JP2014092486A - Analysis chip and analysis device - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an analysis chip having a simple structure with which analyses can be accurately made.SOLUTION: An analysis chip (1) according to an aspect of the invention includes: a filter (6) that blocks the permeation of components that are not to be analyzed; an analysis unit (5) that analyzes a component to be analyzed; and a first flow passage and a second flow passage (11 and 12) that connect between the filter and the analysis unit. The filter (6) is placed so that the direction to which the component to be analyzed is taken into the first flow passage, in the filter is different from the moving direction to which the component to be analyzed moves in the first flow passage toward the analysis unit.

Description

  The present invention relates to an analysis chip, an analysis apparatus, and an analysis method.

  Measurement of the concentration of a target substance contained in a sample such as a biological fluid is an analytical technique widely used in the fields of medicine and biochemistry. For example, in the medical field, measurement of glucose concentration in blood and urine is applied as an effective screening test in the diagnosis of diseases such as hypoglycemia and diabetes.

  When components in blood are detected using coloration or fluorescence due to a chemical reaction, blood cells are separated and removed (blood cell separation) from the blood in advance. By performing blood cell separation and detection within the analysis chip, analysis can be easily performed, and the analysis apparatus can be reduced in size and cost.

  As a method for separating blood cells in the analysis chip, a method using a filter medium or a method using centrifugal force is used. In the blood cell separation method using the filter medium, the structure of the analysis chip can be simplified, and thus the analysis chip can be miniaturized.

  Moreover, as a method for performing liquid feeding and pretreatment (treatment such as dilution, quantification, or mixing) in the analysis chip, a method using centrifugal force or a method using a pump is used. In order to analyze a plurality of components at once in the analysis chip, a method using centrifugal force capable of performing liquid feeding and pretreatment in parallel is suitable.

  Patent Document 1 describes an analysis chip including a pretreatment element, a multilayer dry analysis element, and a flow path connecting the pretreatment element and the multilayer dry analysis element. In this analysis chip, blood cells are separated using glass fibers in the pretreatment element using centrifugal force.

  Patent Documents 2 and 3 describe devices for separating blood cells by centrifugation.

Japanese Patent Laying-Open No. 2006-58280 (published March 2, 2006) Patent No. 4752546 (registered on June 3, 2011) JP 2006-52949 A (published February 23, 2006)

  However, the conventional techniques as described above cause the following problems.

  In the analysis chip described in Patent Document 1, a filter medium such as glass fiber and a flow path through which plasma that has passed through the filter medium flows are arranged in a straight line. Therefore, the direction in which plasma in blood passes through the filter medium is the same as the direction in which centrifugal force acts. Therefore, there is a possibility that blood cells leak from the filter medium due to centrifugal force acting on the blood cells. Further, the centrifugal force acting on the blood cells may break the blood cells (hemolysis), and the hemolyzed liquid may leak from the filter medium. If leaked blood cells or hemolyzed liquid enter the analysis section, there arises a problem that the analysis cannot be performed accurately.

  In addition, when adopting a method of separating blood cells using centrifugal force without using a filter medium, there is a problem that the flow path structure becomes complicated in order to perform a plurality of processes with one analysis chip. is there.

  The present invention has been made in view of the current situation, and according to one embodiment of the present invention, an analysis chip capable of performing an analysis accurately with a simple structure can be realized.

  The analysis chip according to one embodiment of the present invention separates an analysis target component from a liquid sample, thereby allowing the analysis target component to pass through and preventing separation of a non-analysis target component that is a component other than the analysis target component. The analysis unit connected to the separation part (filter medium 6), the analysis part for analyzing the analysis target component separated in the separation part, and the separation part and the analysis part, and separated in the separation part A flow channel (first flow channel 11 and second flow channel 12) for moving the target component to the analysis unit, and the separation unit is configured such that the analysis target component separated in the separation unit is The direction of introduction into the flow path is arranged to be different from the moving direction of the analysis target component moving in the flow path to the analysis unit.

  According to one aspect of the present invention, the separation unit transmits the analysis target component in the liquid sample and prevents the non-analysis target component from transmitting. Therefore, the analysis target component is introduced into the flow path, but the non-analysis target component is held in the separation unit. The separation unit is arranged so that the direction in which the analysis target component is introduced into the flow path is different from the moving direction of the analysis target component in the flow path.

  As a result, for example, even when centrifugal force is applied, the analysis target component moves in the flow path and is introduced into the analysis unit, it is held in the separation unit arranged as described above. It is possible to prevent the non-analysis target component from being introduced into the flow path upon application of the centrifugal force. Therefore, it is possible to prevent the introduction of the non-analysis target component into the analysis unit, which causes an analysis error, and thus it is possible to easily perform a highly accurate analysis.

It is a top view which shows the structure of the analysis chip which concerns on 1 aspect of this invention. It is sectional drawing which shows the AA cross section of FIG. It is a top view which shows the structure of the rotating apparatus which concerns on 1 aspect of this invention. It is sectional drawing which shows the cross section of the analyzer which concerns on 1 aspect of this invention, and an analysis chip. It is sectional drawing which shows the structure of the analysis chip of a modification. It is sectional drawing which shows the structure of the analysis chip which concerns on the other aspect of this invention. It is sectional drawing which shows the BB cross section of FIG. It is sectional drawing which shows the other structure of a blood cell separation part. It is sectional drawing which shows other structure of a blood cell separation part. It is a top view which shows the structure of the analysis chip which concerns on the further another aspect of this invention. It is a top view which shows the structure of the analysis chip of a modification. It is a top view which shows the structure of the analysis chip installed in the rotating apparatus of a modification. It is sectional drawing which shows the structure of the analysis chip which concerns on the further another aspect of this invention. It is a top view which shows the structure of the analysis chip which concerns on the further another aspect of this invention. It is sectional drawing which shows CC cross section of FIG. It is sectional drawing which shows the cross section of the analyzer which concerns on the further another aspect of this invention, and an analysis chip.

Embodiment 1
Hereinafter, embodiments of the present invention will be described in detail. Here, an analysis chip for measuring glucose in blood will be described as an example of measuring components in a specimen.

(Configuration of analysis chip 1)
FIG. 1 is a plan view showing the configuration of the analysis chip 1 of the present embodiment. 2 is a cross-sectional view showing an AA cross section of FIG. The analysis chip 1 includes a sample introduction unit 2, a blood cell separation unit 3, a pretreatment unit 4, an analysis unit 5, a waste liquid unit 9, a first flow channel 11, a second flow channel 12, a third flow channel 13, and a first valve unit. 14 and the second valve portion 15. In FIG. 2, the first valve portion 14 and the second valve portion 15 are omitted. The preprocessing unit 4, the analysis unit 5, and the waste liquid unit 9 are spaces (cells) provided in the analysis chip 1. In particular, the preprocessing unit 4 is a space (cell) defined in a predetermined volume.

  The analysis chip 1 includes an upper substrate 16 and a lower substrate 17. The blood cell separation unit 3 is provided on the upper surface side of the upper substrate 16. The upper substrate 16 is formed with grooves as flow paths and recesses as spaces. The first flow path 11, the second flow path 12, the third flow path 13, the pretreatment section 4, the analysis section 5, and the waste liquid section 9 are formed by bonding the upper substrate 16 and the lower substrate 17 together. The upper substrate 16 and the lower substrate 17 are transparent, and can be manufactured using, for example, resin, glass, silicon, or the like.

  The blood cell separation unit 3 includes a column-shaped filter medium 6 (separation unit) and a storage unit 7 that is a cavity provided on the side surface side of the filter medium 6. The side surface of the filter medium 6 faces the storage portion 7. The upper surface side of the filter medium 6 faces the sample introduction part 2 which is a cylindrical space. The lower surface side of the filter medium 6 faces the lower space 8 that is a cylindrical space. The surface of the inner wall of the storage part 7 is hydrophobic. The filter medium 6 can be manufactured using, for example, filter paper, membrane, glass fiber, glass fiber filter paper, microporous material, or polymer material. Further, the frame of the blood cell separation unit 3 (portion surrounding the filtering material 6 and the storage unit 7) can be manufactured using, for example, resin, glass, silicon, or the like, similarly to the substrate. The surface of the inner wall of the lower space 8 may be hydrophilic.

  The blood cell separation unit 3 and the pretreatment unit 4 are connected by a first flow path 11. Specifically, the lower surface of the filter medium 6 is connected to the first flow path 11 via the lower space 8. The lower space 8 and the pretreatment unit 4 are connected by a first flow path 11. A first valve portion 14 is provided in the middle of the first flow path 11.

  The pretreatment unit 4 and the analysis unit 5 are connected by a second flow path 12. A second valve portion 15 is provided in the middle of the second flow path 12. The first valve unit 14 and the second valve unit 15 are provided to perform liquid feeding of the sample in stages.

  The first valve portion 14 and the second valve portion 15 are valves that function by utilizing centrifugal force. The inner walls of the first valve portion 14 and the second valve portion 15 are hydrophobic, and the cross-sectional areas of the passages of the first valve portion 14 and the second valve portion 15 are the first flow path 11 and the second flow passage connected to each other. It is smaller than the cross-sectional area of the two flow paths 12. Therefore, in a state where the centrifugal force does not work (or is small), the movement of the liquid can be stopped by the first valve unit 14 and the second valve unit 15. The liquid can be passed through the first valve portion 14 or the second valve portion 15 by increasing the rotational speed and increasing the centrifugal force. Further, the liquid passing through the first valve portion 14 can be stopped by the second valve portion 15 by making the cross-sectional area of the passage of the second valve portion 15 smaller than the passage of the first valve portion 14. Thereafter, the liquid can be passed through the second valve portion 15 by further increasing the centrifugal force. By changing the cross-sectional area of the passages of the plurality of valve sections in multiple stages, or by changing the degree of hydrophobicity of the inner walls of the plurality of valve sections in multiple stages, three or more valve sections are changed from the stopped state to the passing state. It is also possible to switch sequentially. The first valve portion 14 and the second valve portion 15 are not limited to the above, and may be configured by valves that open and close in response to external operations.

  The first flow path 11 and the waste liquid part 9 are connected by a third flow path 13. The third flow path 13 is connected to the first flow path 11 in the vicinity of the position where the first flow path 11 is connected to the pretreatment unit 4.

  The first flow path 11 and the second flow path 12 extend along the first direction. The pretreatment unit 4 is on the first direction side with respect to the blood cell separation unit 3. The analysis unit 5 is on the first direction side with respect to the preprocessing unit 4. Further, the waste liquid portion 9 is located on the first direction side with respect to the connection portion between the first flow path 11 and the third flow path 13. When a centrifugal force is applied to the analysis chip 1, the direction in which the centrifugal force acts is set along the first direction.

(Analysis method)
Hereinafter, a method for analyzing a specimen using the analysis chip 1 will be described. Blood as a sample (liquid sample) is introduced from the sample introduction unit 2 of the analysis chip 1.

  FIG. 3 is a plan view showing the configuration of the rotating device 20. The rotating device 20 (analyzer) includes a table 20a. The table 20a is rotated about the rotation shaft 20b. The analysis chip 1 in which blood is introduced into the sample introduction unit 2 is installed on the table 20a such that the sample introduction unit 2 is arranged on the inner peripheral side of the table 20a and the analysis unit 5 is arranged on the outer peripheral side. . The sample introduction unit 2 is arranged so as to be positioned on the rotating shaft 20b side with respect to the preprocessing unit 4. When the table 20a is rotated, the centrifugal force acts in a direction from the sample introduction unit 2 toward the analysis unit 5 (first direction in FIG. 1). Further, the rotating device 20 can change the strength of the working centrifugal force by changing the rotation speed.

  The blood introduced into the sample introduction unit 2 is filtered by the filter medium 6. The filter medium 6 separates blood cells, which are non-analysis target components, from blood and allows plasma containing glucose, which is an analysis target component, to pass through. The plasma passes through the filter medium 6 from the upper surface side to the lower surface side of the filter medium 6, that is, in the direction (second direction) from the sample introduction part 2 toward the lower space 8. The second direction is substantially perpendicular to the first direction. However, if the second direction is different from the first direction, it may not be vertical.

  The centrifugal force by the rotating device 20 works not from the filter medium 6 to the lower space 8 but from the filter medium 6 toward the storage section 7. Therefore, even if the centrifugal force is strong, blood cells leak from the filter medium 6 to the storage unit 7. For this reason, blood cells do not leak from the filter medium 6 into the lower space 8. Further, in the sample introduction unit 2, blood cells are pressed toward the inner wall of the sample introduction unit 2 by centrifugal force. Therefore, compared to the case where blood cells are pressed against a filter medium composed of thin fibers or the like as in the prior art, blood cells are less likely to break (has less hemolysis) in the analysis chip 1 of this embodiment.

  The surface of the inner wall of the storage part 7 is hydrophobic. Therefore, it is difficult for plasma containing the analysis target component to enter the storage unit 7. In addition, the storage unit 7 can prevent blood cells that are non-analyzed components once stored in the storage unit 7 from flowing back from the storage unit 7 to the filter medium 6. Even if the blood cells are hemolyzed in the storage unit 7, the storage unit 7 can prevent the liquid component in the hemolyzed blood cells from flowing back from the storage unit 7 to the filter medium 6. Therefore, even when the rotation is stopped, there is an effect of preventing blood cells and hemolyzed liquid components from flowing out from the storage portion 7 to the lower space 8.

  Thereby, the blood cell separation unit 3 can introduce the plasma containing the analysis target component into the lower space 8, and the blood cell that is the non-analysis target component and the liquid component in the blood cell hemolyzed in the storage unit 7 are separated from each other. Passing to the lower space 8 can be prevented.

  The plasma that has passed from the filter medium 6 to the lower space 8 is introduced into the first flow path 11 by centrifugal force. And plasma is sent to the pretreatment part 4 from the 1st channel 11 by centrifugal force. At this stage, plasma can pass through the first valve portion 14 by centrifugal force, but stops at the second valve portion 15.

  When the pretreatment unit 4 is filled with plasma, the overflowed plasma is sent to the waste liquid unit 9 via the third flow path 13. Since the pretreatment unit 4 is regulated to a predetermined volume, the pretreatment unit 4 can quantify plasma. The pretreatment unit 4 includes dilution of the liquid (plasma) containing the analysis target component, decomposition of the protein in the liquid containing the analysis target component, removal of impurities in the liquid containing the analysis target component, and analysis target component. A function of performing a pretreatment such as mixing of a liquid and a reagent or inducing a chemical reaction with respect to a component to be analyzed may be provided. Since the preprocessing unit 4 is provided in the analysis chip 1, preprocessing outside the analysis chip 1 becomes unnecessary. Therefore, the analysis process can be simplified and shortened compared to the case where the pre-processing is performed manually. Further, it is possible to reduce the size and cost of the analyzer compared to the case where a preprocessing mechanism is provided in the analyzer.

  After the excess plasma is drained to the waste liquid section 9, the second valve section 15 is passed through the plasma by centrifugal force by increasing the rotation speed, and the plasma in the pretreatment section 4 is sent to the analysis section 5 by centrifugal force. Liquid. The analysis unit 5 stores a reagent for the reaction that has been dried in advance. The plasma introduced into the analysis unit 5 causes a chemical reaction by contacting with the reagent. For example, a chemical reaction causes coloration or fluorescence. The analysis can be performed by observing the analysis chip 1 in which the plasma and the reagent have reacted with an analyzer.

  When measuring the amount of glucose in the blood, the analysis unit 5 uses glucose oxidase (GOD), peroxidase (POD), 4-aminoantipyrine (AA), and reagents as reagents. Contains N-ethyl-N- (2-hydroxy-3-sulfopropyl) -3-methylaniline, sodium salt (TOOS). GOD and POD are enzymes, and AA and TOOS are color reagents. In the analysis unit 5, glucose in plasma is oxidized by GOD to generate hydrogen peroxide. Hydrogen peroxide oxidizes AA and TOOS using POD as a catalyst, and AA and TOOS condense. The product obtained by this reaction is a multimer having an absorption wavelength peak at 555 nm and exhibits a purple color. By irradiating with light having a wavelength near 555 nm and measuring the amount of absorption of the light, the integrated amount of glucose for which the reaction has been completed at an arbitrary observation time can be obtained.

  FIG. 4 is a cross-sectional view showing cross sections of the analysis device 30 and the analysis chip 1. The analyzer 30 includes a light source 31 and a photodetector 32. The analysis chip 1 is installed in the analysis device 30 so that the analysis unit 5 is positioned between the light source 31 and the photodetector 32. The light detector 32 measures the amount of light transmitted from the light source 31 through the analysis unit 5. From the amount of transmitted light, the amount of glucose in plasma can be specified. The analysis device 30 may include the rotation device 20.

  The analysis chip 1 is not limited to blood, and can be used to remove a part of a component in a specimen by a separation unit (filter material) and introduce a liquid containing an analysis target component into the analysis unit.

  In the analysis chip 1 of the present embodiment, the direction in which the specimen is filtered by the filter medium 6 (second direction) is the direction in which centrifugal force acts (direction from the filter medium 6 to the preprocessing unit 4 or the analysis unit 5: first. Direction). Therefore, since centrifugal force does not act in the direction of filtration, particles that are non-analysis target components (separation target components) in the sample are less likely to leak from the filter medium 6. Therefore, it is possible to prevent the non-analysis target component from being mixed into the preprocessing unit 4 and the analysis unit 5. Therefore, if the analysis chip 1 is used, the analysis target component in the sample can be accurately measured. Further, the separation target component can be separated and the liquid containing the analysis target component can be fed using centrifugal force acting in a certain direction. Therefore, the flow channel structure of the analysis chip 1 can be simplified.

(Modification)
Note that the analysis chip may be configured without a storage unit.

  FIG. 5 is a cross-sectional view illustrating a configuration of the analysis chip 40 that does not include a storage unit. The analysis chip 40 has the same configuration as the analysis chip 1 except that the storage unit is not provided. The direction in which the sample passes through the filter medium 6 (second direction) is perpendicular to the direction in which the sample that has passed through the filter medium 6 is introduced into the pretreatment unit 4 by the first flow path 11 (first direction). . Therefore, it is possible to prevent blood cells from passing through the filter medium 6 due to the centrifugal force acting in the first direction. Further, since the blood cells are not pressed against the filter medium 6 by the centrifugal force, the destruction of the blood cells can be prevented.

[Embodiment 2]
Another embodiment of the present invention will be described below. For convenience of explanation, members having the same functions as those described in the above-described embodiment are denoted by the same reference numerals and description thereof is omitted.

  FIG. 6 is a cross-sectional view showing the configuration of the analysis chip 50 of the present embodiment. FIG. 7 is a cross-sectional view showing a BB cross section of FIG. 6. The analysis chip 50 differs from the analysis chip 1 shown in FIG.

  The blood cell separation unit 51 of the analysis chip 50 includes a storage unit 52 and a plurality of fourth channels 53 (storage unit connection channels). The plurality of fourth flow paths 53 are provided on the side surface side of the filter medium 6. The storage part 52 is located away from the side surface of the filter medium 6, and the side surface of the filter medium 6 and the storage part 52 are connected by a plurality of fourth flow paths 53.

  The surface of the inner wall of the storage portion 52 and the surface of the inner wall of the fourth flow path 53 are hydrophobic. Therefore, it is difficult for plasma containing the analysis target component to enter the fourth flow path 53. In addition, by providing the fourth flow path 53, the cross-sectional area that passes when blood cells flow backward is reduced. Therefore, the storage unit 52 and the fourth flow channel 53 can prevent blood cells that are non-analysis target components once stored in the storage unit 52 from flowing back from the storage unit 52 to the filter medium 6. Further, the storage part 52 and the fourth flow channel 53 can prevent the liquid component in the hemolyzed blood cells from flowing back from the storage part 52 to the filter medium 6. Furthermore, since the surface of the inner wall of the fourth flow channel 53 is hydrophobic, the capillary force acting in the opposite direction to the direction in which the blood cells move in the fourth flow channel 53 is increased, and the effect of preventing backflow is high. Become.

  According to the analysis chip 50 of this embodiment, the backflow of the component to be separated from the storage unit 52 to the filter medium 6 can be prevented more effectively than the analysis chip 1. Therefore, the separation target component can be separated and the analysis target component can be analyzed with high accuracy.

  In addition, since a part of the side surface of the filter medium 6 is in contact with the wall, alignment when the filter medium 6 is attached to the upper substrate 16 or the blood cell separator 51 is easy.

(Modification)
FIG. 8 is a cross-sectional view showing another configuration of the blood cell separation unit. The blood cell separation unit 55 illustrated in FIG. 8 includes a storage unit 56. The storage portion 56 is provided corresponding to a part of the side surface of the filter medium 6 and is disposed so as to be positioned in the first direction with respect to the filter medium 6. Since the centrifugal force acts in the first direction, blood cells and the like leaking from the filter medium 6 are stored in the storage unit 56. By not providing the storage part 56 on the side surface opposite to the first direction of the filter medium 6, the effect of preventing the non-analysis target component from flowing backward from the storage part 56 to the filter medium 6 is enhanced.

  FIG. 9 is a cross-sectional view showing still another configuration of the blood cell separator. The blood cell separation unit 57 shown in FIG. 9 includes a plurality of storage units 58. The storage portion 58 is provided corresponding to a part of the side surface of the filter medium 6, and is disposed so as to be positioned in the first direction with respect to the filter medium 6. Similarly to the blood cell separation unit 55 of FIG. 8, the blood cell separation unit 57 is also highly effective in preventing the non-analysis target component from flowing backward from the storage unit 56 to the filter medium 6.

  Further, in the blood cell separation unit 55 in FIG. 8 and the blood cell separation unit 57 in FIG. 9, since a part of the side surface of the filter medium 6 is in contact with the wall, alignment is performed when the filter medium 6 is attached to the upper substrate or the blood cell separation unit. Easy.

[Embodiment 3]
Still another embodiment of the present invention will be described below. For convenience of explanation, members having the same functions as those described in the above-described embodiment are denoted by the same reference numerals and description thereof is omitted.

  FIG. 10 is a plan view showing the configuration of the analysis chip 60 of the present embodiment. The analysis chip 60 has a disk shape and is configured by disk-shaped substrates (upper substrate and lower substrate). The analysis chip 60 has a center axis (hole) 61 for fixing to the rotation axis of the rotation device. The analysis chip 60 includes one sample introduction unit 2 and one blood cell separation unit 3. The analysis chip 60 includes a plurality of (five) analysis units 62.

  Each analysis unit 62 includes a pretreatment unit 4, an analysis unit 5, a waste liquid unit 9, a first channel 11, a second channel 12, a third channel 13, a first valve unit 14, and a second valve unit 15. Prepare. The configuration of each element of the analysis unit 62 is the same as that shown in FIG. However, the configurations of the preprocessing unit 4 and the analysis unit 5 may be different for each analysis unit 62. For example, by providing different reagents in the plurality of analysis units 5, it is possible to simultaneously detect and analyze a plurality of different components in blood. The first flow path 11 of each analysis unit 62 extends radially with respect to the central axis.

  The analysis chip 60 includes a fifth flow path 63 for connecting the plurality of analysis units 62 to the blood cell separation unit 3. The fifth flow path 63 is formed along the circumferential direction, and connects the first flow path 11 of each analysis unit 62 to the blood cell separation unit 3. The surface of the inner wall of the fifth flow path 63 is preferably hydrophilic.

  When the analysis chip 60 is installed in the rotating device and rotated, the plasma that has passed through the filter medium of the blood cell separation unit 3 is introduced into the fifth flow path 63 by centrifugal force and / or capillary force, The liquid is sent to the first flow path 11. Due to the rotation of the analysis chip 60, the plurality of analysis units 62 can perform liquid feeding and pretreatment in parallel. And in the analysis part 5 of each analysis unit 62, reaction with a reagent can be performed in parallel. By observing the plurality of analyzers 5, it is possible to individually detect and analyze a plurality of components in blood.

  According to the analysis chip 60 of the present embodiment, it becomes easy to simultaneously analyze a plurality of analysis target components in a sample in parallel.

  Note that the sample introduction unit 2 and the blood cell separation unit 3 may be provided, for example, at the end 63a of the fifth channel 63.

(Modification)
The blood cell separation unit 3 can also be configured to be positioned in the vicinity of the rotation axis.

  FIG. 11 is a plan view showing the configuration of the analysis chip 65. The analysis chip 65 has a disk shape. The analysis chip 65 includes the blood cell separation unit 3 and a plurality of analysis units 62, similarly to the analysis chip 60 of FIG. The analysis chip 65 is fixed to the rotation device so that the rotation axis of the rotation device coincides with the center. In the analysis chip 65, the blood cell separation unit 3 is disposed so as to be positioned on the rotation axis (center) of the analysis chip 65. The blood cell separator 3 and the fifth channel 63 are connected by a seventh channel 66 extending from the center of the analysis chip 65 toward the outer peripheral side.

  Since the blood cell separation unit 3 is positioned in the vicinity of the rotation axis of the rotating device, the centrifugal force acting on the blood cell separation unit 3 can be reduced. Therefore, blood cells separated by the filter medium 6 can be prevented from being introduced into the analysis unit 62 by centrifugal force. Moreover, it is possible to prevent the blood cells separated by the filter medium 6 from being destroyed by centrifugal force.

  Note that the analysis chip may not have a disk shape.

  FIG. 12 is a plan view showing the configuration of the analysis chip 64 installed in the rotating device 20. Similar to the analysis chip 60 of FIG. 10, the analysis chip 64 includes the blood cell separation unit 3 and a plurality of analysis units 62. The analysis chip 64 is installed in the rotation device 20 so that the rotation shaft 20b is positioned on the extension line of the first flow path of each analysis unit. By installing the analysis chip 64 on the rotating device 20 and rotating it, a plurality of components to be analyzed can be analyzed in parallel as in the analysis chip 60.

  The analysis chip 64 may be fixed to the rotation device 20 such that the blood cell separation unit 3 of the analysis chip 64 is positioned on the rotation shaft 20b of the rotation device 20.

[Embodiment 4]
Still another embodiment of the present invention will be described below. For convenience of explanation, members having the same functions as those described in the above-described embodiment are denoted by the same reference numerals and description thereof is omitted.

  FIG. 13 is a cross-sectional view showing the configuration of the analysis chip 70 of the present embodiment. The analysis chip 70 includes a lower filter medium 71 (absorber) in a lower space on the lower surface side of the filter medium 6. The lower filter medium 71 connects the filter medium 6 and the first flow path 11. The lower filter medium 71 can be manufactured using, for example, filter paper, membrane, glass fiber, glass fiber filter paper, microporous material, or polymer material. The filter medium 6 and the lower filter medium 71 may be made of the same material or different materials. Further, the filter medium 6 and the lower filter medium 71 may be integrated.

  The lower filter medium 71 absorbs liquid by capillary force. By connecting the lower surface of the filter medium 6 and the first flow path 11 with the lower filter medium 71, the plasma that has passed through the filter medium 6 is introduced into the first flow path 11 by the capillary force of the lower filter medium 71. Therefore, for example, plasma can be introduced into the first flow path 11 by capillary force without applying centrifugal force. Therefore, it becomes easy to introduce the liquid containing the analysis target component into the first flow path 11.

[Embodiment 5]
Still another embodiment of the present invention will be described below. For convenience of explanation, members having the same functions as those described in the above-described embodiment are denoted by the same reference numerals and description thereof is omitted.

  FIG. 14 is a plan view showing the configuration of the analysis chip 80 of the present embodiment. FIG. 15 is a cross-sectional view showing a CC cross section of FIG. The analysis chip 80 is different from the analysis chip 1 of FIG. 1 in that the analysis chip 80 includes an open hole 81 (atmospheric open part) and a sixth flow path 82 that connects the open hole 81 and the lower space 8. The open hole 81 is provided on the side opposite to the first direction with respect to the blood cell separator 3 (that is, the side opposite to the first flow path 11). However, the position of the opening hole 81 is not limited to this, and can be provided at an arbitrary position.

  In the analysis chip 80, air (atmosphere) can be introduced from the open hole 81 into the lower space 8. Therefore, for example, even when the sample introduction part 2 is sealed after blood introduction, or when the upper surface side of the filter medium 6 is filled with blood cells or blood, an air introduction path to the first flow path 11 is secured. Is done. Therefore, plasma can be easily sent from the lower space 8 to the first flow path 11.

[Embodiment 6]
Still another embodiment of the present invention will be described below. For convenience of explanation, members having the same functions as those described in the above-described embodiment are denoted by the same reference numerals and description thereof is omitted.

  FIG. 16 is a cross-sectional view showing cross sections of the analysis device 35 and the analysis chip 1. The analysis device 35 includes light sources 31 and 33 and photodetectors 32 and 34. The analysis chip 1 is placed in the analysis device 35 so that the analysis unit 5 is positioned between the light source 31 and the photodetector 32 and the storage unit 7 is positioned between the light source 33 and the photodetector 34. Installed. The light detector 32 measures the amount of light transmitted from the light source 31 through the analysis unit 5. From the amount of transmitted light, the amount of glucose in plasma can be specified.

  The light source 33 irradiates the storage unit 7 with irradiation light. The light detector 34 measures the amount of light transmitted from the light source 33 through the storage unit 7. The photodetector 34 can detect the amount of light absorbed by the liquid components of the blood cells stored in the storage unit 7 or the hemolyzed blood cells.

  Thereby, the analyzer 35 can measure the amount of blood cells introduced into the first flow path 11 from the filter medium 6 or the amount of liquid components of the hemolyzed blood cells present in the storage unit 7 by centrifugal force. it can. As a result, the analyzer 35 can warn (notify) the user that there is a possibility that a blood cell or a liquid component of the hemolyzed blood cell may be introduced into the first flow path 11 or the analysis unit 5. It is also possible to evaluate the ease of hemolysis of blood cells contained in the specimen. Therefore, the analyzer 35 prevents analysis errors from occurring and enables more accurate analysis.

[Summary]
[Aspect 1] The analysis chip according to an aspect of the present invention separates an analysis target component from a liquid sample, thereby allowing the analysis target component to pass therethrough, and for non-analysis target components other than the analysis target component. A separation unit (filter medium 6) that prevents permeation, an analysis unit for analyzing the analysis target component separated in the separation unit, the separation unit and the analysis unit are connected, and separation is performed in the separation unit A flow path (first flow path 11 and second flow path 12) for moving the analyzed component to be analyzed to the analysis section, wherein the separation section is separated by the separation section. The direction in which the target component is introduced into the flow path is arranged to be different from the moving direction of the analysis target component that moves in the flow path to the analysis unit.

  According to said structure, a separation part permeate | transmits the analysis target component in a liquid sample, and prevents permeation | transmission of a non-analysis target component. Therefore, the analysis target component is introduced into the flow path, but the non-analysis target component is held in the separation unit. The separation unit is arranged so that the direction in which the analysis target component is introduced into the flow path is different from the moving direction of the analysis target component in the flow path.

  As a result, for example, even when centrifugal force is applied, the analysis target component moves in the flow path and is introduced into the analysis unit, it is held in the separation unit arranged as described above. It is possible to prevent the non-analysis target component from being introduced into the flow path upon application of the centrifugal force. Therefore, it is possible to prevent the introduction of the non-analysis target component into the analysis unit, which causes an analysis error, and thus it is possible to easily perform a highly accurate analysis.

  “Aspect 2” In the analysis chip according to Aspect 1, the separation unit is configured such that the direction in which the analysis target component separated in the separation unit is introduced into the flow channel passes through the flow channel to the analysis unit. You may arrange | position so that it may become a substantially perpendicular | vertical direction with respect to the moving direction of the said to-be-analyzed component to move.

  According to said structure, the analysis object component isolate | separated in the isolation | separation part is introduce | transduced into a flow path from the substantially perpendicular | vertical direction with respect to the moving direction in the said flow path.

  Thus, for example, even when a centrifugal force is applied and the analysis target component moves in the flow channel, the centrifugal force prevents the non-analysis target component from being introduced into the flow channel more reliably. can do.

  "Aspect 3" In the analysis chip according to Aspect 1 or 2, the separation unit includes any one of filter paper, membrane, glass fiber, glass fiber filter paper, microporous material, and polymer material. Also good.

  According to said structure, it becomes possible to isolate | separate a non-analysis object component easily by filtration and to prevent the permeation | transmission.

  “Aspect 4” In the analysis chip according to the above aspects 1 to 3, at least part of a side surface of the separation unit that is different from the surface where the analysis target component is introduced into the flow path is centrifuged to the analysis target component. A storage unit may be arranged in which when the force is applied, the non-analysis target component is moved from the separation unit and stored.

  According to said structure, the non-analysis target component currently hold | maintained at the isolation | separation part is stored in a storage part by centrifugal force.

  Thereby, the introduction of the non-analysis target component into the flow path can be more reliably prevented.

  “Aspect 5” In the analysis chip according to aspect 4, the inner wall of the storage portion may have hydrophobicity.

  According to said structure, it can prevent that the analysis object component in a liquid sample permeates into a storage part from a isolation | separation part. In addition, it is possible to prevent the non-analysis target component once stored in the storage unit from flowing back to the separation unit. Further, it is possible to prevent the liquid component in the non-analysis target component damaged by, for example, centrifugal force from flowing back to the separation unit in the storage unit.

  As a result, the analysis target component can be reliably introduced into the flow path, and the non-analysis target component and the liquid component in the non-analysis target component damaged in the storage unit can be reliably introduced into the flow path. Can be prevented.

  “Aspect 6” In the analysis chip according to aspect 4 or 5, the separation unit and the storage unit may be connected by a plurality of storage unit connection channels (fourth channel 53). .

  According to said structure, the backflow to the separation part of the non-analysis object component which moved to the storage part from the separation part can be prevented more reliably.

  “Aspect 7” In the analysis chip according to aspect 6, the inner walls of the plurality of storage unit connection flow paths may be hydrophobic.

  According to said structure, it can prevent that the analysis object component in a liquid sample permeates into the said several storage part connection flow path from a isolation | separation part. In addition, it is possible to prevent the non-analysis target component once stored in the storage unit from flowing back to the separation unit.

  Further, it is possible to prevent the liquid component in the non-analysis target component damaged by, for example, centrifugal force from flowing back to the separation unit in the storage unit.

  As a result, the analysis target component can be reliably introduced into the flow path, and the non-analysis target component and the liquid component in the non-analysis target component damaged in the storage unit can be more reliably introduced into the flow path. Can be prevented.

  “Aspect 8” In the analysis chip according to Aspects 1 to 7, the separation part and the flow path are configured to be connected via an absorber (lower filter medium 71) that absorbs liquid by capillary force. May be.

  According to said structure, the analysis object component isolate | separated in the isolation | separation part is introduce | transduced in a flow path by the capillary force produced by the structure of an absorber. Therefore, it becomes easy to introduce the analysis target component into the flow path.

  “Aspect 9” In the analysis chip according to the above aspects 1 to 8, an air opening portion (open hole 81) connected to the flow path for introducing air into the flow path may be formed.

  According to the above configuration, for example, even when the inlet for introducing the liquid sample formed in the separation unit is blocked or when the separation unit is filled with the liquid sample, Introduction of the atmosphere is ensured. Thereby, the component to be analyzed can be easily introduced into the flow path.

  “Aspect 10” The analysis chip according to the above aspects 1 to 9 includes a pre-processing unit for performing pre-processing of analysis in the analysis unit on the liquid containing the analysis target component in the middle of the flow path. May be.

  According to said structure, the analysis object component introduced into the flow path from the isolation | separation part is introduce | transduced into an analysis part through the pre-processing by a pre-processing part. Thereby, various analyzes in the analysis unit can be made possible by performing pre-processing according to the content of the analysis performed in the analysis unit in the pre-processing unit.

  “Aspect 11” In the analysis chip according to aspect 10, the pretreatment includes dilution of the liquid containing the analysis target component, quantification of the liquid containing the analysis target component, and decomposition of the protein in the liquid containing the analysis target component. Or a process including any one of removal of impurities in the liquid containing the analysis target component, mixing of the liquid containing the analysis target component and a reagent, and inducing a chemical reaction with respect to the analysis target component. Good.

  According to the above configuration, it is possible to analyze components in various liquid samples or to increase the accuracy of the analysis. In addition, since pre-processing outside the analysis chip is unnecessary, the analysis can be simplified and shortened. In addition, since pre-processing can be performed inside the analysis chip, the external device can be reduced in size and cost.

  “Aspect 12” In the analysis chip according to the above aspects 1 to 11, a reagent that causes a chemical reaction by contact with the analysis target component may be stored in the analysis unit.

  According to said structure, the analysis object component introduced into the analysis part contacts with the reagent preserve | saved at this analysis part, and produces a chemical reaction. And an analysis object component can be analyzed by observing this reaction result. Thereby, analysis can be performed easily.

  “Aspect 13” In the analysis chip according to the aspects 1 to 12, the liquid sample may be blood, and the non-analysis target component may be a blood cell.

  According to said structure, the analysis of various components in blood can be performed.

  [Aspect 14] In the analysis method according to one aspect of the present invention, the analysis component is analyzed in the analysis unit using the analysis chip according to aspects 1 to 13.

  “Aspect 15” An analyzer according to an aspect of the present invention is an analyzer that performs analysis on the analysis target component in the analysis unit provided in the analysis chip according to aspects 1 to 13, wherein A separation mechanism is provided, and a rotation mechanism capable of installing the analysis chip is provided so that the analysis part is arranged on the outer peripheral side.

  According to said structure, the to-be-analyzed component in a flow path can be moved with a centrifugal force, and can be introduce | transduced into an analysis part. The separation unit is arranged so that the direction in which the analysis target component is introduced into the flow path is different from the moving direction of the analysis target component in the flow path. Therefore, it is possible to prevent the non-analysis target component held in the separation unit from being introduced into the flow path due to the application of the centrifugal force. Therefore, it is possible to prevent the introduction of the non-analysis target component into the analysis unit, which causes an analysis error, and thus it is possible to easily perform a highly accurate analysis.

  “Aspect 16” In the analyzer according to aspect 15, the rotation mechanism unit (table 20a) is provided with the analysis chip so that the separation unit is disposed in the vicinity of the rotation axis of the rotation mechanism unit. May be possible.

  According to the above configuration, a centrifugal force is generated by rotating the analysis chip by the rotation mechanism unit, and this centrifugal force is smaller as it is closer to the rotation axis of the rotation mechanism unit. Therefore, it is possible to prevent the non-analysis target component separated in the separation unit from being introduced into the flow path by centrifugal force and the non-analysis target component from being damaged by the centrifugal force.

  “Aspect 17” In the analysis device according to the aspect 15 or 16, the separation unit includes a centrifugal separation of the analysis target component on at least a part of a side surface different from the surface where the analysis target component is introduced into the flow path. A storage unit in which the non-analyzed component is moved from the separation unit and stored when a force is applied is disposed, and a light source that irradiates irradiation light to the storage unit, and irradiation from the light source And a detector (photodetector 34) that detects the amount of absorption of the irradiation light that has passed through the storage portion due to the non-analyzed component or the liquid component in the damaged non-analyzed component. May be.

  According to said structure, a detector detects the absorption amount by the liquid component in the non-analysis target component which exists in the storage part, or the damaged non-analysis target component with the irradiation light irradiated with respect to the storage part .

  As a result, the analysis device calculates the amount of the non-analytical component introduced into the flow path from the separation unit or the amount of the liquid component in the damaged non-analytical component existing in the storage unit by centrifugal force. Can be measured. Therefore, the analyzer can also warn that a non-analysis target component or a liquid component in the damaged non-analysis target component may be introduced into the flow path or the analysis unit. It is also possible to evaluate the ease of breakage of non-analyzed components. Therefore, generation of analysis errors can be prevented, and more accurate analysis can be performed.

  The present invention is not limited to the above-described embodiments, and various modifications are possible within the scope shown in the claims, and embodiments obtained by appropriately combining technical means disclosed in different embodiments. Is also included in the technical scope of the present invention. Furthermore, a new technical feature can be formed by combining the technical means disclosed in each embodiment.

  The present invention can be used for an analysis chip and an analysis apparatus.

1, 40, 50, 60, 64, 65, 70, 80 Analysis chip 2 Sample introduction unit 3, 51, 55, 57 Blood cell separation unit 4 Pretreatment unit 5 Analysis unit 6 Filter material (separation unit)
7, 52, 56, 58 Storage unit 8 Lower space 9 Waste liquid unit 11 First channel 12 Second channel 13 Third channel 14 First valve unit 15 Second valve unit 16 Upper substrate 17 Lower substrate 20 Rotating device ( Analysis equipment)
20a Table (rotating mechanism)
20b Rotating shaft 30, 35 Analyzing device 31, 33 Light source 32, 34 Photodetector (detector)
53 4th channel (container connection channel)
61 Central axis 62 Analysis unit 63 5th flow path 63a End part 66 7th flow path 71 Lower filter material (absorber)
81 Open hole (atmosphere open part)
82 6th channel

Claims (5)

By separating the analysis target component from the liquid sample, the separation unit transmits the analysis target component and prevents the non-analysis target component, which is a component other than the analysis target component, from passing through;
An analysis unit for analyzing the analysis target component separated in the separation unit;
A flow path for connecting the separation unit and the analysis unit and moving the analysis target component separated in the separation unit to the analysis unit,
The separation unit is configured such that a direction in which the analysis target component separated in the separation unit is introduced into the flow path is different from a moving direction of the analysis target component that moves in the flow path to the analysis unit. An analysis chip that is arranged.   At least a part of the side surface of the separation unit that is different from the surface into which the analysis target component is introduced into the flow path is the non-analysis target component when the centrifugal force is applied to the analysis target component. The analysis chip according to claim 1, further comprising a storage unit that is moved and stored from the separation unit.   The analysis chip according to claim 2, wherein the separation unit and the storage unit are connected by a plurality of storage unit connection channels.   The analysis chip according to claim 3, wherein inner walls of the plurality of storage unit connection channels have hydrophobicity. In the analysis part with which the analysis chip according to any one of claims 2 to 4 is provided, it is an analysis device which performs analysis to the analysis object ingredient,
A rotation mechanism capable of installing the analysis chip such that the separation unit is disposed on the inner peripheral side and the analysis unit is disposed on the outer peripheral side;
A light source for irradiating irradiation light to the storage unit;
And a detector for detecting an absorption amount of the irradiation light irradiated from the light source and passed through the storage portion by a non-analysis target component or a liquid component in the damaged non-analysis target component. Analysis equipment.

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