Method and apparatus for providing foreground illumination calibration for sample container characterization

Abstract

A method for calibrating an imaging device adapted to characterize features of a sample container, such as a cap color or a cap type. The method includes: providing a calibration tube including an imaging surface at an imaging position of a first imaging device; illuminating the imaging surface with light emitted from a plurality of front light sources; adjusting a drive current to each of the plurality of front light sources to establish a substantially uniform intensity of the imaging surface; recording drive current values ​​of the plurality of front light sources; replacing the calibration tube with a calibration tool having a calibration surface with a known reflectivity; and measuring a target intensity value of the calibration tool at a corresponding drive current value. A calibration tool, an imaging device, a quality inspection module, and a health inspection method are provided as other aspects.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application claims the benefit of U.S. Provisional Patent Application No. 62 / 929,068, filed on October 31, 2019, entitled “METHODS AND APPARATUS PROVIDING CALIBRATION OF FOREGROUND ILLUMINATION FOR SAMPLE CONTAINER CHARACTERIZATION,” the disclosure of which is incorporated herein by reference in its entirety. Technical Field

[0003] The present invention relates to imaging methods and imaging devices adapted to image sample tubes (specimen containers), and more particularly to methods and devices for calibrating such imaging devices. Background Art

[0004] Automated testing systems can perform clinical chemistry or assays using one or more reagents to identify analytes or other components in biological samples (specimens), such as serum, plasma, urine, interstitial fluid, cerebrospinal fluid, etc. For convenience and safety reasons, these samples are almost always contained in sample tubes (e.g., collection tubes). Sample tubes can be capped, and in some cases, these caps can include colors and / or shapes that provide information about the type of test to be performed, the type of additives contained in the tube (e.g., serum separators, procoagulants such as thrombin, anticoagulants and specific types thereof, such as EDTA or sodium citrate, or antiglycolytic additives), and / or whether the sample tube has vacuum capability, etc.

[0005] Improvements in automated testing have been accompanied by corresponding advances in automated pre-analytical sample processing, such as batch preparation, sample centrifugation for separation of sample components, removal of the top cover (decapping) for easy sample access, aliquot preparation, and pre-screening for hemolysis (H), icterus (I) and / or hyperlipidemia (L) (hereinafter referred to as "HIL") or normal (N), and / or the presence of artifacts (such as clots, bubbles or foam) in the sample. Such automated pre-analytical sample processing can be part of a laboratory automation system (LAS). In some cases, the LAS automatically transports samples contained in sample tubes for pre-analytical sample processing and to an analysis station containing a clinical chemistry analyzer and / or an assay instrument (individually and collectively referred to herein as an "analyzer") for testing. The test involves generating an altered reaction, such as fluorescence or luminescence emission, which can be read and / or otherwise manipulated to determine the presence and / or concentration of an analyte or other component contained in the sample.

[0006] The LAS can process any number of different samples contained in labeled sample tubes (e.g., including barcode labels) at one time, and the sample tubes can be of all different sizes and types, including different cap types and colors, which can also be mixed. The LAS can automatically route sample tubes for pre-analytical processing operations, all before the samples are actually subjected to clinical analysis or assays performed by one or more analyzers.

[0007] In some embodiments of automated pre-analytical sample processing, a quality check module may receive a sample tube containing a sample and pre-screen the sample for the presence of an interferent, such as a HIL. Pre-screening for HIL involves capturing one or more digital images of the sample tube and sample, and then processing the image data to determine if H, I, and / or L are present, and if so, possibly determining an index (relative amount) of H, I, and / or L, or may determine that the sample is normal (N). The presence of interferents in the sample may adversely affect the test results of the analyte or component measurement obtained later from the analyzer.

[0008] In some HILN pre-processing systems, the sample container and sample are digitally imaged and processed, such as with a computer-assisted model-based system (such as by using artificial intelligence), so that the presence or absence of interferents (HIL) can be determined, or normality (N) can be determined. The type and color of the cap can also be discerned. During imaging, images of the sample tube (including the cap) and sample can be captured from multiple viewpoints. As part of the pre-screening process, the size and type of the sample container and the amount of sample present can also be characterized.

[0009] However, such imaging systems may experience performance variations under certain conditions, and even from one imaging system to the next.Therefore, improved methods and apparatus operable to image such samples and / or sample containers are sought. Summary of the invention

[0010] According to a first aspect, a calibration method is provided. The calibration method comprises: providing a calibration tube including an imaging surface at an imaging position of a first imaging device; illuminating the imaging surface with light emitted from a plurality of front light sources; adjusting a drive current to each of the plurality of front light sources to establish a substantially uniform intensity of the imaging surface; recording drive current values ​​of the plurality of front light sources; replacing the calibration tube with a calibration tool having a calibration surface with a known reflectivity; and measuring a target intensity value of the calibration tool at a corresponding drive current value.

[0011] In another aspect, a quality inspection module is provided. The quality inspection module includes: an imaging location within the quality inspection module, configured to accommodate a sample container to be characterized; an imaging device, configured to capture images of the imaging location from multiple viewpoints; multiple light sources, configured to provide front illumination for the imaging device; a calibration tube, including an imaging surface located at the imaging location during a first calibration phase; and a calibration tool having multiple calibration surfaces of known reflectivity located at the imaging location during a second calibration phase, respective calibration surfaces of the multiple calibration surfaces being arranged to be viewed from each of the multiple viewpoints.

[0012] In another aspect, a calibration method is provided. The calibration method includes: providing a previously calibrated imaging device that has been previously calibrated according to an initial calibration method; placing a calibration tool having a calibration surface of known reflectivity at an imaging position of the previously calibrated imaging device; illuminating the calibration surface with light emitted from one or more previously calibrated front light sources; measuring intensity values ​​at an area of ​​interest of the calibration surface; and verifying that the previously calibrated imaging device is still performing within specifications based on the measured intensity values ​​of the area of ​​interest.

[0013] Still other aspects, features and advantages of the present disclosure may become apparent from the following description illustrating a plurality of example embodiments. The present invention may also be capable of having other and different embodiments, and several of its details may be modified in various aspects, all without departing from the scope of the present disclosure. In addition, although specific advantages have been enumerated, various embodiments may include all, some, or none of the enumerated advantages. The present disclosure will cover all modifications, equivalents and substitutes falling within the scope of the claims. BRIEF DESCRIPTION OF THE DRAWINGS

[0014] The drawings described below are for illustrative purposes and are not necessarily drawn to scale. The drawings are not intended to limit the scope of the present invention in any way. Therefore, the drawings are to be regarded as illustrative in nature rather than restrictive;

[0015] Figure 1 illustrates a top perspective schematic diagram of a quality inspection module including an imaging device configured to implement a calibration method according to one or more embodiments;

[0016] Figure 2 illustrates a side plan view of a sample tube containing a separated (e.g., centrifuged) sample and a first cap type therein;

[0017] Figure 3 illustrates a side view of a sample container containing a separated (e.g., centrifuged) sample and further comprising a gel separator and a second cap type;

[0018] Figure 4A illustrates a top view (with the top removed for illustration purposes) of a quality inspection module including an imaging device and a calibration tube located at an imaging position according to one or more embodiments;

[0019] Figure 4B illustrates a top view (with the top removed for illustration purposes) of a quality inspection module including a calibration tool mounted at an imaging location according to one or more embodiments;

[0020] Figure 4C illustrates a front view of a calibration tool including a calibration surface according to one or more embodiments;

[0021] Figure 4D The present invention illustrates a method according to one or more embodiments. Figure 4C A top view of a calibration tool illustrating a plurality of calibration surfaces arranged in a triangle;

[0022] Figure 4E illustrates a front view of another calibration tool including a calibration surface according to one or more embodiments;

[0023] Figure 5A illustrates a front view of a calibration tool including a region of interest (ROI) illuminated at a target intensity and viewed by an imaging device with a first light source turned on, according to one or more embodiments;

[0024] Figure 5Billustrates a front view of a calibration tool including a region of interest (ROI) illuminated at a target intensity as viewed by an imaging device with a further side light source turned on and a first light source turned off, according to one or more embodiments;

[0025] Figure 6 illustrates a flow chart of a calibration method adapted to calibrate an imaging device according to one or more embodiments;

[0026] Figure 7 illustrates a flow chart of a calibration method adapted to calibrate a new imaging device based on target intensities obtained from a first imaging device according to one or more embodiments;

[0027] Figure 8 illustrates a flow chart of a portion of a calibration method according to one or more embodiments, wherein a new calibration tool is different than a calibration tool used to calibrate a first imaging device;

[0028] Fig.9A illustrates a photograph of the illumination intensity of a light source (light panel 104B) captured by an imaging device 106B according to one or more embodiments;

[0029] Fig. 9B illustrates a photograph of the illumination intensity of a light source (light source 104C) captured by imaging device 106C according to one or more embodiments;

[0030] Fig.10 illustrates a flow chart of a calibration method that enables a health check of a previously calibrated imaging device in accordance with one or more embodiments;

[0031] Fig.11A and 11B illustrates a side view and a top view, respectively, of a calibration tool that enables a health check of a previously calibrated imaging device according to one or more embodiments;

[0032] Fig. 11C Illustrated is a partial side view of a calibration tool that enables a health check of a previously calibrated imaging device, wherein a region of interest has been divided into a plurality of regions, in accordance with one or more embodiments. DETAILED DESCRIPTION

[0033] Foreground illumination is used for sample container (e.g., sample tube) characterization, and in particular for identifying sample container type and / or properties based on cap color and / or cap appearance (cap shape). According to an embodiment, the present disclosure relates to a method and apparatus that is configured and used to implement foreground illumination calibration, such as within a sample tube characterization device (e.g., with a quality inspection device), to ensure consistent and accurate foreground illumination. Improving foreground calibration can improve discrimination capabilities at least with respect to cap color.

[0034] In some embodiments, the present invention relates to methods and apparatus configured and used to implement foreground illumination calibration across multiple sample tube characterization systems (e.g., across multiple quality inspection devices or similar imaging machines). As used herein, foreground illumination means illumination of a front portion of a sample tube by one or more illumination sources (e.g., light panels) located at a position in front of the sample tube. For example, in some embodiments, foreground illumination can include foreground illumination from multiple illumination devices (e.g., multiple illumination panels), which can be located at different positions in front of the sample tube, such as on opposite front sides of an imaging device.

[0035] In a first broad aspect, embodiments of the present invention provide a method and apparatus configured and adapted to calibrate foreground illumination in an optical imaging device. The present disclosure is particularly useful in a sample tube quality inspection device that involves foreground illumination of a sample tube at an imaging position therein. For example, foreground illumination can be used to illuminate a cap on a sample tube, image the cap, and then discern the cap color and / or cap shape.

[0036] In addition, embodiments of the present invention provide a method and apparatus configured to calibrate the lighting device of an imaging device so that the imaging device can capture one or more images of a sample tube, wherein the one or more captured images can be used to characterize one or more features of the sample tube, such as the top cover color and / or the top cover type. Foreground lighting can also be used to characterize the tube size (height and / or width). In a quality inspection device, quality inspection of the specimen and sample tube is used to ensure the appropriateness of one or more tests performed on the sample contained in the sample tube or the alignment with the sample tube type. For example, if the identified color of the top cover and / or the shape of the top cover are not fully aligned with the test to be performed, an error can be marked to the operator / technician. For example, a phlebotomist may have mistakenly used an inappropriate tube type for an already scheduled test. For example, a sample tube containing a procoagulant may have been used when a sample tube containing an anticoagulant is required in a specific test to be run. Improved characterization of the top cover type and / or shape can help detect these incorrect scenarios. Therefore, samples can be avoided before being sent to an analyzer, thereby saving analyzer resources and potentially avoiding tests that may produce erroneous results. In other embodiments, sample tube characterization can be used for automated tube sorting.

[0037] In particular, embodiments of the present invention relate to a calibration apparatus and calibration method configured to provide image data from one or more imaging devices that have been properly calibrated. In further embodiments, methods and apparatus are provided that enable rapid calibration of one or more (multiple) similar imaging devices (e.g., a large number of clones of a master imaging device).

[0038] To ensure consistent lighting across multiple imaging devices (machines) and across imaging devices contained within each imaging device, it is proposed that foreground lighting be performed in multiple stages. In a first stage, golden device settings are achieved. In another stage, a calibration tool is utilized to provide device-dependent settings. In yet another stage, device-dependent settings may be provided without a tool. In other embodiments, a health check may be provided to confirm calibration or adjust calibration if outside of pre-established specifications.

[0039] In some embodiments, the sample 212 (test specimen) described herein is collected in a sample tube 102, such as a blood collection tube, and can be whole blood, which after separation (e.g., after fractionation using centrifugation) includes a sedimented blood portion 212SB and a serum and plasma portion 212SP, such as Figure 2 and Figure 3As shown. The sedimented blood portion 212SB (sometimes referred to as the "concentrated cell portion") consists of blood cells (such as white blood cells (WBCs), red blood cells (RBCs), and platelets (thrombocytes) that are aggregated and separated from the serum or plasma portion 212SP. The sedimented blood portion 212SB is typically found at the bottom portion of the sample tube 102. The serum or plasma portion 212SP is a liquid component of the blood that is not part of the sedimented blood portion 212SB. It is typically found above the sedimented blood portion 212SB. The main difference between plasma and serum is the content of coagulation components (mainly fibrinogen). Plasma is an unclotted liquid, while serum refers to plasma that has been clotted under the influence of endogenous enzymes or exogenous components or procoagulants. In some sample tubes 102, a small (e.g., stopper) may be used that positions itself between the sedimented blood portion 212SB and the serum or plasma portion 212SP during fractionation, such as Figure 3 As shown. Gel separator 313 acts as a barrier between the two sections. The type of sample present may be related to the color of the cap and / or the shape of the cap.

[0040] According to one or more embodiments, the calibration device and calibration method described herein can be used to calibrate an imaging device that is configured to perform a pre-analytical test (pre-screening). For example, in one or more embodiments, the device and method can be implemented to accurately calibrate an optical imaging device. In particular, one or more embodiments of the present disclosure provide for calibration of an optical imaging device that is configured to characterize a sample and / or a sample tube as a prerequisite for further testing. For example, a sample can be pre-screened for the presence of hemolysis (H), icterus (I), and / or lipemia (L) or normal (N) (collectively referred to as HIL).

[0041] Figure 1 An embodiment of a sample tube quality inspection device 100 is shown in FIG. 1 , with which the calibration method according to the present invention can be used. Figure 1An example of an optical imaging system 101 within a quality inspection device 100 is shown, the quality inspection device 100 including a plurality of light sources (e.g., light panels 104A-104C) and a plurality of imaging devices 106A-106C. In some operations, the light panels 104A-104C are primarily used to backlight the sample tube 102, i.e., illuminate from the back side of the sample tube 102, so that an imaging device (e.g., a camera, a CMOS sensor, etc.) can inspect the fluid properties of the sample 212 contained in the sample tube 102. The inspection can be performed from a plurality of viewpoints 1, 2, 3. In backlighting, the associated imaging device is provided on the front side of the sample tube 102, and the illumination source is provided behind the sample tube 102. For example, the fluid property may be the HILN, the volume or size of one or more components of the sample 212, or the presence of artifacts therein (e.g., clots, foam, bubbles). Foreground illumination is the subject of this calibration method, not backlighting.

[0042] Under the same lighting setup (configuration) that can be used for back lighting, the light panel 104A facing the imaging device 106A and the reading of the sample tube 102 can be turned off, while the other two light panels 104B and 104C in front of the sample tube 102 are turned on to provide front lighting of the sample tube 102. Front lighting is most useful for characterizing the physical characteristics of the sample tube 102. Characterizing the physical characteristics of the sample tube 102 can include determining the size (e.g., the height and / or width of the sample tube 102), determining the color of the top cover 214, the type of top cover 214, and / or reading a bar code and / or other markings provided on a label 218 applied to or provided on the sample tube 102 (collectively referred to as 218i, see Figure 2-3 ). While tube characterization operations such as reading of barcode 218i may not have strict consistency requirements as long as adequate front lighting is provided, there are some features of tube type classification, such as those based on cap color and / or cap appearance, where consistent lighting, and particularly consistent lighting across multiple imaging devices (machines), can ensure proper performance and characterization thereof.

[0043] like Figure 1As shown, the light panels 104A-104C and the imaging devices 106A-106C can be arranged to capture and provide lateral 2D images of the sample container 102, and possibly lateral images of the sample 212 (if contained therein), from one or more different lateral viewpoints (e.g., three viewpoints 1, 2, and 3 as shown). During image capture for sample characterization, the sample container 102 and the sample 212 can be backlit, i.e., illuminated behind the sample container 102 and the sample 212 for each viewpoint 1-3. The resulting illumination can come from the light panels 104A-104C. For example, backlighting can be provided by the light panel 104A for the imaging device 106A, by the light panel 104B for the imaging device 106B, and by the light panel 104C for the imaging device 106C. In backlighting, for each respective viewpoint 1-3, the sample tube 102 is positioned between a respective light panel 104A-104C and a respective imaging device 106A-106C. Backlighting with the light panels 104A-104C may be coupled with high dynamic range (HDR) image processing of the images taken by the imaging devices 106A-106C and processing thereof by the computer 143. The characterization method and apparatus 100 may be used to quantify the sample 212, including quantification of the intensity of light transmitted through the sample at different spatial locations.

[0044] In some embodiments, the characterization method and apparatus can be used to determine the location of the interface boundary of the serum or plasma portion 212SP and / or the sedimentation blood portion 212SB and / or the gel separator 313 (if present), and use image processing (e.g., HDR image processing) together with backlighting and / or foreground lighting to determine the volume and / or depth of these respective components with high accuracy. In some embodiments, the characterization apparatus and methods described herein can be used to determine the characterization of physical (geometric) or other features of the sample tube 102, such as the tube type (via identification of its height and / or width), the cap type and / or the cap color. According to some embodiments, the characterization method includes identifying the cap type and the cap color, and optionally identifying the tube size (height and / or width). The characterization method for identifying the cap type and the cap color, and optionally identifying the tube size (height and / or width) can use front (front) lighting with a front light source (such as a combination of light panels 104A-104C), depending on the viewpoint of interest for each front image capture implemented.

[0045] In short, the illuminated 2D image dataset for one or more viewpoints (e.g., viewpoints 1, 2, and / or 3) can be used to characterize the sample container 102 and / or quantify the sample 212. In particular, the foreground-illuminated 2D image dataset for one or more viewpoints can be used to characterize the sample container 102 to determine, for example, the tube type and cap type and their color, and possibly other geometric features of the sample container 102 and / or the sample 212. The 2D image dataset obtained using backlighting with the light panels 104A-104C can also be used to determine or verify information about the sample 212, such as whether there are interferents in the sample, such as hemolysis (H), icterus (I), and / or hyperlipidemia (L) (hereinafter "HIL"), or whether the sample is normal (N), or even the presence of artifacts (e.g., clots, foam, or bubbles) contained therein.

[0046] Reference again Figure 1 In one or more embodiments, the quality inspection module 100 can be provided as part of the LAS. The LAS can include a track 108 that functions to transport the sample 102 to one or more analyzers (not shown) of the LAS, and to the quality inspection module 100, which can be provided at any suitable location on or along the track 108. For example, the quality inspection module 100 can be located at a loading station, adjacent to or as part of an analyzer, or elsewhere along the track 108 so that the sample 212 and sample container 102 can be characterized. In some embodiments, the characterization can be performed while the sample container 102 resides on a carrier 122 that can move along the track 108 (see also Figure 4A ). However, for clarity, the quality inspection module 100 including backlighting and front lighting may not be included on the track 108, and the sample container 102 including the sample 212 may be loaded and unloaded from the quality inspection module 100 either manually or with the action and assistance of a robot.

[0047] In some embodiments, the characterization may include data processing (e.g., HDR image processing) including capturing multiple images at multiple exposures (e.g., exposure times and / or aperture settings) and with background and foreground illumination. Image processing may include using multiple different spectra with different nominal illumination wavelengths (e.g., colors). Multiple images may be obtained using imaging devices 106A-106C for multiple viewpoints 1-3 with front illumination and back illumination.

[0048] Panelized illumination can be used to generate images using corresponding light panels in light panels 104A-104C for each viewpoint 1-3. Spectral light sources for back and front lighting can include red (R) light sources, green (G) light sources, and blue (B) light sources. Optionally, white light (W), near infrared (NIR) or even infrared (IR) light sources can be used. The quality inspection module 100 can obtain images under multiple exposures for each spectrum. For example, 4 to 8 images under different exposures (e.g., exposure time and / or aperture setting) can be obtained under each spectrum (or wavelength range). Multiple images under these different spectra can then be further processed by the computer 143 to generate characterization results. Any suitable segmentation and / or characterization method can be used for characterization of the sample container 102, such as disclosed in, for example, U.S. patent application publications US2018 / 0365530 and US2019 / 0041318.

[0049] As part of the image processing, calibration is performed to properly adjust the image intensity to ensure that the front and / or back lighting has the appropriate intensity for each spectrum of light used for illumination. Figure 1-11C Further details of a calibration method for an imaging device of a quality inspection module(s) are described below.

[0050] Typically, the sample to be automatically processed 212 ( Figure 2 and Figure 3 ) may be provided in a sample container 102, which may be capped with a cap 214 ( Figure 2 and Figure 3 ). The cap 214 can have different shapes and / or colors (e.g., red, royal blue, light blue, dark green, light green, black, gray, tan, orange, or yellow, or a combination of colors), which can have significance in terms of what test the sample container 102 is used for, the type of additives contained therein, whether the specimen should be under vacuum, etc. Other colors or color combinations that have significance can be used. According to one aspect, it may be desirable to image the cap 214 to characterize information about the cap 214 so that it can be used to perform a cross-check with the test order and verify that the correct sample tube 102 is indeed used for the test so ordered.

[0051] Each sample container 102 may be provided with identification information 218i (i.e., a label), such as a barcode, letters, numbers, alphanumerics, or a combination thereof, which may be machine-readable. For example, the identification information 218i may indicate the patient's identification and the test to be performed on the sample 212 or other information from the laboratory information system (LIS), or may be otherwise associated with it via the laboratory information system (LIS) 147 or other database. Such identification information 218i may generally be provided on a label 218 that is adhered to the sample container 102 or otherwise provided on the side of the sample container 102. The label 218 generally does not extend all the way around the sample container 102, or extends all the way along the height of the sample container 102. In some embodiments, multiple labels 218 may be adhered, and the multiple labels 218 may overlap slightly with each other. Therefore, although the label 218 may block the view of a portion of the sample 212, some portions of the sample 212 may still be viewed from certain viewpoints (one or more of viewpoints 1-3). One or more embodiments of the characterization method and quality inspection module 100 may enable characterization of the sample 212 and / or sample container 102 by imaging the sample container 102 and the sample 212 from multiple viewpoints (e.g., from all viewpoints 1 , 2 , and 3 ) without rotating the sample container 102 .

[0052] like Figure 2 and Figure 3 As best shown in FIG. 2 , the sample 212 may include a serum or plasma portion 212SP and a sedimented blood portion 212SB contained within a tube 215. Air 216 may be provided above the serum or plasma portion 212SP, and a boundary between the air 216 and the serum or plasma portion 212SP is defined herein as a liquid-air interface (LA). A boundary between the serum or plasma portion 212SP and the sedimented blood portion 212SB is defined herein as a serum-blood interface (SB), and Figure 2 The interface between the air 216 and the cap 214 is referred to herein as the tube-cap interface (TC). The height of the serum or plasma portion 212SP is (HSP) and is defined as Figure 2 The height of the sedimented blood portion 212SB from the top of the serum or plasma portion 212SP at LA to the top of the sedimented blood portion 212SB at SB. The height of the sedimented blood portion 212SB is (HSB) and is defined as Figure 2 The height from the bottom of the settled blood portion 212SB to the top of the settled blood portion 212SB at SB. Figure 2 HTOT in is the total height of the sample 212 and is defined as HTOT = HSP + HSB.

[0053] In the case where the gel separator 313 is used (see Figure 3 ), the height of the serum or plasma portion 212SP is (HSP), and is defined as the height from the top of the serum or plasma portion 212SP at LA to the top of the gel separator 313 at SG. The height of the sedimented blood portion 212SB is (HSB), and is defined as the height from the bottom of the sedimented blood portion 212SB to the bottom of the gel separator 313 at BG. Figure 3 HTOT in is the total height of the sample 212 and is defined as HTOT = HSP + HSB + the height of the gel separator 313 .

[0054] In each case, the wall thickness is Tw, the outer width is W, and the inner width of the sample container 102 is Wi. The height (HT) of the tube is defined herein as the height from the bottom-most portion of the tube 215 to the bottom of the top cover 214. Characterization methods can determine any of these geometric properties, such as disclosed in, for example, U.S. Patent Publications US2018 / 0364268, US2018 / 0365530, US2018 / 0372648, US2019 / 0271714, and US2019 / 0041318.

[0055] As discussed above, the carrier 122 can move the sample container 102 along the track 108 and stop at the imaging position 109 of the quality inspection device 100. The carrier 122 can be a passive, non-motorized disk that can be configured to carry a single sample container 102 on the track 108, where the track 108 is movable, or the carrier 122 can be automatic, including an onboard drive motor that can be programmed to move about the track 108 and stop at a preprogrammed position (such as, the imaging position 109). In either case, the carrier 122 can include a holder ( Figure 1 Not shown, but in Figure 4A ), the holder is configured to hold the sample container 102 in a generally vertical orientation so that it can be easily imaged from multiple viewpoints (e.g., from viewpoints 1-3). The holder may include a plurality of fingers or leaf springs or a combination thereof that may vertically support and secure the sample container 102 in the carrier 122, but some of the fingers or leaf springs may be laterally movable or flexible to accommodate sample containers 102 of different sizes (widths) to be accommodated therein.

[0056] The quality inspection device 100 can be controlled by a computer 143, which can be a microprocessor-based central processing unit (CPU) with suitable memory and suitable regulating electronics, drivers and software for operating various automated equipment components. The computer 143 can control the operation of the quality inspection device 100 and the characterization, processing and imaging, including the operation of the light panels 104A-104C and the imaging devices 106A-106C, and the operation of the track 108 described herein. Optionally, the track can be controlled by a different computer or controller in communication with the computer 143.

[0057] Pre-screening the sample 212 allows accurate quantification of the relative amounts of the serum or plasma portion 212SP and / or the sedimentation blood portion 212SB, and / or the ratio between them. In addition, the pre-screening can determine the physical vertical position of the TC, LA, SB or SG and BG, and / or the bottommost portion of the sample container 102. Quantification ensures that if there is not enough serum or plasma portion 212SP available for the scheduled test, the sample 212 can be stopped to avoid advancing to one or more analyzers. In this way, inaccurate test results can be avoided by avoiding possible aspiration of air, sedimentation blood portion 212SB and / or gel separator 313. Therefore, the ability to accurately quantify the physical position of LA and SB or SG can not only minimize the possibility of aspirating air, but also minimize the possibility of aspirating the sedimentation blood portion 212SB or gel separator 313 (if present). Therefore, clogging and contamination of the sample aspiration pipette (not shown) used for aspirating the serum or plasma portion 212SP for the analyzer or at the aliquoting station can be avoided or minimized. As discussed above, proper characterization of the cap 214 and / or tube 102 may allow for additional quality checks to ensure that the proper sample tube is used for the test being scheduled.

[0058] refer to Figure 1 and Figures 4A-4E, a first embodiment of a quality inspection device 100 is shown and described, which includes an illumination source embodied as a light panel assembly 104A-104C, which may include a spectrally switchable light source. Images obtained by the quality inspection device 100 can allow for accurate aspiration pipette and / or gripper positioning, determination of a sufficient amount (e.g., volume or height) of serum or plasma portion 212SP for a scheduled test, identification of H, I and / or L or N (hereinafter HILN), identification of artifacts (such as clots, bubbles or foam) in the sample 212, and characterization of cap color and / or cap type and / or tube for verification of tube type and size. Thus, use of the quality inspection module 100 can help avoid gripper collisions, pipette clogs, air aspiration by the pipette, identify HILN, identify artifacts, and / or determine via cap characterization and / or tube size that the appropriate sample tube 102 is being used for the scheduled test so that valuable analyzer resources are not wasted and confidence in the test results can be improved.

[0059] Reference Figure 4A , an embodiment of a quality inspection device 100 is shown. The quality inspection device 100 may include imaging devices 106A-106C, which are configured to capture one or more digital images (i.e., one or more pixelated images) at an imaging position 109 from multiple lateral viewpoints (e.g., from viewpoints 1-3). The imaging devices 106A-106C may be digital cameras, charge coupled devices (CCDs), photodetector arrays, CMOS sensors, etc. Other suitable imaging devices for generating digital pixelated images may be used. The imaging devices 106A-106C may be capable of acquiring digital images having any suitable image size so as to capture an image including at least the top cover 214 and the serum or plasma portion 212SP. Other image sizes may be used.

[0060] The imaging devices 106A-106C may be provided in close proximity to the imaging location 109 and trained or focused to capture the view window at the imaging location 109, including the expected location of the sample container 102. In some embodiments, the sample container 102 may be placed or stopped at the imaging location 109, such as by a carrier stopped on a track 108, or by a robot (not shown) placed in a holder located at the imaging location 109, so that the sample container 102 is approximately centered in the view window and the imaging location 109.

[0061] Reference again Figure 1 and 4A-4E, the quality inspection device 100 may include spectrally switchable illumination sources 104A-104D, as shown, provided by light panel assemblies 104A-104D to provide spectrally switchable illumination (back illumination and / or front illumination as desired). The spectrally switchable illumination sources (e.g., light panels) 104A-104C may be spectrally switchable between at least two spectra, and in some embodiments, spectrally switchable between 3 or more discrete spectra. The light sources 104A-104C may be constructed as described in U.S. Patent Publication 2018 / 0372648.

[0062] The light arrays in the light panels 104A-104C can provide switchable multi-spectrum lighting. For example, in one embodiment, the light arrays can include a plurality of independently switchable lighting elements, or lighting elements that can be switched in groups, such as light emitting diodes (LEDs) having different light emission spectra. The switching of the lighting elements can be accomplished by software operable on a computer 143, which is coupled to an appropriate power supply and driver. Thus, by selecting only some of the lighting elements for illumination at a time, the light panels 104A-104C can be illuminated at a plurality of different spectra having different nominal wavelengths.

[0063] For example, the LEDs may include LEDs of different colors, such as a red LED (R), a green LED (G), and a blue LED (B), which may emit spectra at different nominal wavelengths. For example, the light panel assemblies 104A-104C may each emit red light at 634nm+ / -35nm, green light at 537nm+ / -35nm, and blue light at 455nm+ / -35nm. In particular, the light array may include clusters of R, G, and B LEDs, which may be arranged in a repeating pattern along the height of the light panels 104A-104C. For each panel, each LED of the same color may be illuminated simultaneously. For example, in order to achieve front illumination, each red LED of the panels (e.g., light panels 104B and 104C) may be turned on simultaneously to provide red illumination from those light panel assemblies, thereby front-illuminating the sample container 102 containing the sample 212 at the imaging position 109 during its imaging. Similarly, each green LED may be turned on simultaneously to provide green illumination during imaging. Similarly, each blue LED can be turned on simultaneously to provide blue illumination during imaging. It should be appreciated that R, G, and B are merely examples, and that for certain types of foreground light imaging, other wavelength light sources may be selected, such as a white light source (e.g., a wavelength range of about 400 nm to about 700 nm). In other embodiments, UV (a wavelength range of about 10 nm to about 400 nm), near infrared (a wavelength range of about 700 nm to about 1250 nm), or even mid-infrared (a wavelength range of about 1250 nm to about 2500 nm) may be included and may sometimes be turned on for certain types of imaging.

[0064] Calibration Method

[0065] Reference now Figure 6 , a flow chart of a calibration method 600 is shown and will be described. The calibration method 600 is useful for calibrating an imaging device, and the type of imaging device 101 included in the quality inspection device 100 will now be described.

[0066] At the first stage, a golden device setting is established for an ideal foreground illumination provided on the sample tube 102. For this purpose, a calibration tube 102C of representative diameter (e.g., the average diameter expected in the field) has, for example, a blank label 119 (e.g., a single layer of white paper, which may have an adhesive backing) wrapped around the body of the sample tube 102 to enable adjustment of the drive current of the foreground illumination until it reaches a preset intensity (e.g., 180 out of 255 intensity levels) at the imaging position 109. The target intensity I Tis chosen to be as close to the maximum as possible, but includes a safety margin to avoid saturation under varying conditions, such as label materials with higher reflectivity used in the field. This adjustment is required to ensure a substantially balanced (uniform) distribution of light from the two light sources 104B, 104C from both sides and across each of the multiple color channels (wavelengths), despite the cylindrical shape of the sample tube 102. This first stage can be done programmatically or manually, as it only needs to be done once.

[0067] In the described embodiment of the method 600, at a first stage, such as in block 602, a calibration tube 102C including an imaging surface 114 may be provided at an imaging location 109. The imaging location 109 is located within an imaging chamber 110 formed by a collection of walls of a housing 112 of a first imaging device 101 (for purposes of illustration, Figure 1 and 4A -4B has its top plate removed). Housing 112 may include one or more tunnels 112A, 112B to allow carrier 122 to enter and / or exit chamber 110, but may restrict external light from entering chamber 110. In some cases, doors may be provided in tunnels 112A, 112B that may be closed when imaging.

[0068] Imaging position 109 can be located within chamber 110, and its center can be located at the intersection of normal vectors (normal vectors 1, 2, and 3) projected from each of imaging devices 106A-106C. Imaging surface 114 can be formed by, for example, a blank label 119 thereon. Blank label 119 can be applied to the front surface of the tube body of calibration tube 102C facing imaging device 106A, but can be completely surrounded for other viewpoints 2-3. In other embodiments, imaging surface 114 can be painted flat white or other colors. Calibration tube 102C can reside on a calibration carrier or another suitable carrier or holder, such as carrier 122 shown in, for example, U.S. Patent Publication 2018 / 0372648. Calibration tube 102C can be positioned at imaging position 109 in other ways.

[0069] The method further includes, in block 604, illuminating the imaging surface 114 with light emitted from a plurality of front light sources (104B, 104C). This illumination is referred to as "front illumination," which is direct illumination of the imaging surface 114. According to the method 600, in block 606, the drive current of each of the front light sources 104A, 104B is adjusted to achieve and establish a "substantially uniform" light intensity on the imaging surface 114. "Substantially uniform" light intensity means that when measured on a pixel-by-pixel basis, the light intensity at 120 degrees in front of the region of interest 1131 (+ / - 60 degrees from vector 1) is uniform within + / - 20% of the maximum intensity in the region of interest 1131. In some embodiments, the light intensity on the region of interest 1131 may be uniform within + / - 10%, + / - 5%, or even + / - 3% in some embodiments. In some embodiments, the substantially uniform light intensity on the region of interest 1131 on the imaging surface 1125 may be measured by the imaging device 106A for viewpoint 1. Light intensity measurements for the other viewpoints 2, 3 may be made by the imaging devices 106B, 106C. Other suitable means for measuring intensity may be used.

[0070] Possible alternative intensity measurement solutions can be used to measure whether a substantially uniform light intensity is provided on the imaging surface 114. For example, a photometer can be used to manually measure the brightness at the imaging surface 114. A spectrometer can be used to determine and / or verify the color distribution at the imaging surface 114. Adjustments to the drive current for each light source 104A, 104B, and 104C can come from an adjustable current or voltage source. Optionally, when the average intensity is too high or too low compared to a target intensity (such as 180 out of 255 intensity levels), the methods described herein can adjust the exposure of the sensors of the imaging devices 106B, 106C to avoid drawing too low or too high a drive current.

[0071] Since each imaging device (machine) may have slightly different sensor and illumination properties, carrying the drive current to other machines does not guarantee the reproduction of the same foreground illumination. Therefore, the goal is to reproduce that light intensity at the other machines, not the drive current.

[0072] According to the method 600, once substantially uniform light intensity on the imaging surface 114 is achieved, the drive current values ​​C1, C2 for each of the front light sources 104B, 104C, respectively, may be recorded in a memory of the computer 143 as recorded drive currents in block 608.

[0073] Once the light setup is substantially uniform, the calibration tube 102C may be replaced with a polygonal object (calibration tool) of known reflectivity on each imaging surface (calibration tool 124), such as Figure 4C-4DAs shown, or alternatively as Figure 4E shown.

[0074] As used herein, "reflectivity" refers to a surface reflectance property that determines the proportion of incident light of a particular wavelength (e.g., red [~620nm], green [~540nm], or blue [~450nm]) that is reflected from the imaging surface to the imaging sensor of the corresponding imaging device 106A, 106B, 106C or other intensity measuring device. The imaging surface can have a uniformly distributed reflectivity, where one reflectivity value R1 can represent the reflectivity property of the entire surface, or it can have varying distributed reflectivities for different portions of the imaging surface. By "known reflectivity" as used herein, it is meant that the reflectivity value of the imaging surface is known to a relatively high degree of accuracy and precision (e.g., >95%, >97%, or even >99%) through measurements from a reflectance spectrometer or based on manufacturing specifications for the surface material. The calibration tool 124 can be designed so that each substantially flat side includes a calibration surface facing one of the imaging devices 106A-106C. Thus, in the case of using three imaging devices 106A-106C, this can produce something like Figure 4D The prismatic shape shown in the top view of the prism shape includes calibration surfaces 125, 125' and 125" formed, for example, in triangles. The calibration tool 124 shown herein provides a unique design for implementing calibration in an imaging device 101 of a quality inspection device 100 or other machine in which a sample tube 102 is to be imaged, such as for pre-screening or sorting.

[0075] Therefore, according to method 600, in block 610, the calibration tube 102C at the imaging position 109 is replaced with a calibration tool 124. The calibration tool 124 has a calibration surface 125 of a known reflectivity R1 value for viewpoint 1. The calibration tool 124 may have a surface of known reflectivity that has been certified to facilitate calibration. Similar calibration surfaces 125', 125" of known reflectivity R1 may be provided for viewpoints 2 and 3, respectively. The calibration tool 124 may be as shown in FIG. Figure 4C and 4D The calibration tool 124 may include a holding portion 127 that may be shaped like the bottom of the sample tube 102 so that the calibration tool 124 may be accommodated in a holder of the carrier 122 (see Figure 4A ), and is held at the imaging position 109 of a carrier 122 of the same type used to characterize the sample tube 102. Optionally, the calibration tool 124 may be as Figure 4EThe calibration tool 124 is configured as shown and includes a holding portion 127 , which may take the shape of a plate, so that the calibration tool 124 may be coupled to the calibration carrier at the imaging location 109 , or otherwise positioned at the imaging location 109 .

[0076] The material of the imaging device facing the side of the calibration tool 124 for viewpoints 1-3 should have the following properties:

[0077] - spectral surface reflectance (R1) calibrated by laboratory measurements,

[0078] - nearly constant spectral reflectance (essentially neutral with respect to the illumination wavelength),

[0079] - optimized for diffuse reflection (minimizing reflections),

[0080] - The average surface reflectivity level R1 is approximately matched to ensure adequate but not excessive illumination levels at approximately target drive current settings (e.g., to the LED of the light source) and exposure times.

[0081] The surface reflectance measurements of each individual calibration surface 125, 125', and 125" of each calibration tool 124 can be accessed in a database and linked to a unique serial number, which can be encoded, for example, in a data matrix 129. For example, the data matrix 129 can be received as a tag for each surface 125, 125', and 125". The data matrix 129 can include a code that can be read by each imaging device 106A-106C to look up the corresponding surface reflectance measurement R1, which is used as a normalization factor in intensity calibration, in recording the golden device setup, and in reproducing the setup in a target device (e.g., a second imaging device that is a substantial clone of the first imaging device 101). As a result, the calibration method 600 becomes largely independent of the calibration tool 124 used in each step of the method.

[0082] In order to record each individual intensity of the calibration tool 124, the front illumination can be turned on separately and jointly, thereby extracting intensity values ​​from at least one region of interest in each viewpoint 1-3 separately and jointly. Figure 4B In FIG. 6 , the front illumination for imaging device 106A comes from light sources 104B and 104C (eg, a light panel). Method 600 records target intensity IT1 at imaging device 106A reflected from calibration tool 124 when only light source 104B is turned on, and target intensity IT2 at imaging device 106A when only light source 104C is turned on. T2 . Then, you can open them jointly and record the intensity values.

[0083] Figure 5A and5B 1 and 106A. The average intensity of a region of interest (ROI) 131 on the calibration tool 124 as viewed by the imaging device 106A is shown. The black rectangle on each image indicates the central area of ​​the calibration tool 124 used as the ROI 131. As stated above, when both light sources 104B and 104C are turned on, the intensity value I at the imaging device 106A is recorded. T12 Ideally, this value should be equal to the target intensity I at imaging device 106A. T1 and target intensity I T2 The method can repeat the same record of target intensity for each other imaging device 106B, 106C with respect to the corresponding front illumination for each illumination wavelength of light (e.g., R, G, and B). In this way, the method completes the first stage of golden device setup using the target intensity value on the calibration tool 124 at the ideal light panel current setting of C1, C2 at the first imaging device 101 ("golden device").

[0084] Therefore, according to the method 600, in block 612, an intensity value is measured for each of the plurality of front light sources 104B, 104C at the corresponding recorded driving currents C1, C2 as the target intensity value I T1 ,I T2 For example, when the light source 104B is turned on and driven at the driving current C1, and the light source 104C is turned off, the target intensity value I of the calibration surface 125 is measured. T1 Similarly, with light source 104C turned on and driven at drive current C2 and light source 104B turned off, a target intensity value I of calibration surface 125 is measured. T2 It is also possible to measure the joint target intensity I with both light sources 104B, 104C turned on. T12 .

[0085] exist Figure 6 In the illustrated embodiment, in block 614, the same process of blocks 602-612 may be followed for each additional wavelength of the light source 104B, 104C that will be used to characterize the sample tube 102 and the cap 114 during characterization. For example, each of the illuminations in 604 may be used for a different wavelength of light, such as, for example, R, G, B, W, IR, and / or NIR. And the target intensity value I in block 602 T1 ,I T2 Each of these can be measured by imaging device 106A and recorded at each illumination wavelength R, G, B, W, IR and / or NIR. A joint target intensity value I can also be recorded T12 The target intensity values ​​described in this article are I T1 ,I T2 ,I T12It may be obtained as an average of multiple measurements taken on the calibration surface 125 (such as within the region of interest 131 ), or as an average of all pixels or blocks (a set of pixels) in the region of interest 131 .

[0086] Similarly, given that a plurality of imaging devices 106A-106C and light sources 104A-104C are arranged around the imaging position 109 and are configured to capture lateral images of the sample tube 102 from a plurality of viewpoints 1, 2, and 3, the method 600 may also be used to perform foreground illumination calibration for other light sources 104B-104C, i.e., for example, the method 600 may be repeated for other viewpoints 2, 3 in block 616. Thus, each of the light sources 104A and 104B may also be used to calibrate the foreground illumination for viewpoint 2 and the intensity I recorded by the imaging device 106C. T1 ,I T2 and I T12 Similarly, light sources 104A and 104C can also be calibrated for viewpoint 3 and intensity I recorded by imaging device 106B. T1 ,I T2 and I T12 This can also be done for all used light sources (e.g. R, G, B, W, IR and / or NIR).

[0087] The imaging devices 106A-106C may be provided proximate to the image window and trained or focused to capture the image window, i.e., the imaging position 109 of the expected position including the surface of the sample tube 102. During calibration, each image may be triggered and captured in response to a trigger signal sent by the computer 143. Each of the captured images may be processed according to one or more embodiments of the method 600 to provide a target intensity value I T1 ,I T2 and I T12 These target intensity values ​​may be recorded as their representative values ​​(eg, mean, median, or mode values) for each image representing all pixels of the calibration surface 125 at its ROI 131 .

[0088] For each of the above settings, all of these multiple images taken at multiple corresponding spectra (e.g., R, G, B, W, NIR, and / or IR) can be acquired in rapid succession, so that, for example, the entire set of images from multiple viewpoints 1, 2, and 3 can be acquired in less than a few seconds. Other lengths of time may be used.

[0089] The calibration method 600 includes imaging that ideally occurs before the imaging device 101 of the quality inspection module 100 actually performs pre-screening imaging measurements. Thus, the calibration can be used for more than one pre-screening operation (e.g., pre-screening of multiple sample tubes 102) before re-calibration is performed again. In some embodiments, a single calibration method 600 can be performed for a particular rack of sample tubes 102, for a number of sample tubes 102, over a day, week, month, or other period of time, after a certain number of sample tubes 102 have been pre-screened, or over any other suitable calibration period or interval.

[0090] Once the target intensity values ​​on the calibration tool 124 are recorded, the method is ready to use these values ​​and the tool 124 (or a similar calibration tool) to calibrate one or more additional imaging devices 101 (e.g., multiple machines). First, the calibration tool 124 (or a similar calibration tool) is moved to the center point (imaging position) of the new imaging device (machine). Then, the drive currents C1, C2 of the light source (e.g., plate) are adjusted until we reach the target intensity I T1 ,I T2 and / or possible I T12 Similar to the previous recordings, each light source (eg, panel) can be adjusted separately and / or jointly for each viewpoint and wavelength of light.

[0091] For example, to calibrate the front illumination of the cloning imaging device 106A, we can first calibrate the current C1 of the cloning light source 104B until the average intensity of the ROI 131 on the calibration tool 124 reaches the recorded value I T1 Then, the method 700 calibrates the driving current C2 of the light source 104C to achieve the target intensity I T2 , while turning off the light source 104B. Optionally, the joint target intensity I may be found by adjusting the current C2 of the light source 104C. T12 , while maintaining the current of light source 102B at the calibrated current C1. To speed up method 700, two or more preset drive current settings (e.g., C1, C2) can be used to measure the corresponding intensities. Using these drive current values, a first-order or second-order equation can be used to approximate the current-intensity curve to predict the current that will generate the target intensity (e.g., I T1 , I T2 ) drive current. Using this estimate, the target intensity can be reached with about 4 iterations. Using this curve fitting can be used to speed up the calibration method.

[0092] Thus, according to method 700, calibration on a first imaging device 101 (golden device) can be used to calibrate other similar (cloned) imaging devices that can be provided in other quality inspection modules that are the same or substantially the same as the quality inspection module 100 that implemented the first calibration method 600. The calibration method 700 can be used to calibrate such additional imaging devices, such as Figure 7 shown.

[0093] Figure 7 A flow chart of a calibration method 700 that can operate with any clone of a first imaging device 101 (golden device) is illustrated. According to one or more embodiments, in 702, the calibration method 700 includes moving the calibration tool 124 to an imaging position (imaging position 109) of a new imaging device to be calibrated (a clone of the first imaging device 101). In block 704, the drive current C1, C2 of each light source (light source 104A, 104B) is adjusted so as to achieve a target intensity measured for the first imaging device, such as a target intensity I T1 ,I T2 ,I T12 Two or more of .

[0094] According to one or more embodiments, the method 700 is used and by using the target intensity I from the first imaging device 101 T1 ,I T2 and / or T12 Calibration of a second imaging device that is a clone of imaging device 101 and possibly subsequent imaging devices may utilize a calibration tool different from calibration tool 124. One advantage of method 700 is that foreground lighting calibration may be automated to ensure consistent lighting across multiple machines (clones of imaging device 101).

[0095] Therefore, one embodiment of the calibration method involves installing the calibration tool 124 at an imaging position of a second imaging device (e.g., a clone of the first imaging device 101), and then calibrating a first drive current C1 of a first light source (a clone of the first light source 104B) of the second imaging device until an average intensity of a region of interest on the calibration tool 124 reaches a measured target intensity value of the first light source 104B of the first imaging device 101. The method further includes calibrating a second drive current C2 of a second light source (e.g., a clone of the second light source 104C) of the second imaging device until an average intensity of the ROI on the calibration tool 124 reaches a measured target intensity value of the second light source 104C of the first imaging device 101 when the first light source is turned off.

[0096] The calibration method may include recording a first target intensity value I of a first light source 104B among a plurality of front light sources of the first imaging device 101. T1, and records the joint target intensity I of the plurality of front light sources (light source 104B and light source 104C illuminated together) which can be used to calibrate such a second imaging device T12 .

[0097] Another embodiment of the calibration method may include installing a calibration tool 124 at an imaging position 109 of a second imaging device (e.g., a clone of the first imaging device 101), and then calibrating a first drive current C1 of a first light source (e.g., a clone of the light source 104B) of the second imaging device until an average intensity of an area of ​​interest on the calibration tool 124 reaches a first target intensity value I of the first light source (e.g., the first light source 104B) of the first imaging device. T1 The method further includes calibrating a second drive current C2 of a second light source (e.g., a clone of light source 104C) of a second imaging device until an average intensity of the ROI on the calibration tool 124 reaches a combined target intensity I of the plurality of front light sources while keeping the first light source of the second imaging device on. T12 .

[0098] In these instances, the new calibration tool may have a different surface reflectivity value than calibration tool 124. Figure 8 The method 800 shown may use a normalization factor N f In block 802 , based on the surface reflectance value Rs1 of the calibration tool 124 used to perform calibration of the first imaging device 101 (the golden device) and the reflectance value R of the new calibration tool used to calibrate another imaging device (the clone of the first imaging device 101 ), a calibration tool 124 is constructed. snew To determine the normalization factor. Normalization factor N f is expressed as:

[0099] N f = R snew / R s1 .

[0100] In 804, the target intensity for calibrating the new imaging device (clone of the first imaging device 101) is determined and expressed as:

[0101] I T1new = I T1 N f

[0102] I T2new = I T2 N f .

[0103] These new target strength values ​​I T1new and I T2newIt can be used together with a new calibration tool installed in the new imaging device at its imaging position 109 to calibrate the new imaging device by adjusting the drive current of the front light source of each corresponding clone for a specific viewpoint 1-3 and wavelength. For example, clones of light sources 104B, 104C for viewpoint 1, clones of light sources 104A, 104C for viewpoint 2, and clones of light sources 104A, 104B for viewpoint 3. Clones as used herein refer to imaging components such as light sources 104A-104C, imaging devices 106A-106C, housings, etc. that will affect the images being cloned (functional copies) of those of the first imaging device 101. Some changes can be made to the components of the second imaging device as long as they do not affect its optical properties.

[0104] Using the methods described herein, consistent illumination can be provided across multiple imaging devices of a machine. This allows for characteristic sample tube type characterization based on cap color and appearance, which is useful, for example, for tube sorting purposes, or even for identifying incorrect sample tube usage for a scheduled test.

[0105] Device-dependent settings without calibration tools

[0106] Once you have a calibrated drive current for a particular imaging device 101 (machine), you can recalibrate the foreground illumination without using the calibration tool 124. This is useful when a light source (e.g., light panel) gradually degrades or is replaced, while the entire setup in terms of the geometrical layout of the imaging devices 106A-106C and the light sources 104A-104C remains unchanged. Based on the previous calibration method 600 using the calibration tool 124, the target intensity can be measured directly on the light source 104A-104C (e.g., light panel) instead of using the calibration tool 124.

[0107] For example, when there is no calibration tool 124, in order to calibrate light source 104B serving as the front light source of imaging device 106A and light source 104C serving as the front light source of imaging device 106A, the intensity value of light source 104B observed by imaging device 106B and the intensity value of light source 104C observed by imaging device 106C are recorded when light source 104C and light source 106C are separately turned on with their corresponding calibrated driving currents C1 and C2.

[0108] Imaging device 106B ( Fig.9A ) and the sample image of the light source 104B observed by the imaging device 106C is as follows Fig. 9B. These are sample images for recalibration without calibration tool 124. Front illumination of imaging device 106A from light source 104B and light source 104C is directly calibrated when (a) light source 104B is observed by imaging device 106B and (b) light source 104C is observed by imaging device 106C. The black rectangle on each image indicates the center area of ​​the board, which is used as region of interest (ROI) 931.

[0109] Therefore, the calibration method may further include: measuring a first intensity value I1 at an area of ​​interest 931 of a first front light source (e.g., light source 104B) among the plurality of front light sources using a first imaging device (e.g., imaging device 106B) directly facing the first front light source (e.g., light source 104B) without the calibration tool 124 at the imaging position 109, and measuring a second intensity value I2 at an area of ​​interest 931 of a second front light source (e.g., light source 104C) among the plurality of front light sources using a second imaging device (e.g., imaging device 106C) directly facing the second front light source (e.g., light source 104C). The first intensity value I1 and the second intensity value I2 may then be used to recalibrate the front lighting first imaging device 101. This recalibration may occur from time to time at any suitable interval as a front lighting quality check.

[0110] It is to be noted that since the calibration tool 124 has a relatively lower reflectivity value than the light source (plate), the direct light observed from the imaging device without the calibration tool 124 will easily saturate the intensity. Therefore, it may be desirable to, for example, reduce the exposure time of the corresponding light source while keeping its drive current the same as C1, C2, and then use the imaging device 106B, 106C directly facing the corresponding light source 104B, 104C to record its intensity at the ROI 931 of the corresponding light source 104B, 104C. With these tool-independent target intensity settings, we can calibrate the foreground illumination separately by directly using the image of the corresponding imaging device 106B, 106C. We can also adopt a similar curve fitting method as discussed above to accelerate the method. According to this recalibration method, when trying to restore the drive current without the calibration tool 124, a current difference of less than 5% can be obtained.

[0111] The tool-free approach allows health checks to be run without requiring an operator / system to manually load any special tools, where such health checks can be done automatically. This automated approach allows health checks to be run on a periodic or other incremental basis, thereby ensuring the quality / performance required in medical testing devices (such as quality inspection equipment).

[0112] According to another embodiment, a calibration method is provided that can perform a health check on a previously calibrated imaging device. In particular, referring to Fig.10 A calibration method 1000 is shown and described. The calibration method 1000 includes, in block 1002, providing a previously calibrated imaging device (e.g., imaging device 100) that has been previously calibrated according to an initial calibration method (e.g., calibration method 600 or other suitable calibration method). The calibration method 1000 further includes, in block 1004, placing a calibration tool 1124 having a calibration surface 1125 of known reflectivity R1 at an imaging position 109 of the previously calibrated imaging device 100. The calibration tool 1124 can be any type of tool having a calibration surface 1125 of known reflectivity R1 for each viewpoint, such as Fig.11A and 11B The cylindrical calibration tool 1124 is shown. The calibration tool 1124 has a calibration surface 1125 of a known reflectivity R1 value. In this embodiment, the calibration surface 1125 can extend 360 degrees around the circumference of the calibration tool 1124 and can be applied as a label or as a painted surface. Therefore, the calibration surface can be viewable from multiple viewpoints (such as, viewpoints 1, 2, and 3). The calibration tool 1124 can have a certified reflective surface to facilitate the calibration method. Therefore, the calibration surface 1125 of known reflectivity R1 can be provided for each of viewpoints 1, 2 and 3, respectively. The calibration tool 1124 can further include a retaining portion 1127, which can be the shape of the bottom of the sample tube 102, so that the calibration tool 1124 can be accommodated in the carrier 122 in a vertical orientation at the imaging position 109 of the previously calibrated imaging device 100 (see Figure 4A ).

[0113] The calibration method 1000 further includes, in block 1006, illuminating the calibration surface 1125 with light emitted from one or more front light sources calibrated according to the initial calibration method. For example, the one or more light sources for front illumination may include light sources 104B, 104C for viewpoint 1. Similarly, the one or more light sources for front illumination for viewpoint 2 may be light sources 104A and 104C. Similarly, the one or more light sources for front illumination for viewpoint 3 may be light sources 104A and 104B.

[0114] The calibration method 1000 further includes: in box 1008, measuring the intensity value at the region of interest 1131 of the calibration surface 1125. This can be done for each viewpoint 1, 2 and 3. In this embodiment, the region of interest (ROI) 1131 is a region that is almost as wide as the calibration tool 1124 and is high enough to cover the area in which the serum or plasma portion 212SP may be located during imaging in use. In addition, the region of interest 1131 should have approximately the same size as the region of interest (ROI) used for initial calibration. Finally, the method 110 includes: in box 1110, verifying that the previously calibrated imaging device 100 is still performing within specifications based on the measured intensity value of the region of interest (ROI) 1131.

[0115] like Fig.11A As shown, the calibration tool 1124 may include a data matrix 1129 that is readable from at least one viewpoint (such as viewpoint 1 as shown). The data matrix may be a unique serial number that may be encoded, for example, in the data matrix 129. As shown, the data matrix 1129 may be read by the imaging device 106A to look up the corresponding surface reflectance measurement R in a database. Alternatively, the surface reflectance value itself may be encoded in the data matrix 1129. If the same calibration tool 1124 is used for the initial calibration, the reflectance value R1 may be used. However, if a different calibration tool is used for the initial calibration, the normalization factor N should be used as described below. f Normalize the reflectivity value R1. Normalization factor N f is expressed as:

[0116] N f = R1 / R old

[0117] Where R old is the reflectivity of the initial calibration surface used.

[0118] According to another aspect of the calibration method 1000, if the previously calibrated imaging device 100 is found to be outside of the allowable specifications when attempting to verify that the previously calibrated imaging device is within specifications in box 1010, the corresponding intensity value of the region of interest 1131 can be adjusted in box 1012. The desired intensity at the region of interest 1131 is the calibrated intensity value of the region of interest that has been pre-calibrated according to the initial calibration method. Depending on the manner in which the intensity exceeds the specification, the adjustment can be upward or downward. The specification can be a band of preset intensities, such as + / - 5% from a target nominal intensity value, for example. In particular, the adjustment in box 1012 can include adjusting the drive current to one or more front light sources to establish the desired intensity at the region of interest 1131.

[0119] It should be appreciated that initial calibration may be accomplished by any method in which measurements of the intensity of a region of interest (ROI) are obtained. In some embodiments, a previously calibrated imaging device 100 may be initially calibrated according to a reference Figure 6 The calibration tool 1124 may be calibrated using the method described. In some embodiments, the calibration tool 1124 having a calibration surface 1125 of known reflectivity R1 may include a gray surface. The gray surface may substantially surround the circumference of the calibration tool 1124 and may extend vertically so that the gray surface is at least as large as the region of interest 1131. As shown, the calibration tool 1124 includes a cylindrical outer surface. However, the calibration tool may have other configurations, such as having a flat surface for each respective viewpoint 1, 2, 3.

[0120] Further health checks may be performed using the calibration tool 1124 to verify other aspects of the health of the previously calibrated imaging device 100. In particular, a white balance health check and / or an ambient light health check may be performed. The ambient light health check helps ensure that there is not excessive light (in any color channel). The white balance health check may verify that all three imaging devices 106A, 106B, 106C are internally white balanced. The gray imaging surface 1125 of the calibration tool 1124 is used as a reference material because the expectation is that all three color channels (RGB) will output similar values ​​(within tolerance) to the sensors of the imaging devices 106A, 106B, 106C.

[0121] In the case where the calibration tool 1124 has a cylindrical outer surface, the image of the region of interest 1131 for each viewpoint 1, 2 and 3 may be divided vertically into a plurality of sub-regions, such as Fig. 11C Three equal-sized sub-regions A, B and C are shown. In particular, a region of interest (ROI) 1131 is extracted for each viewpoint 1, 2 and 3 by each corresponding imaging device 106A, 106B, 106C, and each image is processed by dividing each image vertically into three sub-regions (equal sub-regions A, B, C). For each sub-region A, B and C, the R / G / B values ​​received by the sensors of the corresponding imaging devices 106A, 106B and 106C will ideally be within the pre-designed tolerances. Color values ​​outside the tolerance will indicate an inappropriate white balance for the sub-region, which can then be adjusted. For example, incorrect white balance may result in the detection of the wrong cap color. In addition, sub-regions A and C and region B may cause a maximum intensity tolerance check to be performed (for all color channels) to ensure that there is not too much ambient light for any channel. The presence of too much external / ambient light may result in a faded barcode.

[0122] Although the present invention is susceptible to various modifications and alternative forms, its specific system, device and method embodiments have been shown by way of example in the drawings and described in detail herein. However, it should be understood that this is not intended to limit the present disclosure to the specific systems, devices or methods disclosed, but on the contrary, the present invention is intended to cover all modifications, equivalents and substitutes falling within the scope of the claims.

Claims

1. A calibration method, comprising: providing a calibration tube including an imaging surface at an imaging position of an imaging device; illuminating the imaging surface with light emitted from a plurality of front light sources; adjusting a drive current to each of the plurality of front light sources to establish a substantially uniform intensity across the imaging surface; Recording driving current values ​​of the plurality of front light sources; replacing the calibration tube with a calibration tool having a calibration surface of known reflectivity; as well as The target intensity value of the calibration tool is measured at the corresponding driving current value. 2 . The calibration method according to claim 1 , wherein the measurement of the target intensity value of the calibration tool at the driving current value is performed by an imaging device. 3 . The calibration method of claim 1 , wherein adjusting the drive current to each of the plurality of front light sources occurs sequentially.

4. A calibration method according to claim 1, wherein the target intensity value comprises an average intensity of a region of interest on the calibration tool.

5. The calibration method according to claim 1, further comprising: installing the calibration tool at an imaging position of a separate imaging device; as well as The drive current is adjusted to a current value of each front light source of the separate imaging device to achieve the same target intensity value measured for the imaging device.

6. The calibration method according to claim 5, further comprising: The driving current is adjusted to a current value of each front light source so that an intensity value of each front light source of the separate imaging device is the same as a target intensity value of each front light source of the imaging device.

7. The calibration method according to claim 1, further comprising: installing a calibration tool at an imaging location of a separate imaging device; calibrating a first drive current of a first light source of the separate imaging device until an average intensity of a region of interest on the calibration tool reaches a measured target intensity value of the first light source of the imaging device; as well as A second drive current of a second light source of the separate imaging device is calibrated until an average intensity of an area of ​​interest on the calibration tool reaches a measured target intensity value of the second light source of the imaging device when the first light source is turned off.

8. The calibration method according to claim 1, further comprising: recording a first target intensity value of a first light source of the plurality of front light sources, and A combined target intensity of the plurality of front light sources is recorded.

9. The calibration method according to claim 8, further comprising: installing a calibration tool at an imaging location of a separate imaging device; calibrating a first driving current of a first light source of the separate imaging device until an average intensity of a region of interest on the calibration tool reaches a first target intensity value of the first light source of the imaging device; as well as A second drive current of the second light source of the separate imaging device is calibrated until an average intensity of an area of ​​interest on the calibration tool reaches a combined target intensity of the plurality of front light sources while keeping the first light source of the separate imaging device on.

10. The calibration method according to claim 1, further comprising: In the absence of a calibration tool at the imaging location, measuring a first intensity value at a region of interest of a first front light source of the plurality of front light sources using a first imaging device directly facing the first front light source, and A second intensity value at a region of interest of a second front light source of the plurality of front light sources is measured using a second imaging device directly facing the second front light source.

11. The calibration method according to claim 10, further comprising: Later, the imaging device is recalibrated using the first intensity value and the second intensity value. 12 . The calibration method according to claim 1 , wherein illuminating the imaging surface with the light emitted from the plurality of front light sources is performed for each spectrum of light used for illumination.

13. The calibration method of claim 1, wherein the plurality of front light sources comprises a spectrally switchable illumination source, the illumination source being spectrally switchable between at least two spectra.

14. The calibration method of claim 1, wherein the imaging location is located within an imaging chamber formed by a collection of walls of a housing of the imaging device.

15. The calibration method of claim 1, wherein the calibration tube is located at the imaging position and resides on a carrier.

16. A calibration method according to claim 1, wherein the substantially uniform intensity of the imaging surface is measured by an imaging device and is uniform within + / - 20% of the average intensity in the region of interest when measured on a pixel-by-pixel basis.

17. The calibration method of claim 1, wherein replacing the calibration tube with a calibration tool having a calibration surface of known reflectivity comprises: An alternative is to use a calibration tool that is prism-shaped, with each flat side facing the imaging device.

18. The calibration method of claim 17, wherein each side of the calibration tool corresponding to each viewpoint has a certified reflective surface with a known reflectivity value.

19. The calibration method according to claim 1, comprising: providing a previously calibrated imaging device that has been previously calibrated according to the calibration method of claim 1; placing a calibration tool having a calibration surface of known reflectivity at an imaging location of a previously calibrated imaging device; illuminating the calibration surface with light emitted from one or more previously calibrated front light sources; measuring intensity values ​​of a region of interest of the calibration surface; as well as A previously calibrated imaging device is verified to still be performing within specifications based on the measured intensity values ​​of the region of interest.

20. A quality inspection module, comprising: an imaging location within the quality inspection module configured to receive a sample container to be characterized; an imaging device configured to capture images of the imaging location from a plurality of viewpoints; a plurality of light sources configured to provide front lighting for the imaging device; a calibration tube including an imaging surface located at said imaging position during a first calibration phase; as well as A calibration tool having a plurality of calibration surfaces of known reflectivity located at the imaging position during the second calibration phase, wherein a respective calibration surface of each of the plurality of calibration surfaces is arranged to be viewed from a respective one of the plurality of viewpoints.

Images