JPH0619350B2 - Body fluid component analysis method and apparatus - Google Patents

Description

TECHNICAL FIELD The present invention relates to a method for analyzing a body fluid component such as protein and an analyzer used for this method. This invention is an improved invention of the technique disclosed in Japanese Patent Application No. 58-219753.

Structure of conventional example and its problems Most of the body fluid components mainly contained in blood are extremely small, but they play important roles in life support such as water regulation, substance transport and immunity.

Until now, sedimentation reaction,
Immunological techniques such as agglutination (which is constitutionally the same as precipitation but mainly refers to passive agglutination) have been used.

Typical examples of precipitation reactions include immunoelectrophoresis and single radial immunodiffusion (SRID). In recent years, radioimmunoassay (RIA), laser nephelometry (LN), enzyme immunoassay. Law (EI
A method) etc. have been developed. And RIA method, EIA
The method is routinely used as a measurement method in nanogram units, and the SRID method and LN method are routinely used as measurement methods in milligram units.

Immunoelectrophoresis and SRID methods take a long time (1 to several days)
As it was observed by diffusion and sedimentation in the gel over time, there were many chances of inclusion of error factors such as influence of other fine particles and denaturation, and accuracy and reproducibility were difficult.

The RIA method and EIA method have high sensitivity and high accuracy, but since radiation and enzymes are used, it takes time and labor to prepare the reagent, and there are restrictions on storage and preservation, and careful consideration is required. So there is a need for a non-isotopic, easier way.

As a representative of agglutination reaction, with Singer in 1956
There is a latex agglutination reaction developed by Plotz et al. Although this measurement method has a very high sensitivity of the reaction itself, it has a weakness that it is a semi-quantitative method because it is a visual method, and despite the fact that various drawbacks of the precipitation reaction method have not been solved, The development of the agglutination reaction method was delayed as compared with the reaction method.

Since 1970, methods have been developed to optically quantify latex aggregation.

Et al., F. Hoffman, LaRoche & Co. AKtiengesellschaft et al. (UK patent 1384399), Sawai et al. In Japan (Japanese Patent Publication Sho 58-115).
No. 75) is well known.

LA system in recent years, (Latex Agglutination Syste
m), LPIA system (Latex photometric Immuno As
say S.), PACIA system (Partile Agglutination Cou
A device called nt Immuno Assay S.) (Japanese Patent Laid-Open No. 56-158947) draws on those flows, has a wide measurement range, is quick and accurate, and is attracting attention as a new body fluid component measuring instrument. . They are latex agglutination (LA
Law) is also called.

However, the former two irradiate the whole suspension sample solution with near infrared rays or visible light, and to measure the nephelometry by scattering or absorption coefficient not by individual particles but by gloss, the precipitation reaction is irradiated with laser light. Similar to the LN method for measuring the turbidity by the above method, an error factor such as the influence of the hue or the state difference of the samples such as milky serum, bilirubin serum and hemolytic serum (hemoglobin) on the turbidity value cannot be avoided. The LA method has a higher dilution rate than the LN method and is an efficient measurement method in a short time, so errors due to these are considerably alleviated, but at high concentrations (0.25 g / dl of hemoglobin, 25 mg / dl or more of bilirubin) In this case, a measurement error occurs as described above.

The PACIA system counts the number of individual unaggregated particles, measures the volume of the sample solution, and quantifies the body fluid component from the concentration of unaggregated particles after a fixed time.

In any case, in addition to specific aggregation due to the binding of antigen and antibody, factors that cause particle aggregation (such as natural aggregation during reagent storage) and aggregation form differences such as multiple aggregations are the absolute accuracy of the latex agglutination measurement method. And has a great impact on reproducibility.

OBJECT OF THE INVENTION The object of the present invention is to provide non-aggregated particles, two-aggregated particles, 3,
Directly counting 4, 5 agglomerated particles etc. and grasping the actual state of agglomeration to cover the above drawbacks,
It is an object of the present invention to provide a body fluid component analysis method and an apparatus thereof, which enables simpler and more accurate body fluid component measurement.

According to the method for analyzing a body fluid component of the first invention, an antigen-antibody reaction is caused by mixing a sample with a reagent containing an antigen contained in a body fluid or an antibody that specifically reacts with the antibody or an insoluble carrier to which the antigen is attached. And a step of obtaining the number of particles by the degree of aggregation of particles contained in the sample solution while flowing the sample solution after the antigen-antibody reaction, (Where, K is the number of aggregation, omega _K is a weighting factor, P _K is the number of particles in the aggregation number K, n is an integer of 2 or greater to be added into K aggregates) process of obtaining the agglomeration rate X ₂ from It includes and.

The particles are sieved according to size (aggregation number), the number of particles for each size is calculated, and the aggregation rate X ₂ is calculated by the above formula (A), that is, data is obtained for each particle. Therefore, both individual data and total data are extremely accurate. In the case of the turbidimetric method, the problem of error due to hue difference, absorption, scattering, interference, etc. does not occur, and the problem of error due to natural coagulation before measurement does not occur. .

In particular, in order to obtain the aggregation rate X ₂ , the weighting factor ω _K to be added to the agglomerate is determined for each agglomeration number K, and this is taken into account in the calculation, so such a weighting factor is taken into account at all. The error can be reduced compared to the case of the prior art (Japanese Patent Application No. 58-219753), which does not exist, and high-precision measurement becomes possible.

Also, as is clear from the above formula (A), relative value calculation (ratio)
Since the aggregation rate X ₂ is calculated by the method, there is an effect that a volume quantification device can be eliminated.

The body fluid component analysis method according to the second aspect of the invention is, instead of the formula (A) in the first aspect of the invention, From this, the aggregation rate X ₃ is obtained.

The effect of the second invention is similar to the effect of the first invention described above.

In addition, the calculation of the formulas (A) and (B) may be performed automatically by a computer, manually, or may be performed by handwriting.

A body fluid component analyzer according to a third aspect of the present invention comprises a constant temperature means for inactivating serum in a sample solution to suppress non-specific aggregation, and a sample solution delivery means for delivering a sample solution that has undergone antigen-antibody reaction.
A detection tube that receives the sent sample solution and passes the particles in the sample solution in a row, and a detector tube that projects light and receives the scattered light from the particles to detect the particle passage and the size of the passing particles. Particle detecting means, a discriminating means for discriminating the detection signal by the particle detecting means according to its size (agglomeration number), a counting means for counting the number of discriminated signal by particle size, and a particle size discriminating means. It is provided with a calculating means for calculating the aggregation rate X ₂ from the formula (A) based on the number of signals and a displaying means for displaying the calculation result.

The above-mentioned non-specific aggregation means particle aggregation other than particle aggregation based on antigen-antibody specific aggregation. By suppressing this non-specific aggregation, the antigen-antibody reaction can be carried out more reliably, which allows the aggregation rate to be measured with higher accuracy.

According to experiments, the optimum serum temperature for suppressing non-specific aggregation is around 56 ° C.

Further, since the whole system is automated, there is an advantage that not only high measurement accuracy but also extremely quick processing can be performed.

The body fluid component analyzer of the fourth invention comprises a constant temperature means for inactivating serum in the sample solution to suppress non-specific aggregation, and a sample solution delivery means for delivering the antigen-antibody reacted sample solution.
A detection tube that receives the sent sample solution and passes the particles in the sample solution in a row, and a detector tube that projects light and receives the scattered light from the particles to detect the particle passage and the size of the passing particles. Particle detecting means, a discriminating means for discriminating the detection signal by the particle detecting means according to its size (agglomeration number), a counting means for counting the number of discriminated signal by particle size, and a particle size discriminating means. An arithmetic means for calculating the agglutination rate X ₂ from the formula (A) based on the number of signals, a display means for displaying the calculation result, and a width of the sample liquid which is projected onto the detection tube and flows through the detection tube And a dilution ratio control means for automatically maintaining the dilution of the sample solution substantially constant by controlling the sample solution delivery means based on the detection result.
Examples of the dilution rate control means include means for continuously adjusting the dilution rate.

According to this, since the adverse effect of the fluctuation of the flow rate of the sample liquid on the calculation of the agglutination rate is eliminated in advance, there is an advantage that the agglutination rate can be calculated with extremely high accuracy.

The body fluid component analyzer of the fifth invention calculates the agglutination rate X ₃ based on the formula (B), and is otherwise the same as the third invention.

The body fluid component analyzer of the sixth invention calculates the aggregation rate X ₃ based on the formula (B), and is otherwise the same as the fourth invention.

Description of Embodiments An embodiment of the body fluid component analyzer will be described with reference to FIGS. 1 to 7. As shown in FIG. 1, this body fluid component analyzer includes a particle detection block A having a sample liquid transfer and particle detection function, a signal processing block B having a noise removal and function amplification function, pulse amplitude discrimination and pulse counting. And a data processing block C having a display function.

The particle detection block A includes (1) a detection tube 1 having an electromagnetic valve 2 for removing bubbles and a detection tube 1
A reaction tank 5 which is pipe-joined to press-fit the counting sample solution into the container and includes a stirring motor 3 and a thermostatic device 4, and a tank 5.
A constant temperature bath 6 at about 56 ° C. for inactivating the serum before injection, an on-off valve 18, and a sheath liquid for wrapping the counting sample liquid in the detection tube 1 in a sheath shape (sheath shape) and flowing. A drive including a sheath liquid tank 7 pipe-connected so as to be press-fitted, a pump 17 for pumping the sample liquid and the sheath liquid directly or through a one-stage pressure regulator 8, and a control circuit 19 for controlling the pressure regulator 8, the pump 17, and the like. Sample liquid delivery means D including a control device 9 (valves and pipes for replenishing each liquid in the tank 5, the constant temperature bath 6, and the sheath liquid tank 7 are not shown), and (2) the center of the detection tube 1 is arranged in a line. A semiconductor laser (laser generator) 11 for emitting light to irradiate the particles flowing in the direction of elliptical focusing light having a flow direction of 10 μm and a perpendicular direction of 300 μm,
Cylindrical lens system 12, beam stopper (light blocking means) 13 that blocks transmitted light, lens system 14 that guides particle scattered light, stray light blocking plate 15, and photodiode that receives particle scattered light and converts it into an electrical signal. (Photoelectric conversion means)
16, a light emitting diode 11a for detecting the width of the central portion of the sheath flow, a condenser lens 12a, a charge coupled device (C
CD) 20 and optical particle detection means E. The charge-coupled device 20 is connected to the control circuit 19 and the detection width is fed back to the pressure regulator 8 to automatically stabilize the dilution ratio of the sample liquid and the sheath liquid. Note that the dilution rate may be continuously adjusted manually instead of automatically.

The signal processing block B includes a small signal amplification circuit (amplifier) 2
1, a laser noise elimination circuit (limiter) 22 for clamping and clipping a pulse signal, a function amplifier circuit 2 including a linear amplifier 23a and a logarithmic amplifier (logarithmic amplification means) 23b which are switched by a changeover switch Sw.
3 and an output circuit 24 including a filter and a buffer.

The data processing block C includes a pulse amplitude discrimination circuit (that is, a particle size (aggregation number) discrimination means) 25, a means F for counting the number of discriminated particle size signals, and a number of particle size signals. An arithmetic means G for calculating the agglutination rate from the above, and an arithmetic means H for calculating the sample liquid concentration from the calculated agglutination rate,
And control for controlling the drive control circuit 19 of the particle detection block A so as to increase or decrease the sample liquid delivery amount in accordance with the decrease or increase in the count value of the particles (monomers) having the aggregation number 1 per unit time. A microcomputer 26 including means I and the like, a display circuit 27 for displaying data such as the number of signals by particle size, agglutination rate, and sample solution concentration in an analog or digital manner, and the above data. The display means J in a broad sense includes a printing circuit 28 for printing.

The test serum is diluted with a buffer (TTB: tristoline syn-buffer) (40,000 times in the case of Ig-G), and polystyrene latex (0.2 to 5 μm) treated with an antibody is diluted.
Diameter) suspended latex particle liquid (LP liquid 0.01%)
The mixture is mixed in a reaction tank 5 with a thermostat 4, and a screw is rotated by a motor 3 to prevent sedimentation and agitate to promote aggregation.

Simultaneously with mixing, a positive pressure of about 0.3 kg / cm ² is applied by the pump 17, and a positive pressure is also applied to the sheath tank 7 through the pressure regulator 8.
The sheath liquid (0.8% physiological saline) and the agglomerated sample liquid (liquid in the reaction tank 5) are pressure-fed to the detection tube 1.

The detection tube 1 is set so that the sheath liquid around the aggregated sample liquid from the reaction tank 5 is wrapped in a sheath shape and flows at a speed of about 5 m / sec. An electromagnetic valve 2 for removing bubbles is provided on the upper part, and the sheath direction is in the direction of gravity. This is to prevent bubbles from adhering to the sheath forming port and prevent bubbles from affecting the formation of the sheath flow. Even if the sheath liquid is disturbed (deterioration in formation) and the particles remain in the detection tube 1, the latex particles have a slightly higher specific gravity than the sheath liquid. Is discharged promptly without remaining, so that no contamination occurs.

The particles formed by the sheath flow formed in the detection tube 1 are aligned in a line, and the light from the semiconductor laser 11 is focused by the cylindrical lens system 12 (a minor axis of 10 μm in the particle flow direction and a major axis of 300 μm in the perpendicular direction). Oval)
Pass through the inside at high speed. The light receiving side is based on the principle of the dark field method of the microscope. When there are no particles, the beam stopper 13 blocks light, so there is no light reception output, and when particles pass, the scattered light is received by the photodiode 16 through the stray light shielding plate 15. To be done.

The semiconductor laser 11 as a light emitting source is optimal for incorporation into a device in terms of shape and price as compared with the conventional He-Ne laser, but it has a drawback that it has a lot of laser noise, so that it needs some ingenuity for practical use.
In this device, the received light optical axis is perpendicular to the flowing direction of particles,
By offsetting the emitted light optical axis from the received light optical axis by 6 degrees, it is possible to prevent a part of the emitted light from being reflected and returned, and to avoid returning light due to reflection so that noise is not induced by the returning light and noise is increased. There is.

As shown in FIG. 7, the characteristic of the scattered light output with respect to the angle between the light emitting optical axis and the light receiving optical axis shows a vibration characteristic when the particle diameter of the projection target becomes large, and therefore the angle is about 6 degrees in terms of detection stability and sensitivity. When this was done, it was experimentally confirmed that this constituent device was optimal.

Since the noise component of the straight-ahead light is much stronger than the signal, the lower half of the optical axis on which the laser light straight-ahead light on the front light-receiving lens 14a hits, that is, the half on the side opposite to the side where the semiconductor laser 11 exists, As shown in FIG. 2, a beam stopper 13 for shielding light is used to prevent light from entering the light receiving surface when there are no particles.

Further, a stray light blocking plate 15 having a 0.4 mm diameter pinhole for blocking stray light from various angles other than the scattered light from the particles and passing only the scattered light by the particles is provided.

Furthermore, the residual noise component of scattered light removes the low-frequency induced wave, clamps the base voltage of the signal to a constant voltage, and then clips the noise superimposed on the base voltage. A laser noise removal circuit (limiter) The noise problem is solved by using 22.

Semiconductor lasers are more compact than He-Ne lasers,
Although it is inexpensive, it has a lot of noise, but this device can significantly reduce the adverse effects of noise, and thus it is possible to employ a compact and inexpensive semiconductor laser.

The output of the photodiode 16 is amplified by the amplification circuit 21 of the signal processing block B by 60 dB, the noise is removed by the laser noise removal circuit 22, and the amplified waveform is passed through the linear amplifier 23a. FIG. 3 shows the number of particles (pulse frequency) on the axis. FIG. 4 is a similar representation of the waveform after passing through a logarithmic (log) amplifier 23b instead of the linear amplifier 23a.

It can be seen that the variation of the center of amplitude and the amplitude spread logarithmically as the number of agglomerates and the number of three agglomerates progress. It becomes difficult to compare two aggregation modes, three aggregation modes, etc., by performing the same discrimination process. This device solves this problem by using the logarithmic amplifier 23b.

In the discrimination circuit 25, the discrimination voltage is set in the middle of the two voltages giving the peak value of the adjacent cohesion mode voltage, and the pulse discriminated by each discrimination voltage is passed through the exclusive OR circuit for every two adjacent discrimination voltages to output each output in the aggregation mode. It is counted as another count value and sent to the microcomputer 26.

The microcomputer 26 uses the discrimination circuit 25 to output a non-aggregated (monomer), 2 aggregated (doublet), 3 aggregated (triplet), 4 aggregated, 5 aggregated or more, 6-mode pulse train of count values other than latex (satellite). Upon receiving the signal, a predetermined counter (counting means F) counts within a predetermined gate time (5 seconds).

Next, the calculating unit G calculates the following value as the aggregation rate,
The result is sent to the predetermined storage unit.

X ₂ = (ω ₂ · P ₂ + ω ₃ + P ₃ + ω ₄ · P ₄ + ω ₅ · P ₅ ) / (P ₁ + P ₂ + P ₃ + P ₄ + P ₅ ) ... (C) ω ₂ = 1, ω ₃ = 2.3, ω ₄ = 3.8, ω ₅ = 5.3, X ₂ : aggregation rate, P ₂ : doublet number, P ₃ : triplet number, P ₄ : 4 aggregation number, P ₅ : 5 or more aggregation number The weighting factor ω is As shown in the chart of FIG. 8, since the number of bonding groups is different in the aggregation mode, the average value thereof is taken. For example, even with the same four aggregates, the number of bonding groups is 2 for 3, 2 for 4, 2 for 1, and 5 for 3.8, so (3 × 2 + 4 × 2 + 5) ÷ 5 = 3.8 There is.

5 (A) to 6 (C) show a flow chart and a method of obtaining a calibration curve from the data in the storage unit to the concentration calculation as the final result.

That is, in step, the aggregation rate at time 0 (natural aggregation rate) is measured and calculated, in step, the aggregation rate at time t ₁ is measured and calculated, and in step, the aggregation rate at time t ₂ is measured. The calculation is repeated, and the same procedure is repeated thereafter, and the aggregation rate at time t _n is measured and calculated in step. As a result of the above, in step, an aggregation growth curve is obtained [see FIG. 6 (A)]. Then, in step, the natural growth is reduced to obtain a true growth curve [see FIG. 6 (B)]. In the step, the aggregation rate at time T, which has the best S / N ratio in the measurement items (kind of protein), is compared with a known standard aggregation rate.
Then, in step, the correlation between the known protein concentration and the aggregation rate is converted into the protein concentration to be obtained based on the aggregation rate obtained in step [see FIG. 6 (C)].

The aggregation rate can be calculated using the other denominator There are some things that are different, and those with slightly different properties can be obtained depending on the combination. The reproducibility is high by using the formula (C).

Further, the linearity of the calibration curve can be improved by making the number of monomers constant as follows, and the measurement concentration range can be expanded. In addition, it is useful for finding errors. That is, the monomer pulse train signal is converted into an analog voltage through the integrating circuit, and the control means I is operated so that the pump 17 operates faster when the number of pulses decreases.
Feedback to the control circuit 19. That is,
The transfer pressure applied to the reaction tank 5 is increased according to the decrease in the number of monomers by changing the bias of the pump pressure sensor of the control circuit 19, and the sample liquid amount and the sheath liquid amount in the detection tube 1 are continuously changed. Can be changed. Thereby, the transfer amount of the sample solution can be increased to apparently accelerate the aggregation reaction rate, and the aggregation growth curve can be made more linear.

An example of the type of output to the printing circuit 28 and the display circuit 27 is: AFP (α-fetoprotein): 2 mg / ml, CEA (carcinoembryonic antigen): 0.5 μg / ml, Ig-G (immunity) Globulin G): 10 mg / ml, etc.

The above example includes the following items.

The function amplifier circuit 23 is configured to include a linear amplifier 23a and a logarithmic amplifier 23b which are switched by a switch Sw.

The optical particle detecting means E is configured such that an angle is formed between the light emitting optical axis and the light receiving optical axis, and the light emitting lens 14a is provided with the beam stopper 13.

The control means I of the microcomputer 26 feeds back to the drive control circuit 19 of the particle detection block A to increase the amount of the sample solution delivered when the number of particle monomers decreases, thereby keeping the number of monomers constant and linearizing the calibration curve. Has improved.

As an embodiment of the third invention, it is conceivable that none of the above-mentioned items or any two or one items are included. In addition, a switch in which the switch Sw and the linear amplifier 23a are removed can be considered.

Further, regarding the first and second inventions which are method inventions, the particle detecting means is not limited to the optical one, and
The automatic calculation of the agglomeration rates X ₂ and X ₃ is also not limited.
Of course, the presence or absence of the above items 1 to 3 does not matter.

EFFECTS OF THE INVENTION Both the first and second inventions relating to the body fluid component analysis method are based on the fact that data on the degree of aggregation is obtained for each of the particles, so that there is an effect that the measurement accuracy can be made extremely high.

In particular, in order to obtain the aggregation rate, the weighting coefficient to be added to the aggregation is determined for each aggregation number K, and this is taken into consideration in the calculation. Therefore, the prior art that does not include such weighting coefficient at all ( The error can be reduced more than in the case of Japanese Patent Application No. 58-219753), and high-precision measurement becomes possible.

In particular, this body fluid component analysis method can obtain an aggregation rate that better reflects the concentration of the target antigen or antibody, as compared to the case where the number ratio of the polymer and the monomer is simply obtained, and as a result, the antigen or antibody There is an advantage that the concentration can be measured with higher accuracy and higher sensitivity. Since the system of the present invention is a system in which insoluble carriers are aggregated through an antigen or an antibody as a medium, even if it is aggregated in one bit, aggregation of three aggregates is larger than aggregation of two aggregates, that is, the aggregate number n is larger. It should be considered that the amount of the antigen or the antibody is large, of course, as in the present invention, the weighting factor is determined in consideration of the aggregation number, and the aggregation rate is calculated based on this weighting factor, as described above. The concentration of the antigen or antibody can be measured with higher accuracy and higher sensitivity.

Further, since the aggregation rate is calculated by the relative value calculation (ratio), there is an effect that a volume quantification device can be eliminated.

Further, according to the body fluid component analyzers of the third to sixth inventions, the antigen-antibody reaction is performed more reliably by suppressing non-specific aggregation which is particle aggregation other than particle aggregation based on antigen-antibody specific aggregation. Therefore, the aggregation rate can be measured with higher accuracy.

Further, since the entire system is automated, there is an effect that not only high measurement accuracy but also extremely rapid processing can be performed.

[Brief description of drawings]

FIG. 1 is a conceptual diagram showing the construction of an embodiment of a body fluid component analyzer, FIG. 2 is a front view of the light-shielding means, FIGS. 3 and 4 are correlation graphs of pulse amplitude and particle number, and FIG. Flow chart, (A) and (B) of FIG. 6 are graphs of aggregation growth curves, (C) of FIG. 6 is a correlation graph of protein concentration and aggregation rate, and FIG. 7 is between emission optical axis and reception optical axis. The correlation graph between the angle and the scattered light intensity, and FIG. 8 is a chart as a basis for determining the weighting coefficient. 1 ... Detection tube, 6 ... Constant temperature chamber (constant temperature means), 25 ... Discrimination circuit (discrimination means), D ... Sample liquid delivery means, E ... Particle detection means, F ... Counting means, G ... Computing means, J ……
Display means

Claims (10)

[Claims] 1. A process of causing an antigen-antibody reaction by mixing a sample with a reagent containing an antibody or an insoluble carrier having an antigen attached thereto, which reacts specifically with the antigen or the antibody contained in a body fluid, and the above-mentioned antigen-antibody reaction The process of obtaining the number of particles by the degree of agglomeration for the particles contained in this sample solution while flowing the sample solution of (Where, K is the number of aggregation, omega _K is a weighting factor, P _K is the number of particles in the aggregation number K, n is an integer of 2 or greater to be added into K aggregates) process of obtaining the agglomeration rate X ₂ from A method for analyzing a body fluid component, including: 2. A process of causing an antigen-antibody reaction by mixing a sample with a reagent containing an antibody or an insoluble carrier having an antigen attached thereto, which specifically reacts with the antigen or the antibody contained in a body fluid, and the above-mentioned antigen-antibody reaction The process of obtaining the number of particles by the degree of agglomeration for the particles contained in this sample solution while flowing the sample solution of (Where K is the aggregation number, ω _K is a weighting coefficient added to _K aggregations, P _K is the number of particles with the aggregation number K, and n is an arbitrary integer of 2 or more), the process of obtaining the aggregation rate X _3. A method for analyzing a body fluid component, including: 3. A constant temperature means for inactivating serum in a sample solution to suppress non-specific aggregation, a sample solution delivery means for delivering an antigen-antibody-reacted sample solution, and the delivered sample solution. A detection tube for receiving and passing particles in the sample liquid in a row, a particle detection means for projecting light onto the detection tube and receiving scattered light from the particles to detect particle passage and the size of the passing particles, Discrimination means for discriminating the detection signal by the particle detection means according to its size (aggregation number), counting means for counting the number of discriminated signals by particle size, and an equation based on the number of signals by particle size (However, K is the aggregation number, ω _K is a weighting factor added to _K aggregates, P _K is the number of particles with the aggregation number K, and n is an integer of 2 or more), and the aggregation rate X ₂ is calculated. A body fluid component analyzer comprising a calculation means and a display means for displaying the calculation result. 4. The body fluid component analyzer according to claim 3, wherein the constant temperature means keeps the blood serum at a temperature of about 56 ° C. 5. A constant temperature means for inactivating serum in a sample solution to suppress non-specific aggregation, a sample solution delivery means for delivering an antigen-antibody-reacted sample solution, and the delivered sample solution. A detection tube for receiving and passing particles in the sample liquid in a row, a particle detection means for projecting light onto the detection tube and receiving scattered light from the particles to detect particle passage and the size of the passing particles, Discrimination means for discriminating the detection signal by the particle detection means according to its size (aggregation number), counting means for counting the number of discriminated signals by particle size, and an equation based on the number of signals by particle size (However, K is the aggregation number, ω _K is a weighting factor added to _K aggregates, P _K is the number of particles with the aggregation number K, and n is an integer of 2 or more), and the aggregation rate X ₂ is calculated. A calculation means, a display means for displaying the calculation result, a width of the sample solution which is projected onto the detection tube and flows through the detection tube, and the sample solution delivery means is controlled based on the detection result to control the sample. A body fluid component analyzer provided with a dilution ratio control means for automatically maintaining the dilution of the liquid substantially constant. 6. The body fluid component analyzer according to claim 5, wherein the dilution rate control means includes means for continuously adjusting the dilution rate. 7. A constant temperature means for inactivating serum in a sample solution to suppress non-specific aggregation, a sample solution delivery means for delivering an antigen-antibody-reacted sample solution, and the delivered sample solution. A detection tube for receiving and passing particles in the sample liquid in a row, a particle detection means for projecting light onto the detection tube and receiving scattered light from the particles to detect particle passage and the size of the passing particles, Discrimination means for discriminating the detection signal by the particle detection means according to its size (aggregation number), counting means for counting the number of discriminated signals by particle size, and an equation based on the number of signals by particle size (However, K is the aggregation number, ω _K is a weighting factor added to _K aggregates, P _K is the number of particles with the aggregation number K, and n is an arbitrary integer of 2 or more), and the aggregation rate X ₃ is calculated. A body fluid component analyzer comprising a calculation means and a display means for displaying the calculation result. 8. The body fluid component analyzer according to claim 7, wherein the constant temperature means keeps the blood serum at a temperature of around 56 ° C. 9. A constant temperature means for inactivating serum in a sample solution to suppress non-specific aggregation, a sample solution delivery means for delivering an antigen-antibody-reacted sample solution, and the delivered sample solution. A detection tube for receiving and passing particles in the sample liquid in a row, a particle detection means for projecting light onto the detection tube and receiving scattered light from the particles to detect particle passage and the size of the passing particles, Discrimination means for discriminating the detection signal by the particle detection means according to its size (aggregation number), counting means for counting the number of discriminated signals by particle size, and an equation based on the number of signals by particle size (However, K is the aggregation number, ω _K is a weighting factor added to _K aggregates, P _K is the number of particles with the aggregation number K, and n is an arbitrary integer of 2 or more), and the aggregation rate X ₃ is calculated. A calculation means, a display means for displaying the calculation result, a width of the sample solution which is projected onto the detection tube and flows through the detection tube, and the sample solution delivery means is controlled based on the detection result to control the sample. A body fluid component analyzer provided with a dilution ratio control means for automatically maintaining the dilution of the liquid substantially constant. 10. The body fluid component analyzer according to claim 9, wherein the dilution rate control means includes means for continuously adjusting the dilution rate.