invention, a method of operating a proposed open loop liquid processing system comprises the steps of: detecting a state in which the second one

electrical contact (9 '') of the pipetting device comes into contact with the sample liquid (4); - Switching the liquid processing system on

Volume measurement;

Aspirate the sample liquid (4) through the

Pressure generating means; and

Determine a volume of the aspirated

Sample liquid (4 ') as a function of the capacitance of the measuring capacitor.

According to another aspect of the present invention, a method of operating a proposed fluid processing system in a closed loop system comprises the steps of:

- Detecting a state in which the second

electrical contact (9 '') of the pipetting device comes into contact with the sample liquid (4);

- Switching the liquid processing system on

Volume measurement; and

Aspirate the sample liquid (4) through the

Pressure generating means based on a predetermined

Volume signal.

It is expressly stated that the

above variants are arbitrarily combinable. Only those combinations of

Variants are excluded, which would lead to contradictions through the combination. BRIEF DESCRIPTION OF THE DRAWINGS

Non-limiting embodiments of the present invention will be explained below with reference to figures. Show it:

Fig. 1 is an enlarged schematic representation of a

Embodiment of a pipette tip of a pipetting device according to the invention;

Fig. 2 is a schematic representation of a

Embodiment of an inventive

Pipetting device, which is operated with a working fluid;

Fig. 3a) is a schematic diagram of an electrical

Connection of a pipetting device in a state in which the

Pipetting device not in the

Immersed sample liquid,

b) the schematic diagram of the electric

interconnected pipetting device according to Fig. 3a) in a state in which the

Pipetting device is immersed in the sample liquid; and

4) an exemplary sample container carrier from a liquid processing system.

In the figures, like reference numerals represent like elements. DETAILED DESCRIPTION OF THE INVENTION

Fig. 1 shows greatly simplified in a schematic

Representation of an embodiment of a tube 1 from a pipette tip 2 of a pipetting device. The tube 1 consists for example of glass or a plastic and is part of the pipette tip 2. Although the tube 1 as

Cylindrical cylinder is shown, it may be any elongated hollow body and take any shape in cross section, e.g. oval, rectangular, etc. In the channel of this tube 1 is through an opening 3 at one end of the tube 1 a

Sample liquid 4 'from a sample container (not shown) sucked into the tube 1 or from this

delivered by e.g. by means of a pump, a piston or plunger (not shown) which is in fluid communication with the other end of the tube 1, the pressure in the tube 1 is reduced or increased. Around the tube 1 around a first electrode 5 is arranged wholly or partially enveloping. This first electrode 5 can

For example, from a deposited on the tube 1 conductive coating, such as a copper layer, or adhered to the tube 1 conductive foil, such as a copper foil exist. This first electrode 5 can be applied to a specific reference potential, eg ground. If now the sample liquid 4 is applied to another potential via an electrical contact by means of a voltage source, then the first electrode 5 and the first electrode 5 are formed Sample liquid 4 ^Λ as a counter electrode (= second electrode) together a measuring capacitor 6, such as

schematically indicated by a capacitor switching symbol. The measuring capacitor 6 has, depending on the volume of

Sample liquid 4 which is currently in the tube 1, a different size capacity. Thus, there is a direct relationship between the capacitance of this measuring capacitor 6 and the volume of

Sample liquid 4 which is in the tube 1, i. the aspiration (or aspiration) of sample liquid increases the capacity and when dispensing (or

Dispensing) of sample liquid reduces the capacity. By determining the capacity of the

Measuring capacitor 6 by means of a suitable measuring unit, which includes, for example, a capacitance-to-digital converter (so-called. CDC converter, not shown), thus directly the volume of the located in the tube 1 sample liquid 4 ^{Λ are} determined.

Fig. 2 shows an example in which a working fluid 7 (also called system liquid) is used for pressure transmission. The tube 1 is partly with the

Working fluid 7 and partly filled with the sample liquid 4 ^Λ , wherein an air gap 8 is established between the two liquids, which prevents the

Working fluid 7 with the sample liquid 4 ^λ comes into contact. As shown in the embodiment according to Figure 2, the (electrically conductive) working fluid 7 via a first electrical contact 9 ', which with the Working fluid 7 is in fluid communication, electrically

connected. Here, the first electrical contact 9 'with respect to the first electrode 5 and the second electrode 4' (sample liquid) is electrically isolated. The first electrical contact 9 'can apply the working fluid 7 to a guard potential or connect it to a guard potential. Also included is a second electrical contact 9 "which is connected to the (electrically conductive)

Sample liquid 4 'is in fluid communication. The second electrical contact 9 '' is also electrically insulated from the first electrode 5. This second electrical contact 9 '' provides the suction or delivery of the

Sample liquid 4 'an electrical connection with the sample liquid 4' ago, so that at least a portion of the sample liquid 4 ', which is located in the tube 1, the second electrode of the measuring capacitor forms. The

Sample liquid 4 'can be grounded via the second electrical contact 9' 'or connected to ground potential. In one embodiment, the tube 1 at least in the region of the opening 3 made of an electrically conductive material and in this case the second electrical contact 9 '' form, or alternatively consist of an electrically non-conductive material which may be provided as a dielectric of the measuring capacitor.

As further schematically shown in Fig. 2, is a

Measuring capacitance MC (measuring capacitance) over the region of the tube 1 between the first electrical contact 9 'and the second electrical contact 9 '' determinable. Furthermore, a measurable capacity of the sample liquid MSC (measured sample capacitance) in the region of the tube 1 between the highest point of the sample liquid column and the second electrical contact 9 '' determinable. Other measuring ranges can also be recorded, as explained in more detail below.

Figures 3a) and 3b) show schematically each one

electrical interconnection of the pipetting device. Here, a state is shown in Fig. 3a), in which the

Pipetting device is not immersed in the stored in a sample container sample liquid 4, while in Fig. 3b), a state is shown in which the tube 1 is immersed in the sample liquid 4. It should be mentioned that beyond the description of the in

Sample container stored sample liquid with the

Reference character 4 is characterized, while the recorded in the pipetting sample liquid is the reference numeral 4 'awarded.

The tube 1 is enveloped by the first electrode 5 and the second electrode is formed by the sample liquid 4 'itself (see Fig. 3b)).

The first electrical contact 9 ', the first electrode 5 and the second electrical contact 9''are in each case via a first switching element S9', second switching element S5 and third switching element S9 '' interconnected. The shading by the switching elements S9 ', S5 and S9''is

by way of example and for illustration - a

Of course, any switching can be done this way

implemented to be controlled by a processor, computer or other control device.

The first electrical contact 9 'establishes an electrical contact with the working fluid 7. A measuring unit CAP (more on this in the following) can be electrically connected to the working fluid 7 via the first electrical contact 9 '. For this purpose, the measuring unit CAP is a low-impedance

Converter circuit WS electrically connected to the first electrical contact 9 ', wherein a switch over the first switching element S9' can be realized. The low-resistance converter circuit WS serves to reduce parasitic capacitances, which i.a. can be caused by the working fluid 7, and can with a

high-impedance input and a low-impedance output

be provided. The working fluid 7 can via the first

Switching element S9 'also applied to ground potential or switched.

The first electrode 5 can be connected or disconnected via the second switching element S5 to the measuring unit CAP. In the state shown in Fig. 3a), the first electrode 5 is disconnected from the measuring unit CAP, while in the state shown in Fig. 3b) it is connected to the measuring unit CAP (more on this later). The first electrode 5 can over the second switching element S5 are also applied to ground potential. The measuring unit CAP determines in

Depending on the capacity of the measuring capacitor formed a volume of the sucked or discharged

Sample liquid 4 '. In other words, that serves

Measuring unit CAP for determining the capacity of the

Measuring capacitor and thus the volume of

Sample liquid 4 'in the tube 1. The measuring unit CAP is, for example, a capacitance-to-digital converter

Capacitance-to-Digital Converter (CDC), which converts capacitance into voltage and is based on the sigma-delta converter method The CDC method determines its size in farads as a digital value for an unknown capacitance Commercially available CDC

The devices are the FDC1004 from Texas Instruments and the AD7745 from Analog Devices. The measuring unit CAP can be connected to ground at another end.

The second electrical contact 9 "provides a

electrical contact with the sample liquid 4 'forth, which in turn via the third switching element S9' 'is electrically coupled to the measuring unit CAP. The

Sample liquid 'can also be electrically separated from the measuring unit CAP via the third switching element S9' 'and applied to ground potential.

In the state shown in Fig. 3a) is the

Pipetting device is not immersed in the sample liquid 4 and serves here for liquid level detection. In this state, in a mode 1, the second electrical contact 9 "is connected to the measuring unit CAP via the third switching element S9" and isolated from ground. The second electrical contact 9 '' is insulated from ground in a state and connected to the measuring unit CAP, in which the second electrical contact 9 '' and the sample liquid 4 are spaced from each other and the second electrical contact 9 '' not in the sample liquid 4 is immersed

(liquid level detection). As a result, between the second contact 9 ¹ 'at the opening 3 of the tube 1 and the sample liquid 4 in the sample container itself

Measuring capacitor formed. In this state, the

Sample liquid 4 via the bottom of the sample container, in which the sample liquid is 4, capacitively coupled to ground. A work table (not shown) on which the sample container is stored in e.g. one

Sample container carrier is arranged, it is connected to ground as reference potential. As previously mentioned, in the liquid level detection, the second electrical

Contact 9 '' disconnected from ground and connected to the measuring unit CAP, while the second electrode 5 of the

Measuring unit CAP is disconnected.

After a dipping of the tube 1 is detected in the sample liquid 4 (see Fig. 3b)), the switches

Pipetting on the determination of the volume of sample liquid 4 'in the tube 1 um. In one

exemplary mode 2, the first electrode 5 with the unit CAP connected and the first electrical contact 9 'connected to the low-impedance converter circuit WS. Furthermore, the third switch S9 "separates the second electrical contact 9" from the measuring unit CAP and switches the second electrical contact 9 "to ground or applies it to ground potential. By now grounding the second electrical contact 9 ", influences of sample container capacity can be eliminated. Further, by connecting the first electrical contact 9 'to the low-resistance converter circuit WS, possible influences by the working fluid 7 are eliminated.

In summary, therefore, the second electrical contact 9 '' in a state connected to ground and of the

Measuring unit CAP separated, in which the second electrical contact 9 '' and the sample liquid 4 are in communication with each other or the second electrical contact 9 '' is immersed in the sample liquid 4 in the sample container. In this state, the measuring capacitor between the sample liquid 'in the tube 1 and the first

Electrode 5 is formed and this enables the pipetting device to determine the volume of sample liquid 4 'in the tube 1 substantially continuously and free of measuring influences.

In other words, parasitic effects can be eliminated by not connecting the first electrode 5 until the volume of sample liquid 4 'is determined by the measuring unit CAP and (substantially) simultaneously the second electrical contact 9 "is disconnected from the measuring unit CAP and grounded. Here, it does not matter whether the tube 1 is immersed in the sample container 4 stored sample liquid 4 or not. A significant advantage is thus that

Pipetting measurements not only during aspiration, but also during non-contact dispensing

Sample liquid 4 'can be made.

For example, partial sample volumes can be reliably determined in the case of multiple dispense.

In a first variant of a mode 3, the first electrical contact 9 'is connected to the low-resistance converter circuit WS by the first switching element S9', the first electrode 5 is grounded by the second switching element S5, and the second electrical contact 9 'is formed. 'by the third switching element S9' ¹ with the

Measuring unit CAP connected. Thereby, a possible influence of the sample container capacity by subtracting mode 1 can be eliminated. Further, by the first

electrical contact 9 'with the low-resistance

Converter circuit WS is connected, possible

Influences by the working fluid 7 eliminated. Here, since the first electrode 5 is grounded, it is further advantageous to eliminate potential influences by laboratory equipment. An advantage of the additional modes is that a sample container capacity measured in parallel by an alternately measured basic capacity without

Sample liquid (mode 1) can be subtracted. In a second variant of mode 3, the third electrical contact 9 '' can be connected to the measuring unit CAP, while the first electrode 5 and the first

electrical contact 9 'can be applied to ground

(Not shown). Thus, no active guard would be necessary. This configuration may be advantageous if a ground connection is present at the other end of the tube 1 and the sample liquid 4 has a high conductivity. By advantageously fast switching between the first and second variant possible interference can be reduced or eliminated. Further details are given below.

There are applications in which larger ones

Sample liquid 4 'recorded volume that can exceed the maximum capacity of the tube 1. In this case, the sample liquid 4 'in addition to the second electrical contact 9' 'also contacts the first

electrical contact 9 'and the air gap 8 via the first electrical contact 9' upwards away

wandered out. In this case, can on a

example mode 4 are switched. In this mode 4, the first electric contact 9 'is connected to the measurement unit CAP through the first switching element S9', the first electrode 5 is grounded through the second switching element S5, and the second electric contact 9 '' becomes the third switching element S9 '' also connected to the measuring unit CAP. A boom (Z-bar) the Pipetting device, which is grounded, can serve as an external electrode. A possible influence of

Sample container capacity can be eliminated by subtracting Mode 1. Furthermore, a possible influence of the working fluid 7, which in this example neither the second electrical contact 9 '' nor the first

electrical contact 9 'contacted, be eliminated. Further, by grounding the first electrode 5, influences by laboratory equipment are also eliminated.

The described different modes are given in Table 1 below. The details refer to what the first electrical contact 9 ', the first electrode 5 and the second electrical contact 9''are respectively coupled by switching a respective one of the switching elements S9 ¹ , S5 and S9'', namely whether with the low-resistance converter circuit WS, the measuring unit CAP or ground GND. For example, the mode 1, as in the

Table and previously described that 9 '(first electrical contact) by S9' (first switching element) with WS (low-impedance converter circuit) is connected

(Switch S9 'above), 5 is connected through S5 to WS (switch S5 above), and 9' 'through S9' 'with CAP

(Measuring unit) is connected (switch S9 '' center). Mode S9 ^λ S5 S9 ^Λ Application / Purpose

1 WS WS CAP - Immersion Detection (before the

Immersion) -> none

Influences due to working fluid (applies to S9 ^, ) or through a laboratory device (concerns S5)

- Sample container capacity

(after immersion) no influences

Working fluid (relates to 39 ^, ) or sample fluid

(concerns S5)

2 WS CAP GND - Volume measurement of the

Sample liquid MSC A - Influence of

Sample container capacity

(39 ^{, Λ} is on mass) and influence of the working fluid

{S9 * coupled with WS) can be eliminated

3 WS GND CAP - Volume measurement of

Sample liquid MSC B - Influence of

Sample container capacity can be eliminated by subtracting Mode 1; No Influence of

System fluid (S9 'coupled to WS);

- Possible measurement distortions by laboratory equipment can be eliminated (first electrode 5 is grounded)

4 CAP GND CAP - Volume measurement of

Sample liquid with enlarged

Measuring capacitor (Z-bar is grounded) ->

sample liquid

contacted 9 ^{, λ} and 9 \ · air gap is above 9 ^Λ ;

- influence of

Sample container capacity can be determined by subtracting mode

1 are eliminated;

- influence of the working fluid can be eliminated (no longer contacted); Possible measurement distortions by laboratory equipment are eliminated (first electrode 5 is grounded)

Table 1 Fig. 4 shows an example of a

Liquid processing system with a

Pipetting device, in which the tube 1 can be wrapped by a copper foil as the first electrode 5. The sample liquid 4 is located in a sample tube 10 as a sample container, which together with other

Sample tubes is arranged in a sample container carrier 11, which stands on a work table 12. The conductive work surface is connected to ground, with the sample liquid 4 capacitively coupled to the work table 12 also being grounded.

LIST OF REFERENCE SIGNS

1 tube

2 pipette tip 3 opening in the pipette tip, pipetting opening

4 sample liquid in the sample container

4 sample liquid in the tube = second, variable

Electrode ("liquid electrode") of the measuring capacitor

5 first, fixed electrode of the measuring capacitor 6 illustrative measuring capacitor

7 working fluid or system fluid

8 air gap

9 'first electrical contact for the working fluid

9 '' second electrical contact for the sample liquid 10 sample containers, e.g. sample tube

11 sample container carriers

12 Worktable CAP Measuring unit MC Measuring capacity

MSC measurable capacity of sample liquid

S9 'first switching element

S5 second switching element

S9 ' ¹ third switching element

WS low-impedance converter circuit

Claims

1. A pipetting device with a tube (1), wherein a fluid space of the tube (1) at least partially with a

Working fluid (7) is filled, which at a first end of the tube (1) with a pressure generating means is operatively connected, designed for sucking or dispensing a

Sample liquid (4 ') via an opening (3) provided at a second end of the tube (1), wherein the working fluid (7) and the sample liquid (4') are electrically isolated from each other via an air gap (8), wherein at

Pipetting a first electrode (5) is formed, which together with a second electrode (4 '), which is formed by at least a portion of the accommodatable in the tube sample liquid (4'), a measuring capacitor (6), which with a measuring unit (CAP)

is operatively connected, which is formed, depending on the capacity of the measuring capacitor (6) to determine a volume of the sucked or dispensed sample liquid (4 '), further comprising a first electrical contact (9') which of the first electrode (5) and second electrode (4 ') is electrically insulated and is adapted to be electrically connected to the

Working fluid (7) produce, wherein the first electrical contact (9 ') via a low-impedance converter circuit (WS) is electrically connected to the measuring unit (CAP).

2. The pipetting device according to claim 1, wherein the low-resistance converter circuit (WS) is designed to reduce parasitic capacitances which can be caused by the working fluid (4 ').

3. Pipetting device according to claim 1 or 2, wherein the low-resistance converter circuit (WS) is provided with a high-impedance input and a low-impedance output.

4. The pipetting device according to one of the preceding claims, further comprising a second electrical contact (9 '') which is electrically isolated from the first electrode (5) and is adapted to, when sucking or discharging the sample liquid (4 ') an electrical connection with the sample liquid (4 ') produce, so that at least a portion of the

Sample liquid (4 '), which is located in the tube (1), the second electrode (4') of the measuring capacitor (6), wherein the first electrode (5) with the

Measuring unit (CAP) is electrically connected.

5. Pipette device according to one of the preceding claims, wherein the first electrode (5), the tube (1) partially or completely envelops.

6. Pipetting device according to claim 4 or 5, wherein the tube (1) at least in the region of the opening (3) consists of an electrically conductive material and the second electrical contact (9 '') forms, or alternatively consists of an electrically non-conductive material, which is provided as a dielectric of the measuring capacitor.

7. Pipetting device according to one of claims 4 to 6, wherein the second electrical contact (9 '') via a capacitive coupling via the sample liquid (4).

can be created, which is located in a sample container (10) from the sample liquid sucked or can be dispensed into the sample liquid.

8. Pipetting device according to one of claims 4 to 7, wherein the second electrical contact (9 '') via a third switching element (S9 '') to the measuring unit (CAP), the low-resistance converter circuit (WS) or ground is connectable.

9. The pipetting device according to claim 8, further comprising the first electrical contact (9 ') and the first electrode (5) via a respective first switching element (S9') and second switching element (S5) with the measuring unit (CAP), the low-resistance converter circuit ( WS) or ground can be connected, wherein by switching the respective couplings between the first electrical contact (9 '), the first electrode (5) and the second electrical contact (9' ') with each of the measuring unit (CAP), the low-resistance

Converter circuit (WS) or mass physical effects, which can have a negative effect on the measurement results are essentially eliminated.

10. A pipetting device according to claim 8 or 9, wherein the second electrical contact (9 '') in a state opposite

Ground isolated and connected to the measuring unit (CAP), in which the second electrical contact (9 '') and the sample liquid (4) are spaced from each other or the second electrical contact (9 '') not in the

Sample liquid (4) is immersed.

11. A pipetting device according to claim 8 or 9, wherein the second electrical contact (9 '') is connected to ground in a state separated from the measuring unit (CAP) in which the second electrical contact (9 '') and the

Sample liquid (4) communicate with each other or the second electrical contact (9 '') in the

Sample liquid (4) is immersed.

12. liquid processing system comprising a

Pipetting device according to one of claims 1 to 11, a measuring unit (CAP), which is formed in

Dependency of the capacitance of the measuring capacitor to determine a volume of the sucked or discharged sample liquid (4 '), and a low-resistance converter circuit (WS), wherein the first electrical contact (9') _/ which is adapted to make an electrical connection with the

To produce working fluid (7), and the measuring unit (CAP) are electrically connected to each other via the low-resistance converter circuit (WS).

The fluid processing system of claim 12, further comprising a pressure generating means, wherein

Pressure generating means is connected to a controller which is adapted to be in a closed

Control circuit based on the volume of suctioned and discharged by the measuring unit (CAP)

Sample liquid (4 ') and a predetermined

Target volume of sucked or delivered

Sample liquid (4 ') to apply a pressure for the suction or discharge of the sample liquid (4') to the working fluid (7).

14. A fluid processing system according to claim 12 or 13, further comprising a motorized transport unit, such as a robotic arm, on which the

Pipetting device is arranged, wherein the controller is additionally adapted to send signals to the

Transport unit to move the pipetting device so that the opening (3) of the tube (1) is precisely positioned, in particular in one with the

Sample liquid (4) filled sample container (10), such as a sample tube or a microplate.

15. Liquid processing system according to one of

Claims 12 to 14, further comprising a third Switching element (S9 ¹ ') which electrically connects the second electrical contact (9'') to the measuring unit (CAP)

connects or disconnects.

16. Liquid processing system according to one of

Claims 12 to 15, further comprising a third

Switching element (S9 '') which electrically connects or isolates the second electrical contact (9 '') with ground.

17. The fluid processing system of claim 16, wherein the third switching element (S9 '') isolates the second electrical contact (9 '') from ground in a state in which the second electrical contact (9 ¹ ') and the

Sample liquid (4) are spaced from each other or the second electrical contact (9 '') not in the

Sample liquid (4) is immersed.

18. The liquid processing system according to claim 16, wherein the third switching element (S9 '') connects the second electrical contact (9 '') to ground in a state in which the second electrical contact (9 '') and the sample liquid (4 ) or the second electrical contact (9 '') is immersed in the sample liquid (4).

19. Method of operating a

A liquid processing system according to any of claims 12 to 18 in an open loop, comprising the steps of:

- Detecting a state in which the second

- Switching the liquid processing system on

Volume measurement;

Aspirate the sample liquid (4) through the

Pressure generating means; and

Determine a volume of the aspirated

20. Method of operating a

A liquid processing system according to any one of claims 12 to 18 in a closed loop, comprising the steps of:

- Detecting a state in which the second

- Switching the liquid processing system on

Volume measurement; and

Aspirate the sample liquid (4) through the

Pressure generating means based on a predetermined volume signal.