Classifications

• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
  • B01F25/00—Flow mixers; Mixers for falling materials, e.g. solid particles
  • B01F25/105—Mixing heads, i.e. compact mixing units or modules, using mixing valves for feeding and mixing at least two components
• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
  • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
  • G01N30/02—Column chromatography
  • G01N30/04—Preparation or injection of sample to be analysed
  • G01N30/16—Injection
• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
  • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
  • G01N30/02—Column chromatography
  • G01N30/26—Conditioning of the fluid carrier; Flow patterns
  • G01N30/38—Flow patterns
• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
  • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
  • G01N30/02—Column chromatography
  • G01N30/62—Detectors specially adapted therefor
• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
  • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
  • G01N30/02—Column chromatography
  • G01N30/62—Detectors specially adapted therefor
  • G01N30/74—Optical detectors
• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
  • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
  • G01N30/02—Column chromatography
  • G01N30/88—Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86
• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
  • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
  • G01N30/02—Column chromatography
  • G01N30/62—Detectors specially adapted therefor
  • G01N30/74—Optical detectors
  • G01N2030/746—Optical detectors detecting along the line of flow, e.g. axial
• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
  • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
  • G01N30/02—Column chromatography
  • G01N30/88—Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86
  • G01N2030/8809—Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86 analysis specially adapted for the sample
  • G01N2030/8813—Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86 analysis specially adapted for the sample biological materials
  • G01N2030/8822—Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86 analysis specially adapted for the sample biological materials involving blood
• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
  • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
  • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
  • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
  • G01N33/72—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving blood pigments, e.g. haemoglobin, bilirubin or other porphyrins; involving occult blood

Definitions

• the present invention relates to a liquid homogenization unit and a high-performance liquid chromatography apparatus provided with the same.
• the present invention relates to a liquid homogenization unit that is incorporated in a liquid flow system and positively generates a vortex of a liquid, and a high-performance liquid chromatography apparatus including the same.
• HPLC high-performance liquid chromatography
• HbAlc hemoglobin Ale
• the device prepares a sample solution by diluting blood with a predetermined diluent, and uses an eluent to separate each hemoglobin component such as HbAlc contained in the sample solution into the column. Let it unfold.
• each hemoglobin component contained in the sample solution elutes from the column while being separated from each other.
• the absorbance of the eluate flowing out of the column is constantly measured by a detector provided after the column. Based on the absorbance thus measured, the absolute amounts of HbAlc and other hemoglobin eluted from the column are determined. Then, the device finally calculates the proportion of HbAlc present in the total amount of hemoglobin including HbAlc.
• the measured value of HbAlc fluctuated depending on the dilution ratio of blood. If they are derived from the same blood, it is expected that the same abundance ratio of HbAlc will be measured regardless of the dilution ratio of blood, that is, regardless of the blood concentration in the sample solution. However, in practice, the measured values differed depending on the blood concentration, and constant values were not obtained.
• the hemoglobin concentration of the eluent rises with time, the liquid replacement progresses slower near the wall surface of the measurement flow channel than at the center of the flow channel cross section, and a low hemoglobin concentration tends to be maintained. It is in.
• the eluent flowing through the measurement channel has a concentration gradient that decreases from the center to the periphery of the channel cross section.
• the value is lower than the value to be measured in an ideal eluent state in which the concentration gradient is not formed. Re, the value is actually measured.
• HbA0 hemoglobin AO
• the effect of the above-mentioned laminar flow can be reduced because the rate of change in HbAO concentration is reduced, but the separation peaks derived from each hemoglobin in the chromatogram tend to overlap. It is not preferable. It is also not preferable in that it requires more time and an eluent. In particular, in a saccharified hemoglobin measuring device using HPLC, it is desired to reduce the measuring time, and spending a long time in column separation is against such a demand. In order to alleviate the above-mentioned problem that has occurred in the measurement channel ⁇ of the detector, a glycated hemoglobin measuring device provided with a diffusion coil has been conventionally proposed.
• the diffusion coil is a spiral pipe and is provided at a position near the detector where the measurement flow path is formed.
• the diffusion coil generates convection in the eluate eluted from the column, whereby the hemoglobin contained in the eluate is positively three-dimensionally diffused. Due to the diffusion effect of the convection in the diffusion coil, the concentration gradient of the eluent flowing through the measurement flow channel in the cross section of the flow channel is reduced, and the measured value of HbAO is stabilized to a constant value.
• the conventional glycated hemoglobin analyzer using a diffusion coil can stabilize the measured value of HbAO, which is a high concentration component, but has the following problems.
• a dilute solution which is inherently insensitive to laminar flow, is also affected by the convection of the diffusion coil, and the peaks derived from the low concentration components of hemoglobin are dull.
• Hemoglobin low-concentration components include HbAlc: As a result, the analytical capacity of a saccharified hemoglobin analyzer decreases.
• the eluent is subjected to convection before flowing into the measurement flow path, so that the eluent flowing into the measurement flow path has a hemoglobin component not only in the flow path radial direction but also in the flow direction. Is spread to a considerable extent. Due to the diffusion in the flow direction, the degree of separation between the components separated by the column is reduced in the line after the column. As a result, the full width at half maximum of the peak derived from each component in the chromatogram increases, and the analysis time becomes longer than before as compared to the time required for separation. Disclosure of the invention
• the present invention aims to eliminate or mitigate the above-mentioned problems.
• a liquid homogenization unit includes a supply flow path and a discharge flow path, a first intermediate flow path communicating with the supply flow path, and a second intermediate flow path communicating with the first intermediate flow path and the discharge flow path.
• the first intermediate flow path extends in a direction crossing the second intermediate flow path.
• the second intermediate flow path is substantially cylindrical, and the first intermediate flow path is connected to the second intermediate flow path at a position deviated from the axis thereof.
• the first intermediate flow path is from the supply flow path to the second intermediate flow path. It is provided in a tapered shape.
• the first intermediate channel has a uniform cross section:
• the first intermediate flow path extends at right angles to the second intermediate flow path.
• the second intermediate flow path has a substantially cylindrical shape, and the first intermediate flow path has a first portion connected to the supply flow channel and a second portion connected to the second intermediate flow channel.
• the first portion is provided in a tapered shape from the supply flow path toward the second portion, the second portion has a uniform cross section, and the second intermediate flow It is connected to the road at a position offset from its axis.
• the second portion of the first intermediate flow path extends at right angles to the second intermediate flow path.
• the supply channel and the second intermediate channel have a substantially circular cross section
• the first intermediate channel includes a first portion connected to the supply channel and the second intermediate channel.
• a first portion extending in a direction deviated from an axis of the supply flow path, and the second portion extends from the first portion to the second portion. 2 It is provided with a tapered shape toward the intermediate flow path.
• the first intermediate channel has a smaller cross section than the second intermediate channel.
• the supply channel and the first intermediate channel are connected at an obtuse angle.
• the unit body further includes a unit body having a first end face and a second end face facing the first end face, and first and second lids, wherein the second intermediate flow path includes a unit main body having the first end face. From the second end face to the second end face, the supply flow path is opened to the first end face, and the first intermediate flow path is provided at the first end face with the supply flow path and the second flow path.
• the discharge flow path is open at the second end face and communicates with the second intermediate flow path
• the first lid is provided with the supply flow path
• the second lid is provided on the first end face so as to close the first intermediate flow path and the second intermediate flow path
• the second lid body closes the second intermediate flow path and the discharge flow path.
• the first and second lids have at least a transparent portion corresponding to the second intermediate flow path, and the second intermediate flow path is a measurement flow path adaptable to absorbance measurement It is.
• a vortex is generated in the second intermediate flow path.
• the liquid flows from the first intermediate flow path into the second intermediate flow path, the liquid flows through the second intermediate flow path while swirling. Therefore, when the liquid contains a solute, the solute is actively diffused by the vortex in the cross section of the second intermediate flow path.
• the high performance liquid chromatography system high performance liquid chromatography apparatus which includes a detector for detecting the column, the absorbance of the eluate from the column
• the detector comprises: a supply flow path into which the eluate from the column flows, a measurement flow path for measuring the absorbance of the eluate, and discharging the eluate after the absorbance measurement.
• a vortex flow path for guiding the eluate flowing into the supply flow path to the measurement flow path, wherein the vortex flow generation path crosses the measurement flow path. And generate a vortex in the measurement channel.
• a sample obtained by diluting a sample containing at least two or more components with a diluent and an eluent as a mobile phase are supplied to the column, and the sample is analyzed based on the absorbance detected by the detector. Measure the abundance ratio of at least one component contained therein.
• the specimen is blood, and the proportion of glycated hemoglobin contained in hemoglobin in the blood is measured.
• the measurement flow path has a substantially cylindrical shape, and the vortex flow generation path is connected to a position displaced from the axis of the measurement flow path.
• the vortex flow path is tapered from the supply flow path to the measurement flow path.
• the vortex flow path has a uniform cross section.
• the vortex generation path extends at right angles to the measurement flow path.
• the vortex generation path has a smaller cross section than the supply flow path and the measurement flow path.
• the same effect as described above with respect to the first aspect can be obtained. Therefore, good absorbance measurement can be performed on a liquid that does not have a concentration gradient in the radial direction of the measurement channel cross section.
• FIG. 1 is a block diagram showing a saccharified hemoglobin bottle measuring device as an example of the high performance liquid chromatography device according to the present invention.
• FIG. 2 is a perspective view showing a cross section of a part of a detector provided in the saccharified hemoglobin measuring device shown in FIG.
• FIG. 3 is a front view of a cell provided in the detector shown in FIG.
• FIG. 4 is a cross-sectional view taken along line IV-IV in FIG.
• FIG. 5 is an enlarged view of the vicinity of the vortex flow path of the cell shown in FIG.
• Figure 6 is a graph showing the relationship between the dilution ratio of the blood to be tested and the measured value of HbAlc.
• FIG. 7 is an enlarged view near a vortex flow generation path according to another embodiment.
• FIG. 8 is an enlarged view near the vortex flow generation path in another embodiment.
• FIG. 9 is a front view of a cell according to another embodiment.
• FIG. 10 is a cross-sectional view of the cell shown in FIG. 9, taken along line XX.
• FIG. 11 is a cross-sectional view of the cell shown in FIG. 9 along line XI-XI.
• FIG. 12 is a cross-sectional view of the cell shown in FIG. 9, taken along line XII—XII.
• FIG. 13 is a rear view of the cell shown in FIG. 9 c
• FIG. 14 is an enlarged view of the vicinity of the vortex flow path in the cell shown in FIG. BEST MODE FOR CARRYING OUT THE INVENTION
• FIG. 1 is a block diagram showing a saccharified hemoglobin measuring device as an example of the high performance liquid chromatography device according to the present invention.
• This saccharified hemoglobin measuring device is composed of a sample pretreatment unit 1, an analysis unit 2, an injection valve 3, a control unit 4, and a drainage unit. Including liquid part 5.
• the sample pretreatment section 1 includes a sample preparation section 11 and a liquid sending pump 12.
• the analysis unit 2 includes an eluent preparation unit 21, a liquid sending pump 22, a column 23, and a detector 24.
• the injection valve 3 includes an injection loop 31 and has six ports 3a to 3f. Port 3 a is connected to column 23, and port 3 b is connected to pump 22.
• the port 3c is connected to one end of the injection loop 31 and the other end of the injection loop 31 is connected to the port 3f.
• the ports 3 d and 3 e are both connected to the sample preparation unit 11.
• the sample pre-processing unit 1 performs a predetermined process on a blood sample before analysis.
• the prepared sample is temporarily introduced into the injection loop 31 of the injection valve 3.
• the sample injected from the injection loop 31 is separated into components by the column 23, and thereafter, the absorbance of the solution eluted from the column 23 is measured by the detector 24.
• the injection valve 3 is appropriately switched between a state where the injection loop 31 is connected to the sample preparation unit 11 of the sample pretreatment unit 1 and a state where it is connected to the column 23 of the analysis unit 2.
• the control device 4 includes a microcomputer and the like, and includes a liquid feed pump 12 of the sample pretreatment unit 1, a liquid feed pump 22 of the analysis unit 2, an injection valve 3, and a pump and valve of the liquid discharge unit 5. Drive control. Further, the control device 4 displays the measurement result on a display unit (not shown) based on the detection signal from the detector 24 and prints it on a recording unit (not shown).
• the drainage unit 5 processes drainage from the sample pretreatment unit 1 and the analysis unit 2 generated during operation of the apparatus.
• the sample preparation unit 11 prepares a sample by aspirating a predetermined amount of blood from a sample storage container (not shown) and diluting it with a predetermined diluent.
• the sample thus prepared is stored in a dilution tank (not shown) built in the sample preparation unit 11.
• the liquid sending pump 12 sends the sample prepared in the sample preparation section 11 from the dilution tank to the injection loop 31 via the port 3e and the port 3f.
• the injection loop 31 has a capacity for holding a predetermined amount of sample.
• the eluent preparation unit 21 prepares an eluent as a mobile phase.
• the eluent preparation unit 21 includes a plurality of eluent tanks for storing eluents having mutually different concentrations, and a plurality of these eluent tanks. And a manifold for merging the flow paths of the eluent from the eluent tank.
• the sample temporarily held in the injection loop 31 is supplied to the column 23 together with the eluent, and is developed in the column 23 by the eluent .
• Each hemoglobin component contained in the sample has a different adsorptive power to column 23, so the time required for each component of hemoglobin to elute is different.
• the elution time of hemoglobin by column 23 are separated for each target component based on the difference between
• the detector 24 is equipped with a spectrophotometer or the like, and measures the absorbance of the hemoglobin-containing eluate eluted from the column 23.
• FIG. 2 is a perspective view showing a cross section of a part of a detector provided in the saccharified hemoglobin measuring device shown in FIG.
• the detector 24 includes a cell 41, a light emitting element housing section 42, and a light receiving element housing section 43.
• a disc-shaped transparent plate 45 and a circular lens 46 are provided between the cell 41 and the light-emitting element housing part 42.
• a disc-shaped transparent plate 47 and a circular lens are provided between the cell 41 and the light receiving element housing 43.
• An O-ring 51 serving as a lens press is interposed between the light emitting element housing 42 and the lens 46, and a lens press is provided between the light receiving element housing 43 and the lens 48.
• As an o-ring 52 are interposed.
• ⁇ ring 5 1
• a light emitting element such as a halogen lamp is installed in the light emitting element housing 42, and a light receiving element such as a photodiode or photo A transistor is installed.
• a backing (not shown) is interposed between the cell 41 and the light-emitting element housing 42, and a packing (not shown) is also provided between the cell 41 and the light-receiving element housing 43. Is interposed.
• the cell 41 has a supply channel 56 for receiving the eluent from the column 23 into the cell 41, and a measurement channel 55 for securing an optical path for measuring the absorbance of the eluent.
• a discharge channel 57 is formed to guide the eluent passing through 5 to the outside of the detector 24.
• the transparent plate 45 and the transparent plate 47 provided in contact with the cell 41 may be entirely transparent in order to secure an optical path, and are formed in the cell 41.
• the portion corresponding to the measurement flow channel 55 that is, only the vicinity of the central portion may be transparent.
• FIG. 3 is a front view of a cell 41 provided in the detector shown in FIG.
• FIG. 4 is a cross-sectional view taken along line IV-IV in FIG.
• the measurement flow channel 55 penetrates substantially the center of the cell 41 in the thickness direction, and is formed in a straight line.
• the start end of the measurement flow channel 55 opens on the front side of the cell 41, and the end end opens on the back side of the cell 41.
• the supply flow path 56 extends linearly from the right end face of the cell 41 to below the measurement flow path 55, as shown by a broken line in FIG. 3, where it is bent at a right angle and is represented in FIG. As shown, it extends linearly to the front side of cell 41.
• the supply flow path 56 communicates with the start end of the measurement flow path 55 via the vortex flow generation path 58.
• the discharge flow path 57 extends upward from the end of the measurement flow path 55 on the rear side of the sensor 41, bends at a right angle, and extends to the front side of the cell 41. It is further bent at a right angle and linearly extends to the upper surface of the cell 41.
• FIG. 5 is an enlarged view of the vicinity of the vortex flow path 58 in the front view of the cell 41 shown in FIG.
• a groove 59 extending from the end of the supply channel 56 to the beginning of the measurement channel 55 is formed at the front of the cell 41, and this groove 59 defines a part of the vortex flow path 58.
• the groove 59 opens on the front side of the cell 41.
• FIG. 2 when the transparent plate 47 is brought into contact with the front side of the cell 41, a closed space is defined by the groove 59 and the transparent plate 47 except at both ends. That is, the transparent plate 47 defines another part of the vortex flow path 58.
• FIG. 2 shows a closed space defining the vortex flow path 58.
• substantially the entire groove 59 is inclined with respect to a line segment B connecting the axis 56 a of the supply channel 56 and the axis 55 a of the measurement channel 55. It is formed in a tapered shape toward. Therefore, the opening of the vortex flow generation path 58 with respect to the measurement flow path 55 is shifted from the line segment B at the periphery of the measurement flow path 55.
• the vicinity of the opening of the groove 59 with respect to the measurement flow path 55 has a shape substantially parallel to the line segment B. Therefore, the vicinity of the opening of the vortex flow generation path 58 with respect to the measurement flow path 55 intersects at right angles to the solution flow direction in the measurement flow path 55.
• the cross-sectional shape of the groove 59 in the direction perpendicular to the solution flow direction of the vortex flow generation path 58 is semicircular in both the tapered portion and the vicinity of the opening.
• the hemoglobin measuring device equipped with the detector having the configuration as a liquid homogenizing unit as described above operates as follows: First, the control device 4 controls each part of the sample preparation unit 11 to control the components. A sample is prepared. Specifically, a predetermined amount of blood is aspirated from a sample storage container (not shown), and this blood is diluted with a predetermined diluent at a predetermined dilution ratio, and diluted in a sample preparation unit 11. It is stored in a tank (not shown). The operation of the control device 4 allows the injection valve 3 shown in FIG. 1 to communicate with the ports 3a and 3b, communicate with the ports 3c and 3d, and communicate with the ports 3e and 3f. State.
• the blood sample prepared as described above in the sample preparation unit 11 is injected by the pump 12 from the dilution tank of the sample preparation unit 11 into the injection loop via the port 3 e of the injection valve 3 and the boat 3 f. 3 Introduced in 1.
• the excess sample returns to the dilution tank of the sample preparation section 11 through the boat 3c and the boat 3d.
• the operation of the control device 4 causes the injection valve 3 to communicate with the port 3b and the boat 3c, communicate with the boat 3d and the boat 3e, and communicate with the boat 3 ⁇ and the boat 3a.
• the eluent is supplied from a predetermined eluent tank selected from a plurality of eluent tanks (not shown) of the eluent preparation unit 21 to the port 3 b of the injection valve 3. Is sent.
• Such an eluent flows into the column 23 through the boat 3c, the emission loop 31, the port 3f, and the port 3a.
• the sample temporarily held in the injection loop 31 is pushed by the eluent and flows into the column 23.
• the cleaning liquid is sent from the cleaning liquid tank (not shown) to the port 3 e of the injection valve 3 by the operation of the liquid sending pump 12.
• This washing liquid flows from port 3d to the dilution tank of sample preparation section 11 as drainage.
• the sample remaining in the sample flow path in the sample pretreatment section 1 is removed by the cleaning liquid.
• the blood sample to be measured next is again prepared by dilution or the like in the sample pretreatment section 1.
• the connection state of the injection valve 3 is switched by the operation of the control device 4.
• Port 3a communicates with port 3b
• port 3c communicates with port 3d
• port 3e communicates with boat 3f. Therefore, the eluent sent from the eluent preparation unit 21 to the port 3b of the injection valve 3 by the operation of the pump 22 is injected via the boat 3a without passing through the injection loop 31. Flows out of valve 3 and is supplied to column 23.
• the sample injected into the column 23 together with the eluent is developed in the column 23 by the eluent as the mobile phase.
• Each hemoglobin component is separated by the column 23 based on the difference in adsorption power between each component of the hemoglobin contained in the sample and the column 23.
• the eluate eluted from the column 23 is supplied to a detector 24 provided after the column 23.
• the absorbance of the eluate passing through the measurement channel 55 formed in the detector 24 is measured by the detector 24. For the absorbance measurement, use light of a wavelength at which each hemoglobin component shows absorption.
• the detection signal from the detector 24 is input to the control unit 4, and the chromatogram derived from these is measured based on the absorbance measured for each hemoglobin component such as HbAlab, HbF, HbAlc, and HbAO contained in blood. The result is printed for record. The abundance ratios of these components are also calculated and displayed as measurement results.
• the eluate that has passed through the detector 24 is discharged to a waste liquid storage facility outside the device.
• the drainage sucked by the drainage unit 5 is also discharged to a drainage storage facility outside the machine.
• a vortex generation path is provided between a measurement flow path 55 for performing absorbance measurement in the detector 24 and a supply flow path 56 for introducing an eluent into the detector 24.
• Five and eight are provided. Therefore, during the operation of the above apparatus, the eluent eluted from the column 23 first flows into the detector 24 from the supply channel 56, and then passes through the vortex generation channel 58 to the measurement channel 55. Leads to.
• the vortex flow path 58 shown in FIG. 5 is inclined with respect to the line B connecting the axis 56 a of the supply channel 56 and the axis 55 a of the measurement channel 55.
• the opening of the vortex flow path 58 with respect to the measurement flow path 55 is located at a position deviating from the line segment B at the periphery of the measurement flow path 55. Therefore, the eluent flowing through the measurement channel 55 has a rotating component in the cross section of the channel. More specifically, at the beginning of the measurement flow path 55, the eluent flows into the measurement flow path 55 in a direction deviating from the axis 55a, and the eluent instantaneously spirals. Flows. That is, due to the presence of the vortex flow path 58, a vortex is generated in the eluent passing through the measurement flow path 55 in the direction indicated by the arrow F in FIG.
• the saccharified hemoglobin measuring device can output a constant measurement value of the HbAlc abundance ratio regardless of the sample concentration, as long as the sample is derived from the same blood sample.
• FIG. 6 is a graph showing the relationship between the dilution ratio of the blood to be tested and the measurement result of HbAlc by the glycated hemoglobin measuring device.
• the horizontal axis is the reciprocal of the blood dilution factor
• the vertical axis is the ratio of HbAlc to total hemoglobin in blood.
• the solid line represents the measurement results obtained by the saccharified hemoglobin measuring device according to the above embodiment, and the measured value of the proportion of HbAlc is substantially constant.
• the dashed line shows the measurement results using a conventional saccharified hemoglobin measuring device without a diffusion coil. The measured value of the HbAlc abundance ratio increases as the dilution factor decreases. Become.
• the saccharified hemoglobin measuring device compared to a conventional saccharified hemoglobin measuring device without a diffusion coil, the HbAlc with respect to the change in the dilution ratio of blood was smaller than that of the conventional saccharified hemoglobin measuring device. Changes in the measured values are extremely small.
• the conventional glycated hemoglobin measuring device equipped with a diffusion coil the change in the measured value of HbAlc with respect to the change in the dilution ratio of blood is relatively small, but the analysis of HbAlc and other low-concentration components is relatively small.
• the analysis time of the eluted components can be greatly increased, as the c that has been confirmed by experiments, according to the present invention, elution in the flow passage cross section of the measuring channel 5 5 Since the concentration of the solution can be made uniform, the change in the measured value of HbAlc can be remarkably reduced by eliminating the measurement error of HbAO caused by the variation of the sample concentration.
• the vortex flow path 58 gradually tapered from the supply flow path 56 side to the measurement flow path 55 side is provided.
• a vortex flow path 61 may be provided which gradually tapers from the supply flow path 56 side to the measurement flow path 55 side as shown in FIG.
• the vortex flow path 61 has a tapered shape along a direction inclined with respect to a line B connecting the axis 56 a of the supply channel 56 and the axis 55 a of the measurement channel 55. Has become.
• a vortex generation path 62 having a uniform flow path cross-sectional area from the end of the supply flow path 56 to the start end of the measurement flow path 55 may be provided.
• the vortex flow path 62 is provided parallel to and offset from a line segment B connecting the axis 56 a of the supply channel 56 and the axis 55 a of the measurement channel 55. . That is, the axis 6 2 a force of the vortex generation path 62 and the axis of the supply flow path 56
• the vortex flow path 62 is formed so as to have a torsion relationship with the center 56 a and the axis 55 a of the measurement channel 55. Also. It is preferable that the cross-sectional area of the vortex flow generation path 62 be smaller than the cross-sectional area of the measurement flow path 55 and the cross-sectional area of the supply flow path 56.
• FIG. 9 is a front view of a cell 71 according to another embodiment. FIG.
• FIG. 10 is a cross-sectional view of the cell 71 shown in FIG. 9 taken along the line XX.
• FIG. 11 is a cross-sectional view of the cell 71 shown in FIG. 9, taken along line XI—XI.
• FIG. 12 is a cross-sectional view of the cell 71 shown in FIG. 9 taken along the line XII—XII.
• FIG. 13 is a rear view of the cell 71 shown in FIG.
• FIG. 14 is an enlarged view of the vicinity of the vortex flow path in the cell 71 shown in FIG.
• the cell 71 has a supply channel 72 for receiving the eluent eluted from the column, a measurement channel 74 for securing an optical path for measuring the absorbance of the eluent, and a channel 7 for supplying the eluent.
• the vortex flow path 73 for generating a vortex in the measurement channel 74 and the discharge channel 75 for discharging the eluate after the absorbance measurement are formed.
• the supply channel 72 and the vortex generation channel 73 are not orthogonal.
• the supply channel 72 and the vortex generation channel 73 are connected so that the flow of the eluent forms an angle of approximately 135 degrees at the intersection.
• the change in the flow direction of the eluent when flowing from the supply flow path 72 to the vortex flow generation path 73 is gentler than that of the cell 41.
• the dynamic pressure of the eluent near the intersection of the supply flow path 72 and the vortex generation path 73 is reduced, and the eluent flows smoothly in the flow system of the entire device equipped with the cell 71.
• the diffusion of hemoglobin in the flow direction due to convection of the eluent is reduced.
• the other configuration is substantially the same as that of the cell 41. Therefore, the cell 71 according to the present embodiment has the same effect as the case where the cell 41 is used.
• the concentration of the eluent in the cross section of the measurement flow path 72 can be made uniform, so that the measurement error of HbAO caused by the variation in the sample concentration can be eliminated to measure the HbAlc.
• the change in the value can be significantly reduced.
• the ability to analyze low-concentration components due to the diffusion coil in a conventional saccharified hemoglobin measurement device decreases, and the analysis time of elution components decreases. Can avoid the increase Wear.
• the overall configuration of the saccharified hemoglobin measuring device, the specific configuration of the detector 24 and the cells 41, 71, and the specific shape of the vortex flow paths 58, 73 are limited only to the above embodiments. Not something.
• the liquid homogenization unit including the supply flow path, the vortex flow generation path, the measurement flow path, and the discharge flow path is mounted on the high-performance liquid chromatography apparatus, so that the liquid homogenization unit can be used.
• the liquid homogenization unit according to the present invention may be used in an apparatus other than the high performance liquid chromatography apparatus.
• the high-performance liquid chromatography device equipped with the liquid homogenization unit according to the present invention may be configured as a measuring device other than the saccharified hemoglobin measuring device.

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• 1999
  • 1999-09-29 JP JP27645099A patent/JP4210781B2/ja not_active Expired - Lifetime
• 2000
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  • 2000-09-28 US US10/089,399 patent/US7364701B1/en not_active Expired - Lifetime
  • 2000-09-28 EP EP00962958.5A patent/EP1219962B1/en not_active Expired - Lifetime

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