JP3223380B2 - Measurement / dilution of minute sample, particle measurement device, and measurement method - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an apparatus and a method for measuring, diluting, and measuring a small amount of a sample, and more particularly to a method for measuring a minute amount of a liquid sample with high accuracy and further diluting a small amount of a sample with a high dilution ratio. The present invention relates to the measurement and dilution of a small amount of sample, which can be continuously and rapidly measured and diluted with various kinds of samples, and a particle measuring device and a measuring method.

[0002]

2. Description of the Related Art As a technique for measuring the volume of a trace liquid, there is, for example, an "optical trace quantifier" disclosed in Japanese Patent Publication No. 60-86439. This apparatus quantitatively measures a sample in a fluid channel having a transparent portion by an optical method, and measures the amount of the sample in the channel. As typified by this example, especially in an automatic chemical analyzer or the like, it is necessary to measure the volume of a very small amount of liquid. Requires a few microliters or more, and it is difficult to measure and quantify a small volume smaller than that.

[0003]

In the above prior art, a sample in a fluid channel having a transparent portion is quantitatively determined by an optical method, and the amount of the sample in the channel is measured. The measurement is performed by moving along the road to the measurement part. For this reason, the sample that easily adheres to the flow path wall surface remains in the flow path before and after the measurement, causing an error. Furthermore,
Variations in meniscus at the sample boundary also cause errors. Also, when quantifying a small amount of sample, it is necessary to use a fine fluid flow path, for example, human blood and the like, by passing through the fine flow path, the components may change, etc. There was a problem.

An object of the present invention is to measure, quantify, dilute, and transport a very small amount of liquid sample of 1 microliter or less with high accuracy, and to perform these operations continuously and at high speed. Measurement and dilution of small amounts of sample,
It is to provide a particle measuring device and a measuring method.

[0005]

To accomplish the above object means to provide a process, a weighing device for small samples weighing the liquid sample micro-volume, constituting two parallel planes sandwiching the liquid sample Upper and lower plates
And spotting the liquid sample on a lower plate,
An area measuring means for measuring an area of the liquid sample which has been spread out in a flat plate by pressing the plate and the upper plate .

In addition, a small volume of a liquid sample is measured.
Micro sample weighing deviceAnd, The liquid sample
Sandwiched at regular intervals, and at least one of them allows light to pass through
Two parallel planesMake up the upper and lower plate
When,The liquid sample is spotted on the lower plate,
Pressing plate and top plateFixed by
The surface of the liquid sample spread out into a flat plate having a thickness of
Means for optically measuring the product, said area and said constant thickness
Means for determining the volume of the liquid sample from
It is characterized by the following.

A recess is formed in one of the two planes, a small amount of the liquid sample is sandwiched in the recess, and the two planes are overlapped and spread out in a flat plate shape. The area of the sample can be measured, and the fixed interval can be formed by sandwiching a thin spacer between the two planes. Further, the volume of the liquid sample can be measured by taking an image of the liquid sample spread between the two planes with a television camera and performing image processing on an image signal from the television camera.

Further, a micro-volume of liquid sample weighed dilution, a metering diluter traces sample to create a sample dilution of a constant concentration, a liquid sample of the micro-volume, in parallel at regular minute intervals An upper and lower platform that at least one of them has two planes through which light passes
Dotted to the lower plate of the rate , the lower plate
And by measuring the area of the liquid sample is spread in a flat plate shape by pressing an upper plate, and measuring the volume of liquid sample, two plates adhered of the measured liquid sample, as it is It is characterized in that a sample diluent having a constant concentration is prepared by immersing in a fixed amount of diluent and stirring.

[0009] The two planes each include an inner surface of a bottom surface of the dilution container through which light passes and a flat plate surface provided on a stirring rod, and the diluted liquid measured in the dilution container to which the measured liquid sample adheres. And agitating the mixture with the stirring rod, a sample diluent having a constant concentration can be prepared.

In addition, a small volume of a liquid sample is measured and diluted.
A small amount of sample to create a constant concentration of sample diluent
The diluter according to claim 1, wherein the liquid sample has a small volume.
At least one that is installed in parallel with a small interval
The upper and lower presses make up two planes through which light passes.
Spot on the lower plate of the
By pressing the upper plate, it spreads into a flat plate shape
Measuring the area of the liquid sample
By measuring the volume of the liquid sample, the measured liquid sample, by flowing the diluent quantified between the two plates and flushing the diluent together with the diluent,
A constant concentration of sample diluent can be made. In addition, by providing a large number of the two planes, it is possible to continuously measure and dilute many kinds of trace liquid samples, and to continuously produce many kinds of sample diluents having a constant concentration.

[0011] Further, a particle measuring apparatus for a small amount of sample, in which a small amount of liquid sample containing minute particles is measured and diluted to prepare a sample diluent having a constant concentration, and the number of particles or the particle volume per fixed volume in the diluent is measured. And an upper part and a lower part, each of which is provided with two planes through which at least one of the micro liquid samples is disposed in parallel at a predetermined minute interval and at least one of which transmits light.
And the lower plate is spotted on the lower plate.
By measuring the area of the liquid sample is spread in a flat plate shape by pressing a plate and top plate, the volume of the liquid sample containing the fine particles were measured, the measured liquid sample of the two Pre
Which was circulated dilution quantified during over preparative swept away in the diluted solution per particle measuring unit, and measuring the number of particles or particle volume in the diluent per given volume in particles measuring unit It is.

In addition, a small volume liquid sample is measured.
A method for measuring a small amount of a sample, comprising:
At least one installed in parallel with a certain small interval
Upper and lower play comprising two planes through which light passes
Spot on the lower plate of the
Press and spread to flat plate
Measuring the area of the liquid sample
Measuring the volume of the liquid sample.
You. Also, there is provided a method for measuring a small volume of a liquid sample having a small volume having an electrical property such as electric resistance or dielectric constant, wherein the liquid sample is provided with two electrically conductive liquids disposed in parallel at a predetermined minute interval. A flat plate made of members
That the one of the flat plate of Chi spotted, pressed against the other flat plate
The liquid sample and the
The liquid contact area with the conductive member flat plate, electrical resistance or RiMotomu Me by measuring the electrostatic capacity of the liquid sample sandwiched between the two flat plate, from said predetermined small gap between the contact area It is characterized by measuring the volume of a sample.

[0013]

According to the above construction, the edge of the trace liquid sample spread on the flat surface can be measured by optical means or the like. Therefore, the contact area of the trace liquid sample with the flat surface can be easily measured. The volume of a trace liquid sample can be measured with high accuracy. In addition, since two planes with the measured liquid sample attached can be immersed in the quantified diluent and agitated as it is, it is possible to easily and continuously create many types of highly accurate, constant-concentration sample diluents. Becomes possible. Further, the number of particles or the volume of particles in a diluent per fixed volume can be measured by diluting a trace liquid sample containing fine particles.

Further, since the electrical properties such as the electric resistance and the dielectric constant of the trace liquid sample vary depending on the contact area with the plane, it is necessary to determine the change of these electrical properties of the liquid sample by using a conductive member on the plane. Accordingly, the contact area with the plane of the conductive member can be obtained, and the volume of the liquid sample can be measured without using optical means.

[0015]

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS Some embodiments of the present invention will be described below with reference to the drawings.

(Embodiment 1) As a first embodiment of the present invention, an example of a system for measuring and diluting a small amount of a liquid sample to measure the particle concentration will be described with reference to FIGS. 1 and 2. FIG. These figures show an example of a device configuration for continuously measuring the concentration of particles in various kinds of minute samples containing particles after measuring and diluting a minute liquid sample. .

As shown in FIG. 1 and FIG. 2, this embodiment comprises a diluent supply tube 1, a diluent flow 2 before dilution, a diluent flow 3 containing a sample, a diluent transport tube 4,
A holding mechanism 5 for holding the sample, a sample spotting pipetter arm 6A for moving the sample spotting pipetter 6,
A sample continuous supply mechanism 7, a lower plate arm rotation mechanism 8, a transparent plate fixing stage 9, a diluent supply syringe pump 10, a plate drying air supply tube 11,
Waste liquid transport tube 12, particle measurement signal line 13, image signal line 15 for transmitting image signals from camera 14, particle measurement unit 16 for measuring particles contained in diluent, spotting for spotting a small amount of sample It comprises a lower plate arm 17 having a surface 17A for transporting the sample to the area measuring section, a transparent plate 18 for pressing the sample and measuring the area of the sample with the camera 14 from above. Two holes 19 are formed in the transparent plate 18, one of which is connected to the diluent supply tube 1 and the other to the diluent transport tube 4. And this transparent plate 18
And the sample spotting surface 17A of the lower plate arm 17 are pressed at a fixed minute interval, and the spread area of the liquid sample spread between the transparent plate 18 and the sample spotting surface 17A is measured. .

The following operation is performed by the above configuration.

(1) The pipetting device 6 picks up a liquid sample from the continuous sample supply mechanism 7 by the movement of the pipetting arm 6A.

(2) The operation of the sample mounting pipettor arm 6A causes the sample mounting pipetter 6 to move to a predetermined position of the lower plate arm 17 (the sample mounting surface 17).
A) A small amount of liquid sample is spotted on A).

(3) The lower plate arm 17 is rotated by the operation of the lower plate arm rotating mechanism 8, and the sample carries the spotting surface 17A to below the upper plate fixed stage 15.

(4) The holding mechanism 5 is the lower plate arm 1
The sample spotting surface 17A of No. 7 is extruded upward, and the sample is pressed between the transparent plate 18 and the sample spotting surface 17A.

(5) The volume of the trace sample is measured by measuring the area of the sample spread between the transparent plate 18 and the sample spotting surface 17A with the area measuring camera 14. The image signal from the area measuring camera 14 is
The image signal is sent to an image processing device (not shown) by an image signal line 15.

(6) The diluent flows from the diluent supply tube 1 in the flow direction 2 while the transparent plate 18 and the lower plate arm 17 are aligned. At this time, the diluent is flowed in a fixed amount to dilute the measured sample to a predetermined concentration. The liquid sample sandwiched between the transparent plate 18 and the sample spotting surface 17A of the lower plate arm 17 is washed away by the diluent, flows with the diluent through the diluent transport tube 4 in the flow direction 3, and flows into the particle measuring unit 16 Transported up to.

(7) When the feeding of the diluent is completed, the holding mechanism 5 is moved downward, and the transparent plate 18 and the lower plate arm 17 are separated. The diluent remaining on the sample spotting surface 17A of the transparent plate 18 and the lower plate arm 17 evaporates in a short time by blowing dry air from the plate drying air supply tube 11.

(8) The particle measuring section 16 measures the concentration of particles contained in the diluent containing particles supplied from the diluent transport tube 4. At this time, for example, an electric resistance method is used in which a sample of a certain volume is flowed through the micropores, and the number and volume of particles contained therein are measured based on fluctuations in electric resistance before and after the micropores. The measured electric resistance signal is sent to a particle measurement signal processing device (not shown) via the particle measurement signal line 13.

(9) The sample after the measurement is completed is transported to a predetermined place through the waste liquid transport tube 12.
Further, a cleaning liquid is poured into the particle measuring unit 16 to clean the inside.

(10) The sample is continuously supplied from the continuous sample supply device 7, and the above operations (1) to (2) are performed.
Up to a high speed continuously.

In the system for measuring the particle concentration of a minute sample containing particles as described above, a minute sample can be diluted at a high magnification, so that a highly accurate measurement can be performed even on a sample having a very high particle concentration. Further, the present system can continuously perform high-speed measurement, dilution, transport, and particle concentration measurement of various kinds of minute samples. Note that the transparent plate 18 does not necessarily have to be colorless and transparent.
What is necessary is just to be able to measure the area of the spread liquid sample by the transmitted light.

Second Embodiment Next, as a second embodiment, an example of an apparatus in a case where a method for measuring and diluting a trace amount of liquid sample is configured as a system will be described with reference to FIG. FIG. 3 is an example of an apparatus configuration for continuously measuring and diluting a trace liquid sample with respect to various kinds of trace samples.

In FIG. 3, the present embodiment shows a diluent supply tube 1, a diluent flow 2 before dilution, a diluent flow 3 containing a sample, a diluent transport tube 4, a holding mechanism 5, an area measurement. Camera 14, sample point mounting pipettor 6
A lower plate 21, a lower plate transport belt 22, a transparent belt 23, a measurement window 24, a lower stage 2
5 etc.

The lower plate 21 has a concave portion 26 and two holes 19 formed by a micromachining technique. A plurality of lower plates 21 are installed on the lower plate transport belt 22. The transport belt 22 is made of a material such as rubber, for example, and moves in the moving direction 22A. The transparent belt 23 is made of a material such as a plastic film, for example.
It moves in the direction of movement 23A. The lower plate 21 and the transparent belt 23 are kept clean and dry.

First, a small amount of sample 27 is spotted on one of the lower plates 21 by the sample spotting pipetter 6. The lower plate 21 is transported by the lower plate transport belt 22 moving in the movement direction 22A, and moves onto the lower stage 25. The lower stage 25 is provided with two stage holes 28, which are connected to the holes 19 provided in the lower plate 21.
The lower plate transport belt 22 functions as a packing, connects the holes 19 and the stage holes 28, and prevents leakage of the diluent. One of two stage holes 28 provided in the lower stage 25 is connected to the diluent supply tube 1, and the other is connected to the diluent transport tube 4.

Thereafter, by pressing the holding mechanism 5 downward, the transparent belt 23 is pressed against the lower plate 21, and the area of the sample 27 spread on the transparent belt 23 is measured by the measurement window 24 provided on the holding mechanism 5. The volume of the sample 27 is obtained in the same manner as in the first embodiment.

Next, the transparent belt 23 and the lower plate 21
The diluent is allowed to flow from the diluent supply tube 1 in the direction of arrow 2 while keeping the alignment. At this time, the diluent is flowed in a fixed amount to dilute the measured sample to a predetermined concentration. The sample 27 sandwiched between the lower plate 21 and the transparent belt 23 is washed away with the diluent, flows with the diluent through the diluent transport tube 4 in the direction of arrow 3, and is transported to a predetermined location.

When the feeding of the diluent is completed, the holding mechanism 5
Is moved upward, and the lower plate 21 and the transparent belt 23 are separated. Different samples are successively spotted on the lower plates 21 on the lower plate transport belt 22 by the sample spotting pipetter 6, and similar measurement and dilution are continuously performed. Further, the transparent belt 23 is connected to the lower plate, and the portion used for the measurement moves in the moving direction 23A because the diluent is attached, and the next measurement is performed on the unused portion.

In this embodiment, the measurement, dilution, and transportation of various kinds of minute samples can be continuously performed at high speed by the above operation. Further, in the present embodiment, it is not necessary to wash and dry the lower plate 21 and the transparent belt 23 used for the measurement. Further, in the present embodiment, the remaining of the sample and the diluent does not affect the next measurement.

(Embodiment 3) Next, as Embodiment 3, a method for measuring and diluting a small amount of liquid sample by taking out the main part of Embodiment 2 alone will be described with reference to FIGS. 4 and 5. FIG. FIG. 4 is a configuration diagram of the present embodiment, and FIG. 5 is a sectional view of a measurement state of the present embodiment.

As shown in FIG. 4, in the lower plate 21 used in the present method, a concave portion 26 and two holes 19 are formed by a micro-machining technique as in the second embodiment. One of the two holes 19 formed in the lower plate 21 is connected to the diluent supply tube 1, and the other is connected to the diluent transport tube 4. The lower plate 21 and the transparent plate 29 are kept clean and dry.

First, a small amount of sample 2 was prepared in the same manner as in Example 2.
7 is spotted. The spotting is performed on the concave portion 26 of the lower plate 21 and between the two holes 19. Thereafter, as shown in FIG. 5, the transparent plate 29 is pressed against the lower plate 21 in the same manner as in the second embodiment, and the area of the sample 27 spread on the transparent plate 29 is measured to determine the volume of the sample 27.

Next, the transparent plate 29 and the lower plate 2
The diluent is allowed to flow from the diluent supply tube 1 in the direction of arrow 2 in FIG. At this time, the diluent is flowed in a fixed amount to dilute the measured sample to a predetermined concentration. The sample 27 sandwiched between the lower plate 21 and the transparent plate 29 is washed away by the diluent, flows with the diluent through the diluent transport tube 4 in the direction of arrow 3 in the figure, and is transported to a predetermined place. With the above operation, the measurement, dilution, and transport of a small amount of sample are performed.

In this embodiment, similarly to the second embodiment, the sample can be diluted only by flowing the re-diluting liquid for dilution. Further, the diluent is transported to a predetermined place through the diluent transport tube, which is advantageous when the present embodiment is systematized.

(Embodiment 4) Next, another method for measuring and diluting a small amount of a sample according to the present invention will be described with reference to FIGS. FIG. 6 and FIG. 7 are configuration diagrams of a method of measuring a small amount of sample and a method of dilution different from those of the third and fourth embodiments.

As shown in FIG. 6, in the lower plate 30 used in this embodiment, grooves 31 and holes 32 are formed by a micro-machining technique as in the second embodiment. Lower plate 3
The hole 32 formed at 0 is connected to the diluent supply tube 1. The lower plate 30 and the transparent plate 29 are kept clean and dry.

First, a small amount of the liquid sample 27 is spotted on the groove 31 of the lower plate 30 as in the second embodiment. Thereafter, the transparent plate 29 is pressed against the lower plate 30 in the same manner as in Example 2, and the area of the sample 27 spread on the transparent plate 29 is measured by an area measuring camera or the like, and the volume of the sample 27 is obtained.

Next, as shown in FIG.
The diluent 9 flows from the diluent supply tube 1 in the direction of the diluent flow 2 while the lower plate 9 is pressed against the lower plate 30. At this time, the diluent is flowed in a fixed amount to dilute the measured sample to a predetermined concentration. The sample 27 sandwiched between the lower plate 30 and the transparent plate 29 is washed away by the diluent and enters the diluent container 33 together with the diluent. The diluent 34 mixed with the sample is stirred in the diluent container 33 to mix the sample and the diluent. With the above operation, the measurement and dilution of the trace sample are performed.

In this embodiment, it is possible to dilute the sample only by flowing the re-diluted solution, and it is not necessary to operate the lower plate 30 and the transparent plate 29 after the quantification of the sample 27.

(Embodiment 5) Next, an embodiment of the apparatus for measuring a small amount of sample according to the present invention will be described with reference to FIGS. 8, 9 and 10. FIG. 8 is a configuration diagram of the present embodiment, FIG. 9 is a configuration diagram of a state in which weighing is performed in the configuration of FIG. 8, and FIG. 10 is a configuration diagram of FIG. 9 viewed from the side.

First, as shown in FIG. 8, a small amount of the liquid sample 27 is spotted on the lower plate 35. At this time,
The lower plate 35 allows the sample 27 to lie on its plane,
It is desirable that the material be in contact with a spherical surface with a certain contact angle. It is also desirable that the transparent plate 29 be made of a material with which the sample 27 comes into contact with a certain contact angle on its plane. This is sample 27
This is to prevent the from spreading on a plane. Also,
The lower plate 35 is desirably of such a color that its surface makes a contrast with the color of the sample 27 and the liquid portion can be easily identified.

To collect a small amount of the liquid sample 27, the sample spotting pipetter 6 is used. The sample spotting pipetter 6 is formed of a thin pipe. After sucking the liquid sample from the tip, a small amount of the sample is discharged in a state where the tip is in contact with the lower plate 35, and is attached to the lower plate 35. A sample may be attached to the tip of a needle-like bar instead of the sample spotting pipettor 6 and attached to the lower plate 35 to sample a small amount of the sample 27.

Since the liquid sample to be collected will be quantified thereafter, it is not necessary to sample with high precision. It is sufficient that sampling can be performed with an amount close to the target (error range within 20% of the target amount).

Next, as shown in FIGS. 9 and 10, the transparent plate 29 is made to approach the lower plate 35 in parallel with a slight gap 36 therebetween. The plate interval 36 at this time is set so that the liquid sample 27 is sandwiched between two flat plates (the transparent plate 29 and the lower plate 35) and spreads in a circular shape to some extent.

If the plate interval 36 is known, the sample 27 sandwiched between the two planes is measured by measuring the area of the sample 27 spread on the transparent plate 29.
Can be determined. The area of the sample is measured by the area measuring camera 14. The area measurement is, for example, T
If the area is calculated by performing image processing on a signal from the camera using a V camera, a CCD camera, or the like, the area can be obtained at high speed. When the sample 27 is a transparent substance such as water, the angle of illumination from above the transparent plate 29 is adjusted, and the area between the sample and the air is captured by the area measuring camera 14 to measure the area.

According to the present embodiment, a very small amount of the liquid sample 27 can be measured by adjusting the plate interval 36. For example, when the amount of the sample 27 is 1 microliter, if the plate interval 36 is set to 100 micrometers, the sample 27
9 spreads in a circle with a radius of about 1.8 mm. in this way,
By enlarging the image of the sample 27 spread on the transparent plate 29 and capturing it with a camera, and processing the image, a liquid sample of 1 microliter or less can be measured with high precision.

The present embodiment has a simple configuration as compared with a method of taking a sample into a space of a fixed volume and quantifying the sample.
There are few errors. In addition, if the lower plate and the transparent plate are kept in a clean state, there is no possibility that impurities are mixed into the sample from the outside or that the sample is excessively attached to a place other than the measuring section, thereby causing an error.

(Embodiment 6) Next, another method for measuring a small amount of sample according to the present invention will be described with reference to FIG. Lower plate 3
7 is made of a material such as silicon, for example, and forms a concave portion 26 having a uniform depth and high precision as shown in FIG. 11 by a micromachining technique such as etching. The depth of the concave portion 26 is set to correspond to the plate interval shown in FIG. The sample 27 is spotted on the concave portion 26, and the transparent plate 29 is overlaid on the lower plate 37. The sample in the recess 26 of the lower plate 37 is sandwiched between two parallel plates. According to this embodiment, the volume of a small sample can be easily measured by measuring the area of the sample.

Example 7 In the analysis of a liquid sample, it may be necessary to dilute the sample to a certain concentration. FIG. 12 is a block diagram of a dilution method for diluting a weighed sample to prepare a diluent having a constant concentration. FIG.
A method for diluting a trace liquid sample weighed using No. 2 will be described.

In FIG. 12, a diluent 34 quantified by an amount for diluting the weighed sample 27 to a predetermined concentration is placed in a dilution container 33. The transparent plate 29 and the lower plate 35 after the measurement of FIG.
7 is immersed in the diluent 34 with the adhered state. next,
The diluent 34 is agitated so that the sample 27 attached to the transparent plate 29 and the lower plate 35 is evenly mixed in the diluent 34. With the above procedure, the weighed sample can be diluted.

According to the present embodiment, it is possible to dilute all of the weighed liquid sample in addition to the diluting liquid without adhering the reduced amount of the liquid sample to portions other than the plate and reducing it.
Further, according to the present embodiment, since the amount of the liquid sample to be diluted is very small, the necessary diluent can be diluted with a small amount.
In the case of dilution with a dilution ratio of about tens of thousands, a large amount of diluent is required, so that the dilution is usually performed in two or more steps. Can be diluted.

Embodiment 8 Next, another method for measuring and diluting a small amount of sample according to the present invention will be described with reference to FIG. FIG. 13 is a configuration diagram of a method for measuring a small amount of sample and a method of dilution, which are different from the seventh embodiment.

In FIG. 13, the dilution container 33 has a transparent bottom 38 and a flat shape. The bottom 38 of the dilution vessel 33 functions as the transparent plate 29 in the previous embodiment. First, the sample 27 is spotted on the inner surface of the bottom portion 38 of the dilution container 33 in the same manner as in the above-described embodiment. The inner surface of the dilution container 33 is kept clean and dry.

Next, a stirring rod 40 having a pressing plate 39 at the tip is pressed against the bottom 38 of the dilution container 33. At this time, the holding plate 39 is set in parallel with the inner surface of the bottom portion 38 of the dilution container 33 at a slight interval. Stirring rod 40
The press plate 39 is also kept clean and dry. The sample 27 is spread on the inner surface of the bottom 38 of the dilution container 33 and spreads in a circular shape. Sample 2 spread in a circle
7 is measured from below by the area measuring camera 14,
The volume can be determined.

Next, the sample is diluted. An appropriate amount of diluent 34 for diluting the weighed sample 27 is poured into the dilution container 33. The stirring of the diluent is performed by rotating the stirring rod 40 used for performing the quantitative determination.

According to this embodiment, as in the case of the seventh embodiment, dilution having many advantageous points is possible. Further, according to the present embodiment, the transparent plate and the lower plate as in the seventh embodiment are not required, and these are present in the diluent and do not hinder the stirring. Further, according to the present method, since the measurement and the stirring are performed using the stirring rod 40, the system can be simplified.

(Embodiment 9) Next, another method for measuring a small amount of a sample according to the present invention will be described. FIG. 14 is a configuration diagram of another method for measuring a small amount of a sample according to the present invention. In the present embodiment, the flat plate 42 sandwiching the sample 41 is made of a conductive metal. In the present embodiment, it is assumed that the electrical properties of the sample 41, such as the resistance and the dielectric constant, are known. First, as shown in FIG. 14, in a state where the sample 41 is sandwiched, the electric resistance value or the capacitance between the flat plates 42 is measured by the sensor 43. Since the electrical resistance and the capacitance of the sample 41 sandwiched between the flat plates 42 vary depending on the area in contact with the flat plate 42, the contact area of the sample can be obtained by measuring these. The signal from the sensor 43 is amplified by an amplifier 44 and is calculated by a computer 45.
Send to The computer 45 calibrates the temperature of the sample 41, the resistance and the capacitance of the flat plate 42, and obtains the area of the sample 41 in contact with the flat plate 42 by calculation. This embodiment does not require optical means such as a camera as a measuring means, and is advantageous when a minute amount of a sample having a known electric property is measured.

[0066]

As described above, according to the present invention, a very small amount of liquid sample of 1 microliter or less can be measured with high accuracy.
Quantification, dilution, and transportation are possible, and these operations can be performed continuously and at high speed.

[Brief description of the drawings]

FIG. 1 is a configuration diagram showing a system according to a first embodiment of the present invention.

FIG. 2 is a partially enlarged view of FIG. 1;

FIG. 3 is a configuration diagram illustrating a system according to a second embodiment of the present invention.

FIG. 4 is a configuration diagram showing a third embodiment of the present invention.

FIG. 5 is a partial sectional view of FIG. 4;

FIG. 6 is a configuration diagram illustrating a weighing method according to a fourth embodiment of the present invention.

FIG. 7 is a configuration diagram showing a dilution method of Example 4.

FIG. 8 is a configuration diagram showing a fifth embodiment of the present invention.

FIG. 9 is a configuration diagram showing a state where weighing is performed in the configuration of FIG. 8;

FIG. 10 is a configuration diagram when FIG. 9 is viewed from the side.

FIG. 11 is a configuration diagram showing a sixth embodiment of the present invention.

FIG. 12 is a configuration diagram showing a seventh embodiment of the present invention.

FIG. 13 is a configuration diagram showing an eighth embodiment of the present invention.

FIG. 14 is a configuration diagram showing a ninth embodiment of the present invention.

[Description of sign]

 DESCRIPTION OF SYMBOLS 1 Diluent supply tube 2 Diluent flow before dilution 3 Diluent flow including sample 4 Diluent transport tube 5 Holding mechanism for sandwiching sample 6 Pipetter for sample mounting 6A Pipetter arm for sample mounting 7 Sample continuous supply Mechanism 8 Lower plate arm rotation mechanism 9 Transparent plate fixing stage 10 Syringe pump for diluent supply 11 Air supply tube for plate drying 12 Waste transport tube 13 Particle measurement signal line 14 Camera 15 Image signal line 16 Particle measurement unit 17 Lower plate Arm 17A Spotting surface 18 Transparent plate 19 Hole 21 Lower plate 22 Lower plate transport belt 23 Transparent belt 22A, 23A Moving direction 24 Measurement window 25 Lower stage 26 Recess 27 Small amount sample 28 Stage hole 29 Transparent plate 30 Lower Plate 31 grooves 32 hole 33 diluent container 34 dilutions 35 lower plate 36 spacing 36 37 bottom plate 38 dilution container bottom 39 pressing plate 40 stirring rod 41 Sample 42 metal flat plate 43 sensors 44 amplifier 45 computer

──────────────────────────────────────────────────続 き Continuation of the front page (72) Inventor Hideo Eno 502 Kandachi-cho, Tsuchiura-shi, Ibaraki Machinery Research Laboratory, Hitachi, Ltd. (56) References JP-A-1-307608 (JP, A) JP-A-62- 69139 (JP, A) JP-A-3-165219 (JP, A) JP-A-3-68816 (JP, A) JP-A-2-278125 (JP, A) JP-A-62-168055 (JP, A) (58) Field surveyed (Int.Cl. ⁷ , DB name) G01F 17/00 G01N 1/00-1/20 G01N 35/00-35/08

Claims (12)

(57) [Claims] 1. An apparatus for measuring a small amount of a liquid sample, comprising: an upper plate and a lower plate which define two parallel planes sandwiching the liquid sample.
And the liquid sample is spotted on the lower plate.
By pressing the part plate and the upper plate ,
An area measuring means for measuring an area of the liquid sample which is spread out in a flat plate shape. 2. A metering device small samples weighing the micro-volume of a liquid sample, sandwiching said liquid sample at regular intervals, and upper and lower at least one of constituting two parallel plane passing light Plate and front
The liquid sample is spotted on the lower plate,
Means for optically measuring the area of the liquid sample that has been spread out into a flat plate having a certain thickness by pressing the plate and the upper plate, and obtaining the volume of the liquid sample from the area and the certain thickness. And a means for measuring a minute amount of sample. 3. The device for measuring a small amount of sample according to claim 2, wherein a concave portion is formed in one of the two planes, a small amount of the liquid sample is sandwiched in the concave portion, and the two planes are formed. An apparatus for measuring a measurement sample, comprising measuring an area of the liquid sample which is superimposed and spread into a flat plate shape. 4. An apparatus according to claim 2, wherein said predetermined interval is formed by sandwiching a thin spacer between said two planes. 5. An apparatus according to claim 2, wherein the liquid sample expanded between the two planes is photographed by a television camera, and an image signal from the television camera is subjected to image processing. An apparatus for measuring a small amount of a sample, which measures the volume of a liquid sample. 6. A method for measuring and diluting a small volume of a liquid sample,
A metering diluter traces sample to create a sample dilution of a constant concentration, a liquid sample of the micro-volume,
Upper and lower plates, at least one of which is arranged in parallel at a fixed minute interval and at least one of which forms two planes through which light passes
It was spotted on the bottom plate of the bets, the lower plate and the upper
By measuring the area of the liquid sample is spread in a flat plate shape by pressing a part plate, measuring the volume of the liquid sample, two plates adhered of the measured liquid sample, it is quantitatively A measuring and diluting apparatus for a small amount of sample, wherein a sample diluent having a constant concentration is prepared by immersing the sample in a diluted diluent and stirring. 7. The device for measuring and diluting a small amount of a sample according to claim 6, wherein the two planes include an inner surface of a bottom surface of a dilution container through which light passes, and a flat surface provided on a stirring rod,
Injecting the measured amount of diluent into the dilution container to which the measured liquid sample adheres, and stirring the mixture with the stirring rod to create a sample diluent having a constant concentration, thereby diluting a small amount of the sample. apparatus. 8. A method for measuring and diluting a small volume of a liquid sample,
An apparatus for diluting a small amount of a sample for preparing a sample diluent having a constant concentration, wherein at least one of the minute amount of the liquid sample is disposed in parallel at a fixed minute interval and at least one of the upper and lower surfaces constitutes two planes through which light passes. And lower plate
The lower plate and the upper plate
The volume of the liquid sample was determined by measuring the area of the liquid sample is spread in a flat plate shape by pressing a plate, the measured liquid samples were quantified during the two plate dilution An apparatus for measuring and diluting a small amount of sample, wherein a sample diluent having a constant concentration is prepared by flowing a liquid and flushing the diluent together with the diluent into a diluting container. 9. An apparatus for measuring and diluting a small amount of sample according to claim 8, wherein a large number of two planes are provided, so that measurement and dilution of various kinds of small amount of liquid sample are continuously performed, and a large number of sample diluting solutions having a constant concentration are obtained. A measuring and diluting device for small amounts of samples, characterized by the continuous production of different types. 10. An apparatus for measuring the amount of particles or a volume of particles in a dilute solution, by diluting a dilute liquid sample containing microparticles, by measuring and diluting the dilute solution, and measuring the number or volume of particles in the diluent. And an upper portion and at least one of the trace liquid samples, which are arranged in parallel at a constant minute interval , constitute two planes through which light passes.
The lower plate is spotted on the lower plate,
By measuring the area of the liquid sample is spread in a flat plate shape by pressing the rate and the upper plate, the volume of the liquid sample containing the fine particles were measured, the measured liquid sample of the two play
And distributed the diluted solution was quantified during the preparative swept away in the diluted solution per particle measuring unit, small samples, characterized by measuring the number of particles or particle volume in the diluent per given volume in particles measuring unit Particle measurement device. 11. A metering method of trace samples weighing the micro-volume of liquid sample, upper part at least one is installed parallel to and spaced a predetermined minute distance the liquid sample constitutes the two planes passing light And lower plate
The lower plate and the upper plate
By measuring the area of the liquid sample spread in a flat plate by pressing the plate and ,
A method for measuring a small amount of a sample, comprising measuring a volume of the liquid sample. 12. An electrical resistance or trace sample metering method for metering a liquid sample of trace volume having the electrical properties of the dielectric constant or the like, which is installed parallel to and spaced a predetermined minute distance the liquid sample two Flat consisting of two conductive members
One flat plate spotted out of the plate, pressing the other flat plate
The liquid sample spread in a flat shape by
Wherein the contact area between the conductive member flat plate, electrical resistance or RiMotomu Me by measuring the electrostatic capacity of the liquid sample sandwiched between the two flat plate <br/>, the constant and the contact area with the A method for measuring a small amount of a sample, comprising measuring a volume of the liquid sample from a minute interval.