IDENTIFICATION OF SAMPLE CELLS IN A CHROMATOGRAPHY AUTOSAMPLER
20230204610 · 2023-06-29
Inventors
- Daniel Hoffmeyer (Santa Clara, CA, US)
- Husam Al-Esawi (El Dorado Hills, CA, US)
- Tobias Metz (Germering, DE)
- Til Richardsen (Kirchseeon, DE)
- Christoph Hollnagel (Gauting, DE)
Cpc classification
G01N2035/00831
PHYSICS
G01N2035/00801
PHYSICS
G01N35/00732
PHYSICS
International classification
G01N35/00
PHYSICS
Abstract
Methods and systems are provided for the identification of sample cells in a sample tray that is placed in a chromatography autosampler. A cell gripper and labels are also provided to facilitate such identification.
Claims
1. A method for identification of sample cells of a sample tray placed in a chromatography autosampler, each sample cell having (i) a container having a side wall, and (ii) a cap having an end surface visible from the sample tray, the method comprising: top scanning, with a camera assembly of a machine vision (MV) module of the autosampler, the end surfaces of all the sample cells; and determining, with a computing device, an identity of each of the sample cells within the sample tray based upon the top scanning; wherein the computing device controls the MV module.
2. The method according to claim 1, wherein the sample tray includes a machine-readable tray identifier, and wherein top scanning includes scanning the tray identifier.
3. The method according to claim 1, further comprising determining the position of each of the sample cells within the sample tray based upon a unique label affixed to a respective end surface of each sample cell.
4. The method according to claim 1, wherein the chromatography autosampler comprises the computing device.
5. The method according to claim 1, further comprising: gripping, lifting, and rotating, with a cell gripper of the autosampler, each of the sample cells such that each of the sample cells is gripped while in the sample tray, lifted from the sample tray, and rotated above adjacent sample cells of the sample tray; side scanning, with the MV module, the side walls of each of the sample cells, with the camera assembly; and returning, with the cell gripper, each of the sample cells to the sample tray.
6. The method according to claim 5, wherein the rotating includes rotating each of the sample cells about 540°.
7. The method according to claim 5, wherein the side scanning includes scanning a bar-code label provided on the side wall of each of the sample cells.
8. The method according to claim 5, wherein the side wall of each sample cell is translucent or transparent, and wherein the side scanning includes determining (i) a top liquid level within each sample cell, and (ii) a bottom liquid level at a lowermost portion of an inner volume of each sample cell.
9. The method according to claim 8, wherein the method further comprises (i) determining the amount of a sample within each sample cell based upon the top liquid level within a respective sample cell, (ii) adjusting the needle position based upon the top liquid level and the bottom liquid level within a respective sample cell, and/or (iii) limiting an insertion depth of the sample needle based upon a position of the bottom liquid level of a respective sample cell.
10. The method according to claim 5, wherein the container and/or cap of each sample cell includes an identifying color, and wherein at least one of the top scanning and side scanning includes scanning the identifying color.
11. The method according to claim 5, the method further comprising comparing, with the computing device, the top scanning and the side scanning to determine whether a gripped sample cell is the correct sample cell for further processing.
12. The method according to claim 1, the method further comprising aspirating a sample from each of the sample cells with a sampling needle assembly, separating analytes of the sample with a chromatography column, and detecting said analytes of the sample with a chromatography detector.
13. A method for identification of sample cells of a sample tray placed in a chromatography autosampler, each sample cell having (i) a container having a side wall, and (ii) a cap having an end surface visible from the sample tray, the method comprising: gripping, lifting, and rotating, with a cell gripper of the autosampler, each of the sample cells such that each of the sample cells is gripped while in the sample tray, lifted from the sample tray, and rotated above adjacent sample cells of the sample tray; side scanning, with a camera assembly of a machine vision (MV) module of the autosampler, the side walls of each of the sample cells; and returning, with the cell gripper, each of the sample cells to the sample tray.
14. The method according to claim 13, further comprising: top scanning, with the camera assembly of the MV module, the end surfaces of all the sample cells.
15. The method according to claim 14, further comprising: determining, with a computing device, an identity of each of the sample cells within the sample tray based upon the top scanning and/or the side scanning; wherein the computing device also controls the MV module and the cell gripper.
16. The method according to claim 15, wherein the chromatography autosampler comprises the computing device.
17. The method according to claim 14, wherein the sample tray includes a machine-readable tray identifier, and wherein top scanning includes scanning the tray identifier.
18. The method according to claim 13, wherein the rotating includes rotating each of the sample cells about 540°.
19. The method according to claim 13, wherein the side scanning includes scanning a bar-code label provided on the side wall of each of the sample cells.
20. The method according to claim 13, wherein the side wall of each sample cell is translucent or transparent, and wherein the side scanning includes determining (i) a top liquid level within each sample cell, and (ii) a bottom liquid level at a lowermost portion of an inner volume of each sample cell.
21. The method according to claim 20, wherein the method further comprises (i) determining the amount of a sample within each sample cell based upon the top liquid level within a respective sample cell, (ii) adjusting the needle position based upon the top liquid level and the bottom liquid level within a respective sample cell, and/or (iii) limiting an insertion depth of the sample needle based upon a position of the bottom liquid level of a respective sample cell.
22. The method according to claim 14, wherein the container and/or cap of each sample cell includes an identifying color, and wherein at least one of the top scanning and side scanning includes scanning the identifying color.
23. The method according to claim 15, the method further comprising comparing, with the computing device, the top scanning and the side scanning to determine whether a gripped sample cell is the correct sample cell for further processing.
24. The method according to claim 13, the method further comprising determining the position of each of the sample cells within the sample tray based upon the unique label of each sample cell.
25. The method according to claim 13, the method further comprising aspirating a sample from each of the sample cells with a sampling needle assembly, separating analytes of the sample with a chromatography column, and detecting said analytes of the sample with a chromatography detector.
Description
BRIEF DESCRIPTION OF THE DRAWINGS
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DETAILED DESCRIPTION
[0049] Reference will now be made in detail to various embodiments of the present invention(s), examples of which are illustrated in the accompanying drawings and described below. While the invention(s) will be described in conjunction with exemplary embodiments, it will be understood that the present description is not intended to limit the invention(s) to those exemplary embodiments. On the contrary, the invention(s) is/are intended to cover not only the exemplary embodiments, but also various alternatives, modifications, equivalents, and other embodiments, which may be included within the spirit and scope of the invention(s) described herein.
[0050] Autosamplers play a vital role in chromatography systems as they hold and manage multiple samples that will undergo analysis by the system. The increasing prevalence and capabilities of charge-coupled devices (CCD) have opened the door for many applications to utilize machine vision (MV) in providing imaging-based automatic inspection and analysis. Utilizing machine vision within automated sample handling devices offers various advantages and unique solutions that may automate identification of sample cells (and the samples therein) and provide other quality assurances during automated sample-handling processes.
[0051] For example, machine vision may be used to recognize a variety of barcodes, characters, colors, landmarks, shapes, and/or other unique identifies used to identify a sample within a sample cell, which may eliminate the manual step traditionally performed by a user to link a specific sample to a prescribed chromatography method or protocol. Automating this step with machine vision may facilitate ease of use, especially for a user dealing with higher volumes of samples. And machine vision may also provide a means to identify the sample tray, which may be configured to provide data such as the type of vial (e.g., holding a sample vs. holding standards), the volume of the vial, the total number of vials that may be loaded into the tray, and/or tray location.
[0052] To prevent mismatches between user or lab-protocol and sample inventory inside the instrument, machine vision may be utilized to provide confirmation that the correct sample is being handled and/or drawn. Also, machine vision may be utilized to scan unique identifiers provided on the end surfaces of the sample cells that are visible from the sample tray while the cells are located in the sample tray, which identifiers may then be processed by a computing device. To improve reliability and performance machine vision may also be utilized in accordance with various aspects of the present invention to determine liquid level and volume tracking within sample cells.
[0053] Turning now to the drawings, wherein like components are designated by like reference numerals throughout the various figures, attention is directed to
[0054] As shown in
[0055] One will also appreciate that the sample trays may have various dimensions and configurations. For example, the illustrated sample trays are dimensioned and configured to hold a 5×8 array of 2 mL containers. One will appreciate that the sample trays may be configured to hold fewer or more sample cells (e.g., 21, 54, 64, 96, 100, or more), and they may be configured to hold smaller or larger sample cells (e.g., 0.5 mL, 0.7 mL, 10 mL, 20 mL, or more).
[0056] With reference to
[0057] With referenced to
[0058] The annular section may include a machine-readable end identifier 55 having machine-readable characters. For example, the end section may include alphanumeric characters or other suitable graphics that can be digitally captured, translated, and/or otherwise processed. The side section may include a machine-readable side identifier 57 having machine-readable indicia or characters. For example, the side identifier may include alphanumeric characters, a bar code and or other suitable graphics which can be digitally captured, translated, and/or otherwise processed. For example, the alphanumeric characters may be processed by optical character recognition (OCR).
[0059] A tether 58 may be provided to interconnect annular section 51 and side section 52 of the label. Such a tether provides tamper-proof indication that a respective cap and container remain together so long as the tether remains untorn and interconnects the annular section 51 mounted to the cap and the side section 52 mounted to the container. In various embodiments, the tether may have a length that is dimensioned and configured to allow a snap cap to be removed from a vial without tearing the annular section from the side section. Such configuration ensures that the snap cap and the vial remain paired and have not been inadvertently used with other caps and vials, which may thus reduce the chance of cross-contamination.
[0060] Advantageously, end identifier 55 is readily visible when the sample cell is located in an open-top sample tray whereby the end identifier may be readily scanned from above, alone or together with other sample cells located in the sample tray.
[0061] One will appreciate that a sheet 59 may be provided including a plurality of labels, as shown in
[0062] Carousel 36 may rotate sample tray 35 to and from a load position adjacent cell gripper 38, for example, to and from the lower left tray position shown in
[0063] In various embodiments, and with reference to
[0064] In the illustrated embodiment, gripper jaws 62 are horizontally slidable within a gripper head 64 and are biased toward a closed position (see
[0065] A motor assembly 68 is configured to rotate the jaw assembly about an axis A (see
[0066] A solenoid assembly 73 is configured to move the gripper jaws between their open and closed positions. The solenoid assembly selectively moves plunger 65 up and down extending through the hollow motor shaft 71 to operate the jaw assembly by moving cam 67 against gripper jaws 62 to selectively move the jaws between their open and closed positions. One will appreciate that various solenoid assemblies may be utilized, such as the Ledex Brand low-profile linear solenoids by Johnson Electric. And one will appreciate that the assembly may be a one-way linear actuator, a two-way linear actuator, or a stepped linear actuator.
[0067] With reference to
[0068] One will appreciate that various gripper assemblies could be utilized in accordance with various aspects of the present invention. For example, gripper assembly 38a may include pivoting gripper fingers 62a configured to grip the cap and/or neck of the vial (see
[0069] The MV module is provided with cameras and/or other digital imaging devices configured to scan and digitally image the side walls and/or the annular end surfaces of the sample cells within the autosampler. For example, the MV module may include a vertically-directed top camera 80 configured to scan the annular end surfaces of the sample cells, and a horizontally-directed side camera 81 configured to scan the side wall of each sample cell. One will appreciate that various cameras may be utilized including, but not limited, to the Advantage 100 series OEM smart cameras and the AE2 Advantage image engines, both by the Cognex Corporation, as well as other suitable digital imaging devices.
[0070] The top camera may be vertically directed downward such that it can capture in image of one or more sample cells 32 located in sample tray 35 (see
[0071] The side camera may be horizontally directed from one side of the autosampler such that it can capture an image of a sample cell 32 as it is supported and rotated by cell gripper 38 about axis A (see
[0072] Autosampler 33 may include a sampling needle assembly 83 that is fluidly connected to other components of a chromatography system in order to analyze constituents of the samples within the sample cells. For example, system 30 may be a chromatography system including the autosampler along with a sample injection valve 84 to introduce samples to a downstream HPLC or ion chromatography column 86 and, in turn, a conductively or other suitable detector 87. The column and detector may thus separate and detect analytes of interest within the samples contained within each of the sample cells.
[0073] Turning now to computing device 42, the computing device may have a number of components. In some embodiments, some or all of the components included in the computing device may be attached to one or more motherboards and enclosed in a housing (e.g., including plastic, metal, and/or other materials). In some embodiments, some of these components may be fabricated onto a single system-on-a-chip (SoC) that may include one or more processing devices and one or more storage devices. Additionally, in various embodiments, the computing device may include interface circuitry for coupling to the one or more components using any suitable interface (e.g., a Universal Serial Bus (USB) interface, a High-Definition Multimedia Interface (HDMI) interface, a Controller Area Network (CAN) interface, a Serial Peripheral Interface (SPI) interface, an Ethernet interface, a wireless interface, or any other appropriate interface). For example, the computing device may include display device interface circuitry (e.g., a connector and driver circuitry) to which a display device may be coupled.
[0074] The computing device may include one or more processing devices. As used herein, the term “processing device” may refer to any device or portion of a device that processes electronic data from registers and/or memory to transform that electronic data into other electronic data that may be stored in registers and/or memory. The processing device(s) may include one or more digital signal processors (DSPs), application-specific integrated circuits (ASICs), central processing units (CPUs), graphics processing units (GPUs), cryptoprocessors (specialized processors that execute cryptographic algorithms within hardware), server processors, or any other suitable processing devices.
[0075] The computing device may include one or more storage devices. The storage device may include one or more memory devices such as random access memory (RAM) (e.g., static RAM (SRAM) devices, magnetic RAM (MRAM) devices, dynamic RAM (DRAM) devices, resistive RAM (RRAM) devices, or conductive-bridging RAM (CBRAM) devices), hard drive-based memory devices, solid-state memory devices, networked drives, cloud drives, or any combination of memory devices. In some embodiments, the storage device may include memory that shares a die with a processing device. In such an embodiment, the memory may be used as cache memory and may include embedded dynamic random access memory (eDRAM) or spin transfer torque magnetic random access memory (STT-MRAM), for example. In some embodiments, the storage device may include non-transitory computer readable media having instructions thereon that, when executed by one or more processing devices, cause the computing device to perform any appropriate ones of or portions of the methods disclosed herein.
[0076] One will also appreciate that the computing device may include one or more logic elements. As used herein, the term “logic” may include an apparatus that is to perform a set of operations associated with the logic. For example, any of the logic elements may be implemented by one or more computing devices programmed with instructions to cause one or more processing devices of the computing devices to perform the associated set of operations. In a particular embodiment, a logic element may include one or more non-transitory computer-readable media having instructions thereon that, when executed by one or more processing devices of one or more computing devices, cause the one or more computing devices to perform the associated set of operations. As used herein, the term “module” may refer to a collection of one or more logic elements that, together, perform a function associated with the module. Different ones of the logic elements in a module may take the same form or may take different forms. For example, some logic in a module may be implemented by a programmed general-purpose processing device, while other logic in a module may be implemented by an application-specific integrated circuit (ASIC). In another example, different ones of the logic elements in a module may be associated with different sets of instructions executed by one or more processing devices. A module may not include all of the logic elements depicted in the associated drawing; for example, a module may include a subset of the logic elements depicted in the associated drawing when that module is to perform a subset of the operations discussed herein with reference to that module.
[0077] Computing device 42 may be configured to control various components of the autosampler including the carousel, cell gripper, gantry, and MV module. The computing device may either be integrated into the autosampler itself, integrated into the chromatography system, or be part of a personal computer (PC) that sends signals to communicate with and control the autosampler or the system. The memory portion can include software or firmware instructions on how to control the various components. For example, the computing device may be configured to run the Chromeleon™ chromatography data system (CDS) or other software platform, or configured to communicate with a PC that does so.
[0078] The computing device may operate cell gripper 38 and gantry 39 to grip, lift, and rotate individual sample cells 32 above adjacent sample cells in sample tray 35. The computing device may also operate the MV module to control the vertically-directed top camera to scan the annular end surfaces of all sample cells positioned in the sample tray, and control the horizontally-directed side camera to scan the side wall of individual sample cells while rotated by the cell gripper. By processing images of the label's (i) annular section 51 captured by the top camera and (ii) side section 52 captured by the side camera, the computing device may determine the identity of the sample in the sample cell and the position of each sample cell within the sample tray based upon the scanned annular end surfaces and/or side walls of each sample cell.
[0079] In accordance with various aspects of the present invention, the computing device maybe configured with a sample-cell scan sequence in which the jaw assembly is moved to the side of the sample tray (
[0080] One exemplary method of identifying sample cells in accordance with various aspects of the present invention can now be described. A user attaches labels to individual sample cells containing samples, loads the sample cells into a sample tray, and loads the sample cell into an autosampler. In various embodiments, a top camera may confirm an identifier on the sample tray before the scanning process begins. The top camera scans the end surfaces of all sample cells visible from above the sample tray, individually or simultaneously, and the computing device registers the position of each sample cell within the particular sample tray. The gripper lifts the individual sample cells and presents their side label to a side camera. The gripper rotates the sample cell to present the full label (and/or full side wall) of the sample cell to the side camera. And the gripper returns the sample cell to its sample tray location. The sample cell (and sample within) is now physically registered with a position within a sample tray and may thus be tracked by the computing device.
[0081] In various embodiments, the gripper is configured to rotate the sample cell approximately 360° in order to scan the circumference of the sample cell and fully capture an image of any label affixed thereto. And in various embodiments, the gripper is configured to rotate the sample cell approximately 540°, 720°, or more in order to account for latency times of readers.
[0082] Scanning the full side wall of the sample cell not only allows identification and tracking, such scanning may allow for identification of specific vial sizes, determination of sample needle positions within the sample cell, determination of liquid levels within the sample cell (see, e.g.,
[0083] With reference to
[0084] Each individual sample cell of the sample tray is gripped, lifted, and rotated with a cell gripper of the autosampler. In particular, each of the sample cells is gripped while in the sample tray, lifted from the sample tray, and rotated above adjacent sample cells of the sample tray.
[0085] Each individual sample cell is scanned by a side camera of the MV module in which the side wall of each sample cell is canned by the side camera. The scanning may include the scanning of alphanumeric characters and/or a bar code provided on the side wall of each of the sample cells. Preferably each sample cell is rotated about 360° to ensure the entire circumference of the side wall is scanned.
[0086] Each individual sample cell is then returned to the sample tray by the cell gripper, and the process repeated until all sample cells are similarly scanned. The computing device then identifies the samples within each sample cell and its position within the sample tray based upon the top scanning and/or the side scanning.
[0087] In various embodiments, the side wall of each sample cell is translucent or transparent to allow digital imaging of the liquid and its level within the sample cell. The side scanning may include scanning the full side wall surface of the sample cell allowing the computing device to process the scanned image(s) and determine a top liquid level within each sample cell, and a bottom liquid level at a lowermost portion of an inner volume of each sample cell. And in various embodiments, the computing device processes the scanned image(s) and determines the amount of a sample within each sample cell based upon the top liquid level within a respective sample cell. The computing device may also adjust sample needle positions during sample draw based upon the top liquid level and the bottom liquid level within a respective sample cell. And the computing device may limit an insertion depth of the sample needle during sample draw based upon a position of the bottom liquid level of a respective sample cell, which bottom liquid level would be indicative of the inner bottom surface of the sample cell or potential foreign objects within the sample cell that may damage the sample needle.
[0088] In various embodiments, the container and/or cap of each sample cell may include identifying colors. In such cases, the top scanning and/or the side scanning may capture color images and allow the computing device to identify various parameters of the sample cell and/or sample therein based upon such identifying colors. For example, one color may be utilized to identify sample sells containing standards as opposed to samples.
[0089] Advantageously, side and top scanning of the sample cells in accordance with various aspects of the present invention obviates the need for a user to manually map the various sample cells within a corresponding sample tray. Since labels provided on the sample cells include unique identifiers, the sample identification may be known regardless of where the user places it in the sample tray.
[0090] For convenience in explanation and accurate definition in the appended claims, the terms “up” or “upper”, “down” or “lower”, “left” and “right” are used to describe features of the exemplary embodiments with reference to the positions of such features as displayed in the figures.
[0091] In many respects, various modified features of the various figures resemble those of preceding features and the same reference numerals followed by subscript “a” designate corresponding parts.
[0092] The foregoing descriptions of specific exemplary embodiments of the present invention(s) have been presented for purposes of illustration and description. They are not intended to be exhaustive or to limit the invention(s) to the precise forms disclosed, and obviously many modifications and variations are possible in light of the above teachings. The exemplary embodiments were chosen and described in order to explain certain principles of the invention(s) and their practical application, to thereby enable others skilled in the art to make and utilize various exemplary embodiments of the present invention(s), as well as various alternatives and modifications thereof.