Substance Preparation Evaluation System

Abstract

To provide automatic substance preparation and evaluation.SOLUTION: Automatic substance preparation and evaluation systems and methods are provided for preparing and evaluating a fluidic substance such as a sample with bodily fluid in a container and / or in a dispense tip. The systems and methods can detect volumes, evaluate integrity, and check particle concentrations in the container and / or the dispense tip. In one embodiment, a method of evaluating a fluidic substance in a container comprises: capturing, using an image capture device, an image of at least a portion of the container; using at least one computing device to obtain a plurality of color parameters of at least a portion of the image; and generating a sample classification result for the fluidic substance contained in the container based on the plurality of color parameters, where the sample classification result is representative of a concentration of at least one interferent in the fluidic substance.SELECTED DRAWING: Figure 1

Description

Technical Field

[0001] (Cross - Reference to Related Applications) This application was filed as a PCT international patent application on October 27, 2017, and claims the benefit of priority to U.S. Provisional Patent Application No. 62 / 414,655, filed on October 28, 2016, and U.S. Provisional Patent Application No. 62 / 525,948, filed on June 28, 2017. The entire disclosures of these are hereby incorporated by reference in their entirety into this specification.

[0002] (Field of the Invention) The present invention generally relates to the field of automated substance preparation and evaluation. Specifically, the present invention relates to methods and systems for evaluating fluid substances such as, for example, samples with body fluids in a container and / or at a dispensing tip. Further, the present invention relates to computer program elements for instructing a computer device and / or a processing device to perform any of the steps of a method for evaluating a fluid substance. The present invention also relates to a computer - readable medium storing such computer program elements.

Summary of the Invention

Means for Solving the Problems

[0003] It may be an object of the present invention to provide improved methods and systems for automatically evaluating fluid substances with improved reliability, improved quality, improved accuracy, and improved throughput.

[0004] The object of the present invention is solved by the subject matter of the independent claims, to which further embodiments are incorporated in the dependent claims and the following description.

[0005] According to a first aspect of the present disclosure, a method for evaluating a fluid substance in a container is provided. In particular, the method according to the first aspect may refer to a method for operating a dispensing tip evaluation system as exemplarily described with reference to FIG. 1, and / or a method for operating a sample quality detection device as exemplarily described with reference to FIGS. 42-55. Further, the method according to the first aspect may refer to a method for operating a volume detection system as exemplarily described with reference to FIGS. 5-15 and / or FIGS. 9-21. Also, the method of the first aspect may refer to a method for operating a correlation data generation system as exemplarily described with reference to FIGS. 8-21.

[0006] The method according to the first aspect comprises capturing an image of at least a part of the container using an image capturing device, the image capturing device may comprise an image capturing unit, acquiring a plurality of color parameters of at least a part of the image using at least one computer device and / or at least one processing device, generating a sample classification result of the fluid substance contained in the container based on the plurality of color parameters and comprising. Wherein the sample classification result represents and / or indicates the concentration of at least one interfering substance in the fluid substance. Herein, and hereinafter, the image capturing device and / or the image capturing unit may refer to, for example, a dispensing tip image capturing unit.

[0007] According to an embodiment of the method of the first aspect, the step of acquiring a plurality of color parameters comprises generating a histogram of at least a part of the image, the histogram comprising a plurality of color channels, acquiring a plurality of average values and / or an average of the plurality of color channels, the plurality of color parameters comprising the plurality of average values of the plurality of color channels, and comprising. Among them, the average and / or the mean value may be determined for each of the color channels or for a part of the color channels.

[0008] According to an embodiment of the method of the first aspect, the step of obtaining a plurality of color parameters includes generating a histogram of at least a part of the image, the histogram comprising a plurality of color channels, obtaining and / or determining a plurality of Riemann sums of the plurality of color channels, the plurality of color parameters including the plurality of Riemann sums of the plurality of color channels, and Among them, the Riemann sum may be obtained and / or determined for each of the color channels or for a part of the color channels.

[0009] According to an embodiment of the method of the first aspect, the step of obtaining a plurality of color parameters includes generating a histogram of at least a part of the image, the histogram comprising a plurality of color channels, obtaining a plurality of modes of the plurality of color channels, obtaining a plurality of maximum values of the plurality of color channels, and / or obtaining a plurality of minimum values of the plurality of color channels, the plurality of color parameters including the plurality of modes, maximum values, and / or minimum values of the plurality of color channels, and

[0010] According to an embodiment of the method of the first aspect, the step of obtaining a plurality of color parameters includes generating a histogram of at least a part of the image, the histogram comprising a plurality of color channels, obtaining a plurality of histogram heads of the plurality of color channels, obtaining a plurality of histogram tails of the plurality of color channels, Obtaining the plurality of histogram head rates of the plurality of color channels, and / or Obtaining the plurality of histogram tail rates of the plurality of color channels, wherein the plurality of color parameters include the plurality of histogram heads, histogram tails, histogram head rates, and / or histogram tail rates of the plurality of color channels, step including.

[0011] According to an embodiment of the method of the first aspect, the plurality of color parameters include at least one of the plurality of averages of the color channels, the plurality of Riemann sums of the color channels, the plurality of modes of the color channels, the plurality of maximum values of the color channels, the plurality of minimum values of the color channels, the plurality of histogram heads of the color channels, the plurality of histogram tails of the color channels, the plurality of histogram head rates of the color channels, the plurality of histogram tail rates of the color channels, or any combination of the foregoing.

[0012] According to an embodiment of the method of the first aspect, the plurality of color channels include, for example, a red component, a green component, and a blue component in the RGB model. However, any other type of color model, such as the CMYK color model, may also be used.

[0013] According to an embodiment of the method of the first aspect, the sample classification result includes at least one classification identifier, and at least one classification identifier is correlated with at least a part of the plurality of color parameters and / or correlated with the concentration of at least one interfering substance in the fluid substance.

[0014] According to an embodiment of the method of the first aspect, the method further includes generating a flagging result based on the sample classification result, and the flagging result indicates the quality of the fluid substance. Alternatively, or in addition, the quality of the fluid substance is based on the sample eligibility result.

[0015] According to an embodiment of the method of the first aspect, at least one interfering substance is one or more selected from hemoglobin, jaundice, and lipemia.

[0016] According to an embodiment of the method of the first aspect, the container is a dispensing tip configured to aspirate a fluid substance and / or a sample.

[0017] According to an embodiment of the method of the first aspect, the image capture device is configured and / or arranged to capture an image of a part of the fluid substance and / or the container from the side of the container.

[0018] According to an embodiment of the method of the first aspect, the method further comprises identifying and / or determining a reference point in the image using at least one computer device, wherein the reference point is associated with the container, and identifying and / or determining the surface level of the fluid substance in the container in the image using at least one computer device, and determining and / or measuring the distance between the reference point and the surface level, and converting the distance into the volume of the fluid substance based on correlation data, wherein the correlation data includes information about the correlation between the volume in the container and the distances from the reference point to a plurality of surface levels in the container, including. However, it should be noted that the term "correlation data" may also refer to an equation and / or a functional relationship between distance and volume.

[0019] According to an embodiment of the method of the first aspect, the distance is measured by a pixel distance.

[0020] According to an embodiment of the method of the first aspect, the container is a dispensing tip configured to suck a fluid substance, and the step of identifying a reference point includes identifying and / or determining a reference line formed on the dispensing tip, for example, a reference line formed on the body of the dispensing tip.

[0021] According to an embodiment of the method of the first aspect, the reference line is identified based on pattern matching of the captured image and / or based on segmentation.

[0022] According to an embodiment of the method of the first aspect, the step of identifying the reference line includes searching for a pattern representing the reference line in the captured image.

[0023] According to an embodiment of the method of the first aspect, the step of identifying the reference line includes comparing at least a part of the captured image with a reference image.

[0024] According to an embodiment of the method of the first aspect, the method further includes determining a matching rate, a matching score, and / or a correlation value of a part of the captured image and the reference image.

[0025] According to an embodiment of the method of the first aspect, the method further includes supplying the liquid to a further container, determining the volume of the supplied liquid, capturing a further image of the container, determining the pixel distance between reference points in the image associated with the further container, correlating the determined volume with the determined pixel distance and including.

[0026] According to an embodiment of the method of the first aspect, the method further includes generating correlation data based on the determined volume and the determined pixel distance.

[0027] According to an embodiment of the method of the first aspect, the correlation data is generated based on a plurality of correlations between a plurality of determined pixel distances and a plurality of determined volumes of the liquid supplied to the further container.

[0028] According to an embodiment of the method of the first aspect, the supplied liquid comprises a dye solution. Alternatively, or in addition, the volume of the supplied liquid is determined based on spectrophotometry.

[0029] According to an embodiment of the method of the first aspect, the step of determining the volume of the supplied liquid includes the step of determining the mass of the supplied liquid.

[0030] Note that any embodiment of the method according to the first aspect as described above can be combined with one or more further embodiments of the method according to the first aspect as described above. This may make it possible to provide particularly advantageous synergistic effects.

[0031] According to a second aspect of the present disclosure, a computer program element is provided that, when executed on a computer device of a system for evaluating a fluid substance, instructs the computer device and / or the system to perform the steps of the method according to the first aspect and / or according to any embodiment of the first aspect.

[0032] According to a third aspect of the present disclosure, a non-transitory computer-readable medium is provided on which the computer program element according to the second aspect of the present disclosure is stored.

[0033] According to a fourth aspect of the present disclosure, a system for evaluating a fluid substance is provided. In particular, the system according to the fourth aspect may refer to, for example, a dispensing tip evaluation system as exemplarily described with reference to FIG. 1, and / or a sample quality detection device as exemplarily described with reference to FIGS. 42-55. Also, the system according to the fourth aspect may refer to a volume detection system as exemplarily described with reference to FIGS. 1, 6-15, and / or FIGS. 9-21. Also, the system according to the fourth aspect may refer to a correlation data generation system as exemplarily described with reference to FIGS. 8-21.

[0034] The system according to the fourth aspect comprises a sample pipetting device having a dispensing tip. The sample pipetting device may refer to a substance pipetting device. Among them, the sample pipetting device is configured to at least partially engage with the dispensing tip and aspirate the fluid substance into the dispensing tip. The system may further comprise an image capture unit and at least one computer device that may be provided with and / or refer to a processing device. Among them, the image capture unit is configured to capture an image of at least a part of the fluid substance in the dispensing tip, and the computer device is configured to obtain a plurality of color parameters of at least a part of the image and generate a sample classification result of the fluid substance contained in the dispensing tip based on the plurality of color parameters, and the sample classification result represents and / or indicates the concentration of at least one interfering substance in the fluid substance. quality detection device as exemplarily described with reference to FIGS. 42-55. Also, the system according to the fourth aspect may refer to a volume detection system as exemplarily described with reference to FIGS. 1, 6-15, and / or FIGS. 9-21. Also, the system according to the fourth aspect may refer to a correlation data generation system as exemplarily described with reference to FIGS. 8-21.

[0035] In other words, the present system may comprise a sample pipetting operation device having a dispensing tip, the sample pipetting operation device being configured to engage with the dispensing tip, the sample pipetting operation device being configured to aspirate a fluid substance into the dispensing tip. The system may further comprise an image capture unit configured to capture an image of at least a part of the fluid substance in the dispensing tip, at least one computer device, and at least one computer-readable storage medium storing instructions that, when executed by the at least one computer device, cause the system to capture an image of at least a part of the fluid substance in the dispensing tip using the image capture unit, obtain a plurality of color parameters of at least a part of the image, and generate a sample classification result of the fluid substance contained in the dispensing tip based on the plurality of color parameters, the sample classification result representing the concentration of at least one interfering substance in the fluid substance.

[0036] According to an embodiment of the system of the fourth aspect, the computer device further generating a histogram of at least a part of the image, the histogram comprising a plurality of color channels, obtaining a plurality of average values of the plurality of color channels, and / or obtaining a plurality of Riemann sums of the plurality of color channels configured to perform, and / or the software instructions further cause the system to perform these. Among them, the plurality of color parameters include a plurality of averages and / or a plurality of Riemann sums of the color channels.

[0037] According to an embodiment of the system of the fourth aspect, the sample classification result comprises at least one classification identifier, and the at least one classification identifier is correlated with at least a part of a plurality of color parameters and / or with the concentration of at least one interfering substance in the fluid substance. Among them, the sample classification result may include at least one of the plurality of classification identifiers, and the plurality of classification identifiers are correlated with the plurality of color parameters.

[0038] According to an embodiment of the system of the fourth aspect, the computer device further identifies a reference point in the image, wherein the reference point is associated with the dispensing tip, and identifies the surface level of the fluid substance within the dispensing tip in the image, and determines and / or measures the distance between the reference point and the surface level, and converts the distance into the volume of the fluid substance based on correlation data, wherein the correlation data includes information about the correlation between the volume within the dispensing tip and the distances from the reference point to a plurality of surface levels within the dispensing tip, and is configured to perform, and / or the software instructions further cause the system to perform these. Among them, the correlation data may also refer to an equation and / or a functional relationship between the distance and the volume.

[0039] According to an embodiment of the system of the fourth aspect, the computer device is configured to determine a reference line formed on the body of the dispensing tip and to determine a reference point based on the determined reference line. Among them, the reference point in the image may include the reference line formed on the body of the dispensing tip. reference line.

[0040] According to an embodiment of the system of the fourth aspect, the computer device is configured to determine the reference line based on pattern matching of the captured image and / or based on segmentation.

[0041] According to an embodiment of the system of the fourth aspect, the computer device is configured to search for and / or identify a pattern representing a reference line in a captured image.

[0042] According to an embodiment of the system of the fourth aspect, the computer device is configured to compare at least a part of the captured image with a reference image.

[0043] According to an embodiment of the system of the fourth aspect, the computer device is configured to determine a matching rate, a matching score, and / or a correlation value of a part of the captured image and the reference image.

[0044] According to an embodiment of the system of the fourth aspect, the image capture unit is configured and / or arranged to capture an image of a part of the fluid substance from the side of the dispensing tip.

[0045] According to an embodiment of the system of the fourth aspect, the system further includes a sample pipetting operation module, and the image capture unit is attached to the sample pipetting operation module.

[0046] According to an embodiment of the system of the fourth aspect, the system further includes a light source positioned opposite to the image capture unit and positioned on the side of the dispensing tip, and the light source is configured to irradiate the dispensing tip from the side of the dispensing tip.

[0047] According to an embodiment of the system of the fourth aspect, the system further includes a light source and a sample pipetting operation module, the light source and the image capture unit are attached to the sample pipetting operation module, and / or the light source and the image capture unit are configured to move horizontally, for example, together with the sample pipetting operation module so that an image of the dispensing tip can be captured at any position of the sample pipetting operation module. Specifically, the image may be captured at any position along the track and / or along the sample transfer guide of the sample pipetting operation module.

[0048] According to an embodiment of the system of the fourth aspect, the sample pipetting device is configured to aspirate liquid into a further dispensing tip, the system is configured to determine the volume of the aspirated liquid, the image capture unit is configured to capture a further image of the further dispensing tip, the computer device is configured to determine the pixel distance between reference points in the image associated with the further dispensing tip, and to correlate the determined volume with the determined pixel distance.

[0049] According to an embodiment of the system of the fourth aspect, the computer device is configured to generate correlation data based on the determined volume and the determined pixel distance.

[0050] According to an embodiment of the system of the fourth aspect, the correlation data is generated based on a plurality of correlations between a plurality of determined pixel distances and a plurality of determined volumes of liquid aspirated into the further dispensing tip.

[0051] According to an embodiment of the system of the fourth aspect, the aspirated liquid comprises a dye solution. Alternatively, or in addition, the system is configured to determine the volume of the aspirated liquid based on spectrophotometry. Alternatively, or in addition, the system is configured to determine the volume of the aspirated liquid based on spectrophotometry.

[0052] According to an embodiment of the system of the fourth aspect, the system is configured to determine the mass of the aspirated liquid and to determine the volume of the aspirated liquid based on the determined mass of the aspirated liquid.

[0053] Note that any embodiment of the system according to the fourth aspect as described above can be combined with one or more further embodiments of the system according to the fourth aspect as described above. This may make it possible to provide particularly advantageous synergistic effects.

[0054] Furthermore, note that any features, functions, characteristics, and / or elements of the system according to the fourth aspect, as described above and below, may be features, functions, characteristics, steps, and / or elements of the method according to the first aspect, as described above and below. Conversely, any features, functions, characteristics, steps, and / or elements of the method according to the first aspect, as described above and below, may be features, functions, characteristics, and / or elements of the system according to the fourth aspect, as described above and below.

[0055] According to a fifth aspect of the present disclosure, a system for evaluating a fluid substance is provided. In particular, the system according to the fifth aspect may refer to an advanced alignment detection device, as exemplarily described with reference to FIGS. 56 - 58, for example. The system according to the fifth aspect may further refer to a dispensing tip evaluation system and / or a volume detection system, as exemplarily described with reference to FIGS. 1, 5 - 15, and / or FIGS. 9 - 21, for example. Also, the system according to the fifth aspect may refer to a correlation data generation system, as exemplarily described with reference to FIGS. 8 - 21.

[0056] The system according to the fifth aspect comprises a sample pipette operating device configured to at least partially engage with a dispensing tip, the sample pipette operating device being configured to aspirate a fluid substance into the dispensing tip, the dispensing tip having at least one reference line. The sample pipette operating device may refer to a substance pipette operating device. The system further comprises an image capture unit configured to capture an image of at least a portion of the dispensing tip, and at least one computer device, the at least one computer device may include a processing device, the processing device being identifying at least one reference line of the dispensing tip from a portion of the image of the dispensing tip, and determining at least one characteristic of the at least one reference line, and Comparing at least one characteristic of at least one reference line with a threshold value configured to perform, the threshold value being for at least one computer device representing an inconsistency of the dispensing tip and comprising. The computer device may be configured to determine whether at least one characteristic of at least one reference line meets the threshold value, the threshold value representing an inconsistency of the dispensing tip. Among them, the inconsistency may refer to an inconsistency with respect to the image capture unit and / or with respect to the sample pipetting operation module.

[0057] The system may also comprise at least one computer-readable data storage medium storing software instructions, the software instructions, when executed by at least one processing device and / or by a computer device, cause the system to , identifying at least one reference line of the dispensing tip from an image of the dispensing tip, obtaining one or more characteristics of at least one reference line, determining whether the characteristic of at least one reference line meets a threshold value, the threshold value representing an inconsistency of the dispensing tip, and perform.

[0058] According to an embodiment of the system of the fifth aspect, at least one reference line comprises a first reference line and a second reference line formed on the dispensing tip.

[0059] According to an embodiment of the system of the fifth aspect, at least one reference line comprises a first reference line and a second reference line formed on the dispensing tip, and the at least one computer device further determining and / or calculating the length of the first reference line, determining and / or calculating the length of the second reference line, Determining and / or calculating the angle of a line relative to at least one of a first reference line and a second reference line, the line connecting a pre-determined point on the first reference line and a pre-determined point on the second reference line; Obtaining at least one characteristic of at least one reference line based thereon; Determining a dispensing tip misalignment, e.g., relative to an image capture unit and / or relative to a sample pipetting operation module, based on at least one of the length of the first reference line, the length of the second reference line, and the angle of the line; and / or software instructions are further configured to cause the system to perform these.

[0060] According to an embodiment of the system of the fifth aspect, the system is configured to prevent a sample pipetting device from aspirating a fluid substance into the dispensing tip in response to determining a misalignment, and / or software instructions are further configured to cause the system to perform this. As an example, a computer device may be configured to generate and / or output an interrupt signal in response to determining a misalignment.

[0061] According to an embodiment of the system of the fifth aspect, at least one computer device is further configured to flag and / or initiate aspiration of a fluid substance into the dispensing tip in response to determining a misalignment, and / or software instructions are further configured to cause the system to perform this.

[0062] According to an embodiment of the system of the fifth aspect, at least one computer device is further configured to: Identify at least one reference line of the dispensing tip from a portion of an image of the dispensing tip; Identify the surface level of a fluid substance within the dispensing tip in the image; Determine and / or measure the distance between the at least one reference line and the surface level; A step of determining the volume of a fluid substance by converting a distance into the volume of the fluid substance based on correlation data, wherein the correlation data includes information about the correlation between the volume inside the dispensing tip and the distance from at least one reference line to a plurality of surface levels inside the dispensing tip. configured to perform, and / or software instructions further cause the system to perform these. Among them, the correlation data can also refer to an equation and / or a functional relationship between distance and volume.

[0063] According to an embodiment of the system of the fifth aspect, the computer device is configured to determine a reference line based on pattern matching of the captured image and / or based on segmentation.

[0064] According to an embodiment of the system of the fifth aspect, the computer device is configured to search for a pattern representing a reference line in the captured image.

[0065] According to an embodiment of the system of the fifth aspect, the computer device is configured to compare at least a part of the captured image with a reference image.

[0066] According to an embodiment of the system of the fifth aspect, the computer device is configured to determine the matching rate, matching score, and / or correlation value of a part of the captured image and the reference image.

[0067] According to an embodiment of the system of the fifth aspect, at least one reference line includes a first reference line and a second reference line formed on the dispensing tip, and at least one computer device further determining and / or calculating the length of the first reference line in the image; determining and / or calculating the length of the second reference line in the image; Determining and / or calculating the angle of a line with respect to at least one of a first reference line and a second reference line, wherein the line connects a pre-determined point on the first reference line and a pre-determined point on the second reference line Based on at least one of the length of the first reference line, the length of the second reference line, and the angle of the line, determining a dispensing tip misalignment, e.g., with respect to an image capture unit and / or with respect to a sample pipetting operation module Adjusting the volume of the fluid substance based on the determination of the misalignment Is configured to perform, and / or the software instructions further cause the system to perform these

[0068] According to an embodiment of the system of the fifth aspect, the dispensing tip misalignment includes a lateral misalignment and a depth misalignment. Among them, the lateral misalignment may refer to the displacement of the dispensing tip with respect to the optical axis of the camera and / or the image capture unit. The depth misalignment may refer to the displacement of the dispensing tip along the optical axis of the camera and / or the image capture unit

[0069] According to an embodiment of the system of the fifth aspect, at least one reference line includes a first reference line and a second reference line formed on the dispensing tip, and at least one computer device further Identifying a pre-determined point of the first reference line in the image Identifying a pre-determined point of the second reference line in the image Defining an alignment line connecting the pre-determined point of the first reference line and the pre-determined point of the second reference line Determining the angle of the alignment line with respect to at least one of the first reference line and the second reference line Comparing the angle with a threshold angle value Is configured to perform, and the threshold angle value represents the lateral misalignment of the dispensing tip, and / or the software instructions further cause the system to perform these Among them, it may be determined whether the angle of the alignment line is less than a threshold angle value, and the threshold angle value represents a side surface mismatch at the dispensing tip.

[0070] According to an embodiment of the system of the fifth aspect, the pre-determined point of the first reference line is the center point of the first reference line in the image, and the pre-determined point of the second reference line is the center point of the second reference line in the image.

[0071] According to an embodiment of the system of the fifth aspect, the system is configured to prevent the sample pipetting operation device from aspirating a fluid substance into the dispensing tip in response to determining that the angle of the alignment line with respect to at least one of the first reference line and the second reference line satisfies and / or exceeds a threshold angle value, and / or the software instructions further cause the system to do this. The system and / or the computer device may be configured to generate and / or output an interrupt signal in response to determining that the angle of the alignment line with respect to at least one of the first reference line and the second reference line satisfies and / or exceeds a threshold angle value. Therefore, the system may be configured to prevent the substance pipetting operation device and / or the sample pipetting operation device from aspirating a fluid substance into the dispensing tip in response to determining that the angle of the alignment line is at least the threshold angle value.

[0072] According to an embodiment of the system of the fifth aspect, at least one computer device further flags the aspiration of a fluid substance into the dispensing tip in response to determining that the angle of the alignment line with respect to at least one of the first reference line and the second reference line meets and / or exceeds a threshold angle value, and / or is configured to start the aspiration of the fluid substance into the dispensing tip, for example, by flagging the aspiration, and / or the software instructions further cause the system to do this. Therefore, the system may be configured to flag the aspiration of a fluid substance into the dispensing tip in response to determining that the angle of the alignment line is at least the threshold angle value.

[0073] According to an embodiment of the system of the fifth aspect, at least one computer device further determining and / or identifying the length of at least one reference line based on the captured image of the tip, obtaining the actual length of at least one reference line, calculating the ratio between the length of at least one reference line and the actual length of at least one reference line, determining the depth misalignment of the dispensing tip based on the ratio and is configured to perform, and / or the software instructions further cause the system to perform these.

[0074] Alternatively, or in addition, the software instructions further cause the system to identify the length of the first reference line from the captured image of the tip, obtain the actual length of the first reference line, calculate the ratio between the length of the first reference line and the actual length of the first reference line, determine the depth misalignment of the dispensing tip based on the ratio and perform.

[0075] According to an embodiment of the system of the fifth aspect, the system is further configured to, and / or the software instructions further cause the system to, adjust the determined volume of the fluidic substance based on the ratio.

[0076] According to an embodiment of the system of the fifth aspect, the system further comprises a light source and a sample pipetting module, the light source and the image capture unit being attached to the sample pipetting module and / or the light source and the image capture unit being attached to the sample pipetting module. It is configured to move, for example horizontally, together with the sample pipetting module so that images can be captured at any position of the sample pipetting module. As an example, images may be captured at any position along the track and / or along the sample transport guide of the sample pipetting module.

[0077] According to an embodiment of the system of the fifth aspect, the sample pipetting device is configured to aspirate liquid into the further dispensing tip, and the system is configured to determine a volume of the aspirated liquid, the image capture unit is configured to capture a further image of the further dispensing tip, and the computing device is configured to determine a pixel distance between reference points in the image associated with the further dispensing tip, and to correlate the determined volume with the determined pixel distance.

[0078] According to an embodiment of the system of the fifth aspect, the computing device is configured to generate correlation data based on the determined volume and the determined pixel distance.

[0079] According to an embodiment of the system of the fifth aspect, correlation data is generated based on multiple correlations between multiple determined pixel distances and multiple determined volumes of liquid aspirated into the further dispensing tip.

[0080] According to an embodiment of the system of the fifth aspect, the aspirated liquid comprises a dye solution and / or the system is configured to determine the volume of the aspirated liquid based on spectrophotometry.

[0081] According to an embodiment of the system of the fifth aspect, the system is configured to determine the mass of the aspirated liquid and to determine the volume of the aspirated liquid based on the determined mass of the aspirated liquid.

[0082] Note that any embodiment of the system according to the fifth aspect as described above may be combined with one or more further embodiments of the system according to the fifth aspect as described above. This may make it possible to provide particularly advantageous synergistic effects.

[0083] According to a sixth aspect of the present disclosure, a method for evaluating a fluid substance in a container is provided. Among other things, the method according to the sixth aspect may refer to a method for operating a tip alignment detection device, an aliquot tip integrity evaluation device, a volume detection system, and / or an aliquot tip evaluation system, as exemplified with reference to, for example, FIGS. 1, 5-15, 9-21, and / or 56-68.

[0084] The method according to the sixth aspect comprises capturing an image of at least a part of the container using an image capture device, wherein the container may be an aliquot tip, and determining and / or identifying a first reference line and a second reference line of the container from the image of the container using at least one computer device, and determining and / or obtaining at least one characteristic of at least one of the first reference line and the second reference line and. Among them, at least one characteristic comprises at least one of the length of the first reference line, the length of the second reference line, and the angle of a line with respect to at least one of the first reference line and the second reference line, and the line connects a pre-determined point of the first reference line and a pre- determined point of the second reference line. The method according to the sixth aspect further includes a step of comparing at least one characteristic of at least one of the first reference line and the second reference line with a threshold value representing the misalignment of the dispensing tip.

[0085] In other words, the method according to the sixth aspect includes the step of capturing an image of at least a part of the container using an image capturing unit; the step of identifying the first reference line and the second reference line of the dispensing tip from the image of the dispensing tip using at least one computer device; the step of obtaining one or more characteristics of the first and second reference lines, the characteristics including at least one of the length of the first reference line, the length of the second reference line, and the angle of a line with respect to the reference line, and the line connecting a pre-determined point of the first reference line and a pre-determined point of the second reference line; the step of determining whether the characteristic of at least one reference line meets a threshold value, the threshold value representing the misalignment of the dispensing tip; and may include.

[0086] According to an embodiment of the method of the sixth aspect, the first reference line and the second reference line are determined based on pattern matching of the captured image and / or based on segmentation.

[0087] According to an embodiment of the method of the sixth aspect, the step of determining the first reference line and the second reference line includes the step of searching for a pattern representing the first reference line and / or the second reference line in the captured image.

[0088] According to an embodiment of the method of the sixth aspect, the step of determining the first reference line and the second reference line includes the step of comparing at least a part of the captured image with a reference image.

[0089] According to an embodiment of the method of the sixth aspect, the method further includes the step of determining a matching rate, a matching score, and / or a correlation value of a part of the captured image and the reference image.

[0090] According to an embodiment of the method of the sixth aspect, the container contains a fluid substance, and the method further identifying a surface level of the fluid substance in the container in the captured image; determining a distance between at least one of the first reference line and the second reference line and the surface level; determining a volume of the fluid substance by converting the distance into a volume of the fluid substance based on correlation data, wherein the correlation data includes information about a correlation between a volume in the container and distances from at least one of the first reference line and the second reference line to a plurality of surface levels in the container; and wherein the correlation data may also refer to an equation and / or a functional relationship between the distance and the volume.

[0091] According to an embodiment of the method of the sixth aspect, the method further determining a length of the first reference line in the image; determining a length of the second reference line in the image; determining an angle of a line with respect to at least one of the first reference line and the second reference line, the line connecting a pre-determined point of the first reference line and a pre-determined point of the second reference line; determining a non-conformance of the container based on at least one of the length of the first reference line, the length of the second reference line, and the angle of the line; adjusting the volume of the fluid substance based on the determination of the non-conformance and Among them, the inconsistency may refer to an inconsistency with respect to the image capture unit and / or with respect to the sample pipetting operation module.

[0092] According to an embodiment of the method of the sixth aspect, the container inconsistency includes a side inconsistency and a depth inconsistency. Among them, the side inconsistency may refer to the displacement of the dispensing tip with respect to the optical axis of the camera and / or the image capture unit, and the depth inconsistency may refer to the displacement of the dispensing tip along the optical axis of the camera and / or the image capture unit.

[0093] According to an embodiment of the method of the sixth aspect, the method further includes identifying a pre-determined point on a first reference line in the image; identifying a pre-determined point on a second reference line in the image; defining a alignment line connecting the pre-determined point on the first reference line and the pre-determined point on the second reference line; determining an angle of the alignment line with respect to at least one of the first reference line and the second reference line; comparing the angle with a threshold angle value, the threshold angle value representing the side inconsistency of the container; and the steps include.

[0094] According to an embodiment of the method of the sixth aspect, the pre-determined point on the first reference line is the center point of the first reference line in the image, and the pre-determined point on the second reference line is the center point of the second reference line in the image.

[0095] According to an embodiment of the method of the sixth aspect, the method further includes preventing the suction of the fluid substance into the container in response to determining that the angle of the alignment line with respect to at least one of the first reference line and the second reference line meets and / or exceeds the threshold angle value. Therefore, the interruption signal for preventing suction may be generated in response to determining that the angle of the alignment line with respect to at least one of the first reference line and the second reference line meets and / or exceeds the threshold angle value.

[0096] According to an embodiment of the method of the sixth aspect, the method further includes flagging the suction of the fluid substance into the container and / or starting the suction of the fluid substance into the container in response to determining that the angle of the alignment line with respect to at least one of the first reference line and the second reference line satisfies and / or exceeds a threshold angle value.

[0097] According to an embodiment of the method of the sixth aspect, the method further includes determining the length of at least one of the first reference line and the second reference line based on the captured image of the container; for example, obtaining the actual length of at least one of the first reference line and the second reference line from a data storage device; calculating the ratio between the length of at least one of the first reference line and the second reference line and the actual length of at least one of the first reference line and the second reference line; and determining the depth misalignment of the container based on the ratio.

[0098] According to an embodiment of the method of the sixth aspect, the method further includes adjusting the determined volume of the fluid substance based on the ratio.

[0099] Note that any embodiment of the method according to the sixth aspect as described above can be combined with one or more further embodiments of the method according to the sixth aspect as described above. This may make it possible to provide particularly advantageous synergistic effects.

[0100] ​Furthermore, note that any features, functions, characteristics, and / or elements of the system according to the fifth aspect, as described above and below, may be features, functions, characteristics, steps, and / or elements of the method according to the sixth aspect, as described above and below. Conversely, any features, functions, characteristics, steps, and / or elements of the method according to the sixth aspect, as described above and below, may be features, functions, characteristics, and / or elements of the system according to the fifth aspect, as described above and below.

[0101] According to a seventh aspect of the present disclosure, there is provided a computer program element that, when executed on a computer device of a system for evaluating a fluid substance, instructs the computer device and / or the system to perform the steps of the method according to the sixth aspect.

[0102] According to an eighth aspect of the present disclosure, there is provided a non-transitory computer-readable medium storing the computer program element according to the seventh aspect.

[0103] According to a ninth aspect of the present disclosure, there is provided a system for evaluating a fluid substance. The system according to the ninth aspect may refer to, for example, a particle concentration checking system as exemplarily described with reference to FIGS. 69-79, a volume detection system as exemplarily described with reference to FIGS. 5-15, a correlation data generation system as exemplarily described with reference to FIGS. 8-21, and / or a reaction vessel residual volume detection device as exemplarily described with reference to FIGS. 32-34.

[0104] The system according to the ninth aspect comprises a container carriage device configured to support and / or hold one or more containers, a sample pipetting device and / or a substance pipetting device configured to dispense a fluid substance in at least one of the containers on the container carriage device, an image capture device configured to capture an image of at least one of the containers on the container carriage device, and at least one processing device and / or at least one computer device. Among them, the system using the sample pipetting device to dispense at least one fluid substance into the container; using the image capture device to capture an image of the container on the container carriage device; using at least one processing device to analyze the image of the container and determine the volume of at least one fluid substance dispensed in the container; using at least one processing device to analyze the image of the container and determine the particle concentration of the total volume of the fluid substance in the container is configured to perform.

[0105] The system may comprise at least one computer-readable data storage medium storing software instructions, and when the software instructions are executed by at least one processing device, cause the system to dispense one or more fluid substances into the container; acquire an image of the container on the container carriage device; analyze the image of the container and determine the volume of the fluid substance dispensed in the container; analyze the image of the container and determine the particle concentration of the total volume of the fluid substance in the container to be performed.

[0106] According to an embodiment of the system of the ninth aspect, the total volume of the fluid substance comprises at least one body fluid and / or at least one reagent.

[0107] According to an embodiment of the system of the ninth aspect, the system further After dispensing a reagent into at least one fluid substance contained in a container, using an image capture device to capture and / or acquire a first image of the container, wherein the at least one fluid substance comprises at least one body fluid, the step of After mixing the added reagent with at least one fluid substance in the container, using an image capture device to capture and / or acquire a second image of the container; Using at least one processing device to analyze the first image of the container and determine the volume of the dispensed reagent in the container; Using at least one processing device to analyze the second image of the container and determine the particle concentration of the total volume of the fluid substance in the container is configured to perform, and / or the software instructions further cause the system to perform these.

[0108] According to an embodiment of the system of the ninth aspect, the particle concentration comprises the concentration of paramagnetic particles.

[0109] According to an embodiment of the system of the ninth aspect, the at least one reagent comprises a chemiluminescent substrate.

[0110] According to an embodiment of the system of the ninth aspect, the first image is captured about 0.2 seconds after the reagent is dispensed into the container, and the second image is captured about 6.5 seconds after mixing.

[0111] According to an embodiment of the system of the ninth aspect, the image capture device is mounted on a container carriage device, and the image capture device is configured and / or arranged to capture an image of the container from the side of the container.

[0112] According to an embodiment of the system of the ninth aspect, the system further includes a light source, and the light source and the image capture device are mounted on the container carriage device such that the light source is positioned opposite to the image capture device.

[0113] According to an embodiment of the system of the ninth aspect, the container carriage device is a cleaning wheel including a rotatable plate, and the rotatable plate is configured to rotate the container to the image capture device.

[0114] According to an embodiment of the system of the ninth aspect, the system is further configured to detect whether a container is present on the container carriage device by, for example, appropriate hardware and / or software means, and / or the software instructions further cause the system to do this.

[0115] According to an embodiment of the system of the ninth aspect, at least one processing device determining and / or identifying a reference point in the image, the reference point being associated with the container, and determining and / or identifying the surface level of at least one fluid substance in the container within the image, and determining and / or measuring the distance between the reference point and the surface level, and converting the distance into the volume of at least one dispensed fluid substance and / or reagent based on correlation data, the correlation data including information about the correlation between the volume in the container and the distances from the reference point to a plurality of surface levels in the container, and is configured to perform, and / or the software instructions further cause the system to perform these.

[0116] According to an embodiment of the system of the ninth aspect, the step of determining and / or identifying the reference point includes determining and / or identifying the bottom portion of the container.

[0117] According to an embodiment of the system of the ninth aspect, the distance is measured by a pixel distance.

[0118] According to an embodiment of the system of the ninth aspect, the processing device is configured to determine a reference point based on a pattern match of the captured image and / or based on segmentation.

[0119] According to an embodiment of the system of the ninth aspect, the processing device is configured to search for a pattern representing a reference point in the captured image.

[0120] According to an embodiment of the system of the ninth aspect, the processing device is configured to compare at least a part of the captured image with a reference image.

[0121] According to an embodiment of the system of the ninth aspect, the processing device is configured to determine a matching rate, a matching score, and / or a correlation value of a part of the captured image and the reference image.

[0122] According to an embodiment of the system of the ninth aspect, the sample pipetting operation device is configured to aspirate a liquid into a further container, the system is configured to determine the volume of the aspirated liquid, the image capture unit is configured to capture a further image of the further container, the processing device is configured to determine the pixel distance between reference points in the image associated with the further container, and to correlate the determined volume with the determined pixel distance.

[0123] According to an embodiment of the system of the ninth aspect, the processing device is configured to generate correlation data based on the determined volume and the determined pixel distance.

[0124] According to an embodiment of the system of the ninth aspect, the correlation data is generated based on a plurality of correlations between a plurality of determined pixel distances and a plurality of determined volumes of liquid aspirated into a further container.

[0125] According to an embodiment of the system of the ninth aspect, the aspirated liquid comprises a dye solution. Alternatively, or in addition, the system is configured to determine the volume of the aspirated liquid based on spectrophotometry.

[0126] According to an embodiment of the system of the ninth aspect, the system is configured to determine the mass of the aspirated liquid and to determine the volume of the aspirated liquid based on the determined mass of the aspirated liquid.

[0127] According to an embodiment of the system of the ninth aspect, at least one processing device further acquires and / or determines the brightness of the total volume of the fluid substance from an image of the container based on, for example, receiving brightness values from a sensor and / or, for example, based on image processing, and determines the particle concentration of the total volume of the fluid substance based on the brightness of the fluid substance and calibration data, compares the determined particle concentration with a threshold value, and flags the container containing the total volume of the fluid substance in response to determining that the determined particle concentration is below the threshold value and / or the software instructions are further configured to cause the system to perform these.

[0128] According to an embodiment of the system of the ninth aspect, the system further aspirates at least a portion of the fluid substance from the container using a sample pipetting device, captures a third image of at least a portion of the container using an image capture device, Using at least one processing device, comparing a third image with a reference image; Using at least one processing device, determining a match score based on the similarity between the third image and the reference image; Comparing the generated match score with a threshold value; The configured and / or software instructions further cause the system to perform these.

[0129] According to an embodiment of the system of the ninth aspect, the system is further configured to use at least one processing device to determine an area of interest in the third image, and / or the software instructions further cause the system to perform this, and the step of comparing the third image includes comparing the area of interest in the third image with at least a part of the reference image.

[0130] According to an embodiment of the system of the ninth aspect, the area of interest comprises an area adjacent to the bottom of the container.

[0131] According to an embodiment of the system of the ninth aspect, the system further Flagging the result of suction from the container when the match score is equal to and / or below the threshold value, and / or Flagging the result of suction from the container when the match score does not exceed the threshold value The configured and / or software instructions further cause the system to perform these.

[0132] According to an embodiment of the system of the ninth aspect, the container carriage device comprises a plurality of container slots, each container slot being configured to support a container, and the system further Using an image capture device to capture a fourth image of one of the plurality of container slots at a first position of the container carriage device; Using at least one processing device, comparing a fourth image with a reference image; Using at least one processing device, generating a match score based on the similarity between the fourth image and the reference image; Comparing the match score with a threshold; configured to perform and / or software instructions further cause the system to perform these.

[0133] According to an embodiment of the system of the ninth aspect, a match score that exceeds and / or meets the threshold represents the absence of a container in one of the plurality of container slots.

[0134] According to an embodiment of the system of the ninth aspect, the system is configured to remove a container from one of the plurality of container slots when the match score is below the threshold, and / or software instructions further cause the system to remove a container from one of the plurality of container slots when the match score does not meet the threshold.

[0135] According to an embodiment of the system of the ninth aspect, the system is configured to move the container carriage device to a second position after determining that the match score exceeds and / or meets the threshold and / or in response thereto. Alternatively, or in addition, software instructions further cause the system to move the container carriage device to a second position after determining that the match score exceeds the threshold.

[0136] Note that any embodiment of the system according to the ninth aspect as described above can be combined with one or more additional embodiments of the system according to the ninth aspect as described above. This may make it possible to provide particularly advantageous synergistic effects.

[0137] According to a tenth aspect of the present disclosure, a method for evaluating a fluid substance in a container is provided. The method according to the tenth aspect may refer to, for example, a method for operating a particle concentration check system as exemplarily described with reference to FIGS. 69-79, and / or, for example, a method for operating a volume detection system as exemplarily described with reference to FIGS. 5-15.

[0138] The method according to the tenth aspect comprises dispensing at least one fluid substance into the container using a sample pipetting operation device; capturing and / or acquiring at least a partial image of the container arranged on a container carriage device using an image capturing device, the container carriage device being configured to support and / or hold one or more containers; analyzing the image of the container using at least one computer device to determine the volume of at least one dispensed fluid substance in the container; analyzing the image of the container using at least one computer device to determine the particle concentration of the total volume of the fluid substance in the container and. Wherein the term "total volume of the fluid substance" may refer to at least one dispensed fluid substance, optionally at least one added reagent.

[0139] According to an embodiment of the method of the tenth aspect, the step of capturing and / or acquiring an image of the container comprises after dispensing a reagent into at least one fluid substance contained in the container, capturing and / or acquiring a first image of the container using an image capturing device, the at least one fluid substance comprising at least one body fluid; After adding a reagent and / or, for example, mixing the added reagent with at least one fluid substance in a container, using an image capture device to capture and / or obtain a second image of the container including Among them, the step of analyzing the image of the container and determining the volume of at least one dispensed fluid substance includes the step of analyzing the first image of the container and determining the volume of the dispensed reagent contained in the container. The step of analyzing the image of the container and determining the particle concentration of the total volume of the fluid substance includes the step of analyzing the second image of the container and determining the particle concentration of the total volume of the fluid substance in the container.

[0140] Note that any embodiment of the method according to the tenth aspect as described above can be combined with one or more further embodiments of the method according to the tenth aspect as described above. This may make it possible to provide particularly advantageous synergistic effects.

[0141] Furthermore, any feature, function, characteristic, and / or element of the system according to the ninth aspect as described above and below may be a feature, function, characteristic, step, and / or element of the method according to the tenth aspect as described above and below. Conversely, any feature, function, characteristic, step, and / or element of the method according to the tenth aspect as described above and below may be a feature, function, characteristic, and / or element of the system according to the ninth aspect as described above and below.

[0142] According to an eleventh aspect of the present disclosure, a computer program element is provided that, when executed on a computer device of a system for evaluating a fluid substance, instructs the computer device and / or the system to perform the steps of the method according to the tenth aspect.

[0143] According to a twelfth aspect of the present disclosure, there is provided a non-transitory computer-readable medium storing computer program elements according to the eleventh aspect.

[0144] According to a thirteenth aspect of the present disclosure, there is provided a method for evaluating a fluid substance in a container. The method according to the thirteenth aspect may refer to, for example, a method for operating a volume detection system as exemplarily described with reference to FIGS. 5-15, a method for operating a dispensing adjustment system as exemplarily described with reference to FIGS. 35-36, a method for operating a correlation data generation system as exemplarily described with reference to FIGS. 8-21, and / or a method for operating a residual volume detection device as exemplarily described with reference to FIGS. 32-34.

[0145] The method according to the thirteenth aspect comprises dispensing a fluid substance into a container using a substance dispensing device, determining and / or measuring the volume of the fluid substance in the container using at least one computer device, receiving operation information of the substance dispensing device, the operation information including operation parameters of the fluid substance dispensing device, receiving a target dispensing volume of the fluid substance, comparing the determined volume of the fluid substance with the target dispensing volume, generating calibration information for the substance dispensing device, and adjusting the operation parameters of the substance dispensing device based on the calibration information. The method according to the thirteenth aspect further comprises

[0146] According to an embodiment of the method of the thirteenth aspect, the step of determining and / or measuring the volume of the fluid substance comprises capturing an image of at least a part of the container using an image capturing device, Using at least one computer device to identify a reference point in an image, the reference point being associated with a container, and Using at least one computer device to identify the surface level of a fluid substance within a container in an image; and Determining the distance between the reference point and the surface level; and Converting the distance into a volume of the fluid substance based on correlation data, the correlation data including information about a correlation between a volume within the container and distances from the reference point to a plurality of surface levels within the container; and Including.

[0147] According to an embodiment of the method of the thirteenth aspect, the method further includes Supplying liquid to a further container; and Determining the volume of the supplied liquid; and Capturing a further image of the container; and Determining the pixel distance between reference points in the image associated with the further container; and Correlating the determined volume with the determined pixel distance; and Including.

[0148] According to an embodiment of the method of the thirteenth aspect, the method further includes generating correlation data based on the determined volume and the determined pixel distance.

[0149] According to an embodiment of the method of the thirteenth aspect, the correlation data is generated based on a plurality of correlations between a plurality of determined pixel distances and a plurality of determined volumes of liquid supplied to a further container.

[0150] According to an embodiment of the method of the thirteenth aspect, the supplied liquid comprises a dye solution. Alternatively, or in addition, the volume of the supplied liquid is determined based on spectrophotometry.

[0151] According to an embodiment of the method of the 13th aspect, the step of determining the volume of the supplied liquid includes the step of determining the mass of the supplied liquid.

[0152] According to an embodiment of the method of the 13th aspect, the method further comprises aspirating at least a portion of the fluid substance from the container, and capturing an image of at least a portion of the container using an image capture device, and comparing the image with a reference image, and generating a match score based on the similarity between the image and the reference image and.

[0153] According to an embodiment of the method of the 13th aspect, the method further comprises comparing the match score with a threshold value, and / or determining that the match score exceeds the threshold value and.

[0154] According to an embodiment of the method of the 13th aspect, the method further comprises determining an area of interest in the image, and the step of comparing the images comprises comparing the area of interest in the image with at least a portion of the reference image.

[0155] According to an embodiment of the method of the 13th aspect, the area of interest includes an area adjacent to the bottom of the container.

[0156] According to an embodiment of the method of the 13th aspect, the method further comprises flagging the result of aspiration from the container when the match score meets and / or falls below the threshold value.

[0157] According to an embodiment of the method of the 13th aspect, the method further comprises arranging a plurality of containers in a plurality of container slots of a container carriage device, and Using an image capture device, capturing an image of one of a plurality of container slots at a first position of a container carriage device; comparing the image with a reference image; generating a match score based on the similarity between the image and the reference image; and including.

[0158] According to an embodiment of the method of the thirteenth aspect, the method further comprises: comparing the match score with a threshold value, and / or determining that the match score exceeds and / or meets a threshold value, wherein a match score exceeding the threshold value represents the absence of a container in one of the plurality of container slots; and including.

[0159] According to an embodiment of the method of the thirteenth aspect, the method further comprises removing a container from one of the plurality of container slots when the match score is below the threshold value.

[0160] According to an embodiment of the method of the thirteenth aspect, the method further comprises moving the container carriage device to a second position after determining that the match score exceeds and / or meets the threshold value.

[0161] Note that any embodiment of the method according to the thirteenth aspect as described above can be combined with one or more further embodiments of the method according to the thirteenth aspect as described above. This may make it possible to provide particularly advantageous synergistic effects.

[0162] Furthermore, note that any features, functions, characteristics, and / or elements of the system according to the ninth aspect as described above and below may be features, functions, characteristics, steps, and / or elements of the method according to the thirteenth aspect as described above and below. Conversely, any features, functions, characteristics, steps, and / or elements of the method according to the thirteenth aspect as described above and below may be features, functions, characteristics, and / or elements of the system according to the ninth aspect as described above and below. may be.

[0163] According to a fourteenth aspect of the present disclosure, there is provided a computer program element that, when executed on a computer device of a system for evaluating a fluid substance, instructs the computer device and / or the system to perform the steps of the method according to the thirteenth aspect.

[0164] According to a fifteenth aspect of the present disclosure, there is provided a non-transitory computer-readable medium storing the computer program element according to the fourteenth aspect. The present invention provides, for example, the following. (Item 1) A method for evaluating a fluid substance in a container, comprising: capturing an image of at least a part of the container using an image capture device; acquiring a plurality of color parameters of at least a part of the image using at least one computer device; generating a sample classification result of the fluid substance contained in the container based on the plurality of color parameters; and wherein the sample classification result represents the concentration of at least one interfering substance in the fluid substance. (Item 2) The step of acquiring a plurality of color parameters comprises: generating a histogram of at least a part of the image, the histogram comprising a plurality of color channels. A step of obtaining a plurality of average values of the plurality of color channels, wherein the plurality of color parameters include the plurality of average values of the plurality of color channels, and The method according to item 1, comprising: (Item 3) The step of obtaining a plurality of color parameters A step of generating a histogram of at least a part of the image, wherein the histogram includes a plurality of color channels, and A step of obtaining a plurality of Riemann sums of the plurality of color channels and The method according to any one of items 1 and 2, wherein the plurality of color parameters include the plurality of Riemann sums of the plurality of color channels. (Item 4) The step of obtaining a plurality of color parameters A step of generating a histogram of at least a part of the image, wherein the histogram includes a plurality of color channels, A step of obtaining a plurality of modes of the plurality of color channels, and / or A step of obtaining a plurality of maximum values of the plurality of color channels, and / or A step of obtaining a plurality of minimum values of the plurality of color channels, wherein the plurality of color parameters include the plurality of modes, maximum values, and / or minimum values of the plurality of color channels The method according to any of the above items, comprising: (Item 5) The step of obtaining a plurality of color parameters A step of generating a histogram of at least a part of the image, wherein the histogram includes a plurality of color channels, A step of obtaining a plurality of histogram heads of the plurality of color channels, and / or A step of obtaining a plurality of histogram tails of the plurality of color channels, A step of obtaining a plurality of histogram head ratios of the plurality of color channels, and / or A step of obtaining a plurality of histogram tail rates of the plurality of color channels, wherein the plurality of color parameters include the plurality of histogram heads, histogram tails, histogram head rates, and / or histogram tail rates of the plurality of color channels The method according to any one of the above items, including (Item 6) The plurality of color parameters include at least one of a plurality of averages of the color channels, a plurality of Riemann sums of the color channels, a plurality of modes of the color channels, a plurality of maximum values of the color channels, a plurality of minimum values of the color channels, a plurality of histogram heads of the color channels, a plurality of histogram tails of the color channels, a plurality of histogram head rates of the color channels, a plurality of histogram tail rates of the color channels, or any combination of the foregoing, according to the method of any one of the above items (Item 7) The plurality of color channels include a red component, a green component, and a blue component, according to the method of any one of Items 2-6 (Item 8) The sample classification result includes at least one classification identifier The at least one classification identifier is correlated with at least a part of the plurality of color parameters and / or correlated with the concentration of the at least one interfering substance in the fluid substance, according to the method of any one of the above items (Item 9) The method further includes a step of generating a flagging result based on the sample classification result, and the flagging result indicates the quality of the fluid substance, according to the method of any one of the above items (Item 10) The at least one interfering substance is one or more selected from hemoglobin, jaundice, and lipemia, according to the method of any one of the above items (Item 11) The container is a dispensing tip configured to aspirate the fluid substance, according to the method of any one of the above items (Item 12) The method according to any of the preceding items, wherein the image capture device is configured and / or arranged to capture the image of the fluid substance and / or the container from the side of the container. (Item 13) Using the at least one computer device, identifying a reference point in the image, the reference point being associated with the container; Using the at least one computer device, identifying the surface level of the fluid substance in the container in the image; Determining the distance between the reference point and the surface level; Converting the distance into a volume of the fluid substance based on correlation data, the correlation data including information about the correlation between the volume in the container and the distances from the reference point to a plurality of surface levels in the container; The method according to any of the preceding items, further comprising. (Item 14) The method according to item 13, wherein the distance is measured by a pixel distance. (Item 15) The container is a dispensing tip configured to aspirate the fluid substance, The method according to any of items 13 or 14, wherein the step of identifying a reference point includes identifying a reference line formed on the dispensing tip. (Item 16) The method according to item 15, wherein the reference line is identified based on pattern matching and / or segmentation of the captured image. (Item 17) The method according to any of items 15 or 16, wherein the step of identifying the reference line includes searching for a pattern representing the reference line in the captured image. (Item 18) The method according to any of items 15-17, wherein the step of identifying the reference line includes comparing at least a part of the captured image with a reference image. (Item 19) The method according to item 18, further comprising the step of determining a matching rate and / or a correlation value of the part of the captured image and the reference image. (Item 20) The step of supplying a liquid to a further container, The step of determining the volume of the supplied liquid, The step of capturing a further image of the container, The step of determining a pixel distance between reference points in the image associated with the further container, The step of correlating the determined volume with the determined pixel distance The method according to any of the above items, further comprising the steps of: (Item 21) The method according to item 20, further comprising the step of generating correlation data based on the determined volume and the determined pixel distance. (Item 22) The method according to item 21, wherein the correlation data is generated based on a plurality of correlations between a plurality of determined pixel distances and a plurality of determined volumes of the liquid supplied to the further container. (Item 23) The supplied liquid comprises a dye solution, and / or The volume of the supplied liquid is determined based on spectrophotometry. The method according to any of items 20-22. (Item 24) The method according to any of items 20-23, wherein the step of determining the volume of the supplied liquid comprises the step of determining the mass of the supplied liquid. (Item 25) A computer program element that, when executed on a computer device of a system for evaluating a fluid substance, instructs the computer device to perform the steps of the method according to any of items 1-24. (Item 26) A non-transitory computer-readable medium storing the computer program element according to item 25. (Item 27) A system for evaluating a fluid substance, A sample pipette operation device having a dispensing tip, wherein the sample pipette operation device is at least partially engaged with the dispensing tip and into the dispensing tip A sample pipette operation device configured to aspirate a fluid substance, An image capture unit, At least one computer device Comprising, The image capture unit is configured to capture at least a partial image of the fluid substance in the dispensing tip, The computer device, Obtaining a plurality of color parameters of at least a part of the image; Generating a sample classification result of the fluid substance contained in the dispensing tip based on the plurality of color parameters And configured to perform, The sample classification result represents the concentration of at least one interfering substance in the fluid substance, a system. (Item 28) The computer device further, Generating a histogram of at least a part of the image, the histogram comprising a plurality of color channels, a step, Obtaining a plurality of average values of the plurality of color channels, and / or Obtaining a plurality of Riemann sums of the plurality of color channels And configured to perform, The plurality of color parameters include the plurality of averages and / or the plurality of Riemann sums of the plurality of color channels, the system according to item 27. (Item 29) The sample classification result comprises at least one classification identifier, The system according to any one of items 27 and 28, wherein the at least one classification identifier is correlated with at least a part of the plurality of color parameters and / or is correlated with the concentration of the at least one interfering substance in the fluid substance. (Item 30) The computer device further identifying a reference point in the image, the reference point being associated with the dispensing tip, and identifying a surface level of the fluid substance within the dispensing tip in the image; determining a distance between the reference point and the surface level; converting the distance into a volume of the fluid substance based on correlation data, the correlation data including information about a correlation between a volume within the dispensing tip and distances from the reference point to a plurality of surface levels within the dispensing tip, The system according to any one of items 27-29, configured to perform the above. (Item 31) The system according to any one of items 27-30, wherein the computer device is configured to determine a reference line formed on a body of the dispensing tip and to determine the reference point based on the determined reference line. (Item 32) The system according to item 31, wherein the computer device is configured to determine the reference line based on pattern matching and / or segmentation of the captured image. (Item 33) The system according to any one of items 31 and 32, wherein the computer device is configured to search for a pattern representing the reference line in the captured image. (Item 34) The computer device is configured to compare at least a part of the captured image with a reference image The system according to any one of items 31-33. (Item 35) The computer device is configured to determine a matching rate and / or a correlation value of the part of the captured image and the reference image, according to the system described in item 34. (Item 36) The image capture unit is configured and / or arranged to capture the image of the part of the fluid substance from a side surface of the dispensing tip, according to the system described in any one of items 27-35. (Item 37) Further comprising a sample pipette operation module, The image capture unit is attached to the sample pipette operation module, according to the system described in any one of items 27-36. (Item 38) Further comprising a light source positioned opposite to the image capture unit and positioned on a side surface of the dispensing tip, The light source is configured to irradiate the dispensing tip from the side surface of the dispensing tip, according to the system described in any one of items 27-37. (Item 39) Further comprising a light source and a sample pipette operation module, The light source and the image capture unit are attached to the sample pipette operation module, and / or The light source and the image capture unit are configured to move together with the sample pipette operation module so that an image of the dispensing tip can be captured at any position of the sample pipette operation module, according to the system described in any one of items 27-38. (Item 40) The sample pipette operation device is configured to suck liquid into a further dispensing tip, The system is configured to determine the volume of the sucked liquid, The image capture unit is configured to capture a further image of the further dispensing tip, The computer device is configured to determine a pixel distance between reference points in the image associated with the further dispensing tip, and to correlate the determined volume with the determined pixel distance, the system according to any one of items 27 - 39. (Item 41) The computer device is configured to generate correlation data based on the determined volume and the determined pixel distance, the system according to item 40. (Item 42) The correlation data is generated based on a plurality of correlations between a plurality of determined pixel distances and a plurality of determined volumes of the liquid aspirated into the further dispensing tip, the system according to one item of item 41. (Item 43) The aspirated liquid comprises a dye solution, and / or The system is configured to determine the volume of the aspirated liquid based on spectrophotometry, the system according to any one of items 40 - 42. (Item 44) The system is configured to determine the mass of the aspirated liquid and to determine the volume of the aspirated liquid based on the determined mass of the aspirated liquid, the system according to any one of items 40 - 43. (Item 45) A system for evaluating a fluid substance, A sample pipette operating device configured to engage at least partially with a dispensing tip, the sample pipette operating device being configured to aspirate a fluid substance into the dispensing tip, the dispensing tip having at least one reference line, a sample pipette operating device, An image capture unit configured to capture an image of at least a part of the dispensing tip, At least one computer device, Identifying the at least one reference line of the dispensing tip from the part of the image of the dispensing tip, Determining at least one characteristic of the at least one reference line; Comparing the at least one characteristic of the at least one reference line with a threshold value; configured to perform, the threshold value being for at least one computer device representing a misalignment of the dispensing tip; A system comprising. (Item 46) The system according to item 45, wherein the at least one reference line comprises a first reference line and a second reference line formed on the dispensing tip. (Item 47) The at least one reference line comprises a first reference line and a second reference line formed on the dispensing tip, The at least one computer device further comprises Obtaining at least one characteristic of the at least one reference line, wherein obtaining the at least one characteristic comprises Determining the length of the first reference line; Determining the length of the second reference line; Determining an angle of a line with respect to at least one of the first reference line and the second reference line, the line connecting a pre-determined point of the first reference line and a pre-determined point of the second reference line; Based on; Determining the misalignment of the dispensing tip based on at least one of the length of the first reference line, the length of the second reference line, and the angle of the line; The system according to any one of items 45-46, configured to perform. (Item 48) The system according to any one of items 45-47, configured to prevent the sample pipetting device from aspirating the fluid substance into the dispensing tip in response to determining the misalignment. (Item 49) The at least one computer device is further configured to flag and / or initiate suction of the fluid substance into the dispensing tip in response to determining the inconsistency, for the system according to any one of items 45 - 48. (Item 50) The at least one computer device further identifying at least one reference line of the dispensing tip from the portion of the image of the dispensing tip; identifying a surface level of the fluid substance within the dispensing tip in the image; determining a distance between the at least one reference line and the surface level; converting the distance into a volume of the fluid substance based on correlation data, the step of determining the volume of the fluid substance, wherein the correlation data includes information about a correlation between a volume within the dispensing tip and distances from the at least one reference line to a plurality of surface levels within the dispensing tip; for the system according to any one of items 45 - 49. (Item 51) The computer device is configured to determine the reference line based on pattern matching and / or segmentation of the captured image, for the system according to item 50. (Item 52) The computer device is configured to search for a pattern representing the reference line in the captured image, for the system according to any one of items 50 and 51. (Item 53) The computer device is configured to compare at least a portion of the captured image with a reference image, for the system according to any one of items 50 - 52. (Item 54) The computer device is configured to determine a matching rate and / or a correlation value of the portion of the captured image and the reference image, for the system according to item 53. (Item 55) The at least one reference line includes a first reference line and a second reference line formed on the dispensing tip. The at least one computer device further determining a length of the first reference line in the image; determining a length of the second reference line in the image; determining an angle of a line with respect to at least one of the first reference line and the second reference line, the line connecting a pre-determined point of the first reference line and a pre-determined point of the second reference line; determining the misalignment of the dispensing tip based on at least one of the length of the first reference line, the length of the second reference line, and the angle of the line; adjusting the volume of the fluid substance based on the determination of the misalignment The system according to any one of items 45 - 54, configured to perform. (Item 56) The misalignment of the dispensing tip includes a side misalignment and a depth misalignment. The system according to any one of items 45 - 55. (Item 57) The at least one reference line includes a first reference line and a second reference line formed on the dispensing tip. The at least one computer device further identifying a pre-determined point of the first reference line in the image; identifying a pre-determined point of the second reference line in the image; defining an alignment line connecting the pre-determined point of the first reference line and the pre-determined point of the second reference line; determining an angle of the alignment line with respect to at least one of the first reference line and the second reference line; comparing the angle with a threshold angle value configured to perform, and the threshold angle value represents a side surface mismatch of the dispensing tip, the system according to any one of items 45 - 56. (Item 58) The pre - determined point of the first reference line is the center point of the first reference line in the image, and the pre - determined point of the second reference line is the center point of the second reference line in the image, the system according to any one of items 47 - 57. (Item 59) The system is configured to prevent the sample pipetting device from sucking the fluid substance into the dispensing tip in response to determining that the angle of the alignment line with respect to at least one of the first reference line and the second reference line satisfies and / or exceeds the threshold angle value, the system according to any one of items 57 - 58. (Item 60) The at least one computer device is further configured to flag the suction of the fluid substance into the dispensing tip and / or start the suction of the fluid substance into the dispensing tip in response to determining that the angle of the alignment line with respect to at least one of the first reference line and the second reference line satisfies and / or exceeds the threshold angle value, the system according to any one of items 57 - 59. (Item 61) The at least one computer device is further determining the length of the at least one reference line based on the captured image of the tip; obtaining the actual length of the at least one reference line; calculating a ratio between the length of the at least one reference line and the actual length of the at least one reference line; determining a depth mismatch of the dispensing tip based on the ratio configured to perform, the system according to any one of items 45 - 60. (Item 62) The system according to item 61, further configured to adjust the determined volume of the fluid substance based on the ratio. (Item 63) The system further includes a light source and a sample pipetting operation module. The light source and the image capture unit are attached to the sample pipetting operation module and / or The light source and the image capture unit are configured to move together with the sample pipetting operation module such that an image of the dispensing tip can be captured at any position of the sample pipetting operation module, the system according to any one of items 45 - 62. (Item 64) The sample pipetting device is configured to aspirate liquid into a further dispensing tip. The system is configured to determine the volume of the aspirated liquid. The image capture unit is configured to capture a further image of the further dispensing tip. The computer device is configured to determine a pixel distance between reference points in the image associated with the further dispensing tip and to correlate the determined volume with the determined pixel distance, the system according to any one of items 45 - 63. (Item 65) The computer device is configured to generate correlation data based on the determined volume and the determined pixel distance, the system according to item 64. (Item 66) The correlation data is generated based on a plurality of correlations between a plurality of determined pixel distances and a plurality of determined volumes of liquid aspirated into the further dispensing tip, the system according to item 65. (Item 67) The aspirated liquid comprises a dye solution and / or The system according to any one of items 64 - 66, configured to determine the volume of the aspirated liquid based on spectrophotometry. (Item 68) The system according to any one of items 64 - 67, configured to determine the mass of the aspirated liquid and to determine the volume of the aspirated liquid based on the determined mass of the aspirated liquid. (Item 69) A method for evaluating a fluid substance in a container, comprising: capturing an image of at least a part of the container using an image capture device; determining a first reference line and a second reference line of the container from the image of the container using at least one computer device; determining at least one characteristic of at least one of the first reference line and the second reference line, wherein the at least one characteristic comprises at least one of the length of the first reference line, the length of the second reference line, and the angle of a line with respect to at least one of the first reference line and the second reference line; connecting the line to a pre - determined point of the first reference line and a pre - determined point of the second reference line; comparing the at least one characteristic of at least one of the first reference line and the second reference line with a threshold value representing a dispensing tip mismatch; and a method comprising the above. (Item 70) The method according to item 69, wherein the first reference line and the second reference line are determined based on pattern matching of the captured image and / or based on segmentation. (Item 71) The method according to any one of items 69 and 70, wherein the step of determining the first reference line and the second reference line comprises searching for a pattern representing the first reference line and / or the second reference line in the captured image. (Item 72) The step of determining the first reference line and the second reference line includes the step of comparing at least a part of the captured image with a reference image, the method according to any one of Items 69-71. (Item 73) The method according to Item 72, further comprising the step of determining a matching rate and / or a correlation value between the part of the captured image and the reference image. (Item 74) The container contains a fluid substance, and the method further comprises identifying a surface level of the fluid substance in the container in the captured image; determining a distance between at least one of the first reference line and the second reference line and the surface level; determining the volume of the fluid substance by converting the distance into the volume of the fluid substance based on correlation data, the correlation data including information about the correlation between the volume in the container and the distances from at least one of the first reference line and the second reference line to a plurality of surface levels in the container, the step The method according to any one of Items 69-73, comprising (Item 75) The method further comprises determining a length of the first reference line in the image; determining a length of the second reference line in the image; determining an angle of a line with respect to at least one of the first reference line and the second reference line, the line connecting a pre-determined point of the first reference line and a pre-determined point of the second reference line, the step determining the non-conformance of the container based on at least one of the length of the first reference line, the length of the second reference line, and the angle of the line; adjusting the volume of the fluid substance based on the determination of the non-conformance The method according to any one of items 69 - 74, including (Item 76) The method according to any one of items 69 - 75, wherein the inconsistency of the container includes a side inconsistency and a depth inconsistency. (Item 77) Identifying a pre - determined point of the first reference line in the image; Identifying a pre - determined point of the second reference line in the image; Defining a matching line connecting the pre - determined point of the first reference line and the pre - determined point of the second reference line; Determining an angle of the matching line with respect to at least one of the first reference line and the second reference line; Comparing the angle with a threshold angle value, wherein the threshold angle value represents a side inconsistency of the container. The method according to any one of items 69 - 76, further including (Item 78) The method according to item 77, wherein the pre - determined point of the first reference line is the center point of the first reference line in the image, and the pre - determined point of the second reference line is the center point of the second reference line in the image. (Item 79) The method according to any one of items 77 - 78, further including preventing the suction of the fluid substance into the container in response to determining that the angle of the matching line with respect to at least one of the first reference line and the second reference line meets and / or exceeds the threshold angle value. (Item 80) The method according to any one of items 77 - 79, further including flagging the suction of the fluid substance into the container and / or starting the suction of the fluid substance into the container in response to determining that the angle of the matching line with respect to at least one of the first reference line and the second reference line meets and / or exceeds the threshold angle value. (Item 81) Determining at least one of the lengths of the first reference line and the second reference line based on the captured image of the container; Obtaining the actual length of at least one of the first reference line and the second reference line; Calculating a ratio between the length of at least one of the first reference line and the second reference line and the actual length of at least one of the first reference line and the second reference line; Determining a depth inconsistency of the container based on the ratio; The method according to any one of items 69 - 80, further comprising: (Item 82) Further comprising adjusting the determined volume of the fluid substance based on the ratio. The method according to item 81. (Item 83) A computer program element that, when executed on a computer device of a system for evaluating a fluid substance, instructs the computer device to perform the steps of the method according to any one of items 69 - 82. (Item 84) A non - transitory computer - readable medium storing the computer program element according to item 83. (Item 85) A system for evaluating a fluid substance, A container carriage device configured to support one or more containers; A sample pipette operation device configured to dispense a fluid substance in at least one of the containers on the container carriage device; An image capture device configured to capture an image of at least one of the containers on the container carriage device; At least one processing device; Comprising, the system Dispensing at least one fluid substance into a container using the sample pipetting operation device; Capturing an image of the container on the container carriage device using the image capturing device; Analyzing the image of the container using the at least one processing device and determining the volume of the at least one dispensed fluid substance in the container; Analyzing the image of the container using the at least one processing device and determining the particle concentration of the total volume of the fluid substance in the container A system configured to perform. (Item 86) The system according to item 85, wherein the total volume of the fluid substance comprises at least one body fluid and / or at least one reagent. (Item 87) The system further comprises After dispensing a reagent into the at least one fluid substance contained in the container, capturing a first image of the container using the image capturing device, wherein the at least one fluid substance comprises at least one body fluid; After adding and / or mixing the at least one fluid substance and the reagent in the container, capturing a second image of the container using the image capturing device; Analyzing the first image of the container using the at least one processing device and determining the volume of the dispensed reagent in the container; Analyzing the second image of the container using the at least one processing device and determining the particle concentration of the total volume of the fluid substance in the container The system according to any one of items 85-86, configured to perform. (Item 88) The system according to any one of items 85-87, wherein the particle concentration comprises the concentration of paramagnetic particles. (Item 89) The system according to any one of items 85-88, wherein the at least one reagent comprises a chemiluminescent substrate. (Item 90) The system according to any one of items 85-89, wherein the first image is captured at about 0.2 seconds after the reagent is dispensed into the container, and the second image is captured at about 6.5 seconds after mixing. (Item 91) The system according to any one of items 85-90, wherein the image capture device is mounted on the container carriage device, and the image capture device is configured and / or arranged to capture the image of the container from the side of the container. (Item 92) The system according to any one of items 85-91, further comprising a light source, wherein the light source and the image capture device are mounted on the container carriage device such that the light source is positioned opposite to the image capture device. (Item 93) The container carriage device is a cleaning wheel comprising a rotatable plate, The system according to any one of items 85-92, wherein the rotatable plate is configured to rotate the container to the image capture device. (Item 94) The system according to any one of items 85-93, further configured to detect whether the container is present on the container carriage device. (Item 95) The at least one processing device determining a reference point in the image, the reference point being associated with the container, determining a surface level of the at least one fluid substance in the container in the image, determining a distance between the reference point and the surface level, A step of converting the distance into the volume of at least one dispensed fluid substance and / or reagent based on correlation data, wherein the correlation data includes information about the correlation between the volume in the container and the distance from the reference point to a plurality of surface levels in the container The system according to any one of items 85-94, configured to perform (Item 96) The system according to any one of items 85-95, wherein the step of determining the reference point includes the step of determining the bottom portion of the container (Item 97) The system according to any one of items 95-96, wherein the distance is measured by a pixel distance (Item 98) The system according to any one of items 95-97, wherein the processing device is configured to determine the reference point based on pattern matching and / or segmentation of the captured image (Item 99) The system according to any one of items 95 and 98, wherein the processing device is configured to search for a pattern representing the reference point in the captured image (Item 100) The system according to any one of items 95-99, wherein the processing device is configured to compare at least a part of the captured image with a reference image (Item 101) The processing device is for the part of the captured image and the coincidence rate of the reference image And / or the system according to item 100, configured to determine a correlation value (Item 102) The sample pipette operation device is configured to aspirate liquid into a further container The system is configured to determine the volume of the aspirated liquid The image capture unit is configured to capture a further image of the further container The processing device is configured to determine a pixel distance between reference points in the image associated with the further container, and to correlate the determined volume with the determined pixel distance, the system according to any one of items 85 - 101. (Item 103) The processing device is configured to generate correlation data based on the determined volume and the determined pixel distance, the system according to item 102. (Item 104) The correlation data is generated based on a plurality of correlations between a plurality of determined pixel distances and a plurality of determined volumes of liquid aspirated into the further container, the system according to item 103. (Item 105) The aspirated liquid comprises a dye solution, and / or The system is configured to determine the volume of the aspirated liquid based on spectrophotometry, the system according to any one of items 102 - 104. (Item 106) The system is configured to determine the mass of the aspirated liquid and to determine the volume of the aspirated liquid based on the determined mass of the aspirated liquid, the system according to any one of items 102 - 105. (Item 107) The at least one processing device further obtaining and / or determining the luminance of the total volume of the fluid substance from the image of the container; and determining a particle concentration of the total volume of the fluid substance based on the luminance of the fluid substance and calibration data; and comparing the determined particle concentration with a threshold; and flagging the container containing the total volume of the fluid substance in response to determining that the determined particle concentration is below the threshold and performing, the system according to any one of items 85 - 106. (Item 108) The system further using the sample pipetting device to aspirate at least a portion of the fluid substance from the container; using the image capture device to capture a third image of at least a portion of the container; using the at least one processing device to compare the third image with a reference image; using the at least one processing device to determine a match score based on the similarity between the third image and the reference image; comparing the generated match score with a threshold value and is configured to perform the steps of any one of items 85 - 107. (Item 109) The system further is configured to use the at least one processing device to determine an area of interest in the third image, and the step of comparing the third image includes comparing the area of interest in the third image with at least a portion of the reference image, and is a system according to any one of items 85 - 108. (Item 110) The area of interest includes a region adjacent to the bottom of the container, and is a system according to item 109. (Item 111) The system further is configured to flag the result of the aspiration from the container when the match score is equal to and / or less than the threshold value, and is a system according to any one of items 108 - 110. (Item 112) The container carriage device includes a plurality of container slots, each container slot being configured to support a container, The system further using the image capture device to capture a fourth image of one of the plurality of container slots at a first position of the container carriage device; using the at least one processing device to compare the fourth image with a reference image; using the at least one processing device to generate a match score based on a similarity between the fourth image and the reference image; comparing the match score with a threshold; The system according to any one of items 85 - 111, configured to perform the above. (Item 113) The system according to item 112, wherein the match score exceeding and / or meeting the threshold represents the absence of the container in the one of the plurality of container slots. (Item 114) The system according to any one of items 108 - 113, configured to remove the container from the one of the plurality of container slots when the match score is below the threshold. (Item 115) The system according to any one of items 108 - 114, configured to move the container carriage device to a second position after determining that the match score exceeds and / or meets the threshold. (Item 116) A method for evaluating a fluid substance in a container, comprising: dispensing at least one fluid substance into the container using a sample pipetting operation device; capturing, using an image capture device, at least a partial image of the container arranged on a container carriage device, the container carriage device being configured to support one or more containers; analyzing the image of the container using at least one computer device to determine a volume of the at least one dispensed fluid substance in the container; Using the at least one computer device to analyze the image of the container and determine the particle concentration of the total volume of the fluid substance in the container A method comprising the steps of: (Item 117) The step of capturing the image of the container After dispensing a reagent into the at least one fluid substance contained in the container, using the image capture device to capture a first image of the container, wherein the at least one fluid substance includes at least one body fluid After mixing the added reagent with the at least one fluid substance in the container, using the image capture device to capture a second image of the container including The step of analyzing the image of the container and determining the volume of the at least one dispensed fluid substance includes analyzing the first image of the container and determining the volume of the dispensed reagent contained in the container The method according to item 116, wherein the step of analyzing the image of the container and determining the particle concentration of the total volume of the fluid substance includes analyzing the second image of the container and determining the particle concentration of the total volume of the fluid substance in the container (Item 118) A computer program element that, when executed on a computer device of a system for evaluating a fluid substance, instructs the computer device to perform the steps of the method according to any one of items 116-117 (Item 119) A non-transitory computer-readable medium storing the computer program element according to item 118 (Item 120) A method for evaluating a fluid substance in a container, comprising Using a substance dispensing device to dispense a fluid substance into a container Determining the volume of the fluid substance in the container using at least one computer device; Receiving operation information of the substance dispensing device, the operation information including operation parameters of the fluid substance dispensing device; Receiving a target dispensing volume of the fluid substance; Comparing the determined volume of the fluid substance with the target dispensing volume; Generating calibration information for the substance dispensing device; Adjusting the operation parameters of the substance dispensing device based on the calibration information; A method comprising the above steps. (Item 121) The step of determining the volume of the fluid substance includes: Capturing at least a partial image of the container using an image capture device; Identifying reference points in the image using at least one computer device, the reference points being associated with the container; Identifying the surface level of the fluid substance in the container in the image using the at least one computer device; Determining the distance between the reference point and the surface level; Converting the distance to the volume of the fluid substance based on correlation data, the correlation data including information about the correlation between the volume in the container and the distances from the reference point to a plurality of surface levels in the container; The method according to item 120, comprising the above steps. (Item 122) Supplying liquid to a further container; Determining the volume of the supplied liquid; Capturing a further image of the container; Determining the pixel distance between reference points in the image associated with the further container; correlating the determined volume with the determined pixel distance The method according to any one of items 120-121, further comprising this step. (Item 123) The method according to item 122, further comprising generating correlation data based on the determined volume and the determined pixel distance. (Item 124) The method according to item 123, wherein the correlation data is generated based on a plurality of correlations between a plurality of determined pixel distances and a plurality of determined volumes of the liquid supplied to the further container. (Item 125) The supplied liquid comprises a dye solution, and / or The method according to any one of items 122-124, wherein the volume of the supplied liquid is determined based on spectrophotometry. (Item 126) The method according to any one of items 122-125, wherein the step of determining the volume of the supplied liquid includes the step of determining the mass of the supplied liquid. (Item 127) aspirating at least a portion of the fluid substance from the container; capturing an image of at least a portion of the container using an image capture device; comparing the image with a reference image; generating a match score based on the similarity between the image and the reference image; The method according to any one of items 120-126, further comprising this step. (Item 128) comparing the match score with a threshold value, and / or determining that the match score exceeds the threshold value The method according to item 127, further comprising this step. (Item 129) The method further comprises determining an area of interest within the image, The step of comparing the images includes the step of comparing the area of interest in the images with at least a part of the reference image, the method according to any one of items 127-128. (Item 130) The area of interest includes a region adjacent to the bottom of the container, the method according to item 129. (Item 131) The method according to any one of items 127-130, further including the step of flagging the result of the suction from the container when the matching score meets and / or falls below the threshold. (Item 132) Arranging a plurality of containers in a plurality of container slots of a container carriage device; Using an image capture device to capture an image of one of the plurality of container slots at a first position of the container carriage device; Comparing the image with a reference image; Generating a matching score based on the similarity between the image and the reference image; The method according to any one of items 127-131, further including the above steps. (Item 133) Comparing the matching score with a threshold value, and / or Determining that the matching score exceeds and / or meets the threshold value, wherein the matching score exceeding the threshold value represents the absence of the container in the one of the plurality of container slots; The method according to item 132, further including the above step. (Item 134) The method according to any one of items 127-133, further including the step of removing the container from the one of the plurality of container slots when the matching score is below the threshold value. (Item 135) The method according to any one of items 127 - 134, further comprising the step of moving the container carriage device to a second position after determining that the matching score exceeds and / or meets a threshold value. (Item 136) A computer program element that, when executed on a computer device of a system for evaluating a fluid substance, instructs the computer device to perform the steps of the method according to any one of items 120 - 135. (Item 137) A non - transitory computer - readable medium storing the computer program element according to item 136.

Brief Description of the Drawings

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DETAILED DESCRIPTION OF THE INVENTION

[0245] With reference to the drawings, in which like reference numerals refer to like parts and assemblies throughout several views, various embodiments are described in detail. References to various embodiments do not limit the scope of the claims appended hereto. Additionally, any example described herein is not intended to be limiting and merely describes some of the many possible embodiments of the appended claims.

[0246] FIG. 1 is a block diagram of an exemplary instrument 100 for analyzing a biological sample. In some embodiments, the instrument 100 includes a substance preparation system 102, a preparation evaluation system 104, and a substance evaluation system 106. One or more containers 110 are used with the systems of the instrument 100 and include a dispensing tip 112 and a container 114. Also shown is one or more container carriage devices 116 provided within the instrument 100. Further, the preparation evaluation system 104 includes a volume detection system 120, a dispensing tip evaluation system 122, and a carriage detection system 126. In some embodiments, the volume detection system 120 utilizes a dispensing tip image capture unit 130 and a container image capture unit 132. In some embodiments, the dispensing tip evaluation system 122 uses the dispensing tip image capture unit 130, and the particle concentration check system 124 uses the container image capture unit 132. In some embodiments, the carriage detection system 126 uses a carriage image capture unit 134.

[0247] As described in the summary section of the present disclosure, a system for evaluating a fluid substance according to a fourth aspect, a fifth aspect, and / or a ninth aspect may each refer to an instrument 100 for analyzing a biological sample, and / or each may refer to one or more components and / or devices of the instrument 100. It should be noted that further, a method for evaluating a fluid substance according to a first aspect, a sixth aspect, a tenth aspect, and / or a thirteenth aspect as described in the summary section of the present disclosure may each refer to a method for operating the instrument 100, and / or each may refer to a method for operating one or more components and / or devices of the instrument 100.

[0248] The biological sample analysis instrument 100 operates to analyze biological samples for various purposes. In some embodiments, the biological sample analysis instrument 100 is configured to analyze blood samples and operates to collect, examine, process, store, and / or transfuse blood and its components.

[0249] The substance preparation system 102 operates to prepare one or more substances for further analysis by the substance evaluation system 106. In some embodiments, the substance preparation system 102 operates to aliquot the substance 118 using the container 110, aspirate the substance 118 from the container 110, and dispense the substance 118 into the container 110.

[0250] The preparation evaluation system 104 operates to evaluate the preparation of a substance for subsequent analysis by the substance evaluation system 106. In some embodiments, the preparation evaluation system 104 utilizes one or more image capture units to determine whether the substance 118 is properly prepared for analysis. As described herein, the preparation evaluation system 104 provides a direct and simple measurement of the volume or integrity of the substance 118 to determine whether the substance 118 is properly prepared so that the substance evaluation system 106 can produce reliable results using the substance 118.

[0251] The substance evaluation system 106 operates to evaluate the substance 118 prepared by the substance preparation system 102. As an example, the substance evaluation system 106 performs an immunological assay as described with reference to FIG. 2.

[0252] The container 110 is used to prepare one or more substances 118 to be analyzed by the substance evaluation system 106. The container 110 can be of various types such as a sample tube (also referred to herein as a sample tube), a pipetting tip, and a container. In some embodiments, the container 110 includes a dispensing tip 112 and a container 114.

[0253] The dispensing tip 112 is provided to the substance preparation system 102 to aliquot or aspirate the substance 118 from other containers such as the container 114. For example, the dispensing tip 112 is used to aliquot a sample from a sample tube or aspirate a sample or reagent from a sample container or reagent container. Examples of the dispensing tip 112 are described and illustrated in more detail with reference to FIGS. 13 and 14.

[0254] The container 114 is provided to the substance preparation system 102 to contain the substance 118 for preparation and analysis. In some embodiments, the substance preparation system 102 dispenses the substance 118 into the container 114. Examples of the container 114 include a sample container, a diluent container, and a reaction container, which are described in more detail herein.

[0255] The container carriage device 116 enables the substance preparation system 102, the preparation evaluation system 104, and the substance evaluation system 106 to use the container 110 in various manners 、It is configured to hold and carry the container 110 at various locations within the instrument 100. Examples of the container carriage device 116 are further described and illustrated in more detail with reference to FIG. 2, including container racks (e.g., sample racks, reagent racks, and diluent racks), sample presentation units, container carriage units (e.g., sample carriage units, reaction vessel carriage units, and reagent carriage units), container transfer units (e.g., sample transfer units, reagent transfer units, incubator transfer units, and reaction vessel transfer units), and container holding plates or wheels (e.g., sample wheels, incubators, and washing wheels).

[0256] The substance 118 is prepared, evaluated, and examined for various tests and analyses within the instrument 100. The substance 118 includes any substance that can be aliquoted, aspirated, and dispensed within the instrument 100. In some embodiments, the substance 118 has fluid properties and is thus referred to herein as a fluid substance. In some embodiments, the fluid substance 118 is a single fluid substance. In other embodiments, the fluid substance 118 is a mixture of multiple substances.

[0257] The volume detection system 120 of the preparation and evaluation system 104 operates to detect the volume of the fluid substance 118 within the container 110 and determine whether the volume held within the container 110 is appropriate as a target. As described herein, the volume detection system 120 is configured to detect the volume at the dispensing tip 112 using the dispensing tip image capture unit 130 and the volume at the container 114 using the container image capture unit 132.

[0258] The dispensing tip evaluation system 122 of the dispensing evaluation system 104 operates to evaluate the integrity of the fluid substance 118. In some embodiments, the dispensing tip evaluation system 122 detects any interfering substances that can interfere with the analysis procedure and produce inaccurate results. As described herein, the dispensing tip evaluation system 122 is configured to use the dispensing tip image capture unit 130 to determine the quality of the fluid substance 118 at the dispensing tip 112 and the alignment of the dispensing tip 112 with respect to the dispensing tip image capture unit 130.

[0259] The particle concentration check system 124 operates to determine the particle concentration in a fluid substance contained in a container, such as any suitable type of container, including reaction vessels, sample vessels, dilution vessels, cuvettes, or vessels used throughout the process in the instrument 100. In some embodiments, the reaction vessel particle concentration check system 1700 uses the container image capture unit 132.

[0260] The dispensing tip image capture unit 130 operates to capture an image of the dispensing tip 112 at one or more locations. In some embodiments, the dispensing tip image capture unit 130 is fixed at a specific location within the instrument 100. In other embodiments, the dispensing tip image capture unit 130, which can move either independently of other components of the instrument 100 or together with one or more components of the instrument 100, is movably disposed within the instrument 100. Some embodiments of the instrument 100 include multiple dispensing tip image capture units 130. As described herein, the dispensing tip image capture unit 130 can include the camera unit 550 (e.g., FIG. 11) and the camera unit 2550 (FIGS. 11 and 67).

[0261] The container image capture unit 132 operates to capture an image of the container 114 at one or more locations. In some embodiments, the container image capture unit 132 is fixed at a specific location within the instrument 100. In other embodiments, the container image capture unit 132, which can move either independently of other components of the instrument 100 or together with one or more components of the instrument 100, is movably disposed within the instrument 100. Some embodiments of the instrument 100 include a plurality of container image capture units 132. As described herein, the container tip image capture unit 132 includes a camera unit 730 (e.g., FIG. 24). In , the container image capture unit 132, which can move, is movably arranged within the instrument 100. Some embodiments of the instrument 100 include a plurality of container image capture units 132. As described herein, the container tip image capture unit 132 includes a camera unit 730 (e.g., FIG. 24).

[0262] The carriage image capture unit 134 operates to capture an image of the container carriage device 116, with or without the container 110, at one or more locations. In some embodiments, the carriage image capture unit 134 is fixed at a specific location within the instrument 100. In other embodiments, the carriage image capture unit 134, which can move either independently of other components of the instrument 100 or together with one or more components of the instrument 100, is movably disposed within the instrument 100. Some embodiments of the instrument 100 include a plurality of carriage image capture units 134.

[0263] Continuing to refer to FIG. 1, in some embodiments, the instrument 100 operates to communicate with the management system 136 via the data communication network 138. For example, the instrument 100 includes a communication device (such as the communication device 246 in FIG. 3) through which the instrument 100 communicates with the management system 136.

[0264] In some embodiments, the management system 136 is located remotely from the instrument 100 and is configured to perform diagnostics based on data from the instrument 100. Additionally, the instrument 100 can evaluate the performance of the instrument and generate a report. One example of the management system 136 includes one or more computer devices that execute a PRO Services Remote Service Application available from Beckman Coulter, Inc. (Brea, CA).

[0265] The Beckman Coulter PRO Services Remote Service Application can provide a secure continuous connection between the biological sample analysis instrument 100 and a remote diagnostics command center (e.g., the management system 136) via a network (e.g., network 138). The biological sample analysis instrument 100 may be connected to the remote diagnostics command center via the Internet through an Ethernet port, Wi-Fi, or a cellular network.

[0266] Still referring to FIG. 1, data communication network 138 communicates digital data between one or more computer devices such as between data collection device 108 and data processing system 136. Examples of network 138 include local area networks and wide area networks such as the Internet. In some embodiments, network 138 includes a wireless communication system, a wired communication system, or a combination of wireless and wired communication systems. The wired communication system can transmit data using electrical or optical signals in various possible embodiments. The wireless communication system typically transmits signals in the form of optical signals or high frequency (RF) signals via electromagnetic waves. The wireless communication system typically includes an optical or RF transmitter for transmitting an optical or RF signal and an optical or RF receiver for receiving the optical or RF signal. Examples of wireless communication systems include Wi-Fi communication devices (such as utilizing a wireless router or wireless access point), cellular communication devices (such as utilizing one or more cellular base stations), and other wireless communication devices.

[0267] FIG. 2 schematically illustrates an embodiment of the biological sample analysis instrument 100 of FIG. 1. In the illustrated embodiment, the instrument 100 is configured as an immunological assay analyzer. As described above, the instrument 100 includes a substance preparation system 102, a preparation evaluation system 104, and a substance evaluation system It includes item 106. In some embodiments, the substance preparation system 102 includes a sample supply board 140, a sample presentation unit 142, a reaction vessel feeder 144, a reaction vessel carriage unit 146, a sample transfer unit 148, a pipette operation tip feeder 150, a sample pipette operation device 152, a sample wheel 158, a reagent carriage unit 160, a reagent pipette operation device 162, a reagent storage device 164, a reagent loading device 166, an incubator transfer unit 170, an incubator 172, a reaction vessel transfer unit 174, a cleaning wheel 176, and a substrate loading device 180. In some embodiments, the substance evaluation system 106 includes an optical measurement device 190 and an evaluation processing device 192. Some embodiments of the substance evaluation system 106 are further associated with at least some of the operations performed by the incubator transfer unit 170, the incubator 172, the reaction vessel transfer unit 174, the cleaning wheel 176, and the substrate loading device 180.

[0268] The sample supply board 140 is configured to receive a plurality of sample tubes in a plurality of sample racks. In some embodiments, a user (e.g., a medical technician) loads one or more racks of sample tubes onto the sample supply board 140. The sample supply board 140 can move the rack to the sample presentation unit 142 for pipetting operations and receive the pipetted rack that is returned by the sample presentation unit 142 after the pipetting operation.

[0269] The sample presentation unit 142 operates to transfer one or more racks of sample tubes to a designated location. In some embodiments, the sample supply board 140 operates to provide one sample rack to the sample presentation unit 142. Further, the sample presentation unit 142 can operate to identify the rack and the sample IDs on the rack. The sample presentation unit 142 transfers the rack to the sample pipetting operation location where the sample pipette aliquot from the sample tubes in the rack. When the sample pipette aliquots from one of the sample tubes in the rack, the sample presentation unit 142 advances another sample tube in the rack for the next pipetting operation. After all of the sample tubes have been pipetted, the sample presentation unit 142 returns the rack to the sample supply board 140. The sample presentation unit 142 can include a sample rack presentation unit. In other embodiments, the sample presentation unit 142 is configured to transfer a pack carrying a single tube. It is understood that the sample presentation unit 142 can also be configured and used for other types of containers such as cups or vessels.

[0270] The reaction vessel feeder 144 supplies a plurality of reaction vessels to the reaction vessel carriage unit 146. The user can load a large number of new empty reaction vessels into the reaction vessel feeder 144. In some embodiments, the reaction vessel feeder 144 operates to orient the reaction vessels when supplying the reaction vessels to the reaction vessel carriage unit 146.

[0271] The reaction vessel carriage unit 146 operates to transfer reaction vessels from the reaction vessel feeder 144 to the sample transfer unit 148. In some embodiments, the reaction vessel carriage unit 146 picks up one or more reaction vessels from the reaction vessel feeder 144 and transfers the reaction vessels to the sample transfer unit 148.

[0272] The sample transfer unit 148 operates to transfer empty reaction vessels from the reaction vessel carriage unit 146 to the sample wheel 158 and the reagent carriage unit 160. Further, the sample transfer unit 148 operates to transfer the aliquoted sample containers to the reagent carriage unit 160 and return and transfer the sample containers from the reagent carriage unit 160 to the sample wheel 158. The sample transfer unit 148 can further operate to dispose of the sample containers and diluent containers used in the pre-determined process. It can be done.

[0273] The pipetting tip feeder 150 supplies pipetting tips to the sample pipetting device 152. In this document, the pipetting tip is an example of the dispensing tip 112, and thus can also be referred to as the dispensing tip 112 in this specification. In some embodiments, a plurality of pipetting tips in a rack are loaded into an array in the pipetting tip feeder 150. The pipetting tips are transferred to and engaged with the sample pipetting device 152 for pipetting operations. Once used, the pipetting tips are disengaged from the sample pipetting device 152 for disposal, and the sample pipetting device 152 can return to the pipetting tip feeder 150. The user can discard the solid waste, including the used pipetting tips.

[0274] The sample pipetting device 152 performs various pipetting operations. The sample pipetting device 152 receives the pipetting tip from the pipetting tip feeder 150 and engages the pipetting tip with the sample pipetting device 152. In some embodiments, the sample pipetting device 152 engages the pipetting tip by pushing a pipettor mandrel into the pipetting tip and lifts the pipettor mandrel that fits into the pipetting tip. As described in this specification, some embodiments of the pipetting tip can be disposable after single or multiple uses.

[0275] In some embodiments, the sample pipetting device 152 includes a sample aliquot pipetting unit (the “sample aliquot gantry”) 152A and a sample precision pipetting unit (the “sample precision gantry”) 152B.

[0276] The sample aliquot pipetting unit 152A is operative to pipette an aliquot of a sample from a sample tube located within the sample presentation unit 142 and dispense the aliquot of the sample into a sample container on the sample wheel 158. The sample aliquot pipetting unit can dispose of a used pipetting tip when the pipetting operation is completed for each sample. As described herein, the sample aliquot pipetting unit 152A can include a camera unit 550, which is further described herein with reference to FIGS. 11, 12A, and 12B, for example.

[0277] The sample precision pipetting unit 152B is operative to pipette a sample from a sample container located on the reagent carriage unit 160. The sample precision pipetting unit can then dispense the sample into a reaction vessel. In some embodiments, the sample can first be dispensed into a dilution container to create a sample dilution (e.g., with a wash buffer provided by the reagent pipetting device 162) prior to being dispensed into the reaction vessel. The sample precision pipetting unit can dispose of a used pipetting tip when a pre-determined assay is completed. As described herein, the sample precision pipetting unit 152B can include a camera unit 2550, which is further described herein with reference to FIGS. 11, 12A, 12B, and 67.

[0278] The sample wheel 158 stores the aliquoted samples in the sample containers thereon. In some embodiments, the sample wheel 158 operates to maintain the samples at a lower temperature, such as about 4 - 10 °C, to reduce the analyte concentration that would otherwise change by evaporation. The sample containers can be transferred back to the sample wheel 158 after reagent pipetting operations, if additional testing is required.

[0279] The reagent carriage unit 160 is configured to support a plurality of containers and transfer the containers to different locations. In some embodiments, the reagent carriage unit 160 is configured to hold a plurality of four containers (e.g., three or four containers) that can be used simultaneously for each reagent pipettor of the reagent pipetting operation device 162. In some embodiments, the reagent carriage unit 160 is thermally controlled at about 30 °C - 40 °C. In other embodiments, the reagent carriage unit 160 is maintained at about 37 °C, for example, to ensure a consistent kinetic reaction of the enzyme.

[0280] In some embodiments, the reagent carriage unit 160 is configured to hold reaction vessels, dilution vessels, and sample containers and transport the containers for sample pipetting and reagent pipetting operations. In some embodiments, the reagent carriage unit 160 includes a carriage shuttle that is movable along a pre-determined path. For example, the reagent carriage unit 160 is moved close to the sample transfer unit 148 to receive the reaction vessels, dilution vessels, and sample containers from the sample transfer unit 148. Further, the reagent carriage unit 160 can move to the reagent pipetting operation device 162 to pipette reagents and to the sample precision pipetting operation unit 152B to pipette samples. In some embodiments, the reagent carriage unit 160 moves to the sample transfer unit 148 to remove the dilution vessels and sample containers and to the culture transfer unit 170 to remove the reaction vessels.

[0281] The reagent pipetting device 162 operates to pipette reagents from the reagent storage device 164 into the reaction vessels on the reagent carriage unit 160. In some embodiments, the reagent pipetting device 162 includes multiple pipettors that can perform pipetting operations simultaneously in different tests to support throughput. In some embodiments, the reagent pipetting device 162 is thermally controlled at about 30°C to 40°C. In other embodiments, the reagent pipetting device 162 is maintained at about 37°C, for example, to ensure a consistent binding reaction rate for enzyme reactions.

[0282] The reagent storage device 164 stores reagents. The reagent storage device includes a reagent transfer unit configured to transfer reagent packs to pre-determined locations. In some embodiments, the reagent storage device 164 can transfer reagent packs from the reagent loading device 166 to the reagent storage device 164, from the reagent storage device 164 to the pipetting location for pipetting operations by the reagent pipetting device 162, from the pipetting location back to the reagent storage device 164, from the pipetting location to the disposal location when the reagent is consumed, from the reagent storage device 164 to the disposal location when the reagent expires, and from the reagent storage device 164 to the reagent loading device 166 to unload the reagent pack. In some embodiments, the reagent storage device 164 is thermally controlled at about 2°C to 15°C. In other embodiments, the reagent storage device 164 is maintained at about 4°C to 10°C.

[0283] The reagent loading device 166 operates to load one or more reagent packs. A user can load reagent packs into the reagent loading device 166.

[0284] The incubator transfer unit 170 transfers reaction vessels to and from the incubator 172. In some embodiments, the incubator transfer unit 170 transfers one or more than one of the reaction vessels pipetted from the reagent carriage unit 160 to the incubator 172. Further, the incubator transfer unit 170 can transfer one or more than one reaction vessel from the incubator 172 to the reagent carriage unit 160. The incubator transfer unit 170 can also remove the read or completed reaction vessels from the incubator 172.

[0285] The incubator 172 is thermally controlled to maintain a pre-determined temperature. In some embodiments, the incubator 172 is maintained at about 30°C to 40°C. In other embodiments, the incubator 172 is maintained at about 37°C, for example, to ensure immunological and enzymatic reactions. As an example, the incubator 172 performs assay incubation.

[0286] The reaction vessel transfer unit 174 transfers reaction vessels to and from the incubator 172. In some embodiments, the reaction vessel transfer unit 174 transfers the cultured reaction vessels from the incubator 172 to the wash wheel 176, transfers the assay reaction vessels from the wash wheel 176 to the incubator 172, transfers the reaction vessels containing substrates from the wash wheel 176 to the incubator 172 for substrate incubation or enzymatic reaction, transfers the washed reaction vessels from the incubator 172 to the optical measurement device 190 after substrate incubation, and transfers the read or completed reaction vessels from the optical measurement device 190 to the incubator 172. The used reaction vessels can be delivered to a disposal location.

[0287] The washing wheel 176 receives and supports the reaction vessel thereon such that various aspects of the diagnostic process are performed using the substance evaluation system 106. Embodiments of the washing wheel 176 are described and illustrated in further detail with reference to FIGS. 23-25. In some embodiments, the washing wheel 176 is a thermally controlled device that separates bound or free analytes from particles after incubation. In some embodiments, the washing wheel 176 is maintained at about 30° C. to 40° C. In other embodiments, the washing wheel 176 is maintained at about 37° C. to ensure, for example, an enzymatic reaction.

[0288] The substrate pipetting device 178 is operative to dispense a substrate into the washed reaction vessel. One example of a substrate is a chemiluminescent substrate for an immunoassay enzymatic reaction, such as Lumi-Phos 530, that can generate light to provide a detection corresponding to the quantity of analyte captured on magnetic particles.

[0289] The substrate loading device 180 is operative to load one or more substrates supplied thereto. In some embodiments, the substrate loading device 180 includes a set of two bottles, one of which is in use and the other of which is arranged for an unloading and new loading process. The substrate pipetting device 178 can be operative to draw the substrate from the bottle in use.

[0290] The light measurement device 190 is operative to detect and measure light (e.g., light L in FIG. 4) resulting from the immunoassay. In some embodiments, the light measurement device 190, which can also be referred to as a luminometer, includes a light-tight enclosure containing a photomultiplier tube (PMT) for reading the scale of chemiluminescence from the reaction vessel containing the substrate. The reaction vessel can be transferred to and removed from the light measurement device 190 by the reaction vessel transfer unit 174.

[0291] The evaluation processing device 192 receives information about the amount of light detected by the optical measurement device 190 and operates to evaluate the analysis based on the information.

[0292] FIG. 3 illustrates an exemplary architecture of a computer device that can be used to implement aspects of the present disclosure, including the biological sample analysis instrument 100, or various systems of the instrument 100 such as the substance preparation system 102, the preparation evaluation system 104, and the substance evaluation system 106. Further, one or more devices or units included in the systems of the instrument 100 can also be implemented with at least some of the components of the computer device, as illustrated in FIG. 3. Such a computer device is designated herein as reference numeral 200. The computer device 200 is used to execute the operating systems, application programs, and software modules (including software engines) described herein. In some embodiments, the computer device 200 includes at least one processing device 202 such as a central processing unit (CPU). Various processing devices are available from various manufacturers, for example, Intel or Advanced Micro Devices. In this embodiment, the computer device 200 also includes a system memory 204 and a system bus 206 that couples the various system components including the system memory 204 to the processing device 202. The system bus 206 is one of any number of types of bus structures including a memory bus or memory controller, a peripheral bus, and a local bus using any of a variety of bus architectures.

[0293] In some embodiments, the computer device 200 includes at least one processing device 202 such as a central processing unit (CPU). Various processing devices are available from various manufacturers, for example, Intel or Advanced Micro Devices. In this embodiment, the computer device 200 also includes a system memory 204 and a system bus 206 that couples the various system components including the system memory 204 to the processing device 202. The system bus 206 is one of any number of types of bus structures including a memory bus or memory controller, a peripheral bus, and a local bus using any of a variety of bus architectures.

[0294] Examples of computer devices suitable for computer device 200 include desktop computers, laptop computers, tablet computers, mobile devices (such as smartphones, iPod (registered trademark) mobile digital devices, or other mobile devices), or other devices configured to process digital instructions.

[0295] System memory 204 includes read-only memory 208 and random access memory 210. A basic input / output system 212, which contains basic routines that act to transfer information within computer device 200 during startup and the like, is typically stored in read-only memory 208.

[0296] In some embodiments, computer device 200 also includes a secondary storage device 214, such as a hard disk drive, for storing digital data. Secondary storage device 214 is connected to system bus 206 by a secondary storage interface 216. Secondary storage devices and their associated computer-readable media provide a non-volatile storage of computer-readable instructions (including application programs and program modules), data structures, and other data for computer device 200.

[0297] The exemplary environment described herein employs a hard disk drive as the secondary storage device, but other types of computer-readable storage media are also used in other embodiments. Examples of these other types of computer-readable storage media include magnetic cassettes, flash memory cards, digital video disks, Bernoulli cartridges, compact disk read-only memory, digital versatile disk read-only memory, random access memory, or read-only memory. Some embodiments include non-transitory media.

[0298] Some program modules, including operating systems 218, one or more application programs 220, other program modules 222, and program data 224, can be stored in secondary storage device 214 or memory 204.

[0299] In some embodiments, computer device 200 includes an input device that enables a user to provide input to computer device 200. Examples of input device 226 include keyboard 228, pointer input device 230, microphone 232, and touch sensor type display 240. Other embodiments include other input devices 226. Input devices are often connected to processing device 202 through an input / output interface 238 coupled to system bus 206. These input devices 226 can be connected by any number of input / output interfaces such as parallel ports, serial ports, game ports, or universal serial buses. Wireless communication between the input device and interface 238 is also possible, and in some contemplated embodiments includes infrared, BLUETOOTH® wireless technology, WiFi technology (802.11a / b / g / n, etc.), cellular, or other high frequency communication systems.

[0300] In this exemplary embodiment, touch sensor type display device 240 is also connected to system bus 206 via an interface such as video adapter 242. Touch sensor type display device 240 includes a touch sensor for receiving input from a user when the user touches the display. Such sensors can be capacitive sensors, pressure sensors, or other touch sensors. The sensors detect not only contact with the display, but also the location of the contact and the movement of the contact over time. For example, the user can move a finger or stylus across the screen to provide written input. The written input is evaluated and, in some embodiments, converted to text input.

[0301] In addition to the display device 240, the computer device 200 can include various other peripheral devices (not shown), such as speakers or printers.

[0302] The computer device 200 further includes a communication device 246 configured to establish communication across a network. In some embodiments, when used in a local area networking environment or a wide area networking environment (such as the Internet), the computer device 200 is typically connected to the network through a network interface such as a wireless network interface 248. Other possible embodiments use other wired and / or wireless communication devices. For example, some embodiments of the computer device 200 include an Ethernet (registered trademark) network interface or a modem for communicating across a network. In still other embodiments, the communication device 246 is capable of short-range wireless communication. The short-range wireless communication is one-way or two-way short- to medium-range wireless communication. The short-range wireless communication can be established according to various technologies and protocols. Examples of short-range wireless communication include radio frequency identification (RFID), near field communication (NFC), Bluetooth (registered trademark) technology, and Wi-Fi technology.

[0303] The computer device 200 typically includes at least some form of computer-readable medium. The computer-readable medium includes any available medium that can be accessed by the computer device 200. As an example, the computer-readable medium includes computer-readable storage media and computer-readable communication media.

[0304] A computer-readable storage medium includes volatile and non-volatile, removable and non-removable media implemented in any device configured to store information such as computer-readable instructions, data structures, program modules, or other data. Computer-readable storage media includes random access memory, read-only memory, electrically erasable programmable read-only memory, flash memory or other memory technologies, compact disc read-only memory, digital versatile discs or other optical storage devices, magnetic cassettes, magnetic tape, magnetic disk storage or other magnetic storage devices, or any other medium that can be used to store desired information and can be accessed by a computer device 200, but is not limited thereto.

[0305] A computer-readable communication medium typically embodies computer-readable instructions, data structures, program modules, or other data in a modulated data signal, such as a carrier wave or other transport mechanism, and includes any information delivery medium. The term "modulated data signal" refers to a signal that sets or changes one or more of its characteristics in such a manner as to encode information in the signal. By way of example, computer-readable communication media includes wired media such as a wired network or direct wired connection, as well as wireless media such as acoustic, radio frequency, infrared, and other wireless media. Any combination of the foregoing is also included within the scope of computer-readable media.

[0306] A blood sample is whole blood, serum, plasma, and other blood components or fractions. In some embodiments, the biological sample analysis instrument 100 is configured to analyze one or more body fluid sample types. Body fluids are blood, urine, saliva, cerebrospinal fluid, amniotic fluid, feces, mucus, cell or tissue extracts, and nucleic acid extracts. Samples, also referred to as specimens, are taken in donor centers, physicians' offices, phlebotomists' offices, hospitals, clinics, and other medical settings, but are not limited thereto. The collected body fluids and their components are then often processed, tested, and distributed in or through clinical laboratories, hospitals, blood banks, physicians' offices, or other medical settings. In the present disclosure, the instrument 100 is described as performing immunoassays that primarily measure the presence or concentration of macromolecules in solution through the use of antibodies or immunoglobulins. Such macromolecules are also referred to herein as analytes. In other embodiments, however, the instrument 100 includes any type of biological sample analyzer. For example, the instrument 100 can be a clinical chemistry analyzer, a blood typing analyzer, a nucleic acid analyzer, a microbiology analyzer, or any other type of in vitro diagnostic (IVD) analyzer.

[0307] Figure 4 is a schematic diagram illustrating an exemplary method 300 for immunoassay. In some embodiments, the method 300 includes operations 302, 304, 306, 308, 310, 312, and 314. In some embodiments, at least some of the operations in the method 300 are performed by the material preparation system 102, the preparation evaluation system 104, and / or the material evaluation system 106 of the instrument 100.

[0308] In operation 302, a cuvette 320 (e.g., a reaction vessel) is transported to a pre-determined position, and a first reagent containing magnetic particles 322 is dispensed into the cuvette 320. In some embodiments, the cuvette 320 is a reaction vessel and is transported to the wash wheel 176.

[0309] In operation 304, a sample or specimen 324 is dispensed into cuvette 320. In some embodiments, a sample pipetting device 152, to which a pipetting tip supplied from a pipetting tip feeder 150 is engaged, aspirates the sample 324 from a sample container transported to a pre-determined position. Once the sample is dispensed into the cuvette 320, the cuvette 320 may undergo mixing, if required, to produce magnetic particle carriers respectively formed by an antigen and magnetic particles in the combined sample 324.

[0310] In operation 306, the cuvette 320 undergoes a first washing process in which the magnetic particle carriers are magnetically collected by a magnetic collection unit 326 and the bound / free separation is performed by a bound / free washing suction nozzle 328. As a result, unreacted substances 330 in the cuvette 320 are removed.

[0311] In operation 308, a second reagent 332 such as a labeled reagent containing a labeled antibody is dispensed into the cuvette 320 As a result, immune complexes 334 respectively formed by the combined magnetic particle carriers and the labeled antibody 332 are produced.

[0312] In operation 310, a second bound / free washing process is performed to magnetically collect the magnetic particle carriers by a magnetic collection structure 336. Further, the bound / free separation is performed by a bound / free washing suction nozzle 338. As a result, the labeled antibody 332 not bound to the magnetic particle carriers is removed from the cuvette 320.

[0313] In operation 312, a substrate containing an enzyme 340 is dispensed into the cuvette 320 and then mixed. After a reaction time required for the enzyme reaction has elapsed, the cuvette 320 is transported to a photometric system such as a photometric device 190.

[0314] In operation 314, the enzyme 340 and the immune complex 334 are both bound through the reaction of the substrate 340 with the enzyme on the labeled antibody 332, and light L is emitted from the immune complex 334 and measured by a photometric system such as the light measurement device 190. The light measurement device 190 operates to calculate the amount of antigen contained in the sample according to the amount of light measured.

[0315] Referring to FIG. 5-39, an embodiment of the volume detection system 120 is described.

[0316] FIG. 5 is a block diagram of an embodiment of the volume detection system 120 of FIG. 1. In some embodiments, the volume detection system 120 includes a dispensing tip volume detection device 400 and a container volume detection device 402. The volume detection system 120 further includes a correlation data generation system 404 that generates correlation data 406.

[0317] The dispensing tip volume detection device 400 operates to detect the volume of the fluid substance 118 aspirated into the dispensing tip 112.

[0318] The fluid substance 118 may be of any suitable type to be dispensed into the container and presented for further analysis. In various embodiments, the fluid substance 118 may be a sample to be analyzed, a sample preparation component, a diluent, a buffer, a reagent, or any combination of the foregoing. When the fluid substance 118 involves blood or its components, examples of the fluid substance 118 include whole blood, plasma, serum, red blood cells, white blood cells, platelets, diluents, reagents, or any combination thereof. The fluid substance 118 may be other types of body fluid substances such as saliva, cerebrospinal fluid, urine, amniotic fluid, feces, mucus, cell or tissue extracts, nucleic acids, or any other type of body fluid, tissue, or substance suspected of containing the analyte of interest. When the fluid substance 118 is a reagent, the reagent may be of various types known for use in the analysis of biological samples. Some examples of reagents include liquid reagents containing label-specific binding reagents, such as antibodies or nucleic acid probes, liquid reagents containing reactive and / or non-reactive substances, red blood cell suspensions, and particle suspensions. In other embodiments, the reagent can be a chemiluminescent substrate.

[0319] As described herein, the dispensing tip 112 can be of various types and can be used in different processes. One example of the dispensing tip 112 is a pipetting tip that can be used with the sample pipetting device 152. The dispensing tip volume detection device 400 can utilize the dispensing tip image capture unit 130. Examples of the dispensing tip volume detection device 400 are illustrated and described in further detail with reference to FIGS. 9-21.

[0320] The container volume detection device 402 operates to detect the volume of the fluid substance 118 contained within the container 114. As described herein, the container 114 can be of various types Moreover, it can be used in different processes. Examples of the container 114 include a reaction container, a sample container, and a dilution container that are used throughout the process in the instrument 100. The container volume detection device 402 can utilize the container image capture unit 132. Examples of the container volume detection device 402 are illustrated and described in more detail with reference to FIGS. 22-39.

[0321] The correlation data generation system 404 generates correlation data 406. The correlation data 406 provides information used by the volume detection system 120 to determine the volume of the fluid substance 118 received in the container 110. In some embodiments, the correlation data generation system 404 is a device independent of the volume detection system 120. In other embodiments, the correlation data generation system 404 is configured to use at least some resources of the volume detection system 120.

[0322] FIG. 6 is a flowchart illustrating an exemplary method 410 for operating the volume detection system 120. In some embodiments, at least some of the operations in the method 410 are performed by the substance preparation system 102, the preparation evaluation system 104, and / or the substance evaluation system 106 of the instrument 100. In other embodiments, other components, units, and devices of the instrument 100 are used to perform at least one of the operations in the method 410.

[0323] In operation 412, the fluid substance 118 is provided into the container 110. In some embodiments, the substance preparation system 102 can perform operation 412. In other embodiments, the container 110 is pre-loaded with the fluid substance 118 before the container 110 is loaded into the instrument 100 and used by the instrument 100.

[0324] In operation 414, the container 110 containing the fluid substance 118 is transported to image capture units such as the dispensing tip image capture unit 130 and the container image capture unit 132.

[0325] In operation 416, the image capture unit captures an image of the container 110. In some embodiments, the image of the container 110 is a digital image at a pre-determined resolution.

[0326] In operation 418, the preparation evaluation system 104 (e.g., the volume detection system 120) analyzes the image to determine the volume of the fluid substance 118 within the container 110. An example of operation 416 is described in more detail with reference to FIG. 7.

[0327] In operation 420, the preparation evaluation system 104 (e.g., the volume detection system 120) determines whether the determined volume falls within a tolerance range. When the determined volume is outside the tolerance range, the provision of the fluid substance 118 into the container 110 is considered inappropriate. In some embodiments, such a tolerance range is determined based on the allowable deviation from the target volume of the fluid substance 118 intended to be provided into the container 110. When it is determined that the detected volume falls within the tolerance range (in operation 420, "yes"), method 410 proceeds to perform the next pre-determined step. Otherwise (in operation 420, "no"), method 410 proceeds to operation 422.

[0328] In operation 422, the preparation evaluation system 104 (e.g., the volume detection system 120) flags the container 110 to indicate that the volume of the fluid substance 118 within the container 110 is not appropriate for a subsequent process. Alternatively, the preparation evaluation system 104 operates to stop a related inspection or analysis process within the instrument 100. In other embodiments, the evaluation results can be used to automatically adjust inspection results that may be in error due to an inappropriate volume of the fluid substance. In yet other embodiments, as described in this specification, the evaluation results can be used to automatically adjust the volume of the fluid substance in response to the volume determination.

[0329] FIG. 7 is a flowchart illustrating an exemplary method 430 for performing operation 418 of FIG. 6. Specifically, method 430 provides a process for analyzing a captured image of container 110 to determine the volume of fluid substance 118 contained within container 110.

[0330] At operation 432, preparation evaluation system 104 (e.g., volume detection system 120) detects reference points within the image. The reference points are associated with container 110. In some embodiments, the reference points include the location or a portion of a detectable structure formed on container 110. In other embodiments, the reference points are configured as part of container 110. Other examples of reference points are possible. Various image processing methods can be used to detect the surface level of fluid substance 118 within the image.

[0331]

[0332] At operation 434, preparation evaluation system 104 (e.g., volume detection system 120) detects the surface level of fluid substance 118 within container 110 in the image. Various image processing methods can be used to detect the surface level of fluid substance 118 within the image.

[0333]

[0334] At operation 436, preparation evaluation system 104 (e.g., volume detection system 120) measures the distance between the reference point and the surface level. In some embodiments, the distance is measured by the pixel distance between the reference point and the surface level within the image. In some embodiments, the pixel distance is calculated based on the Euclidean distance between two pixel points. At operation 438, preparation evaluation system 104 (e.g., volume detection system 120) converts the distance to a volume based on correlation data 406. Correlation data 406 includes information about the correlation between the volume within container 110 and the distances from the reference point to multiple different surface levels within container 110. An exemplary method for generating correlation data is described with reference to FIG. 8.FIG. 8 is a flowchart illustrating an exemplary method 450 for operating the correlation data generation system 404 to generate correlation data 406. In some embodiments, a portion of the instrument 100 is used as the correlation data generation system 404. In other embodiments, the correlation data generation system 404 generates correlation data independently of the instrument 100.

[0335] In operation 452, the correlation data generation system 404 supplies a liquid to a container. The container used in method 450 is the same container 110 that undergoes the volume detection process herein. The liquid used in method 450 need not be the same as the fluid substance 118 used in the instrument 100.

[0336] In operation 454, the correlation data generation system 404 captures an image of the container having the liquid.

[0337] In operation 456, the correlation data generation system 404 extracts the distance between a reference point (i.e., the reference point as described in operation 432) and the fluid surface within the image captured in operation 454. In some embodiments, the distance can be determined in a similar manner as at least some of the operations of method 430, such as operations 432, 434, and 436.

[0338] In operation 458, the correlation data generation system 404 measures the volume of the liquid supplied to the container. Various methods can be used to determine the volume of liquid within the container. Some of such methods are described herein.

[0339] In operation 460, the correlation data generation system 404 correlates the distance calculated in operation 456 and the volume measured in operation 458.

[0340] In operation 462, the correlation data generation system 404 determines whether a sufficient number of correlations are being made to generate correlation data 406. If so (in operation 470, "Yes"), method 450 proceeds to operation 464. Otherwise (in operation 470, "No"), method 450 returns to operation 452 where liquid is supplied to the container, and subsequent operations are performed to determine additional correlations between distance and the volume of liquid in the container. To obtain a sufficient range of correlation data, the amount of liquid supplied to the container can vary in different cycles of the correlation process. Additionally, the amount of liquid supplied to the container can remain substantially the same for some of the correlation cycles to obtain reliable results for a particular volume or volume range.

[0341] In operation 464, the correlation data generation system 404 creates correlation data 408 based on the plurality of correlations performed in operation 460. In some embodiments, the correlation data 408 can be estimated to infer the relationship between distance and volume. For example, a correlation curve, look-up table, or mathematical formula can be created from the correlation data 408 to fit the data and estimate the relationship between distance and the volume in the container.

[0342] Referring to FIGS. 9-21, an embodiment of the dispensing tip volume detection device 400 of FIG. 5 is described.

[0343] FIG. 9 illustrates an embodiment of the dispensing tip volume detection device 400 of FIG. 5. In some embodiments, the dispensing tip volume detection device 400 includes a sample aspiration volume detection device 500. Additionally, the dispensing tip volume detection device 400 uses tip volume correlation data 506 generated by a tip volume correlation data generation system 504.

[0344] The sample aspiration volume detection device 500 operates to determine the volume of a sample aspirated into the sample pipetting tip of the sample pipetting device 152. Examples of the structure and operation of the sample aspiration volume detection device 500 are described below.

[0345] The tip volume correlation data generation system 504 generates tip volume correlation data 506. The tip volume correlation data 506 provides information used by the dispensing tip volume detection device 400 to determine the volume of a fluid substance received within a dispensing tip (e.g., a sample pipetting tip). In some embodiments, the tip volume correlation data generation system 504 is a device independent of the dispensing tip volume detection device 400. In other embodiments, the tip volume correlation data generation system 504 is configured to use at least some resources of the dispensing tip volume detection device 400. The tip volume correlation data generation system 504 and the tip volume correlation data 506 are included in, or are examples of, the correlation data generation system 404 and the correlation data 406 as illustrated in FIG. 5.

[0346] Reliable clinical diagnosis requires accurate and precise aspiration and dispensing of the substance to be analyzed. For example, in an automated analyzer that analyzes a sample such as blood or any other body fluid, variations in the dispensed amounts of the sample and other substances such as reagents within a reaction vessel relative to a specified quantity can affect the analysis results and reduce the reliability of the test and analysis. Therefore, it is beneficial to establish a technique for measuring the amount aspirated or dispensed with high accuracy and selecting only the aspirated or dispensed samples whose amount is within a suitable range. One method of measuring the liquid volume is to detect the level of the liquid surface by determining the height of the liquid inside the container using the resonance frequency. In other cases, air pressure is used to determine the viscosity of the liquid (e.g., the sample) aspirated by the dispensing tip. In still other cases, a flow sensor is used to determine the flow rate of the liquid aspirated or dispensed.

[0347] ​However, these approaches have various disadvantages. For example, detecting the liquid surface level using the resonance frequency and detecting the fluid viscosity using the air pressure can determine the liquid volume in the container, but cannot quantify the liquid volume aspirated or dispensed. The flow rate sensor can quantify the volume of the liquid passing through the pipes where the flow rate sensors are arranged, but cannot reliably measure the liquid volume aspirated or dispensed. These methods do not have a process for identifying inaccurate sample aspiration in case of incorrect results.

[0348] As will be described in more detail herein, the dispensing tip volume detection device 400 employs an image processing method for quantifying the volume of the fluid substance (e.g., sample) aspirated. The volume of the fluid substance is aspirated into a transparent or translucent container such as a conical dispensing tip. The container is imaged and a reference point is detected within the image. The dispensing tip volume detection device measures the distance from the meniscus of the fluid substance to the reference point and correlates the distance to the volume using a volume calibration curve. If the volume aspirated inside the container is not within the specifications of the aspiration accuracy or precision, the entire aspiration or inspection is flagged. The user or operator can receive information about the result of the aspiration.

[0349] FIG. 10 schematically illustrates an exemplary structure of a sample aspiration system 510 related to the sample aspiration volume detection device 500. In the illustrated embodiment, the sample aspiration volume detection device 500 is mainly described and illustrated as an example of the dispensing tip volume detection device 400. However, it is understood that any type of dispensing tip volume detection device 400 can be used in the same or similar manner as the sample aspiration volume detection device 500.

[0350] In some embodiments, the sample aspiration system 510 includes a sample pipette operating module 512 that is movable along a sample transfer guide 514 between different positions. The sample pipette operating module 512 can move to a tip supply position 516, a sample dispensing position 518, a tip disposal position 520, and a sample aspiration position 522. In some embodiments, the sample pipette operating module 512 includes a base 524 and a mandrel 526 supported at the base 524. The sample pipette operating module 512 includes a vertical transfer unit 528 configured to vertically move the base 524 including the mandrel 526 relative to a sample container 530. The mandrel 526 is configured to carry a dispensing tip 112, also referred to herein as a pipette operating tip or probe, a suction tip or probe, or a disposable tip or probe 112.

[0351] On the instrument 100, the sample is aspirated by the dispensing tip so as to avoid the risk of contamination. The sample pipette operating module 512 can move to the tip supply position 516 and lower the base 524 of the module 512 vertically to insert the mandrel 526 into one of the dispensing tips 112 supplied by a dispensing tip supply unit 534. Next, the sample pipette operating module 512 moves to the sample aspiration position 522 where the sample pipette operating module 512 operates to aspirate a pre-determined volume of the sample 540 from the sample container 530. Once the sample is aspirated, the sample aspiration volume detection device 500 detects the volume of the sample aspirated into the dispensing tip 112. In some embodiments, the sample aspiration volume detection device 500 includes a dispensing tip image capture unit 130 to capture an image of the dispensing tip 112 as part of the volume detection process. Thereafter, the sample pipette operating module 512 moves to the sample dispensing position 518 to dispense the aspirated volume of the sample into the reaction container 536 and then moves to the tip disposal position 520 to discard the dispensing tip 112 into a dispensing tip disposal unit 538. ​

[0352] In some embodiments, the sample aspiration system 510 is implemented with at least some of the components of the instrument 100, as shown in FIG. 2. For example, the sample pipetting operation module 512 corresponds to the sample pipetting device 152 (including the sample aliquot pipetting unit 152A and the sample precision pipetting unit 152B) of the instrument 100. The sample container 530 can correspond to a sample tube. The dispensing tip supply unit 534 can correspond to the pipetting operation tip feeder 150. The reaction container 536 can correspond to a sample container, a reaction container, or any other container.

[0353] FIGS. 11, 12A, and 12B illustrate the sample aspiration system 510 of FIG. 10. FIG. 11 is a perspective view of the sample aspiration system of FIG. 10, FIG. 12A is a side view of the sample aspiration system 510, and FIG. 12B is another side view of the sample aspiration system 510 illustrating the sample pipetting operation module 512 at the sample aspiration position 522 for volume detection using the sample aspiration volume detection device 500.

[0354] As shown, the dispensing tip image capture unit 130 includes the first camera unit 550 and its associated components mounted on the sample aliquot pipetting unit 152A. In some embodiments, the first camera unit 550 and such other components are configured to move with the corresponding mandrel and dispensing tip of the sample aliquot pipetting unit 152A.

[0355] In some embodiments, camera unit 550 includes a complementary metal oxide semiconductor (CMOS) image sensor for acquiring color digital images. In other embodiments, camera unit 550 includes a charge-coupled device (CCD) image sensor for acquiring color digital images. As shown in FIG. 12, camera unit 550 is located on the side of dispensing tip 112. Other embodiments of camera unit 550 are configured to acquire black and white or grayscale photographs. One example of camera unit 550 includes a model named ADVANTAGE 102, which is available from Cognex Corporation (Natick, MA), such as AE3-IS machine vision color camera + IO board (e.g., part number AE3C-IS-CQBCKFS1-B).

[0356] The dispensing tip image capture unit 130 can further include a light source 552 for the camera 550. The light source 552 is used to irradiate the dispensing tip 112 and its surroundings to be photographed as desired. The light source 552 can be arranged in various locations. In the illustrated embodiment, the light source 552 is positioned behind the dispensing tip 112 opposite the camera unit 550 and is thus used as a backlight. Other locations for the light source 552 are possible. One example of the light source 552 includes the MDBL series available from Moritex Corporation (Japan).

[0357] In other embodiments, camera unit 550 includes a light source 551, such as an LED light, that is operable to emit light toward dispensing tip 112. In this configuration, the light source 552 can be replaced by a screen 553 that is arranged opposite the camera unit 550 such that the dispensing tip 112 is positioned between the camera unit 550 and the screen 553. The screen 553 reflects light toward the aperture of the camera, whereby the camera It is used to emit light back in the direction of the field of view (FOV) of the knit. The screen 553 is made of one or more various materials that can provide different reflection intensities. For example, the screen 553 includes a retroreflective sheet, and one embodiment thereof is 3M TM Scotchlite TM sheet 7610. In other embodiments, the light source 552 can be used together with the light source 551 from the camera unit 550 and the screen 553.

[0358] In some embodiments, the camera unit 550 and the light source 552 (or the screen 553) are attached to the sample pipetting operation module 512 and are configured to move horizontally together with the sample pipetting operation module 512 so that an image of the dispensing tip 112 is captured at any position of the sample pipetting operation module 512. For example, an image of the dispensing tip 112 containing the aspirated sample can be taken at any position after the sample is aspirated (i.e., the sample aspiration position 522) and before the sample is dispensed (i.e., the sample dispensing position 518). In other embodiments, the camera unit 550 is attached to the sample pipetting operation module 512 while the light source 552 (or the screen 553) is not attached to the sample pipetting operation module 512. In still other embodiments, the camera unit 550 is not attached to the sample pipetting operation module 512 while the light source 552 (or the screen 553) is attached to the sample pipetting operation module 512. In yet other embodiments, neither the camera unit 550 nor the light source 552 (or the screen 553) is attached to the sample pipetting operation module 512.

[0359] In addition, the dispensing tip image capture unit 130 can include a second camera unit 2550 and its associated components mounted on the sample precision pipette operation unit 152B. The second camera unit 2550 and its associated components can be configured similarly to the first camera unit 550 and its associated components.

[0360] In some embodiments, the second camera unit 2550 and such other components are configured to move with the corresponding mandrel and dispensing tip of the sample aliquot pipette operation unit 152A.

[0361] The second camera unit 2550 can be configured similarly to the first camera unit 550. One example of the camera unit 2550 includes a model named ADVANTAGE 102, which is available from Cognex Corporation (Natick, MA), such as an AE3-IS machine vision color camera + IO board (e.g., part number AE3-IS-CQBCKFP2-B).

[0362] The dispensing tip image capture unit 130 can further include a light source 2552 for the camera 2550. The light source 2552 is used to irradiate the dispensing tip 112 and its surroundings to be photographed as desired. The light source 2552 can be arranged in various locations. In the illustrated embodiment, the light source 2552 is positioned behind the dispensing tip 112 opposite the camera unit 2550 and is thus used as a backlight. Other locations for the light source 2552 are also possible. One example of the light source 2552 includes the MDBL series available from Moritex Corporation (Japan).

[0363] In other embodiments, the camera unit 550 includes a light source 2551, such as an LED light, operable to emit light toward the dispensing tip 112. In this configuration, the light source 2552 is replaced by a screen 2553 arranged opposite the camera unit 550 such that the dispensing tip 112 is positioned between the camera unit 2550 and the screen 2553. The screen 2553 is used to reflect light back toward the direction of the field of view (FOV) of the camera unit by reflecting light toward the opening of the camera. The screen 2553 is made of one or more different materials capable of providing different reflection intensities. For example, the screen 2553 includes a retroreflective sheet, one example of which is 3M Company (Maplewood, MN) available 3M TM Scotchlite TM sheet 7610. In other embodiments, the light source 2552 can be used with the light source 2551 and the screen 2553 from the camera unit 2550.

[0364] In some embodiments, the camera unit 2550 and the light source 2552 (or the screen 2553) are configured to be stationary and independent of the movement of the sample pipetting operation module 512. Other configurations are also possible in other embodiments.

[0365] As described herein, the camera unit 2550 and its associated components can be used for tip alignment detection, as further illustrated in FIG. 67.

[0366] Referring to FIGS. 13 and 14, an example of the dispensing tip 112 is described. Specifically, FIG. 13 is a schematic perspective view of an example of the dispensing tip 112, and FIG. 14 is a cross-sectional view of the distal end of the dispensing tip 112.

[0367] The dispensing tip 112 extends from a proximal end 560 and a distal end 562. The dispensing tip 112 includes a base portion 564 at the proximal end 560 configured to attach the dispensing tip 112 to a mandrel 526 of a sample pipetting operation module 512. The dispensing tip 112 further includes an elongated body portion 566 extending from the base portion 564. The dispensing tip 112, including the base portion 564 and the body portion 566, defines a pipetting operation passage (or channel) 572 for aspirating, containing, and dispensing a fluid substance. In some embodiments, the dispensing tip 112 (including the dispensing tip 112) is disposable. In other embodiments, the dispensing tip 112 (including the dispensing tip 112) is not disposable or can be used multiple times before being disposed of.

[0368] In some embodiments, the dispensing tip 112 includes a reference line 570 detectable by a dispensing tip image capture unit 130. The reference line 570 can be formed at various locations on the dispensing tip 112. In some embodiments, the reference line 570 is formed on the body portion 566 of the dispensing tip 112. In other embodiments, the reference line 570 is formed on the base portion 564 of the dispensing tip 112. Some examples of the reference line 570 are positioned such that the surface level or meniscus of the fluid substance aspirated into the dispensing tip 112 is arranged between the reference line 570 and the distal end 562 of the dispensing tip 112. In other embodiments, the reference line 570 is positioned such that the meniscus of the aspirated fluid substance is arranged above the reference line 570 with respect to the distal end 562 (i.e., between the reference line 570 and the proximal end 560).

[0369] The reference line 570 is provided on the dispensing tip 112 in various manners. In some embodiments, the reference line 570 is a detectable structure such as a protrusion, a bulge, a depression, a notch, or any other visible element formed on the dispensing tip 112. In other embodiments, the reference line 570 is a marker or an indicator painted or attached onto the dispensing tip 112. The reference line 570 can be integrally formed or molded into the dispensing tip 112. Alternatively, the reference line 570 is fabricated separately and attached to the dispensing tip 112.

[0370] Reference line 570 is used as a reference point when the image of dispensing tip 112 is analyzed to determine whether a sample is properly aspirated for analytical testing. As described herein, sample aspiration volume detection device 500 measures the volume of the aspirated sample in dispensing tip 112 by measuring the distance between reference line 570 and the sample meniscus. Since reference line 570 is formed on dispensing tip 112, reference line 570 provides a consistent reference point for volume measurement as compared to any reference point provided by structures other than dispensing tip 112. For example, if a part or point in mandrel 526 is used as a reference point, the position of mandrel 526 relative to dispensing tip 112 varies depending on the insertion depth of dispensing tip 112 up to mandrel 526, thereby causing inaccurate volume measurement. In contrast, reference line 570 is stationary relative to dispensing tip 112 and can therefore provide accurate measurements. Since reference line 570 is formed on dispensing tip 112, reference line 570 provides a consistent reference point for volume measurement as compared to any reference point provided by structures other than dispensing tip 112. For example, if a part or point in mandrel 526 is used as a reference point, the position of mandrel 526 relative to dispensing tip 112 varies depending on the insertion depth of dispensing tip 112 up to mandrel 526, thereby causing inaccurate volume measurement. In contrast, reference line 570 is stationary relative to dispensing tip 112 and can therefore provide accurate measurements.

[0371] As shown in FIG. 14, pipetting operation passage 572 includes a tapered section 574 whose inner diameter becomes smaller from proximal end 560 to distal end 562. Pipetting operation passage 572 further includes a straight section 576 having a constant inner diameter at or adjacent to distal end 562. Straight section 576 can improve the accuracy and precision of aspirating small volumes such as about 2 - 5 μL while still providing a dispensing tip 112 capable of aspirating large volumes such as 250 μL for aliquoting.

[0372] FIG. 15 is a flowchart illustrating an exemplary method 600 for operating dispensing tip volume detection device 400. In the illustrated embodiment, method 600 is mainly described with respect to sample aspiration volume detection device 500. However, method 600 is also equally applicable to other types of dispensing tip volume detection devices 400. In some embodiments, method 600 is performed by sample aspiration system 510 and sample aspiration volume detection device 500.

[0373] Generally, method 600 uses a measurement algorithm to analyze the aspirated volume in the dispensing tip and flags the aspiration result or inspection result if the calculated aspirated volume is outside the tolerance range.

[0374] In operation 602, the sample aspiration system 510 operates to aspirate a fluid substance such as sample 540 (FIG. 10) into the dispensing tip 112 as programmed.

[0375] In operation 604, the sample aspiration system 510 transports the dispensing tip 112 containing the aspirated sample 540 to the dispensing tip image capture unit 130. In some embodiments, the dispensing tip image capture unit 130 is arranged to capture an image of the dispensing tip 112 after aspiration without transportation.

[0376] In operation 606, the dispensing tip image capture unit 130 of the sample aspiration volume detection device 500 captures an image of the dispensing tip 112. In some embodiments, the image of the dispensing tip 112 is a digital image with a pre-determined resolution.

[0377] In operation 608, the sample aspiration volume detection device 500 analyzes the image to determine the volume of the sample 540 within the dispensing tip 112. An example of operation 608 is described in more detail with reference to FIGS. 16-19.

[0378] In operation 610, the sample aspiration volume detection device 500 determines whether the determined volume falls within the tolerance range. When the determined volume is outside the tolerance range, the aspiration of the sample 540 in the dispensing tip 112 is considered inappropriate. In some embodiments, such a tolerance range is determined based on the allowable deviation from the target aspiration volume of the sample 540 intended to be aspirated into the dispensing tip 112. The tolerance range can vary depending on the target aspiration volume. Examples of the tolerance range are as follows.

[0379] [Table 1]

[0380] When it is determined that the detected volume falls within the tolerance range (in operation 610, "Yes"), method 600 proceeds to perform the next pre-determined step. Otherwise (in operation 610, "No"), method 600 proceeds to operation 612.

[0381] In operation 612, the sample aspiration volume detection device 500 flags the aspiration to indicate that the aspirated sample volume in the dispensing tip 112 is not appropriate for subsequent processes. In other embodiments, the entire test result using the aspirated sample can be flagged to indicate or suggest that the test result may be inappropriate. Alternatively, the sample aspiration volume detection device 500 operates to stop the associated test or analysis process in the instrument 100. In other embodiments, the evaluation result can be used to automatically adjust the test result that may be in error due to an inappropriate volume of the fluid substance. In yet other embodiments, as described herein, the evaluation result can be used to automatically adjust the volume of the fluid substance in response to the volume determination.

[0382] Referring to FIGS. 16-19, an example of operation 608 of FIG. 15 is described where the captured image is analyzed to determine the sample volume in the dispensing tip. Specifically, FIG. 16 is a flowchart illustrating an exemplary method 630 for performing operation 608 of FIG. 15. Method 630 is also described with reference to FIGS. 17-19, which illustrate an exemplary analysis of the captured image 620 of the dispensing tip.

[0383] In operation 632, the sample aspiration volume detection device 500 detects the reference line 570 of the dispensing tip 112 in the captured image 620. Various image processing methods can be used to detect the reference line 570 in the image 620. In some embodiments, the reference line 570 is detected by a pattern matching function that searches for a pattern representing the reference line based on a pre-trained reference image. For example, such a pattern matching function is stored in the system and performs a pattern search that scans the captured image for patterns recognized as reference lines. The correlation value or match rate (e.g., match %) is adjustable. Other methods are possible in other embodiments. One example of such an image processing method is Cognex Corporation (Natick, MA), which can be implemented by Cognex In-Sight Vision Software available from.

[0384] In operation 634, the sample aspiration volume detection device 500 detects the center point 650 of the reference line 570. As illustrated in FIG. 17, once the reference line 570 is detected, the center point 650 can be calculated as the midpoint of the reference line 570.

[0385] In operation 636, the sample aspiration volume detection device 500 aspirates in the dispensing tip 112 detects the surface level 652 (FIG. 18) of the sampled sample volume. Various image processing methods can be used to detect the surface level 652 in the image. In some embodiments, similar to operation 632, the surface level 652 is detected by a pattern matching function based on a pre-trained reference image. Other methods are possible in other embodiments.

[0386] In operation 638, the sample aspiration volume detection device 500 detects the center point 654 of the surface level 652. As illustrated in FIG. 18, once the surface level 652 is detected, the center point 654 can be calculated as the midpoint of the line of the surface level 652.

[0387] In operation 640, the sample aspiration volume detection device 500 measures the distance L1 (FIG. 19) between the center point 650 of the reference line 570 and the center point 654 of the surface level 652. In some embodiments, the distance L1 is measured by the pixel distance between the center points 650 and 654 in the image 620. In some embodiments, the pixel distance is calculated based on the Euclidean distance between two pixel points.

[0388] In operation 642, the sample aspiration volume detection device 500 converts the distance L1 to a volume based on the tip volume correlation data 506. The correlation data 506 includes information about the correlation between the volume in the dispensing tip 112 and the distance L1 between the center point 650 of the reference line 570 and the center points 654 of a plurality of different surface levels 652 in the dispensing tip 112. In some embodiments, the correlation data 506 can be plotted on a correlation curve 660 as illustrated in FIG. 20. An exemplary method of generating the correlation data 506 is described with reference to FIG. 21.

[0389] FIG. 20 is an exemplary correlation curve 660 corresponding to the correlation data 506. In some embodiments, the correlation curve 660 shows the relationship between the distance L1 (e.g., pixel distance) between the center points 650 and 654 and the volume V1 of the aspirated sample in the dispensing tip 112. The correlation curve 660 can be obtained by plotting a plurality of discrete data points included in the correlation data 506, which is described with reference to FIG. 21. As illustrated in FIG. 20, the correlation curve shows that as the distance L1 increases, the aspirated volume V1 generally decreases. Since the reference line 570 is formed on the dispensing tip 112 such that it is arranged above the surface level 652, the distance L1 is generally inversely correlated with the volume V1.

[0390] FIG. 21 is a flowchart illustrating an exemplary method 670 for operating a tip volume correlation data generation system 504 to generate tip volume correlation data 506.

[0391] In some embodiments, the correlation data 506 is created using spectroscopic techniques. For example, the tip volume correlation data generation system 504 uses a dye solution to show the correlation between the extracted pixel distance information and the fluid volume information in the dispensing tip. A spectrophotometer can be used to measure the absorbance of the dye at a specific wavelength. In some embodiments, the tip volume correlation data generation system 504 selects a plurality of points (e.g., 5, 10, 50, 100, and 110 μL) within a target volume range, aspirates these volume settings by the dispensing tip, and takes an image of the dispensing tip for pixel distance calculation. Next, the tip volume correlation data generation system 504 plots a calibration curve between the pixel distance calculated from the image and the volume calculated by the spectrophotometer.

[0392] In operation 672, the tip volume correlation data generation system 504 aspirates a dye solution into the dispensing tip 112.

[0393] In operation 674, the tip volume correlation data generation system 504 captures an image of the dispensing tip 112 containing the dye solution.

[0394] In operation 676, the tip volume correlation data generation system 504 extracts the distance between the reference line 570 and the surface line of the dye solution in the image captured in operation 674. In some embodiments, the distance is measured by pixel distance. In some embodiments, the distance is determined in a similar manner to at least some of the operations of method 630, such as operations 632, 634, 636, 638, and 640. Other methods are possible in other embodiments.

[0395] During operations 678, 680, and 682, the tip volume correlation data generation system 504 measures the volume of the dye solution aspirated into the dispensing tip 112. Various methods can be used to determine the dye solution volume. In the illustrated embodiment, an optical approach is used as described below.

[0396] In operation 678, the tip volume correlation data generation system 504 dispenses the dye solution into a secondary container having a known volume of diluent.

[0397] In operation 680, the tip volume correlation data generation system 504 measures the optical density of the diluted dye solution dispensed into the secondary container. In some embodiments, a spectrophotometer is used to measure the optical density of the dye solution. The spectrophotometer measures the amount of light of a specified wavelength passing through the diluted dye solution within the secondary container.

[0398] In operation 682, the tip volume correlation data generation system 504 converts the optical density to the volume of the dye solution within the dispensing tip.

[0399] In operation 684, the tip volume correlation data generation system 504 correlates the distance calculated in operation 676 and the volume calculated in operation 682.

[0400] In operation 686, the tip volume correlation data generation system 504 determines whether a sufficient number of correlations are being made to generate the tip volume correlation data 506. If so (in operation 686, "Yes"), the method 670 proceeds to operation 688. Otherwise (in operation 686, "No"), the method 670 returns to operation 672 where the dye solution is aspirated into the dispensing tip 112, and subsequent operations are performed to determine an additional correlation between the distance and the volume of the dye solution within the dispensing tip. To obtain a sufficient range of correlation data, different amounts of the dye solution are aspirated into the dispensing tip 112 in different correlation cycles. Additionally, the amount of the dye solution aspirated into the dispensing tip can remain substantially the same for some of the correlation cycles so as to obtain reliable results for a particular volume or volume range.

[0401] In operation 688, the tip volume correlation data generation system 504 creates the tip volume correlation data 506 based on the multiple correlations performed in operation 684. In some embodiments, the correlation data is plotted as a correlation curve (e.g., correlation curve 660 of FIG. 20) by plotting the pixel distance of each image along with the corresponding aspirated volume measured by a spectrophotometer. The correlation curve is used to estimate the relationship between the distance and the volume within the dispensing tip 112.

[0402] The dispensing tip volume detection device 400, as described with reference to FIGS. 9 - 21, can be modified to be suitable for various applications. In some embodiments, the dispensing tip volume detection device 400 is used for any fluid substance other than patient samples. In some embodiments, the dispensing tip image capture unit of the dispensing tip volume detection device 400 does not use a backlight setting. Further, the dispensing tip image capture unit is a camera and backlight that move with the sample pipette operation module and other associated devices. In contrast to the cartridge set, it can be performed using a fixed camera and a backlight setting. The reference line of the dispensing tip can be something other than a line formed on the dispensing tip. In some embodiments, a mandrel for the dispensing tip is used as a reference point. In some embodiments, the pattern matching function associated with the dispensing tip volume detection device 400 employs various algorithms such as a discovery line or a compartment. In some embodiments, the measured volume range can exceed 110 μL. In some embodiments, the dispensing tip volume detection device 400 is used for any container in various shapes (e.g., cylindrical, conical, rectangular, and square) other than the sample pipetting operation tip as illustrated herein. In other embodiments, the tip volume correlation data generation system 504 employs any liquid other than the dye solution and uses techniques other than spectroscopy. For example, a JIG tip with a plurality of reference lines corresponding to known volumes can be used.

[0403] One example of the image processing method used above can be implemented by Cognex In-Sight Vision Software available from Cognex Corporation (Natick, MA), which provides various tools such as edge detection ("Edge"), pattern matching ("Pattern Match"), and histogram analysis ("Histogram").

[0404] In some embodiments, the measured volume of the aspirated sample can be used to adjust the relative light units (RLU) of the test result. Since the sample volume (as well as the substrate / reagent volume, etc.) correlates with the RLU for immunoassays, this correlation can be measured and used as a reference for adjustment. Further, the measured volume can be used as feedback to adjust the reagent volume for improved ratio matching and assay performance.

[0405] Referring now to FIGS. 22 - 39, an example of the container volume detection device 402 of FIG. 5 is described.

[0406] FIG. 22 illustrates an embodiment of the container volume detection device 402 of FIG. 5. In some embodiments, the container volume detection device 402 includes a reaction vessel dispensing volume detection device 700, a reaction vessel residual volume detection device 702, a dispensing adjustment device 704, and a reaction vessel detection device 706. The reaction vessel dispensing volume detection device 700 uses container volume correlation data 712 generated by a container volume correlation data generation system 710.

[0407] The reaction vessel dispensing volume detection device 700 is operative to determine the volume of a fluid substance 118 dispensed into a container 114 such as a reaction vessel. Examples of the structure and operation of the reaction vessel dispensing volume detection device 700 are described and illustrated with reference to FIGS. 27-31.

[0408] The reaction vessel residual volume detection device 702 is operative to determine the volume of a fluid substance 118 remaining in a container 114 such as a reaction vessel. Examples of the reaction vessel residual volume detection device 702 are described and illustrated with reference to FIGS. 32-34.

[0409] The dispensing adjustment device 704 is operative to adjust the operation of a substance dispensing device such as a pipettor and a pump device based on the measurement of the volume of a fluid substance dispensed into a container 114 such as a reaction vessel. Examples of the dispensing adjustment device 704 are described and illustrated with reference to FIGS. 35 and 36.

[0410] The reaction vessel detection device 706 is operative to detect the presence or absence of a container 114 such as a reaction vessel. Examples of the reaction vessel detection device 706 are described and illustrated with reference to FIGS. 37-39.

[0411] The container volume correlation data generation system 710 generates container volume correlation data 712. The container volume correlation data 712 provides information used by the container volume detection device 402 to determine the volume of a fluid substance dispensed into a container (e.g., a reaction vessel). In some embodiments, the container volume correlation data generation system 710 is a device independent of the container volume detection device 402. In other embodiments, the container volume correlation data generation system 710 is configured to use at least some resources of the container volume detection device 402. The container volume correlation data generation system 710 and the container volume correlation data 712 are included in, or are examples of, the correlation data generation system 404 and the correlation data 406, as illustrated in FIG. 5.

[0412] Prior to referring to FIGS. 23 - 26, it should be noted that reliable clinical diagnosis requires accurate and precise aspiration and dispensing of the substance being analyzed. For example, in an automated analyzer that analyzes a sample such as blood or any other type of body fluid, variations in the dispensed or aspirated amount of a sample and other substances such as reagents within a container (e.g., a pipetting tip or reaction vessel) relative to a specified amount can affect the analysis results and reduce the reliability of the test and analysis. Further, in the clinical diagnostic industry, it is difficult to accurately and precisely control and match the volumes of fluids dispensed from different pump units. Thus, it is beneficial to establish a technique for measuring the amount aspirated or dispensed with high accuracy and selecting only the aspirated or dispensed samples for which the amount is within a suitable range. One method of measuring liquid volume is to monitor the fluid pressure within a fluid conduit and correlate the fluid pressure to the dispensed volume. In other cases, a flow sensor is used to determine the flow rate of the liquid being aspirated or dispensed. In still other cases, a chemiluminescence signal from a controlled dispensing of an IA reagent is used to detect the presence of an excess residual volume in a container after aspiration from the container. In still other cases, a chemiluminescence signal from a controlled dispensing of an IA reagent is used to determine the volume dispensing characteristics of a plurality of pump devices.

[0413] However, these approaches have several disadvantages. For example, a pressure sensor can determine fluid viscosity but cannot quantify the dispensed volume. A flow sensor can quantify the volume of liquid passing through the tubing in which the flow sensor is arranged, but cannot reliably measure the volume of liquid aspirated or dispensed. Further, due to location offsets, it is difficult to correlate low-volume measurement in-line with an accurate reaction vessel. Also, a chemiluminescence signal cannot detect a small residual fluid volume following aspiration. The chemiluminescence signal does not provide a precise direct estimate of volume matching characteristics between different pump devices. The chemiluminescence signal confounds reagent characteristics and lot-to-lot variations with the system variables of interest such as dispensed volume or residual volume.

[0414] As will be described in more detail herein, the container volume detection device 402 employs an image processing method for quantifying the volume of a fluid substance dispensed and aspirated into a container (e.g., a reaction vessel). The volume of the fluid substance is dispensed or aspirated into a transparent or translucent container such as a transparent cylindrical container. The container is imaged and reference points are detected within the image. In some embodiments, the bottom features of the container are used as reference points within the image. The container volume detection device measures the distance from the meniscus of the fluid substance to the reference point and correlates the distance to volume using a volume calibration curve. If the volume dispensed into the container is not within the specifications of the accuracy of aspiration, the entire dispense or inspection is flagged. A user or operator can receive information about the results of the aspiration.

[0415] In addition, the measured volume of the fluid substance dispensed into the container is recorded for different combinations of pumps and pipettors within the system, to calibrate the combinations of pumps and pipettors and improve the accuracy of controlling different pumps and pipettors within the system for use.

[0416] Furthermore, the container volume detection device 402 can detect the presence of a small residual fluid volume remaining in the container following aspiration. In some embodiments, a pattern recognition algorithm is used for such residual volume detection.

[0417] With reference to FIGS. 23-26, an exemplary structure and operation of a container carriage device 720 that includes a container volume detection device 402 are described.

[0418] FIG. 23 illustrates an exemplary container carriage device 720 that includes a container volume detection device 402. In the illustrated embodiment, the container carriage device 720 is implemented as a cleaning wheel, such as cleaning wheel 176 (FIG. 2) in instrument 100. Thus, the container carriage device 720 is also referred to herein as cleaning wheel 720. In embodiments, other types of container carriage devices 720 are used with the container volume detection device 402.

[0419] As illustrated, the container carriage device or cleaning wheel 720 is configured to perform various aspects of the diagnostic process. In some embodiments, the cleaning wheel 720 includes a housing unit 722 and a rotatable plate 724 relative to the housing unit 722. The cleaning wheel 720 includes a plurality of container seats 726 that are formed in the rotatable plate 724 and configured to receive and support a container 728. When the container carriage device 720 is configured as a cleaning wheel, such a container 728 includes a reaction vessel. Thus, the container 728 is also referred to herein as reaction vessel 728.

[0420] In some embodiments, the container volume detection device 402 is mounted on the cleaning wheel 720. As described above, the container volume detection device 402 includes a container image capture unit 132. An exemplary structure of the container image capture unit 132 is described in further detail with reference to FIGS. 24 and 25.

[0421] Referring to FIGS. 24 and 25, an exemplary structure of the container volume detection device 402 including the container image capture unit 132 is described. Specifically, FIG. 24 is another perspective view of the container carriage device 720 of FIG. 23 illustrating the container image capture unit 132, and FIG. 25 is a top view of the cleaning wheel 720 with the container volume detection device 402 including the container image capture unit 132.

[0422] The container image capture unit 132 includes a camera unit 730 and a light source 732. In some embodiments, the camera unit 730 includes a complementary metal oxide semiconductor (CMOS) image sensor for acquiring color digital images. In other embodiments, the camera unit 730 includes a charge coupled device (CCD) image sensor for acquiring color digital images. Other embodiments of the camera unit 730 are configured to acquire black and white or grayscale photographs. The light source 732 is used to irradiate the container 728, the slot 736, and / or the periphery of the container 728 and / or the slot 736 as desired for imaging. The light source 732 can be fixed in various locations. In the illustrated embodiment, the light source 732 is positioned behind the container 728 facing the camera unit 730 and thus is used as a backlight. Other locations for the light source 732 are also possible. One example of the light source 732 includes the MDBL series available from Moritex Corporation (Japan).

[0423] In other embodiments, the camera unit 730 radiates light toward the container 728 It includes a light source 731 such as an LED light that is operable thereto. In this configuration, the light source 732 can be replaced by a screen 733 that is arranged opposite the camera unit 730 such that the container 728 is positioned between the camera unit 730 and the screen 733. The screen 733 is used to reflect light back towards the direction of the field of view (FOV) of the camera unit by reflecting light towards the opening of the camera. The screen 733 is made of one or more different materials that can provide different reflection intensities. For example, the screen 733 includes a retroreflective sheet, one example of which is 3M TM Scotchlite TM sheet 7610. In other embodiments, the light source 732 can be used together with the light source 731 and the screen 733 from the camera unit 730. One example of the camera unit 730 includes a model named ADVANTAGE 102 that is available from Cognex Corporation (Natick, MA).

[0424] In some embodiments, the camera unit 730 and the light source 732 (or the screen 733) are attached to the housing unit 722 of the cleaning wheel 720. The camera unit 730 and the light source 732 (or the screen 733) are arranged such that as the rotatable plate 724 is rotated relative to the housing unit 722, the reaction container 728 supported by the rotatable plate 724 is positioned between the camera unit 730 and the light source 732 (or the screen 733).

[0425] In some embodiments, the housing unit 722 defines a slot 736 that exposes one of the reaction vessels 728 between the camera unit 730 and the light source 732 (or the screen 733). When the reaction vessel 728 is aligned with the camera unit 730 and the light source 732 (or the screen 733) through the slot 736 of the housing unit 722, an image of the reaction vessel 728 can be captured by the camera unit 730. In other embodiments, where the housing unit 722 is made of an opaque material, the housing unit 722 includes a transparent or translucent region that replaces the slot 736. The transparent or translucent region enables the camera unit 730 to capture an image therethrough.

[0426] One example of the camera unit 730 is the ADV102 Machine Vision Camera with a part number such as ADV102 - CQBCKFW1 - B available from Cognex Corporation (Natick, MA).

[0427] As described above, the patient sample contained in the reaction vessel is transported among the various modules, units, or devices in the instrument 100. Various aspects of the diagnostic process in the instrument 100 are performed in the wash wheel 720. The wash wheel 720 transports a plurality of reaction vessels 728 around it. The reaction vessels 728 on the wash wheel 720 can correspond to a plurality of test results. In this configuration, the camera unit 730 and the light source 732 (or the screen 733) are fixed to the wash wheel 720. The camera unit 730 faces into the wash wheel 720 where the light source 732 (or the screen 733) is located. The camera unit 730 captures an image of the reaction vessel 728 that moves through the field of view (FOV) of the camera unit 730 between the camera unit 730 and the light source 732 (or the screen 733). In some embodiments, the reaction vessel 728 is stationary when the image of the reaction vessel 728 is captured by the camera unit 730. In other embodiments, the camera unit 730 captures an image of the reaction vessel 728 while the reaction vessel 728 is moving. An image of the reaction vessel can be captured for each reaction vessel 728. The camera unit 730 takes images in a plurality of steps throughout the entire diagnostic process as the rotatable plate 724 rotates relative to the housing unit 722. In some embodiments, when the diagnostic process is not in progress, a reaction vessel is placed at a location between the camera unit 730 and the light source 732 (or the screen 733) (e.g., the container seat 726 located in the slot 736). It is possible to carry.

[0428] The cleaning wheel 720 is operable in different operating modes. In some embodiments, the cleaning wheel 720 is operated in an inspection processing mode or a diagnostic routine mode. In other embodiments, the cleaning wheel 720 is operable in an inspection preparation mode such as priming. In the inspection processing mode, the cleaning wheel 720 holds one or more containers on the rotatable plate 724 and rotates the containers for a pre-determined analytical test. In the diagnostic routine mode, also referred to herein as the automatic system diagnosis (ASD), the instrument 100 is in an idle state and does not initiate an inspection. In some embodiments, in the diagnostic routine mode, the cleaning wheel 720 is operated to perform at least one of the operations of the preparation evaluation system 104 such as container dispense volume detection (e.g., by the reaction vessel dispense volume detection device 700), container residual volume detection (e.g., by the reaction vessel residual volume detection device 702), dispense adjustment (e.g., by the dispense adjustment device 704), and container detection (e.g., by the reaction vessel detection device 706). In other embodiments, the operations of the preparation evaluation system 104 can be performed in the inspection processing mode.

[0429] In some embodiments, the cleaning wheel 720 is operated with a plurality of dispensing tips that can have different profiles and accuracies based on their hydraulic characteristics. In the inspection processing mode, two or more of the plurality of dispensing tips can dispense substances into the containers on the cleaning wheel 720. In the diagnostic routine mode, the dispensing tips can be operated independently, and thus the operating conditions of each dispensing tip can be monitored and evaluated, for example, in the dispense adjustment performed by the dispense adjustment device 704.

[0430] FIG. 26 is a flowchart illustrating an exemplary method 750 of operating the container volume detection device 402 along with the cleaning wheel 720. In some embodiments, at least some of the operations in method 750 are performed by the substance preparation system 102, the preparation evaluation system 104, and / or the substance evaluation system 106 of the instrument 100. In other embodiments, other components, units, and devices of the instrument 100 are used to perform at least one of the operations in method 750. In some embodiments, method 750 includes operations 752, 754, 756, 758, and 760.

[0431] In operation 752, the substance preparation system 102 operates to aspirate an excess volume of the fluid substance from the reaction vessel 738 on the cleaning wheel 720. In some embodiments, the excess volume of the fluid substance remains in the reaction vessel 738 after one or more pre-determined analysis procedures on the cleaning wheel 720. Such an excess substance volume in the reaction vessel needs to be removed from the reaction vessel 738 for subsequent processes, such as before the substrate is dispensed into the reaction vessel, as illustrated in FIG. 4.

[0432] In operation 754, the substance preparation system 102 transports the reaction vessel 738 to the container image capture unit 132 on the cleaning wheel 720.

[0433] In operation 746, the container volume detection device 402 performs residual volume detection in the reaction vessel 738. In some embodiments, the reaction vessel residual volume detection device 702 operates to perform the residual volume detection.

[0434] In operation 748, the substance preparation system 102 operates to dispense a fluid substance (e.g., a substrate as illustrated in FIG. 4) into the reaction vessel 738.

[0435] In operation 760, the container volume detection device 402 performs dispensed volume detection in the reaction vessel 738 It is performed. In some embodiments, the reaction vessel dispensing volume detection device 700 operates to perform dispensing volume detection.

[0436] FIG. 27 is a flowchart illustrating an exemplary method 800 for operating the reaction vessel dispensing volume detection device 700. Although method 800 is mainly described with respect to the reaction vessel dispensing volume detection device 700, method 600 is also similarly applicable to other types of container volume detection devices 402. In some embodiments, method 800 is performed by the container carriage device 720 (e.g., a cleaning wheel) and the reaction vessel dispensing volume detection device 700.

[0437] Generally, method 800 analyzes the volume of a fluid substance dispensed or aspirated into a container and flags the dispensing or aspiration result, or the inspection result, if the calculated volume is outside the tolerance range.

[0438] In operation 802, a fluid substance is dispensed into a reaction vessel 728 supported, for example, within the container carriage device 720 as programmed. Examples of fluid substances include samples, diluents, reagents, substrates, or any combination thereof as described herein. For example, a diluent or reagent is used during the diagnostic mode for the cleaning wheel.

[0439] In operation 804, the container carriage device 720 transports the reaction vessel 738 containing the dispensed substance to the container image capture unit 132. In some embodiments, the container image capture unit 132 is arranged to capture an image of the reaction vessel 738 after dispensing without transportation. In other embodiments, the dispensing in operation 802 occurs at a location where the container image capture unit 132 is arranged in a fixed position and captures an image of the reaction vessel 738 without moving the reaction vessel 738 after dispensing.

[0440] In operation 806, the container image capture unit 132 of the reaction vessel dispensing volume detection device 700 captures an image of the reaction vessel 738. In some embodiments, the image of the reaction vessel 738 is a digital image with a pre-determined resolution.

[0441] In operation 808, the reaction vessel dispensing volume detection device 700 analyzes the image to determine the volume of the fluid substance within the reaction vessel 738. Examples of operation 808 are described in further detail with reference to FIGS. 28 and 29.

[0442] In operation 810, the reaction vessel dispensing volume detection device 700 determines whether the determined volume falls within a tolerance range. When the determined volume is outside the tolerance range, the dispensing of the fluid substance in the reaction vessel 738 is considered inappropriate. In some embodiments, such a tolerance range is determined based on the allowable deviation from the target dispensing volume of the fluid substance intended to be dispensed into the reaction vessel 738. The tolerance range can vary depending on the target aspiration volume and other factors. As an example, when the target dispensing volume (V) is 200 μL, this is considered acceptable if 194 μL ≤ V ≤ 206 μL. In other examples, this is considered acceptable when the standard deviation (V(n)) is equal to or less than ±1 μL.

[0443] When it is determined that the detected volume falls within the tolerance range (in operation 810, "Yes"), method 800 subsequently performs the next pre-determined step. Otherwise (in operation 810, "No"), method 800 proceeds to operation 812.

[0444] In operation 812, the reaction vessel dispensing volume detection device 700 dispenses within the reaction vessel 738 Flag the dispensing to indicate that the resulting volume is not appropriate for subsequent processes. In other embodiments, the overall test results using the dispensed fluid material can be flagged to indicate or suggest that the test results may be inappropriate. Alternatively, the reaction vessel dispensing volume detection device 700 operates to stop the associated test or analysis process within the instrument 100. In other embodiments, the evaluation results can be used to automatically adjust the test results, which may be in error due to an inappropriate volume of the fluid material (as an example, within a certain volume range, the RLU is proportional to the substrate volume, at a certain point, exceeds the illuminometer aperture range, then stalls, and decreases by the dilution factor). In still other embodiments, the evaluation results can be used to automatically adjust the volume of the fluid material in response to the volume determination.

[0445] Referring to FIGS. 28 and 29, an example of operation 808 of FIG. 27 is described where the captured image is analyzed to determine the volume dispensed into the reaction vessel. Specifically, FIG. 28 is a flowchart illustrating an exemplary method 830 for performing operation 608 of FIG. 27. Method 830 is described with reference to FIG. 29, which also illustrates an exemplary analysis of the captured image 780 of the reaction vessel.

[0446] In operation 832, the reaction vessel dispensing volume detection device 700 detects a reference portion 784 of the reaction vessel 738 within the captured image 780. In some embodiments, the reference portion 784 includes the bottom portion of the reaction vessel 738. Other portions of the reaction vessel 738 can be used as the reference portion 784.

[0447] Various image processing methods can be used to detect the bottom portion 784 within the image 780. In some embodiments, the bottom portion 784 is detected by a pattern matching function that searches for a pattern representing the bottom portion based on a pre-trained reference image. For example, such a pattern matching function performs a pattern search that scans an image captured for a pattern stored in the system and recognized as the bottom portion. The correlation value or match rate (e.g., match %) is adjustable. Other methods are possible in other embodiments. One example of such an image processing method can be implemented by Cognex In-Sight Vision Software available from Cognex Corporation (Natick, MA), which provides various tools such as edge detection ("Edge"), pattern matching ("Pattern Match"), and histogram analysis ("Histogram").

[0448] In operation 834, the reaction vessel dispensing volume detection device 700 detects the center point 786 of the bottom portion 784. As illustrated in FIG. 29, once the bottom portion 784 is detected, the center point 786 can be calculated as the midpoint of the bottom portion 784.

[0449] In operation 836, the reaction vessel dispensing volume detection device 700 detects the surface level 788 (FIG. 29) of the volume disposed within the reaction vessel 738. Various image processing methods can be used to detect the surface level 788 within the image 780. In some embodiments, similar to operation 832, the surface level 788 is detected by a pattern matching function based on a pre-trained reference image. Other methods are possible in other embodiments.

[0450] In operation 838, the reaction vessel dispensing volume detection device 700 detects the center point 790 of the surface level 788. As illustrated in FIG. 29, once the surface level 788 is detected, the center point 790 can be calculated as the midpoint of the line of the surface level 788.

[0451] In operation 840, the reaction vessel dispensing volume detection device 700 measures the distance L2 (FIG. 29) between the center point 786 of the bottom portion 784 and the center point 790 of the surface level 788. In some embodiments, the distance L2 is measured by the pixel distance between the center points 786 and 790 in the image 780. In some embodiments, the pixel distance is calculated based on the Euclidean distance between two pixel points.

[0452] In operation 842, the reaction vessel dispensing volume detection device 700 converts the distance L2 to a volume based on the container volume correlation data 712 (FIG. 22). The correlation data 712 includes information about the correlation between the volume in the reaction vessel 738 and the distance L2 between the center point 786 of the bottom portion 784 and the center points 790 of a plurality of different surface levels 788 in the reaction vessel 738. In some embodiments, the correlation data 712 can be plotted on a correlation curve 860 as shown in FIG. 30. An exemplary method of generating the correlation data 712 is described with reference to FIG. 31.

[0453] FIG. 30 is an exemplary correlation curve 860 corresponding to the correlation data 712. In some embodiments, the correlation curve 860 shows the relationship between the distance L2 (e.g., pixel distance) between the center points 786 and 790 and the volume V2 of the dispensed fluid substance 782 in the reaction vessel 738. In the illustrated embodiment, the correlation curve 860 shows the relationship between the mass of the fluid substance dispensed into the reaction vessel 738 and the pixel height of the fluid substance in the reaction vessel 738. The mass can be converted to volume based on the density of the fluid substance. The pixel height of the fluid substance in the reaction vessel corresponds to the distance D2.

[0454] The correlation curve 860 can be obtained by plotting a plurality of discrete data points included in the correlation data 712, as described with reference to FIG. 31. As illustrated in FIG. 30, the correlation curve indicates that as the distance L2 increases, the dispensed volume V2 (or mass M2) generally increases. Since the bottom portion 784 of the reaction vessel 738 is selected as the reference point, the distance L2 generally correlates linearly with the volume V2 (or mass M2). For example, the distance L2 and the volume V2 generally correlate linearly for volumes greater than 10 μL.

[0455] FIG. 31 is a flowchart illustrating an exemplary method 870 for operating a container volume correlation data generation system 710 to generate container volume correlation data 712.

[0456] In some embodiments, the correlation data 712 is created using gravimetric analysis. For example, the container volume correlation data generation system 710 uses different volumes of fluid to show the correlation between the extracted pixel distance information and the fluid volume information within the container. In some embodiments, the container volume correlation data generation system 710 selects a plurality of points (e.g., 190, 195, 200, 205, and 210 μL) within a target volume range, dispenses these volume settings into the container, and takes an image of the container for pixel distance calculation. The container volume correlation data generation system 710 then plots a calibration curve between the pixel distance calculated from the image and the mass calculated by gravimetric analysis. The mass is then converted to volume using the density of the fluid.

[0457] In operation 872, the container volume correlation data generation system 710 measures the mass of an empty container, such as the reaction vessel 738.

[0458] In operation 874, the container volume correlation data generation system 710 dispenses fluid into the container.

[0459] In operation 876, the container volume correlation data generation system 710 captures an image of the container containing the fluid.

[0460] In operation 878, the vessel volume correlation data generation system 710 extracts the distance between a reference portion of the vessel, such as the bottom portion 784 of the reaction vessel 738, and the surface line of the fluid in the image captured during operation 876. In some embodiments, the distance is measured by pixel distance. In some embodiments, the distance is determined in a manner similar to at least some of the operations of method 830, such as operations 832, 834, 836, 838, and 840. Other methods are possible in other embodiments.

[0461] During operations 880, 882, and 884, the vessel volume correlation data generation system 710 measures the volume of fluid dispensed into the vessel. Various methods can be used to determine the fluid volume. In the illustrated example, a weight approach is used as described below.

[0462] In operation 880, the vessel volume correlation data generation system 710 measures the mass of the vessel containing the dispensed fluid.

[0463] In operation 882, the vessel volume correlation data generation system 710 calculates the mass of the fluid contained in the vessel. In some embodiments, the mass of the fluid in the vessel can be calculated by subtracting the mass of the empty vessel (obtained in operation 872) from the total mass of the vessel containing the fluid (obtained in operation 880).

[0464] In operation 884, the vessel volume correlation data generation system 710 converts the fluid mass to volume based on the density of the fluid.

[0465] In operation 886, the vessel volume correlation data generation system 710 correlates the distance calculated in operation 878 and the volume obtained in operation 884.

[0466] In operation 888, the vessel volume correlation data generation system 710 determines whether a sufficient number of correlations are being made to generate vessel volume correlation data 712. If so (in operation 888, "yes"), method 870 proceeds to operation 890. Otherwise (in operation 888, "no"), method 870 returns to operation 874 where another fluid is dispensed into the vessel, and subsequent operations are performed to determine additional correlations between distance and the volume of fluid within the vessel. Different amounts of fluid are dispensed into the vessel in different correlation cycles in order to obtain a sufficient range of correlation data. Additionally, the amount of fluid dispensed into the vessel can remain substantially the same for some of the correlation cycles so as to obtain reliable results for the correlations.

[0467] In operation 890, the vessel volume correlation data generation system 710 creates vessel volume correlation data 712 based on the plurality of correlations performed in operation 886. In some embodiments, the correlation data 712 is illustrated as a correlation curve (e.g., correlation curve 860 of FIG. 30) by plotting the pixel distances of each image along with the corresponding dispensed volume. The correlation curve is used to estimate the relationship between distance and the volume within the vessel.

[0468] Referring to FIGS. 32 - 34, an exemplary operation of the reaction vessel residual volume detection device 702 is described.

[0469] FIG. 32 is a flowchart illustrating an exemplary method 900 for operating the reaction vessel residual volume detection device 702. In some embodiments, method 900 includes operations 902, 904, 906, 908, 910, and 912.

[0470] Generally, method 900 analyzes the vessel to determine whether the vessel contains a residual volume after being aspirated. If the vessel contains a volume outside of the tolerance range, the aspiration result or inspection result is flagged. If the vessel contains a volume outside of the tolerance range, the aspiration result or inspection result is flagged.

[0471] In operation 902, the reaction vessel residual volume detection device 702 aspirates a substance from a container such as the reaction vessel 738.

[0472] In operation 904, the reaction vessel residual volume detection device 702 transports the container to the container image capture unit 132. In some embodiments, the container image capture unit 132 is arranged to capture an image of the container after aspiration without transportation. In other embodiments, the aspiration in operation 902 occurs at a location where the container image capture unit 132 is arranged in a fixed position and captures an image of the container without moving the container after aspiration.

[0473] In operation 906, the container image capture unit 132 captures an image of the container. In some embodiments, the image of the container is a digital image with a pre-determined resolution.

[0474] In operation 908, the reaction vessel residual volume detection device 702 analyzes the image to determine the presence of a substance in the container. Examples of operation 908 are described in more detail with respect to FIGS. 33 and 34.

[0475] In operation 910, the reaction vessel residual volume detection device 702 determines whether the presence of the residual volume falls within a tolerance range. When the presence of the residual volume is outside the tolerance range, the aspiration of the substance from the container is considered inappropriate. The tolerance range represents the range of residual volume in the reaction vessel that can be tolerated for an acceptable inspection result. For example, the reaction vessel does not need to be aspirated completely empty for an acceptable inspection result. In some embodiments, such a tolerance range is determined from the perspective of the pattern matching score between the captured image and the pre-trained image, as further explained in FIG. 33. As an example, if a residual volume of 4 μL or less in the reaction vessel is considered acceptable, a pattern matching score that can be interpreted as similar to an image of a reaction vessel containing a volume of 4 μL will be used as the tolerance threshold.

[0476] When it is determined that the presence of the residual volume falls within the tolerance range (in operation 910, "Yes"), method 900 proceeds to perform the next pre-determined step. Otherwise (in operation 910, "No"), method 900 proceeds to operation 812.

[0477] In operation 912, the reaction vessel residual volume detection device 702 flags the suction result to indicate that the suction from the vessel is not appropriate for subsequent processes. In other embodiments, the entire inspection result using the suctioned vessel can be flagged to indicate, or suggest, that the inspection result may be inappropriate. Alternatively, the reaction vessel residual volume detection device 702 operates to stop the associated inspection or analysis process within the instrument 100. In other embodiments, the evaluation result can be used to automatically adjust the inspection result that may be in error due to an inappropriate volume of the fluid substance.

[0478] Referring to FIGS. 33 and 34, an example of operation 908 of FIG. 32 is described where the captured image is analyzed to determine the residue 952 within the container. Specifically, FIG. 33 is a flowchart illustrating an exemplary method 930 for performing operation 908 of FIG. 32. Method 930 is also described with reference to FIG. 34, which illustrates an exemplary analysis of the captured image 942 of the container.

[0479] In operation 932, the reaction vessel residual volume detection device 702 detects the area of interest 946 within the captured image 942. In some embodiments, the area of interest 946 includes the bottom portion of the container 944. In some embodiments, the container 944 within the image represents the reaction vessel 738 discussed above. Other portions of the reaction vessel 738 can be used as the reference portion 784.

[0480] Various image processing methods can be used to detect the bottom portion 946 within the image 942. In some embodiments, the bottom portion 946 is detected by a pattern matching function that searches for a pattern representing the bottom portion based on a pre-trained reference image. For example, such a pattern matching function performs a pattern search that scans an image captured for a pattern stored in the system and recognized as a bottom portion. The correlation value or match rate (e.g., match %) is adjustable. Other methods are possible in other embodiments. One example of such an image processing method can be implemented by Cognex In-Sight Vision Software available from Cognex Corporation (Natick, MA), which provides various tools such as edge detection ("Edge"), pattern matching ("Pattern Match"), and histogram analysis ("Histogram").

[0481] In operation 934, the reaction vessel residual volume detection device 702 compares the area of interest 946 with the reference image 948. In some embodiments, the reference image 948 includes a portion 950 corresponding to the area of interest 946. In other embodiments, the reference image 948 is only a portion 950 corresponding to the area of interest 946 of the captured image 942.

[0482] In some embodiments, the reference image 948 represents an image of the same empty container 944. Since ideal suction leaves no residual fluid in the bottom portion of the container 944, a pre-trained image of the empty container 944 is used as the reference image 948. In other embodiments, other images can be used as the reference image 948.

[0483] In operation 936, the reaction vessel residual volume detection device 702 generates a match score between the captured image 942 and the reference image 948. The match score represents how closely the captured image 942 matches the reference image 948. The match score is used as a measurement criterion to determine a cutoff for the presence of excessive residual fluid within the container.

[0484] In operation 938, the reaction vessel residual volume detection device 702 determines whether the match score meets the threshold value. If the match score meets the threshold value (operation 938, "yes"), it is considered that there is no residual fluid or acceptable residual fluid in the vessel, and the method 930 proceeds to a pre-determined next step. Otherwise (operation 938, "no"), the method 930 continues at operation 940. For example, if the match score is below a pre-determined threshold or cutoff value, it is considered that there is excessive residual fluid in the vessel, and the method 930 proceeds to operation 940.

[0485] In operation 940, the reaction vessel residual volume detection device 702 flags the aspiration result to indicate that the aspiration from the vessel is not appropriate for subsequent processing. In other embodiments, the entire test result using the aspirated vessel can be flagged to indicate or suggest that the test result may be inappropriate. Alternatively, the reaction vessel residual volume detection device 702 operates to stop the associated testing or analysis process in the instrument 100. In other embodiments, the evaluation result can be used to automatically adjust the test result that may be erroneous due to an inappropriate volume of fluidic material.

[0486] Alternatively, the method 930 may use other algorithms to perform image comparisons and assign cutoff values. Examples of such approaches utilize common classification tools such as logistic regression, support vector machines, neural networks, convolutional neural networks, and classification trees.

[0487] 35 and 36, an exemplary operation of the dispense adjustment device 704 is described.

[0488] FIG. 35 is a block diagram of an exemplary system 960 in which the dispense adjustment device 704 is operated.

[0489] Generally, the dispensing adjustment device 704 can perform built-in adjustments of pipettes and pumps and thereby use the volume measurement capacity of the container image capture unit 132 to improve pipetting accuracy and overall system accuracy. In the illustrated embodiment, single or multiple volume dispensing is performed into a container and then transferred to a wash wheel for measurement. As described above, the results of volume measurement, which can be performed by the reaction vessel dispensing volume detection device 700, are obtained, and the dispensing adjustment device 704 determines accuracy for each combination of pump and pipette. In some embodiments, the measured volume associated with a pump is used to adjust the operating parameters of the pump and pipette combination. As an example, the step resolution for each pump can be adjusted or an offset can be added to the software instructions for each pump. After adjustment, the dispensing adjustment device 704 can re-check the pump for accuracy and readjust the pump as needed. In some embodiments, the dispensing adjustment device 704 performs such adjustment operations while the instrument is idle for clinical testing. In other embodiments, the dispensing adjustment device 704 performs adjustment operations during instrument initialization. In some embodiments, the dispensing adjustment device 704 periodically performs adjustment operations and monitors trends in pump performance so that a user or repair department can remotely monitor the status and make maintenance decisions such as sending a repair technician for maintenance or component replacement.

[0490] As shown in FIG. 35, the substance preparation system 102 dispenses a fluid substance 118 into one or more containers 114 (e.g., reaction vessel 728 on a wash wheel). The reaction vessel dispensing volume detection device 700 then performs volume measurement within the container 114 and provides the results of the volume measurement 962 to the dispensing adjustment device 704 as described herein. In some embodiments, the dispensing adjustment device 704 analyzes the results of the volume measurement 962 and then generates calibration information 964 that can be used to calibrate the substance preparation system 102 to improve dispensing accuracy.

[0491] Figure 36 is a flowchart illustrating an exemplary method 970 for operating the dispensing adjustment device 704. In some embodiments, method 970 includes operations 972, 974, 976, 978, 980, and 982.

[0492] In operation 972, the dispensing adjustment device 704 receives one or more operating parameters of the material preparation system 102. As described above, the material preparation system 102 includes one or more material dispensing devices such as a sample pipetting device 152, a reagent pipetting device, and a substrate pipetting device 178 that operate to dispense a fluid material 118 into a container 114. The operating parameters include various information about the configuration, settings, and operating status of the material dispensing device. In some embodiments, such a material dispensing device includes a pump device that operates a dispensing unit (e.g., a pipettor). Some examples of pump devices are operated by various types of motors such as a stepper motor. When a stepper motor is used, the operating parameters can include a step resolution that is controlled to adjust the amount of dispensing through the pipettor.

[0493] In operation 974, the dispensing adjustment device 704 receives a target dispensing volume of the fluid material 118. The target dispensing volume represents the volume of the fluid material 118 that is intended to be dispensed into the container 114 based on the operating parameters of the material dispensing device.

[0494] In operation 976, the dispensing adjustment device 704 receives the detected volume that has been dispensed into the container 114.

[0495] In operation 978, the dispensing adjustment device 704 compares the detected volume with the target volume. As an example, a first substance dispensing device that includes a first pump device using a first pipettor is configured to dispense a target volume of 100 μL into a container. After dispensing, it is detected that the volume dispensed into the container is 99.9 μL. Then, the dispensing adjustment device 704 compares the target volume of 100 μL and the detected volume of 99.9 μL and determines that there is a difference of 0.1 μL between the target volume and the detected volume in the first substance dispensing device.

[0496] In some embodiments, multiple dispensing instances from a single substance dispensing device are considered as a group. As an example, a particular substance dispensing device performs a first dispensing, a second dispensing, and a third dispensing using a pump device and a container (or three containers) with a target volume of 100 μL. After three dispensing instances, it is detected that the volume dispensed into the container is 100.5 μL in the first dispensing instance, 99.5 μL in the second dispensing instance, and 100 μL in the third dispensing instance. In some embodiments, all of the detected volumes can be used together to calibrate the substance dispensing device. For example, the standard deviation of the three detected volumes (e.g., 0.5 μL in this example) can be used to calibrate the substance dispensing device, for example, by adjusting the step resolution of its stepping motor. In this example, calibration information 964 is generated and used to reduce the standard deviation. In other embodiments, as described above, each of the detected volumes can be used to calibrate the substance dispensing device for each dispensing instance.

[0497] In other embodiments, a plurality of dispensing instances from a plurality of substance dispensing devices are considered a group. As an example, with a target volume of 100 μL, a first substance dispensing device performs a first dispensing, a second substance dispensing device performs a second dispensing, and a third substance dispensing device performs a third dispensing. After dispensing, it is detected that the volume dispensed by the first substance dispensing device is 100.5 μL, the volume dispensed by the second substance dispensing device is 99.5 μL, and the volume dispensed by the third substance dispensing device is 100 μL. In some embodiments, all of the detected volumes can be used together to calibrate the substance dispensing device. For example, the standard deviation of the three detected volumes (e.g., 0.5 μL in this example) can be used to calibrate the substance dispensing device, for example, by adjusting the step resolution of its stepping motor. In this example, calibration information 964 is generated and used to reduce the standard deviation. In other embodiments, as described above, the detected volumes can be used to calibrate individual substance dispensing devices.

[0498] In operation 980, the dispensing adjustment device 704 generates calibration information 964 for the substance dispensing device. The calibration information 964 includes information for controlling the substance dispensing device such that the volume dispensed by the substance dispensing device is changed closer to the target volume. If the substance dispensing device includes a stepping motor, the calibration information 964 includes adjusting the step resolution of the stepping motor to adjust the volume dispensed by the stepping motor.

[0499] In operation 982, the dispensing adjustment device 704 adjusts the operating parameters of the substance dispensing device based on the calibration information 964. The substance dispensing device can operate to dispense the same or different volumes based on the modified operating parameters. In the above example where three dispensing instances are considered a group, the volume dispensed into the container is detected again after calibration.

[0500] Referring to FIGS. 37-39, an exemplary operation of the reaction vessel detection device 706 is described.

[0501] FIG. 37 is a flowchart illustrating an exemplary method 1000 for operating the reaction vessel detection device 706. In some embodiments, method 1000 includes operations 1002, 1004, 1006, 1008, 1010, and 1012.

[0502] Generally, during system initialization or reset, the containers inside the cleaning wheel need to be removed. The reaction vessel detection device 706 can utilize the container image capture unit 132 to determine whether all or some of the containers have been removed during this initialization sequence. In some embodiments, the cleaning wheel operates to send out to all positions such that each container location is checked by the image capture unit. At each cleaning wheel send-out position, the reaction vessel detection device 706 can perform image processing, such as a pattern matching algorithm, to check for the presence of a container by comparing the captured image with a reference image (e.g., an image of the cleaning wheel without a container). Contrasted with other approaches that examine or utilize the volume inside the container, the reaction vessel detection device 706 according to the exemplary embodiments of the present disclosure provides reliable results. When the reaction vessel detection device 706 looks for a close match to the geometry of the container, a large deviation from the reference image will indicate the presence of a container, and a small deviation will indicate the absence of a container. If a presence is determined, the system can remove the container and check again to confirm that the container has been successfully removed. Once it is determined that a container is not present at a given wheel location, the wheel can be sent to the next position and the process repeated.

[0503] In the illustrated example, the reaction vessel detection device 706 is mainly described with respect to the cleaning wheel 720. However, in other embodiments, the reaction vessel detection device 706 is used with other types of container carriage devices.

[0504] In operation 1002, the reaction vessel detection device 706 uses the container image capture unit 132 to capture an image of the container slot 1044 (FIG. 39) (e.g., slot 736) on the cleaning wheel 720.

[0505] In operation 1004, the reaction vessel detection device 706 analyzes the image to determine the presence or absence of a container 1042 (FIG. 39) (e.g., reaction vessel 738) on the cleaning wheel 720. An example of operation 1004 will be described in more detail with reference to FIGS. 38 and 39.

[0506] In operation 1006, the reaction vessel detection device 706 determines whether the container is present in the container slot. If so (in operation 1006, "yes"), method 1000 continues in operation 1008. Otherwise (in operation 1006, "no"), method 1000 proceeds to operation 1010.

[0507] In operation 1008, the reaction vessel detection device 706 removes the container from the container slot of the cleaning wheel 720. In other embodiments, other devices in the instrument 100 (such as a transfer or carriage device as shown in FIG. 2) operate to remove the container from the cleaning wheel 720. In yet other embodiments, the container is manually removed from the cleaning wheel 720.

[0508] In operation 1010, the reaction vessel detection device 706 determines whether all positions of the cleaning wheel 720 have been analyzed through the previous operations (e.g., operations 1002, 1004, 1006, and 1008). If so (in operation 1010, "yes"), method 1000 proceeds to the next pre-determined step. Otherwise (in operation 1010, "no"), method 1000 proceeds to operation 1012.

[0509] In operation 1012, the reaction vessel detection device 706 moves the cleaning wheel 720 to the next position and repeats operations 1002 and subsequent operations.

[0510] Referring to FIGS. 38 and 39, an embodiment of operation 1004 of FIG. 37 is described where the captured image is analyzed to determine the presence of a container on the wash wheel. Specifically, FIG. 38 is a flowchart illustrating an exemplary method 1020 for performing operation 1004 of FIG. 37, which is also described with reference to FIG. 39 that illustrates an exemplary analysis of the captured image 1040 of the container slot 1044 on the wash wheel.

[0511] In operation 1022, the reaction vessel detection device 706 detects a region of interest 1046 within the captured image 1040. In some embodiments, the region of interest 1046 includes at least a portion of the container slot 1044 (e.g., slot 736) of the wash wheel 720. In some embodiments, the region of interest 1046 includes a bottom portion of the container, or a portion within the image corresponding to the location of the bottom portion of the container. An exemplary method for detecting the region of interest can be implemented by Cognex In-Sight Vision Software available from Cognex Corporation (Natick, MA) that provides various tools such as edge detection ("Edge"), pattern matching ("Pattern Match"), and histogram analysis ("Histogram").

[0512] In operation 1024, the reaction vessel detection device 706 compares the region of interest 1046 with a reference image 1048. In some embodiments, the reference image 1048 includes a portion corresponding to the region of interest 1046. In other embodiments, the reference image 1048 itself corresponds to the region of interest 1046 of the captured image 1040.

[0513] In some embodiments, the reference image 1048 represents an image of the container slot 1044 without the container 1042 therein (FIG. 39). In other embodiments, other images can be used as the reference image 948. For example, the reference image can be an image of the container slot with a container therein.

[0514] In operation 1026, the reaction vessel detection device 706 generates a match score between the captured image 1040 and the reference image 1048. The match score represents how closely the captured image 1040 matches the reference image 1048. The match score is used as a measurement criterion to determine a cut-off for the presence of the container 1042 in the slot 1044 of the wash wheel 720.

[0515] In operation 1028, the reaction vessel detection device 706 determines whether the match score meets a threshold. If the match score meets the threshold (in operation 1028, "Yes"), it is considered that the container does not exist in the slot of the wash wheel, and the method 1020 proceeds to operation 1030. Otherwise (in operation 1028, "No"), it is considered that the container exists in the slot of the wash wheel, and the method 1020 continues in operation 1032. For example, if the match score is below a pre-determined threshold or cut-off value, it is considered that the container exists in the slot of the wash wheel, and the method 1020 proceeds to operation 1032.

[0516] In operation 1030, the reaction vessel detection device 706 confirms the non-presence of the container 1042 in the slot 1044 of the wash wheel 720.

[0517] In operation 1032, the reaction vessel detection device 706 confirms the presence of the container 1042 in the slot 1044 of the wash wheel 720.

[0518] As described with reference to FIG. 22-39, the container volume detection device 402 can be modified to be suitable for various applications. For example, the container volume detection device 402 can be applied to any analyzer that prepares and / or uses a fluid substance to detect a target analyte, such as an in vitro diagnostic (IVD) analyzer. In some embodiments, the container volume detection device 402 and its method can be applied to any device or unit other than a wash wheel. Some embodiments of the container volume detection device 402 can be applied to total reaction volume checks. In some embodiments, the calibration curve used in the container volume detection device 402 is established between the pixel distance and the colorimetric volume results obtained using a spectrophotometer. In other embodiments, the calibration curve used in the container volume detection device 402 is established between the pixel distance and the alkaline phosphatase reaction results obtained using a photon counting module. In still other embodiments, the calibration curve used in the container volume detection device 402 is established using a JIG reaction vessel along with a line at a known volume height on the outer wall. With respect to residual volume detection in the container volume detection device 402 (e.g., for volumes greater than 10 μL), line finding or grayscale matching may be applicable.

[0519] According to an exemplary embodiment of the present disclosure, the container volume detection device 402 can be used in a variety of other applications. In some embodiments, the container volume detection device 402 is used to detect dispensing tip misalignment. For example, the container image capture unit 132 is used to determine whether the dispensing tip is off-center when it enters the field of view. In other embodiments, the container volume detection device 402 is used to detect wheel positioning integrity. For example, the container image capture unit 132 is used to determine whether the wash wheel is tilted or mispositioned. In still other embodiments, the container volume detection device 402 is used to detect any abnormal conditions such as splashing, foaming, or poor magnetization. In still other embodiments, the container volume detection device 402 is used to detect RV integrity such as scratches, discoloration, and permeability. In still other embodiments, the container volume detection device 402 is used to detect tip alignment integrity.

[0520] The light source used in the container volume detection device 402 does not need to be located behind the reaction vessel. Other locations for the backlight device are possible. Alternatively, the light source can be incorporated into the camera unit and configured to irradiate from the camera unit. Such a light source incorporated into the camera unit can be used with a screen located behind the reaction vessel as illustrated herein. In some embodiments, the camera unit used in the container volume detection device 402 is configured to monitor the temperature of the container and / or the wash wheel using the IR spectrum.

[0521] As described above, the reaction vessel detection device 706 of the container volume detection device 402 can be applied to any container carriage device other than the wash wheel. As described above, the dispensing adjustment device 704 of the container volume detection device 402 can operate to use the measured level to measure the level of the substrate volume, adjust the RLU of the test result, and fine-tune the calibration to improve accuracy.

[0522] According to an exemplary embodiment of the present disclosure, the instrument 100 employs various program solutions to implement image evaluation operations as described herein, such as pattern matching. In some embodiments, such program solutions are developed using off-the-shelf software solutions. One example of a program solution is the In-Sight Explorer Software (also referred to as In-Sight Vision Software) available from Cognex Corporation (Natick, MA).

[0523] Referring now to FIGS. 40 and subsequent figures, an example of a dispensing tip evaluation system 122 is described.

[0524] FIG. 40 is a block diagram of an example of the dispensing tip evaluation system 122 of FIG. 1. In some embodiments, the dispensing tip evaluation system 122 includes a dispensing tip integrity evaluation device 1100.

[0525] The dispensing tip integrity evaluation device 1100 is operative to evaluate the quality of the fluid substance 118 drawn into the dispensing tip 112 and the alignment of the dispensing tip 112. As described herein, the dispensing tip 112 can be of various types and can be used in different processes. One example of the dispensing tip 112 is a pipetting tip that can be used with a sample pipetting operation device 152. The dispensing tip integrity evaluation device 1100 can utilize a dispensing tip image capture unit 130. An example of the dispensing tip integrity evaluation device 1100 is illustrated and described in further detail with reference to FIG. 41.

[0526] FIG. 41 is a block diagram of an example of the dispensing tip integrity evaluation device 1100 of FIG. 40. In some embodiments, the dispensing tip integrity evaluation device 1100 includes a sample quality detection device 1112 and a tip alignment detection device 1114.

[0527] In some embodiments, the dispensing tip integrity assessment device 1100 is implemented with the sample aspiration system 510 of FIG. 10. In other embodiments, the dispensing tip integrity assessment device 1100 can be used in other types of systems operable to aspirate or dispense fluid substances using a container.

[0528] The sample quality detection device 1112 operates to detect the quality of a sample aspirated into the sample pipetting tip of the sample pipetting operation device 152. Examples of the structure and operation of the sample quality detection device 1112 are described with reference to FIGS. 42-55.

[0529] In addition to detecting the quality of the sample in the dispensing tip, the sample quality detection device 1112 can also be used to detect the quality of the fluid substance 118 contained in the container 114. As described herein, the container 114 can be of various types and can be used in different processes. Examples of the container 114 include a reaction container, a sample container, and a dilution container that are used throughout the process in the instrument 100. In some embodiments, the sample quality detection device 1112 can utilize the container image capture unit 132.

[0530] The tip alignment detection device 1114 operates to detect tolerances and misalignments of the dispensing tip 112 with respect to the sample pipetting operation module 512 and / or the dispensing tip image capture unit 130. The allowable tolerance of the dispensing tip 112 and / or the misalignment of the dispensing tip 112 can reduce the accuracy of detecting the volume of the aspirated sample within the dispensing tip 112, for example, as performed by the dispensing tip volume detection device 400 of the present specification. The tip alignment detection device 1114 further operates to adjust or correct the detected volume of the liquid aspirated into the dispensing tip 112 based on the detection of tolerances and misalignments. Examples of the structure and operation of the tip alignment detection device 1114 are described with reference to FIGS. 56-68.

[0531] Referring to FIGS. 42-55, an embodiment of the sample quality detection device 1112 is described.

[0532] FIG. 42 illustrates an embodiment of the sample quality detection device 1112. In some embodiments, the sample quality detection device 1112 includes an image capture device 1120, an image evaluation device 1122, a classification data generation device 1124, and a classification device 1126. Also shown are the aspirated sample 1130, the image 1132, one or more color parameters 1134, the classification data 1136, and the sample classification result 1138.

[0533] The sample quality detection device 1112 operates to evaluate the quality of a sample aspirated using a dispensing tip and determine whether the sample has sufficient quality for subsequent analysis. If it is determined that the sample quality is impaired, the instrument can inform the user about the sample quality and / or stop the inspection.

[0534] In some embodiments, a sample provided in a sample tube (e.g., sample 324 in FIG. 4) contains various interfering substances or interferents that can compromise sample integrity and affect clinical testing. Such samples containing interfering substances above the acceptable level can cause false but believable results that cannot be easily detected. For chemical and immunological assay systems, examples of interfering substances include hemoglobin, bilirubin (also referred to herein as jaundice, a medical condition caused by bilirubin), and lipids (also referred to herein as lipemia, a medical condition caused by lipids). Depending on the assay, the concentrations of hemoglobin, jaundice, and lipemia should be limited to pre-determined levels to ensure that no interference occurs that causes distorted results.

[0535] Various methods are used to evaluate sample quality. Some examples of such methods include chemical analyzers that use spectrophotometers. Using such a spectrophotometer to determine sample quality is an event independent of the chemical analysis of the sample and, thus, may require additional samples to determine sample integrity, depending on the manufacturer. Since the spectrophotometer uses specific wavelengths for measurements, the system requires either an LED or a collimated light source and uses complex mathematical processing due to spectral overlap of interfering substances with the end products of some assays. Also, hyperlipidemic samples often exhibit volume displacement, which can affect the sample volume in an assay. Thus, methods for evaluating sample quality require separate tests to do so, incurring additional costs. As a result, the primary sample test can be delayed because it can only be performed after the quality check. Alternatively, if the primary sample test and the sample quality test are performed simultaneously, a compromised sample can only be flagged during or after the primary sample test. In this case, the sample needs to be recollected, causing a delay in the test results.

[0536] In contrast, the sample integrity detection device 1112 is incorporated with the instrument 100 and uses various components of the instrument 100 that are configured for the analysis of samples. Thus, a single instrument can perform both the evaluation of the quality of the sample and the analysis of the sample without causing delays and additional costs.

[0537] As described above, in some embodiments, the sample integrity detection device 1112 is used with the sample aspiration system 510 of FIG. 10. In other embodiments, the sample integrity detection device 1112 can be used in other types of systems operable to aspirate fluid substances using a container.

[0538] In the illustrated embodiment, the sample integrity detection device 1112 is mainly described in the context of an immunoassay analyzer, as shown in FIGS. 2 and 4. For example, the sample integrity detection device 1112 operates to detect the concentration of interfering substances such as hemoglobin, jaundice, and lipemia in the sample aspirated into the dispensing tip. However, in other embodiments, the sample integrity detection device 1112 is used to evaluate the quality of the sample in other types of instruments.

[0539] Generally, the sample integrity detection device 1112 acquires an image of a transparent cylindrical container with fluid inside. The sample integrity detection device 1112 then extracts information about individual pixels within the region of interest in the image. The information about the pixels is used to classify the fluid. The sample integrity detection device 1112 includes a classifier model that employs classifiers used to group the fluid into categories. If the color of the fluid aspirated into the container is not within the pre-determined specifications, the aspiration or inspection is flagged. In some embodiments, the operator of the instrument receives information about the fluid aspiration when it is determined that the fluid integrity is outside the specifications for a given fluid.

[0540] Still referring to FIG. 42, the image capture device 1120 operates to capture an image 1132 of the sample 1130 being aspirated using the dispensing tip 1180 (FIG. 45). In some embodiments, the sample 1130 is an example of the sample 540, and the dispensing tip 1180 is an example of the dispensing tip 112 as shown in FIG. 10. In some embodiments, the image capture device 1120 operates to capture more than one image of the sample 1130 being aspirated using the dispensing tip 1180 at varying time intervals. For example, the image capture device 1120 operates to continuously capture two images of the sample 1130 being aspirated using the dispensing tip 1180 approximately 30 milliseconds apart or at any other time interval. In some embodiments, the image capture device 1120 utilizes a dispensing tip image capture unit 130 that includes a camera unit 550 and a light source 552. In some embodiments, the light source 552 of the image capture device 1120 generates a white backlight. In other embodiments, the light source 552 provides one or more colored backlights that can either be fixed or variable during image capture. In some embodiments, the light source 552 can generate backlights with different exposure times. For example, the light source 552 can generate a backlight with an exposure time of approximately 6 milliseconds, and the image capture device 1120 operates to capture a first image immediately after an exposure time of approximately 6 milliseconds and a second image in approximately 30 seconds. In one embodiment, the first image is acquired approximately 0.2 seconds after the reagent is dispensed into the container. In an embodiment, the second image is acquired approximately 6.5 seconds after mixing. In a further embodiment, the first image is acquired approximately 0.2 seconds after the reagent is dispensed into the container, and the second image is acquired approximately 6.5 seconds after mixing. The varying exposure times can improve the evaluation of the images captured for color parameters. For example, if the sample has a high concentration, a longer exposure time will likewise result in a brighter image so that the image evaluation device 1122 can effectively evaluate different color parameters.

[0541] The image evaluation device 1122 is operative to process and evaluate a captured image 1132 and generate one or more color parameters 1134. The color parameters 1134 are used to determine the concentration level of interfering substances contained in the sample 1130. An example of the image evaluation device 1122 is illustrated and described in further detail with reference to FIGS. 44-48.

[0542] The classification data generation device 1124 is operative to generate classification data 1136. As described below, the classification data 1136 includes a list of classification labels for different amounts of interfering substances that are used by the classification device 1126 to generate a sample classification result 1138. An example of the classification data generation device 1124 is illustrated and described in further detail with reference to FIGS. 49-53.

[0543] The classification device 1126 is operative to generate a sample classification result 1138 based on the color parameters 1134 and the classification data 1136. The sample classification result 1138 includes information indicative of the quality of the sample 1130. For example, the sample classification result 1138 includes information representing the concentration levels of interfering substances such as hemoglobin, jaundice, and lipemia in the aspirated sample 1130, indicating that the concentration levels of the interfering substances are acceptable, either individually or in combination. Accordingly, the sample classification result 1138 is used to determine whether the sample 1130 has sufficient quality for laboratory analysis in the instrument 100. An example of the classification device 1126 is illustrated and described in further detail with reference to FIGS. 54-55.

[0544] FIG. 43 is a flowchart illustrating an exemplary method 1150 for operating the sample integrity detection device 1112. In some embodiments, the method 600 is performed by the sample aspiration system 510 (FIG. 10) and the sample integrity detection device 1112.

[0545] Generally, method 1150 analyzes the quality of the sample in the dispensing tip from the perspective of the concentration of interfering substances such as hemoglobin, jaundice (bilirubin), and lipemia, and flags the test result if the evaluated quality is classified outside the acceptable range.

[0546] In operation 1152, the sample aspiration system 510 operates to aspirate a fluid substance such as sample 1130 into the dispensing tip 1180 (FIG. 45) (an example of the dispensing tip 112 as shown in FIG. 10) as programmed.

[0547] In operation 1154, the sample aspiration system 510 transports the dispensing tip 1180 containing the aspirated sample 1130 to the image capture device 1120 (including the dispensing tip image capture unit 130). In some embodiments, the dispensing tip image capture unit 130 of the image capture device 1120 is arranged to capture an image of the dispensing tip 1180 after aspiration without transportation.

[0548] In operation 1156, the dispensing tip image capture unit 130 captures an image 1132 of the dispensing tip 1180. In some embodiments, the image 1132 of the dispensing tip 1180 is a digital image with a pre-determined resolution. In some embodiments, the dispensing tip image capture unit 132 can capture more than one image of the dispensing tip 1180 at varying time intervals. For example, the dispensing tip image capture unit 132 can capture two images of the dispensing tip 1180 about 30 milliseconds apart or at any other time interval. In operation 1158, the sample integrity detection device 1112 analyzes the image 1132 to determine the level of interfering substances in the sample 1130 within the dispensing tip 1180. An example of operation 1158 is described in more detail with reference to FIGS. 44 - 55.

[0549] In operation 1160, the sample integrity detection device 1112 determines whether the interfering substance level falls within the tolerance range. When the determined level is outside the tolerance range, the dispensing tip 1 The aspiration of sample 1130 within 12 is considered inappropriate. The tolerance range can vary depending on the type of sample and / or the type of interfering substances therein. In some embodiments, whether the determined interfering substance level falls within the tolerance range can be evaluated using a classification identifier or classifier, as described below.

[0550] When it is determined that the detected interfering substance level falls within the tolerance range (in operation 1160, "yes"), method 1150 subsequently performs the next pre-determined step. Otherwise (in operation 1160, "no"), method 1150 proceeds to operation 1162.

[0551] In operation 1162, the sample integrity detection device 1112 flags the aspiration to indicate that the aspirated sample 1130 within the dispensing tip 1180 is not suitable for subsequent processes. In other embodiments, the entire test result using the aspirated sample can be flagged to indicate or suggest that the test result may be inappropriate. Alternatively, the sample integrity detection device 1112 operates to stop the associated test or analysis process within the instrument 100. In other embodiments, the evaluation result can be used to automatically adjust the test result, which may be in error due to compromised sample quality.

[0552] Referring to FIGS. 44 - 55, an example of operation 1158 of FIG. 43 is described where the captured image 1132 is analyzed and the quality of the sample aspirated into the dispensing tip is determined. In some embodiments, operation 1158 is performed by the image evaluation device 1122, the classification data generation device 1124, and the classification device 1126 of the sample integrity detection device 1112.

[0553] Figure 44 is a flowchart illustrating an exemplary method 1170 of operating the image evaluation device 1122 of FIG. 42. In some embodiments, method 1170 includes operations 1172, 1174, and 1176. Method 1170 is also described with reference to FIG. 45, which illustrates an exemplary analysis of the captured image 1132.

[0554] In operation 1172, the image evaluation device 1122 identifies the location of the dispensing tip 1180 within the image 1132. Various image processing methods can be used to detect the dispensing tip 1180 within the image 1132. In some embodiments, the dispensing tip 1180 is located by a pattern matching function that searches for a pattern representing the dispensing tip based on a pre-trained reference image. Such image processing methods can be implemented in various programming languages such as Python (e.g., its contour discovery function). An exemplary method of such image processing methods can be implemented by Cognex In-Sight Vision Software available from Cognex Corporation (Natick, MA), which provides various tools such as edge detection ("Edge"), pattern matching ("Pattern Match"), and histogram analysis ("Histogram").

[0555] In operation 1174, the image evaluation device 1122 detects a pre-determined region of interest 1182. The region of interest 1182 is a region of the image 1132 that is evaluated to determine the quality of the sample 1130 within the dispensing tip 1180. The region of interest 1182 is pre-set as a region that can be repeatedly detected as including the sample 1130 within different images 1132. Various methods can be used to detect the region of interest 1182. An example of such a method is described with reference to FIG. 46. In some embodiments, there may be more than one pre-determined region of interest, and thus, the image evaluation device 1122 detects more than on...

Claims

A method for evaluating a liquid substance in a container, comprising: using a substance dispensing device to dispense the liquid substance into the container; using at least one computer device to determine the volume of the liquid substance in the container; receiving operation information of the substance dispensing device, the operation information including operation parameters of the substance dispensing device; receiving a target volume of the liquid substance intended to be dispensed into the container; comparing the determined volume of the liquid substance with the target volume; generating calibration information for the substance dispensing device; adjusting the operation parameters of the substance dispensing device based on the calibration information; The method further comprises: aspirating at least a portion of the liquid substance from the container; using an image capture device to capture an image of at least a portion of the container; comparing the image with a reference image; determining a first matching score based on the similarity between the image and the reference image; determining, based on the first matching score, whether the container contains a residual volume of the liquid substance after at least a portion of the liquid substance has been aspirated from the container; A method further comprising the above steps. **Claim 2** Determining the volume of the liquid substance comprises: using an image capture device to capture an image of at least a portion of the container; using at least one computer device to identify reference points in the image, the reference points being associated with the container; using at least one computer device to identify the surface level of the liquid substance in the container within the image; determining the distance between the reference points and the surface level; converting the distance into the volume of the liquid substance based on correlation data, the correlation data including information about the correlation between the volume of the liquid contained in the container and the distances from the reference points to multiple surface levels of the liquid contained in the container; The method according to claim 1, further comprising the above steps. **Claim 3** Supplying the liquid to a further container, the further container having the same configuration as the container; determining the volume of the supplied liquid; capturing a further image of the further container; Determining a pixel distance between a surface level of the supplied liquid contained within the further container in the further image and a reference point in the further image; Correlating the determined volume with the determined pixel distance, thereby generating correlation data, wherein the volume of the liquid substance within the container is determined using the correlation data; The method according to claim 1, further comprising.

4. The distance is measured by a pixel distance, and the method comprises: Supplying a liquid to a further container, the further container having the same configuration as the container; Determining the volume of the supplied liquid; Capturing a further image of the further container; Determining a pixel distance between a surface level of the supplied liquid contained within the further container in the further image and a reference point in the further image; Correlating the determined volume with the determined pixel distance; Generating the correlation data based on the determined volume and the determined pixel distance; The method according to claim 2, further comprising.

5. The method according to claim 4, wherein the correlation data is generated based on a plurality of correlations between a plurality of determined pixel distances and a plurality of determined volumes of the liquid supplied to the further container.

6. The supplied liquid comprises a dye solution, and The volume of the supplied liquid is determined based on spectrophotometry. The method according to any one of claims 3 to 5.

7. Determining the volume of the supplied liquid includes determining the mass of the supplied liquid. The method according to any one of claims 3 to 6.

8. Comparing the first match score with a threshold value, and / or Determining whether the first match score is below a threshold value, wherein the first match score being below the threshold value indicates that the container contains a residual volume of the liquid substance; The method according to any one of claims 1 to 7, further comprising.

9. Further comprising determining an area of interest within the image, and Comparing the images includes comparing the area of interest within the image with at least a portion of the reference image. The method according to any one of claims 1 to 8.

10. The method according to claim 9, wherein the area of interest includes an area adjacent to the bottom of the container.

11. The method according to claim 8, further comprising flagging the result of the suction from the container when the first match score is below the threshold, indicating that at least a portion of the liquid substance suctioned from the container is not suitable for a subsequent process.

12. Arranging a plurality of containers in a plurality of container slots of a container carriage device, Using an image capture device to capture an image of one of the plurality of container slots at a first position of the container carriage device, Comparing the image with a reference image, Determining a second match score based on the similarity between the image and the reference image, Determining whether a container is present or not present in the one of the plurality of container slots based on the second match score The method according to any one of claims 1 to 11, further comprising.

13. Comparing the second match score with a threshold, and / or Determining that the second match score exceeds and / or meets the threshold, wherein the second match score exceeding the threshold represents the non-presence of the container in the one of the plurality of container slots, The method according to claim 12, further comprising.

14. The method according to claim 13, further comprising removing the container from the one of the plurality of container slots when the second match score is below the threshold.

15. The method according to claim 13, further comprising moving the container carriage device to a second position after determining that the second match score exceeds and / or meets the threshold.

16. A computer program element that, when executed on a computer device of a system for evaluating a liquid substance, instructs the computer device to perform the steps of the method according to any one of claims 1 to 15.

17. A non-transitory computer-readable medium storing the computer program element according to claim 16.

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