JP4580074B2 - Blood measuring device, whole blood immunoassay device, and sampling probe used in these devices - Google Patents

Description

[0001]
BACKGROUND OF THE INVENTION
The present invention relates to a blood measurement device including a whole blood immunoassay device and a sampling probe used in this device.
[0002]
[Prior art]
Among various blood measuring devices, for example, a whole blood immunoassay device measures a hematocrit value which is a useful guide for diagnosing anemia and other disease states.
[0003]
The hematocrit value is a volume ratio obtained by pressing blood cells in a whole blood sample (specimen, which is appropriately referred to as whole blood) to a predetermined volume (that is, the volume of the pressed blood cell / the whole blood sample). It is.
[0004]
Since this hematocrit value represents the blood cell volume / the whole blood sample, it becomes an index for converting the concentration of the whole sample into a concentration in a component other than blood (blood concentration). Like CRP (C-reactive protein), When measuring a component that does not contain a measurement sample, it is necessary to convert the whole blood measurement value into a blood component concentration, and therefore it is necessary to measure a hematocrit value in addition to the whole blood measurement value.
[0005]
As a method for obtaining this hematocrit value, a method for obtaining a hematocrit value from electric conductivity is an existing technique, instead of a method for obtaining an Hgb value (hemoglobin concentration) by absorptiometry in the cyanmethemoglobin method and converting it to a hematocrit value. is there.
[0006]
As an example, in the whole blood immunoassay device, as shown in FIG. 6, electrodes 64 and 65 that are conducted by the specimen are provided in the middle of a tube 63 that connects the sampling probe 61 of the specimen / reagent to the suction pump 62, There is a method of measuring the hematocrit value of the specimen 66 based on the electrical conductivity between the electrodes 64 and 65 when the specimen 66 is sucked between the electrodes 64 and 65.
[0007]
[Problems to be solved by the invention]
However, in this method, since it is necessary to introduce the specimen 66 to the electrodes 64 and 65, there is a problem in that a large amount of the specimen 66 is required and time is required.
[0008]
That is, since only a very small amount of sample (whole blood) is required for immunoassay, only a small amount of sample 66 needs to be sampled by the probe 61. In order to measure the hematocrit value by the above method, Since it is necessary to introduce the sample 66 to the electrodes 64 and 65, a large amount of the sample 66 was required, and the time was also wasted.
[0009]
Thus, the problem of introducing a sample in vain is not limited to the above-described whole blood immunoassay device, but is also a problem common to various blood measurement devices that measure the electrical conductivity of a sample.
[0010]
The present invention has been made in view of such circumstances, and its purpose is to measure the hematocrit value based on the electrical conductivity of the specimen or the electrical conductivity of the specimen at the same time as sampling the specimen. And a sampling probe suitable for use in the measurement apparatus.
[0013]
The present invention provides a whole blood immunoassay apparatus having movable sampling probe over the housing part and the immunoassay portion of the specimen container containing a whole blood sample, the two electrodes which conduct immersed in the whole blood sample, the Bei example the tip of the sampling probe to be used in the suction of the whole blood sample contained in the sample container, the whole said blood sample a time of sampling is accommodated in the specimen container the whole blood sample is the sampling probe said said two electrodes have you up before moving to the immunoassay portion of the measurement cell on the basis of the electrical conductivity caused by conducted by the whole blood sample after being sucked into, the immunoassay section wherein for correcting the plasma component volumetric error for measured values Yes configured to measure a hematocrit value of a whole blood sample, the sampling probe, the two Electrode is characterized in that it comprises a cylindrical body having an insulating property which is provided in a state of being isolated from each other (claim 1).
[0014]
Also by this means, when an amount of sample necessary for immunoassay is sampled, the electrode at the tip of the probe is conducted by the sample, and the electrical conductivity of the sample is measured. The hematocrit value of (whole blood) can be obtained. Therefore, according to the apparatus of claim 1, the electrical conductivity of the specimen is measured simultaneously with the sampling only by sampling a small amount of specimen at the probe tip. In addition, the apparatus according to claim 1 can measure the hematocrit value of the specimen based on the electrical conductivity.
[0016]
In any of the above structures, the sampling probe having the electrode at the tip portion is configured by using the inner tube for sample sampling, so that a sampling probe suitable for use in the above apparatus is provided at low cost. .
[0017]
At this time, if the outer cylinder of the probe body is heat-shrinkable and this cylinder is heat-shrinked (Claim 4 ), for example, a troublesome work such as adhesion is not required, and a double-tube structure is formed. The probe body can be obtained, and if the tip of the outer cylinder constituting the electrode is drawn and the end of the probe is pressed against the inner surface of the drawing, positioning of one end of the probe is achieved. Therefore, there is an advantage that the sampling probe can be configured only by fixing only the other end side of the probe body to the outer cylinder.
[0018]
DETAILED DESCRIPTION OF THE INVENTION
Embodiments of the present invention will be described with reference to the drawings. 1 to 3 show one embodiment of the present invention.
DETAILED DESCRIPTION OF THE INVENTION
Hereinafter, embodiments of the present invention will be described with reference to the drawings. 1 to 3 show a whole blood immunoassay device as an example of a blood measurement device. In these drawings, reference numeral 1 denotes a device case, which is a container 4 of a specimen container 3 that contains whole blood 2 as a specimen. And an immunoassay unit 5 and a probe unit unit 6 that moves linearly across the specimen container storage unit 4 and the immunoassay unit 5.
[0019]
7 is a measurement key provided in the specimen container storage unit 4, 8 is a dispenser, 9 is a diluent container, 10 is a hemolytic reagent container, 11 is a pump, and 8 to 11 are all connected to the electromagnetic valve unit 12. It is connected. A waste liquid container 13 is connected to the pump 11.
[0020]
The immunoassay unit 5 is configured to measure CRP. That is, in FIG. 2, 14 is a cell for measuring CRP (hereinafter referred to as CRP cell), and a CRP measurement flow photometric cell 14c provided with a light irradiation unit 14a and a light detection unit 14b communicates with the bottom. The liquid stored in the flow photometric cell 14c can be appropriately stirred.
[0021]
15 to 17 are containers containing reagents used for CRP measurement, which are hemolytic reagent (hereinafter referred to as R1 reagent), buffer (hereinafter referred to as R2 reagent), anti-human CRP-sensitized latex immunoreagent (hereinafter referred to as R3). A reagent).
[0022]
The CRP cell 14 and the reagent containers 15 to 17 are arranged in a straight line with respect to the set position of the sample container 3 in the sample container storage unit 5, and these 14 to 17 are lids that are swung up and down by a solenoid 18. 19 is configured to be collectively opened and closed. Reference numeral 20 denotes a cooler box including an electronic cooler 21 made of, for example, a Peltier element, and contains reagents R2 and R3 in the illustrated example.
[0023]
In the configuration diagram of the probe unit 6, reference numeral 22 in the figure denotes a probe unit, and this probe unit 22 is horizontally aligned by a timing belt 24 provided in the horizontal direction along a vertically extending base member 23. It can be reciprocated.
[0024]
Reference numeral 25 denotes a motor for driving the timing belt 24, and reference numeral 26 denotes a pair of guide members for guiding a guided member 27 provided in the probe unit 22. These are attached to the base member 23 via appropriate members. .
[0025]
Reference numeral 28 denotes a sample / reagent sampling probe which is connected to the pump 11 via a tube 29 and is attached to a probe holder 31 which moves in the probe unit 22 in the vertical direction by a timing belt 30.
[0026]
The distal end side (lower end side) of the sampling probe 28 is configured such that a probe washer 32 provided in the probe unit 22 is inserted and the outer periphery of the distal end portion is cleaned.
[0027]
The sampling probe 28 is provided with electrodes 33 and 34 that are immersed in the specimen 2 and conducted at the tip, and based on the electrical conductivity between the electrodes 33 and 34 when the specimen 2 is sampled, the sampling probe 28 It is configured to measure a hematocrit value.
[0028]
A motor 35 drives the timing belt 30, and a sensor 36 detects whether the sampling probe 28 is at the home position (fixed position).
[0029]
Reference numeral 37 denotes a microcomputer (MCU) as a control / arithmetic apparatus that performs overall control of each part of the apparatus and performs various calculations using the output from the CRP measurement unit 5, and 38 is based on commands from the MCU 37. A driver for sending drive signals to the motors 25 and 35 of the solenoid valve unit 12 and the probe unit unit 6, 39 is a signal processing unit for processing output signals from the CRP measurement unit 5 and sending them to the MCU 37, and 40 is processed by the MCU 37. A device for displaying the obtained result, for example, a color display, and 41 is a printer as an output device.
[0030]
The outline of the operation of the whole blood immunoassay apparatus will be described. First, when the measurement key 7 is turned on, the sampling probe 28 located at the fixed position moves to the position of the R2 reagent, and aspirates the R2 reagent. The outer surface of the probe 28 is washed, moves to the position of the R1 reagent, and sucks the R1 reagent. Thereafter, the outer surface of the sampling probe 28 is washed and moved to the sample container housing 4 to suck the sample (whole blood) 2 in the sample container 3 for CRP measurement. Is moved to the CRP cell 14 position, the specimen 2, R1 reagent, and R2 reagent are discharged into the CRP cell 14, and the hemolysis reaction proceeds between the specimen 2, R1 reagent, and R2 reagent, and the interfering substance To remove.
[0031]
Next, the sampling probe 28 aspirates the R3 reagent and discharges the R3 reagent into the CRP cell 14, and the R3 reagent is mixed into the reaction liquid of the sample 2, R1 reagent, and R2 reagent and sufficiently stirred. Then, an immune reaction occurs and CRP measurement is performed, and data at that time is taken into the MCU 37 via the signal processing unit 39.
[0032]
In the MCU 37, based on the data obtained by the CRP measurement in the CRP measurement unit 5, the absorbance change per predetermined time is obtained from a calibration curve obtained in advance from serum (or plasma) at a known concentration, and then CRP in whole blood is obtained. A concentration is obtained.
[0033]
In this case, since CRP measurement uses whole blood to which an anticoagulant is added as the sample 2, it is necessary to correct a plasma component volume error caused by using this whole blood.
[0034]
In this correction, when the sample 2 is sampled by the sampling probe 28, the sample (whole blood) is sampled based on the electrical conductivity generated when the sampling probe 28 is immersed in the sample 2 and the electrode is conducted by the sample. A hematocrit value (Hct) of 2 is obtained, and using this hematocrit value, the CRP concentration in whole blood obtained by CRP measurement is corrected by the following correction formula to obtain the CRP concentration in plasma.
[0035]
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.
[0036]
Each measurement value obtained by the MCU 37 is stored, for example, in a memory built in the MCU 37, and is displayed item by item on the display device 40 or printed by the printer 41.
[0037]
Next, the structure of the sampling probe 28 will be described. The sampling probe 28, as shown in FIG. 3, short small diameter of the small cylindrical body having an insulating property (eg ceramic, hereinafter, simply referred to as "tubular body") 42, Ho and the cylindrical body 42 Isuzu same diameter In this case, an electrically conductive long inner cylinder (for example, made of stainless steel) 43 is made of a heat-shrinkable Teflon (trade name of DuPont) having an insulating property in a state in which the inner cylinder 43 is projected. The cylindrical body 44 is thermally contracted, and the projecting surface portion of the inner cylinder 43 and the end portion of the cylindrical body 44 are made of, for example, Araldite (trade name of Nagase Sangyo Co., Ltd.). The probe body 45 having a double-cylinder structure is formed by bonding with an adhesive.
[0038]
On the other hand, for example, a stainless steel outer cylinder 46 having an inner diameter slightly larger than the outer diameter of the probe body 45 is prepared, and the distal end portion 46a of the outer cylinder 46 is drawn to the inner diameter of the probe body 45. The probe body 45 is inserted into the outer cylinder 46 in a state where the end of the probe body 45 is pressed against the inner surface of the drawing process and the end of the cylinder 44 is protruded. The end portion and the protruding surface portion of the cylindrical body 44 are bonded with an adhesive such as Araldite, for example, and the vicinity of the distal end portion of the inner cylinder 43 of the probe body 45 and the distal end portion 46a of the outer cylinder 46 are connected to the electrodes 33 and 34, respectively. Thus, the sampling probe 28 is configured.
[0039]
In the drawing, 57 is a connecting member for the fork-like member 31a of the probe holder 31, 58 and 59 are extraction port members for the electrodes 33 and 34, and the connecting member 57 is connected to the outer cylinder 46 and to the port member. 58 and 59 are fixed to the inner cylinder 43 and the outer cylinder 46 by, for example, silver brazing.
[0040]
According to the sampling probe 28 having the above-described configuration, when the sampling probe 28 is inserted into the sample container 3 and the amount of the sample 2 necessary for immunoassay is sampled, the electrodes 33 and 34 at the tip of the probe are conducted by the sample 2, The electrical conductivity of the specimen 2 is measured.
[0041]
Based on the electrical conductivity between the electrodes 33 and 34 at this time, the hematocrit value of the sample (whole blood) 2 is obtained. Therefore, in the sampling probe 28 having the above structure, a small amount of sample is provided at the probe tip. By sampling 2, the electrical conductivity of the specimen 2 and the hematocrit value can be measured based on the electrical conductivity simultaneously with the sampling of the specimen 2.
[0042]
In the above embodiment, the present invention has been described for the whole blood immunoassay device. However, the electrical conductivity of the specimen 2 is measured by using the sampling probe 28 having the above configuration in various blood measurement devices. You may make it do.
[0043]
A sampling probe 28 with electrodes 33, 34 according to another embodiment is shown in FIGS. 4 (A)-(C) and FIGS. 5 (A)-(D). The sampling probe 28 shown in FIG. 4 (A) has a structure in which the throttle portion 46a at the tip of the sampling probe 28 shown in FIG. 4 is cut off. The sampling probe 28 shown in FIG. In the sampling probe 28 shown in FIG. 4, the insulating cylinders 42 provided in these have a function of eliminating the step between the inner cylinder 43 and the cylinder 44 and preventing the specimen 2 from remaining. is there.
[0044]
The sampling probe 28 shown in FIG. 4B inserts the inner cylinder 43 into the insulating cylinder 44 in a state where the tip of the conductive inner cylinder 43 protrudes slightly. The cylindrical body 44 is inserted into the conductive outer cylinder 46 with the tip slightly protruding, and the outer cylinder 46 is insulative protective cylinder with the tip of the outer cylinder 46 protruding slightly. 4A and 4B, electrodes 33 and 34 are constituted by the tip portions of the inner cylinder 43 and the outer cylinder 46 in FIGS.
[0045]
In the sampling probe 28 shown in FIG. 4C, the metal materials 51 and 52 constituting the electrodes 33 and 34 are fixed to the outer surface portion of the insulating cylindrical body 50, for example, with a phase of 180 degrees (for example). (Selecting means such as vapor deposition and adhesion).
[0046]
In the sampling probe 28 shown in FIG. 5A, a cylindrical body 53 constituting the electrode 33 is provided inside the distal end side of the insulating cylindrical body 44 and the electrode 34 is separated from the cylindrical body 53. A cylindrical probe 54 is provided on the outer surface of the cylindrical body 44, and the sampling probe 28 shown in FIG. 5B includes the cylindrical probe 54 constituting the electrode 34 in the sampling probe 28 shown in FIG. It is provided on the inner surface of the cylindrical body 44.
[0047]
The sampling probe 28 shown in FIG. 5 (C) fixes a metal material 55 constituting the electrode 33 to the outside of the distal end side of the insulating cylinder 44 (selects means such as vapor deposition and adhesion), while this metal material. The sampling probe 28 shown in FIG. 5 (D) is formed by providing a cylindrical body 56 constituting the electrode 34 on the outer surface portion of the cylindrical body 44 in a state where it is isolated from the sampling probe 55. 28, a cylindrical body 56 constituting the electrode 34 is provided on the inner surface of the cylindrical body 44.
[0048]
【The invention's effect】
As described above, according to the present invention, a measurement apparatus capable of measuring a hematocrit value with a small amount of sample and simultaneously with sampling of the sample based on the electric conductivity or electric conductivity of the sample, and the apparatus. A sampling probe suitable for use is provided.
[Brief description of the drawings]
FIG. 1 is a perspective view of a whole blood immunoassay device seen through a device case.
FIG. 2 is a block diagram of an apparatus for measuring whole blood immunity.
FIG. 3 is a cross-sectional view of a sampling probe in which a main part is extracted and enlarged.
FIGS. 4A to 4C are configuration diagrams of a distal end portion of a sampling probe according to another embodiment, respectively.
FIGS. 5A to 5D are configuration diagrams of a distal end portion of a sampling probe according to still another embodiment.
FIG. 6 is a configuration diagram of a conventional electrode arrangement.
[Explanation of symbols]
4 ... Sample container housing part, 5 ... Immunoassay part, 28 ... Sampling probe, 33,34 ... Electrode.

Claims (4)

In a whole blood immunoassay device equipped with a sampling probe capable of moving between a container container containing a whole blood sample and an immunoassay part, two electrodes immersed in the whole blood sample and conducting are connected to the sample container. Bei example the tip of the sampling probe to be used in the suction of the contained whole blood sample was, the whole blood sample to a time of sampling is accommodated in the sample container of the whole blood sample is aspirated into the sampling probe said said two electrodes have you up before moving to the immunoassay portion of the measurement cell on the basis of the electrical conductivity caused by conducted by the whole blood sample after plasma for measurement of the immunoassay section Yes and configured to measure the hematocrit value of the whole blood sample to correct the component volume error, the sampling probe, the two electrodes each other Whole blood immunoassay apparatus comprising a cylindrical body having an insulating property which is provided in a state of being isolated in. A sampling probe used in the whole blood immunoassay device according to claim 1 , wherein an inner cylinder having conductivity is inserted and held inside the cylinder to constitute a probe body having a double cylinder structure, while the inner diameter is In order to measure the hematocrit value of the whole blood sample at the distal end portion of the inner cylinder and the outer cylinder by inserting and holding the probe body inside the outer cylinder having a conductivity slightly larger than the outer diameter of the probe body A sampling probe comprising the two electrodes. 3. The sampling probe according to claim 2 , wherein a small cylindrical body having an insulating property having substantially the same diameter as that of the inner cylinder is provided closer to the tip of the probe body than the inner cylinder in the cylindrical body. The outer cylinder of the probe body has heat shrinkability, and this cylinder is inserted into a small cylinder having insulation and an inner cylinder having conductivity and then thermally contracted to form a double cylinder structure. 4. The sampling probe according to claim 2 or 3 , comprising the probe body.

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