EP0562358A2 - Pipetting system - Google Patents

Abstract

Method for producing a pipetting system in which, for each liquid volume to be taken up, the indicated liquid volume deviates from the correct value by a preset amount, and which contains a piston pipette and a pipette tip which can be stuck onto the latter, the piston pipette having adjustment devices for altering the piston travel and indicating devices for the liquid volume pipetted in each case, and the ratio of the piston travel to the liquid volume indicated being determined by a pipette correction factor, the pipette tip having a tip orifice, a volume zone connected thereto for receiving adjustable liquid volumes, and a plug-on orifice connected thereto for the piston pipette, and a dead space being formed between the tip orifice and the piston, the pipette correction factor, the profile of the inner cross-section along the tip, and the dead space being matched to one another, and a preset deviation of the correct liquid volume from the liquid volume indicated being achieved for any liquid volume to be taken up. <IMAGE>

Description

The invention relates to a pipetting system with a piston-type pipette and a pipette tip which can be plugged thereon according to the preamble of claim 1.

From DE-PS 25 26 296 a pipetting system of the type mentioned above is known, the piston stroke pipette of which has a cone for attaching the pipette tip. Starting from the tip opening, the pipette tip has a strongly conical section and then a weaker conical section with respect to the inner contour up to the push-on opening. Such a pipette tip has a deep and in particular slim when immersed Vessel has the disadvantage that a pipette carrying it can come into contact with the vessel and become contaminated. This is fundamentally not the case with a pipette tip which, according to EP-A-0 182 943, has a long cylindrical nose starting from a tip opening, followed by a strongly conical and then a plug-on opening.

In the pipetting systems mentioned, the setting range of absorbable liquid quantities extends from the tip opening over all different sections of the pipette tip. If a small piston stroke is set, liquid is only drawn into the strongly conical (or cylindrical) initial area. With a larger piston stroke, the weaker conical (or the conical and then the cylindrical) area is reached. What is common to the pipetting systems is that, in cooperation with an adjustable piston stroke pipette, they absorb liquid volumes that can unacceptably deviate from the displayed liquid volume, the deviation being possible differently across the setting range. For this reason, the pitch of a spindle of the piston stroke pipette for the adjustment of the piston stroke is tentatively determined so that the correctness deviation between the liquid volume taken up and displayed is tolerable across the entire setting range. The resulting deviations in accuracy are accepted and can only be determined on the basis of subsequent measurements.

In addition to neglecting accuracy deviations of unknown size over the setting range, the disadvantage here is that the separation of the piston-stroke pipette and pipette tip makes it difficult to change the pipette tip. Should e.g. If a piston-type pipette with a pipette tip of the first type is equipped with a pipette tip of the second type, the given spindle pitch no longer guarantees that the deviations in accuracy are tolerable over the setting range.

US Pat. No. 5,024,109 already discloses a method and an apparatus for correcting the error of a piston stroke pipette. The height of the liquid in the pipette tip for the desired liquid volume, the changes in the dead volume due to the liquid column in the tip and the required piston displacement for the desired liquid volume and the change in the dead volume are determined. The height of the liquid column for a desired volume is based on the tip geometry determined, especially for a conical tip. The change in dead volume is determined on the basis of hydrostatic considerations that are linked to the height of the liquid column. The piston displacement is determined from the sum of the desired volume and the change in the dead volume. This technology uses an electromechanical pipette that is connected to a control computer. Before use, data from the pipette tip, the pipetting system and the liquid must be entered into the computer. This pipetting technique is complex.

Proceeding from this, the object of the invention is to improve the pipetting system of the type mentioned at the outset, so that work can be carried out simply and precisely over the entire setting range of pipetting liquid to be taken up. Furthermore, the pipetting system is intended to enable the piston-stroke pipettes or pipette tips to be exchanged, with the aim of continuing to work precisely and simply.

The solution to this problem is given in claims 1 and 10. Advantageous refinements can be found in the subclaims.

The invention is based on the knowledge that the pipette correction factor, cross-sectional profile along the tip, dead volume and, if appropriate, zero point shift of the display are decisive for the amount of the accuracy deviations over the setting range. By coordinating these influencing factors with one another, it is consequently possible to implement a predetermined correctness deviation from the displayed liquid volume in the setting range, which can also be zero, for each liquid volume taken up. In contrast to conventional pipetting systems, according to the invention no longer becomes correct. Deviations are minimized by selecting the spindle pitch according to the specification of the other influencing variables, but all the above influencing variables are coordinated with one another in such a way that predetermined correctness deviations are achieved. In such a pipetting system, the exact value of the liquid volume taken up is then known for each liquid volume displayed. Compared to the previously known electronic pipette with control computer, there is no need to calculate the piston stroke for each pipetting process in order to achieve the specified deviation from the correctness. At most, an adaptation to the respective liquid density may be necessary. This can be done by exchanging tips, changing the dead volume or the pipette correction factor according to the respective Liquid. If the correctness deviations deviate from zero and pipetting is to be carried out without errors, the piston stroke can always be adjusted by means of the display so that the volume of liquid taken up corresponds to the intended volume. Furthermore, according to the invention, pipette tips can be adapted to conventional piston-stroke pipettes in such a way that predetermined deviations in accuracy are achieved. In this way, if necessary, a pipetting system can be equipped with an extended pipette tip, which avoids touching the wall and accompanying contamination. Conversely, it is also possible to ensure predetermined correctness deviations by matching a piston stroke pipette to existing pipette tips.

The deviation in accuracy can be defined in different ways. For practical handling, the specification of a constant absolute or relative accuracy deviation is particularly favorable, because then the difference between the volume of liquid taken up and the one displayed is easiest to determine.

If a conventional pipetting system is to be converted into one according to the invention, in particular by exchanging a pipette tip, a vote can be carried out for each volume of liquid absorbed requires a predefined deviation from the volume of liquid absorbed by the conventional pipetting system instead of the volume of liquid displayed. Then the differences of the pipetted liquid volume from the conventionally pipetted volume are known with the same display. This knowledge can be of interest for comparative investigations with a modified pipette tip.

As a rule, the liquid level in the setting range of receivable liquid volumes always rises up to a working range of the pipette tip. To compensate for changes in cross-section, including discontinuities in the start area of the pipette tip, the adjustment can include a zero point shift of the displayed liquid volume relative to the piston stroke.

In practice, values of the pipette correction factor, dead volume and possibly zero point shift are sometimes specified, in particular if the pipetting system is to be implemented by adapting a pipette tip to an existing piston stroke pipette. To achieve the specified deviation from the correctness, it is then sufficient to adjust the cross-sectional profile along the tip to the specified influencing variables.

If the working area of the pipette tip is essentially cylindrical, in particular a constant absolute accuracy deviation can be achieved over the entire setting range of absorbable liquids. For a small tip opening and a sufficiently large volume area for receiving adjustable amounts of liquid, this can have a gradually widening transition area. The transition area preferably has a transition radius or transition cone, the cone angle being kept as small as possible to avoid undesirable effects (fountain effect). A work area is preferably arranged downstream of the transition area. Particularly for use with relatively long and slim vessels, the pipetting system has a pipette tip with a thin suction tube adjacent to the tip opening. Then the top preferably has an expanding transition and a subordinate work area.

Its pipette correction factor can be adjustable in order to adapt the pipetting system to different liquid densities or air pressures. In the simplest case, this can be done by replacing a spindle for adjusting the piston stroke. A display device with an expandable scale can also be used.

For the above purpose, the display can also be shifted to zero by means of similar measures.

An adjustable dead volume can also be provided. This is possible in particular by exchanging pipette tips, a pipette tip for lighter liquids having the same diameter having to be made longer. To change the dead volume, it is also possible to use intermediate pieces between the piston-stroke pipette and the pipette tip.

According to the invention, the influencing variables can be adjusted experimentally to achieve the specified accuracy deviations. In this case, an accuracy deviation from the displayed liquid volume can first be specified for each liquid volume taken up. These deviations can now be realized by coordinating the pipette correction factor, cross-sectional profile along the tip and dead volume. Since the pipette correction factor and the dead volume are usually no longer changed after the selection has been made, the values for these influencing parameters are initially at least provisionally determined, it being possible to orientate them on values of known pipetting systems. Then the last one remains Influencing variable of the cross-sectional profile along the pipette tip, with which the specified accuracy deviations can be ensured. Trials, for example, result in clear values for this if the other influencing factors have been selected beforehand. If the cross-sectional profile found cannot be realized, the predefined influencing variables would have to be corrected or even a different correctness deviation had to be specified.

Der Volumenfehler resultiert daraus, daß die Flüssigkeitssäule am Luftpolster zwischen Flüssigkeitsspiegel und Kolben (= "Totvolumen") hängt und nach unten zieht, wobei das Luftpolster entsprechend vergrößert wird.Because of the complexity of an empirical coordination, the following physical-mathematical model is preferably used for the calculation: The piston stroke volume V _{piston of} a piston stroke pipette is larger than the absorbed liquid volume V liquid by the volume _{error ΔV.} .

${\text{(A) V}}_{\text{piston}}{\text{= V}}_{\text{Liquid}}{\text{+ Δ}}^{\text{V}}$

The volume error results from the liquid column hanging on the air cushion between the liquid level and the piston (= "dead volume") and pulling downwards, the air cushion being enlarged accordingly.

oder: ${\text{(B) p}}_{\text{o}}{\text{· V}}_{\text{t}}{\text{= (p}}_{\text{o}}{\text{- Δp)·(V}}_{\text{t}}\text{+ ΔV)}$

mit:
V_t = Luftpolster, Totvolumen von Pipette und Spitze
P₀ = Außendruck, atmosphärischer Druck
Δp = Druckänderung entsprechend hydrostat. Druck der Flüssigkeitssäule in der Pipettenspitze
aus (B) folgt:

und:

weiter

und unter Berücksichtigung, daß Δp « p_o
ergibt sich:

Totvolumen und atmosphärischer Druck werden als bekannt vorausgesetzt. Die Druckänderung Δp entspricht dem hydrostatischen Druck der Flüssigkeitssäule der Höhe h:

$\text{(D) p = ρ . g . h}$

mit:
ρ = spezifisches Gewicht
g = Erdbeschleunigung
Die Höhe h der Flüssigkeitssäule ist durch das pipettierte Flüssigkeitsvolumen und den Querschnittsverlauf der Pipettenspitze bestimmt:

mit
Q (y) = Querschnitt im Abstand y von Spitzenöffnung
Aus (A), (C) und (D) folgt:

Mit (E) und (F) läßt sich die Abhängigkeit des Kolbenhubs V_Kolben vom aufgenommenen Flüssigkeitsvolumen V_Flüss. errechnen, ggfs. unter Zuhilfenahme numerischer Methoden.The changes in volume and pressure in the air cushion can be attributed to the dead volume of the pipette and tip Describe the ambient pressure using a thermal equation of state. For the calculation of ΔV it is assumed: ideal gas, T = const.
with this applies: $\text{pV = const.}$

or: ${\text{(B) p}}_{\text{O}}{\text{· V}}_{\text{t}}{\text{= (p}}_{\text{O}}{\text{- Δp) · (V}}_{\text{t}}\text{+ ΔV)}$

With:
V _t = air cushion, dead volume of pipette and tip
P₀ = external pressure, atmospheric pressure
Δp = pressure change corresponding to hydrostat. Pressure of the liquid column in the pipette tip
from (B) follows:

and:

continue

and taking into account that Δp «p _o
surrendered:

Dead volume and atmospheric pressure are assumed to be known. The pressure change Δp corresponds to the hydrostatic pressure of the liquid column of height h:

$\text{(D) p = ρ. g. H}$

With:
ρ = specific weight
g = gravitational acceleration
The height h of the liquid column is determined by the pipetted liquid volume and the cross-sectional profile of the pipette tip:

With
Q (y) = cross section at a distance y from the tip opening
From (A), (C) and (D) it follows:

With (E) and (F) the dependence of the piston stroke V _piston on the absorbed liquid volume V _{liquid can be.} calculate, if necessary with the help of numerical methods.

mit
a = Pipettenkorrekturfaktor
b = Nullpunktsverschiebung
Für den Zusammenhang von a und Spindelsteigung S gilt:

Aus (F) und (G) folgt:

Daraus ergibt sich für die absolute Richtigkeitsabweichung R_abs. :

mit:
R_abs. = V_Flüss. - V_Anz.
Für die relative Richtigkeitsabweichung R_rel. gilt:

${\text{(J) R}}_{\text{rel.}}{\text{= R}}_{\text{abs.}}{\text{/V}}_{\text{Flüss.}}$

mit:

Mit (I) bzw. (J) und (E) können nun Pipettenkorrekturfaktor a, Nullpunktsverschiebung b, Querschnittsverlauf Q (y) und Totvolumen V_t so aufeinander abgestimmt werden, daß jedem aufgenommenen Flüssigkeitsvolumen V_Flüss. eine vorgegebene Richtigkeitsabweichung R_abs. bzw. R_rel. zugeordnet ist. Zweckmäßigerweise wird man dafür die Richtigkeitsabweichungen vom angezeigten Flüssigkeitsvolumen vorgeben, Pipettenkorrekturfaktor, Nullpunktsverschiebung und Totvolumen zumindest vorläufig wählen und dann den Querschnittsverlauf berechnen. Andererseits ist die Vorgabe spezieller Querschnittsverläufe entlang der Spitze möglich. Speziell folgt bei zylindrischer Pipettenspitze aus (E):

${\text{(K) V}}_{\text{Flüss.}}\text{= Q · h}$

mit:
Q = const.
Aus (I) und (K) ergibt sich:

Wird der Verlauf der Richtigkeitsabweichung vorgegeben, folgt daraus der Zusammenhang zwischen dem Totvolumen, der Pipettenkorrekturfaktor und der Nullpunktsverschiebung. Soll die absolute Richtigkeitsabweichung R_abs. für alle
V_Flüss. konstant sein, muß gelten:

und
R_abs. = b/a
Mit dem Formelsatz (L) lassen sich sämtliche Bestimmungsgrößen festlegen. Dafür sind nur noch Größen für zwei der Einflußfaktoren Totvolumen, Pipettenkorrekturfaktor und Nullpunktsverschiebung vorzugeben.The piston stroke is limited by stops, the spacing of which can be adjusted by means of a spindle which is coupled to the display device. As a result, there is between V _piston and the indicated liquid volume V _Qty. a linear relationship:

${\text{(G) V}}_{\text{piston}}{\text{= a · V}}_{\text{No.}}\text{+ b}$

With
a = pipette correction factor
b = zero offset
For the relationship between a and spindle pitch S:

From (F) and (G) it follows:

This results in R _abs for the absolute accuracy _deviation. :

With:
R _abs. = V _liquid. - V _Anz.
For the relative accuracy deviation R _rel. applies:

${\text{(J) R}}_{\text{rel.}}{\text{= R}}_{\text{Section.}}{\text{/ V}}_{\text{Liquid}}$

With:

With (I) or (J) and (E), pipette _{correction factor} a, zero point shift b, cross-sectional _profile Q (y) and dead volume V _t can now be coordinated with one another in such a way that each volume of liquid V liquid _{taken up.} a predetermined accuracy deviation R _abs. or R _rel. assigned is. For this purpose, the correctness deviations from the displayed liquid volume are expediently specified, pipette correction factor, zero point shift and dead volume are selected at least provisionally and the cross-sectional profile is then calculated. On the other hand, it is possible to specify special cross-sectional profiles along the tip. In the case of a cylindrical pipette tip, it follows from (E):

${\text{(K) V}}_{\text{Liquid}}\text{= Q · h}$

With:
Q = const.
From (I) and (K) we get:

If the course of the accuracy deviation is specified, the relationship between the dead volume, the pipette correction factor and the zero point shift follows from this. If the absolute accuracy deviation R _abs. for all
V _liquid must be constant:

and
R _abs. = b / a
With the formula (L) all determinants can be determined. For this purpose, only sizes for two of the influencing factors dead volume, pipette correction factor and zero point shift have to be specified.

Fig. 1

Zusammenwirken von Pipettenspitze und Kolbenhubpipette in einem Diagramm mit der Differenz von (angezeigtem) Flüssigkeitsvolumen und Kolbenhub auf der Ordinate und dem Kolbenhub auf der Abszisse;

Fig. 2

Pipettenspitzen P₁, P₂ und P₃ zu den Kurven A, B und C in Fig. 1;

Fig. 3

eine Pipettenspitze in stark vergrößertem, vierfach abgebrochenem Längsschnitt;

Fig. 4

einen oberen Abschnitt einer kolbenbetriebenen Pipette; und

Fig. 5

einen unteren Abschnitt einer kolbenbetriebenen Pipette, dessen Querschnitt B-B mit dem Querschnitt A-A des oberen Abschnittes zusammenfällt.

Further details and advantages of the subject matter of the invention will become apparent from the following description of the accompanying drawings. The drawings show:

Fig. 1

Interaction of pipette tip and piston stroke pipette in a diagram with the difference between the (displayed) liquid volume and piston stroke on the ordinate and the piston stroke on the abscissa;

Fig. 2

Pipette tips P₁, P₂ and P₃ to curves A, B and C in Fig. 1;

Fig. 3

a pipette tip in a greatly enlarged, fourfold broken longitudinal section;

Fig. 4

an upper portion of a piston operated pipette; and

Fig. 5

a lower section of a piston-operated pipette, the cross section BB of which coincides with the cross section AA of the upper section.

The pipette according to FIGS. 4 and 5 is disclosed in the applicant's US patent application US SN 07/694 234 dated May 1, 1991. Reference is made to this disclosure. The pipette has a housing 1. At the upper end of the housing there is an actuating button 2 which can be moved against the spring 3. The button 2 is connected to a piston rod 7 which extends through a spindle 6. As shown in FIG. 5, the lower end of the rod 7 carries a connecting piece 8, which has a carrier 9 for a piston 10. A spring 18 presses a lower sleeve 19 for guiding the piston 9, 10 against an inner conical surface 21 of the housing 1. The sleeve 19 is supported on the housing via a flexible sealing ring 20.

When the button 2 is pressed vertically downward, the piston 9, 10 is pressed into the cylinder chamber 11, pushing air out of the cylinder chamber 11 through the tube 12. At the lower end of the tube 12, an attachable pipette tip is attached, which is shown in Fig. 3 on an enlarged scale. The pipette tip is attached to a conical seat at the lower end of the tube 12 in a manner not shown. The cylinder chamber 11, the tube 12 and the pipette tip define the dead volume of the pipette.

When the button 2 is pressed vertically downward, the piston 9, 10 is displaced until it reaches the upper end of the tube 12, which is held by a stationary part in the cylinder chamber. This forms a lower stop for the piston movement.

The piston rod 7 is provided with a flange 22 on which the spindle 6 rests in the initial position of the rod 7 and the piston 9, 10. This flange 22 defines the upper stop for the piston 9, 10. The upper stop is adjustable as follows: The button 2 is connected to a downwardly extending sleeve 5 which is rotatably held in the housing. The spindle 6, which surrounds the rod 7, is rotatably connected to the rotatable sleeve 5. The outer thread of the spindle 6 works together with an internal thread of a part 36 which is fastened in the housing 1. When the knob 2 is turned, the spindle 6 is screwed into or out of the threaded part 36. The spindle 7 is axially adjusted, whereby the setting of the stop for the flange 22 of the rod 7 is set, which is effective when the piston 9, 10 returns to an initial position when the button 2 is released and reset by the spring 3 . The stroke of the piston is limited by the upper stop of the piston rod in its initial position.

If the spindle 6 is rotated manually by means of the button 2, a wheel 15 is adjusted via a worm gear. For this purpose, the sleeve 5 has teeth 52 on the outside. The rotation of the wheel 15 is indicated by a scale that is visible through a window 53. The scale is calibrated to adjust the upper stop so that a desired amount of liquid is drawn into the pipette tip, which is attached to the lower end of the tube 12.

As already mentioned, FIGS. 4 and 5 show a part of the dead volume 11 and 12 as well as the setting means and display means 51 for setting and displaying the desired amount of liquid.

In Fig. 1, the curves A₁ and A₂ represent the behavior of cylindrical pipette tips P₁ according to Fig. 2. In these pipettes, the negative volume error - Δ V increases linearly with increasing piston stroke. The curve A₁ corresponds to a pipette tip with a smaller one and the curve A₂ a pipette tip with a larger cross section.

The volume error - Δ V of the pipette tip is compensated for by tuning the piston stroke pipette. By setting the pipette correction factor, the difference between the displayed liquid volume V _Qty. and the piston stroke V _piston in dependence on the piston stroke just chosen so that the displayed liquid volume V _Anz. the absorbed volume of liquid V _Liquid. corresponds. Here the piston stroke pipette with the curve K₁ and the larger pipette correction factor a of the pipette tip with the curve A₁ and the piston stroke pipette with the curves K₂ of the pipette tip with the curve A₂ are assigned. The diagram illustrates that for each piston stroke V _piston the difference between the indicated liquid volume V Qty _. and the absorbed volume of liquid V _Liquid. is zero.

The curve B in Fig. 1 is assigned to the pipette tip P₂ of Fig. 2. This has a thin suction tube adjacent to the tip opening, which initially causes a relatively high rise in the liquid column with a small piston stroke. As a result, the negative volume error - Δ V is also relatively high in this initial range. If the liquid column fills the suction tube, is when rising into the adjacent cylindrical working volume, there is a smaller increase in the negative volume error.

The curve C in Fig. 1 corresponds to the pipette tip P₃ of Fig. 2. This has a conical transition area to a cylindrical working volume adjacent to a thin suction tube. 1, a region of attenuated slope of the volume error for the transition area adjoins the steep initial section, which finally leads to a region of weak slope for the cylindrical working section.

Curves B and C correspond to a piston stroke pipette in which the difference between the indicated liquid volume V _Qty. to piston stroke V _piston over the piston stroke is represented by curve K₃. This has a zero point shift NV on the ordinate, ie with the piston in the starting position a liquid volume V _Qty. displayed. The zero point shift is selected so that with a piston stroke V _piston which causes an increase in the liquids in the working area of the pipette tip, a compensation of the volume error is just achieved. The system thus has an error curve F that of maximum initial value falls to a value zero, which is reached when the liquid column rises into the working area.

The pipette tip in FIG. 3 for the system according to the invention has at the bottom a tip opening 1 for liquid passage, to which a thin suction tube 2 is connected. The suction tube 2 opens into a transition cone 3, which communicates at the other end with an expanded working area 4. The working area 4 opens at the top into a push-on cone 5 with a push-on opening 6 for a piston stroke pipette with an adjustable piston stroke.

In the setting range of absorbable amounts of liquid, the liquid always rises through the tip opening 1 and the suction tube 2 and the transition cone 3 up to the working area 4. In order to achieve an approximately constant absolute correctness deviation of the amount of liquid taken up from the displayed amount of liquid over the entire setting range, the pipette tip in the working area 4 is shaped approximately circularly on the inside.

For better demoldability during injection molding, a slight taper is provided both in the area of the suction tube 2 and in the working area 4, which practically does not impair the desired deviation in accuracy. The transition cone has a clear cone angle, which is approx. 7 ° to avoid a fountain effect.

The pipette tip according to the invention typically has a total length of approximately 100 mm, of which approximately 25 mm are accounted for by the suction tube 2. The diameter increases from approx. 0.5 mm in the tip opening 1 to approx. 3 mm at the beginning of the working area 4.

Claims (18)

Method for producing a pipetting system, which has a predefined deviation from the indicated liquid volume for each liquid volume to be picked up, with a piston stroke pipette and a pipette tip which can be plugged thereon, the piston stroke pipette having setting devices for changing the piston stroke as well as display devices for the respective liquid volume pipetted and the ratio of piston stroke to indicated liquid volume is determined by a pipette correction factor, the pipette tip has a tip opening, an associated volume area for receiving adjustable liquid volumes and an associated plug-in opening for the piston-stroke pipette, and a dead volume is formed between the tip opening and the piston, characterized in that the pipette correction factor, course of the internal cross section along the top and dead volume can be coordinated with each other and thus tuned for everyone the volume of liquid a predetermined deviation from the indicated volume of liquid is reached. A method according to claim 1, characterized in that a constant absolute deviation of the correctness of the liquid volume to be recorded from the displayed liquid volume is predetermined over the entire adjustable liquid volume. A method according to claim 1, characterized in that a constant relative correctness deviation of the liquid volume to be recorded from the displayed liquid volume is predetermined over the entire setting range of recordable liquid volumes. Method according to one of claims 1 to 3, characterized in that a correctness deviation of the liquid volume to be recorded from the recorded liquid volume of a conventional pipetting system instead of from the displayed liquid volume is specified over the entire setting range of recordable liquid volumes. Method according to one of Claims 1 to 4, characterized in that the deviation in accuracy in the entire working range is predetermined to be essentially zero. Method according to one of claims 1 to 5, characterized in that the pipette correction factor, the course of the inner cross section and the dead volume are coordinated with a zero point shift of the indicated liquid volume relative to the piston stroke. Method according to one of claims 1 to 6, characterized in that the course of the inner cross section along the tip is matched to predetermined values of pipette correction factor, dead volume and, if applicable, zero point shift. Method according to one of claims 1 to 7, characterized in that a working area of the pipette tip is assigned to the setting range of receivable liquid volumes, into which the liquid level rises in the entire setting range. Method according to one of claims 1 to 8, characterized in that the pipetting correction factor, the course of the inner cross-section, dead volume and possibly zero point shift taking into account the relationships

or

${\text{R}}_{\text{rel.}}{\text{= R}}_{\text{Section.}}{\text{/ V}}_{\text{Liquid}}\text{= relative error in accuracy}$

With:
R _abs. = V _liquid. - V _Anz. = absolute deviation from correctness

Q (y) = cross section at a distance y from the tip opening
V _Qty = indicated liquid volume
ρ = density
g = gravitational acceleration
h = height of the liquid column
V _t = dead volume
P _o = ambient pressure
a = pipette correction factor
b = zero offset
be coordinated. Pipetting system, which has a specified deviation from the indicated liquid volume for each liquid volume to be picked up, with a piston stroke pipette and a pipette tip that can be plugged onto it, the piston stroke pipette having setting devices for changing the piston stroke as well as display devices for the liquid volume being pipetted and the ratio of piston stroke to the indicated liquid volume by one Pipette correction factor is determined, the pipette tip has a tip opening, an associated volume area for receiving adjustable liquid volumes and an associated plug-in opening for the piston-stroke pipette, and a dead volume is formed between the tip opening and the piston, characterized in that the working area of the pipette tip is essentially cylindrical. System according to claim 10, characterized in that the working area of the pipette tip is preceded by a gradually widening transition area. System according to claim 11, characterized in that the transition region is determined by the smallest possible angle. System according to one of claims 10 to 12, characterized in that the pipette tip has a thin suction tube adjacent to the tip opening. System according to one of claims 10 to 13, characterized in that the pipette correction factor is adjustable. System according to one of claims 10 to 14, characterized in that the zero point shift of the display is adjustable. System according to one of claims 10 to 15, characterized in that the dead volume is adjustable. System according to claim 16, characterized in that the dead volume can be adjusted by exchanging pipette tips and / or intermediate pieces between piston-stroke pipette and pipette tip. System according to claim 1, characterized in that the dead volume is adjustable by variable adjustment of the lower piston stroke stop.

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