Device for detection of a fluidic interface in a transparent measuring tube.

The invention relates to a device for detecting a fluid phase boundary in a transparent measuring tube, as well as equipped with such a detection device for the automatic exact metering device small amounts of liquid.

Means for detecting a fluid phase boundary in a measuring tube are often needed. As fluid phase boundary there is any interface between a liquid and a standing to this in phase boundary contact optically distinguishable phase, which may be gaseous, liquid or solid, to be considered.

Commonly used are primarily devices for the detection of the ride height of a liquid in an upright flow tube which is referred to hereinafter as riser. They are known in the art according to a common English expression as LLD (Liquid Level Detector). In particular, the invention is directed to applications in connection with devices for the analysis of body fluids (mainly blood and urine). This involves in particular to the detection of the fluid phase boundary of samples or liquid reagents.

As far as the liquid is located in an open vessel, her ride height can detect by means of a plunging from above the probe, the probe usually simultaneously is a pipette tip, can be supplied to or sucked by a reagent or sample liquid. There is a liquid detector which upon immersion at the tip of the probe or pipette - generates a signal in the liquid - may also shortly before immersion. For this purpose, different principles are known, for example based on the determination of the electrical resistance or the electrical capacitance between two attached to the tip of the pipette electrodes. There are also already optical principles for such applications has been discussed (European Patent 0,250,671). In these methods, the position of the probe or pipette are a measure of the level of the liquid when immersed in the liquid.

The invention is not directed in particular, but exclusively to the determination of the fluid phase boundary in a closed upward riser. For such applications optical principles of measurement have been proposed in which the riser tube is illuminated with a least one light source having illumination device, a light receiving device is provided with at least one light receiver, which receives part of the light passing through the riser pipe and the liquid contained therein light and by its location-dependent intensity distribution dependent electrical signals converts. The signals of the light receiving means to be supplied to an electronic evaluation device in order to derive the desired information about the surface level of the liquid level in the riser.

The realization of this seemingly simple principle causes considerable problems, especially when the ride height is to be determined in a capillary tubing with very thin inner diameter with high precision.

In German Patent 28 55 651 is on the problems with the various known optical measuring principles (provision of darkening by a colored liquid and the brightening by a clear liquid; reflection and scattered light principle; meniscus scanning) pointed. It is proposed a specific electronic circuit, to compensate for the optical problems by improving the signal processing.

In the detection of liquids in medical analysis devices the problem is more difficult, especially in that the reagents and samples are usually only very slightly colored. Moreover, the coloring from sample to sample or reagent to reagent is different, yet the ride height to be detected regardless of these differences accurately. In German Patent 28 55 651 has already noted that a previous proposal to solve these problems provides exploit the cylindrical lens effect of the liquid present in the riser. For example, the focused by the liquid-filled tube light can be kept away by a diaphragm from the photocell. When the liquid level in the riser pipe as far drops that the entity of the pipe is empty, the focal length of the cylindrical lens changes a portion of the light incident on the photocell.

Also in the European patent application 0185285, the problem of detection of a substantially transparent medical fluids is discussed. In order to solve the above-described principle here is used, wherein the liquid-filled tubing in this case serves as a lens to focus a narrow band of light to the light source (based on the riser) opposite surface. It is important that the riser has a certain (cylindrical) shape and the geometrical conditions of the focus will be strictly adhered to. It is also described an embodiment in which the light receiving means comprises a plurality of light receivers in the form of photocells, photoresistors, photodiodes, phototransistors or the like, which are each arranged opposite a light emitter in parallel with the riser pipe, so that they are arranged a plurality of closely one above the other form light barriers. Although this arrangement provides a convenient height level detection, however, can meet only low demands in terms of resolution and precision of the surface level determination. The reaction is carried at a distance from the photosensitive elements of 1 mm and reached a precision of the volume measurement in the riser of about 100 ul. It follows that a relatively thick tubing was used with an inner diameter of about 5 mm. For detection of the phase boundary in a capillary-shaped flow tube with an internal diameter of for example less than 1 mm which is used in the European patent application, on the different focusing of the filled and the empty measuring tube based principle not suitable.

In an apparatus described in German patent application 36 05 403, the detection of the liquid level object based on the fact that a continuous transition of the measured light intensity in the area of ​​liquid level is attained. For this purpose, a parallel to the riser pipe extending line-shaped light source in conjunction with a number of directly provided on the riser detectors is used. It is considered absolutely essential that a difference in the detected light intensity between the liquid-filled and the gas-filled portion of the riser is. This difference is ensured that either the liquid is colored, or (as in the previously described devices) of the cylindrical lensing effect during the passage of the light is used through the riser.

In the scientific article "Optical device for the measurement of small volume changes" of AK Davies et al. Applied Optics, 1986, 1245 f is described an apparatus which is intended for detecting the volume level object (and thus the volume) in a capillary of 50 ul. This proposal requires a high technical effort. The light is narrowband filtered. There must be a specific angle of incidence (28 °) can be selected under which the light impinges on the capillary. The photocell behind it must be additionally screened by special arrangements of diaphragms. Nevertheless, the detection of the phase boundary between the liquid and air is not possible in all areas of the capillary, but only the central 20% of the capillary can be used. This is based on the evaluation of an analog signal change principle requires an accurate calibration.

In order to enable an accurate, reliable determination of the position of the phase boundary, in particular in a measuring tube with a very small (capillaries) Diameter (in particular in cases where the optical brightness of the media little or does not differ on both sides of the phase boundary) depends the invention according to a first main aspect, an apparatus for detecting a fluid phase boundary in a transparent measuring tube with a lighting device having at least one light source for illumination of the measuring tube, a light reception means with at least one light receiver, which receives through the measuring tube, light passing and from its location-dependent intensity distribution dependent electrical signals converted and an evaluation unit for processing the signals of the light receiving means into an information about the position of the fluid phase boundary in the measuring tube, wherein the illumination device for the steady illumination of a detection section of the measuring tube is formed and the light receiving means an imaging optical system for imaging comprises the detection section in an image plane and a number of closely adjacent light-sensitive elements in the image plane.

The photosensitive elements in the image plane of serving advantageously as an imaging optical system lens are preferably a linear array of CCD elements (charged coupled devices). The distance of the light-sensitive elements is preferably less than 50 microns.

According to the invention, the position of a fluid phase boundary in a measuring tube with a very small diameter of less than 1 mm, particularly preferably be detected even less than 0.5 mm reliably and accurately.

The invention allows the position determination of the fluid phase boundary in such a thin capillaries with no moving parts. Characterized in that the liquid column is detected in the measuring tube for an extended detection section with high resolution, it is additionally possible, typical error sources, such as air bubbles or impurities, to eliminate by means of a process performed by a microprocessor-controlled evaluation detection algorithm.

The lighting of the detection portion must be continuous in the sense that (in contrast to light barriers) none of sudden changes in the spatial distribution of the illumination intensity. Such continuous illumination can be achieved by various known means, for example by means of an elongated extended (for example tubular), parallel to the measuring tube extending light source, a plurality of parallel to the measuring tube close together arranged light sources or illumination optics which a light simple light source (eg halogen lamp) expands accordingly. Much preferred, however, is an embodiment in which the illumination means comprises a light diffusing means, in particular with a direction parallel to the measuring tube extending ground glass (or other diffusion surface). This makes it possible with low design cost and without precise positioning of the light source is a particularly accurate detection of the phase boundary.

The structure is relatively simple. There are no screens, filters or screens required. It can be an extremely high accuracy and precision can be achieved. For example, nl were detected reliably with the invention in a capillary having an internal diameter of 0.2 mm and a pitch of the CCD elements (pixels) of 25 microns volume differences of +/- 1st

The system operates without moving parts and without delay. It is possible to detect the time change of the position of the phase boundary and exactly, for example, to determine their moving speed.

According to a second main aspect, the invention is not directed to an apparatus for the automatic exact metering of small quantities of liquid, is in a LLD (or other phase boundary detector) is used, which is preferably, but not necessarily, formed according to the first main aspect.

Further, the invention is directed to an apparatus for automatically dispensing precise small amounts of liquid. Such devices are also referred to as (automatic) pipettors. They are in connection with the analysis of body fluids, in particular in respective analyzers often used to transfer sample and reagents from one vessel to another vessel. The dosage of the liquid is based on the movement of a piston in a precision tube. The piston is usually driven by a stepper motor whose movement is transmitted to a spindle drive via a toothed belt. This spindle drive moves a carriage which is usually rigidly connected to the piston. The precision of the dosage with such a piston pump is dependent on the precision of the stepping motor and the accuracy of the transmission elements (toothed belts, spindle drive). To ensure high precision mechanical parts must be produced very accurately and are consequently expensive. The mechanical moving parts to wear out and need to ensure the accuracy, periodic inspection. Additional errors in the dosage accuracy can be caused by differences in consistency, toughness or the fat content of the liquid to be dosed. Such differences are in the blood and the usual in medical analysis reagent liquids containing proteins and other giant molecules, particularly pronounced.

To make an automatic pipettor with high accuracy, in particular for metering of very small sample volumes are available, the invention is directed according to a second main aspect to an apparatus for automatic exact metering of small amounts of liquid. It comprises a phase boundary detection means ( "Phase Boundary Detection Means, PBDM") that automatically detects through which a fluid phase boundary in a measuring tube and a position of the phase boundary in a detection section of the measuring tube corresponding electrical signal is generated. With a first end of the measuring tube, a liquid transfer opening is for sucking and discharging liquid in fluid communication. With a second end of the measuring tube is an auxiliary fluid transfer device (Auxiliary fluid transfer Means, AFTM) for the precisely controlled supply and aspiration of an auxiliary fluid and from the measuring tube in fluid communication. It comprises means for supplying auxiliary fluid (Auxiliary fluid Supply Means, AFSM) and means for suction of the auxiliary fluid (Auxiliary fluid Withdrawl Means, AFWM) on. An electronic control unit is provided to drive the auxiliary fluid transfer device in response to the signal corresponding to the position of the fluid phase boundary in such a manner are that sucked or discharged by suction or supply of auxiliary fluid to the measuring tube precisely defined amounts of liquid.

The detection device for detection of the fluid phase boundary preferably corresponds to the first main aspect of the invention. In this case, a thin capillary tubes are used as a measuring tube which is directly immersed in the liquid, the height of the liquid level with the LLD according to the first main aspect of the invention at a relatively short distance above the suction opening is precisely determined. Since the sample volume thereby can be measured directly in the serving as pipette tip capillary tube and therefore the aspirated volume is determined directly and immediately, different conditions, such as air pressure, room temperature or viscosity of the liquid have a virtually negligible influence on the dosing accuracy.

Here, d may be as measuring tube be formed as a single-use (disposable) capillary, which is used in an automatic mounting the pipettor. Thereby, the risk of transmission of liquid residues on the respective next metered liquid volume ( "carry-over") is completely avoided. In prior constructions led disposable pipette tips automatic pipettors due to unavoidable differences in the coupling to the pipettor to major precision problems when pipetting very small volumes.

Generally, however, another LLD can in conjunction with the pipettor according to the second main aspect of the invention can be used which automatically detects the height level of a liquid in a closed up riser tube and a resultant electrical signal generated, which is supplied to the control unit to the suction precise control and discharge of the liquid. Known devices of this type have been mentioned in the introduction.

The auxiliary fluid may be a gas or a liquid. A liquid may expediently be supplied by means of a piston pump precisely controlled or aspirated. If the Kilfsflüssigkeit with the liquid to be dosed is immiscible, at the phase boundary, direct contact between the two liquids can be made. Even with an immiscible liquid can be carried out by sucking a gas bubble between auxiliary liquid and liquid to be metered. This separation of two different liquids with the aid of a gas bubble is used in the analysis technique. In this case, one of the phase boundaries between the liquid to be metered or the auxiliary liquid and the gas bubble is detected.

Preferred is an embodiment in which the auxiliary fluid is a gas, in particular is air and the measuring tube is vertical as the tubing substantially. The phase boundary is the liquid level which separates the liquid column in the riser of the gas space thereabove, the supplied gaseous auxiliary fluid and from which it is sucked off. In this case, the transfer means for the auxiliary fluid preferably has a selector valve means, which may consist of a multi-way valve or a plurality of individual valves. In any case, at least one shut-off valve should be (ie a valve, which easily switches between an open and closed position) be located close to the upper end of the riser.

The inventive automatic pipettor is particularly suitable for fully automated pipetting of very small volumes of liquid (in the range between 20 nl and 20 ul, ie 2 x 10⁻⁸ l to 2 x 10⁻⁵ l). Here, a very high precision. In 100 nl dispensing volume coefficient of variation (CV) is for example a maximum of 1% (ie 10⁻¹⁰l). In this case, a thin capillary is employed as the measuring tube with an inner diameter between 0.1 mm and 0.3 mm, immediately immersed in the liquid to be pipetted (ie, the liquid transfer opening is part of the measuring tube).

The control of a metered quantity of liquid by means of an optical LLD is known from German Patent 35 15 890th However, the device described there permits only a relatively coarse dosage of a relatively large amount of liquid (0.3 ml = 300 ul). The function differs in essential elements of the apparatus described herein. In particular, the liquid is sucked by means of a flow tube downstream the injector nozzle from the measuring tube. There are connected to the opposite of the liquid transfer opening end of the measuring tube neither means for supplying even for sucking an auxiliary fluid. With the known device it is not possible to perform a fast and carry-low dosage of a sequence of different fluids, such as is required in clinical analyzers. It is likewise impossible for dosing liquids which are present in very small quantities and must be dosed with virtually no dead volume.

The function of automatic pipettor invention is practically not affected by mechanical wear. Switching valves are only subject to low wear, which does not affect its function over a long service life. Although is in a preferred embodiment a gas pump used as gas extraction and / or gas supply device, is also subject to mechanical wear these, but which is insignificant for the accuracy of dosing. It can be a simple and relatively inexpensive gas pump can be used.

In addition, a permanent monitoring possible if the sucked or ejected quantity of liquid consistent with the desired predetermined amount. In conventional automatic pipettors contrast, for example, errors caused by clogging of the needle or the fact that the stepper motor individual steps not be detected only with expensive options "lose" or.

The device works with different metering liquids, in particular blood, serum and protein-containing liquid reagents properly, even if those in composition, viscosity and hydrophobicity (surface tension) to differ. Changes in the liquids have practically no influence on the pipetting. Also changes in environmental conditions (eg, temperature changes) can be in contrast to conventional pipettors relatively easily taken into account in the control algorithm and thereby eliminated.

The invention is explained below on the basis of an exemplary embodiment schematically illustrated in the figures; show it:<dl id="dl0001"><dt>Fig. 1</dt><dd>A schematic diagram of an automatic pipettor with liquid level detection device;</dd><dt>FIG. 2 to FIG. 5</dt><dd>Schematic diagrams of different arrangements of the illumination device and the light receiving means at a liquid level detection device according to the invention;</dd><dt>Fig. 6</dt><dd>a plot of a measured intensity distribution depending on the location of the photosensitive member in the image plane,</dd><dt>Fig. 7</dt><dd>a practical embodiment of a device according to FIG. 1 in side view.</dd></dl>

The shown in Figure 1 automatic pipettor 1 consists essentially of a detection device 2 for detecting a fluid phase boundary 10 in the detecting section 8 of the measuring tube 9, and an auxiliary fluid transfer device 16, to which a change-over valve 3 and a gas pump 4 belongs. An electronic central unit 5 includes a control unit 6 for the gas pump 4 and the change-over valve 3 and an evaluation unit for the detection device 7 second

The detection device 2 is in the case illustrated a liquid level detection device (LLD), ie the phase boundary 10 is the boundary between air and liquid in a space formed as a vertical riser 11 measuring tube 9. The LLD serves the height of the liquid level 10 in the riser 11 automatically detect. To this end, the riser 11 is illuminated by a light source 12 via light diffusing means 13 with diffuse light. The light diffusing means 13 is in the illustrated case a focusing screen 14, wherein the riser 11 is located on the side remote from the light source 12 side of the ground glass screen 14 and the ground glass 14 and the riser 11 are arranged approximately parallel to each other. Overall, the light source 12 and the light diffusing means 13 constitute an illumination device 15 for illuminating the riser eleventh

In the illumination device 15 opposite side of the riser pipe 11 is a light receiving device 17, which consists of an optical imaging system 18 for imaging of the riser in an image plane 19 and, arranged in the image plane 19 row 20 of photosensitive elements, which in the illustrated preferred case of CCD elements (pixels) 21 are.

The light source 12 may consist of one or more lamps, for example halogen lamps, tungsten lamps or the like. The light diffusing means is preferably an illuminated from the rear side focusing screen 14, however, in the present invention preferred diffuse illumination of the riser pipe 11, for example, also with a diffusely reflecting surface can be realized, which is such an illuminated from the side that preferably no light from the light source directly falls on the riser 11th Both in the case of a ground glass screen and in the case of a diffusely reflective surface of the riser tube 11 facing surface, which may be referred to as a diffusion surface 14a should be at a uniform distance (that is, approximately parallel to) extend to this.

The riser pipe 11 is preferably a capillary with an inner diameter of less than 1 mm, particularly preferably less than 0.5 mm. Its lower end is in fluid communication with a fluid transfer opening 11a, through which the liquid can be sucked and discharged. "Stand in fluid communication (fluid communication)" is to be understood that the fluid transfer port 11a - as shown - an opening of the riser pipe 11 itself or by means of a tube or hose can be in indirect communication with the riser 11th

The optical imaging system 18 is conveniently made of a shutter 22 and a (in the drawing only as a lens indicated) lens 23rd

The number of photosensitive elements may be part of a two-dimensional array in circumstances that not only extends parallel to the riser pipe 11, but also perpendicular to it in the image plane 19th When sufficient and particularly advantageous, however, a purely linear arrangement of the CCD pixel has proven with their distance, preferably less than 50 microns up to 25 microns.

In the illustrated embodiment, the light source 12, the riser 11 and the row 20 of the CCD pixels 21 are located in one plane. In this arrangement (and dosage a clear liquid) supply CCD pixel, to which the liquid-filled region of the capillary is imaged, a higher output signal than the pixels on which the air-filled region of the capillary is imaged.

This situation is illustrated by FIG. 2. In addition to the figure 1 corresponding representation of LLD it shows a graph A of the output signals of the CCD pixels 21 as a function of the location X of the capillary riser 11, which is depicted on it.

The graph A shows this relationship, however, greatly simplified. In truth, the signal differences are much smaller.

In an experimental setup of the invention, a 12.5 cm long capillary having an internal diameter of 400 microns was used as a riser eleventh As the light source 12 was a halogen lamp, the light diffusing means 13 formed by a bright focusing screen, which proceeded to the riser 11 at a distance of 7 cm parallel. The row 20 of photosensitive elements consisted of a CCD line sensor having 1024 pixels with a dimension of 0.025 mm x 1 mm. As an optical imaging system used was a camera lens with f = 1.8 and 50 mm focal length. The distance between the light source 12 and the image plane 19 was about 20 cm, wherein the riser was 11 arranged approximately in the middle.

The output signal of the CCD line sensor has been transferred via an interface to a standard personal computer, which served as the evaluation device. 7 The assignment of the CCD output signals to the values ​​"capillary filled" or "capillary empty" carried out by means of an appropriately set threshold. The interface should allow parallel processing of data so that the position of the liquid level is ensured in real time.

With this structure, the air-liquid interface could be detected in the riser 11 with an accuracy of +/- 1 pixel.

Further experiments have shown that with additional optimization measures, in particular a magnifying optical imaging system 18 and by using a CCD line with lower pixel pitch, the resolution in the detection of the liquid level 10 in the riser 11 can be further improved. This is true even in capillaries having an internal diameter of 0.2 mm when using the illustrated in Fig. 1 and 2 principal structure. In this case, volume differences can be detected by less than +/- 1 nl. This advantageous result has in view of the difficult conditions, in particular in the detection of the level of a non-colored liquid can be considered surprising. This is also confirmed by the fact that use much more complex process in the initially described prior art and yet significantly inferior results are obtained.

The graphs B, C, D of Figures 3 to 5 illustrate the dependence of the measurement signal of the angular position of the light source 12 and the light diffusing means 13. In this case, a plan view is shown in each case, the axis of the riser tube 11 thus extends perpendicular to the drawing plane. When changing the drawn in the figures azimuth angle α (related to an axis perpendicular to the plane of the riser 11), the difference of the pixel output signals that correspond to the liquid-filled and air-filled portion of the riser 11 is reduced.

In the illustrated case α greater than 10 °, the difference between the liquid-filled and air-filled capillary is reduced when azimuths increasingly and at angles above 15 °, the ratio is reversed: CCD pixels on which the image of the air-filled portion of the riser is ready 11 have a higher output than those which correspond to the fluid-filled portion of the capillary. In a second angular range of between 20 ° and 90 °, which is shown in Figure 5, so there is again a difference signal. However, it is somewhat less than in the arrangement in a plane according to FIG 2 in this area.

If the measuring device is designed so that the brightness of the liquid filled part area and the gas-filled part area of ​​the measuring section of the riser pipe 11 significantly differ (as in Figure 2, 3 and 5), the evaluation of the output signal of the row 20 of light-sensitive elements 21 is particularly easy , As mentioned it is generally sufficient to set a threshold so that it lies approximately in the middle between the output signals corresponding to the filled or empty capillary. In this case, a very good accuracy can be achieved without a high-precision adjustment of components is required. As shown schematically in Figures 2 to 5, the intensities change only slightly over a relatively wide angle ranges.

Even a slight tilting of the illumination device 15 around a horizontal (in the drawing plane of the figures 3-5 runs) axis of up to 10 ° affects the quality of the detection is not essential. Also hereto shows the tolerance of the described technique to positioning inaccuracies.

A particular advantage of the phase boundary detection apparatus according to the invention (PBDM) is that more precise localization of the phase boundary, it allows, even in such cases in which the brightness of the adjacent to the phase boundary regions of the measuring tube or only very slightly different.

Figure 6 shows the signal of the CCD pixels in an experiment in which the contains the CCD's shown the measuring section 8 of the measuring tube 9 in successive portions of water (W), silane-oil (O) and more water (W). The oil does not mix with water, so that W / O or O / W form between the water and the oil phase boundaries.

The course of the intensity I depending on the measurement site X is slightly curved in FIG. 6 This is due to the fact that the illumination of the detecting section in this figure the underlying experiment was not completely constant, but increased slightly from bottom to top. This is for the evaluation accuracy when using an appropriate evaluation method (such as those described below) without significance. It is however important that the illumination (as already explained) is continuous.

From the figure it can be seen that the measured intensities in the vicinity of phase boundaries in the oil and in the water is virtually impossible to distinguish. Nevertheless, at the phase boundary itself well measurable minima of

determined intensity, which can be evaluated by the evaluation unit to detect the location of the phase boundary. For this purpose preferably the measured outputs of the CCD pixels are first subjected to a digital low-pass filtering. Such methods, for example by means of a Hamming, Blackman, or Hanning window function are known. They lead to a smoothing of the signal path. This false indications of a phase boundary can be avoided due to random jitter.

In the filtered waveform signal minimum can be determined by means of a limit value again. This is expediently set to a multiple of the statistical fluctuation of the pixel signals below the signal mean value of a defined neighborhood (for example, 10 pixels). A below this threshold lying intensity is detected as a phase boundary.

To improve the detection of the phase boundary in addition, in critical cases, it may be expedient to differentiate the filtered waveform and in the resulting waveform (ie, the first derivative of the measured signal curve) to set a threshold for detecting the phase boundary.

As mentioned comprises the shown in Figure 1 automatic pipettor 1 next to the LLD 2, the change-over valve 3, the gas pump 4 and the associated control unit 6. The switch-over valve 3 is in the illustrated preferred embodiment consists of a quick shut-off valve 25 and two switch valves 26 and 27th

The valves 26, 27 each have a first side 26a, 27a of a terminal and on a second side 26b, 27b of two terminals, wherein by switching the valve either a connection between the one terminal of the first side and one of the terminals of the second side will be produced. The first side 26a of the valve 26 is connected to the pressure side 4a of the gas pump 4, while the first side 27a of the valve 27 is in communication with the suction side 4b of the gas pump.

Of the two terminals of the second side of the valves 26,27 in each case one is connected to a Y-line system 28 by which a connection to the side facing away from the riser pipe 11 connecting the shut-off valve 25 is prepared. The respective other terminal of the second side 26b, 27b of the valves 26,27 is connected to the outside air. The valves 26,27 are synchronously switched so that in a first position (shown in the figure by solid lines), the pressure side of the gas pump 4 is connected to the shut-off valve 25, (shown in phantom in the figure) while in a second position, the suction 4b is connected to the shut-off valve 25th For limiting the pressure generated by the gas pump 4, a bypass 29 is provided with at least one pressure relief valve 30th

In order to suck through the liquid transfer port 11a of the riser 11 liquid, the switching valves 26,27 are placed in the position shown in dashed lines, so that a generated gas from the pump 4 under pressure at the stop valve 25 abuts. When opening this valve a connection is established to the gas chamber 11b of the riser 11 above the liquid level 10th The liquid is sucked and the liquid level 10 rises under control of LLD 2 on. Once the liquid level 10 has reached a corresponding to the desired suction volume level state, the valve 25 is closed. The valve control signal is generated by the control unit 6 in response to a 7 generated by the evaluation unit the electric signal which corresponds to the height level of the liquid 10, by comparison with a desired value corresponding to the desired ride height.

Surprisingly, it has been found that with such an arrangement, the liquid level 10 can be brought into a defined position with very high precision. It is important that a sufficiently quick stopcock 25 is inserted. Practically proven has a fast solenoid valve (Lee) valve with a switching frequency of 2000 Hz. In addition, the check valve 25 should be placed as close to the upper end of the riser. Preferably, the dead volume between the upper end of the detection section 8 and the shut-off valve 25 should be 9 most as large as the internal volume of the detection portion 8 of the measuring tube.

The selector valve 3, as the skilled worker is familiar, be constructed in other ways, for example by means of a four-way valve or four-way valves, which are switched in sync so that each at the desired time gas supplied to the gas chamber 11b, of this is discharged.

In the embodiment illustrated in Figure 1, the suction in the flow tube 9 or the ejection from the measuring tube 9 is controlled by supply or discharge of a gas as auxiliary fluid. The phase boundary 10 is an interface between the located in the lower part 9 of the measuring tube 32 and the liquid column located in the gas chamber 11b air. Alternatively, however, as mentioned, also be used instead of a liquid of the gas (the air). In the case of a metering device such a liquid pump (a piston pump, for example) would be in place of the gas pump is provided which sucks liquid from a liquid reservoir or in this or emits an other container. Thus, even though different fluids (gases or liquids) may be used to suck in as an auxiliary fluid, the liquid to be metered in the measuring tube 9 or eject from this, the embodiment (air in particular) is provided with a gas is particularly preferred because it is particularly simple and every contact the liquid to be dosed with another liquid excludes.

In the depicted in Figure 7 practical embodiment of an automatic pipetting device, the components are mounted on a common frame 33rd The illumination device 15 has a light-tight closed housing, in which the light source is not shown. At the tubing 11 facing side of the illumination device 15, the focusing screen 14 is fixed. Also, the light receiving means 17 is housed, including the optical imaging system 18 enclosed in a common light-tight housing. The interconnections between the gas pump 4, the switching valves 25,26, the pressure relief valve 30 and the solenoid valve 25 are formed by hoses. The riser pipe 11 is a very thin capillary that is attached by means of a supporting member 34 on the frame 33rd

In the illustrated embodiment, the riser 11 is fixed. It can therefore not up for the pipetting and are moved downward. If such a motion is desired, it can be in the context of the present invention either realized in that the riser pipe 11 up in precisely predetermined and measurable way and is moved downward and this motion by the evaluation unit 7 when calculating the ride height ( and the resulting volume) is taken into account in the riser. A second possibility is to use a fixed riser pipe and connected to the lower end of a flexible hose, a separately movable pipetting with the fluid transfer port.