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EP-4206679-B1 - PIPETTING TIP SCANNER

EP4206679B1EP 4206679 B1EP4206679 B1EP 4206679B1EP-4206679-B1

Inventors

  • STUMPF, MAX
  • VILAJ, Volfgang

Dates

Publication Date
20260506
Application Date
20211229

Claims (16)

  1. Method of measuring the alignment of one or more pipetting tips (2) in relation to a pipetting head (4) in an automated pipetting system (1) comprising: mounting the one or more pipetting tips (2) on one or more adapters (3) of the pipetting head (4) approximately perpendicular to the pipetting head (4) mounting surface, mapping the orifices (21) at the protruding end of the one or more pipetting tips (2) with an image capture device (5) comprising a sensor (6) placed in face and distant of the orifices (21), sending the acquired data from mapping the orifices (21) of the one or more pipetting tips (2) to a data processor (7), generating an image of the orifices (21) of the one or more pipetting tips (2) from said acquired data, determining the center positions of orifices (21) relative to the pipetting head (4), and calculating alignment information for the one or more pipetting tips (2) with respect to a virtual regular grid assumed to the pipetting head (4) mounting surface., characterized in that mapping the orifices (21) comprises scanning the orifices (21) by moving the pipetting head (4) and/or the sensor (6) relative to one another.
  2. The method according to claim 1, further comprising: determining the center positions of orifices (21) relative to the pipetting head (4) by sub-pixel interpolation of peaks or a pattern found in said image of the orifices (21) generated.
  3. The method according to anyone of claims 1 and 2, further comprising: moving the pipetting head (4) and/or the sensor (6) relative to one another with a known temporal profile of relative positions.
  4. The method according to anyone of claims 1 to 3, whereas calculating alignment information for the one or more pipetting tips (2) comprises converting the sub-pixel positions into positions in a measure of length.
  5. The method according to anyone of claims 1 to 4, whereas calculating alignment information for the one or more pipetting tips (2) comprises calibrating the sensor (6) with a calibrated image on an axis parallel to the pipetting head (4) and perpendicular to the movement axis of the pipetting head (4) and/or the sensor (6) relative to one another.
  6. The method according to anyone of claims 1 to 5, further comprising: creating a cross-correlation matrix from the scanned image and a template of a pipetting tip (2), and determining the center positions of orifices (21) of the one or more pipetting tips (2) by sub-pixel interpolation of peaks in the cross-correlation matrix.
  7. The method according to anyone of claims 1 to 6, further comprising: scanning the one or more adapters (3) of the pipetting head (4) with an image capture device (5) comprising a sensor (6) by moving the pipetting head (4) and/or the sensor (6) relative to one another, sending the acquired data from scanning the one or more adapters (3) to the data processor (7), calculating positions of the one or more adapters (3) in relation to the pipetting head (4), and using this information to calculate the alignment of the one or more pipetting tips (2) with respect to the one or more adapters (3) of the pipetting head (4).
  8. A computer program comprising instructions which, when the program is executed by a data processor (7), cause an automated pipetting system (1) to mount one or more pipetting tips (2) on one or more adapters (3) of a pipetting head (4) mounting surface, map the orifices (21) at the protruding end of the one or more pipetting tips (2) with an image capture device (5) comprising a sensor (6) placed in face and distant of the orifices (21), send the acquired data from mapping the orifices (21) of the one or more pipetting tips (2) to a data processor (7), generate an image of the orifices (21) of the one or more pipetting tips (2) from said acquired data, determine the center positions of orifices (21) relative to the pipetting head (4), and calculate alignment information for the one or more pipetting tips (2) with respect to a virtual regular grid assumed to the pipetting head (4) mounting surface., characterized in that the computer program further comprises instructions which, when the program is executed by a data processor (7), cause the automated pipetting system (1) to scan the orifices (21) at the protruding end of the one or more pipetting tips (2) with the image capture device (5) comprising a sensor (6) placed in face and distant of the orifices (21) by moving the pipetting head (4) and/or the sensor (6) relative to one another.
  9. The computer program according to claim 8 further comprising instructions which, when the program is executed by a data processor (7), cause an automated pipetting system (1) to determine the center positions of orifices (21) relative to the pipetting head (4) by sub-pixel interpolation of peaks or a pattern found in said image of the orifices (21) generated, and convert the sub-pixel positions into positions in a measure of length.
  10. The computer program according to anyone of claims 8 to 9 further comprising instructions which, when the program is executed by a data processor (7), cause an automated pipetting system (1) to create a cross-correlation matrix from the scanned image and a template of a pipetting tip (2), and determine the center positions of orifices (21) of the one or more pipetting tips (2) by sub-pixel interpolation of peaks in the cross-correlation matrix.
  11. The computer program according to anyone of claims 8 to 10 further comprising instructions which, when the program is executed by a data processor (7), cause an automated pipetting system (1) to scan the one or more adapters (3) of the pipetting head (4) with an image capture device (5) comprising a sensor (6) by moving the pipetting head (4) and/or the sensor (6) relative to one another, send the acquired data from scanning the one or more adapters (3) to the data processor (7), calculate positions of the one or more adapters (3) in relation to the pipetting head (4), and use this information to calculate the alignment of the one or more pipetting tips (2) with respect to the one or more adapters (3) of the pipetting head (4).
  12. Contactless measurement system (10) for measuring the alignment of one or more pipetting tips (2) in an automated pipetting system (1) comprising: one or more adapters (3) on a pipetting head (4) connected to a robotic pipetting arm (11) for mounting the one or more pipetting tips (2), an image capture device (5) comprising a sensor (6) joined to a worktable (9) for capturing an image of the orifices (21) of the one or more pipetting tips (2) or of the one or more adapters (3) of the pipetting head (4), a data processor (7) for receiving the image data acquired by the sensor (6), for calculating alignment information for the one or more pipetting tips (2) with respect to a virtual regular grid assumed to the pipetting head (4) mounting surface, characterized in that the contactless measurement system (10) further comprises a mechanism for moving the pipetting head (4) and/or the sensor (6) relative to one another for scanning the orifices (21) at the protruding end of the one or more pipetting tips (2) or the one or more adapters (3) of the pipetting head (4).
  13. The contactless measurement system (10) according to claim 12, whereas the image capture device (5) comprises a light source (8) for illuminating the object to be scanned, and an optical subsystem reflecting the object to be scanned onto the sensor (6).
  14. The contactless measurement system (10) according to anyone of claims 12 to 13, whereas the image capture device (5) is a flatbed document scanner.
  15. Use of a contactless measurement system (10) according to anyone of claims 12 to 14 in an application for pipetting liquid samples, whereas the contactless measurement system (10) assists in analyzing the position of one or more pipetting tips (2) in an automated pipetting system (1).
  16. Automated pipetting system (1) comprising a contactless measurement system (10) according to one of the claims 12 to 14.

Description

The present invention relates generally to a method and system for contactless measurement of an array of objects and for confirming the correct positioning of objects in an automated system. Specifically, the invention relates to a method and system for screening the pipetting tip positions in an automated pipetting system and for calculating and confirming the correct positioning of pipetting tips in an automated pipetting system. Contactless measurement systems use a range of physical properties to sense the environment, e.g., light, electricity, magnetic fields, and temperature. Contactless measurement systems can be used for laboratory automation arrangements, where they may be used for measuring and confirming the correct positioning of objects, and where contactless measurement systems are essential for a constant monitoring of a number of parameters. In many of these applications, especially when working with biologic or hazardous samples, it is important that the measurement system used is contactless. The risk for contamination can be kept minimal or can be eliminated completely, depending on the requirements. Contactless measurement systems can for example detect liquid levels in tubes and microwell plates, or it can sense the temperature of liquids. It may be desirable to measure the position of labware before a protocol is started. This can help to avoid the abandonment of a procedure and having to go back to the beginning of a protocol which comes with a loss of time and material. When working with smallest amounts of for example biologic material, as can be the case in forensics or tumor detection, a disruption due to a misalignment of laboratory equipment can be a most damaging event. In high-throughput laboratory protocols, pipetting in and out of multi-well plates, e.g., 96-well or 384-well plates, can be done with pipetting arrangements allowing the mounting of up to 96 or 384 pipettes at a time. These numerous pipettes in close proximity have to be mounted on the moveable robotic arm so that they are arranged in a parallel fashion and perpendicular to the working table. If one pipetting tip is slightly bent or not aligned properly, this may be enough to lead to the disruption mentioned above. To detect such deviations before the run is started, the coordinates of the lower ends of the pipetting tips, also called orifices, may be measured. US20200191812A1 addresses an image capture device for capturing images of barcodes of test tubes in a test tube rack, for use with automated robotic systems used in research and analytic laboratories in pharmaceutical, biotechnology and veterinary industries. The image capture device has a transparent window adjacent to the test tube rack to be imaged. A lighting arrangement illuminates the barcodes, and a mirror is arranged to relay light rays reflecting from the barcodes to the camera. An interface is provided for outputting the captured image to a host computer for decoding of the barcodes. WO 2012/158308 A2 addresses a system for tracking a position of a pipette with respect to a multi well plate targeted at applications for pipetting reagents, e.g., solid reagents such as pills, for use in immunoassays and DNA analysis in clinical diagnostics and forensic laboratories. This system tracks the dispensing and extracting of reagents to and from arrays of well locations. It selectively illuminates locations to indicate the progress of pipetting operations. A control logic (CPU or microcontroller) can guide the user through pipetting processes and indicate errors. A capacitive sensor detects positions of a pipette with respect to the locations in the area or with reference to X- and Y-axis. A control logic coupled to the sensor and a well designator develops the control signals in response to the detected positions. It has a touchscreen display with a user-interface area. US20200376672 discloses a detector for generating 3D position information of an object positioned in a position determination space by producing at least two images of the object in the determination space. EP1489425 discloses a position detector where an object is moved by a robotic system within scanning beams and the shading of the scanning beams is observed synchronously. This known solution for contactless measuring and tracking the position of pipetting tips in the state of the art is restricted to capturing the position of only one pipetting tip at a time. On the other hand, the known image capture device that may cover a larger area, namely a test tube rack, is constructed such that it captures images of barcodes of test tubes in a test tube rack only, while it does not calculate and confirm the correct positioning of an array of pipetting tips in an automated pipetting system. It is thus an object of the present invention to provide for a method of measuring the alignment of one or more pipetting tips in an automated pipetting system and of delivering alignment information for