METHOD FOR ASSIGNING A PIPETTE TIP TO A PIPETTE TIP CLASS ON THE BASIS OF THE PNEUMATIC BEHAVIOUR THEREOF
20230347334 · 2023-11-02
Inventors
Cpc classification
B01L3/0275
PERFORMING OPERATIONS; TRANSPORTING
B01L2200/148
PERFORMING OPERATIONS; TRANSPORTING
B01L2400/0487
PERFORMING OPERATIONS; TRANSPORTING
International classification
Abstract
A method for assigning a pipette tip to a certain class of pipette tips from a plurality of different pipette tip classes, the method including the following steps: coupling the pipette tip to a gas displacement device such that a device-side volume formed in the gas displacement device and a tip-side volume formed by the pipette tip communicate with each other, and thereby forming a measuring volume including the communicating volumes of the device-side volume and the tip-side volume; operating the gas displacement device and thereby changing the gas pressure in the measuring volume; detecting the gas pressure in the measuring volume over a detection time period; determining at least one absolute value of at least one characteristic variable characterizing the detected gas pressure; comparing the at least one determined absolute value with at least one predetermined calibration value; and, depending on the comparison result, assigning the pipette tip to a pipette tip class and outputting an item of class assignment information representing the assigned pipette tip class.
Claims
1-15. (canceled)
16. A method for assigning a pipette tip to a particular class of pipette tips out of a plurality of different pipette tip classes, where the pipette tip classes differ with regard to a nominal pipetting volume or nominal pipetting volume range of the pipette tips assigned to the respective pipette tip classes and/or with regard to a shape of the pipette tips assigned to the respective pipette tip classes or a shape range of the pipette tips assigned to the respective pipette tip classes, the method comprising the following steps: Coupling the pipette tip to a gas displacement device in such a way that a device-side volume formed in the gas displacement device and a tip-side volume formed by the pipette tip communicate with one another, thereby forming a measurement volume comprising the communicating volumes: device-side volume and tip-side volume, Operating the gas displacement device and thereby changing a gas pressure in the measurement volume, Acquiring the gas pressure in the measurement volume over an entire acquisition period, Ascertaining at least one quantitative value of at least one characteristic variable characterizing the acquired gas pressure, Comparing the at least one ascertained quantitative value with at least one predetermined calibration value, and Depending on the comparison result: Assigning the pipette tip to a pipette tip class and outputting a class assigning information which represents the assigned pipette tip class.
17. The method according to claim 16, wherein operating the gas displacement device comprises displacing a piston in a cylinder along a cylinder axis.
18. The method according to claim 17, wherein operating the gas displacement device comprises displacing a piston in a first direction and subsequently in a direction opposite to the first direction.
19. The method according to claim 16, wherein the ascertaining of at least one quantitative value is based on gas pressure values which are or were acquired during the operation of the gas displacement device, where the operation effects the acquired gas pressure values.
20. The method according to claim 19, wherein operating the gas displacement device comprises displacing a piston in a cylinder along a cylinder axis, the operation of the gas displacement device comprises a displacement of the piston at a constant piston velocity for a constant displacement duration, that the acquisition of a gas pressure in the measurement volume takes place during the constant displacement duration, and that the ascertaining of at least one quantitative value is based on gas pressure values acquired during the constant displacement duration.
21. The method according to claim 16, wherein the ascertaining of at least one quantitative value is based on gas pressure values which are or were acquired temporally after the operation of the gas displacement device which effects the acquired gas pressure values.
22. The method according to claim 21, wherein the operation which effects the acquired gas pressure values comprises the production of a gas pressure surge in the measurement volume.
23. The method according to claim 22, wherein operating the gas displacement device comprises displacing a piston in a first direction and subsequently in a direction opposite to the first direction, the production of a gas pressure surge in the measurement volume comprises a piston movement in two opposite directions in the cylinder with a stroke magnitude per direction of at least 0.5 mm each with a total movement duration of no more than 12 ms.
24. The method according to claim 21, wherein the acquisition duration comprises at least the time interval from the beginning of a gas pressure change until the first return to the initial value at the beginning of the gas pressure change.
25. The method according to claim 24, wherein the acquisition duration comprises at least twice the time interval from the beginning of a gas pressure change until the first return to the initial value at the beginning of the gas pressure change.
26. The method according to claim 24, wherein the acquisition duration comprises at least three times the time interval from the beginning of a gas pressure change until the first return to the initial value at the beginning of the gas pressure change.
27. The method according to claim 21, wherein the acquisition duration comprises no more than ten times the time interval from the beginning of a gas pressure change until the first return to the initial value at the beginning of the gas pressure change.
28. The method according to claim 21, wherein the acquisition duration comprises no more than six times the time interval from the beginning of a gas pressure change until the first return to the initial value at the beginning of the gas pressure change.
29. The method according to claim 16, wherein the characteristic variable is a mean of the acquired gas pressure.
30. The method according to claim 16, wherein the characteristic variable comprises at least one variable which characterizes a temporally transient course of the acquired gas pressure.
31. A pipetting device, comprising a pipetting duct with a coupling formation which is configured for detachable coupling of a pipette tip, where the pipetting device comprises: A pipetting duct filled with working gas, which penetrates through the coupling formation, A gas displacement device which is in a hydromechanically communicating operative connection with the pipetting duct and is configured to displace working gas in the pipetting duct, A pressure sensor which is arranged and configured to acquire and output a pressure of the working gas, A control device for controlling the operation of the gas displacement device and of the pressure sensor, A data storage device comprising at least one storage medium for storing data output by the pressure sensor which represent at least one pressure value of the working gas, where in the data storage device there are stored data which represent at least one calibration value for a comparison with at least one quantitative value of at least one characteristic variable which characterizes the acquired working gas pressure, wherein the pipetting device is configured for implementing the method according to claim 16.
32. The pipetting device according to claim 31, wherein the gas displacement device comprises a cylinder whose cylindrical cavity at least contributes to the formation of the pipetting duct, where in the cylinder there is accommodated in a displaceable manner a pipetting piston along a cylinder axis which defines an axial direction and a radial direction orthogonal to the latter as a working gas displacement component.
33. The pipetting device according to claim 32, wherein the pipetting piston exhibits at least one permanent magnet and the cylinder exhibits current-carrying conductor coils at least in an axial drive section radially outside the pipetting duct, where the current-carrying conductor coils form a stator and the pipetting piston a rotor of an electromagnetic linear motor, where the control device is configured for energizing the conductor coils with current.
Description
BRIEF DESCRIPTION OF THE DRAWINGS
[0068] The invention may take physical form in certain parts and arrangement of parts, a preferred embodiment of which will be described in detail and illustrated in the accompanying drawings which forms a part hereof and wherein:
[0069]
[0070]
[0071]
[0072]
DESCRIPTION OF PREFERRED EMBODIMENTS
[0073] Referring now to the drawings wherein the showings are for the purpose of illustrating preferred and alternative embodiments of the invention only and not for the purpose of limiting the same, in
[0074] The piston 14 comprises two end caps 16 (for the sake of clarity, in
[0075] The end caps 16 are preferably formed of low-friction material comprising graphite or mica, as is known for example from commercially available caps supplied by Airpot Corporation of Norwalk, Connecticut (US). In order to be able to exploit as fully as possible the low friction offered by this material, the pipetting duct 11 preferably comprises a cylinder 12 made of glass such that during a movement of the piston 14 along the duct axis K, the graphite- or mica-comprising material slides with extremely low friction along a glass surface.
[0076] The piston 14 thus forms a rotor of a linear motor 20, whose stator is formed by the coils 22 surrounding the pipetting duct 11 (here by way of example there are depicted only four coils).
[0077] Let it be pointed out expressly that
[0078] The linear motor 20, more precisely its coils 22, are actuated via a control device 24 which is connected with the coils 22 for signal transmission. The transmission of electric current for energizing the coils and thereby for producing a magnetic field through them also counts as a signal. In the control device 24 there is integrated a data storage device 25, in which the operating system of the pipetting device 10 is stored and in which sensor data from sensors connected with the control device 24 for signal transmission, such as for instance the position sensor arrangement 36 or also a pressure sensor 34 explained further below, can be stored.
[0079] At the dosing-side end 12a of the cylinder 12 there is coupled detachably in a way which is known per se a pipette tip 26. The connection of the pipette tip 26 with the dosing-side longitudinal end 12a of the cylinder 12 is likewise depicted merely in a rough schematic manner. The dosing-side longitudinal end 12a of the cylinder 12 is configured for detachable coupling of the pipette tip 26 as a coupling section 13 with a coupling formation 13a. Likewise, the end section of the pipette tip 26 which during pipetting operation is located nearer to the pipetting duct 11 is configured as a mating coupling section 27 with a mating coupling formation 27a. In the operational coupled state, the coupling section 13 of the pipetting duct 11 or more specifically of the cylinder 12 and the mating coupling section 27 of the pipette tip 26 overlap axially. The coupling formation 13a and the mating coupling formation 27a are in frictional and/or positive locking engagement, which holds the pipette tip 26 at the cylinder 12.
[0080] As part of the coupling section 13, there can for example be provided a stripping-off component 13b at the pipetting device 10, which is moveable along the duct path K in order to strip off a coupled pipette tip 26 from the coupling section 13. The operation of the stripping-off component 13b can also be controlled by the control device 24.
[0081] The pipette tip 26 defines a pipetting space or more specifically accommodating space 28 in its interior, which is accessible at the coupling-remote longitudinal end 26a solely through a pipetting aperture 30. The pipette tip 26, during its coupling to the cylinder 12, extends the pipetting duct 11 up to the pipetting aperture 30.
[0082] In the example depicted in
[0083] Between the piston 14 and the pipetting aperture 30 there is situated only working gas 32, which serves to transmit force between the piston 14 and a dosing fluid.
[0084] According to an alternative indicate in
[0085] A pressure sensor 34 can acquire the pressure inside the pipetting duct 11, to which also the accommodating space 28 which is connected in a pressure-communicating manner belongs, the pressure of the working gas 32 between the pipetting aperture 30 or an aspirated dosing fluid and the dosing-side end face 14a of the piston 14, and transmit it via a signal line to the control device 24. The pressure sensor 34 or more specifically pressure signals supplied by it, which represent the pressure of the working gas 32, can be used to control the pipetting device 10 in the conventional quasi-synchronous pipetting operation both for aspirating and for dispensing dosing fluid.
[0086] The position sensor arrangement 36 for acquiring the piston's position is provided at the pipetting duct 11 and connected for signal transmission with the control device 24.
[0087] In the coupled state, a filter-free pipette tip 26 and the cylinder 12 form a contiguous measurement volume 40 in the region between the pipetting aperture-side piston surface 14a and the pipetting aperture 30. When the pipette tip 26 exhibits a filter 38, the contiguous measurement volume 40 extends between the pipetting aperture-side piston surface 14a and the filter 38.
[0088] In the region of the coupling formation 13a there is configured at the pipetting duct 11a constriction, i.e. in the region of the coupling formation 13a the duct cross-section of the pipetting duct 11 is smaller than on both sides of the coupling formation 13a. The smaller duct cross-section of the pipetting duct section 11a in the region of the coupling formation 13a is, however, still greater than the aperture cross-section of the pipetting aperture 30.
[0089] In the case of a pressure surge in the working gas 32 induced by a rapid movement of the piston 14 along the duct path K, the working gas component in the pipetting duct section 11a or more specifically in the measurement part-volume 40a contained therein in the coupling formation 13a with a narrower duct cross-section acts as a mass, whereas the working gas components in the pipetting duct section 11b situated above it in the cylinder 12 with a larger duct cross-section or more specifically in the measurement part-volume 40b contained therein and in the pipetting duct section 11c situated below it in the pipette tip 26 with a likewise larger duct cross-section or more specifically in the measurement part-volume 40c contained therein, each acts as a gas spring.
[0090] In
[0091] At the position “0” in the upper diagram of
[0092] The graph 42 of the piston movement of
[0093] The phase 42a at a constant non-zero velocity, is followed by a phase 42b in which the piston 14 is stationary at a distance of approximately 56 mm from its starting point for a little less than half a second. Subsequently the pipetting piston 14 is moved back to it starting position at 0 mm, where during this movement the piston exhibits a constant velocity in the interval from approximately 1.42 sec to approximately 1.89 seconds. This phase of the return movement of the pipetting piston 14 to the starting point at a constant velocity is labelled here 42c.
[0094] Since, as already mentioned earlier, the cross-sectional area of the pipetting aperture 30 is considerably smaller than the smallest cross-sectional area of the pipetting duct in the pipetting duct section 11a, gas flows from the environment through the pipetting aperture more slowly than the piston 14 enlarges the measurement volume 40 by its movement. The same applies to the return movement of the piston 14: working gas flows through the pipetting aperture 30 more slowly out of the accommodating space 28 than the piston 14 reduces the enlarged measurement volume 40.
[0095] Thereby during the enlargement of the measurement volume 40 in the phase 42a, there is underpressure in the measurement volume 40 and during the decrease of the measurement volume during the phase 42c there is overpressure in the measurement volume 40, after the plateau phase 40b during which the piston 14 is stationary and the pressure of the working gas 32 in the measurement volume 40 equalizes with the ambient pressure of the external environment outside the pipette tip 26.
[0096] In the bottom half of
[0097] The pressure courses in the bottom half of
[0098] Due to the phases 42a and 42c of the piston movement at a constant non-zero velocity, there take place in the coupled pipette tips phases of constant underpressure or constant overpressure respectively of the working gas 32 in the pipetting duct 11 or more specifically in the measurement volume 40 relative to the ambient pressure. Phases of constant underpressure which were effected through the movement phase 42a of an increase in the measurement volume 40 through movement of the pipetting piston 14 away from its starting position at a constant velocity, are likewise labelled “a” in the bottom half of
[0099] The mean pressure values ascertainable during the phases 44a, 46a, and 48a and/or during the phases 44c, 46c, and 48c, in which the value of the pressure of the working gas 32 in the measurement volume 40 is in any case essentially constant, are a reliable indicator of the coupled pipette tip 26. Given the same shape and/or the same nominal pipetting volume of coupled pipette tips 26, and with always the same movement profile of the pipetting piston 14 in the measurement volume 40 in the phases with essentially constant relative underpressure and essentially constant relative overpressure of the working gas 32 relative to the ambient pressure, there always set in essentially the same mean pressure values. These can be ascertained in a laboratory under a calibration operation and stored in the data storage 25 for a comparison with the pressure values ascertained during the implementation of the present method.
[0100] In order to take into consideration fabrication tolerances of the pipette tips 26, a class of pipette tips with an essentially identical nominal pipetting volume and/or essentially identical shape can have value ranges assigned to it extending from a lower limit to an upper limit, such that a spread of ascertained mean pressure values of pipette tips of one and the same pipette tip class always lies within an unambiguous range of values.
[0101] As is apparent from
[0102] The piston 14 is actuated meanwhile by the control device 24 to move in accordance with the movement curve 42. The pressure of the working gas 32 is acquired during the piston movement. In this process, the phases 44a, 46a, and/or 48a and 44c, 46c, and/or 48c respectively of essentially constant working gas pressures are ascertained and the mean pressure values occurring during these phases ascertained. The mean pressure values are compared with predetermined calibration values, and depending on the comparison result the coupled pipette tip 26 is assigned to a predetermined pipette tip class.
[0103] The mean working gas pressure during phases of constant under- and/or overpressure is a characteristic variable within the meaning of the present application. The concrete values of the mean working pressure during these phases are the assigned quantitative values of this characteristic variable.
[0104] The first embodiment of the method according to the invention, elucidated in more detail in connection with
[0105] When the pipette tip 46 carries a filter 38, the second embodiment of the method presented here can be used. Needless to say, the second embodiment can also be used for filter-free pipette tips 26 in assigning them to a pipette tip class.
[0106]
[0107] In the present example, the pipetting piston 14 was moved for a predetermined stroke, approximately 1 mm, towards the coupling formation 13a and subsequently back away from the coupling formation 13a. The total movement of the pipetting piston 14 lasted no longer than 4 ms. Through this very quick movement of the pipetting piston 14 in a very short time, there was produced a pressure pulse which decays in the measurement volume 40 due to attenuation through internal friction in the working gas 32.
[0108] The pressure curve of a pipette tip with a nominal pipetting volume of 10 μl is once again shown in
[0109] The pressure curves 50, 52, 54, and 56 of
[0110] Whereas the pipette tips with a nominal pipetting volume of 300 μl and of 1000 μl still complete the first half-oscillation and also the first full oscillation in approximately the same time, the pressure courses obtained with them differ considerably from one another as from the first negative amplitude, i.e. the second occurring amplitude of the acquired oscillation form.
[0111] As is further apparent from
[0112] The pressure courses of pipette tips with a nominal pipetting volume of 10 μl and of 50 μl differ not only quite obviously in terms of period and amplitude from the previously considered corresponding values of the pipette tips with a nominal pipetting volume of 300 μl and of 1000 μl, they also differ among themselves. Whereas the amplitudes of the pressure courses of the pipette tips with a nominal pipetting volume of 10 μl and of 50 μl in the first and in the second half-oscillation are still approximately equal in magnitude, they differ quite considerably from one another as from the third half-oscillation. The periods of the pressure courses of the pipette tips with a nominal pipetting volume of 10 μl and of 50 μl are already different for the first half-oscillation, since the pressure course of the smaller pipette tip with a nominal pipetting volume of 10 μl returns measurably and significantly later to its initial value than the pressure course of the pipette tip with 50 μl nominal pipetting volume.
[0113] The characteristic variables to be used for differentiating the belonging of pipette tips to predetermined pipette tip classes can be ascertained during the production of calibration value files. In the present example of
[0114] Thus according to the second embodiment, the working gas 32 in the measurement volume 40 is excited into oscillating by means of a pressure surge through the quick movement of the piston 14 described above. The temporal course of the excited pressure oscillation is acquired, and is quantified based on predetermined characteristic variables by ascertaining their quantitative values. The quantitative values thus ascertained are compared with predetermined calibration values. Depending on the comparison result, the pipette tip 26 coupled during the pressure excitation and the acquisition of the pressure oscillations is assigned to a predetermined pipette tip class.
[0115] A pipette tip 26 with working gas 32 excited into oscillating in the measurement volume 40 can be regarded as a Helmholtz resonator, with the working gas column in the measurement part-volume 40a as an oscillating mass and with the working gas components in the measurement part-volumes 40b and 40c as air springs.
[0116] The behavior of a Helmholtz resonator, in the present case the pressure changes in the working gas 32 as a response to a movement of the piston 14, can always be modelled by a differential equation of the same structure. Such a differential equation can be written generally as follows:
a.sub.n.Math.p.sup.(n)+ . . . +a.sub.2.Math.p.sup.(2)+a.sub.1.Math.p.sup.(1)+a.sub.0.Math.p=b.sub.m.Math.x.sup.(m)+ . . . +b.sub.2.Math.x.sup.(2)+b.sub.1.Math.x.sup.(1)+b.sub.0.Math.x
[0117] with p as the pressure of the working gas 32, x as the position of the piston 14 along the duct path K relative to its starting position, (n) as the nth derivative with respect to time, (m) as the mth derivative with respect to time, and with a.sub.i and b.sub.j as coefficients on the left or the right side respectively of the differential equations. Through value-based determination of the coefficients a.sub.i and b.sub.j, the pressure curves 50 to 56 can likewise be characterized and compared with assigned calibration values. In this sense, the coefficients a.sub.i and b.sub.j also constitute characteristic variables and their value-based determination the associated quantitative values in the sense of the present application. The value-based determination of the coefficients can take place sufficiently accurately, analytically and/or numerically, with the help of the ascertained curves, using average computing powers available today as can readily be present in control devices 24.
[0118]
[0119] Whereas in the case of pipette tips 26 without a filter 38, the assigning of a coupled pipette tip 26 to a pipette tip class can be performed either by means of the slow first embodiment of the method presented here in accordance with
[0120] In
[0121] Due to the filters 38 present in the accommodating space 28, the measurement volumes 40 of the different pipette tips 26 differ from one another less strongly than in the preceding example of filter-free pipette tips 26.
[0122] Nevertheless,
[0123] As transpires from
[0124] In the way described above, it is possible before using a pipette tip 26 just coupled to examine quickly and reliably whether the coupled pipette tip 26 is the correct pipette tip 26 for the pipetting task to be subsequently carried out with it or not. Pipetting errors up to the point of damaging the pipetting device 10 are thereby avoided.
[0125] By means of an output device 41, the control device 24 can output to operating personnel the pipette tip class thus ascertained which was assigned to the pipette tip 26.
[0126] While considerable emphasis has been placed on the preferred embodiments of the invention illustrated and described herein, it will be appreciated that other embodiments, and equivalences thereof, can be made and that many changes can be made in the preferred embodiments without departing from the principles of the invention. Furthermore, the embodiments described above can be combined to form yet other embodiments of the invention of this application. Accordingly, it is to be distinctly understood that the foregoing descriptive matter is to be interpreted merely as illustrative of the invention and not as a limitation.