JPS60111963A - Method and apparatus for analyzing components of body fluids - Google Patents

Abstract

PURPOSE:To rapidly and simply perform the measurement of components in body fluids with high accuracy, by generating antigen antibody reaction by mixing a reagent and a specimen and calculating an agglutination ratio by a predetermined method while flowing the specimen solution. CONSTITUTION:Serum to be examined is diluted with a buffer solution while the diluted solution is mixed with a suspension of polystyrene latex to which the adhesion treatment of an antibody is applied and the resulting mixture is introduced into a reaction tank 5 with a thermostatic apparatus 4 and positive pressure is applied to a sheath tank 7 by a pump 17 through a pressure regulator 8 while said mixture is stirred through a motor 3 to supply the sheath solution and the agglutinated specimen solution to a detection pipe 1 under pressure. Particles are passed through the focus of condensed beam due to the cylindrical lens system 12 of beam from a semiconductor laser source 11 at a high speed in a state arranged into almost one line. Scattered beam by particles is received by a photodiode 16 through a beam blocking plate 15. The output thereof is applied to a microcomputer 26 through an amplifier 21, a limiter 22, an amplifier 23a, filter buffer and a discriminating circuit 25 to calculate an agglutination ratio. By this method, measurement of components in body fluids is performed rapidly and simply with high accuracy.

Description

DETAILED DESCRIPTION OF THE INVENTION Field of Industrial Application This invention relates to a method for analyzing body fluid components such as proteins, and an analysis apparatus used in this method.

Structure of the conventional example and its problems Many body fluid components mainly contained in blood are in extremely small quantities, but they play an important role in maintaining life, such as in the Bp4 node of water, transport of substances, and immunity.

Until now, the methods of measuring these trace components of body fluids include sedimentation reactions,
Immunological techniques such as agglutination reactions (essentially the same as precipitation reactions, but mainly referring to passive agglutination reactions) have been used.

Typical precipitation reactions include immunoelectrophoresis and SR1D (radial immunodiffusion), and in recent years, radioimmunoassay) and laser nephelometry (SR1D) have been widely used.
N method), enzyme immunoassay method (EIA method), etc. have been developed. Then °ζ, RIA method, EIA method in nanogram units, 5RID method! The LN method has become routine as the 11th milligram measurement method.

Immunoelectrophoresis and 5RID methods take a long time (1 to several days)
However, since this method involves looking at diffusion and sedimentation within a gel, there are many opportunities for error factors such as the effects of other particles and denaturation to occur, making accuracy and reproducibility difficult.

The RIA method and EIA method are highly sensitive and accurate, but since they use radiation and enzymes, they require time and effort to prepare reagents, and there are regulations regarding storage and storage, which require careful consideration. Therefore, a simpler, non-isotropic method is being sought.

As a representative example of agglutination reactions, Sing was developed in 1956.
There is a latex agglutination reaction developed by Er and Plotz et al. Although this measurement method has a very high sensitivity of the reaction itself, it has the weakness of being a semi-quantitative method because it is a visual method. The development of the aggregation reaction method was delayed compared to the reaction method.

Since 1970, methods have been developed to optically quantify latex aggregation. Dezelc et al., F.
Hoffman, Lakoche & Co.
Gesellschaft et al. (UK patent 138439)
9), and the one by Sawai et al. in Japan is well-known (
Latex Agglutination System
m).

Recent devices called LA systems and Lj)IA systems are a descendant of these systems, and are attracting attention as new body fluid component measuring instruments because of their wide measurement range, speed, and good titness. They are latex agglomeration method (LA method)
Also called.

However, L
Similar to the N method, chyle serum, bilirubin serum, hemolysate i'i
Error factors such as differences in hue and state of samples such as hemoglobin (hemoglobin) that affect the nephelometric value cannot be avoided. The LA method is
Compared to the N method, the dilution rate is higher and it is an efficient measurement method in a short time, so errors caused by these are considerably reduced.
51 .mu./rU or more), a measurement error occurs as described above.

Furthermore, the nonlinearity of the LA method and the Ll)IA method makes it difficult to detect errors and limits the measurement range. In addition, calibration errors due to natural aggregation differences before measurement (a degree conversion errors) and calibration errors due to aggregation mode differences are also error factors that cannot be ignored from the perspective of improving accuracy. This is because spontaneous aggregation may occur during storage.

Purpose of the invention The purpose of the invention is to obtain non-agglomerated particles, two-aggregated particles, 3.4
．． A body fluid component analysis method that overcomes the above drawbacks and enables quick, easy, and highly accurate determination of body fluid components δ by directly counting five aggregated particles individually and understanding the actual state of aggregation. and to provide the equipment.

Structure of the Invention The method for analyzing body fluid components of the first invention involves mixing a sample with a reagent containing an antibody that specifically reacts with an antigen or antibody contained in a body fluid, or an insoluble carrier to which an antigen is attached, to cause an antigen-antibody reaction. a step of flowing the antigen-antibody-reacted sample solution and counting the number of particles according to the degree of aggregation of particles contained in the sample solution, and a step of calculating the number of particles according to the degree of aggregation of the particles contained in the sample solution, and the formula % formula % (1) (where n is aggregation number, Pn is the number of particles with aggregation number n, M
The method includes the step of calculating the aggregation rate X from the number of particles (monomers) with an aggregation number of 1, where k is an arbitrary natural number of 2 or more.

Sort the particles by size and aggregation number), calculate the number of particles for each size, and calculate the aggregation rate Both individual data and comprehensive data are of extremely high quality.Hue difference, light absorption, and scattering in the case of turbidimetry.

There is no problem of errors due to interference or the like, and there is no problem of errors due to natural aggregation before measurement, and even objects in which natural aggregation is in progress can be measured.

The body fluid component analysis method of the second invention is based on the first invention (where n is the aggregation number, P n is the number of particles with an aggregation number n, T is the total number of particles, and k is any natural number of 2 or more). This is to calculate the rate Y.

In this case, although the accuracy is inferior to the first invention, the reproducibility is high. The rest is the same as the first invention.

Note that the calculation of equation (11, f2) may be performed automatically using a calculator or manually, or may be performed by hand.

The body fluid component analyzer of the third invention includes a sample liquid sending means for sending out a sample liquid that has undergone antibody-antigen reaction, and a detection tube that receives the sent sample liquid and allows particles in the sample liquid to pass through in a row. , a particle detection means for projecting light into the detection tube and receiving light scattered by the particles to detect passing particles and the size of the passing particles; and a particle detection means for discriminating the detection signal by the particle detection means according to the size and number of aggregations). A device comprising a discrimination means, a counting means for counting the number of signals of the discriminated particle sizes, a calculation means for calculating an aggregation rate from the number of signals for each particle size, and a display means for displaying the calculation result. It is.

The calculation of the aggregation rate is preferably based on the above formula (1) or formula (2), but other formulas may be used. In this case, since the entire system is automated, it has the advantage of not only high measurement accuracy but also extremely rapid processing.

A body fluid component analyzer according to a fourth aspect of the present invention is the third aspect of the present invention, further comprising an amplifying means for logarithmically amplifying the detection signal by the particle detecting means, and a discriminating means for determining the magnitude of the amplified signal by the amplifying means. It is configured to discriminate according to the number of agglomerations).

In other words, when using normal linear amplification means,
As the amplitude center and the amplitude dispersion increase logarithmically as we progress from 2 aggregation to 3 aggregation - 11 (see Figure 3), a comparison by the number of aggregations (signal size) is possible. It becomes difficult. When the logarithmic amplification means of the third invention is adopted as a countermeasure against this, the spread is suppressed and the amplitude center and amplitude are made uniform for each aggregation number (see Fig. 4), making it easy to compare them. This can be done accurately, thereby increasing the measurement accuracy.

The body fluid component analyzer of the fifth invention is related to the improvement of the particle detection means in the third invention, and includes a detection tube through which particles in the sample liquid are passed in a row. A laser generator that irradiates a laser beam from a direction oblique to a direction perpendicular to the flow direction, a light receiving lens that receives light scattered by particles in the sample liquid in the vertical direction, and a photoelectric conversion means behind the light receiving lens. and a light shielding means for making a half of the light-receiving lens on the side opposite to the side where the laser generator is present non-transparent.

That is, since there is an angle between the light emitting optical axis and the light receiving optical axis, it is possible to prevent part of the reflected light from returning to the laser generator and transmitting noise.

In addition, the noise component of the straight light of the laser beam is much stronger than the scattered light detection signal, but since the light receiving lens is provided with a light shielding means at the part where the straight light hits, errors due to the noise component of the straight light can be avoided, thereby further increasing measurement accuracy.

Semiconductor lasers are more compact and cheaper than He-Ne lasers, but on the other hand they produce a lot of noise. According to the fifth invention, however, the negative effects of noise can be significantly alleviated.
Enables the use of compact and inexpensive semiconductor lasers.

In the body fluid component analyzer of the sixth invention, in the third invention, when the count value of particles (monomer) with an aggregation number of 1 per unit time decreases, the amount of sample liquid delivered is increased. A control means for controlling the liquid delivery means is added.

In other words, the number of seven points decreased,
This means that the aggregation reaction rate is fast, and the aggregation growth curve [
(See Figures 6 (A) and (B))), which means that the measurement accuracy decreases, but by increasing the amount of sample liquid delivered, the linearity becomes high and the error factor is removed. It is. This also enables highly accurate measurement.

DESCRIPTION OF THE EMBODIMENTS An embodiment of the body fluid component analyzer will be described with reference to FIGS. 1 to 6. As shown in Figure 1, this analyzer includes a particle detection block A that has sample liquid transfer and particle detection functions;
It consists of a signal processing block B having noise removal and function amplification functions, and a data processing block C having pulse amplitude discrimination and pulse count display functions.

The particle detection block A consists of a detection tube 1 having a solenoid valve 2 for removing bubbles, a reaction tube connected to the detection tube 1 so as to pressurize a counting sample liquid, and equipped with a stirring motor 3 and a constant temperature device 4. A tank 5, a cylinder 6 connected to a tube so as to inject a suspended liquid of polystyrene latex particles to which antibodies or antigens have been attached into the tank 5, and a cylinder 6 in which a counting sample liquid is sheathed in a detection tube 1.
A sheath liquid tank 7 which is pipe-joined to pressurize the sheath liquid to be wrapped and flowed, a DC motor 18 that drives the piston of the cylinder 6, and a sheath liquid tank 7 for pressurizing the sample liquid and sheath liquid either directly or through the one-stage pressure gauge 8. pump 17 and this motor 18. Sample liquid sending means D consisting of a drive control device 9 consisting of a control circuit 19 that controls the pump 17 etc. (valves and pipes for replenishing each liquid in the tank 5, cylinder 6 and sheath liquid tank 7 are not shown), and (2) A light-emitting semiconductor laser (laser generator) 11 for irradiating particles flowing in a line through the center of the detection tube 1 with elliptical focused light of 10 μm in the flow direction and 300 μrn in the perpendicular direction.
, a cylindrical lens system 12, a beam stopper (shading means) 13 that blocks transmitted light, a lens system 14 that guides particle scattered light, a stray light shielding plate 15, and a photodetector that receives particle scattered light and converts it into an electrical signal. It consists of an optical particle detection means E consisting of a diode (photoelectric conversion means) 1G.

Signal processing block B includes a small signal amplification circuit (amplifier) 2
1, a laser noise removal circuit (limiter) 22 that clamps and clips a pulse signal, 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 consisting of a filter and a buffer.

The data processing block C includes a pulse amplitude discrimination circuit (i.e., discrimination means for particle size and aggregation number) 25, a means F for counting the number of signals for each discriminated particle size, and a means for counting the number of signals for each particle size. Calculating means G for calculating the aggregation rate, and calculating means H1 for calculating the sample liquid concentration from the calculated aggregation rate.
and a control means 1 for controlling the drive control circuit 19 of the particle detection block A to increase or decrease the amount of sample liquid sent out in response to a decrease or increase in the count value of particles (monomer) with an aggregation number of 1 per unit time. A microcomputer 26 with built-in information, etc., and the number of signals for each particle size.

It is composed of a display circuit 27 for displaying data such as aggregation rate and sample liquid concentration in an analog or digital manner, and a display means J in a broad sense consisting of a printing circuit L8 for printing the data. There is.

The serum to be tested is diluted (40,000 times for IgG) with a buffer solution (T, T, B: + - ristrinsine buffer), and polystyrene latex (0.2 to 5
A latex particle solution (L-P solution 0.
01%), placed in a reaction tank 5 equipped with a constant temperature device 4, and stirred by rotating a screw with a motor 3 to prevent sedimentation and promote agglomeration.

At the same time as mixing, a positive pressure of about 0.3 kg/CIA is applied by the pump 17, and positive pressure is also applied to the sheath tank 7 through the pressure regulator 8, and the sheath liquid (0.8% physiological saline) and flocculated sample liquid (reaction tank 5) is pumped into the detection tube 1.

The detection tube 1 is set so that the sheath liquid surrounds the aggregated sample liquid from the reaction tank 5 in a sheath shape and flows at a speed of about 5 m/sec. A solenoid valve 2 for removing air bubbles is provided at the upper part, and the direction of the sheath is set in the direction of gravity. This is to avoid air bubbles 41 from forming at the sheath forming port and to prevent air bubbles from affecting the formation of the sheath flow. In addition, even if the sheath liquid is disturbed (not used for formation) and particles remain in the detection tube l, the specific gravity of latex particles is slightly heavier than the sheath liquid, so even if the sample is changed, such as when the sample is turned in the opposite direction, the latex particles will fall to the bottom. Particles are discharged quickly without leaving any residue, therefore no contamination occurs.

Due to the formation of a sheath flow in the detection tube 1, the particles are aligned in a nearly straight line, and the light from the semiconductor laser 11 is focused by the cylindrical lens system 12 to a focal point (with a short axis of 10 μm in the particle flow direction and a long axis of 300 μm in the perpendicular direction). oval)
pass through at high speed. The light receiving side uses the principle of the dark field method of a microscope, and when there are no particles, the light is blocked by the beam stopper 13, so there is no light receiving output, and when a particle passes, the scattered light passes through the stray light shielding plate 15 and is received by the photodiode 16. be done.

Compared to the conventional He--Ne laser, the semiconductor laser 11 serving as the light emitting source is optimal for being incorporated into equipment in terms of size and price, but it has the disadvantage of a lot of laser noise, so it requires some ingenuity for practical use. In this device, the receiving optical axis is perpendicular to the direction in which particles flow, and the emitting optical axis is shifted by 6 degrees from the receiving optical axis to prevent part of the emitted light from being reflected back, and the returned light causes noise. In order to prevent noise from increasing, return light due to reflection is avoided.

Second, since the noise component of the straight light is much stronger than the signal, the lower half of the optical axis where the straight laser light hits the first light-receiving lens 14a, that is, the side opposite to the side where the semiconductor laser 11 is present. A beam stopper 13 blocks half of the beam from light as shown in FIG. 2, so that no light enters the light-receiving surface when there are no particles.

Thirdly, the 0.4 i
A stray light shielding plate 15 having a bottle ball with a diameter of n is provided.

Fourth, the noise component of the scattered light that still remains is removed by removing the low frequency guided wave and clamping the base voltage of the signal to a constant voltage, and then removing the laser noise 1 which clips the noise superimposed on the base voltage. The noise problem is solved by using the circuit (limiter) 22.

The output of the photodiode 16 is processed by the signal processing block B.
After being amplified by 60 dB in the amplifier circuit 21 and having noise removed by the laser noise removal circuit 22, the linear amplifier 23a
FIG. 3 shows the waveform after amplification, with the horizontal axis representing the pulse amplitude and the vertical axis representing the number of particles (pulse frequency). FIG. 4 shows 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 as the number of particles increases from 2 to 3, the center of amplitude and the variation in amplitude expand logarithmically. It is difficult to compare the agglomeration modes of two aggregation and three agglomeration by performing the same discrimination process. In this device, the logarithmic amplifier 23b
I solved this problem by using .

In the discrimination circuit 25, a discrimination voltage is set between the two voltages giving the peak value of the adjacent agglomeration mode voltage, and the pulses discriminated at each discrimination voltage are passed through an exclusive OR circuit for each of the two adjacent discrimination voltages, and each output is condensed. It is counted as a count value for each length mode and sent to the microcomputer 26.

The microcomputer 26 receives the unagglomerated (
monomer), two agglomerated (doubled).

3 aggregation (triblet), 4 aggregation, 5 or more aggregation,
A pulse train signal of 6 modes of counts other than latex (satellite) is received, and a predetermined counter (counting means F) performs counting within a predetermined gate time (5 seconds).

Next, the calculation means G calculates the following value as the aggregation rate,
Send the result to a predetermined storage unit.

X= (21)2 +3P3 +4P4 +5P5)/
X: aggregation rate, M: number of monomers, ■]2: double soto number,
P3: Number of nitriplets, P4: Number of 4 aggregation, P5:
5 or more agglutination numbers (A) or C) in Figures 5 and 6 show the process from data in the storage unit to concentration calculation as the final result using float yards and how to draw a calibration curve. .

That is, in step ■, the aggregation rate at time 0 (natural aggregation rate) is measured and calculated, in step ■, the aggregation rate at time 1 is measured and calculated, and in step ■, the aggregation rate at time t2 is calculated. Measure and calculate, and then repeat the same steps ■
Then, the aggregation rate at t n is measured and calculated. As a result of the above, an agglomerative growth curve is determined in step (2) [see FIG. 6(A)]. Next, in step (2), natural aggregation is reduced to obtain a true growth curve (see FIG. 6(B)). Step ■
Now, the aggregation rate at time T when the SZN ratio is the best for the measurement item (type of protein) is compared with the aggregation rate of a known standard. Then, in step (2), from the correlation between the known protein concentration and the aggregation rate, the desired protein concentration is converted based on the aggregation rate determined in step (2) [see FIG. 6(C)].

The aggregation rate is calculated using the total value (T: total number of detected pulses) as the denominator and the polymer total (P) as the numerator.
: P2 +p3+p4+p5), y=P/
T-(P2+p3+p4 +p5)/T (where T=
P, +p2 +p3+p4+p5) and others, and depending on the combination, products with slightly different properties can be obtained. Y=P/T has high reproducibility.

Furthermore, by keeping the number of monomers constant as follows, the linearity of the calibration curve can be improved and the measurement concentration range can be expanded. It is also useful for discovering errors. In addition, the monomer pulse train signal is passed through an integrating circuit to an analog voltage, and as the number of pulses decreases, a feed bath is applied from the control means 1 to the control circuit 19 so that the motor 18 rotates faster.

Alternatively, the transfer pressure applied to the reaction tank 5 can be controlled by the control circuit 1.
By changing the λias of the pump pressure sensor 9, the ratio of the sample liquid volume in the detection tube 1 to the sheath volume can be continuously changed in accordance with the decrease in the number of monomers. . Thereby, the amount of sample liquid transferred can be increased, the apparent aggregation reaction rate can be accelerated, and the aggregation growth curve can be made more linear.

In addition, an example of the output type to the printing circuit 289 and display circuit 27 is as follows: AFP (CX-fetoprotein): 2 mg/mp.

CEA (carcinoembryonic antigen): Q, 5μl! / II
I (2゜Ig-G (immunoglobulin G): l Om
g/mβ, etc.

The above embodiment includes the following items.

(2) The functional amplifier circuit 23 is configured to include a linear amplifier 23a and a logarithmic amplifier 23b which can be switched by a switch.

(2) The optical particle detection means E has an angle between the light emitting axis and the light receiving optical axis, and is constructed by providing a beam stopper 13 on the light emitting lens 14a.

■ Feedhacking is applied from the control means 1 of the microcomputer 26 to the drive control circuit 19 of the particle detection block A to increase the amount of sample liquid delivered when the number of particle monomers decreases, thereby keeping the number of seven monomers constant and adjusting the calibration curve. Improves linearity.

As an embodiment of the third invention, one that does not include any, any two, or one of the above-mentioned items (1) to (2) can be considered.

As an embodiment of the fourth invention, any one of the above ■ and ■
It is conceivable that Tsudama does not include both. Furthermore, it is conceivable that the switch 3w and the linear amplifier 23a are removed from (2).

As an embodiment of the fifth invention, any one of the above ■ and ■
It is possible to consider one that does not include one or both.

As an embodiment of the sixth invention, any one of the above
There are seven items that do not include one or both.

Further, regarding the first and second method inventions, the particle detection means is not limited to an optical type, and the method of flowing the sample liquid is not limited to that shown in FIG. 1. Also,? M:
The automatic calculation of collection rates X and Y is not limited either. Of course, the presence or absence of the above ■ to ■ does not matter.

Effects of the Invention Both the first and third inventions relating to the body fluid component analysis method are based on obtaining data on the degree of stain resistance for each particle, so they have the effect of making the measurement accuracy extremely high. .

Further, any of the third to sixth inventions relating to the body fluid component analyzer has the effect that measurement can be carried out with extremely high precision and quickly. Furthermore, in the fourth invention, since the amplitude center of the detection signal and the variation in amplitude are suppressed, -JS can be measured with high accuracy. In the fifth invention, the combinations 1 to 1. While it is possible to use an inexpensive semiconductor laser, its disadvantage of large noise can be significantly alleviated, making it possible to perform highly accurate measurements.

In the sixth invention, the linearity of the agglomeration growth curve can be improved, making it possible to perform even more accurate measurements.

[Brief explanation of the drawing]

Fig. 1 is a conceptual diagram of the configuration of an embodiment of a body fluid component analyzer, Fig. 2 is a front view of its light shielding means, Figs. 3 and 4 are correlation graphs between pulse amplitude and particle number, and Fig. 5 is In the flowchart, (A) and (B) of FIG. 6 are graphs of aggregation growth curves, and (C) of FIG. 6 is a graph of the correlation between protein concentration and aggregation rate. 1.-detection tube, 11-semiconductor laser (laser generator),
14a--Light receiving lens, 13-Beam stopper (light shielding means), 16-Photodiode (photoelectric conversion means), 2
3b - Logarithmic amplifier (logarithmic amplification means), 25 - discrimination circuit, D - sample liquid delivery means, E - particle detection means, F - counting means, G - calculation means, ■ - - control means, J - display means

Claims (1)

[Claims] +11 A step of causing an antigen-antibody reaction by mixing a sample with a reagent containing an antibody that specifically reacts with the antigen or antibody contained in the body fluid, or an insoluble carrier to which the antigen is attached;
While flowing the antigen-antibody-reacted sample solution, the particles contained in this sample solution (where n is the number of aggregations, Pn is the number of particles with an aggregation number of n, and M is a particle (monomer) with an aggregation number of 1).
, k is any natural number of 2 or more) to calculate the aggregation rate X. (2) a step of causing an antigen-antibody reaction by mixing the sample with a reagent containing an antibody that specifically reacts with the antigen or antibody contained in the body fluid, or an insoluble carrier to which the antigen is attached;
calculating the agglutination rate Y from the number of particles contained in the sample liquid, T is the total number of particles, and k is any natural number of 2 or more while flowing the antigen-antibody-reacted sample liquid. Component analysis method. (3) A sample liquid sending means for sending out a sample liquid that has undergone antigen-antibody reaction, a detection tube that receives this sent out sample liquid and allows particles in the sample liquid to pass through in a row, and a light beam that is projected onto this detection tube. a particle detection means for detecting the passing of particles and the size of the passing particles by receiving scattered light by the particles; a discrimination means for discriminating the detection signal from the particle detection means according to the size (size and number of aggregation); A body fluid component analysis device comprising a counting means for counting the number of signals for each particle size, a calculation means for calculating an aggregation rate from the number of signals for each particle size, and a display means for displaying the calculation result. (4) A sample liquid sending means that sends out a sample liquid that has undergone antigen-antibody reaction, a detection tube that receives the sent sample liquid and allows particles in the sample liquid to pass through in a row, and a light beam that is projected onto the microtube. Particle detection means receives scattered light by particles and detects passing particles and the size of the passing particles; amplification means logarithmically amplifies a detection signal by this particle detection means; A discrimination means for discriminating by size and (aggregation number) and the number of signals for each discriminated particle size are set to 5.
A body fluid component analyzer comprising a counting means for counting, a calculation means for calculating an aggregation rate from the number of signals for each particle size, and a display means for displaying the calculation result. (5) Try 1lfk without sending out the sample solution that has undergone antigen-antibody reaction.
a sending means, a detection tube that receives the sent sample liquid and allows particles in the sample liquid to pass through in a row, and a detection tube that is arranged in a direction perpendicular to the flow direction of the sample liquid flowing therein. a laser generator that irradiates a laser beam from an inclined direction; a light receiving lens that receives light scattered by particles in the sample liquid in the vertical direction; a photoelectric conversion means behind the light receiving lens; a light shielding means for making the half of the side opposite to the side where the laser generator is present non-transparent; a discrimination means for discriminating the output signal from the photoelectric conversion means according to its size (aggregation number); and a discrimination means according to the discriminated particle size. A body fluid component analysis device comprising a counting means for counting the number of signals, a calculation means for calculating an aggregation rate from the number of signals for each particle size, and a display means for displaying the calculation result. (6) A sample liquid sending means for sending out a sample liquid that has undergone an antigen-antibody reaction, a detection tube that receives this sent out sample liquid and allows particles in the sample liquid to pass through in a row, and a light source that emits light into this detection tube. a particle detection means for detecting the passing of particles and the size of the passing particles by receiving scattered light by the particles; a discrimination means for discriminating the detection signal from the particle detection means according to the size (size and number of aggregation); a counting means for counting the number of separation signals; and a control means for controlling the sample liquid delivery means so as to increase the amount of sample liquid delivered when the count per unit time of particles with an aggregation number of 1 (monomer) decreases. A body fluid component analyzer comprising: a control means for calculating the aggregation rate from the number of signals for each particle size; a calculation means for calculating the aggregation rate from the number of signals for each particle size; and a display means for displaying the calculation result.