WO2009040274A2 - Positionnement automatisé d'un outil de prélèvement pour le prélèvement d'objets cellules - Google Patents
Positionnement automatisé d'un outil de prélèvement pour le prélèvement d'objets cellules Download PDFInfo
- Publication number
- WO2009040274A2 WO2009040274A2 PCT/EP2008/062322 EP2008062322W WO2009040274A2 WO 2009040274 A2 WO2009040274 A2 WO 2009040274A2 EP 2008062322 W EP2008062322 W EP 2008062322W WO 2009040274 A2 WO2009040274 A2 WO 2009040274A2
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- removal tool
- tool
- removal
- cell
- receiving element
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Ceased
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Classifications
-
- G—PHYSICS
- G02—OPTICS
- G02B—OPTICAL ELEMENTS, SYSTEMS OR APPARATUS
- G02B21/00—Microscopes
- G02B21/32—Micromanipulators structurally combined with microscopes
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M33/00—Means for introduction, transport, positioning, extraction, harvesting, peeling or sampling of biological material in or from the apparatus
- C12M33/04—Means for introduction, transport, positioning, extraction, harvesting, peeling or sampling of biological material in or from the apparatus by injection or suction, e.g. using pipettes, syringes, needles
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N1/00—Sampling; Preparing specimens for investigation
- G01N1/02—Devices for withdrawing samples
- G01N1/04—Devices for withdrawing samples in the solid state, e.g. by cutting
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N1/00—Sampling; Preparing specimens for investigation
- G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
- G01N1/2813—Producing thin layers of samples on a substrate, e.g. smearing, spinning-on
- G01N2001/282—Producing thin layers of samples on a substrate, e.g. smearing, spinning-on with mapping; Identification of areas; Spatial correlated pattern
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N1/00—Sampling; Preparing specimens for investigation
- G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
- G01N1/286—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q involving mechanical work, e.g. chopping, disintegrating, compacting, homogenising
- G01N2001/2873—Cutting or cleaving
- G01N2001/288—Filter punches
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N35/0099—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor comprising robots or similar manipulators
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
- G01N35/1009—Characterised by arrangements for controlling the aspiration or dispense of liquids
- G01N35/1011—Control of the position or alignment of the transfer device
Definitions
- the invention relates to a method for the automated positioning of a removal tool for the removal of cell objects and uses of the method. Furthermore, the invention relates to a device for automated positioning of a removal tool.
- a cell object For harvesting very small cell colonies, single cells or parts of cell colonies or single cells, hereafter generally referred to as a cell object, is a very accurate positioning of a picking tool received by a picking element, i. a capillary or cannula, in a certain, small difference height above the cell object to be harvested necessary.
- a picking element i. a capillary or cannula
- Calibration of the used extraction tool prior to removal of the cell object known that allows accurate positioning of not exactly the same removal tools. Calibration is performed by making each picking tool perpendicular to each other by means of two in a horizontal plane running and minimally offset in the vertical direction laser beams is measured. The tip of the extraction tool is then moved to a fixed auxiliary point that represents the origin of a coordinate system. From there, a movement of the removal tool then takes place to the cell object.
- sample containers used in laboratories in the form of petri dishes and titer plates of very different sizes, shapes and materials pose a major problem.
- These commonly used sample containers do not have sufficiently flat bottoms to perform the calibration with a one-time calibration step or a reasonable number of calibration steps set the corresponding height position of the tip of the removal tool for the sample container to be processed in general.
- the application of high-precision containers is very cost-intensive and not possible for many applications due to the required special coatings.
- the invention is therefore based on the object of enabling a more accurate positioning of the removal tool relative to the cell object to be removed.
- the object is achieved in a method for the automated positioning of a removal tool for removal of cell objects, the removal tool being received by a receiving element on a tool head, the spatial position of the cell object being recorded in a sample container by means of an image acquisition unit and an image evaluation unit, and the removal tool be moved by means of a control and storage unit and a traversing mechanism first in a calibration position and then in a position above the cell object. Subsequently, the image acquisition unit and the image evaluation unit also detect the spatial position of the removal tool above the cell object and determine a deviation from the required position.
- Control and storage unit then corrects the position of the removal tool by means of the movement mechanism.
- Detecting and correcting the position of the picking tool over the cell object allows a high precision positioning of the picking tool prior to picking up the cell object.
- the essential advantage of this complete calibration is that no expensive ancillary equipment, such as e.g. is described in DE 10 253 939 Al, is needed.
- the image acquisition unit and the image evaluation unit detect the vertical position of the removal tool in the calibration position.
- the removal tool is then raised and moved to the cell object, detects the vertical position of the cell object and the vertical distance of the removal tool for Cell object reduced to a predetermined differential height.
- the distance between the removal tool and the cell object is optimally adjusted. This is particularly advantageous on uneven floors of sample containers in which the vertical position of the cell objects varies.
- the image acquisition unit detects the position of the removal tool and / or the cell object by means of a focusing system.
- the focusing system makes it possible to determine the vertical position of the removal tool or of the cell object.
- the removal tool is expediently moved vertically toward the cell object and the tool head and / or the receiving element and / or the removal tool are cushioned in the event of a collision of the removal tool with the bottom of the sample container.
- the cushioning prevents deformation or breakage of the sensitive removal tools, which are often made of glass.
- the image acquisition unit and the image evaluation unit monitor the movement of the removal tool and send a signal to the controller in the event of a collision. In this way, the components already present, i. E. the image acquisition unit and the image evaluation unit, a collision to the system or to the user are reported.
- a sensor on the removal tool and / or receiving element and / or tool head preferably detects a relative movement between the removal tool and the receiving element and / or between the receiving element and the tool head and sends a signal to the controller.
- a sensor represents a simple but highly effective means of detecting a collision.
- the controller stops the movement of the removal tool by means of the movement mechanism and moves the removal tool into a position with a predetermined vertical distance to the bottom of the sample container.
- the method is preferably used for removing cell objects from containers with uneven bottoms in the field of cell biology or biochemistry, in particular in the case of beads. Precision is particularly important in this area because of the microscopically small dimensions of the cell objects.
- the object is achieved by a device according to the invention for the automated positioning of a removal tool for the method described above.
- the removal tool is by means of a receiving element on a
- the device has at least one image recording unit with an image evaluation unit, a controller and a travel mechanism.
- the image acquisition unit, the image evaluation unit, the control and the travel mechanism form a control loop for positioning of the removal tool.
- the control loop allows a highly precise adjustment of the position of the removal tool.
- the image acquisition unit expediently comprises a microscope unit with a motorized focusing system.
- a microscope unit is particularly well suited for detecting the cell objects.
- a motorized focusing system also allows high-precision measurement of the vertical position of the target or picking tool.
- the motorized focusing system comprises an autofocus device.
- the automatic focusing device can further automate the detection of the vertical position of the target or picking tool.
- the tool head on a suspension for the receiving element and / or the receiving element on a suspension for the removal tool.
- the suspension prevents deformation or breakage of the sensitive sampling tool in a collision with the bottom of the sample container.
- the tool head and / or the receiving element and / or the removal tool comprise at least one sensor. With the help of the sensor, a collision of the removal tool with the bottom of the sample container can be detected with a simple means.
- the senor is an optical sensor, in particular a light barrier.
- Optical sensors are a proven means of detecting movement. The method according to the invention will be described below with reference to a device for the automated positioning of a removal tool and three exemplary embodiments. Show it :
- Fig. 2 is a removal tool and a Z-stack.
- the device comprises a microscope unit 1 with a number of optical components, in particular an arrangement of deflection prisms 1 a and a lens system 1 b for beam guidance and microscopic imaging.
- the microscope unit 1 is coupled to an image acquisition unit 2, usually a CCD camera or a CCD array.
- An image evaluation unit 3a is provided for processing the image information read from the image acquisition unit 2.
- the image evaluation unit 3a is located in a personal computer 3 and has a running on its BiId processing software.
- a control and storage unit 4 is provided, which is integrated in the personal computer 3 and whose functions by further software compo- be executed.
- the control and storage unit 4 has a monitor or a display 4a.
- the apparatus further includes a harvesting module 5 mounted on a traveling mechanism.
- the traversing mechanism consists of a lifting column 5a and a traverse drive 5b and is controlled by the control and storage unit 4.
- the lifting column 5a and the traversing drive 5b are designed for longer travel distances and serve to bring the harvesting module 5 to a cell culture located in a sample container 8 and a coarse adjustment of the harvesting module 5 whose removal tool 10a held on a tool head 10 can be moved over the sample container 8.
- the highly precise positioning of the removal tool 10a above a cell object located in the sample container 8 takes place by means of a control loop, which is formed from the image acquisition unit 2, the image evaluation unit 3a, the control and storage unit 4 and the movement mechanism. After picking up the cell object by means of the picking tool 10a, the lifting column 5a and the traveling drive 5b move the picking tool 10a to the corresponding separating stations 11 for the removed cell objects.
- the mentioned microscope unit 1 is designed as a transmitted-light microscope.
- a lighting 6 with a number of switchable illumination filters 7 is provided.
- the illumination 6 radiates through the cell culture in the sample container 8.
- the sample container 8 is mounted on a motorized xy-table 9, with which the cell culture with a microscopic setting accuracy of a few micrometers in both the x and y direction under the optical arrangement of illumination 6 and underlying deflection prism Ia can be moved.
- the positioning coordinates of the xy table become 9 transferred to the storage and control unit 4 and set by the storage and control unit 4.
- the microscope unit 1 consists of a commercially available inverted microscope stand on which the motorized xy table 9 is located. Optionally, this microscope unit 1 can also be equipped with a commercially available fluorescence device. In addition, the CCD-chip image pickup unit 2 is mounted on the microscope unit 1, by means of which scanning of the cell objects is possible.
- motorized focus system allows a precise detection of the position of each cell object to be recorded.
- the motorized focus system also includes an autofocus function, which automates the detection of the position of the cell object.
- the commercial personal computer 3 is connected via a network connection with the microscope unit 1 and the movement mechanism.
- a commercially available standard image processing software runs on the personal computer 3, which together with the control and storage unit 4, the image evaluation unit 3a and modules for this image processing software takes over the control of the movement mechanism and the analysis of the image data.
- the removal tool 10a is positioned.
- the movement of the xy stage 9 serves to pre-position the cell culture for a removal of the found cell objects.
- the harvesting module 5 is positioned by the traversing mechanism over the cell culture, while the xy-table 9 on the previously determined positions of the found Cell objects is set and the harvesting module 5 allows removal of the cell objects.
- the removal module 5 has the tool head 10, which is equipped with a lowering and suction mechanism. At the end of the tool head 10 is a conical receiving element for receiving the removal tool 10a.
- the position of the removal tool 10a is detected by the image acquisition unit 2 and, if necessary, precisely corrected by means of the control loop, as described in the following first and third embodiments.
- the removal of the cell objects from the cell culture located in the sample container 8 requires a lowering of the removal tool 10a to the respective cell object.
- a collision of the removal tool 10a with the bottom of the sample container 8 may occur. Therefore, the tool head 10 has a suspension for the receiving element and / or the removal tool 10 a, which absorbs the collision, and a sensor which is arranged on the tool head, on the receiving element or on the removal tool. The sensor reports the collision to the control and storage unit 4 to prevent damage to the picking tool 10a, as described in the second embodiment. Then the respective cell object is taken up.
- the recorded cell objects are stored in a separation battery 11.
- This consists of a series of test tubes or tubes, which can be approached individually by the lifting column 5a and the travel drive 5b and into which the removed by the tool head 10, the removed cell objects.
- the separating stations 11 may also be formed in parts as a magazine for providing removal tools 10 a, which are coupled by a not-shown conical receiving element which is attached to the tool head 10 and the removal tool 10 a, coupled to the tool head 10.
- the conical shape of the receiving element leads to a self-centering of the partially highly precise to be positioned removal tools 10a during recording.
- the removal tool 10a can be removed by a simple, not shown stripping back from the receiving element to allow a recording of the next removal tool 10a.
- the functions described here in principle are controlled by the memory and control unit 4 and run essentially fully automatically.
- the known input means such as keyboard and mouse and a corresponding user interface with the software components running within the memory and control unit 4
- the user has a number of possibilities for influencing the function.
- an adjustment of the magnification factor and a change in the resolution of the image pickup unit 2 is possible.
- an addressing of the harvesting module 5 is possible, in which menu-controlled individual cell objects determined by the microscope unit are selected and assigned to a specific location in the separating battery 11 can be.
- it is also possible to determine an operating mode of the harvesting module 5 in which, depending on the selected cell objects, certain removal tools 10a are received by the conical receptacle of the tool head 10 in order to remove the selected cell objects in a specific manner.
- the horizontal position of the picking tool 10a over the cell object is preset by the manufacturing and recording accuracy as well as the positioning accuracy of a calibration.
- the problem is that the vertical position of cell objects will vary due to uneven bottoms of the sample containers 8 and at least the vertical position of the sampling tool over the cell object may need to be corrected.
- a microscopic optics has only very narrow depth of field.
- a motorized microscope due to the motorisation of the focus drive and a corresponding feedback, e.g. via coupled encoders, which can determine the position of the focusing drive, it is possible to determine the vertical position of easily recognizable objects, i. of the cell object or the removal tool 10a, to automatically determine within the image area via a corresponding image processing function.
- Prerequisite is only a positioning of the cell object or the removal tool 10a in the search area of the autofocus function.
- This area corresponding to the number of images that need to be captured and analyzed as the Z-stack 16, the faster the determination of the vertical position of the object can be made.
- Fig. 2 shows the Z-stack 16, which results from the vertical scanning of the cell culture for determining the vertical position of the cell object.
- a predefined area with an upper limit 12 and a lower limit 13 is scanned in the vertical direction. Similar to the horizontal scanning, in which a sequence of images of the samples takes place, this also happens in the vertical direction.
- the image boundary to the next image is the depth of field 15 of the selected optical system.
- the degree of severity is determined. The image with the highest degree of sharpness is the image in a vertical position closest to the capillary tip. The fewer images needed for analysis, the faster the calibration.
- the method can therefore be applied flexibly according to the respective required accuracies.
- the positioning procedure is as follows:
- the horizontally movable xy-table 9 is equipped with a sample container 8 with a cell culture.
- the receiving element receives a picking tool 10a.
- the xy table 9 is moved to a calibration position within the optical axis of the microscope, wherein a hole in the xy table 9 allows a clear view of the tip of the removal tool 10a to be positioned in this area.
- a method of the receiving element with the removal tool 10a to the calibration position is performed by the measurement position.
- the autofocus function of the image evaluation unit 3a is applied to determine the vertical position of the tip of the extraction tool 10a.
- the limits of the search range of the autofocus function can be specified via the production tolerances and positioning accuracies of the travel mechanism.
- the next step is to read the motor position of the focusing drive in the autofocus position.
- the vertical position of the cell object is detected by the autofocus function.
- the vertical positions of the extraction tool and the cell object are compared, and the optimal vertical position, i. the predetermined difference height of the removal tool 10a is set above the cell object located in the sample container 8.
- the cell object is picked up by the picking tool 10a.
- a new calibration takes place.
- the receiving element is provided with a sensor which signals a collision of the removal tool 10a with the bottom of the sample container. Due to the special construction of the tool head according to DE 10 2004 046 740, it deviates from the bottom of the sample container in the event of a collision of the removal tool and thus enables a detection of the collision without destroying the removal tool 10a.
- the signal is forwarded to the control and storage unit 4, which stops the downward movement of the receiving element immediately and raises the removal tool 10a again to a predetermined distance, so that the removal tool 10a floats over the object to be removed at a defined vertical distance. Since the removal tools 10a used in this embodiment are very thin, fragile needles, the combination of varying tool head 10 and sensitive switching sensor is important in order to avoid a permanent deformation or even destruction of the capillaries.
- the xy table 9 is equipped with a sample container 8 with a cell culture. Thereafter, a removal tool 10a is received by means of a suitable receiving element. Next, the sample container 8 is scanned. The removal tool 10a is moved to a desired cell object and positioned over the cell object. Following this, the receiving element is lowered slowly.
- the tool head with the removal tool 10a now remains in the forced by the impact on the bottom of the sample container 8 vertical position, while the receiving element itself, to which the corresponding sensor is mounted, further lowers. Due to the relative movement between the tool head 10 and the receiving element, a signal is triggered by the sensor, which signals to the control and storage unit 4 of the movement mechanism that the bottom of the sample container 8 was achieved. When the sensor signal is applied, the vertical position of the receiving element is stored and the lowering of the receiving element is set immediately.
- the vertical position to be approached is determined in order to obtain optimum recording conditions.
- the receiving element is raised to the determined position and the cell object is received.
- the detection of the collision by the sensor takes place in detail by detecting a slight movement of the deviating tool head upwards through a fine light beam of a light barrier. This is adjusted so that it is just covered in the rest position of the tool head by its lower edge so far that the sensor is not yet triggered. After reaching the bottom of the sample container through the tip of the removal tool 10 a, the solid or a conical
- Receiving element is connected to the tool head 10, there is a further lowering of the receiving element.
- the tool head 10 remains at the same height.
- the sensor head located on the receiving element also moves further downward, while the tool head 10 shadowing the light beam of the sensor moves upwards relative to the sensor and releases the covered sensor part of the sensor.
- the sensor detects the now incident light and triggers in the sensor unit a switching operation, which signals the collision by an electrical signal at the sensor output to the control and storage unit 4.
- the collision is now known to the control and storage unit 4, which reacts accordingly. greases, the lowering of the receiving element stops and moves to the preset difference height.
- the travels after the collision can be minimized in the range of a few microns up to a few hundredths of a millimeter.
- the difference height can be adjusted by this method with an accuracy in the range of a few micrometers.
- Glass capillaries are mainly used for the uptake of single cells and are therefore correspondingly small at their tip, with openings of up to 1 ⁇ m for patch clamp tests or injections into a single cell.
- the position of the glass capillary can be checked, and by adjusting the focus and readjusting the vertical drive of the tool head 10, a fine adjustment of the glass capillary can be made to the correct position over the cell.
- a fast interaction between image recognition, image processing, control and storage unit 4 and traversing mechanism is a prerequisite for this process.
- a microscope optical system has only very narrow depth of field. Thus, it is with a motorized microscope, due to the mo- torizing of the focusing drive and a corresponding
- a suitable image recognition can determine the horizontal position of the tip of the glass capillary within the image field and output the difference from the image center, to which the removal tool is calibrated, as correction values to the control and storage unit 4 of the movement mechanism. Prerequisite is only the positioning of the glass capillary in the image and search area of the autofocus function and a position detection in the image plane. The smaller this area, corresponding to the number of images taken as a Z-stack and to be analyzed, the faster the determination of the vertical position of the glass capillary can be made.
- the method has substantially the same steps as the method for the special vertical positioning (see Example 1):
- the horizontally movable xy-table 9 is equipped with a sample container 8 with a cell culture.
- the receiving element receives a picking tool 10a.
- the xy table 9 is moved to a calibration position within the optical axis of the microscope, wherein a hole in the xy table 9 allows a clear view of the capillary tip to be positioned in this area.
- a method of the receiving element with the removal tool 10 a to the calibration position.
- the autofocus function of the image evaluation unit 3a is applied to determine the vertical position of the capillary tip.
- the limits of the search range of the autofocus function can be specified via the manufacturing tolerances and positioning accuracies of the travel mechanics.
- the image acquisition unit 2 performs a horizontal position detection for determining the position of the center of the tip of the glass capillary in the image plane.
- the next step is, as in the first embodiment, a readout of the motor position of the focusing drive in the autofocus position.
- the complete spatial coordinates of the capillary tip are transferred to the control and storage unit 4 of the movement mechanism. Furthermore, a done
- the basis for the correction values is a zero position in the image area, to which the starting position of the removal tool 10a is set and to which the detected cell object is positioned for recording. This zero position usually corresponds to the center of the picture.
- the rest of the process corresponds again to the first embodiment: There is a lifting of the receiving element with the removal tool.
- the sample container 8 is subsequently scanned, possibly with the autofocus function.
- the receiving element is moved with the removal tool 10a to a male Zellmony.
- the vertical position of the cell object is detected by the autofocus function.
- the vertical positions of the extraction tool 10a and the cell object are compared, and the optimum vertical position, i. the predetermined difference height of the removal tool 10 a is set above the cell object located in the sample container 8.
- the cell object is picked up by the removal tool 10a. After a change of the removal tool 10a, a new calibration takes place.
- a new calibration takes place.
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Abstract
L'invention concerne un procédé pour le positionnement automatisé d'un outil de prélèvement pour le prélèvement d'objets cellules. Selon l'invention, l'outil de prélèvement est logé dans un élément récepteur sur une tête d'outil, la position spatiale de l'objet cellule dans un contenant d'échantillons est détectée au moyen d'une unité de prise de vue et d'une unité d'évaluation d'image et l'outil de prélèvement est déplacé au moyen d'une unité de commande et de stockage et d'un mécanisme de déplacement d'abord dans une position d'étalonnage, puis dans une position au-dessus de l'objet cellule. Pour permettre un positionnement plus précis de l'outil de prélèvement par rapport à l'objet cellule à prélever, l'unité de prise de vue et l'unité d'évaluation d'image détectent ensuite également la position spatiale de l'outil de prélèvement au-dessus de l'objet cellule et déterminent un écart par rapport à la position requise. L'unité de commande et de stockage corrige alors la position de l'outil de prélèvement au moyen du mécanisme du déplacement.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE102007046267.2 | 2007-09-20 | ||
| DE200710046267 DE102007046267A1 (de) | 2007-09-20 | 2007-09-20 | Automatische Positionierung eines Entnahmewerkzeugs zur Entnahme von Zellobjekten |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| WO2009040274A2 true WO2009040274A2 (fr) | 2009-04-02 |
| WO2009040274A3 WO2009040274A3 (fr) | 2009-08-06 |
Family
ID=40343699
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/EP2008/062322 Ceased WO2009040274A2 (fr) | 2007-09-20 | 2008-09-16 | Positionnement automatisé d'un outil de prélèvement pour le prélèvement d'objets cellules |
Country Status (2)
| Country | Link |
|---|---|
| DE (1) | DE102007046267A1 (fr) |
| WO (1) | WO2009040274A2 (fr) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106995779A (zh) * | 2017-05-03 | 2017-08-01 | 浙江天科高新技术发展有限公司 | 一种用于管道内壁及夹缝表面的微生物采样器及其采样方法 |
| WO2019025626A1 (fr) * | 2017-08-04 | 2019-02-07 | Als Automated Lab Solutions Gmbh | Adaptateur pour la réception d'un capillaire et son utilisation |
| CN112146954A (zh) * | 2020-09-22 | 2020-12-29 | 广州海研生物科技有限公司 | 生物封片设备 |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2378341A1 (fr) | 2010-04-15 | 2011-10-19 | Mmi Ag | Procédé de positionnement sans collision d'un outil de micromanipulation |
| EP2579019A4 (fr) * | 2010-05-28 | 2018-04-25 | Olympus Corporation | Trieur de cellules, système de tri de cellules, et procédé de tri de cellules |
| DE102010035104A1 (de) * | 2010-08-23 | 2012-04-05 | Euroimmun Medizinische Labordiagnostika Ag | Vorrichtung und Verfahren zur automatischen Fokussierung für die Mikroskopie schwach leuchtender Substrate |
| DE102012104708B3 (de) * | 2012-05-31 | 2013-07-18 | Dionex Softron Gmbh | Verfahren zur Probenaufnahme |
| DE102013216938B3 (de) * | 2013-08-26 | 2015-01-08 | Leica Microsystems Cms Gmbh | Verfahren zur Kalibrierung einer Laserablenkeinrichtung einesLasermikrodissektionssystems und Lasermikrodissektionssystem |
| DE102022102711A1 (de) | 2022-02-04 | 2023-08-10 | Lpkf Laser & Electronics Aktiengesellschaft | Vorrichtung und ein zur Durchführung bestimmtes Verfahren zur Untersuchung und/oder Behandlung einer insbesondere biologischen oder medizinischen Probe |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20040257561A1 (en) * | 2000-11-24 | 2004-12-23 | Takao Nakagawa | Apparatus and method for sampling |
| DE10136572B4 (de) * | 2001-07-27 | 2005-11-17 | Eppendorf Ag | Vorrichtung zur optisch kontrollierten Mikromanipulation von biologischen Objekten |
| DE10253939A1 (de) | 2002-11-19 | 2004-06-17 | Cetoni Gmbh Innovative Informationssysteme | Verfahren zur exakten dreidimensionalen Mikropositionierung von Körpern unterschiedlicher Geometrie und/oder Abmessungen im Raum |
| DE102004046740B4 (de) | 2004-06-07 | 2006-07-06 | Aviso Gmbh Mechatronic Systems | Werkzeugkopf für eine Vorrichtung zur automatischen Isolierung und Behandlung von Zellklonen |
| DE102005053669B4 (de) * | 2005-11-08 | 2007-12-13 | Kilper, Roland, Dr. | Probenmanipulationsvorrichtung |
-
2007
- 2007-09-20 DE DE200710046267 patent/DE102007046267A1/de not_active Withdrawn
-
2008
- 2008-09-16 WO PCT/EP2008/062322 patent/WO2009040274A2/fr not_active Ceased
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106995779A (zh) * | 2017-05-03 | 2017-08-01 | 浙江天科高新技术发展有限公司 | 一种用于管道内壁及夹缝表面的微生物采样器及其采样方法 |
| CN106995779B (zh) * | 2017-05-03 | 2023-06-02 | 浙江天科高新技术发展有限公司 | 用于管道内壁及夹缝表面的微生物采样器及其采样方法 |
| WO2019025626A1 (fr) * | 2017-08-04 | 2019-02-07 | Als Automated Lab Solutions Gmbh | Adaptateur pour la réception d'un capillaire et son utilisation |
| US11738335B2 (en) | 2017-08-04 | 2023-08-29 | Als Automated Lab Solutions Gmbh | Adapter for receiving a capillary |
| CN112146954A (zh) * | 2020-09-22 | 2020-12-29 | 广州海研生物科技有限公司 | 生物封片设备 |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2009040274A3 (fr) | 2009-08-06 |
| DE102007046267A1 (de) | 2009-04-02 |
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