JP5470295B2 - Biological sample analyzer and method - Google Patents

Description

  The present invention relates to a biological sample analyzer for analyzing a biological sample such as blood collected in a container, and performs automatic grasping of component separation states, and in particular, the volume of a part (element) used for measurement. The present invention relates to a technology that contributes to optimization of a processing flow for managing an analysis process including a combination of items and a large number of samples.

  Conventionally, an automatic analyzer for analyzing the concentration of a component using a biological sample has been provided. In addition, a process (hereinafter referred to as “preprocess”) that is performed before the biological sample is introduced into the automatic analyzer and a pretreatment system that automatically transports the specimen to the automatic analyzer are put on the market. The system continues to advance, and to date, many parts of the pretreatment process have been automated.

  One of them is a technique related to specimen checking. Among them, as a technique related to the measurement of the amount of specimen, for example, a specimen by installing an imaging means as described in JP-A-11-37845 (Patent Document 1), JP-A-2001-165552 (Patent Document 2), etc. A technique for the automatic detection of quantities has been invented.

  According to the above technique, it is possible to measure the amount of the sample in the pretreatment process that is a stage before being transferred to the automatic analyzer. The number of items that can be measured can be ascertained in advance, the processing flow has been improved, and incidental effects such as prevention of clogging errors in the automatic analyzer have been obtained. It has also contributed to reducing the amount of work, such as eliminating the need for visual checks by users (inspectors).

JP 2000-46837 A

  By the way, one of the biological samples, blood collection, uses a dedicated blood collection tube. There are several types of blood collection tubes, and they are properly used depending on the purpose. For example, a blood collection tube that does not contain a separating agent is used for items that measure whole blood, such as a blood cell test, and items that measure plasma, such as a coagulation test. On the other hand, blood collection tubes containing a separating agent are used in fields where serum is a measurement target, such as biochemical analysis and immunoassay. There are several types of separation agents, and typical examples include gel-like and bead-like ones having different shapes.

  When these samples are subjected to a centrifugal separation process as a part of the pretreatment, the difference in appearance becomes remarkable. Specifically, after centrifugation, a blood collection tube that does not contain a separation agent has a two-layer structure, whereas a blood collection tube that contains a separation agent has a three-layer structure. In addition, the gel-like separating agent separates the layers relatively clearly, whereas the bead-like separating agent may be mixed between the two layers around the boundary of the separated layers.

  The sample transport automation system is charged with a mixture of the above-described various types of samples. There are differences in appearance characteristics and optical characteristics depending on the type of blood collection tube to be handled, so there is no measurement method applicable to all flowing samples, and it is difficult to determine the amount of samples. It was.

  Patent Document 1 describes a sample transport device that omits the opening process for a sample container that has failed to be centrifuged. However, a method for determining whether or not the centrifugation has failed is not disclosed.

  Therefore, an object of the present invention is to manually determine the quality of a centrifuge, the amount of analysis sample, etc. automatically in an apparatus that performs pretreatment of a sample to be put into an automatic analyzer that analyzes the component concentration of a biological sample. An object of the present invention is to provide a biological sample analyzer capable of reducing work, improving processing capability, and speeding up treatment.

  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, the outline of a representative thing is to acquire information on at least one layer among two or more types of layers stored in a container, and based on the acquired information, the container stores the information in the container. An analyzer for analyzing a biological sample constituting a layer, comprising: an irradiating means for irradiating light to a container; and an imaging means for detecting transmitted light transmitted through the container by irradiating light by the irradiating means; The container is provided with an analysis unit that covers all or a part of a side surface with a label, and that analyzes information on a boundary position of a layer inside the container based on a signal intensity detected by the imaging unit. .

Further, another representative outline is a biological sample analyzer for analyzing a biological sample stored in a container, the container is covered with a label all or part of the side surface,
Identification means for detecting the presence of the container and identifying the ID, first irradiation means for irradiating the side surface of the container with light that is susceptible to dimming by the label, and the label on the side surface of the container A second irradiating means for irradiating light having a property of transmitting light, an imaging means for imaging light transmitted through the container by light emitted from the first and second irradiating means, and the imaging means. Analyzing means for processing the captured image, and analyzing means for analyzing information on the boundary position of the layer inside the container based on the signal intensity detected by the imaging means.

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

  In other words, unlike the conventional method, the effect obtained by a typical one is not directly targeted for measurement of the capacity measurement part. Measurement accuracy can be improved by selecting and analyzing a portion that has no influence in the first place. In addition, more accurate measurement values can be provided by using the blood ratio as an external parameter. There is a consistent processing procedure for all the samples handled by the system, and the use of this makes it possible to simplify the processing.

  In addition, by obtaining information on the volume of serum present in the blood collection tube, it is possible to prioritize measurement items. In addition, by automatically determining whether or not the centrifugation is performed from the detection result of the component separation state, it is possible to reduce the work of manually inputting information related to the centrifugal processing that has been conventionally required. 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 a label, and there is no need to change the appropriate method for each test tube. Regardless, consistent processing can be performed and the time to report the results 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 a block diagram which shows the structure of the unit which concerns on one embodiment of this invention. It is explanatory drawing for demonstrating the container and biological sample of the analyzer of the biological sample which concerns on one embodiment of this invention. It is explanatory drawing for demonstrating the profile of the permeation | transmission amount of the light with respect to the biological sample acquired with the biological sample analyzer which concerns on one embodiment of this invention. It is a flowchart which shows the whole process including the imaging mechanism and process of the analyzer of the biological sample which concerns on one embodiment of this invention. It is a flowchart which shows a part of process including the imaging mechanism and process of the analyzer of the biological sample which concerns on one embodiment of this invention. It is a block diagram which shows the unit arrange | positioned at the input module of the biological sample analyzer which concerns on one embodiment of this invention. It is explanatory drawing for demonstrating the profile of the permeation | transmission amount of the light with respect to the biological sample acquired with the biological sample analyzer which concerns on one embodiment of this invention. It is a flowchart which shows the whole process in the unit 22 arrange | positioned at the input module of 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 block diagram showing a centrifugal module and a unit disposed in a biological sample analyzer according to one embodiment of the present invention, and FIG. 3 is a block diagram showing the configuration of the unit according to one embodiment of the present invention. is there.

  In FIG. 1, a biological sample analyzer includes a transport line 2, a loading module 3, a centrifuge module 4, a plugging module 5, a labeling label 5, a labeling module 7, a dispensing module 7, a capping module 8, a classification A preprocessing system 1 composed of a plurality of modules having the module 9 and the storage module 10 as basic elements, an analysis means 80 for analyzing various data to be acquired, a control means 90 for controlling the entire preprocessing system 1, and beyond The automatic analyzer 11 is configured to analyze the components of the connected biological sample. The unit 21 which is a feature of the present embodiment is installed in the centrifuge module 4.

  Briefly describe the role of each module. First, the loading module 3 is a portion for loading the specimen 110 into the biological sample analyzer. The centrifuge module 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 an identifier (for example, the barcode 103) to the container for subdivision. The capping module 8 opens the specimen, and the storage module 10 sorts the specimen container.

  In FIG. 2, main elements constituting the centrifugal separation module 4 are a conveyance line 2, a centrifuge 30, an adapter 40, a chuck 50, and a gripper 51. Here, the adapter 40 is a mechanism for temporarily storing the specimen to be input to the centrifuge 30, the chuck 50 is a mechanism for transferring the specimen moving on the line to the adapter, and the gripper 51 is the adapter 40 for moving the adapter 40 to the centrifuge 30. It is a mechanism for transferring to. In addition, the transport line 2 includes an upstream 2a that mainly transports a holder on which a sample is placed and a downstream 2b that mainly transports a holder on which a sample is not mainly placed, each indicated by an arrow (60 to 67) in the figure. Operate in the direction.

  And the unit 21 which concerns on one embodiment of this invention is installed in the position shown in FIG. A part of the conveyance path 2 passes through the inside of the unit 21. There are two branch points (71, 72) in the middle, which are positions where biological samples are analyzed. The analysis result is used as a judgment material for determining the processing flow / destination of the subsequent specimen. Also, RFID reading / writing means for identifying the holder is embedded at the branch point, and the analysis result is immediately recorded as information on the RFID of the holder.

  In FIG. 3, the main elements constituting the unit 21 are two irradiation means (201, 202), one imaging means 211, an analysis means 80 for analyzing an image acquired by the imaging means 211, and two irradiation means (201). 202) and the image pickup means 211.

  In the present embodiment, a white light source is used for the irradiation means (201, 202). Employing a laser as the light source is also effective because the effect is large when the amount of light is strong.

  In addition, CMOS is used for the imaging unit 211. Alternatively, a CCD may be used. The image pickup means 211 is installed on the rotation shaft 212 and has a structure that can rotate in the direction of the arrow 213 in the figure, so that two positions (71, 72) can be picked up by one image pickup means. In addition, the distance, aperture, and focus are adjusted so that the entire blood collection tube can be seen.

  In addition, a black background film 220 is installed in a portion connected to the transport line 2 so that outside light does not enter.

  An analysis unit 80 that acquires and analyzes image data is connected to the tip of the imaging unit 211. The irradiating means (201, 202) and the imaging means 211 are controlled by a command by an electrical signal from the control means 90.

  Next, details of measurement by the unit 21 of the analyzer according to the embodiment of the present invention will be described.

  First, the specimen 110 to be handled will be described with reference to FIG.

  FIG. 4 is an explanatory diagram for explaining the container and holder of the biological sample analyzer and the biological sample according to the embodiment of the present invention. A biological sample is collected using a dedicated blood collection tube 102 (FIG. 4G). Further, in the system, the blood collection tube 102 is transported by being installed on a dedicated holder 101 (FIG. 4 (h)).

  There are several types of specimens 110, and attention can be given to the difference in appearance, which can be classified into six types.

  4A includes a gel-like separation agent 131 and a specimen 111 that has not been subjected to a centrifugal separation process, and FIG. 4B includes a bead-like separation agent 132 that is not subjected to a centrifugal separation process. FIG. 4C shows a specimen 113 that does not contain a separating agent and has not been subjected to centrifugation.

  All of the three types of samples are in the state of whole blood 121 at the time of collection.

  FIG. 4D shows a specimen 114 that contains a gel-like separation agent 131 and has already been subjected to a centrifugal separation process, and FIG. 4E shows a specimen that contains a bead-like separation agent 132 and has already undergone a centrifugal separation process. 115.

  4D and 4E are separated into a layer made of serum 122 and a layer made of clot 123 by centrifugation.

  FIG. 4F shows a specimen 116 that does not contain a separating agent and has already been subjected to a centrifugal separation process.

  This specimen is separated into a layer made of plasma 124 and a layer made of blood cells 125.

  Next, the operation will be described.

  A label (barcode) 103 is affixed to the blood collection tube 102. This label 103 is printed with patient ID, measurement item, diagnosis item, personal information, parameter information, and the like. In actual operation, depending on the relationship between the diameter of the blood collection tube 102 and the size of the label 103, the entire side surface of the blood collection tube 102 may be covered with the label. Moreover, depending on the case, it may affix on the label stuck 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 for accurately measuring the volume of a biological sample with a consistent processing procedure without changing the method for each specimen in these special circumstances.

  For this purpose, the internal state is grasped from the shape of the profile, and it is determined whether the state is in FIG. This will be described with reference to the following processing flow.

  A sample processing procedure (processing flow) will be described along a time series.

  First, the collected specimen is installed on the holder 101 together with the blood collection tube 102 and is introduced into the system via the input module 3. The specimen 110 put into the analyzer is transported to the centrifuge module 4 through the loading module 3 as described above.

  When entering the centrifuge module 4, the specimen 110 proceeds in the direction of the arrow 60 and reaches the branch point 71 that is the first measurement point.

  At the branching point 71, the specimen 110 proceeds in either the direction of stopping at the centrifuge module 4 (arrow 62) or the direction of passing without entering the centrifuge module 4 (arrow 61) according to the command of the control means 90. Note that an RFID read / write function (not shown) installed in the holder 101 is provided at the bottom of the branch point 71.

  At the branch point 71, the specimen 110a is temporarily stopped. When the operation is temporarily stopped, information indicating that the sample exists is transmitted to the control unit 90 via the RFID reading function. Measurement starts with this information as a cue. The control unit 90 instructs the imaging unit 211 to face the sample 110a, and the imaging unit 211 that has been facing an arbitrary direction so far faces the sample 110a. Next, the control unit 90 issues a command to the irradiating unit 201 and the imaging unit, and the irradiating unit 201 irradiates, and at the same time, the imaging unit 211 performs imaging.

  Data acquired by imaging is transmitted to the analysis unit 80. The analysis unit 80 analyzes data. The analysis result is transmitted to the control means 90, and the destination of the sample is instructed based on the analysis result information.

  The analysis will be described below.

  The characteristics of the image data captured by the unit 21 of the analyzer according to the embodiment of the present invention and the analysis method (processing flow) will be described with reference to FIGS.

  FIG. 5 is an explanatory diagram for explaining a profile of the amount of light transmitted to the biological sample acquired by the biological sample analyzer according to the embodiment of the present invention, and FIG. 6 is an embodiment of the present invention. It is a flowchart which shows the whole process including the imaging mechanism and process of the analyzer of the biological sample which concerns.

  The information to be obtained at the first branch point 71 is whether or not the sample 110a that has flowed is centrifuged. This information is used to determine the next destination for the specimen 110a, i.e., whether to drop or pass the specimen to the centrifuge module 4.

  In this regard, whether or not the centrifugation is performed can be determined by the position of the separating agent or the number of boundaries. That is, when focusing on the separation agent, in the specimens (111, 112) that have not been centrifuged, the separation agent is present at the bottom of the blood collection tube (FIGS. 4A and 4B). On the other hand, in the specimens (114, 115) that have been subjected to centrifugation, the separating agent is present in the central portion of the blood collection tube [FIGS. 4 (d), (e)]. In the case where there is no separation agent, the specimen 113 that has not been subjected to the centrifugation is one layer [FIG. 4C], whereas the specimen 116 that has been subjected to the separation is composed of two layers [FIG. 4 (f)]. These features appear as a difference in the amount of light transmitted to the specimen 110, as will be described next. It is assumed that the presence or absence of the centrifugal separation is discriminated using the characteristics found in the profile of the amount of transmitted light.

  Regarding the light transmittance, the separating agent (131, 132) transmits light well, whereas the layers of whole blood 121, blood clot 123, and blood cell 125 do not transmit light very well. In addition, it is known that serum 122 and plasma 124 are slightly permeated. The present invention pays attention to this natural phenomenon and utilizes the property.

  FIG. 5 shows the permeation amount obtained when the specimen 110a is irradiated by the unit 21 of the analyzer according to the embodiment of the present invention. The horizontal axis is the position with respect to the blood collection tube, and the origin side corresponds to the upper surface side of the blood collection tube (the side close to the stopper 104). In addition, since the coordinate of a horizontal axis shows the position on the side surface of the blood collection tube 102, the figure of the blood collection tube was shown side by side in order to make correspondence easy to understand. The vertical axis is the amount of light transmitted, and is normalized with reference to the amount of light transmitted through the most transmissive part (usually the part where no label or inclusion is present).

  Next, the characteristics of the permeation amount will be described for each state of the separating agent.

  (I) A specimen 111 that contains a gel-like separating agent 131 and has not been centrifuged.

  FIG. 5A shows a transmission amount profile 141. The amount of light (141a) that has passed through only the blood collection tube is the largest, and the amount of transmission decreases due to the influence of the label (141b). Since the whole blood 121 does not transmit light, the amount of transmission is close to 0 (141c). Note that, in the whole blood 121 portion, the transmittance decreases to a value close to 0 regardless of the presence or absence of the label 103, so that this region is a region that is not easily affected by the label 103. The permeation amount increases in the part of the separating agent 131 (141d), and the permeation amount further increases in the part without the label (141e). In addition, when the position of the upper surface of the label 103 is lower than the upper surface of the whole blood 121, the step of reducing the amount of light (141b) due to the influence of the label 103 is not performed, and the amount of transmission (141a) of the blood collection tube 102 is The value drops to a value close to 0 (141c).

  (Ii) A specimen 112 that includes a bead-shaped separating agent 132 and has not been centrifuged.

  FIG. 5B shows a transmission amount profile 142. The characteristics are almost the same as the case (i) (141, FIG. 5 (a)). However, since the separation agent 132 has a bead shape, it is slightly shielded from the amount of the gel-like separation agent 131 that permeates from the entire layer (142a, 142b).

  (Iii) A specimen 113 that does not contain a separating agent and has not been centrifuged.

  FIG. 5C shows a transmission amount profile 143. The portion shielded by the whole blood 121 occupies many areas (143a). Near the origin (143b), there is an influence of light that has passed through only the blood collection tube 102 and light shielding by the label (143c, 143d). Further, the bottom aspect of the blood collection tube 102 becomes a lens effect, and the amount of light to be detected increases locally (141e).

  (Iv) A specimen 114 containing a gel-like separating agent 131 and being subjected to centrifugation.

  FIG. 5D shows a transmission amount profile 144. As in the case (i), in the portion above the blood collection tube 102, the amount of light (144a) that has passed through only the blood collection tube is the largest, and the amount of transmission once decreases due to the influence of the label (144b). Further, the amount of permeation decreases due to the shielding of the serum 122 (144c). Thereafter, the amount of permeation increases due to the influence of the separating agent 131 (144d), decreases again at the clot 123, and becomes a value close to 0 (144e). Note that the transmissivity of the blood clot 123 decreases to a value close to 0 regardless of the presence or absence of the label 103, so this area is an area that is not affected by the label 103. In addition, there is a point where the detected light amount locally increases due to the lens effect at the bottom of the blood collection tube 102 (144f).

  (V) A specimen 115 including a bead-shaped separating agent 132 and being subjected to centrifugation.

  FIG. 5E shows a transmission amount profile 145. The characteristics are almost the same as the case (iv) (144) and FIG. 5 (d)). However, the portion of the separating agent 132 is slightly light-shielded as compared with the permeation amount of the gel-like separating agent 131 that is transmitted from the entire layer (145a).

  (Vi) A specimen 116 that does not contain a separating agent and is centrifuged.

  FIG. 5F shows a transmission amount profile 146. Except for no increase in permeation amount due to the separating agent (131, 132), it is almost the same as the cases (iv), (v).

  Using the above features, determine the presence or absence of centrifugation in a consistent procedure. Therefore, processing is performed according to the following flow.

  FIG. 6 shows a flowchart. The irradiation means is irradiated (S101), the transmission amount data is acquired (S102), and then the analysis process is started.

  First, a specimen (111, 112) that contains a separating agent and has not been centrifuged is identified. As a feature common to the above (i) to (vi), in the case where the separating agent is at the bottom, there is a portion having a width and a large permeation amount (flat portion) [141d, 141e in FIG. 5 (b) 142a, 142b]. On the other hand, in the case where the separating agent is not present at the bottom, there is no region with a large permeation amount. This feature is a content that can be extracted regardless of conditions such as the presence or absence of a label and the position of attachment. Of the above data, the amount of permeation at the bottom of the blood collection tube 102 is measured (S103). If there is a wide area where the amount of permeation is large in the measured part, it is regarded as a specimen (111, 112) that contains a separating agent and has not been subjected to centrifugation (S104).

  On the other hand, when there is no region with a large amount of transmission, the state of the specimen 110a corresponds to one of the four types shown in FIGS. 5 (c) to 5 (f). Of these four samples, only the sample that has not been centrifuged is FIG. 5C, and this sample 113 can be specified by paying attention to the number of boundaries found in the profile.

  A method for counting the number of boundaries will be described. First, a feature common to FIGS. 5C to 5F is that the amount of light locally increases at the bottom of the blood collection tube 102. This is because the aspect of the blood collection tube 102 functions as a lens. First, the points (143e [FIG. 5 (c)], 144f [FIG. 5 (d)], 145b [FIG. 5 (e)], 146a [FIG. 5 (f)]) where the light amount increases locally are found. Starting from this point, the transmission amount is scanned in the direction of the upper part a of the specimen 110. The points where the amount of transmission increases rapidly or decreases during scanning are counted. This number is the boundary number N. For example, in FIG. 5C, when the transmission amount is scanned from a point (143e) having a large transmission amount locally toward the upper surface of the blood collection tube 113, the first rising point (143f) and the second time There is an ascending point (143 g), and N is 2. In FIG. 5D, there are three ascending points (144g, 144i, 144j) and one decreasing point (144h), and N is 4. Similarly, N is 4 in FIG. 5 (e), and N is 3 in FIG. 5 (f). Note that, in a scene where the upper surface of the label 103 and the upper surface of the biological sample overlap, there is no decrease in light shielding by the label 103, and thus N is a value one smaller than the above values.

  As described above, the number of boundaries is counted (S105). When the number of boundaries is 1, the sample is regarded as an unexecuted sample (113) (S104). On the other hand, a sample having a boundary number of 3 or more is regarded as a sample (114, 115, 116) that has been centrifuged (S106). In the case of the boundary number 2, (i) a state in which the upper surface of the plasma 124 and the upper surface of the label 103 are overlapped with each other in the sample (116) that is not centrifuged and is centrifuged (ii) There are two possibilities: the state of the specimen (113) that does not contain an agent and has not been centrifuged. As a method for identifying this, the position (143f, 146b) of the point at which the amount of permeation increases sharply for the first time is obtained (S107), and if this position is closer to the upper part than the center position of the blood collection tube, the latter ( ii).

  Whether or not the centrifugation is performed is determined according to the processing flow described above. A sample that has not been centrifuged needs to be put into the centrifuge module (S108). The control unit 90 instructs the sample to move in the direction of the arrow 62 at the branch point 71. On the other hand, the specimen that has already been centrifuged may pass through the centrifuge module 4 (S109). The control means 90 instructs the sample to move in the direction of the arrow 61 at the branch point 71.

  The analysis unit 80 includes a program that is an algorithm for the above flow.

  Next, the measurement at the branch point 72 will be described.

  At the branch point 72, the sample that has been centrifuged is transported from the arrow 65. In addition, the specimen that has not been introduced into the centrifuge module 4 at the branch point 71 is transported. Even at the branch point 72, the sample is temporarily stopped for measurement.

  Similarly to the branch point 71, the branch point 72 is controlled by the control unit 90, the imaging unit 211 faces the sample 110 b, the irradiation unit 202 is irradiated toward the sample, and the imaging unit 211 simultaneously performs imaging. . Data acquired by imaging is transmitted to the analysis means 80 and subjected to analysis. The analysis result is transmitted to the control means 90, and the destination of the sample is instructed based on the analysis result information.

  The specimens at the branch point 72 are all specimens that have been subjected to centrifugation, and the obtained transmittance data is narrowed down to the three types shown in FIGS. Here, the position of the upper surface of the serum 122 or plasma 124 to be measured by the automatic analyzer is measured. The method will be described below.

  The sample amount is measured separately for the sample (114, 115) containing the separating agent (131, 132) and the sample (116) not containing the sample. Since the separating agent has a property of transmitting light, there are portions where the amount of transmission increases (144d, 145a) in a scene including the separating agent (131, 132). Both classifications are performed using this feature.

The actual procedure will be described with reference to FIG. FIG. 7 is a flowchart showing a part of the processing including the imaging mechanism and processing of the biological sample analyzer according to the embodiment of the present invention. The light source is irradiated (S201), transmission amount data is acquired (S202), and then analysis is performed. First, a point L ₁ (144f [FIG. 5 (d)], 145b [FIG. 5 (e)], 146a [FIG. 5 (f)]) where the amount of light locally increases corresponding to the position of the bottom surface of the blood collection tube is found. (S203). From this point, the transmission amount is scanned in the direction of the upper part of the specimen 110. A point L ₂ (144 g [FIG. 5 (d)], 145 c [FIG. 5 (e)], 146 b [FIG. 5 (f)]) where the amount of transmission rapidly rises during scanning is specified (S 204) and recorded. . The distance between L ₂ and L ₁ (L ₂ −L ₁ ) represents the thickness of the clot 123 or blood cell 125 layer. As described above, the region of the blood clot 123 or blood cell 125 is a portion where the transmission amount is close to 0 regardless of the presence or absence of the label 103. By detecting the position by paying attention to the area not affected by the label 103, the detection accuracy is increased.

Further, the scanning of the transmission amount is continued, and the presence of a point L ₃ (144h [FIG. 5 (d)], 145d [FIG. 5 (e)]) at which the transmission amount rapidly decreases is examined (S205). When a point that rapidly decreases is found, the sample contains the separation agent (131, 132), and when it is not found, the sample does not contain the separation agent. For the former scene, the distance between L ₃ and L ₂ (L ₃ -L ₂ ) represents the layer thickness of the separating agent (131, 132).

Next, the layer height of serum 122 or plasma 124 is estimated using L ₁ , L ₂ , and L ₃ . It is known that the blood component is composed at a substantially constant ratio, and the volume ratio of serum 122 to blood clot 123 or plasma 124 to blood cell 125 is approximately 55:45. Using this property, the position of the upper surface of the serum 122 in the specimen (114, 115) containing the separating agent is (L ₂ −L ₁ ) + (L ₃ −L ₂ ) + (L ₂ −L ₁ ) * 55 / 45, that is, (−100L ₁ + 55L ₂ + 45L ₃ ) / 45, the position of the upper surface of the plasma 124 in the specimen 116 not containing the separating agent is (L ₂ −L ₁ ) + (L ₂ −L ₁ ) * 55/45 That is, (−100L ₁ + 100L ₂ ) / 45 can be obtained respectively (S206 to S208). Finally, the capacity is calculated. Specifically, it is derived by the width of the serum layer ((L ₂ −L ₁ ) * 55/45) * π * 3.14 * (inner diameter of blood collection tube / 2) ² .

  Since the operation of attaching the label 103 to the blood collection tube 102 is performed manually by the user, there is an individual difference for each specimen in the position of the label. In addition, the amount of collected blood has a difference in individuality for each specimen. However, regardless of the relative positional relationship between the position of the label and the upper surface of the serum 122 / clot 123, the permeation profile is a similar pattern. Even so, the layer state in the blood collection tube 102 can be easily grasped.

  The position information on the upper surface of the serum 122 and the clot 123 obtained as described above is transmitted to the control means 90 and used for the parameter of the aspiration of the specimen to be performed later, the prioritization of measurement items, and the like. The sample 110b for which the measurement has been completed is transported in the direction of the arrow 66.

  The analysis unit 80 includes a program that is an algorithm for the above flow.

  In addition, the amount of the sample is measured at the branch point 72. However, if the sample is already centrifuged, it can be measured at the branch point 71 on the same principle.

  This method is a measurement method in which the light transmittance is analyzed from the data of the portion not affected by the cover of the barcode label 103, and can be applied regardless of the position where the label 103 is attached. There is the greatest advantage. In addition, by constructing a flowchart that can be applied to all types of samples handled by the system, it is possible to perform uniform processing that does not require switching for each type of sample. This eliminates the need for light intensity adjustment according to the presence or absence of a printed part and test shooting to confirm the presence or absence of a label, which was an essential function in conventional processing methods, and as a result, processing time can be shortened by reducing the number of imaging operations. I can plan. Further, the container rotating operation for searching for the surface on which the barcode 103 is not printed or the surface on which the label is not attached becomes unnecessary.

  By realizing the above-described embodiment, the obtained centrifugation process can be passed without stopping at the centrifuge module 4 by automatic determination of the execution of the centrifugation, thereby shortening the processing time and improving the processing efficiency. , And smooth operation becomes possible. In addition, it is possible to eliminate the labor of the user who individually inputs the necessity of centrifugation into the apparatus. 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.

  When installing the biological sample analyzer in the vicinity of the input module 3 (22).

  The configuration of the biological sample analyzer according to one embodiment of the present invention will be described with reference to FIG. FIG. 8 is a configuration diagram showing units arranged in the input module of the biological sample analyzer according to the embodiment of the present invention.

  In FIG. 8, the main elements constituting the unit 22 according to the present invention are two irradiation means (203, 204), an imaging means 221, a control means 90 for controlling them, and an analysis means 80 for analyzing data. . Here, with respect to the irradiation means (203, 204), one is a first irradiation means 203 that irradiates light having a wavelength in the visible region, and the other is a long wavelength light that is transparent to the label (for example, Infrared light, millimeter wave, etc.) is used.

  The purpose of this unit 22 is to measure the presence / absence of centrifugal separation processing, the volume of the portion to be measured by the automatic analyzer, and the position of the upper surface of the specimen.

  The samples handled by the unit 22 are the six types of samples shown in FIGS. 4A to 4F (111 to 116) as in the previous embodiment.

  The visible light transmittance for each type of specimen is as shown in FIGS.

  On the other hand, the transmittance of light that is transparent to the labeler. The part of the separating agent is well transmitted like visible light. Further, the clot 123 and the blood cell 125 hardly penetrate. However, unlike visible light, it is opaque to serum 122 and plasma 124. The outline is shown in FIG.

  FIG. 9A is a profile of the transmission amount of the second light source with respect to the specimen 114 that has been subjected to the centrifugation including the gel-like separation agent.

  FIG. 9B shows a profile of the transmission amount of the second light source with respect to the specimen 111 that contains a gel-like separating agent and has not been centrifuged.

  FIG. 9C shows a profile of the transmission amount of the second light source with respect to the specimen 116 that has not been separated and does not contain a separating agent.

  FIG. 9D is a profile of the transmission amount of the second light source with respect to the specimen 113 that does not contain a separating agent and has not been centrifuged.

  In addition, since the bead-like separating agent is not permeable, it is difficult to identify the specimen by a long wavelength, so a drawing for this case is not prepared.

  Therefore, a dedicated flowchart is constructed to handle all types uniformly. With reference to FIG. 10, a sample processing procedure will be described in time series. FIG. 10 is a flowchart showing an overall process in the unit 22 arranged in the input module of the biological sample analyzer according to the embodiment of the present invention.

  The collected specimen 110 is placed in the holder 101 and is loaded into the loading module 3. Then, it is conveyed to the unit 22 shown in FIG. The specimen is temporarily stopped at an appropriate measurement position 73 in the unit 22. An RFID reading function is attached to the lower part of the stop position, and the conveyed specimen is recognized.

  When recognizing the sample, the control unit 90 irradiates the first irradiation unit 203 (S301). It is assumed that the two irradiation means (203, 204) are initially present at the bottom, and the irradiation means 203 is moved upward through the drive motor 205 and stopped at an appropriate position. Simultaneously with the irradiation of the light source, the imaging unit 221 captures an image and acquires transmission amount data (S302). The data is transferred to the analysis means 80 and analyzed.

First, the presence of the bead-like separating agent (132) is detected (S303). Since the image acquired first is an image picked up with visible light, the shape of the inclusion can be confirmed by edge detection processing of the image, and from there, it is confirmed whether there is a bead-like shape. If there is a bead-like shape, it is determined that the bead-like separating agent (132) is included at that moment. Next, the permeation amount at the bottom of the blood collection tube 102 is confirmed (S304). When a portion with a large permeation amount exists at the bottom with a width, it is determined that the sample 112 has not been centrifuged (S305) because it corresponds to the state of FIG. 5B. On the other hand, if a portion with a large permeation amount is not found at the bottom, it is identified as the sample 115 that has been subjected to centrifugation, as corresponding to the state of FIG. 5E (S306). The former object 112 performs scanning from the portion of the bottom of the transmission toward the top of the blood collection tube, the transmittance specified points L ₄ become a value close to 0 (S307), the transmittance subjected to further scan A point L _{5 at} which the temperature rises rapidly is specified (S308), and L ₅ is set as the upper surface of the specimen (S309). Further, the thickness of the serum layer obtained after centrifugation is calculated by (L ₅ −L ₄ ) * 0.55. Information that the serum volume is approximately 55% of the whole blood volume is used. On the other hand, for the latter specimen 115, the position of the upper surface of the serum 122 and the serum amount are estimated by the same method as the analysis method used in FIG. 5E in the previous embodiment (S310 to S313).

  When there is no bead-like shape, the bead-like separating agent (132) is not included. In this case, the second irradiation means 204 is irradiated as the next means. The light from the second irradiation means 204 has label transparency. The irradiation means 204 also initially exists at the lowest position, moves upward in response to a command from the control means 90, and stops at an appropriate irradiation position. During this movement, the other irradiation means 203 moves upward and stops at the top. The second irradiation unit 204 emits light (S314), and the imaging unit 221 performs imaging. Data is acquired (S315) and analyzed by the analysis means 80. Subsequent analysis is performed using the data of FIG. The light emitted from the irradiating means 204 has a long wavelength and does not interfere with the label 103, so that similar data can be obtained regardless of the presence or absence of the label 103.

  Next, the transmission amount is scanned from the bottom of the blood collection tube 102, and the number of points that change rapidly is counted (S316).

When the number of points where the permeation amount changes abruptly is 2 or more, the specimen (111, 114) containing the separation agent 131 [FIG. 9 (a) or (b)]. Next, in order to determine whether or not the centrifugation is performed, an attempt is made to specify the position of the separating agent 131. As previously described, since the separation agent 131 has a high permeability, the amount of permeation at the bottom of the blood collection tube 102 is confirmed (S317). If the amount of permeation at the bottom is large, the specimen 111 (for which separation centrifugation has not been performed) ( S318) If the transmittance at the bottom is small, it is determined that the sample 114 has been centrifuged (S319). The former specimens 111 performs scanning from the portion of the bottom of the transmission toward the top of the blood collection tube, and the point L ₆ which transmittance is a value close to 0, the L ₇ that the transmittance increases rapidly identified (S320), the L ₇ and the upper surface of the specimen (S321). Again, using the fact that the volume ratio of serum to clot is 55:45, the thickness of the serum layer obtained after centrifugation is calculated as (L ₇ −L ₆ ) * 0.55. For the latter specimen 114, a method similar to the analysis method in FIG. 5E in the previous embodiment is applied to FIG. 9A to estimate the position of the upper surface of the serum 122 and the amount of serum (S322 to S324). .

On the other hand, when the number of points where the permeation amount changes suddenly is one, it is one of the specimens (113, 116) not including the separation agent [FIG. 9 (c) or (d)]. Here, since the permeation amount profiles in FIG. 9C and FIG. 9D have a similar shape, it is difficult to distinguish whether or not the centrifugation is performed only from this data. However, it can be distinguished by comparing with data photographed with the light irradiated by the first irradiation means 203 (S325). First, a point (153a, 156a) that changes abruptly is found from the data of the transmission amount by the light irradiated by the second irradiation means 204. Starting from this point, the transmission amount data by visible light is scanned toward the bottom of the blood collection tube 102. During scanning, if there is a phenomenon (146b) in which the amount of permeation rapidly decreases, the specimen 116 [FIG. 5 (f)] (S326) that has been subjected to centrifugation, and if there is no such phenomenon, specimen 113 that has not been centrifuged. [FIG. 5 (c)] (S327). For the former sample 116, the plasma volume is calculated by estimating the position of the upper surface of the plasma 124 and the serum volume by the analysis method used in FIG. 5 (f) in the previous embodiment (S328 to S329). On the other hand, the latter specimen 113 performs bottom scanned from part L ₈ transmittance toward the top of the blood collection tube, the transmittance specified points L ₉ which rapidly increases (S330), and the upper surface of the specimen (S331). Again, using the fact that the volume ratio of plasma to whole blood is 55: 100, the thickness of the layer of plasma 124 obtained after centrifugation is calculated as (L ₉ -L ₈ ) * 0.55.

  The capacity is also calculated from the thickness data. The information obtained as described above is transmitted to the control means 90. The control means 90 instructs the specimen 110b to stop at the centrifuge module 4 (S332, S333). The serum volume data is used to prioritize the parameters of sample aspiration and measurement items.

  The analysis unit 80 includes a program that is an algorithm for the above flow.

  As mentioned above, although the invention made | formed by this invention was concretely demonstrated based on embodiment, this invention is not limited to the said embodiment, It is possible to change a seed type in the range which does not deviate from the summary. Needless to say.

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 Sorting module 10 Storage module 11 Automatic analyzer 21, 22 Unit 30 Centrifuge 40 Adapter 50 Chuck 51 Gripper 60 to 67, 213 Arrow 71 Branch point (first time)
72 Branch point (second time)
73 Measurement position 80 Analysis means 90 Control means 101 Holder 102 Blood collection tube 103 Label (bar code)
104 stopper 110 specimen 111 specimen (contains a gel-like separating agent and has not been centrifuged)
112 Specimens (Bead-like separation agent is included and centrifugation is not performed)
113 specimens (separation agent is not included and centrifugation is not performed)
114 specimens (contains gel separation agent and has been centrifuged)
115 Specimens (Bead-like separation agent is included and centrifuged)
116 specimens (centrifuged without separation agent)
121 Whole blood 122 Serum 123 Blood clot 124 Plasma 125 Blood cell 131 Separating agent (gel)
132 Separating agent (bead shape)
141 Transmission profile by first light source (corresponding to specimen 111)
142 Transmission profile by first light source (corresponding to specimen 112)
143 Transmission amount profile by first light source (corresponding to specimen 113)
144 Transmission profile by first light source (corresponding to specimen 114)
145 Transmission amount profile by first light source (corresponding to specimen 115)
146 Transmission amount profile by the first light source (corresponding to the specimen 116)
153 Profile of permeation amount by the second light source (no separation agent is included and centrifugation is not performed)
156 Permeation profile by second light source (centrifugation completed without separation agent)
201, 202, 203, 204 Irradiation means 205, 206, 207 Drive motor 211 Imaging means 212 Rotating shaft 220 Black ground film

Claims (8)

A centrifuge for performing centrifugation on a specimen;
Irradiation means for irradiating light to the container before and after the centrifugal treatment at the upstream position and the downstream position with respect to the centrifuge ,
Imaging means for detecting transmitted light transmitted through the container by light irradiation by the irradiation means ;
A rotating shaft for rotating the imaging means;
Control means for controlling the position of the imaging means by the rotating shaft so that transmitted light can be detected before and after the centrifugation of the container, and the container is covered with a label all or part of its side surface. I,
Based on the signal strength detected at the upstream position of the centrifuge, the presence / absence of centrifugal processing is analyzed, and the boundary position information of the layer inside the container is obtained based on the signal strength detected at the downstream position of the centrifuge. With analysis means to analyze ,
The control device comprises: control means for controlling whether or not the container is carried into the centrifuge based on the signal intensity detected at the upstream position .
The analyzer according to claim 1.
The analysis unit analyzes the information on the boundary position of the layer inside the container based on the position and number of signal intensity changes detected by the imaging unit.
The analyzer according to claim 1.
The layer contained in the container contains a separating agent;
Said analysis means, said locates separating agent, based on the information of the specified position, the analysis device characterized by comprising the step determining whether the implementation of centrifugation.
The analyzer according to claim 1.
The analysis device counts the number of the layers, and determines whether or not a centrifugal process is performed based on the information.
The analyzer according to claim 1.
The biological sample analyzer according to claim 1, wherein the analyzing means calculates a capacity of the layer based on information on a boundary position of the layer.
The analyzer according to claim 1 .
The imaging means, the analyzer being characterized in that disposed in the vicinity of the point of intersection of the light emitted from the irradiation unit.
The analyzer according to claim 1.
The irradiating means is a first irradiating means for irradiating light having the property of being easily dimmed by the label;
Analyzer characterized in that it comprises a and a second irradiating means for irradiating light having a property of transmitting the label.
The analyzer according to claim 7 , wherein
The analysis device is characterized in that the number of the layers is counted based on a difference in transmission amount due to different types of light, and whether or not a centrifugal process is performed is determined based on the information.