JP2010002209A - Body fluid sample analyzer - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To improve measurement accuracy and cleaning performance of a body fluid sample analyzer that analyzes a body fluid sample based on light transmission characteristics of a reaction liquid produced by reaction of the body fluid sample and the reagent, and that has a simple and compact arrangement wherein air bubbles are difficult to accumulate. <P>SOLUTION: This body fluid sample analyzer includes: a reaction cell 2 that stands vertically and that has an insertion bore 21 for the body fluid sample and the reagent; a discharge/suction apparatus 4 that is connected to a bottom part of the reaction cell 2 through a tube 3 and that reciprocates and agitates the body fluid sample and the reagent between the reaction cell 2 and the tube 3 by repeating a discharging and sucking movement; and an optical measurement means 5 that measures the light transmission characteristics of the reaction liquid produced by agitating the body fluid sample and the reagent, wherein the optical measurement means 5 is arranged on the reaction cell 2. <P>COPYRIGHT: (C)2010,JPO&INPIT

Description

  The present invention relates to a body fluid sample analyzer for analyzing a body fluid sample based on the light transmission characteristics of a reaction solution obtained by mixing a reagent with a body fluid sample such as blood.

  Conventionally, body fluid analysis such as blood has been widely performed for medical diagnosis. For example, in Patent Document 1, in order to measure the concentration of C-reactive protein (CRP) contained in blood, a predetermined reagent is mixed with a blood sample to cause CRP aggregation due to immune reaction, and the degree of aggregation An apparatus for measuring the light intensity by light transmittance is disclosed.

Such an apparatus injects a blood sample collected with a sampling nozzle and a reagent into a reaction cell to cause an immune reaction. A liquid transfer pipetter connected to the reaction cell via a small-diameter transparent tube is provided. Connected and driven in the forward / reverse direction, and the blood sample and reagent in the reaction cell are put in and out of the tube to agitate the blood sample and reagent in the reaction cell to promote the immune reaction and It has become. Then, after the stirring, the concentration of C-reactive protein (CRP) is measured by transferring the reaction liquid to a hollow rectangular parallelepiped photometry section provided in the middle of the tube and measuring the light transmittance of the reaction liquid there. It is configured as follows.
JP-A-11-295305

  However, in the above configuration, since the photometry unit and the reaction cell are provided separately and liquid is taken in and out between them during stirring, bubbles are likely to stay in the photometry unit, and the bubbles cause fluctuations in the liquid. May adversely affect accuracy. In addition, since the photometric flow path becomes complicated, there may be a problem in terms of cleaning.

  Furthermore, in this type of body fluid sample analyzer, conventionally, in consideration of the stability of the reagent, the reagent is stored at a low temperature until immediately before being subjected to the reaction, and the reagent is heated in the sampling nozzle and injected into the reaction cell. However, in such a configuration, after heating, stirring in the reaction cell is required, and there is a problem that it takes time for measurement.

  The present invention has been made to solve such problems, and provides a body fluid sample analyzer excellent in measurement accuracy and cleaning ability by adopting a simple and compact configuration in which bubbles do not easily stay. The main objective is to reduce the measurement time by simultaneously heating and stirring the reagent, and so on.

  That is, the body fluid sample analyzer according to the present invention is a body fluid sample analyzer that analyzes the body fluid sample based on the light transmission characteristics of the reaction liquid generated by the reaction between the body fluid sample and the reagent. A reaction cell standing up and down with a reagent insertion port provided on the upper surface, and connected to the bottom of the reaction cell via a tube, and the body fluid sample and reagent between the reaction cell and the tube by repeated discharge and suction operations A discharge / aspirator that stirs while reciprocating and a photometric means for measuring the light transmission characteristics of the reaction liquid produced by stirring the body fluid sample and the reagent, and the photometric means is provided in the reaction cell. It is characterized by.

  In such a case, since the photometry part is provided in the reaction cell having a structure that stands up and down, the upper surface is open, and the bubbles are less likely to stay, adverse effects on the measurement accuracy due to the bubbles can be greatly reduced. Moreover, since the photometric unit is provided in the reaction cell, the structure can be simplified and made compact, so that it is possible to promote the improvement of the cleaning performance and the cost reduction.

  In order to prevent intrusion of stray light, a light blocking lid that can be opened and closed may be provided at the insertion opening.

  As a specific configuration around the photometric means, a part or all of the reaction cell is formed of a transparent wall, and a light emitting element and a light receiving element constituting the photometric means are arranged at a portion facing the transparent wall, and the light emitting element The light emitted from the light can be received by the light receiving element through the reaction cell.

  In order to reduce the measurement time by simultaneously heating and stirring the reagent, the temperature sensor is further provided with a temperature control block that accommodates the reaction cell, and the reciprocating motion in a tube extending from the reaction cell It is preferable that the part into which the body fluid sample and the reagent enter are brought into contact with the outer surface of the temperature control block.

  In order to make it easy to wind the heating means around the temperature control block, to make the number of turns of the tube constant, and to prevent the wound tube from shifting, the outer surface of the temperature control block is It is desirable that a circumferential groove that is the same as or deeper than the outer diameter of the tube is provided and the tube is wound and held in the circumferential groove.

  As a preferable mounting mode of the light emitting element and the light receiving element, a light passage hole is provided in a part facing the temperature control block, and the light emitting element and the light receiving element are provided in a part facing the light passage hole in the temperature control block. An attachment member for fixing is provided, and the attachment member is provided with a pair of element holding plates facing each other for holding the light emitting element and the light receiving element, and a connection plate for connecting one end portions of the element holding plates. In addition, the temperature control block may be sandwiched and attached between the element holding plates.

  As described above, according to the present invention, it is possible to greatly reduce the adverse effect of the bubbles on the measurement accuracy, and it is possible to simplify the configuration and reduce the size of the device. Therefore, it is possible to improve the cleaning performance and promote cost reduction.

  Hereinafter, an embodiment of the present invention will be described with reference to the drawings.

  The body fluid sample analyzer according to the present embodiment performs various analyzes on a human blood sample (whole blood) which is a body fluid sample. In FIG. 1, C-reactive protein contained in the blood is shown in FIG. The density | concentration measurement mechanism 100 which measures the density | concentration of (CRP) is shown typically.

  This concentration measuring mechanism 100 has, as a basic configuration, a reaction cell 2 for storing a blood sample dropped from a sampling nozzle 1 and a reagent, and a liquid transfer device connected to the reaction cell 2 via a small-diameter transparent tube 3. A dispenser 4 serving as a discharge / aspirator is provided. The dispenser 4 is driven forward / reversely, that is, the cylinder 41 is advanced / retracted, and the blood sample and the reagent in the reaction cell 2 are transferred between the tube 3 and the tube 3. By taking in and out, the blood sample and the reagent are agitated to promote the immune reaction and generate a reaction solution. The light transmittance of the reaction solution is measured by the photometric means 5 so that the concentration of C-reactive protein (CRP) can be measured.

  In this embodiment, a latex immunoturbidimetric method is employed for measuring C-reactive protein (CRP). That is, a hemolytic reagent (hereinafter referred to as R1 reagent), a buffer solution (hereinafter referred to as R2 reagent), and an anti-human CRP-sensitized latex immune reagent (hereinafter referred to as R3 reagent) are used as reagents.

  Next, each part of the concentration measuring mechanism 100 will be described in detail.

  As shown in FIG. 1, the sampling nozzle 1 moves to a sample container and a reagent container (not shown) arranged in another place, collects a predetermined amount of blood sample and reagent from them, and also has a reaction cell 2. Returning to the discharge position immediately above, the collected blood sample and reagent are discharged and dropped into the reaction cell 2 in a predetermined order.

  As shown in FIGS. 1 and 3, the reaction cell 2 has a cylindrical shape that stands up and down (more precisely, vertically), and is formed of a transparent wall such as glass. An insertion port is opened on the upper surface of the reaction cell 2, and a blood sample and a reagent dropped from the sampling nozzle 1 are stored in the reaction cell 2 through the insertion port 21. Further, the bottom surface of the reaction cell 2 is tapered so that the center portion thereof is the lowest, and the tube 3 is coupled to a connection port opened at the center portion of the bottom surface.

  As shown in FIG. 3, the reaction cell 2 is accommodated in a metal temperature control block 6 having a substantially cylindrical shape. The temperature control block 6 can be adjusted to a constant temperature (here, about 37 ° C.) by winding heating means (not shown) such as a sheet heater or a wire heater around the temperature control block 6.

  As shown in FIGS. 2 to 4, the tube 3 connected to the bottom of the reaction cell 2 is extended to the outside from one end face of the temperature control block 6, and the extended portion is connected to the temperature control block. The block 6 is wound a plurality of times in a circumferential groove 62 provided on the outer peripheral surface of one end.

  The circumferential groove 62 has a depth equal to or greater than the outer diameter of the tube 3 so that the wound tube 3 is flush with or lower than the outer circumferential surface of the temperature control block 6. Is set. This is for facilitating winding of the heating means around the temperature control block 6. In addition, the number of turns of the tube 3 can be made constant by the circumferential groove 62, and an effect of preventing the wound tube 3 from being displaced in the axial direction of the temperature control block 6 can be obtained. Note that the number of turns of the tube 3, that is, the contact length of the tube 3 with respect to the temperature control block 6, is the longest part into which the blood sample and the reagent (or reaction solution) enter by the stirring operation of the pipetting device 4. Here, the contact end of the tube 3 with the temperature control block 6 is set to be closer to the dispenser 4 than the longest portion. In addition, the same position may be sufficient, and you may make it the contact end with the temperature control block 6 in the tube 3 be slightly on the temperature control block 6 side from the said longest part.

  Reference numeral 8 shown in FIG. 2 and the like is a holding member for preventing the tube 3 from being loosened and ensuring reliable contact with the temperature control block 6. Here, the holding member 8 is formed by using a strip-shaped flat plate disposed so as to cross the circumferential groove 62 along the axial direction of the temperature control block 6.

  The other end surface of the temperature control block 6 is opened, and the opening 61 is made continuous with the insertion port 21 of the reaction cell 2 and the light blocking lid 9 opens and closes the insertion port 21 of the reaction cell 2 (see FIG. 3). However, it is attached to the temperature control block 6.

  As shown in FIGS. 1 and 3, the photometric means 5 is composed of a light emitting element 51 and a light receiving element 52 arranged so as to sandwich the reaction cell 2, and light emitted from the light emitting element 51 is reacted with the reaction cell. 2 so that the light receiving element 52 can receive light. More specifically, the temperature control block 6 is provided with light passage holes 63 and 64 at opposing portions, and the light emitting element 51 and the light receiving element 52 are disposed facing the light passage holes 63 and 64. . Further, the light emitting element 51 and the light receiving element 52 are attached to the temperature control block 6 via the attachment member 7. As shown in FIG. 7 and the like, the attachment member 7 connects a pair of opposing element holding plates 71 and 72 that hold the light emitting element 51 and the light receiving element 52, and one end of the element holding plates 71 and 72 to each other. The element holding plates 71 and 72 of the mounting member 7 are attached to the temperature control block 6 so as to be sandwiched from the radial direction.

  Next, the measurement operation of the concentration measuring mechanism 100 configured as described above will be described. The following operations are automatically performed in response to commands from a control device (not shown) unless otherwise specified.

  When the measurement is started by an operator's instruction, the sampling nozzle 1 at a fixed position moves to the position of the R2 reagent container (not shown), and aspirates and collects the R2 reagent. The R2 reagent at this time is kept at a low temperature (about 15 ° C.). After this reagent aspiration, the sampling nozzle 1 moves upward, and returns to the position of the R2 reagent container through the outer surface cleaning process with the cleaning liquid.

  Next, the sampling nozzle 1 moves to the position of the R1 reagent container (not shown), and aspirates and collects the R1 reagent. The R1 reagent at this time is also kept at a low temperature (about 15 ° C.). After this reagent suction, the sampling nozzle 1 moves upward, and returns to the position of the R1 reagent through an outer surface cleaning process with a cleaning liquid.

  Thereafter, the sampling nozzle 1 moves to the specimen setting position and sucks a blood sample (whole blood sample) in a specimen container (not shown) for CRP measurement. Then, the sampling nozzle 1 moves upward, and returns to the sample setting position through the outer surface cleaning process with the cleaning liquid.

  Next, the sampling nozzle 1 moves onto the reaction cell 2 and discharges the blood sample, R1 reagent, and R2 reagent collected inside the nozzle into the reaction cell 2.

  Thereafter, the cylinder 41 of the potter 4 repeats the advance / retreat drive several times by a predetermined stroke. As a result, the blood sample, the R1 reagent, and the R2 reagent enter and exit between the reaction cell 2 and the tube 3 and are agitated. In the reaction cell 2, a hemolysis reaction proceeds between the blood sample, the R1 reagent, and the R2 reagent, and the interfering substance is removed. At this time, since the reaction cell 2 and the tube 3 are maintained at a high temperature (about 37 ° C.) by the temperature control block 6, the stirring and the heating of the reagent or the reaction solution are performed simultaneously.

  The sampling nozzle 1 is driven and CBC, WBC, Hgb, RBC, PLT, etc. are measured during a certain period (about 60 seconds) necessary for the hemolysis reaction. The data at that time is taken into the control device (not shown).

  Thereafter, the sampling nozzle 1 that has passed through the cleaning process moves to the position of the R3 reagent container (not shown), and aspirates and collects the R3 reagent. Then, it moves onto the reaction cell 2 (step S22), and the R3 reagent is discharged into the reaction cell 2.

  After discharging the R3 reagent, the cylinder 41 of the potter 4 moves forward and backward several times for a certain stroke, and the reaction solution is stirred for the second time. At this time, since the reaction cell 2 and the tube 3 are maintained at a high temperature (about 37 ° C.) by the temperature control block 6, the stirring and the heating of the reagent or the reaction solution are simultaneously performed. Then, the CRP measurement is performed after returning the reaction solution to the reaction cell 2 by returning the cylinder 41 of the pipetting device 4 to the initial position when the immune reaction occurs. The data at that time is taken into the control device (not shown). Thereafter, the reaction cell 2 is washed with a diluent, and all measurements are completed.

  The control device calculates RBC (red blood cell count), red blood cell volume (MCV), and other measured values based on data obtained by CBC measurement, and for a predetermined time based on data obtained by CRP measurement. The CRP concentration in whole blood is determined from a calibration curve in which the change in absorbance per unit is previously determined from serum (or plasma) at a known concentration.

  For CRP measurement, whole blood added with an anticoagulant is used as the specimen 3 as in CBC measurement, and thus it is necessary to correct a plasma component volume error caused by using this whole blood. Therefore, a hematocrit value (Hct) is obtained from RBC (red blood cell count) and red blood cell volume (MCV) obtained by CBC measurement, and using this hematocrit value, CRP concentration in whole blood obtained by CRP measurement is calculated as follows. It is corrected by the correction formula to obtain the CRP concentration in plasma.

That is, if CRP concentration in whole blood is A and hematocrit value is B, CRP concentration C in plasma is
C = A × 100 / (100−B)
It is calculated by the following formula.
Each measured value obtained by the control device is stored in, for example, a memory and is output by a display or a printer.

  Therefore, in such a case, since the photometry unit 5 is provided in the reaction cell 2 having a structure that stands up and down, the upper surface is open, and bubbles do not easily stay, the measurement accuracy due to the bubbles is greatly adversely affected. Can be reduced. And since the photometry part 5 is provided in the reaction cell 2, since a simplification of a structure and compactization can be achieved, it becomes possible to promote improvement of a cleaning capability and cost reduction.

  In addition, the reaction cell 2 and the tube 3 are maintained at a high temperature (about 37 ° C.) by the temperature control block 6 and can stir and heat the generated reaction solution at the same time, so the measurement time is greatly increased. Can be shortened. Moreover, since the tube 3 is wound around the circumferential groove 62, compactness can be maintained.

  The present invention is not limited to the above embodiment. For example, the photometry unit 5 detects the transmitted light with the light emitting element 51 and the light receiving element 52 facing each other. However, the scattered light may be detected with the light emitting element and the light receiving element at an angle of 90 °. . In addition, the tube may be wound around the temperature control block without providing the circumferential groove. In addition, it goes without saying that the present invention can be variously modified without departing from the spirit of the present invention.

The schematic diagram which shows the density | concentration measurement mechanism of the bodily fluid sample analyzer in one Embodiment of this invention. The perspective view which looked at the temperature control block etc. in the embodiment from the downward direction. The front view of the temperature control block etc. in the same embodiment. The side view of the temperature control block etc. in the same embodiment. The bottom view of the temperature control block etc. in the same embodiment. The top view of the temperature control block etc. in the same embodiment. The disassembled perspective view of the temperature control block etc. in the embodiment.

Explanation of symbols

2 ... Reaction cell 21 ... Inlet 3 ... Tube 4 ... Spotting device (discharge / aspirator)
5 ... Photometric means 51 ... Light emitting element 52 ... Light receiving element 6 ... Temperature control block 62 ... Circulating grooves 63, 64 ... Light passage hole 7 ... Mounting members 71, 72 ..Element holding plate 73 ... Connection plate 9 ... Light blocking lid

Claims (6)

A bodily fluid sample analyzer for analyzing the bodily fluid sample based on the light transmission characteristics of a reaction liquid generated by reacting the bodily fluid sample with a reagent,
A reaction cell standing up and down with an insertion port for a body fluid sample and a reagent provided on the upper surface, and connected to the bottom of the reaction cell via a tube, and between the reaction cell and the tube by repeating discharge and suction operations A discharge / aspirator that agitates the body fluid sample and the reagent while reciprocating; and a photometric means for measuring light transmission characteristics of the reaction liquid generated by agitating the body fluid sample and the reagent, wherein the photometric means is the reaction A body fluid sample analyzer characterized by being provided in a cell.   The body fluid sample analyzer according to claim 1, further comprising a light shielding cover provided at the insertion port so as to be openable and closable.   A part or all of the reaction cell is formed of a transparent wall, and a light emitting element and a light receiving element constituting the photometric means are arranged at a portion facing the transparent wall, and light emitted from the light emitting element is placed in the reaction cell. The body fluid sample analyzer according to claim 1, wherein the body fluid sample analyzer is configured to receive light through a light receiving element. It further comprises a temperature-adjustable temperature control block that accommodates the reaction cell inside,
The body fluid sample according to any one of claims 1 to 3, wherein a portion of the tube extending from the reaction cell into which the body fluid sample and the reagent enter by the reciprocating motion is brought into contact with an outer surface of the temperature control block. Analysis equipment.   The bodily fluid sample analyzer according to claim 4, wherein a circumferential groove having the same diameter as or deeper than the outer diameter of the tube is provided on an outer surface of the temperature control block, and the tube is wound and held in the circumferential groove. A light passage hole is provided in a portion facing the temperature control block, and an attachment member for fixing the light emitting element and the light receiving element to a portion facing the light passage hole in the temperature control block is provided,
The mounting member includes a pair of opposing element holding plates that hold the light emitting element and the light receiving element, and a connection plate that connects one end portions of the element holding plates. 6. The body fluid sample analyzer according to claim 4, wherein the body fluid sample analyzer is configured so as to be sandwiched and attached.