JP2012159318A - Analyzer - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a system capable of achieving improvement of processing capacity and reduction of cost by reducing manual work on a device which performs pretreatment of a specimen before feeding it to an automatic analyzer which analyzes constituent concentration of a biological sample.SOLUTION: An analyzer for a biological sample comprises: a laser light source 40 and a white light source 60 for radiating different types of lights from different directions on a blood collecting tube 101; imaging means 70 which captures an image of the blood collecting tube 101 from a side face thereof simultaneously with the radiation of light from the laser light source 40 and the white light source 60; analysis means 80 which processes the image captured by the imaging means 70 and acquires information regarding a layer in the blood collecting tube 101; and control means 90 which controls the laser light source 40, the white light source 60, and the imaging means 70.

Description

  The present invention relates to an analyzer for analyzing a biological sample such as blood collected in a container, and more particularly to an automatic device for automatically grasping the remaining amount, color, and component separation state of components constituting the biological sample. The present invention relates to a pretreatment device for an analyzer.

  Conventionally, techniques for analyzing the concentration of a component using a biological sample have been provided. Then, processing (hereinafter referred to as preprocessing) performed before putting a biological sample into the automatic analyzer, and a preprocessing system for automatically transporting the specimen to the automatic analyzer have appeared, and the development continues. In the market, the number of test items and the number of specimens are increasing, and the pretreatment process is diversifying. As a result, many processes have been automated, contributing to the reduction in the amount of work for users (inspectors).

  However, at present, not all of the pre-processing steps are automated, and there are still portions that require manual work by the operator. A typical example is sample selection.

  For example, if the amount of serum in the sample transported to the automatic analyzer is small, it goes without saying that the measurement result will be delayed due to the limited number of items that can be measured. Since the separation agent is sucked and causes clogging errors, it is desirable to remove the separation agent before putting it into the automatic analyzer. Also, if there is hemolysis or turbidity in the serum, it will be a fatal wound to guarantee the accuracy of the results for blood analysis based on absorbance, so remove it before it is transported to the automatic analyzer, or At least the specimen needs to be specified.

  However, in many cases, the amount of liquid before being put into the automatic analyzer is checked and the serum information of the sample at the pretreatment stage is visually checked. Has been. In addition, there is a concern that re-measurement due to missing a sample to be taken out and reporting delay of measurement results accompanying re-measurement may occur.

  It is a market demand to solve the above-mentioned problems. For example, as described in Patent Document 1, Patent Document 2, etc., a technique related to automatic confirmation of liquid amount and color and automatic detection of foreign matter by installing an imaging means has been invented. I came.

Japanese Patent Laid-Open No. 11-37845 JP 2001-165752 A Japanese Patent No. 036886757 Japanese Patent No. 0380229 Japanese Patent No. 04099231 Japanese Patent No. 03733086 Japanese Patent No. 03733087 Japanese Patent No. 0377355

  By the way, in actual operation in the laboratory, a barcode label on which important information such as a patient ID, personal information, and parameters necessary for apparatus operation is written is attached to the surface of the blood collection tube. Depending on the type of blood collection tube and the size of the label, the entire tube wall may be covered. In addition, a commercially available blood collection tube for normal use is often already attached with a label at the time of purchase. For convenience of operation, there are not a few cases in which the label is affixed several times on the label.

  In this regard, several prior arts corresponding to the blood collection tube to which a label is attached are known. For example, in Patent Document 3, Patent Document 4, and Patent Document 5, a gloss sensor is installed to detect a side surface that is not covered with a label, and a rotating device is used to direct the surface to an imaging device so that a living body in a test tube Solutions have been proposed to measure the volume of the sample.

  Patent Document 6, Patent Document 7, and Patent Document 8 describe a method of measuring the volume of an internal biological sample by installing two or more types of light sources having different light amounts, changing the amount of irradiated light, and transmitting the label. Has been.

  However, the range covered by these prior arts is limited to the area where the contents can be seen through the colorless and transparent tube wall, and verification to the applicability to the scene where the label covers the entire tube wall is not possible. Not done. In addition, even on the surface without the label coating, the shading of the printed part of the barcode transmitted from the opposite side of the surface to be photographed becomes an obstacle, and the difference in shading between the printed part and the non-printed part appears remarkably. In some cases, the measurement of biological samples may become impossible or cause measurement errors. For this reason, in order to obtain an effective measurement result by this method, it is necessary to individually cope with the irradiation conditions by switching the light amount depending on the presence or absence of the label. In addition, at the present time when a processing capacity of 800 samples per hour is demanded on the market, a design that incorporates a rotating operation every time has a concern that the processing speed may be delayed, and thus is not practical.

  Accordingly, an object of the present invention is to provide a container in a pretreatment apparatus that performs pretreatment of a sample to be input in an analyzer that analyzes the component concentration of a biological sample, without being obstructed by printed information affixed to the container. An object of the present invention is to provide an analyzer that can grasp the internal state.

  The above and other objects and novel features of the present invention will be apparent from the description of this specification and the accompanying drawings.

  The outline of typical inventions among the inventions disclosed in the present application will be described as follows.

  That is, a typical outline is a biological sample analyzer that analyzes a biological sample stored in a container, and includes two or more irradiation means for irradiating the container with different types of light, and light from the irradiation means. Imaging means for imaging the container from the side at the same time as the irradiation, analysis means for processing the screen to acquire information on the layers in the container, and control means for controlling the irradiation means and the imaging means, the analysis means comprising: And a method of excluding the area of the barcode printing portion from the image acquired by the analyzing means, adding the gray scale and RGB signal amounts from the remaining area, and specifying the boundary position of the layer. .

  Among the inventions disclosed in the present application, effects obtained by typical ones will be briefly described as follows.

  In other words, the effect obtained by the representative one can reduce the burden on the operator and the risk of infection associated with the work by reducing the conventional manual work. Further, by obtaining information on the volume of serum present in the blood collection tube, it is possible to prioritize measurement items, and as a result, the sample processing flow can be improved to be more efficient. In addition, there is no need to rotate the specimen to find a gap that is not covered with the label, no need to avoid the barcode printing part during imaging, and the barcode printing part. There is an advantage that it is not necessary to switch the processing regardless of whether or not the image is included in the imaging range, and the time until the result report can be expected to be shortened.

It is a block diagram which shows the whole structure of the biological sample analyzer which concerns on one embodiment of this invention. It is a block diagram which shows the structure of the unit installed in the input module vicinity or centrifuge module vicinity of the biological sample analyzer which concerns on one embodiment of this invention. It is explanatory drawing for demonstrating the image imaged with the biological sample analyzer which concerns on one embodiment of this invention. It is explanatory drawing for demonstrating the signal amount of the image imaged with the biological sample analyzer which concerns on one embodiment of this invention. It is explanatory drawing for demonstrating the signal amount of the image imaged with the biological sample analyzer which concerns on one embodiment of this invention. It is explanatory drawing for demonstrating the signal amount of the image imaged with the biological sample analyzer which concerns on one embodiment of this invention. It is a table | surface for demonstrating the characteristic of the boundary of the layer seen in the signal amount data of the image imaged with the analyzer of the biological sample which concerns on one embodiment of this invention. It is explanatory drawing which shows the control means and output message which are imposed on a biological sample after determination of hemolysis with the biological sample analyzer which concerns on one embodiment of this invention.

  Hereinafter, embodiments of the present invention will be described in detail with reference to the drawings. Note that components having the same function are denoted by the same reference symbols throughout the drawings for describing the embodiment, and the repetitive description thereof will be omitted.

  The configuration of a biological sample analyzer according to an embodiment of the present invention will be described with reference to FIGS. FIG. 1 is a block diagram showing the entire configuration of a biological sample analyzer according to an embodiment of the present invention, in which a biological sample (blood) collected from a patient is preprocessed and analyzed by an automatic analyzer. Show.

  FIG. 2 is a configuration diagram showing a configuration of a unit arranged in the vicinity of the input module of the biological sample analyzer according to the embodiment of the present invention.

  In FIG. 1, a biological sample analyzer includes a transfer line 2, an input module 3, a centrifuge module 4, an opening module 5, a labeler 6 for attaching an identifier such as a barcode, a dispensing module 7, a closing module 8, and a classification module. 9, a preprocessing system 1 composed of a plurality of modules having the storage module 10 as a basic element, an analysis means 80 for analyzing various data to be acquired, and a control means 90 for controlling the entire preprocessing system 1, and further connected And an automatic analyzer 11 for analyzing the components of the biological sample. In the vicinity of the centrifugal module 4, a unit (20) that is a feature of the present embodiment is arranged.

  The input module 3 inputs the specimen into the biological sample analyzer, and the centrifuge module 4 centrifuges the input specimen. The capping module opens the centrifuge sample, and the dispensing module performs subdivided dispensing to distribute the sample to the automatic analyzer. The labeler 6 attaches a barcode to the container for subdivision. The capping module 8 opens the specimen, and the storage module 10 sorts the specimen container.

  In the present embodiment, a unit that specifies the boundary position of each layer in the container by excluding the influence of the printed portion of the barcode is shown.

  FIG. 2 is a block diagram showing the configuration of the units (20, 21) in FIG. First, a base 30 for connecting to the pretreatment system 1 is required. On this table 30, as a main element, a dedicated fixture 31 for fixing the blood collection tube 101 vertically, two irradiation means (40, 60), and an imaging means 70 are provided, and an image acquired by the imaging means 70 is analyzed. Is connected to two irradiation means (40, 60) and a control means 90 for controlling the imaging means 70.

  In the present embodiment, a laser light source 40 is used as the irradiation unit 40. The other irradiation means 60 is not necessarily used in this embodiment. The laser light 41 has a vertically long shape by a lens (not shown) so that the blood collection tube 101 can be irradiated at a time. The transmitted light that has passed through the blood collection tube 101 is detected by the imaging means 70. The laser light source 40 and the imaging means 70 may move up and down synchronously to detect transmitted light.

  A CMOS is used for the imaging means 70, but a CCD may be used. The arrangement of the imaging means 70 is as shown in FIG. The distance, aperture, and focus are adjusted so that the entire blood collection tube 101 can be seen. Note that the imaging means 70 employed here has a resolution that can read a barcode.

  An analysis unit 80 that acquires and analyzes image data is connected to the tip of the imaging unit 70. The laser light source 40, the irradiation means 60, and the imaging means 70 are controlled by commands based on electrical signals from the control means 90.

  Next, details of measurement by the units (20, 21) of the analyzer according to the embodiment of the present invention will be described with reference to FIGS. FIG. 3 is an explanatory diagram for explaining a container and a biological sample of a biological sample analyzer according to an embodiment of the present invention, and FIGS. 4 to 6 are biological sample analyzes according to an embodiment of the present invention. It is explanatory drawing for demonstrating the signal amount of the image imaged with the apparatus.

  In operation, a barcode label 118 is attached to the blood collection tube 101. This bar code is printed with patient ID, measurement item, diagnosis item, personal information, parameter information, etc. [FIG. 3 (a)]. Further, in actual operation, depending on the relationship between the diameter of the blood collection tube 101 and the size of the label 118, only a part of the side surface of the blood collection tube 101 may leave the gap 120 and cover the front surface [FIG. 3 (b). ], Which may be entirely covered with a label, and in some cases, may be overlaid on a label paper affixed at the time of shipment. Therefore, the inside is usually in a state that cannot be easily visually observed. The feature of the present invention is to propose a method that can accurately acquire data on the volume and color of a biological sample by a uniform method without changing the method for each specimen in these special circumstances.

  The blood collection tube 101 is fixed to a dedicated fixture 31. In this state, the laser 40 is turned on. When laser light is irradiated to the side surface of the blood collection tube 101, the laser light 41 is strong enough to transmit the paper, so that the contents of the blood collection tube are visible even when the label is entirely covered. [FIG. 3 (c)].

  When white light is used as the irradiation unit 60 and the blood collection tube 101 is additionally irradiated obliquely from above, imaging is performed simultaneously with the irradiation of the white light. By using white light as the irradiation means 60, the layer structure of the biological sample can be more easily recognized due to the synergistic effect of the laser light transmitted through the label and the white light [FIG. 3 (d)]. Although there is no drawing, information on the layer width of the biological sample can be obtained from the image obtained here. Furthermore, since the inside is visible by light irradiation, the color information of the biological sample can be extracted by applying white light.

  An image analysis method that is one of the features of this embodiment will be described. This example is a blood sample collected with a blood collection tube containing a gel-like separating agent, which is centrifuged and separated into three layers from the upper side: serum, separating agent, and blood clot. FIG. 3 (d) shows the result of imaging with the code in place.

The imaging means 70 used in this embodiment is a sensor that can detect three types of colors, R, G, and B, and can identify the intensity of each of the 256 levels from the minimum value 0 to the maximum value 255. The signal amount when converted to gray scale is defined by the square root of the formula ((R / 255) ² + (B / 255) ² + (G / 255) ² ).

  For the image shown in FIG. 3D, along the direction of the arrow 131, information on the gray scale signal amount and the R signal amount, G signal amount, and B signal amount on the center line of the container is acquired. In this embodiment, a case where white light and laser light are simultaneously irradiated will be described. When the white light of the irradiating means 60 is not used, the transmitted light signal of the laser beam is detected as the gray scale signal amount (the lower diagram 202 in FIG. 4), and the RGB signals are obtained separately (the upper diagram 203 in FIG. 4). ).

  FIG. 4 shows an example of the result. The horizontal axis 201 is the coordinate value [pixel] taken along the direction of the arrow 131 of the image, and the vertical axis (202, 203) is the signal amount (grayscale 204, R205, G206, B207). Note that the pixels in the vertical direction of the former image take coordinates so that the value increases toward the bottom of the container, with the uppermost end being 0. The latter value is shown as a value normalized with the maximum value being 1.

  As shown in FIG. 4, unevenness 208 occurs in the signal amount profile due to the influence of shading caused by the print portion 119 and the non-print portion. Since the barcode printing information behaves like noise, the characteristic elements are hidden in it. Data must be processed to extract features from here. However, since the label has individual information on the thickness of the print, the print intervals are not randomly arranged. Therefore, it cannot be removed simply by diverting a method for processing systematic noise as conventionally used. Therefore, a method for excluding the bar code print portion is devised.

  Hereinafter, a method for excluding the bar code print portion will be described.

  First, it is necessary to specify the barcode printing position. The imaging means used in this embodiment is designed so that the narrowest line of the barcode can be read by several pixels or more. As a result, the position of the printed area can be accurately obtained within an error range of about ± 1.

Bar code print information is extracted as follows.
(1) When the barcode is on the camera side The black and white information (printing information) of the barcode is acquired using the transmitted light of the laser. Then, since an image as shown in FIG. 3D is obtained, print information is extracted using this image. The print information is obtained by extracting only monochrome information using a general barcode reader algorithm.

  It should be noted that black and white information can be extracted even when a barcode partially appears on either the left or right side.

(2) When the barcode is on the light source side In this case, black and white information (printing information) is obtained using the transmitted light of the laser if the barcode is visible through the watermark. If the barcode is not visible, there is no need to read it. This is because layer information can be obtained in the state of FIG. 5 without going through the state of FIG.

  This position information is applied to the image, and an area recognized as a barcode printing portion is excluded from the analysis target. FIG. 3E shows an image excluding information on the printed portion, and FIG. 5 shows a graph plotting the signal amount data of this image. The data remaining after excluding the data related to the printed portion corresponds to a portion where the barcode information is not placed, and is a portion that well represents the information of the internal biological sample. As shown in FIG. 5, the above-described processing makes it possible to extract the characteristics of the internal biological sample to some extent.

  Further, in order to facilitate analysis, statistical processing is performed for each area where data is obtained. This is shown in FIG. In FIG. 5, among the local regions where data points remain (this is considered to correspond to the white portion of the barcode), the average value is shown as the center value, and the standard deviation is shown as the error value. It can be seen that by obtaining the data of FIG. 6 excluding the barcode information from FIG. 5, the characteristics of the biological sample appear more clearly.

  The phenomenon appearing in the signal amount analysis result has a characteristic for each layer as described below. Using this property, the position of the boundary surface is specified. Details are shown in FIG. The analyzing unit 80 includes a program in which the judgment of FIG. 7 is converted into an algorithm, and can detect the boundary of each layer based on the data of FIG.

Finally, the volume is calculated using the positional information on the upper and lower boundaries of the serum specified by the above method. Specifically, the height of the serum layer * π * 3.14 * (inner diameter of blood collection tube / 2) ² .

  The above example is an example in which the barcode is in front, but this method can be applied regardless of the position where the barcode is reflected. Then, uniform data processing is possible. This eliminates the need for a function that individually adjusts the amount of light for each specimen according to the presence or absence of a print portion and a test image to confirm the presence or absence of a label, which was an essential function in conventional processing methods. The processing time can be shortened by reducing the number of times. Further, the container rotating operation for searching for the surface on which the barcode is not printed or the surface on which the label is not attached becomes unnecessary.

  By realizing the above embodiment, it is possible to reduce the burden on the operator and the risk of infection associated with the work by reducing the manual work conventionally. In addition, by obtaining information on the volume of serum present in the blood collection tube, it is possible to prioritize measurement items, and as a result, an improvement in the sample processing flow can be expected.

  In the present embodiment, based on the information on the position of the separating agent specified in the first embodiment, it is possible to determine whether or not the centrifugation is performed and to determine which module the sample is sent to. The specific configuration is as follows.

  The biological sample analyzer of Example 1 is installed in the vicinity of the input module 3 (unit 21).

  The position of the separating agent is specified, and whether or not the centrifugation is performed is automatically determined based on the specified position information. If the separating agent is at the bottom of the test tube, the sample is the sample that has not been centrifuged. On the other hand, if the separating agent is not at the bottom, the sample corresponds to the sample that is being centrifuged. This processing is performed by the analysis means 80.

  In the case where the former centrifugation is not performed, the specimen is transported to the centrifugal module 4 as the next processing. On the other hand, in the case where the latter centrifugal separation is performed, the centrifugal module 4 is skipped and conveyed to the opening module 5 or lower as the next processing.

  By this method, the work of the user who has been performed by visual observation is reduced, and stable operation of the system by preventing human error, smooth operation by automatic determination, and faster processing are possible.

  In this embodiment, an example of an analyzer having a function of determining the presence or absence of hemolysis in serum information is shown.

  Conventionally, hemolysis is determined mainly by a method of measuring absorbance in an automatic analyzer. However, in a system equipped with a sample processing / conveying device, a predetermined time is required after the sample is introduced until the sample is conveyed to the automatic analyzer. Therefore, for example, when hemolysis is confirmed and sometimes it is necessary to ask the patient to collect blood again, if the presence or absence of hemolysis is determined by the automatic analyzer, the patient has to wait for a long time and burden It is a great deal. Therefore, it is necessary to quickly determine the presence or absence of hemolysis by a simpler method within the specimen transport automation system. The mechanism will be described below.

  This embodiment meets the above requirements. In this embodiment, white light is used as the irradiation unit 60. The color information of the biological sample can be extracted by applying white light.

  First, a threshold value Rk (k is a rank; k = 1, 2, 3,..., N) for R that is a reference level for determining the presence or absence of hemolysis is set in advance. This threshold value is determined based on the data accumulated so far in another experimental system, and is determined by the degree of influence of hemolysis on the measurement result in the automatic analyzer. To do. This data is stored in the memory of the analysis means 80.

  Further, R / G or R / B or the like may be used as an index instead of using the R value itself as a reference. In this embodiment, for simplification, the method of n = 2 is adopted.

  As a reference for the Rk value, an example 302 of the influence degree 302 on the automatic analyzer and the message 303 output to the display unit of the analysis unit 80 is shown in FIG.

  During operation, in the state of (3) described in FIG. 7 (that is, when transmitted light that has passed through the serum portion is detected), R, G, and B signal amounts are acquired.

  The acquired R is compared with the threshold value previously set in the analyzing means 80, and it is determined which rank it corresponds to.

If R exceeds R ₁ 304, the level of influence on the measurement result in the automatic analyzer is set to a large level, each specimen is removed from the system, and a remeasurement or blood collection instruction 306 is given to the user. On the other hand, if R ₁ 304 or less and R ₂ 305 are exceeded, the processing is continued, but the measurement result in the automatic analyzer may be affected, and a warning message 307 is displayed. In the case of R ₂ 305 or less, it is assumed that there is no influence on the measurement result by the automatic analyzer, and the process is continued without displaying any special message.

  If the above method is used, it is possible to determine the presence or absence of hemolysis in the pretreatment stage. As a result, the time until the output of the measurement result can be shortened. Moreover, it becomes possible to reduce a patient burden.

  In each of the above embodiments, it is possible to provide a biological sample analyzer capable of reducing manual work, improving processing capability, and speeding up treatment.

  Although the invention made by the present invention has been specifically described based on the embodiments, the present invention is not limited to the above-described embodiments, and it goes without saying that the species can be changed without departing from the gist thereof. Nor.

DESCRIPTION OF SYMBOLS 1 Sample pretreatment system 2 Conveyance line 3 Input module 4 Centrifugal module 5 Opening module 6 Labeler 7 Dispensing module 8 Closing module 9 Classification module 10 Storage module 11 Automatic analyzer 20, 21, 22 Unit 30 Base 31 Dedicated fixing Tool 40 Laser light source 41 Laser light (irradiation)
42 Laser light (transmission)
60 White light source 70 Imaging means 80 Analyzing means 90 Control means 101 Blood collection tube 102 Plug 110 Air 111 Serum 112 Separating agent 113 Blood clot 114 Jaundice 118 Bar code label 119 Printing 120 Gap 131 Arrow 201 Horizontal axis (pixel in Y direction)
202 Vertical axis (greyscale signal amount)
203 Vertical axis (R, G, B signal amount)
204 data (grayscale signal level)
205 data (R signal amount)
206 data (G signal amount)
207 data (B signal amount)
208 Unevenness 211 Air / Label Interface 212 Label / Serum Interface 213 Serum / Separant Interface 214 Separation Agent / Clot Interface 221 Signal Amount (Air Layer Passed)
222,225 Signal amount sudden decrease 223,224 RGB ratio change 226 Signal amount rapid increase 227 No signal amount 231 232 Standard deviation 301 Table 302 Influence 303 Message 304 R ₁
305 R ₂
306, 307, 308 Message example

Claims (4)

Information on at least one of the layers composed of two or more types stored in the container is acquired, and the biological sample stored in the container and constituting the layer is analyzed based on the acquired information. An analysis device to perform,
An irradiation means for irradiating the container with light;
Imaging means for irradiating the container with the light emitted from the irradiation means and imaging the transmitted light transmitted through the container;
Analyzing means for processing an image picked up by the image pickup means and obtaining information on the layer in the container;
Control means for controlling the irradiation means and the imaging means,
In the container, at least all or a part of the side surface of the region in which the layer is stored is covered with a label,
The analysis unit excludes the printing information on the label on the image in the image acquired by the imaging unit, and determines the boundary position of the layer based on the signal intensity of the image from which the printing information is excluded. An analyzer characterized by specifying. The analyzer according to claim 1,
The biological sample analysis apparatus characterized in that the analysis means specifies the layer and calculates the volume of the layer based on the information on the boundary position. The analyzer according to claim 1,
The layer contained in the container contains a separating agent;
The analysis device is characterized in that the position of the separating agent is specified, and whether or not the centrifugation process is performed is determined based on information on the specified position. The analyzer according to claim 1,
A second irradiation means for irradiating the container with light having a wavelength different from that of the light;
The biological sample analysis apparatus characterized in that the analysis means identifies the color of the image and determines the quality of the biological sample based on the identified color information.

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