JP2013242246A - Biological sample analyzer and biological sample analytic method - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a biological sample analyzer capable of reducing manual work and improving a throughput.SOLUTION: For example, there are provided a container 103 with a rear face 123 of a special label 121 pasted to an outer wall and with a biological sample housed inside, and irradiation means, imaging means, analyzing means and the like for performing various processing with the container 103 as an object. A color to be a criterion in determining whether a color of the biological sample is normal or abnormal is applied to a prescribed area 124. The imaging means images the area 124 and the biological sample (for example, serum 111 or jaundice 114) beyond the container 103 while the irradiation means irradiates the container 103 with light. The analyzing means processes the imaged image, and determines whether or not the color of the biological sample is normal on the basis of a relative difference between the color of the area 124 and the color of the biological sample.

Description

  The present invention relates to a biological sample analysis apparatus and biological sample analysis method, and more particularly to a technique useful when applied to an analysis apparatus and analysis method for analyzing a biological sample such as blood after selecting it by color or the like. .

  With the advancement of automatic analyzers, the development of sample pretreatment and transfer devices is progressing. The number of items and the number of specimens are increasing year by year, and there is a market need for systems that can be applied to diversifying pretreatment processes. Of these, a particularly strong need is the reduction of user manual work. In fact, not all of the pre-processing steps are automated, and there are still some parts that require manual work by workers.

  A typical example is sample selection. For example, when there is hemolysis or turbidity in serum, it is a fatal injury in assuring the accuracy of the result for blood analysis based on absorbance as a measurement principle. For this reason, it is necessary to remove the sample in advance before being transported to the automatic analyzer, or at least to identify the sample. Moreover, since re-bleeding may be necessary depending on the degree of hemolysis, it is desired to detect the presence or absence of hemolysis at an early stage of the pretreatment process and to quickly respond to the detection result.

  However, in many cases, the serum information of the specimen in the pretreatment stage is checked visually, and an operation of taking out an inconvenient specimen is also performed manually. In particular, detection of jaundice and turbidity is difficult to color-separate from normal serum, and has not been fully automated. In addition, there is a concern that remeasurement due to missing a sample to be taken out, and delay in reporting measurement results accompanying remeasurement.

  It has become a market demand to solve the above-mentioned problems, and for example, a technique for measuring serum information has been created as described in JP-A-63-103945 (Patent Document 1). Further, as described in Japanese Patent No. 2771958 (Patent Document 2), the correction method of the measurement result has been devised, and the measurement accuracy has been improved. Moreover, there exists a technique corresponding to a blood collection tube to which a label is attached, as disclosed in Japanese Patent Application Laid-Open No. 2011-064660 (Patent Document 3) and Special Table 2002-532712 (Patent Document 4).

JP-A 63-103945 Japanese Patent No. 2771958 JP 2011-064660 A JP-T-2002-532712

  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, as in JP 2011-064660 (Patent Document 3) and JP 2002-532712 (Patent Document 4), a technique corresponding to a blood collection tube to which a label is attached is known. Yes. For example, Patent Document 3 proposes a method that includes a peeling unit that peels off a part of a label, and peels off a part on which information is not printed to measure the volume of a biological sample. Patent Document 4 describes a method in which two or more optical probes are provided and the state of an internal biological sample is observed as a preliminary test without contacting the specimen.

  However, at the present time when the processing capability (throughput) of 800 samples per hour is a market requirement, there is a concern that the method of incorporating the bar code peeling operation every time may cause a reduction in processing speed. Also, optical probes are usually expensive, and it is difficult to say that a configuration in which a plurality of optical probes are installed for preliminary tests is sufficient in terms of practicality.

  The present invention has been made in view of the above, and an object of the present invention is to provide a biological sample analyzer capable of reducing manual work and improving throughput. 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.

  Of the inventions disclosed in the present application, the outline of a typical embodiment will be briefly described as follows.

  The biological sample analyzer according to the present embodiment includes a container in which the back surface of the label is attached to the outer wall and the biological sample is stored inside, an irradiation unit, an imaging unit, and an analysis unit that perform various processes on the container. And an automatic analyzer. The irradiating means irradiates the container with light, and the imaging means images the back surface of the label and the biological sample through the container in a state where the light irradiation is performed. The analysis means processes the captured image and determines whether the color of the biological sample is normal or abnormal. The automatic analyzer performs component analysis on the biological sample determined to be normal. Here, the back surface of the label is coated with a reference color serving as a criterion for determining whether the color of the biological sample is normal or abnormal, and the analysis means analyzes the reference color captured through the container and the biological sample. The color of the biological sample is determined based on the relative difference from the color.

  According to the one embodiment, it is possible to reduce manual work and improve throughput in the biological sample analyzer.

1 is a schematic diagram illustrating an example of the overall configuration of a biological sample analyzer according to an embodiment of the present invention. (A)-(e) is a figure which shows the structural example of the special label used with the determination unit in FIG. It is the schematic which shows the structural example of the determination unit in FIG. (A)-(d) is a figure which shows the other structural example of the special label used with the determination unit in FIG. It is explanatory drawing which shows an example of the control method according to the determination result of FIG.

  In the following embodiment, when it is necessary for the sake of convenience, the description will be divided into a plurality of sections or embodiments. However, unless otherwise specified, they are not irrelevant, and one is the other. Some or all of the modifications, details, supplementary explanations, and the like are related. Further, in the following embodiments, when referring to the number of elements (including the number, numerical value, quantity, range, etc.), especially when clearly indicated and when clearly limited to a specific number in principle, etc. Except, it is not limited to the specific number, and may be more or less than the specific number.

  Further, in the following embodiments, the constituent elements (including element steps and the like) are not necessarily indispensable unless otherwise specified and apparently essential in principle. Needless to say. Similarly, in the following embodiments, when referring to the shapes, positional relationships, etc. of the components, etc., the shapes are substantially the same unless otherwise specified, or otherwise apparent in principle. And the like are included. The same applies to the above numerical values and ranges.

  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.

<< Overall configuration and operation of biological sample analyzer >>
FIG. 1 is a schematic diagram showing an example of the overall configuration of a biological sample analyzer according to an embodiment of the present invention. The biological sample analyzer shown in FIG. 1 preprocesses a biological sample (eg, blood) collected from a patient and analyzes the components using an automatic analyzer. The biological sample analyzer includes a plurality of modules such as a transfer line 2, a loading module 3, a centrifuge module 4, an opening module 5, a labeler 6, a dispensing module 7, a closing module 8, a classification module 9, and a storage module 10. Is provided with a preprocessing system 1 having the basic elements. In addition to this, the analysis means 80 for analyzing various data to be acquired and the control means 90 for controlling the entire pretreatment system 1 and the component concentration of the biological sample connected to the pretreatment system 1 and passing through the pretreatment system 1 An automatic analyzer 11 for analyzing the above is provided. The analysis unit 80 and the control unit 90 are realized by a computer system such as a personal computer, for example. Here, a determination unit 22 (22a or 22b) that is a feature of the present embodiment is disposed in the vicinity of the dispensing module 7 or in the vicinity of the centrifugal separation module 4.

  The input module 3 inputs the specimen into the biological sample analyzer. The centrifuge module 4 centrifuges the input specimen. The unplugging module 5 opens the centrifuged sample, and the dispensing module 7 performs subdivided dispensing for distributing the sample to the automatic analyzer 11. The labeler 6 attaches an identifier (for example, the special label 121 in FIG. 2) to the container for subdivision (103 in FIG. 2 described later). The capping module 8 performs capping of the sample, and the storage module 10 stores the capped sample. The classification module 9 classifies sample containers. The transport line 2 is used for transporting specimens between these modules.

  In such a configuration example, the determination of jaundice or the like for a specimen such as blood can be performed using, for example, measurement of absorbance in the automatic analyzer 11. On the other hand, in a system equipped with a sample processing / conveying device as shown in FIG. 1, since a predetermined time is required from when a sample is introduced until the sample is conveyed to the automatic analyzer 11, this time is used. Thus, it is desirable to make a determination of jaundice or the like at an earlier stage in a short time. The biological sample analyzer according to the present embodiment meets such a demand by providing a determination unit 22 (22a or 22b) for determining jaundice or the like. The determination unit 22 is [A] a dispensing module 7 when the subsample after centrifugation and dispensing is a measurement object, and a centrifugation module when [B] the parent sample after centrifugation is a measurement object directly. 4, it is desirable to install each. Hereinafter, the case of the former [A] will be described as an example, but the same applies to the case of the latter [B].

《Special label structure》
FIG. 2A to FIG. 2E are diagrams showing an example of the structure of the special label used in the determination unit in FIG. FIG. 2A shows the surface 122 of the special label 121. Here, information necessary for recognizing the personal ID of the specimen (ie, information on the specimen collection source) is printed in advance (for example, a barcode) 119. FIG. 2B shows a state of the back surface 123 of the special label 121. A color similar to jaundice is preliminarily applied to the predetermined area 124 on the back surface. Here, as shown in FIG. 2C, when the special label 121 is attached to the container (for example, blood collection tube) 103 for dividing the sample by the labeler 6 of FIG. It is designed to have a size that allows a gap to be obtained. Although details will be described later including FIG. 2D and FIG. 2E, the color of the region 124 is used as a reference when determining whether the color of the specimen is normal or abnormal (in this case, whether there is jaundice). The

<Details of judgment unit>
FIG. 3 is a schematic diagram illustrating a configuration example of the determination unit in FIG. The determination unit 22 of FIG. 3 includes a base 30 for connection to the preprocessing system 1, a dedicated fixture 31 for installing a sample, a light source 60, an imaging unit 70, an analysis unit 80, and a control unit 90. The determination unit 22 performs color recognition. For this reason, it is desirable to use a white light source 60. The imaging means 70 is, for example, a color CMOS or CCD camera. Further, the special label 121 described above is attached to the container 103, and a print 119 including information is written on the surface thereof. A gap 120 that is not covered with the special label 121 exists in a part of the side surface of the container 103, and the fixture 31 has a container (specimen) 103 so that the surface on which the gap 120 exists faces the imaging unit 70. Is installed. As described above, the operation of attaching the special label 121 to the container 103 for subdivision is performed by the labeler 6 and does not involve manual operation by the user. Installation is easy.

  Next, a specific determination method and procedure will be described along the sample processing procedure. First, as described above, the processing starts from the work of laying the specimen on the input module 3, and then the specimen is subdivided through a centrifugation process (centrifugal module 4) and an opening process (opening module 5). It is conveyed to the dispensing module 7. In the dispensing module 7, as shown in FIG. 2 (c), a sub-container 103 on which a special label 121 is previously attached by the labeler 6 is prepared. At this time, the back surface 123 of the special label 121 is attached to the side surface (outer wall) of the container (for example, blood collection tube) 103 so as to cover a part of the gap 120, and the special label 121 is attached from the gap 120. The color applied to the area 124 of the back surface 123 of the 121 is in a state where it can be seen through the wall of the container 103.

  The dispensing module 7 dispenses (divides) the serum from the parent sample into the container 103. At this time, the color appearance of the region 124 described above varies depending on the presence or absence of jaundice in the serum. Using this principle, the presence or absence of jaundice is determined. For example, if the degree of jaundice is such that the measurement result of the automatic analyzer 11 in FIG. 1 is not affected, the serum is in a transparent state, so that when viewed from the imaging means 70 in FIG. ), The colored area 124 can be seen through the serum 111. On the other hand, if the degree of jaundice is strong, from the synergistic effect that the serum is cloudy and difficult to transmit light and the color of the region 124 is similar to the color of jaundice, the imaging means 70 of FIG. When viewed, the colored area 124 cannot be seen by the jaundice 114, as shown in FIG. The degree of jaundice is determined by this difference.

  More specifically, in FIG. 3, the light from the light source 60 (for example, white light) is irradiated from the back side of the container 103 and the transmitted light is imaged by the imaging unit 70 on the front side of the container 103. The operation timing and the like at this time are determined by the control means 90. Then, the analysis unit 80 analyzes the image acquired by the imaging unit 70 by software processing or the like, and determines the presence or absence of jaundice based on the relative difference between the color of the region 124 and the color of the specimen. Although not particularly limited, in FIG. 2D, the imaging unit 70 detects, for example, an edge of the region 124, and if the intensity of the edge is larger than a predetermined value, there is no jaundice, and if it is smaller than the predetermined value. It is determined that there is jaundice. Alternatively, for example, whether or not the RGB (R: Red, G: Green, B: Blue) component of the specimen portion outside the region 124 is within a predetermined range centered on the RGB component of the inner portion of the region 124. Is determined. If it is within a predetermined range (that is, if it is the same or similar), it is determined that there is jaundice, and if it is outside the predetermined range (that is, if it is not similar), it is determined that there is no jaundice. In addition, the installation location of the light source 60 is not necessarily limited to the back side of the container 103, and may be the front side of the container 103 or the like depending on circumstances.

  If such a method is used, the degree of jaundice can be determined easily or at low cost. Further, since it is possible to determine the presence or absence of jaundice at an early stage of the preprocessing without waiting for conveyance to the automatic analyzer 11, it is possible to improve the throughput accompanying the analysis of the biological sample. Further, by reducing the conventional manual work, it is possible to reduce the burden on the worker and the risk of infection accompanying the work, and it is possible to prevent problems associated with human error. Note that the degree of color of the region 124 is not necessarily fixed, and can be appropriately determined for each user.

  By the way, as a comparative example, for example, instead of such a relative evaluation using the reference color (124), a method of simply imaging a specimen and absolutely evaluating the color can be considered. However, in this case, it may not be easy to determine determination conditions for absolute evaluation due to differences in imaging environment for each user. On the other hand, when the relative evaluation method as in the present embodiment is used, the difference in the imaging environment is similarly reflected in the reference color (124) together with the color of the sample. It is possible to determine whether the quality is good or bad with high accuracy without being influenced by the difference in the imaging environment.

《Special label structure (variation)》
FIG. 4A to FIG. 4D are diagrams showing other structural examples of the special label used in the determination unit in FIG. Here, it is assumed that hemolysis is determined, the degree of hemolysis is divided into three stages in advance, and two colors corresponding to each boundary are applied to the back surface 123 of the special label 125 as shown in FIG. deep. That is, as shown in FIG. 4 (a), for example, the first reference 126 indicating the color of hemolysis that requires re-bleeding and the first reference 126 that is lighter than the first reference 126 and can continue the processing with a flag. A second reference 127 representing the color of hemolysis is applied. Using such a special label 125, serum is dispensed into the container 103 in the same manner as described above, and then the color on the back of the label is compared with the color of the serum. At this time, the following results are obtained depending on the state of hemolysis.

[1] At the time of hemolysis to the extent that recollection is necessary In this case, the serum is red, and the degree is deeper than the first standard 126 (and the second standard 127). Therefore, as shown in FIG. 4B, both colors (126, 127) applied to the back side of the label are not detected by the high degree of hemolysis 115a.

[2] When the process continues but hemolysis requires flagging In this case, the degree of redness of serum is lighter than the first standard 126 and darker than the second standard 127. Therefore, as shown in FIG. 4C, one color (126) applied to the back side of the label is detected by hemolysis 115b having a low degree, but the other color (127) is not detected.

[3] When there is no hemolysis sufficient for measurement (normal) In this case, as shown in FIG. 4 (d), it is possible to foresee both the first reference 126 and the second reference 127 with the transparent serum 111. As a result, both colors (126, 127) are detected.

<Control method during hemolysis>
FIG. 5 is an explanatory diagram illustrating an example of a control method according to the determination result of FIG. In FIG. 5, each hemolysis degree 201 (that is, [1] high hemolysis 202 corresponding to FIG. 4B, [2] low hemolysis 203 corresponding to FIG. 4C, [3] FIG. 4 ( An example of the processing content 211 and the message 221 corresponding to each is shown according to normal 204 corresponding to d). The processing content 211 is performed by the control unit 90 of FIGS. 1 and 3, and the message 221 is displayed by the control unit 90.

  First, when the determination of high hemolysis 202 in [1] above is performed, the processing of the sample is stopped, the sample is discharged to the discharge port of the system (212), and a message for instructing blood collection is displayed. Output (222). Next, when the determination of the low hemolysis 203 in [2] above is performed, for example, the processing is continued, and the automatic analyzer 11 avoids examination items that are easily affected by hemolysis and is affected by hemolysis. Measurement is performed with priority given to difficult inspection items (213). At this time, a message indicating that there is a low level of hemolysis is displayed, and a flag is added to the sample for management in the data (223). When the determination of normal 204 in [3] above is made, the processing as planned is continued (214).

  As described above, since the serum information existing in the blood collection tube can be obtained at an early stage by using the methods as shown in FIGS. 4 and 5, if prioritization of measurement items or recollection is necessary, an instruction is given at an early stage. It becomes possible. As a result, the sample processing flow can be improved more efficiently (that is, the throughput is improved), and the time until the result report can be shortened. In FIGS. 4 and 5, hemolysis is determined in three stages. Of course, the number of stages and the color of the reference can be changed as appropriate according to the user, and a detailed workflow can be made accordingly. It is also possible to configure for each user.

  As mentioned above, the invention made by the present inventor has been specifically described based on the embodiments. However, the present invention is not limited to the above-described embodiments, and various modifications can be made without departing from the scope of the invention.

  For example, in FIG. 2, the color of the region 124 can be set in a plurality of stages as shown in FIG. Moreover, it is also possible to use FIG. 2 and FIG. 4 in combination. That is, for example, in FIG. 4A, it is also possible to apply the region 124 of FIG. 2B under the second reference 127 and determine jaundice and hemolysis. In some cases, an abnormality may be found in the specimen before the centrifugation, and from this viewpoint, the determination unit 22 can be provided in the input module 3 or the like in FIG.

  Here, as shown in FIG. 2 and the like, the label was attached to the container with a gap provided in part, and imaging was performed from this gap. However, in some cases, the label was attached without providing a gap. It is also possible to use a form in which an image is picked up through a label. In this case, as shown in FIG. 3, the light source and the imaging means are arranged so as to face each other with the container interposed therebetween. Furthermore, in the present embodiment, since a method of capturing an image inside the container and performing analysis is used, depending on the case, not only serum information but also a serum amount can be measured at the same time. In this case, the sample processing flow can be improved to be more efficient, and the serum amount and serum information can be detected by one unit, so that it can be expected to contribute to cost reduction of the apparatus.

  DESCRIPTION OF SYMBOLS 1 ... Pretreatment system, 2 ... Conveyance line, 3 ... Loading module, 4 ... Centrifugal module, 5 ... Opening module, 6 ... Labeler, 7 ... Dispensing module, 8 ... Closing module, 9 ... Sorting module, 10 ... Storage module, 11 ... automatic analyzer, 22, 22a, 22b ... determination unit, 30 ... base, 31 ... fixing tool, 60 ... light source, 70 ... imaging means, 80 ... analyzing means, 90 ... control means, 103 ... container, 111 ... Serum, 114 ... Jaundice, 115a ... Hemolysis (High), 115b ... Hemolysis (Low), 119 ... Printing, 120 ... Gap, 121 ... Special label, 122 ... Front, 123 ... Back, 124 ... Area, 125 ... special label, 126 ... first standard, 127 ... second standard, 201 ... hemolysis degree, 211 ... processing content, 221 ... message, 202-204 ... division of hemolysis degree, 12-214 ... processing content classification of, division of 222, 223 ... message.

Claims (15)

A container in which the back side of the label is affixed to the outer wall and a biological sample is stored inside;
Irradiating means for irradiating the container with light;
Imaging means for imaging the back surface of the label and the biological sample through the container in a state where light irradiation is performed by the irradiation means;
Processing the image captured by the imaging means, and analyzing means for determining whether the color of the biological sample is normal or abnormal;
An automatic analyzer that performs component analysis on the biological sample determined to be normal by the analysis means,
On the back surface of the label, a reference color that is a criterion for determining whether the color of the biological sample is normal or abnormal is applied,
The biological sample analyzing apparatus that determines the color of the biological sample based on a relative difference between the reference color imaged through the container and the color of the biological sample. The biological sample analyzer according to claim 1,
The biological sample is blood;
The analysis means is a biological sample analyzer for determining the presence or absence of jaundice or the presence or absence of hemolysis in the blood. The biological sample analyzer according to claim 2,
An apparatus for analyzing a biological sample in which a print including information on a collection source of the biological sample is written on a surface of the label. The biological sample analyzer according to claim 3, wherein
The label is affixed to cover the outer periphery of the container leaving a part of the gap,
The said imaging means is a biological sample analyzer which images the back surface of the said label through the said clearance gap. The biological sample analyzer according to claim 3, wherein
The analysis device of a biological sample that makes a determination based on whether or not the reference color can be identified due to the color of the biological sample. The biological sample analyzer according to claim 3, wherein
On the back surface of the label, a plurality of reference colors having different color degrees are applied as the reference colors,
The plurality of reference colors serve as determination criteria when determining how abnormal the color of the biological sample is,
The biological sample analyzing apparatus that determines the color of the biological sample based on a relative difference between the plurality of reference colors imaged through the container and the color of the biological sample. The biological sample analyzer according to claim 6, wherein
Furthermore, a control means for controlling each process performed in the biological sample analyzer,
Among the plurality of reference colors, a first color corresponding to the degree that re-bleeding is necessary and a second color corresponding to the degree that the process can be continued are included,
The control means notifies the user when the analysis means determines that the re-collection is necessary, and responds to the case when the analysis means determines that the process can be continued. A biological sample analyzer that manages a biological sample to be distinguished from other biological samples and transports the biological sample to the automatic analyzer. The biological sample analyzer according to claim 3, wherein
An apparatus for analyzing a biological sample, wherein the irradiating means and the imaging means are installed at positions facing each other across the container. (A) a step of preparing a container in which a back surface of a label is attached to an outer wall and a biological sample is stored therein;
(B) irradiating the container with light;
(C) In a state where the light irradiation is performed, imaging the back surface of the label and the biological sample through the container;
(D) a computer system processes the captured image and determines whether the color of the biological sample is normal or abnormal;
(E) comprising a component analysis for the biological sample determined to be normal,
On the back surface of the label, a reference color that is a criterion for determining whether the color of the biological sample is normal or abnormal is applied,
In the step (d), the color of the biological sample is determined based on a relative difference between the reference color imaged through the container and the color of the biological sample. The biological sample analysis method according to claim 9,
The biological sample is blood;
In the step (d), the biological sample analysis method in which the presence or absence of jaundice or the presence or absence of hemolysis in the blood is determined. The biological sample analysis method according to claim 10,
A method for analyzing a biological sample, wherein a print including information on a collection source of the biological sample is written on a surface of the label. The biological sample analysis method according to claim 11,
The label is affixed to cover the outer periphery of the container leaving a part of the gap,
In the step (c), the biological sample analysis method in which the back surface of the label is imaged through the gap. The biological sample analysis method according to claim 11,
In the step (d), the biological sample analysis method in which determination is performed based on whether or not the reference color can be identified due to the color of the biological sample. The biological sample analysis method according to claim 11,
On the back surface of the label, a plurality of reference colors having different color degrees are applied as the reference colors,
The plurality of reference colors serve as determination criteria when determining how abnormal the color of the biological sample is,
In the step (d), the color of the biological sample is determined based on a relative difference between the plurality of reference colors imaged through the container and the color of the biological sample. The biological sample analysis method according to claim 14,
Among the plurality of reference colors, a first color corresponding to the degree that re-bleeding is necessary and a second color corresponding to the degree that the process can be continued are included,
The biological sample analysis method further includes: (f) if it is determined that the re-collection is necessary in the step (d), notifies the user to that effect, and the processing is continued in the step (d). If it is determined that the biological sample corresponding to the biological sample can be distinguished from other biological samples, the biological sample analysis method includes a step of performing component analysis of the corresponding biological sample.

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