Abstract
The invention relates to a pipette auxiliary system for supporting manual pipetting or dispensing of a plurality of samples of a sample-holding arrangement, in particular a microtiter plate. The pipette auxiliary system according to the invention supports the manual pipetting or dispensing of a plurality of samples in a working position of a sample-holding arrangement, the pipette auxiliary system comprising: a base apparatus comprising a positioning device which is designed to position the sample-holding arrangement in the working position inside a positioning space of the base apparatus, said positioning space being opened at least along a plane for the pipetting; the sample-holding arrangement which has a plurality of sample holders; a measurement arrangement comprising a plurality of measurement elements which are positioned at least in the working position underneath this plane and using which the occupancy state of at least one sample holder can be detected in the working position; and an output device or a light arrangement using which the sample-holding arrangement can be illuminated in accordance with this occupancy state of this at least one sample holder.
Claims
1. Pipette auxiliary system (1; 50; 100; 100; 200; 300; 400) for supporting the manual pipetting, or respectively, dispensing of a plurality of samples in a working position of a sample-holding arrangement (20; 120; 120; 120; 220) by means of a user-guided pipette- or dispenser apparatus, with the pipette auxiliary system comprising: a base apparatus (10; 110; 110; 210) with a positioning device (12a, 12b; 112a, 112b; 212a, 212b), which is configured for the positioning of the sample-holding arrangement in the working position inside a positioning space (11; 111, 211) of the base apparatus, which is open at least along one plane (A) for pipetting, the sample-holding arrangement (20; 120; 120; 120; 220), comprising a plurality of sample holders (21; 121; 121; 121; 221), a measurement arrangement (28; 48; 119; 119; 228) comprising a plurality of measurement elements (22, 23; 22; 23; 22; 23; 116; 117; 116; 117; 116; 117; 116; 117; 222, 223; 42), that are, at least in the working position, positioned underneath that plane (A), and with which the occupancy state of at least one sample holder in the working position can be detected, an output device for outputting to the user information on the occupancy state of at least one sample holder, and an electronic control device (13; 33; 113; 213), which is configured to detect the occupancy state of at least one sample holder in the working position by controlling the measurement arrangement and to output, in accordance with the occupancy state of the at least one sample holder, to the user the information on the occupancy state of said at least one sample holder.
2. Pipette auxiliary system according to claim 1, with the plurality of measurement elements being a fixed component of the sample-holding arrangement and the output device being a fixed component of the base apparatus.
3. Pipette auxiliary system according to claim 1, with the plurality of measurement elements and the output device being fixed components of the base apparatus.
4. Pipette auxiliary system (300) according to one of the preceding claims, comprising at least one first and one second base apparatus, at least one first and one second measurement arrangement, and at least one first and one second output device, with the control device being configured to addressing the first measurement arrangement, the second measurement arrangement, the first output device and/or the second output device. the plurality of measurement elements and the output device being fixed components of the sample-holding arrangement.
5. Pipette auxiliary system according to one of the preceding claims, with the output device being a light arrangement (18; 38; 118; 229), with which the sample-holding arrangement can be illuminated in function of the occupancy state of that at least one sample holder.
6. Pipette auxiliary system according to one of the preceding claims, with the pipette auxiliary system comprising said pipetting apparatus or dispenser apparatus, which each comprise said electronic control device or a second control device, controlling the electronically operated pipetting or dispensing of the pipetting apparatus or dispenser apparatus, with said electronic control devices and/or the second control device being configured to control the measurement arrangement and/or the output device via a signal connection.
7. Pipette auxiliary system according to claim 6, with the electronic control device of the pipetting apparatus or dispenser apparatus being configured to control the measurement arrangement and to receive information on the occupancy state in form of occupancy state data.
8. Pipette auxiliary system according to claim 6 or 7, with the electronic control device or the second control device being configured to detect the approach of the at least one sample transfer container, which is connected to the pipetting apparatus or the dispenser apparatus to the at least one sample holder by measurement with the measurement arrangement, and to control the pipetting apparatus or dispenser apparatus in such a way that these release autonomously the intended volume each into the at least one sample holder.
9. Pipette auxiliary system according to claim 6, 7 or 8, with the electronic control device or the second control device being configured to execute a pipetting planning program, according to which the information on the at least one sample holder of the sample-holding arrangement intended as the each next target position for the pipetting is displayed to the user by means of the output device, the manually operated approach of the at least one sample transfer container to the sample-holding arrangement is detected by the measurement arrangement and the position of the reached sample holder is recognized, it is detected by comparison with the planning data of the pipetting planning program whether the reached position is the intended target position according to the plan, and, in case the reached position is the intended target position according to the plan, a predefined sample volume is released automatically to the target position, and, in case the reached position is not the intended target position according to the plan, this automatic release is suppressed.
10. Pipette auxiliary system according to claim 1 or 2, with the measurement elements being configured as electrodes, and in which the measurement arrangement is configured for the measurement of a capacitance value at least one sample holder, in particular for measurement of several capacitance values at a plurality of sample holders and in particular every sample holder, with that capacitance value being influenced by the content of the sample-holding chamber of the sample holder, so that the occupancy state can be measured by a measurement a the capacitance.
11. Pipette auxiliary system according to claim 10, with the measurement elements being designed as electrodes, and with the electrodes comprising an electrically conductive polymer, or consisting thereof.
12. Pipette auxiliary system according to one of the preceding claims, with the electronic control device being configured to implement one of the following functions: The type of illumination of at least one sample holder is dependent on the measured occupancy stat of the sample holder; The type of illumination of at least one second sample holder is dependent on the measured occupancy state of at least one first sample holder; In case of the user approaching at least one sample transfer container to an erroneous sample holder that has not been selected by the electronic control device as target for the next manual pipetting and has in particular been illuminated, the illumination type of the erroneous sample holder is changed, in particular a warning illumination generated by a light element of the at least one erroneous sample holder is activated.
13. Pipette auxiliary system according to one of the preceding claims, comprising an external device, which is arranged separately from the base apparatus, and that comprises a data processing device, with the base apparatus comprising a data processing electronic device, with which the measurement arrangement and the light arrangement are addressed, with the measurement values corresponding to the occupancy states, measured by the measurement arrangement being stored by the electronic control device as occupancy state data in a data storage device of the external device.
14. Pipette auxiliary system according to one of the preceding claims, with each of the sensor devices of the measurement arrangement that comprise at least one measurement element being configured such that the number M of distinguishable occupancy states of the at least one sensor device is 2<=M<=10.
15. Pipette auxiliary system according to one of the preceding claims, with the base apparatus comprising a data-processing electronic control device that addresses the measurement arrangement and the light arrangement, and that contains a micro controller with Touch Sensing Controller (TSC) hardware.
16. Base apparatus for supporting manual pipetting of a plurality of samples in a working position of a sample-holding arrangement, comprising a positioning device, which is configured for the positioning of the sample-holding arrangement according to claim 17 in the working position inside a positioning space of the base apparatus, which is at least along one plane opened for pipetting, an output device, by which an information can be output at the sample-holding arrangement in dependence of the occupancy state, that has been measured by means of the measurement elements of the sample-holding arrangement according to claim 17.
17. Sample-holding arrangement for supporting the manual pipetting of a plurality of samples in a working position of a sample-holding arrangement, which is provided for the positioning in the positioning device of the base apparatus according to claim 16, with the sample-holding arrangement comprising: a plurality of sample holders, a measurement arrangement comprising a plurality of measurement elements which are positioned at least in the working position underneath this plane and using which the occupancy state of at least one sample holder can be detected in the working position.
18. Base apparatus for supporting the manual pipetting of a plurality of samples in a working position of a sample-holding arrangement that comprises a plurality of sample holders, comprising a positioning device, which is configured for positioning a sample-holding arrangement in the working position in a positioning space of the base apparatus, which is opened at least along one plane for pipetting, a measurement arrangement comprising a plurality of measurement elements which are positioned at least in the working position underneath this plane and using which the occupancy state of at least one sample holder can be detected in the working position, and an output device, by which an information can be output at the sample-holding arrangement in dependence of the occupancy state, that has been measured by means of the measurement elements of the sample-holding arrangement.
19. Method for the measurement of an occupancy state of a sample holder by means of the pipette auxiliary system according to claim 1, with the occupancy state being measured by measuring a capacitance or a change of capacitance of at least one measurement element implemented as an electrode, when a sample transfer container of a non-conductive material, filled with a conductive sample, is approached to this electrode and in particular contacts the plane or passes the plane.
20. Production method for the production of a sample-holding arrangement according to claim 17 by means of injection molding.
21. Use of a sample-holding arrangement according to claim 17 in a pipette auxiliary system according to claim 1.
Description
[0139] In the figures:
[0140] FIG. 1a depicts in a perspective lateral view an application scene underlying the invention, in which a complete filling by means of successive column-wise pipetting is executed on a 96 well microtiter plate with a manually operated multi-channel pipette.
[0141] FIG. 1b depicts in a perspective lateral view an application scene underlying the invention, in which a complete filling by means of randomized pipetting is executed on a 96 well microtiter plate with a manually operated single channel pipette.
[0142] FIG. 2a depicts a sample-holding arrangement according to the preferred embodiment of the invention in an exemplary embodiment as preferred component of an exemplary embodiment of the pipette auxiliary system according to the present invention.
[0143] FIG. 2b depicts a base apparatus according to the first preferred embodiment of the invention in an exemplary embodiment as preferred component of an exemplary embodiment of the pipette auxiliary system according to the present invention, that can in particular be utilized with the sample-holding arrangement in FIG. 2a.
[0144] FIG. 2c depicts a pipette auxiliary system, in working position, comprising the sample-holding arrangement from FIG. 2a and the base apparatus from FIG. 2b.
[0145] FIG. 3a depicts a sample-holding arrangement according to a further embodiment example of the invention, as preferred component of an exemplary pipette auxiliary system according to the present invention.
[0146] FIG. 3b depicts a base apparatus according to a further embodiment example of the invention, as preferred component of an exemplary pipette auxiliary system according to the present invention, in particular utilizable with the sample-holding arrangement from FIG. 3a.
[0147] FIG. 3c depicts a pipette auxiliary system, in working position, comprising the sample-holding arrangement from FIG. 3a and the base apparatus from FIG. 3b.
[0148] FIG. 4a through FIG. 4d depict each different phases of the pipetting supported by an exemplary pipette auxiliary system according to the present invention on a sample-holding arrangement, and depict the optical highlighting of the pipetted sample holders resp. the sample holders to be pipetted by an illumination program effectuated by the pipette auxiliary apparatus.
[0149] FIGS. 5a and 5b depict a simplified lateral cross sectional view through a capacitance measuringby means of two cylinder-barrel-shaped electrodessensor device of an exemplary pipette auxiliary system, in the empty and filled state of the only displayed sample holder.
[0150] FIGS. 5c and 5d depict a simplified lateral cross sectional view through a capacitance measuringby means of two cylinder-barrel-shaped electrodes with a round bottomsensor device of an exemplary pipette auxiliary system, in the empty and filled state of the only displayed sample holder.
[0151] FIGS. 5e and 5f depict a simplified lateral cross sectional view through a capacitance measuringby means of two cylinder-barrel-shaped electrodes with a conical bottomsensor device of an exemplary pipette auxiliary system, in the empty and filled state of the only displayed sample holder.
[0152] FIGS. 6a and 6b depict a simplified lateral cross sectional view through a capacitance measuring sensor device of another exemplary pipette auxiliary system, in the empty and filled state of the only displayed sample holder.
[0153] FIGS. 7a and 7b depict a simplified lateral cross sectional view through an optically measuringby means of two optical measurement elementssensor device of another exemplary pipette auxiliary system, in the empty and filled state of the only displayed sample holder.
[0154] FIG. 8a depicts a sample-holding arrangement according to the second preferred embodiment of the invention in an exemplary embodiment as preferred component of an exemplary embodiment of the pipette auxiliary system according to the present invention.
[0155] FIG. 8b depicts a base apparatus according to the second preferred embodiment of the invention in an exemplary embodiment as preferred component of an exemplary embodiment of the pipette auxiliary system according to the present invention, that can in particular be utilized with the sample-holding arrangement in FIG. 8a.
[0156] FIG. 8c depicts a pipette auxiliary system, in working position, comprising the sample-holding arrangement from FIG. 8a and the base apparatus from FIG. 8b.
[0157] FIG. 9a depicts a sample-holding arrangement according to the third preferred embodiment of the invention in an exemplary embodiment as preferred component of an exemplary embodiment of the pipette auxiliary system according to the present invention.
[0158] FIG. 9b depicts a base apparatus according to the third preferred embodiment of the invention in an exemplary embodiment as preferred component of an exemplary embodiment of the pipette auxiliary system according to the present invention, that can in particular be utilized with the sample-holding arrangement in FIG. 9a.
[0159] FIG. 9c depicts a pipette auxiliary system, in working position, comprising the sample-holding arrangement from FIG. 9a and the base apparatus from FIG. 9b.
[0160] FIG. 10a depicts a perspective view of a pipetting system according to the present invention according to another preferred embodiment.
[0161] FIG. 10b depicts a perspective view of a pipetting system according to the present invention according to another preferred embodiment.
[0162] FIG. 11a depicts a sample-holding arrangement according to the second preferred embodiment of the invention in an exemplary embodiment as preferred component of an exemplary embodiment of the pipette auxiliary system according to the present invention.
[0163] FIG. 11b depicts a base apparatus according to the second preferred embodiment of the invention in an exemplary embodiment as preferred component of an exemplary embodiment of the pipette auxiliary system according to the present invention, that can in particular be utilized with the sample-holding arrangement in FIG. 11a.
[0164] FIG. 11c depicts a pipette auxiliary system, in working position, comprising the sample-holding arrangement from FIG. 11a and the base apparatus from FIG. 11b.
[0165] FIG. 12a depicts a simplified lateral cross sectional view through a capacitance measuringby means of two plate-shaped electrodessensor device of an exemplary pipette auxiliary system, in the filled state of the single displayed sample holder, with the sensor device corresponding to the sensor devices depicted in FIGS. 11b and 11c.
[0166] FIG. 12b depicts a simplified lateral cross sectional view through a capacitance measuringby means of two plate-shaped electrodessensor device of an exemplary pipette auxiliary system, in the filled state of the single displayed sample holder.
[0167] FIG. 12c depicts a simplified lateral cross sectional view through a capacitance measuringby means of two plate-shaped electrodessensor device of an exemplary pipette auxiliary system, in the filled state of the single displayed sample holder.
[0168] FIG. 1a depicts a typical application scene underlying the invention. At a 96 well plate 69, a complete filling of the well plate is executed with a manually operated multichannel pipette 70 by means of a successive, column-wise pipetting in direction F. Eight pipette tips 71 correspond to the number and the pattern of a column of 8 wells of the 96 well plate. In the example the pipette tips 71 are successively refilled anew in order to fill all sample holders of the microtiter plate by successive pipetting. The pipetting requires the positioning of the pipette 70 over the target column of the wells of the well plate, the lowering along the vertical direction V and the correct insertion of the pipette tips 71 into the openings of the wells, the continued lowering into the wells and the release of the sample by pipetting. This is followed by the lifting of the pipette from the lowered position and the movement forward along the direction F by exactly one distance between the columns. Above the second column the described processes are repeated correspondingly, equally for the columns number 3 through 12.
[0169] If the user, during the successive filling, fills for example the fifth column by manual pipetting and does not bear that in mind, there is a high likelihood of either not filling in the following pipetting step the next intended target column, e.g. column six, or of inadvertently filling for a second time one of the columns one through five with already filled sample holders. With this invention a pipette auxiliary system is described that guides the user faultlessly in such situations by measuring the occupancy and optical marking.
[0170] FIG. 1b depicts a scenario, in which the user has to fill a well plate 69 by means of an electrical single channel pipette 70. In this figure, the task for the user consists in reliably following a pipetting plan on the well plate that involves the pipetting at individual containers according to a non-successive proceeding. In particular the coordinates of the sample containers to be filled or of the sample containers, from which a sample is intended to be removed and e.g. transferred by pipetting, can be known to the user. In particular in this constellation a substantial effort is required from the user for pipetting at the correct well. This becomes even more difficult in the case of a sample plate with more than 96 well, e.g. 384 wells. In the described scenarios, the invention offers a very beneficial solution.
[0171] FIG. 2a depicts a sample-holding arrangement 20 according to the first preferred embodiment of the invention in an exemplary embodiment as preferred component of an exemplary embodiment of the pipette auxiliary system according to the present invention. The sample-holding arrangement 20 has the format of a well plate produced according to the SBS-standard. The sample-holding arrangement 20 is produced essentially of transparent plastic by means of a two shot molding and exhibits a matrix of 96 sample holders 21 (wells). Here, out of those, a row with 12 sample holders 21 is depicted in a cross section.
[0172] The sample-holding arrangement 20 exhibits a measurement arrangement 28 with a plurality of measurement elements, here e.g. 192 measurement elements, of which a pair 22, 23 of measurement elements implemented as electrodes is positioned so that they each embed the sample-holding chamber of the sample holder 21 like a dielectric between capacitor plates. In FIG. 2c, the working position is depicted with the pipette tips 71 pipetting in order to successively fill the complete well plate 20. From this it results that the measurement elements 22, 23 of the measurement arrangement 28 are arranged, at least in the working position, underneath the plane A with the occupancy state of at least one sample holder 21 in the working position being detectable with one pair 22, 23 of electrodes. The electrodes and the conductors are formed from a conductive polymer, equally the contact sites 26 and 27 of the sample-holding arrangement 20 that are connected electrically with the conductor paths 24 and 25, which in turn are connected electrically with the electrodes 22, 23.
[0173] FIG. 2b depicts a base apparatus 10 according to the first preferred embodiment of the invention in an exemplary embodiment as preferred component of an exemplary embodiment of the pipette auxiliary system according to the present invention, that can in particular be utilized with the sample-holding arrangement 20 in FIG. 2a. The base apparatus 10 comprises: a positioning device exhibiting several barrier elements 12a, 12b, that are configured for the positioning of the sample-holding arrangement in the working position inside a positioning space 11 of the base apparatus, which is opened for pipetting at least along a plane A.
[0174] The base apparatus 10 comprises a light arrangement 18, which is arranged in the working position underneath that plane A with which the sample holders of the sample-holding arrangement 20 can be illuminated in dependence of each measured occupancy state that have been measured by means of the measurement elements 22, 23 of the sample-holding arrangement 20.
[0175] The light elements 19, each implemented in the form of LEDs, can be addressed individually by the electric control device 13 via the conductors of a conductor bundle 14. The light elements are coupled electrically with the control device via the electrical interface 13a.
[0176] The base apparatus comprises preferentially a solid case, fabricated of metal and/or plastic, in which the light arrangement and the control device are arranged. The measurement elements 22, 23 of the microtiter plate 20 are connected electrically via electrical contact sites 26, 27 with the corresponding contact sites 16, 17 that are located on the top side of the plate-like positioning range of the base apparatus 10 in the positioning space 11. The contact sites 16, 17 are each connected via the conductors 15a, 15b with an electrical interface 13b, with which the measurement elements are coupled to the control device 13. All first measurement electrodes 22 of the sensor devices of the row of sample holders 21 depicted here are connected here with the conductor 15a, all second measurement electrodes 23 of the sensor devices of the row of sample holders 21 depicted here are connected here with the conductor 15b. Because of the sensitive measurement electronics for the measurement of very small capacitances, with this design that minimizes the conductor length, reliable measurements of the occupancy state can be carried out successively at all sensor devices of the row, in which 8 sensor devices are measured simultaneously for each column.
[0177] The well plate 20 is positioned reliably in the positioning space 11 by means of the positioning device 12a, 12b.
[0178] FIG. 2c depicts a pipette auxiliary system, in working position, comprising the sample-holding arrangement from FIG. 2a and the base apparatus from FIG. 2b. The pipette auxiliary system 1 serves for supporting the manual pipetting of a plurality of samples in a working position of a sample-holding arrangement 20, with the pipette auxiliary system 1 comprising: a base apparatus 10 with a positioning device 12a, 12b, which is configured for the positioning of the sample-holding arrangement 20 in the working position inside a positioning space 11 of the base apparatus 10, which is opened for pipetting at least along a plane (A), the sample-holding arrangement 20 that comprises a plurality of sample holders 21, a measurement arrangement 28 with a plurality of measurement elements 22, 23 that are arrange at least in the working position underneath that plane A and with which the occupancy state of at least one sample holder 21 in the working position can be detected, and a light arrangement 18 that is arranged at least in the working position underneath that plane A with which the sample-holding arrangement 20 resp. its sample holders 21 can be illuminated in dependence of each measured occupancy states of that at least one sample holder 21.
[0179] In the first preferred embodiment of the invention depicted in FIG. 2c, a plurality of measurement elements 22, 23 is a fixed component of the sample-holding arrangement 20 and the light arrangement 18 is a fixed component of the base apparatus 10.
[0180] FIG. 3a depicts a sample-holding arrangement according to another embodiment example of the invention, as preferred component of an exemplary pipette auxiliary system according to the present invention. Here, the sample-holding arrangement 40 comprises at each upper edge of a sample holder a single ring electrode 42 whose function will be discussed with the help of FIGS. 6a and b. Correspondingly, fewer conductors 44 and contact sites 46 at the sample-holding arrangement are provided here than in the embodiment according to FIG. 2a, and as compared to the embodiment according to FIG. 2b fewer conductors 35a, and contacts 36. Beyond that, the working principle of the pipette auxiliary systems from FIGS. 2a-c and 3a-c is similar.
[0181] The single electrode in the upper section of the sample holder according to FIGS. 3a and 6a is particularly preferred, and can also be combined with the version from FIG. 2a and FIG. 5a/5c, in which pairs of electrodes are stretched along most of the length of the sample holders in vertical direction. Functionally, this renders it possible to obtain with a single pipette auxiliary system an information on whether and when a pipette tip is approaching the measurement chamber and which occupancy state with a liquid sample has the sample holder in its sample holding chamber.
[0182] FIG. 4a through FIG. 4d each depict different phases of the pipetting at a sample-holding arrangement 20 supported by means of an exemplary pipette auxiliary apparatus 1 according to the present invention, and depict the optical highlighting of the pipetted resp. to be pipetted sample holders effectuated by an illumination program of the pipette auxiliary apparatus. When a pipette tip is lowered through the plane A (FIG. 4b) the sample holder is illuminated for example from below with a yellow color, which is symbolized here by a lighter shading of the sample holders located at the far right. The sample holders that have been filled are illuminated from below in a green light, which is symbolized in FIGS. 4c and 4d by a dark shade of the respective sample holders.
[0183] FIGS. 5a and 5b depict a simplified lateral cross sectional view through a sensor device of an exemplary pipette auxiliary system measuring a capacitance by means of two electrodes, in the empty and filled state of the only depicted sample holder. The space between a pair of electrodes 22, 23 that each have the shape of a segment of a cylinder barrel placed around the sample-holding chamber 21 is constituted by a dielectric permeated by an electrical field E, so that a change of the capacitance is detected if the occupancy state in 21 is changed (FIG. 5b). The arrangement in FIGS. 5 c and 5d differs from that in FIGS. 5a and 5b essentially by the fact that the sample-holding chamber 21 of the variant in FIGS. 5c and 5d exhibits an essentially spherical bottom (round bottom). In this case, the electrodes 22, 23 are adjusted to the spherical shape and therefore exhibit in their lower parts spherically shaped plates. Correspondingly, the arrangement in FIGS. 5e and 5f differs from that in FIGS. 5a and 5b essentially by the fact that the sample-holding chamber 21 of the variant in FIGS. 5e and 5f has an essentially conically shaped bottom (conical bottom). In this case, the electrodes 22, 23 are adjusted to that conical shape and therefore exhibit in their lower parts a conically shaped plate. A light element (not depicted) of the output device can be a component of each the sample-holding arrangement 20 or the base apparatus 10.
[0184] FIGS. 6a and 6b depict a simplified lateral cross sectional view through a sensor device of another exemplary pipette auxiliary system measuring a capacitance by means of one electrode, in the empty and filled state of the only depicted sample holder. By means of a single ring electrode 42, which is arranged at the upper edge of the sample holder 41 the approach a conductive pipette tip or a pipette tip of a non-conductive material filled with a conductive aqueous solution is detected. Approaching the pipette tip increases the measured capacitance, so that the occupancy state pipette tip is present can be recognized with a suitable threshold value. In the example, the ring electrode 42 is partially embedded into the material of the sample-holding arrangement 40, the ring electrode 42 is located underneath the plane A. The ring electrode can also be arranged on a surface of the sample-holding arrangement 40 and can for example be deposited as a thin plate, foil, or layer. By means of this arrangement at the surface of the sample-holding arrangement 40 it is ascertained that the sample-holding arrangement 40 including its measurement arrangement is located underneath the plane A. A light element (not depicted) of the output device can be component of each the sample-holding arrangement 40 or the base apparatus 30.
[0185] FIGS. 7a and 7b depict a simplified lateral cross sectional view through a sensor device of another exemplary pipette auxiliary system measuring optically by means of two optical measurement elements, in the empty and filled state of the only depicted sample holder. A light beam (infrared) emitted from the LED 66 reaches the mirror element 83 that deflects the beam through the measurement chamber 8 and to the next mirror element 84. From there, the beam is deflected onto the light sensor 67 that can be in particular a photodiode or a CMOS sensor. The electrical control of the optical measurement elements 66, 67 associated to the optical sensor device and arranged in the base apparatus 60 occurs via the individual conductors 65a, 65b that are also arranged in the base apparatus. By inserting an object, e.g. a liquid sample into the measurement chamber measured by the beam, a change of the occupancy state can be registered optically. A light element (not depicted) of the output device can be component of each the sample-holding arrangement 80 or the base apparatus 30.
[0186] FIG. 8a depicts a sample-holding arrangement 120 according to the second preferred embodiment of the invention in an exemplary embodiment as preferred component of an exemplary embodiment of the pipette auxiliary system according to the present invention. Here, the light elements 118a are each arranged centrally and directly underneath the sample holder 121, so that is can be illuminated symmetrically.
[0187] FIG. 8b depicts a base apparatus according to the second preferred embodiment of the invention in an exemplary embodiment as preferred component of an exemplary embodiment of the pipette auxiliary system according to the present invention, that can be in particular utilized with the sample-holding arrangement in FIG. 8a. The positioning device 112a, 112b is fabricated analog to FIG. 2b. Equally the control device 113.
[0188] FIG. 8c depicts a pipette auxiliary system, in working position, comprising the sample-holding arrangement from FIG. 8a and the base apparatus from FIG. 8b. In the second preferred embodiment of the invention depicted in FIG. 8b, the plurality of measurement elements 116, 117 of the measurement arrangement 119 and the light arrangement 118 with light elements 118a are fixed components of the base apparatus 110. The sample-holding arrangement 120 comprises a plurality of openings 122, 123 for accepting the measurement elements 116, 117 in the working position. Such a sample-holding arrangement 120 that does not have to comprise electrical conductors or electrically conductive areas, can be fabricated easily and precisely by means of injection molding.
[0189] FIG. 9a depicts a sample-holding arrangement according to the third preferred embodiment of the invention in an exemplary embodiment as preferred component of an exemplary embodiment of the pipette auxiliary system according to the present invention. In the third preferred embodiment of the invention depicted in FIG. 9c, the plurality of measurement elements 222, 223 of the measurement arrangement 228 and a plurality of light elements 224 of the light arrangement 229 are fixed components of the sample-holding arrangement. The other components are fabricated essentially analog to the embodiments in FIGS. 2c and 8c.
[0190] FIG. 9b depicts a base apparatus according to the third preferred embodiment of the invention in an exemplary embodiment as preferred component of an exemplary embodiment of the pipette auxiliary system according to the present invention, that can be in particular utilized with the sample-holding arrangement in FIG. 9a.
[0191] FIG. 9c depicts a pipette auxiliary system, in working position, comprising the sample-holding arrangement of FIG. 9a and the base apparatus of FIG. 9b.
[0192] FIG. 10 depicts a perspective view of pipetting system 300 according to the present invention and according to another preferred embodiment. Two base apparatus 10, 10 that can essentially correspond for example to the base apparatus depicted in FIG. 2b are connected via a signal exchange/data exchange connection D. Here, the sample-holding apparatus are designed as depicted in FIG. 2a. The control devices of these base apparatus that can exchange signals between each other are configured to assist the user of the manual pipetting apparatus 70 at the execution of a transfer process. In this, the user should, according to a pipetting planning program, which is executed by at least one control device, take up samples from the first columns of the sample plate 20 by means of the pipette 70 and transfer them into the second sample column of the sample plate 20. The pipetting planning program resp. control device executing this program is configured to illuminate the first column of the sample plate 20 in a color. This is symbolized in FIG. 10 by a darker shade of the first column of sample holders of the sample plate 20. Now, the user takes up the samples by pipetting in that column. After the uptake, the success or failure of the uptake from this first column of the sample plate 20 is signaled to the user by the system through a change of the illumination type of that first column of the sample plate 20. The success has been verified with the measurement arrangement of the sample plate 20. The target position for the samples contained now in the pipette tips 71, here the fourth column from the right, is indicated to the user by an illumination in the second sample plate 20. Now, the user releases the samples by pipetting in that column. After the release, the success or failure of the release into that fourth column of the sample plate 20 is signaled to the user by the system through a change of the illumination type of that fourth column of the sample plate 20. The success has been verified by the measurement arrangement of the sample plate 20. This assistance during the transfer of the sample between two sample-holding arrangements monitored by the pipette auxiliary systems is continued until the pipetting planning program has terminated.
[0193] The FIG. 10b depicts a pipette auxiliary system 400 that comprises as a component a pipette 70. The pipette 70 resp. itstermed here as secondelectronic control device that controls also the electronically operated pipetting of the pipetting apparatus 70 is configured to exchange signals resp. data, in particular data of a pipetting planning program and occupancy state data, via a signal connection, here a wireless data connection W, with the electronic control device of the base apparatus 10 of the pipette auxiliary system. The electronic control device of the pipetting apparatus 70 is configured to control the measurement arrangement via the electronic control device of the pipette auxiliary device and to receive the information on the occupancy state in form of occupancy state data. It would also be possible, that the electronic control device controls also the output devicethis means, that the electronic control device of the pipetting apparatus 70 can be deployed as the electronic control device of a pipette auxiliary system. The electronic control device is configured to detect the approach of the at least one sample transfer container 71 connected with the pipetting apparatus to the at least one sample holder by measurement by means of the measurement arrangement, and to control the pipetting apparatus such that it autonomously releases each intended volume to the at least one sample holder. The electronic control device or the second control device is configured to execute a pipetting planning program, according to which [0194] the information on each next at least one sample holder of the sample-holding arrangement intended as target position for pipetting is displayed to the user by means of the output device,here, a pipetting plan with a non successive pipetting at the wells, which is difficult to execute for the user without support, [0195] the manually operated approach of at least one sample transfer container to the sample-holding arrangement and the recognition of the position of the reached sample holder is detected by means of the measurement arrangement, [0196] it is detected by comparison with the planning data of the pipetting planning program whether the reached position is the intended target position according to the plan, [0197] and, in case the reached position is the intended target position according to the plan, a predefined sample volume is released automatically to the target position, [0198] and, in case the reached position is not the intended target position according to the plan, this automatic release is suppressed.
[0199] By means of a pipette auxiliary system according to the present invention users work without the risk of confusion at sample-holding arrangements consisting in particular of plates, stripes and vessels. The user knows always, which wells are to be filled next in a process, and which occupancy state is present in each sample holder. The base apparatus is a mobile, compact plate positioning tool with a small footprint. It can in particular be built into laboratory-workstations for the additional control of the executed experiments. A sample-holding arrangement can, if necessary, be fabricated as a closed system, in particular when using sample-holding arrangements fabricated by means of a two shot molding process that comprises in particular a conductive polymer as electrically conductive sections.
[0200] If required, a sample-holding arrangement can also be fabricated as open system, i.e. with openings or cavities for the insertion of e.g. capacitance sensor sheets or sensor columns (see FIG. 8a) that are arranged at the base apparatus.
[0201] FIG. 11a depicts a sample-holding arrangement 120 according to the second preferred embodiment of the invention in an exemplary embodiment as preferred component of an exemplary embodiment of the pipette auxiliary system according to the present invention 100. In contrast to the cavities 122, 123 in the embodiment example of FIG. 8a, the sample-holding arrangement 120 comprises here only one single cavity 122 that stretched underneath all sample holders 121 of the sample-holding arrangement 120, and which is opened to the bottom, so that measurement electrodes 116, 117 can reach into the cavity 122.
[0202] FIG. 11b depicts a base apparatus 110 according to the second preferred embodiment of the invention in an exemplary embodiment as preferred component of an exemplary embodiment of the pipette auxiliary system according to the present invention 100, that can be in particular utilized with the sample-holding arrangement in FIG. 11a. The measurement electrodes 116, 117 of the measurement arrangement 119 are connected via conductors 115a, 115b with the control device 113 and are tightly connected with the base apparatus 110 which is designed moreover as the base apparatus 110. The measurement electrodes 116, 117 reach from below along a fraction f=0.15 of the entire height of the positioning space into that.
[0203] FIG. 11c depicts a pipette auxiliary system 100, in working position, comprising the sample-holding arrangement of FIG. 11a and the base apparatus of FIG. 11b. In the working position, two measurement electrodes 116, 117 of a sensor device are arranged each in the range underneath a sample holder 121 and translated laterally with respect to it, so that the sample holder is encompassed by the electrical field that builds up between the electrodes 116 and 117 and that extends also into the range above the electrodes 116, 117. This will be explained in relation to FIG. 12a. The sample holders are of a cylindrical shape, but they can also be shaped conically or be rounded, or they can be shaped differently. As the electrical field generated by the measurement electrodes extends into the volume above this space between the electrodes, also the liquid placed in this range influences on the measurement resp. the liquid place there can be detected and the respective filling level can be distinguished from a different filling level, in which there is no liquid in the volume range above this space between the electrodes and the liquid is placed only in the space between the electrodes. The measurement arrangement 119 is particularly compact and robust.
[0204] FIG. 12a depicts a simplified lateral cross sectional view through a sensor device of an exemplary pipette auxiliary system measuring a capacitance by means of two planar plate-shaped electrodes 116, 117, in the filled state of the only depicted sample holder, with the sensor device corresponding to sensor devices depicted in FIGS. 11b and 11c. The sample-holding arrangement 120 and 120 as well as the sample holder 120 and 120 correspond to each other. A light element (not depicted) of the output device can be a component of each the sample-holding arrangement 120, 120 or the base apparatus 110, 110.
[0205] FIG. 12b depicts a simplified lateral cross sectional view through a sensor device of an exemplary pipette auxiliary system measuring a capacitance by means of two plate-shaped electrodes 116, 117, in the filled state of the only depicted sample holder. Here, the measurement electrodes 116, 117 of the sensor devices are integrated into the surface of the base apparatus 110. The measurement electrodes 116, 117 are here planar and plate-shaped and stretch parallel to the surface of the base apparatus. The measurement electrodes 116, 117 do not reach into the positioning space, in which, in the working position, the sample-holding arrangement 120 is arranged. Therefore, it does not require a cavity for inserting the measurement electrodes, but such a cavity would also be possible, as the electric field that effectuates the measurement extends into the volume range above the measurement electrodes in which also at least the lower section of the sample holder is arranged. By arranging the measurement electrodes in the range underneath the positioning space, this solution is particularly compact and robust. In particular, a protective layer or a coating can be provided above the measurement electrodes, without rendering the measurement ineffective. By this, one obtains a surface, which is easy to clean and that protects the measurement electrodes.
[0206] FIG. 12c depicts a sensor device that differs from the sensor device depicted in FIG. 12b by the fact that the plate-shaped electrodes 116 and 117 exhibit a larger area than the plate-shaped electrodes 116 and 117 from FIG. 12b. This area that extends parallel to the opening of the sample holder directed upwards and that extends in the present example also parallel to the planar bottom of the sample holder 121, is nearly as big as the bottom area and the average cross sectional area of the sample holder in vertical direction. The shape of the electrodes 116, 117 are that of a semicircle each, with the straight edges of the semicircles being parallel to each other and neighboringin the figure visible as the gap between the electrodes.
