JP2001099774A - Device and method for detecting particle - Google Patents

Abstract

PROBLEM TO BE SOLVED: To analyze a liquid sample containing particles of various sizes with a configuration of a low cost. SOLUTION: Electrical resistance type particle detectors 101 are arranged in series, and the sample is supplied to the particle detectors from an upstream side to a downstream side in sequence. The particle detector 101 includes a chamber 1 to which the sample is supplied. An aperture 4 is formed in the chamber 1. Diameter of the aperture 4 gets smaller as one goes from the upstream side to the downstream side so that different detecting sensitivities are provided to the particle detectors 101. The chamber 1 includes openings on the upstream side and on the downstream side. A filter 2 is attached to the opening on the upstream side, and selects the particles so that the particles supplied to the chamber 1 becomes smaller in the downstream side chamber, and clogging of the aperture 4 is prevented.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a technique for analyzing a liquid sample in which various types of material are mixed.

[0002]

2. Description of the Related Art Conventionally, a so-called electric resistance type particle detector has been generally used as one of the devices for measuring the formed components in urine and blood. In the electric resistance type particle detector,
This is a device that allows a sample to pass through an aperture provided between electrodes, and detects a voltage change between the electrodes when a material component in the sample passes through the aperture. The voltage change is proportional to the volume of the material. By monitoring a voltage change equal to or greater than a predetermined value, the number and size of the tangible components can be measured.

[0003] An electric resistance type measuring device is more cost effective than a flow cytometer for measuring the formed components in a liquid sample, and can be constructed in a small size. But it has the advantage of easy installation.

[0004]

However, in the electric resistance type measuring device, the size of particles that can be detected differs depending on the aperture diameter. For example, when measuring the number of blood cells in blood by an electrical resistance method, a blood sample for measuring platelets and red blood cells having a small particle size, and a blood sample for measuring white blood cells having a large particle size are separately adjusted, An aperture having a small diameter (50 μm) is used for detecting the former, and an aperture having a large diameter (100 μm) is used for detecting the latter.

[0005] On the other hand, when a sample in which various components having various sizes and shapes are mixed, for example, a urine sample is measured by an electric resistance method, the following problems occur. To detect small-diameter particles, it is necessary to set the aperture diameter small. However, when the aperture diameter is set to be small, large-diameter particles are clogged in the aperture, and measurement cannot be performed. On the other hand, if the aperture diameter is increased in order to prevent shrinkage, small particles cannot be detected. In other words, when the size of the particles contained in the sample varies over a wide range, there is a problem that it is not possible to perform an appropriate measurement with an electric resistance type device.

Japanese Patent Application Laid-Open No. 50-110388 discloses a detector for measuring a sample containing particles of various sizes. The detector has different aperture diameters at different heights in the sample. However, in reality, it is considered that particles do not aggregate at a specific height in the sample for each size, and large-diameter particles are clogged in a small aperture.

An object of the present invention is to provide a technique capable of detecting particles of each size with high sensitivity without clogging an aperture even in a liquid sample in which the sizes of particles vary over a wide range. Aim.

[0008]

In order to solve the above-mentioned problems, the first invention of the present application provides a particle detecting device provided with a plurality of particle detectors for measuring particles in a liquid sample based on impedance change. The particle detector comprises an aperture;
An electrode for applying a voltage in a direction crossing the aperture, a signal processing unit for detecting a change in impedance between the electrodes, and a chamber for supplying a liquid sample to the aperture are provided.

[0009] The present particle detecting device is configured such that flow paths between the particle detectors are arranged in series so that the liquid sample is sequentially supplied from the upstream particle detector to the downstream particle detector. I have. A filter for selectively passing a liquid sample is provided in a flow path between the particle detectors. The particle detector is formed such that the aperture diameter becomes smaller toward the downstream side.

[0010] The aperture is formed by an aperture forming member that forms a circular fine hole. The aperture forming member is provided in the chamber, and is formed such that the diameter of the aperture becomes smaller toward the particle detector on the downstream side. In this type of detector, a pellet (also referred to as a wafer) made of ruby, artificial ruby, ceramic, or the like is used as the aperture forming member. The chamber is
An upstream opening for introducing the liquid sample into the inside,
A downstream opening for discharging the liquid sample to the outside, and capable of storing the liquid sample. The filter is provided in the flow path between the particle detectors. For example, the filter is attached to the upstream opening of the chamber and selectively passes particles in the liquid sample such that particles supplied into the chamber become smaller in the downstream chamber.

The detection sensitivity of an electric resistance type particle detector is substantially determined by the aperture diameter. Therefore, particle detectors having different aperture diameters are arranged in series from upstream to downstream. As a result, particles of different sizes can be detected by each particle detector, and even a liquid sample having a wide range of particle sizes as a whole can be analyzed with high sensitivity. In order to prevent the aperture from being clogged in each device, a filter is used to selectively pass particles supplied into the chamber. Thereby, the particles in the sample supplied into each chamber become smaller toward the downstream side.

According to a second aspect of the present invention, in the particle detector according to the first aspect, at least three particle detectors are provided, and a filter provided in a flow path between the particle detectors has a particle diameter to be selectively passed. Provided is a particle detection device characterized in that the particle detection device is formed to be smaller toward the downstream side. By providing the filter such that the particle diameter to be passed becomes smaller toward the downstream side, clogging of the aperture whose diameter becomes smaller toward the downstream side can be prevented.

The third invention of the present application includes an aperture, an electrode for applying a voltage in a direction crossing the aperture, a signal processing unit for detecting a change in impedance between the electrodes, and a chamber for supplying a liquid sample to the aperture. What is claimed is: 1. A particle detection method using a plurality of particle detectors for measuring particles in a liquid sample based on a change in impedance, wherein A: a liquid sample is supplied from an upstream particle detector to a downstream particle detector sequentially. B: providing a filter for selectively passing a liquid sample through the flow path between the particle detectors; C: setting the aperture diameter of the particle detector to: Provided is a particle detection method, characterized in that the particle size is reduced toward the downstream side.

The same operation and effect as those of the first invention are provided.

[0015]

DESCRIPTION OF THE PREFERRED EMBODIMENTS Next, the present invention will be specifically described with reference to embodiments. First Embodiment [Configuration] FIG. 1 is a schematic configuration diagram of a first embodiment of a particle detection device according to the present invention. The particle detection device 100 according to the present embodiment includes a plurality of particle detectors 101a, 101b, and 101c. In this embodiment, a particle detection device using three particle detectors will be described as an example. Each of the particle detectors 101a, 101b, 101c,
They are arranged in series from the upstream side to the downstream side so as to sequentially pass through 1a, b, and c.

Each of the particle detectors 101a, b, c includes a chamber 1a, b, c housed in a case 3a, b, c and a filter 2a, b, c. The plurality of chambers 1a, b, c are connected via filters 2b, c. Each of the chambers 1a, b, c has an aperture 4a, b, which has a different aperture diameter for each chamber.
c is formed. Specifically, the aperture diameter is formed so as to decrease as the aperture diameter of the downstream chamber increases. This is because the size of the particles that can be detected by each particle detector 101 is made different.

Each of the cases 3a, b, c is configured to be easily attached and detached, and the filters 2a, b, c can be easily replaced. Depending on the measurement target,
This is because the number of combinations of the particle detectors 101 can be easily increased or decreased. A detection circuit 9a, b, c and a quantitative control circuit 10a, b, c are connected to each case 3a, b, c. The detection circuits 9a, 9b, 9c apply a voltage to the sample in the chamber 1 and detect a voltage change between electrodes (see FIG. 2 described later) provided across the aperture 4. The quantitative control circuits 10a, 10b and 10c aspirate a predetermined amount of the sample in the chamber 1.

The pipette 1 is placed in the most upstream case 3a.
1 are connected. The pipette 11 stores a liquid sample to be measured. Further, the pipette 11 discharges the liquid sample after the measurement and the cleaning liquid that has cleaned the chamber from the cleaning spits 12 to the first container 13. A syringe 15 is connected to the most downstream case 3 c via a first valve 14. The syringe 15 is a second valve 1
7 and connected to the second container 16. Second container 1
A cleaning liquid for cleaning the inside of the chamber is stored in 6. The syringe 15 introduces a liquid sample from the pipette 11 into the chamber 1. The syringe 15 discharges a sample from the chamber 1 and introduces a cleaning solution into the chamber 1.

Sensors 18a and 18b are provided at the upstream and downstream ends of the liquid paths of the connected particle detectors 101a, 101b and 101c. All chambers 1a, b,
This is for detecting whether or not the liquid sample has been supplied to c. FIG. 2 is an enlarged view of the case 3. FIG. 3 is an AA ′ partial cross-sectional view of the case 3. The chamber 1 is formed symmetrically in the vertical direction in the figure. This is for introducing the liquid sample into the chamber 1 evenly. An annular aperture forming member 5 is attached to a side surface of the chamber 1. The side wall of the chamber corresponding to the central part of the aperture forming member 5 is removed, and the apertures 4a,
b and c are formed. The diameters of the apertures 4a, 4b, and 4c are different for each case 3 and are provided so as to decrease from the upstream side to the downstream side. This is to make the detection accuracy of the particles different in each of the particle detectors 101a, 101b, and 101c.

A tube 6 for sucking a sample from the chamber 1 is attached to the aperture 4. The tube 6 is connected to the quantitative control circuit 10. This is for sucking a predetermined amount of the liquid sample from the chamber 1 and passing the liquid sample through the aperture 4. In order to form an electric field crossing the aperture 4, electrodes 7, 8 are provided with the aperture 4 interposed therebetween. The electrodes 7, 8 are connected to the detection circuit 9. This is for measuring a voltage change between the apertures 4. The positive electrode 7 is provided in the tube 6.

FIG. 4 is a partial sectional view taken along the line BB 'of the case 3 of FIG. The negative electrode 8 is provided on the opposite side of the positive electrode 7 across the aperture 4. [Operation] Next, the operation of the particle detection device according to this embodiment will be described. Prior to the measurement, contaminants in the sample are dissolved with an appropriate solvent, if necessary.

First, the first valve 14 is turned on, and the syringe 15 sucks a predetermined amount of the liquid sample from the pipette 11. Thereby, the liquid sample is sequentially introduced into each chamber 1 from the upstream side to the downstream side. In this step, the filters 2a, b, c provided at the upstream openings of the chambers 1a, b, c selectively pass only particles having a size that does not block the aperture diameter of the next chamber. Let it. This is because the aperture diameter of the chamber 1 is formed so as to decrease from the upstream side to the downstream side.

The coarseness and aperture diameter of the filter can be appropriately set depending on the sample to be analyzed. For example, Table 1 shows settings for analyzing urine using three particle detectors. Table 1 shows the roughness of the filter attached to the upstream opening of each chamber 1a, b, c,
The aperture diameters in b and c are shown.

[0024]

[Table 1] After a predetermined time from when the first valve 14 is turned on, the upstream and downstream sensors 18a and 18b detect whether the liquid sample has been introduced into all the chambers. Both sensors 18
If a and b detect a liquid sample, all chambers 1
Liquid samples are introduced into a, b, and c. Syringe 15
Stops the suction of the liquid sample, and the first valve 14 is closed.

Next, in each of the particle detectors 11a, b, and c, the analysis of the liquid sample in each of the chambers 1a, b, and c is started. That is, the detection circuits 9a, 9b, 9c apply voltages to the electrodes 7, 8, respectively. Quantitative control circuits 10a, b,
“c” aspirates a predetermined amount of the detection liquid from the tube 6. As the detection liquid is sucked, the liquid sample in the chamber 1 passes through the aperture 4. Detection circuits 9a, b, c
Detects a voltage change caused by particles in the liquid sample passing through the apertures 4a, b, and c, and measures the number and size of particles.

The apertures 4a, 4b and 4c of the particle detectors 101a, 1b and 1c are set to have a diameter suitable for the target particle to be measured, so that the particles can be detected with high sensitivity. Moreover, particles larger than the aperture diameter are filtered by the filters 2a, b,
Since it is not cut in c and supplied to the chamber,
The aperture 4 is hardly clogged. In the chamber 1 on the upstream side, a liquid sample in which particles smaller in size than the particles to be measured are mixed is analyzed. However, the voltage change due to the small size particles is negligible because it can be regarded as noise. .

After the measurement is completed, the first valve 14 and the second valve 17 are opened, and the syringe 15 discharges the liquid sample in the chamber 1 from the pipette 11 to the first container 13, and the cleaning liquid from the second container to the chamber 1. Is introduced. The discharged liquid sample and the introduced cleaning liquid are sequentially supplied from the downstream to the upstream chamber, and discharged from the pipette 11 to the first container 13 via the cleaning spits 12. Since the volume of the chamber 1 of each particle detector 101 is small, cleaning can be efficiently performed with a small amount of cleaning liquid, and carryover can be reduced.

In the step of cleaning the inside of the chamber 1, it is preferable to pressurize and introduce the cleaning liquid because the flow path of the liquid sample and the filter 2 can be efficiently cleaned. It is more preferable to introduce air into the chamber 1 by introducing air from the first valve 14 into the chamber 1 because the filter 2 and the chamber 1 can be efficiently cleaned and water droplets in the chamber 1 can be easily removed.

The particle detecting device of the present invention can be configured inexpensively and compactly, and can detect the number and size of each particle in a liquid sample containing particles in a wide range with high sensitivity. In addition, particles having very different sizes and concentrations can be measured efficiently and simultaneously for each particle. Specifically, depending on the concentration of the particles to be measured,
The analysis amount of the liquid sample can be set individually for each particle detector.

For example, when measuring urine sedimentation in a urine sample,
The number of cylinders having a large diameter is small and most of them are 1 / μl or less. Conversely, some bacteria have a small diameter and a large number of bacteria, for example, about 1,000 to 100,000 positive specimens / μl. Thus, it is difficult to measure with the same analytical amount. In the particle detection device of the present invention, when measuring urine, a column having a large diameter has a very low concentration (approximately
(1 piece / μl), so that an improvement in accuracy can be expected by increasing the amount of analysis. Conversely, bacteria having a small diameter have a high concentration (approximately 1,000 to 100,000 cells / μl), so that a reduction in the amount of analysis can be expected to shorten the analysis time and reduce the memory.

When a urine sample is measured using a flow cytometer, if the bacteria and the cylinder are to be measured simultaneously and accurately, the amount of analysis must be increased, and a wasteful time is required for the analysis of the bacteria. I will. In the particle detection device of the present invention, after the liquid sample is once introduced into each chamber, the downstream particle detector 11c that measures small particles such as bacteria includes:
Analyze only the amount appropriate for the bacteria. On the other hand, the upstream particle detector 11a that measures a large particle such as a cylinder measures an analysis amount sufficient to accurately analyze the cylinder. This makes it possible to simultaneously and efficiently measure particles having significantly different concentrations and sizes in the sample with high accuracy.

[0032]

The particle detector according to the present invention can accurately measure the size and number of each particle in a liquid sample containing particles having a wide range of sizes.

[Brief description of the drawings]

FIG. 1 is an overall configuration diagram of a particle detection device according to a first embodiment.

FIG. 2 is a configuration diagram of a particle detector according to the first embodiment.

FIG. 3 is a partial sectional structural view taken along line AA ′ of the case in FIG. 2;

FIG. 4 is a partial cross-sectional structural view taken along line BB ′ of the case in FIG.

[Explanation of symbols]

 100; particle detector 101a, b, c; particle detector 1a, b, c; chamber 2a, b, c; filter 3: case 4a, b, c; aperture 5; aperture forming member 6; tube 7; 8; Positive electrode 9a, b, c; Detection circuit 10a, b, c; Quantitative control circuit 11; Pipette 12; Washing spits 13; First container 14; First valve 15; Syringe 16; Second container 17; Valves 18a, b; sensors

Claims (3)

[Claims] 1. A particle detector comprising a plurality of particle detectors for measuring particles in a liquid sample based on a change in impedance, wherein the particle detector comprises an aperture and an electrode for applying a voltage in a direction intersecting the aperture. A signal processing unit that detects a change in impedance between the electrodes, and a chamber that supplies a liquid sample to the aperture, such that the liquid sample is sequentially supplied from the upstream particle detector to the downstream particle detector. A flow path between the particle detectors is arranged in series, and a flow path between the particle detectors is provided with a filter that selectively allows a liquid sample to pass therethrough. A particle detection device characterized in that the aperture is formed so as to have a smaller aperture diameter. 2. The particle detecting device according to claim 1, further comprising at least three particle detectors, wherein a filter provided in a flow path between the particle detectors has a particle diameter to be selectively passed downstream. A particle detection device characterized in that the particle detection device is formed so as to have a smaller size. 3. An aperture, an electrode for applying a voltage in a direction intersecting with the aperture, a signal processing unit for detecting a change in impedance between the electrodes, and a chamber for supplying a liquid sample to the aperture, and based on the impedance change. A particle detection method using a plurality of particle detectors for measuring particles in a liquid sample, wherein the liquid sample is sequentially supplied from an upstream particle detector to a downstream particle detector. A flow path is arranged in series, a filter for selectively passing a liquid sample is provided in a flow path between the particle detectors, and an aperture diameter of the particle detector is formed so as to become smaller toward a downstream side. A particle detection method comprising: