JP2008175810A - Cartridge for analysis, and absorbance measuring device - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a cartridge for analysis with the performance of its separation column maintained while not used yet, and with a measurement specimen separated therefrom in a simple operation by the separation column when used. <P>SOLUTION: In the cartridge 10 for analysis, an operation plate 50 is positioned at a first position while not used yet. Since a state is maintained in which places ranging from an inflow passage 28, via the separation column 29 and an outflow passage 30, as far as this side of an effluent port 16a, are filled with an eluent A, the separation column 29 does not get dry and its intrinsic performance can be maintained. Meanwhile, when used, the operation plate 50 is positioned at a second position, and a state is brought about wherein blood held in a blood holding hole 52 can be introduced into the separation column 29. Further, constituents contained in the blood can be separated from each other since the effluent port 16a is thrown open while supply ports 21a and 22a of first and second cylinders 21 and 22 are all thrown open to cause effluents A and B to get from the inflow passage 28, via the separation column 29 and the outflow passage 30, to an affluent tank 16. <P>COPYRIGHT: (C)2008,JPO&INPIT

Description

  The present invention relates to an analytical cartridge used for analyzing a measurement sample and an absorbance measuring apparatus suitable for the same.

2. Description of the Related Art Conventionally, in hospital inspection facilities and inspection centers, blood is used as a measurement sample, and a specific component contained therein is measured using a liquid chromatography (hereinafter referred to as “LC”) device. For example, Patent Document 1 discloses an LC device that analyzes glycohemoglobin, which is an index for long-term control of diabetes. In this LC apparatus, eluents A and B stored in two bottles are sucked by a liquid feed pump, and sucked by a liquid feed pump via a deaeration device, an eluent switching valve, and an eluent mixing manifold. . The mixed solution of the eluents A and B that has passed through the liquid feed pump is introduced into the separation column together with the blood sample introduced from the sample introduction unit. Then, glycohemoglobin is detected by a spectrophotometer arranged on the downstream side of the column.
JP 2001-74721 A

  Since such an LC apparatus is a large-scale system, it is not suitable for a point-of-care test (POCT) performed by medical staff in the field of medical care or nursing. On the other hand, as a glycohemoglobin detection device considering POCT, for example, a device that uses an analysis cartridge set in an absorbance measurement system, such as DCA2000 of Bayer, is known. However, since DCA2000 does not employ the LC method, development of a simple analytical cartridge that employs the LC method is desired. When developing a simple analytical cartridge that uses the LC method, it is required that the performance of the separation column not deteriorate when it is not used, and that the measurement sample be introduced into the separation column by a simple operation when in use. Is done.

  The present invention has been made in view of such problems, and an analytical cartridge capable of maintaining the performance of a separation column when not in use and capable of separating a measurement sample with a separation column by a simple operation when in use. Is one of the purposes. Another object is to provide an absorbance measurement apparatus capable of performing LC analysis using such an analytical cartridge.

  The present invention adopts the following means in order to achieve at least one of the above objects.

The analytical cartridge of the present invention is:
A separation column;
One or more cylinders for storing liquid to be supplied to the separation column;
An inflow passage for guiding the liquid supplied from the supply port of the one or more cylinders to the inlet of the separation column;
An outflow passage for guiding the liquid flowing out from the outlet of the separation column to a waste liquid port;
A detection passage provided so as to form a part of the outflow passage and capable of detecting a component in the liquid by an external detection device;
A sample holding unit capable of holding a measurement sample; when not in use, the sample holding unit is disposed at a position away from the inflow passage, the waste liquid port is closed, and the supply ports of the one or more cylinders are opened and closed. Positioned at a first position so that a state filled with a predetermined liquid is maintained from the inflow passage to the front of the waste liquid port through the separation column and the outflow passage by being in a predetermined open / close state, In use, the sample holder is disposed at a position that fits the inflow passage, and the waste liquid port is opened, and at least one of the one or more cylinder supply ports is opened to open the supply port. An operation plate positioned at a second position for allowing the liquid supplied from the inflow passage to the inflow passage from the inflow passage to the waste liquid port through the separation column and the outflow passage. ,
It is equipped with.

  When the analysis cartridge of the present invention is not used, the operation plate is positioned at the first position. Then, the sample holding part is disposed at a position away from the inflow passage. In addition, by closing the waste liquid port and opening and closing the supply port of one or more cylinders to a predetermined open / close state, the state filled with the predetermined liquid from the inflow passage to the front of the waste liquid port through the separation column and the outflow passage can be obtained. Maintained. Therefore, the original performance can be maintained because the separation column is immersed in a predetermined liquid without drying when not in use. On the other hand, at the time of use, the operation plate is positioned at the second position while the measurement sample is held in the sample holding portion. Then, since the sample holder is disposed at a position that matches the inflow passage, the measurement sample can be introduced into the separation column. Further, the waste liquid port is opened, and at least one of the one or more cylinder supply ports is opened, and the liquid supplied from the cylinder with the supply port opened to the inflow passage is separated from the inflow passage through the separation column and the outflow passage. In order to reach the waste liquid port, the components contained in the measurement sample can be separated. Thus, according to the present invention, a simple analytical cartridge employing the LC method can be provided. In addition, the performance of the separation column can be maintained when not in use, and the measurement sample can be separated with the separation column by a simple operation of switching the operation plate from the first position to the second position when in use. .

  In the analysis cartridge of the present invention, the waste liquid port may be opened and closed by opening and closing the discharge port or the outflow passage of the separation column. Since the discharge port of the separation column is connected to the waste liquid port by the outflow passage, opening and closing the discharge port or outflow passage of the separation column will eventually open and close the waste liquid port. In addition, when opening and closing the discharge port of the separation column, the front of the waste liquid port means the discharge port of the separation column, and when opening and closing the outflow passage, the front of the waste liquid port means the outflow passage.

  In the analysis cartridge of the present invention, when the operation plate is positioned at the first position, all the supply ports of the one or more cylinders may be closed. By doing so, the system is closed from the inflow passage to the front of the waste liquid port through the separation column, so that the liquid filled therein and the liquid stored in the cylinder do not mix. Further, the liquid filled in the closed system may have the same composition as the liquid stored in any of the cylinders, but may have a different composition.

  In the analysis cartridge according to the present invention, when the operation plate is positioned at the first position, the operation plate stores one supply port of the one or more cylinders or a liquid having the same composition in the one or more cylinders. The cylinder supply ports may be opened and the remaining cylinder supply ports may be closed. In this way, since the system is closed from the cylinder with the supply port open to the waste liquid port through the inflow passage and the separation column, the liquid filled therein and the cylinder with the supply port closed are stored. It does not mix with the liquid being used. In this case, the liquid filled in the closed system is the same as the liquid stored in the cylinder whose supply port is opened. When there is one cylinder, the supply port is opened.

  In the analysis cartridge according to the present invention, when the operation plate is positioned at the second position, the sample holding portion is made to coincide with a supply port of one of the one or more cylinders and the waste liquid port. And all the supply ports of the one or more cylinders may be opened. In this way, the liquid stored in each cylinder can be mixed at a desired ratio and supplied to the inlet of the separation column.

  The analysis cartridge according to the present invention includes one cylinder, and the cylinder is divided into a plurality of chambers by a plurality of movable partition walls slidable in a liquid-tight manner, and liquids having different compositions are respectively contained in the plurality of chambers. When the most distal movable partition is pushed toward the tip of the cylinder during use, the supply movable port sequentially reaches the distal end surface of the cylinder among the plurality of movable partitions. It may be configured such that the room facing the room changes. In this way, it is not necessary to store liquids having different compositions in a plurality of cylinders and mix the liquids in a desired ratio.

  The analysis cartridge of the present invention includes a dilution tank for storing a liquid for diluting the measurement sample, and the operation plate can be positioned at an intermediate position between the first position and the second position. The dilution tank may be provided such that the sample holding portion is disposed inside the dilution tank when the operation plate is positioned at the intermediate position. In this way, the measurement sample can be diluted and supplied to the separation column. As a specific method of dilution, manual amplitude agitation may be performed in a state where the sample holding unit is disposed inside the dilution tank, or vibration agitation by an ultrasonic vibrator may be performed.

  The analysis cartridge of the present invention includes an internal / external communication path that communicates with the outside, and the operation plate is positioned at the first position even when the sample holding portion forms a part of the internal / external communication path. Good. In this way, when the operation plate is positioned at the first position, it is possible to hold the measurement sample on the sample holder from the outside via the internal / external communication path. In the analysis cartridge of the present invention adopting this aspect, the inner and outer communication passages are passages through which the measurement sample can be introduced into the sample holding portion by utilizing capillary action by attaching a liquid measurement sample to the outside. Also good. In this way, the liquid measurement sample can be easily held in the sample holding portion.

  The analysis cartridge of the present invention may include a drop-off prevention mechanism that prevents the operation plate from dropping off. By doing so, there is no possibility that the operation plate is detached from the analysis cartridge due to an operator's operation error. In the analysis cartridge of the present invention adopting this aspect, the drop-off prevention mechanism includes a locking portion provided on the operation plate, and an interval between the first position and the second position. And a locked portion that locks with the locking portion and restricts the movement of the operation plate when moved in the direction of detachment and dropping. In this way, the operation plate can be prevented from falling off with a relatively simple configuration.

  The analysis cartridge of the present invention may include a waste liquid tank that receives the liquid flowing out from the outlet of the separation column through the waste liquid port. In this way, it is not necessary to prepare a waste liquid tank separately from the analysis cartridge. In the analytical cartridge of the present invention adopting this aspect, the one or more cylinders may be accommodated in the waste liquid tank. In this way, the entire analysis cartridge can be made compact compared to the case where the waste liquid tank and one or more cylinders are provided separately. At this time, the outflow passage may be formed so that the downstream side of the detection passage intersects the separation column. In this way, it can be made more compact.

  In the analysis cartridge according to the present invention, the cylinders are arranged so that a plurality of cylinders are substantially parallel to each other, and the separation column has the axial direction substantially orthogonal to the axial direction of the plurality of cylinders and the plurality of cylinders. You may arrange | position so that the supply port of a cylinder may be opposed. In this way, a plurality of cylinders and separation columns can be laid out without waste, and the entire analysis cartridge can be made compact. In the analytical cartridge of the present invention employing this aspect, the detection passage is substantially parallel to the axial direction of the separation column on the side opposite to the side where the plurality of cylinders are arranged in the separation column. It may be formed as follows. If it carries out like this, it can be made compact including a detection channel | path. The layout of the cylinders and separation columns in the analysis cartridge of the present invention is not limited to this.

  In the analysis cartridge of the present invention, the inflow passage may be formed at least partially with a turbulent mixing part or a diverging / merging / mixing part. In this case, the liquid supplied from the cylinder supply port can be sufficiently mixed and then guided to the separation column, so that the analysis accuracy is improved. The analysis cartridge of the present invention may be discarded after being used once for analysis of a measurement sample.

The absorbance measuring apparatus of the present invention is
An installation section on which any of the cartridges for analysis described above can be installed;
A pressing mechanism capable of independently pressing the liquid in the one or more cylinders of the analysis cartridge installed in the installation unit;
A light-emitting element disposed on one side of the detection path and a light-receiving element disposed on the other side of the detection path are configured to allow light emitted from the light-emitting element to enter the detection path and pass through the detection path. A detector that receives the subsequent light at the light receiving element;
It is equipped with.

  In this absorbance measurement apparatus, first, an analysis cartridge is installed in the installation section. The analysis cartridge may be positioned in the second position with the operation plate holding the measurement sample in the sample holding unit before being installed in the installation unit, or after being installed in the installation unit. The plate may be positioned from the first position to the second position. In the state where the operation plate is positioned at the second position, the measurement sample can flow into the separation column, and the liquid after passing through the separation column can flow out to the waste liquid tank. Subsequently, the liquid composition supplied to the separation column can be made a desired composition by individually adjusting the pressing force of the cylinder of the analysis cartridge by the pressing mechanism. In addition, the liquid passing through the detection passage after passing through the separation column can be detected by a detector and the absorbance can be measured. Thus, according to the absorbance measuring apparatus of the present invention, LC analysis using any of the above-described analytical cartridges can be easily performed.

  The pressing mechanism may be constituted by, for example, a piston rod inserted into the cylinder and an actuator (for example, a motor, an air pressure cylinder, a hydraulic cylinder, etc.) that moves the piston rod in the axial direction of the cylinder. Moreover, the detector may be comprised by LED as a light emitting element, and the phototransistor as a light receiving element.

  In the absorbance measuring apparatus of the present invention, the detector includes at least one of a diffusion plate that diffuses light of the light emitting element or a polarizing plate that suppresses the influence of reflected light between the light emitting element and the detection path. It may be configured. When the diffuser plate is used, the illuminance distribution can be made uniform even when the light emitting element employs a light emitting element having a luminance spot such as an LED. Moreover, when a polarizing plate is used, the influence of reflected light or the like can be suppressed. Therefore, in any case, the absorbance measurement can be accurately performed.

  Next, embodiments of the present invention will be described with reference to the drawings. 1 is a front view of an analysis cartridge 10 according to an embodiment of the present invention, FIG. 2 is a plan view of the analysis cartridge 10, and FIG. 3 is a cylinder unit when an operation plate 50 is positioned at a first position. 4 is a perspective view of the column unit 24. FIGS. 5 and 6 are cross-sectional views taken along the line A-A in FIG. 1 when the operation plate 50 is positioned at the first position. It is a perspective view.

  The analysis cartridge 10 is inserted between a cylinder unit 12 having protruding plate portions 14a and 14b on the upper and lower sides of one end surface of a substantially rectangular parallelepiped body 14, and a pair of protruding plate portions 14a and 14b of the cylinder unit 12, respectively. The column unit 24 is integrated with the cylinder unit 12, and the operation unit 40 is disposed between the column unit 24 and the cylinder unit 12. In this embodiment, the analysis cartridge 10 is intended to diagnose diabetes, and separates stable glycated hemoglobin, unstable glycated hemoglobin, and hemoglobin from blood as a measurement sample, and absorbs the respective absorbances. It is used when measuring. The analysis cartridge 10 is a so-called disposable type, and is discarded after being used once for analysis of a measurement sample. The overall size of the analysis cartridge 10 is about 20 mm in width (W), about 55 mm in depth (D), and about 10 mm in height (H).

  The cylinder unit 12 is made of a transparent acrylic resin, and has a waste liquid tank 16 in which the inside of the body 14 is hollowed out, and first and second cylinders 21 and 22 that are arranged substantially parallel to the inside of the waste liquid tank 16. And have. The waste liquid tank 16 receives the waste liquid that has passed through the separation column 29 via the waste liquid port 16a that penetrates the end face of the body 14, and is filled with air when not in use. An air vent hole 18 is provided on the upper surface of the waste liquid tank 16. Since the air vent hole 18 is covered with a hydrophobic porous membrane, gas can pass but liquid cannot pass. The first cylinder 21 is connected to an inflow passage 28 connected to the inlet of the separation column 29 via a first supply port 21 a penetrating the end face of the body 14, and the second cylinder 22 is a second penetrating the end face of the body 14. It is connected to the inflow passage 28 via the supply port 22a. The first cylinder 21 is sealed in a liquid-tight manner by the rubber packing 21b in a state where the eluent A is stored, and the second cylinder 22 is sealed in the state where the rear end is a rubber packing in a state where the eluent B is stored. 22b is liquid-tightly sealed. The eluents A and B are liquids having different salt concentrations. In addition to the waste liquid port 16a, the end surface of the body 14 is provided with a vent port 19 that is an opening on the waste liquid tank 16 side of the capillary passage 36.

  The column unit 24 is made of a transparent acrylic resin, and a plurality of cation-exchangeable silica monolith discs (hereinafter referred to as “disc M”) and hydrophobic silica monolith discs (hereinafter referred to as “disc O”) are laminated and subjected to heat shrinkage. Inflow that collects liquid supplied from the supply ports 21a and 22a of the first and second cylinders 21 and 22 and guides them to the inlet of the separation column 29 while holding the separation column 29 filled in the tube A passage 28 and an outflow passage 30 for guiding the liquid flowing out from the outlet of the separation column 29 to the waste liquid port 16a are provided. Among these, the column holding unit 26 faces the supply ports 21a and 22a of these cylinders 21 and 22 so that the axial direction of the separation column 29 is substantially orthogonal to the axial direction of the first and second cylinders 21 and 22. Are arranged as follows. The separation column 29 held by the column holding unit 26 is formed by laminating a disk M and a disk O each having an inner diameter of 3.2 mm and a thickness of 2 mm so as to be MMMOOO, and pressing the inlet side of the separation column 29. The liquid stopper 34 holds the liquid tight. The average pore diameter of the disk M is 0.5 to 5 μm, preferably 1 to 2.3 μm, and the average pore diameter of the disk O is 1 to 5 μm, preferably 2 to 4.2 μm. The separation column 29 is not limited to this, and may be appropriately selected according to the measurement sample. The inflow passage 28 extends downward from the supply port 22a of the second cylinder 22, and then extends downward from the supply port 21a of the first cylinder 21 along the axial direction of the separation column 29. 21 is formed so as to merge with a passage extending from the supply port 21 a of 21 to the inlet of the separation column 29. The outflow passage 30 is formed so as to extend from the separation column 29 to the opposite side of the cylinder unit 12, extend along the axial direction of the separation column 29, and then intersect with the separation column 29 and connect to the waste liquid port 16 a. This outflow passage 30 also intersects with the inflow passage 28 at the portion that reaches the waste liquid port 16a after the three-dimensional intersection with the separation column 29. Further, a portion of the outflow passage 30 extending along the axial direction of the separation column 29 is a detection passage 32, and a peripheral wall of the detection passage 32 is formed of black acrylic resin. The detection passage 32 can detect a component in the liquid by an absorbance measurement device 60 (see FIG. 9), which is an external detection device, which will be described later. The column unit 24 is formed with an L-shaped passage 27 that communicates with the vent 19 of the cylinder unit 12 via the operation unit 40. The L-shaped passage 27 forms a part of the capillary passage 36 and opens to the outside on the side surface of the column unit 24.

  The operation unit 40 includes a plate holder 42 sandwiched between the cylinder unit 12 and the column unit 24, and an operation plate 50 that is inserted into a slit of the plate holder 42 and operated by an operator. The plate holder 42 is made of soft rubber such as silicone rubber, and is formed by bonding two wall members so that a gap is formed, and this gap is a slit that holds the operation plate 50. The two wall members constituting the plate holder 42 include capillary passage communication holes 44 that allow the vent 19 provided in the cylinder unit 12 and the L-shaped passage 27 provided in the column unit 24 to communicate with each other. A first cylinder communication hole 45 that communicates the supply port 21a of the cylinder 21 and the inflow passage 28, a waste liquid port communication hole 46 that communicates the waste liquid port 16a of the waste liquid tank 16 and the outflow passage 30, and a supply port 22a of the second cylinder 22 And a second cylinder communication hole 47 communicating with the inflow passage 28 is provided in this order. The operation plate 50 is made of a synthetic resin such as polyester or polyethylene, and has a rectangular recess 51 at the lower center. In addition to the blood holding hole 52 for holding blood as a measurement sample, the operation plate 50 is switched to the first cylinder communication hole 45 or the waste liquid port communication hole 46 by the operator's operation. A through hole 54 and a second through hole 56 for switching whether or not to communicate with the second cylinder communication hole 47 by an operator's operation are provided. In the vicinity of the exit of the slit of the plate holder 42, a stopper 58 that can be locked to the vertical edge 51a at the back of the recess 51 of the operation plate 50 and the vertical edge 51b at the front is provided. In addition, since the plate holder 42 is made of hydrophobic soft rubber, liquid tightness is maintained at the connection portion of each hole. Here, the inner surface of each hole of the plate holder 42 is preferably hydrophilic, but may be hydrophobic. The operation plate 50 has a hydrophobic surface, but the inner surface of the blood holding hole 52 is hydrophilic (for example, coated with a hydrophilic material).

  Next, a usage example of the analysis cartridge 10 of the present embodiment configured as described above will be described. First, the case where the analysis cartridge 10 is not used will be described with reference to FIGS. When the analysis cartridge 10 is not used, the operation plate 50 is pushed into the slit of the plate holder 42, and the vertical edge 51b in front of the concave portion 51 of the operation plate 50 and the stopper 58 are locked to operate further. The plate 50 is prevented from being pushed into the back. The position of the operation plate 50 at this time is referred to as a first position. At the first position, the capillary passage communication hole 44 of the plate holder 42 and the blood holding hole 52 of the operation plate 50 communicate with each other, so that the vent 19 of the cylinder unit 12 and the L-shaped passage 27 of the column unit 24 communicate with each other. These constitute the capillary passage 36 as a whole. Further, since the first cylinder communication hole 45 of the plate holder 42 and the first through hole 54 of the operation plate 50 communicate with each other, the supply port 21a of the first cylinder 21 of the cylinder unit 12 and the inflow passage 28 of the column unit 24 are connected. Communicate. On the other hand, since the second through hole 56 of the operation plate 50 is located between the waste liquid port communication hole 46 and the second cylinder communication hole 47 of the plate holder 42, the waste liquid port 16 a and the outflow passage 30 are formed by the operation plate 50. The supply port 22 a and the inflow passage 28 of the second cylinder 22 are also blocked by the operation plate 50. The first cylinder 21 is fully filled with the eluent A, but the supply port 21a of the first cylinder 21 communicates with the inflow passage 28 and the waste liquid port 16a is shut off from the outflow passage 30. The state is filled with the eluent A from the passage 28 through the separation column 29 and the outflow passage 30 to just before the waste liquid port 16a. The second cylinder 22 is fully filled with the eluent B. However, since the supply port 22a of the second cylinder 22 is blocked from the inflow passage 28, the eluent B is only in the second cylinder 22. Exists. Further, since the waste liquid port 16a is blocked from the outflow passage 30, the waste liquid tank 16 is filled with air. The capillary passage 36 communicates the waste liquid tank 16 with the outside.

  As described above, when the analysis cartridge 10 is not used, a patient who undergoes a simple diabetes checker stabs a thin needle lightly into a fingertip to cause slight bleeding, and then presses the bleeding finger against the entrance of the capillary passage 36. Then, blood is introduced into the capillary passage 36 by capillary action. The operator can confirm that the capillary passage 36 is filled with blood by visually observing that the transparent capillary passage 36 is filled with red blood. Here, since the blood holding hole 52 of the operation plate 50 forms a part of the capillary passage 36, the blood is held in the blood holding hole 52. Moreover, since the blood holding hole 52 is coated with a hydrophilic material, the blood is held without a gap.

  Subsequently, the analysis cartridge 10 is switched from the unused state to the used state. That is, the operator pulls the operation plate 50 forward. Then, the stopper 58 engages with the vertical edge 51a in the back forming the recess 51 of the operation plate 50 and prevents the operation plate 50 from being pulled out further. The position of the operation plate 50 at this time is referred to as a second position. 7 and 8 are respectively a cross-sectional view taken along line AA in FIG. 1 and a perspective view of the operation unit 40 when the operation plate 50 is positioned at the second position. In the second position, the blood holding hole 52 for holding the blood of the operation plate 50 and the first cylinder communication hole 45 of the plate holder 42 communicate with each other, so that the supply port 21a and the inflow passage 28 of the first cylinder 21 The blood held in the blood holding hole 52 can be introduced into the inflow passage 28 together with the eluent A. Further, since the waste liquid port communication hole 46 of the plate holder 42 and the first through hole 54 of the operation plate 50 communicate with each other, the waste liquid that has passed through the separation column 29 can be discharged from the outflow passage 30 to the waste liquid tank 16. Further, since the second cylinder communication hole 47 of the plate holder 42 and the second through hole 56 of the operation plate 50 communicate with each other, the eluent B in the second cylinder 22 can be introduced into the inflow passage 28.

  The analysis cartridge 10 after being switched to the use state in this way is set in the cartridge installation portion 60 a of the absorbance measuring device 60. FIG. 9 is a schematic configuration diagram of an absorbance measuring device 60 in which the analysis cartridge 10 is set. The absorbance measuring device 60 moves the first piston rod 61a by the first stepping motor 61 to press the eluent A of the first cylinder 21 through the rubber packing 21b, and independently of this, the second stepping motor 62 is pressed. Then, the eluent B in the second cylinder 22 is pressed through the rubber packing 22b by moving the second piston rod 62a. Then, a controller 63 incorporating a known microcomputer drives and controls the first and second stepping motors 61 and 62 to adjust the pressing force of the eluent A and the pressing force of the eluent B, thereby supplying the separation column 29. The liquid composition to be supplied can be set to a desired composition. On the other hand, the liquid that has passed through the separation column 29 passes through the detection passage 32. Of the light from the LED light source 64 that is a light emitting element, the light that has passed through the dichroic mirror 76 enters the detection path 32 through the lens 65, the diffusion plate 66 and the polarizing plate 67, passes through the detection path 32, and then the lens 68. Enters the phototransistor 69 for measurement which is a light receiving element. On the other hand, the light reflected by the dichroic mirror 76 enters the luminance adjustment phototransistor 78. The light that has entered the measurement phototransistor 69 and the brightness adjustment transistor 78 is detected by the detection circuit 70, and the analog signal after detection is converted into a digital signal by the A / D conversion circuit 72 and input to the controller 63. The controller 63 obtains the luminance based on the digital signal obtained from the luminance adjustment phototransistor 78 via the detection circuit 70 and the A / D conversion circuit 72, so that the luminance of the LED light source 64 becomes uniform. Feedback control of current. The controller 63 controls the lighting circuit 74 so as to repeatedly turn on and off the LED light source 64, and converts the digital signal obtained from the measurement phototransistor 69 through the detection circuit 70 and the A / D conversion circuit 72. Based on the difference between when the LED light source 64 is turned on and when the LED light source 64 is turned off, a graph representing the relationship between the LC retention time and the absorbance is output to a display or printer (not shown). By performing such synchronous detection, absorbance measurement can be performed under a fluorescent lamp instead of in a dark box. Here, an example of absorbance measurement conditions is shown in Table 1. By adopting the absorbance measurement conditions shown in Table 1, the peaks of stable glycohemoglobin, unstable glycohemoglobin and hemoglobin can be separated, and a simple test for diabetes can be performed.

  According to this embodiment described in detail above, a simple analytical cartridge 10 employing the LC method can be provided. The analysis cartridge 10 can maintain the performance of the separation column 29 when not in use, and the blood is separated by a simple operation of switching the operation plate 50 from the first position to the second position when in use. It becomes possible to separate with. That is, when not in use, the operation plate 50 is positioned at the first position, and the state in which the operation plate 50 is filled with the eluent A from the inflow passage 28 to the front of the waste liquid port 16a through the separation column 29 and the outflow passage 30 is maintained. The separation column 29 can maintain its original performance without drying. On the other hand, in use, the operation plate 50 is positioned at the second position, and the blood held in the blood holding hole 52 can be introduced into the separation column 29. Further, the waste liquid port 16a is opened, the supply ports 21a and 22a of the first and second cylinders 21 and 22 are all opened, and the eluents A and B are transferred from the inflow passage 28 to the waste liquid tank 16 through the separation column 29 and the outflow passage 30. Therefore, the components contained in the blood can be separated. Further, the eluents A and B stored in the first and second cylinders 21 and 22 are individually adjusted to mix the eluents A and B at a desired ratio to the inlet of the separation column 29. Can be supplied.

  In addition, since the analysis cartridge 10 includes the waste liquid tank 16, it is not necessary to prepare a waste liquid tank separately from the analysis cartridge 10. Further, when the operation plate 50 is positioned at the first position, the blood as the measurement sample is attached to a portion opened to the outside of the capillary passage 36, thereby easily using the capillary phenomenon. Can be held in the blood holding hole 52. Furthermore, since the stopper 58 for preventing the operation plate 50 from dropping from the plate holder 42 is provided, there is no possibility that the operation plate 50 is detached from the analysis cartridge 10 due to an operator's operation error. The back vertical edge 51a forming the recess 51 of the operation plate 50 corresponds to the locking portion of the present invention, and the stopper 58 corresponds to the locked portion of the present invention. In addition, since the first and second cylinders 21 and 22 are accommodated in the waste liquid tank 16, the entire analysis cartridge 10 is made compact compared to the case where the waste liquid tank and these cylinders are provided separately. can do.

  In addition, the first and second cylinders 21 and 22 are arranged so as to be substantially parallel to each other, and the separation column 29 is arranged so that the axial direction is substantially orthogonal to the axial direction of the first and second cylinders 21 and 22. Since the cylinders 21 and 22 are arranged so as to face the supply ports 21a and 22a, the cylinders 21 and 22 and the separation column 29 can be laid out without waste, and the entire analysis cartridge 10 is compact. Can be The detection passage 32 is formed on the side of the separation column 29 opposite to the side where the first and second cylinders 21 and 22 are disposed so as to be substantially parallel to the axial direction of the separation column 29. In addition, since the downstream side of the detection passage 32 in the outflow passage 30 is formed to intersect the separation column 29 three-dimensionally, the waste liquid tank 16 and the detection passage 32 can be made compact.

  On the other hand, the controller 63 of the absorbance measuring device 60 individually presses the pressing force with which the first and second stepping motors 61 and 62 press the piston rods 61a and 62a, so that the liquid composition supplied to the separation column 29 is desired. Since the composition can be achieved, LC analysis using the analysis cartridge 10 can be easily performed. Further, since the diffusion plate 66 and the polarizing plate 67 are provided between the LED light source 64 and the detection passage 32, changes in the incidence rate and the emission rate to the detection passage 23 are reduced, and stable measurement is possible.

  It should be noted that the present invention is not limited to the above-described embodiment, and it goes without saying that the present invention can be implemented in various modes as long as it belongs to the technical scope of the present invention.

  For example, in the above-described embodiment, when the operation plate 50 is positioned at the first position, the supply port 21a of the first cylinder 21 is opened and the supply port 22a of the second cylinder 22 is closed. The supply ports 21a and 22a may be closed. In this way, since the system is closed from the inflow passage 28 to the front of the waste liquid port 16a, the liquid filled therein and the eluents A and B stored in the cylinders 21 and 22 are mixed. There is no. The liquid filled in the closed system may have the same composition as one of the eluents A and B stored in the first and second cylinders 21 and 22, but may have a different composition.

  In the embodiment described above, the blood held in the blood holding hole 52 is directly introduced into the inflow passage 28. However, as shown in FIG. 10, a diluting solution for diluting the blood held in the blood holding hole 52 is used. A dilution tank 80 for storage may be provided between the vent 19 of the capillary passage 36 and the supply port 21a of the first cylinder 21. In this case, immediately before the start of use of the analysis cartridge 10, the operation plate 50 is disposed at an intermediate position between the first position and the second position, and the blood held in the blood holding hole 52 is placed in the dilution tank 80. Add and dilute with diluent. Thereafter, the operation plate 50 is positioned at the second position so that the diluted sample is guided to the inflow passage 28. In this way, blood as a measurement sample can be diluted and supplied to the separation column 29. The dilution tank 80 may be fully filled with the diluent, but it is preferable to mix air and the diluent in consideration of efficiently diluting the blood in the blood holding hole 52. At this time, since the blood holding hole 52 is coated with a hydrophilic material, there is no possibility that air is mixed in the blood holding hole 52.

  In the analysis cartridge 10 of the above-described embodiment, in order to efficiently mix the eluents A and B in place of the inflow passage 28, a part or all of the inflow passage 128 is zigzag as shown in FIG. A mixing part may be formed. As the turbulent flow mixing section, the inflow passage is formed in a zigzag manner, and a porous filter that promotes mixing of the eluents A and B is disposed in the middle of the inflow passage 28 or immediately above the separation column 29, or a portion having a large diameter. And a thin portion may be repeatedly formed, or a plurality of protrusions may be formed inside the inflow passage. Alternatively, a small-diameter bead is put in a predetermined section of the inflow passage, and both ends of the predetermined section are covered with a net or the like to form a diverging / merging / mixing unit, and the mixed liquid colliding with the beads is diverted and then merged. Good. As the branching / merging / mixing unit, a mixer disclosed in Japanese Patent Application Laid-Open No. 2006-15272 may be used. In the diverging / merging / mixing unit, after diverging, the diverging / merging / mixing units may be re-merged through flow paths having different lengths. In this way, after one of the divided flows, one of them merges later than the other, so that the mixing is performed more efficiently.

  In the analysis cartridge 10 of the above-described embodiment, when the operation plate 50 is positioned at the first position, the supply port 21a of the first cylinder 21 is opened and the supply port 22a and the waste liquid port 16a of the second cylinder 22 are opened. Although closed, the supply ports 21a and 22a and the waste liquid port 16a of the first and second cylinders 21 and 22 may be closed as shown in FIG. In this case, when the operation plate 50 is positioned at the second position, as shown in FIG. 12B, the blood holding hole 52 of the operation plate 50 is connected to the supply port of the first cylinder 21 as in the above-described embodiment. Since the blood is introduced into the inflow passage 28 in accordance with 21a, the first through hole 54 matches the waste liquid port 16a, and the second through hole 56 matches the supply port 22a of the second cylinder 22, the first and first The eluents A and B stored in the two cylinders 21 and 22 can be introduced into the inflow passage 28 at an appropriate ratio.

  In the analysis cartridge 10 of the above-described embodiment, the detection passage 32 is formed along the axial direction of the separation column 29. However, as shown in FIG. For example, you may form so that it may have 40-50 degrees. In this case, the LED light source 64 and the measurement phototransistor 69 of the absorbance measuring device are arranged so that the light passes through the detection passage 132.

  In the embodiment described above, the separate eluents A and B are stored in the two cylinders 21 and 22, but as shown in FIG. 14, a plurality of chambers 120x are formed by the movable partition walls 121 and 122 and the rubber packing 123. , 120y, 120z may be prepared, and separate eluents X, Y, Z may be stored in the respective chambers 120x, 120y, 120z. The operation plate 150 has a first through hole 154 and a second through hole 156 in addition to the blood holding hole 152 similar to the blood holding hole 52 of the above-described embodiment. When the operation plate 150 is positioned at the first position, as shown in FIG. 14A, the blood holding hole 152 constitutes a part of the capillary passage 36, and the first through hole 154 is the cylinder 120. The second through hole 155 is located between the supply port 120a and the waste liquid port 116a. For this reason, the state is filled with the eluent X stored in the first chamber 120x (the most advanced chamber) from the inflow passage 28, through the separation column 29, the outflow passage 30, and before the waste liquid outlet 116a. ing. An escape groove 124 is formed between the inlet 120aa of the passage from the inside of the cylinder 120 to the supply port 120a and the front end surface of the cylinder 120. In this state, blood is introduced into the capillary passage 36 using the capillary phenomenon, and the operation plate 150 is positioned at the second position. Then, as shown in FIG. 14 (b), the blood holding hole 152 coincides with the supply port 120 a of the cylinder 120, so that blood can be introduced into the inflow passage 28. The first through hole 154 is located between the supply port 120a and the waste liquid port 116a. However, since the second through hole 156 communicates with the waste liquid port 116a, the outflow passage 30 communicates with the waste liquid tank 116. Then, after this analytical cartridge is set in the absorbance measuring device 60, the rubber packing 123 of the cylinder 120 is pressed toward the tip of the cylinder 120 by the piston rod. Then, as shown in FIG. 14 (b), the eluent X stored in the first chamber 120x is supplied from the supply port 120a to the separation column 29, and thereafter, as shown in FIG. 15 (a), the movable partition wall When 121 exceeds the inlet 120aa, the eluent X is guided to the inlet 120aa through the escape groove 124, and the eluent Y stored in the second chamber 120y is also supplied to the separation column 29 from the inlet 120aa. For this reason, the mobile phase until the movable partition 121 reaches the tip surface of the cylinder 120 is switched from the composition of the eluent X to the composition of the eluent Y with a concentration gradient. Thereafter, as shown in FIG. 15 (b), when the movable partition wall 122 exceeds the inlet 120aa, the eluent Y is guided to the inlet 120aa through the escape groove 124 and the elution stored in the third chamber 120z. Liquid Z is also supplied to the separation column 29 from the inlet 120aa. For this reason, the mobile phase until the movable partition wall 122 reaches the tip surface of the cylinder 120 is switched from the composition of the eluent Y to the composition of the eluent Z with a concentration gradient. Thereafter, as shown in FIG. 15C, when the rubber packing 123 reaches the front end surface of the cylinder 120, the eluent becomes empty. In this way, the chamber connected to the supply port 120a is switched each time when it reaches the distal end surface of the cylinder 120 in order from the movable partition wall on the distal end side, and different eluents are supplied to the separation column 29. There is no need to store separate compositions of liquid and mix each liquid in the desired ratio.

  In the above-described embodiment, the size of the analysis cartridge 50 is a very compact size having a width (W) of about 20 mm, a depth (D) of about 55 mm, and a height (H) of about 10 mm. For example, it may be twice or three times larger than this, or may be larger. Further, the type, size, and eluent of the separation column 29 to be used may be appropriately determined according to the measurement sample.

  In the embodiment described above, the waste liquid tank 16 is built in the analysis cartridge 10, but the waste liquid tank 16 may be externally attached to the analysis cartridge 10.

  In the above-described embodiment, the vertical edge 51b in front of the concave portion 51 of the operation plate 50 and the stopper 58 are locked to prevent the operation plate 50 from being pushed any further. In a state where is positioned at the second position, the tip (back end) of the operation plate 50 may be prevented from being pushed further by hitting the wall of the body 14. In this case, the vertical edge 51b may be omitted.

  In the embodiment described above, the waste liquid port 16a is opened and closed by the operation plate 50. However, depending on the structure of the analysis cartridge, the waste liquid can be opened and closed by opening and closing the discharge port and the outflow passage 30 of the separation column 29 by the operation plate 50. The mouth 16a may be opened and closed. Since the outlet of the separation column 29 is connected to the waste liquid outlet 16a by the outflow passage 30, opening and closing the outlet of the separation column 29 or opening and closing the outflow passage 30 will eventually open and close the waste liquid outlet 16a. It will be.

FIG. 3 is a front view of the analysis cartridge 10. FIG. 3 is a plan view of the analysis cartridge 10. The perspective view of the cylinder unit 12 when the operation plate 50 is positioned in the 1st position. The perspective view of the column unit 24. FIG. FIG. 2 is a cross-sectional view taken along line AA of FIG. 1 when an operation plate 50 is positioned at a first position. The perspective view of the operation unit 40 when the operation plate 50 is positioned in the 1st position. AA sectional drawing of FIG. 1 when the operation plate 50 is positioned in the 2nd position. The perspective view of the operation unit 40 when the operation plate 50 is positioned in the 2nd position. The schematic block diagram of the light absorbency measuring apparatus 60 which set the cartridge 10 for analysis. Sectional drawing of the cartridge for analysis of other embodiment. Sectional drawing of the column unit of other embodiment. Explanatory drawing of the 1st position and 2nd position of other embodiment. Explanatory drawing of the light absorbency measuring apparatus which set the cartridge for analysis of other embodiment. Operation | movement explanatory drawing of other embodiment (the 1). Operation | movement explanatory drawing of other embodiment (the 2).

Explanation of symbols

  DESCRIPTION OF SYMBOLS 10 Analysis cartridge, 12 Cylinder unit, 14 Body, 14a, 14b Projection board part, 16 Waste liquid tank, 16a Waste liquid port, 18 Air vent hole, 19 Air vent, 21 1st cylinder, 21a Supply port, 21b Rubber packing, 22 2nd cylinder, 22a supply port, 22b rubber packing, 24 column unit, 26 column holding part, 27 L-shaped passage, 28 inflow passage, 29 separation column, 30 outflow passage, 32 detection passage, 34 rubber plug, 36 capillary passage, 40 Operation unit, 42 Plate holder, 44 Capillary passage communication hole, 45 First cylinder communication hole, 46 Waste liquid port communication hole, 47 Second cylinder communication hole, 50 Operation plate, 51 Recess, 51a Vertical edge, 51b Vertical edge, 52 Blood holding hole, 54 through hole, 56 through hole, 58 s 60, absorbance measuring device, 61 first stepping motor, 61a first piston rod, 62 second stepping motor, 62a second piston rod, 63 controller, 64 LED light source, 65 lens, 66 diffuser plate, 67 polarizing plate, 68 Lens, 69 Phototransistor for measurement, Phototransistor, 70 Detection circuit, 72 A / D conversion circuit, 74 Lighting circuit, 76 Dichroic mirror, 78 Phototransistor for brightness adjustment, 80 Dilution tank, 116 Waste liquid tank, 116a Waste liquid port , 120 cylinder, 120a supply port, 120x, 120y, 120z chamber, 121 movable partition, 122 movable partition, 123 rubber packing, 128 inflow passage, 132 detection passage, 150 operation plate, 152 blood holding hole, 154 through hole, 155 Throughbore, 156 through hole, X, Y, Z eluent.

Claims (18)

A separation column;
One or more cylinders for storing liquid to be supplied to the separation column;
An inflow passage for guiding the liquid supplied from the supply port of the one or more cylinders to the inlet of the separation column;
An outflow passage for guiding the liquid flowing out from the outlet of the separation column to a waste liquid port;
A detection passage provided so as to form a part of the outflow passage and capable of detecting a component in the liquid by an external detection device;
A sample holding unit capable of holding a measurement sample; when not in use, the sample holding unit is disposed at a position away from the inflow passage, the waste liquid port is closed, and the supply ports of the one or more cylinders are opened and closed. Positioned at a first position so that a state filled with a predetermined liquid is maintained from the inflow passage to the front of the waste liquid port through the separation column and the outflow passage by being in a predetermined open / close state, In use, the sample holder is disposed at a position that fits the inflow passage, and the waste liquid port is opened, and at least one of the one or more cylinder supply ports is opened to open the supply port. An operation plate positioned at a second position for allowing the liquid supplied from the inflow passage to the inflow passage from the inflow passage to the waste liquid port through the separation column and the outflow passage. ,
Cartridge for analysis. When the operation plate is positioned at the first position, all the supply ports of the one or more cylinders are closed.
The analysis cartridge according to claim 1. When the operation plate is positioned at the first position, one of the one or more cylinders or the cylinder of the one or more cylinders that stores liquid of the same composition is left open. Close the cylinder's supply port,
The analysis cartridge according to claim 1. When the operation plate is positioned at the second position, the sample holding portion is made to coincide with a supply port of one of the one or more cylinders, and all of the waste liquid port and the one or more cylinders are arranged. Open the supply port,
The analysis cartridge according to claim 1. The cylinder is provided with only one cylinder, and is divided into a plurality of chambers by a plurality of movable partition walls slidable in a liquid-tight manner. In the plurality of chambers, liquids having different compositions are stored, and the most movable at the time of use. When the partition wall is pressed toward the tip of the cylinder, the movable partition wall on the tip side among the plurality of movable partition walls sequentially reaches the tip surface of the cylinder, and the room facing the supply port changes each time. Being
The analysis cartridge according to claim 1. The analysis cartridge according to any one of claims 1 to 5,
A dilution tank for storing a liquid for diluting the measurement sample;
The operation plate can be positioned at an intermediate position between the first position and the second position;
The dilution tank is provided so that the sample holder is disposed inside the dilution tank when the operation plate is positioned at the intermediate position.
Cartridge for analysis. The analysis cartridge according to any one of claims 1 to 6,
With internal and external communication passages that lead to the outside,
When the operation plate is positioned at the first position, the sample holding part forms a part of the inner / outer communication path,
Cartridge for analysis. The internal / external communication passage is a passage through which the measurement sample can be introduced into the sample holding portion using a capillary phenomenon by attaching a liquid measurement sample to the outside.
The analysis cartridge according to claim 7. The analysis cartridge according to any one of claims 1 to 8,
An analytical cartridge provided with a drop-off prevention mechanism for preventing the operation plate from dropping off. The drop-off prevention mechanism is configured such that the locking portion provided on the operation plate and the locking plate are moved when the operation plate moves in a direction of falling off the section between the first position and the second position. A locked portion that locks with the portion and restricts movement of the operation plate,
The analysis cartridge according to claim 9. The analysis cartridge according to claim 1,
An analytical cartridge comprising a waste liquid tank for receiving the liquid flowing out from the outlet of the separation column through the waste liquid port. The one or more cylinders are accommodated in the waste liquid tank.
The analysis cartridge according to claim 11. The outflow passage is formed so that the downstream side of the detection passage intersects the separation column.
The analysis cartridge according to claim 12. The cylinders are arranged such that a plurality of cylinders are substantially parallel to each other,
The separation column is disposed so that an axial direction thereof is substantially perpendicular to an axial direction of the plurality of cylinders and opposed to supply ports of the plurality of cylinders.
The analysis cartridge according to claim 1. The detection passage is formed so as to be substantially parallel to the axial direction of the separation column on the side opposite to the side where the plurality of cylinders are arranged in the separation column.
The analysis cartridge according to claim 14. The inflow passage is formed at least partially with a turbulent mixing part or a diverging / merging / mixing part.
The cartridge for analysis according to any one of claims 1 to 15. An installation part capable of installing the analysis cartridge according to any one of claims 1 to 16,
A pressing mechanism capable of independently pressing the liquid in the one or more cylinders of the analysis cartridge installed in the installation unit;
A light-emitting element disposed on one side of the detection path and a light-receiving element disposed on the other side of the detection path are configured to allow light emitted from the light-emitting element to enter the detection path and pass through the detection path. A detector that receives the subsequent light at the light receiving element;
Absorbance measuring apparatus. The detector includes at least one of a diffusion plate that diffuses light of the light emitting element or a polarizing plate that suppresses the influence of reflected light between the light emitting element and the detection path.
The absorbance measuring apparatus according to claim 17.

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