JPH11118702A - Sample-analyzing apparatus with cleaning control function - Google Patents

Abstract

PROBLEM TO BE SOLVED: To efficiently clean a sample path corresponding to nebulosity of a sample and improve analysis accuracy by setting a nephelometric measuring part detecting nebulosity of the sample, a control part controlling an operation of a cleaning part in accordance with the nebulosity of the sample, etc. SOLUTION: A nephelometric measuring part projects light to a sample, detects a scattering light and a passing light and calculates nebulosity from a result of the detection. Specifically, when a sample liquid is present in a chamber 36, photodiodes 39a, 39b detect the passing light passing the sample liquid and scattering light scattered at the sample liquid of the light from an LED 37 and output signals corresponding to intensities of the lights. A control part calculates the nebulosity on the basis of intensities of the passing light and scattering light, and controls an operation of a cleaning part in accordance with the nebulosity. At a cleaning process, a manipulator 43 moves the chamber 36 to insert a nozzle 36a and a nozzle 3 to a waste liquid container 41. Then, valves 2, 33, 34 are opened only for a predetermined time. A cleaning liquid in a container 35 is supplied to each passage to execute cleaning for only a predetermined time.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a sample analyzer having a washing control function. In particular, the present invention relates to an analyzer for analyzing solid matter contained in urine or plasma as a biological sample, in which the degree of washing of the flow path of the analysis sample is changed according to the degree of turbidity of the analysis sample. It is intended to provide an analyzer as described above.

[0002]

2. Description of the Related Art In a conventional analyzer, a predetermined process is performed on a sample, and the flow of the sample is irradiated with light so as to measure forward or side fluorescence and scattered light obtained from particles in the sample. There is known an optical device which has been described, and a device in which a needle-shaped member is inserted into an orifice through which a sample passes in an electric resistance type particle counter to count particles of various sizes (for example, Japanese Patent Application Laid-Open No. 4-334759 and EP-A-242971 A2).

[0003]

When a sample containing a large amount of particles is measured, the flow path of the analyzer is contaminated and affects the next measurement. Especially in biological samples, bacteria may propagate in the sample or crystals may precipitate, and in this case, the amount is also large, so if the bacteria and crystals are about the same size as the measurement target, In particular, it adversely affects the measurement results.

[0004] Therefore, assuming this case, it is preferable for the measurement result to perform thorough washing on the flow path every time after the measurement. However, there is a problem in that it requires time for cleaning, and the cost required for the cleaning solution also increases. The present invention has been made in view of such circumstances, and detects turbidity of a sample and controls washing conditions according to the turbidity so as not to affect the next measurement. A sample analyzer is provided.

[0005]

SUMMARY OF THE INVENTION The present invention provides a turbidity measuring section for measuring turbidity of a sample, a particle analyzing section for analyzing the form and number of particles in the sample, a turbidity measuring section and a particle analyzing section. A cleaning control function including a sample supply unit that supplies a sample to the unit via a flow path, a cleaning unit that cleans the flow path through which the sample flows, and a control unit that controls the operation of the cleaning unit according to the turbidity of the sample The present invention provides a sample analyzer provided with the above.

[0006]

BEST MODE FOR CARRYING OUT THE INVENTION The test particles (formed material) in the sample analyzer of the present invention are used for erythrocytes, leukocytes, casts, mucous (mucous) and epithelial cells contained in urine, and plasma. The fibrin mass contained is chylomicron-like particles of chyle.

[0007] The sample in the present invention refers to a liquid sample containing urine or plasma which is a biological sample, and includes, for example, turbid urine and turbid plasma. The turbid urine includes pus urine, hematuria, saline urine, chyle urine, fatty urine, bacteriuria, and the like, and the turbid plasma includes chyle plasma, hemolyzed plasma, bilirubin plasma, and the like.

In the turbidity measuring section of the present invention, a sample is accommodated in a translucent container, the sample is irradiated with light to detect scattered light and transmitted light intensity, and turbidity is calculated from the detection result. It is preferable to use means.

This is based on the principle that, when the turbidity is large, the transmitted light intensity is reduced and the scattered light intensity is increased. In the present invention, either the transmitted light intensity or the scattered light intensity is used. The turbidity may be calculated by either of them. However, in this case, the transmitted light intensity is easily affected by the color of the sample, and the scattered light intensity is easily affected by particles in the sample. Therefore, it is preferable to use the scattered light intensity in the present invention.

As described above, when a light source and a light-receiving element are installed near a light-transmitting container in order to detect transmitted light and scattered light intensity, the light-transmitting container is attached to a sample for measurement. For example, it is installed at a position before processing is performed, for example,
A stirring chamber for accommodating the sample during sample suction may also be used.

The flow path through which the sample flows, that is, the flow path to be washed by the washing section, is at least a flow path from the sample supply section to the particle analysis section. When a particle analyzer that optically or electrically analyzes is used, it is a flow path including the flow cell, and may include a flow path from the sample supply unit to the turbidimetric measurement unit.

The means for flowing the sample through the flow path can be constituted by means for collecting the sample, sending it to the flow path and discharging it, that is, a positive pressure source and a negative pressure source, a syringe, a valve, a diaphragm pump and the like.

The washing section for washing the flow path is a means for supplying / discharging a washing liquid instead of the sample to / from the flow path through which the sample passes, and is provided from a positive pressure / negative pressure source, a valve, various pumps and the like. Although it can be configured, a part thereof may also be used as a component of the sample supply unit. In addition, for example, a cell sheath or Urinoclean manufactured by Toa Medical Electronics Co., Ltd. can be used as the cleaning liquid.

The control unit according to the present invention controls the operation of the washing unit in accordance with the detected turbidity.
Activate the washing section only when the turbidity exceeds a predetermined value,
This means that at least one control is performed such as (2) changing the operation time of the cleaning unit according to the turbidity value, and (3) changing the type of the cleaning liquid according to the turbidity value. Washing may be performed according to the turbidity of the sample in the previous analysis operation before supplying the sample to the flow path, or may be performed after the analysis operation is completed to prepare for the next analysis operation.

The control section may further have a function of notifying that the turbidity is abnormally high and stopping the sample supply operation of the supply section, that is, stopping the next analysis operation. . This can prevent excessive contamination or clogging of the flow channel caused by a sample having an abnormally high turbidity. Further, the control unit for controlling the operation of the washing unit can be configured integrally with the control unit of the particle analysis unit, for example, integrally with a personal computer.

[0016]

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS The present invention will be described below in detail with reference to the embodiments shown in the drawings. Note that the present invention is not limited to this. FIG. 1 is an explanatory view showing a fluid system and an optical system according to an embodiment. Reference numerals 31 to 34 denote valves, 35 denotes a washing liquid container, 36 denotes a light-transmitting chamber for stirring a sample, and 37 denotes light irradiating a cell 36. The light emitting diode 38 is a condenser lens.

Reference numeral 39a denotes a photodiode provided on the optical path of the light emitting diode 37 for receiving the light of the light emitting diode 37 through the chamber 36, and 39b denotes a light emitting diode 3
7, a photodiode which is provided on an optical path orthogonal to the optical path 7 and receives the scattered light of the sample in the chamber 36; 40, a container for the sample liquid to be analyzed; 41, a waste liquid container;
This is a diaphragm pump that stirs the sample liquid by repeatedly sucking and discharging the sample liquid into and from the chamber 36.

Reference numeral 3 denotes a suction nozzle for sucking the sample liquid from the sample liquid container 40, and reference numeral 36a denotes a suction nozzle for sucking the sample liquid into the chamber 36.
A nozzle 43 for discharging the chamber 36 into the containers 40 and 4
This is a manipulator that is moved during the period of 1. The nozzles 3 and 36a have inner diameters of 0.7 mm and 1.99 mm, respectively, and the nozzle 3 is joined to the nozzle 36a in parallel and integrated.

Further, 1 and 2 are valves, 4 is a syringe, 4a is a motor for driving the syringe 4, 5 is a flow cell, 6 is a sample nozzle, 7a is a first cell, 7b is a second cell, 8 is a valve, 9 Is a sheath liquid container, 10 is a supply port for supplying the sheath liquid to the first cell 7a, 11 is an orifice connecting the first cell 7a and the second cell 7b, and 12 is the first cell 7
a, a platinum electrode provided in the second cell 7b, 14 a second electrode 7b
A drain port 15 is provided on the electrode 1 with the electrode 12 serving as a cathode.
A DC constant current power supply 3 is connected between the electrode 12 and the electrode 13 with the anode as an anode, and an amplifier 16 amplifies the output voltage of the power supply 15 and outputs it as a signal 29.

Further, 17 is a laser light source, 18 is a condenser lens, 19 is a beam stopper, 20 is a collector lens, 21 is a pinhole, 25 is a photodiode,
Reference numeral 6 denotes a sample liquid flow output from the sample nozzle 6, and reference numeral 30 denotes a light shielding plate having a pinhole 21.

FIG. 2 is a block diagram showing a control system of the embodiment. Reference numeral 50 denotes an analysis control unit composed of a personal computer; 51, an input unit (here, a keyboard) for inputting analysis conditions and setting conditions to the analysis control unit 50; And mouse), 5
2 is an output unit for outputting set values and analysis results (here, CR
T). The analysis control unit 50 drives the valves 1, 2, 8, 31 to 34, the manipulator 43, and the motor 4 a according to the conditions input from the input unit 51, and receives outputs from the photodiodes 25, 39 a, 39 b, and the amplifier 16. The analysis processing is performed by the controller and the analysis result is output to the output unit 52.

The turbidity detecting step, the analyzing step, and the washing step performed in such a configuration will be described in more detail. First, in the turbidity detection step, the manipulator 4
3 moves the chamber 36 and inserts the nozzle 36 a and the nozzle 3 into the sample liquid in the container 40.

Next, the valve 32 is opened and the sample liquid is sucked into the chamber 36 by the diaphragm pump 42,
Subsequently, the valve 31 is opened, and the sample liquid is discharged from the chamber 36 to the container 40 by the diaphragm pump 42.

This operation is repeated a plurality of times, and the sample liquid in the container 40 is stirred. During this operation, when the sample liquid is present in the chamber 36, the photodiodes 39a, 39b
Respectively receive the transmitted light and the scattered light of the sample liquid irradiated with the light of the light emitting diode 37, and output signals corresponding to the respective intensities. The analysis control unit 50 calculates the turbidity A based on the detected transmitted light intensity and the scattered light intensity, compares the calculated turbidity A with the set values C1, C2, and (C2> C1), and stores the comparison result.

When the turbidity detecting step is completed as described above, the sample liquid analyzing step is started as described below. However, the turbidity A detected in the turbidity detection step
Is larger than C2, the analysis control unit 50 determines that the sample causes some trouble in the flow path due to excessive turbidity, and outputs that fact to the output unit 52, and the next analysis step Do not start.

When A <C2, first, the valves 1, 2
Is opened for a predetermined time, and the sample liquid is filled between the valves 1 and 2 from the suction nozzle 3 by the negative pressure. If necessary, sample processing (dilution, staining, chemical reaction, etc.) for measurement is performed here. Next, the motor 4a is driven, and the syringe 4 pushes the sample liquid between the valves 1 and 2 to the sample nozzle 6 at a constant flow rate, so that the sample liquid is discharged from the sample nozzle 6 from the sample nozzle 6 to the first cell 7a. You.

At the same time, by opening the valve 8, the first
The sheath liquid is supplied to the cell 7a. As a result, the sample liquid is wrapped in the sheath liquid and further narrowed down by the orifice 11 to form a sheath flow.

By forming the sheath flow as described above, particles contained in the sample solution in advance can be flowed in a line through the orifice 11 one by one. The sample liquid and the sheath liquid that have passed through the orifice 11 are discharged from a drain port 14 provided in the second cell 7b.

The electric resistance between the electrodes 12 and 13 includes the electric conductivity (electrical conductivity) of the sheath liquid, the hole size (cross-sectional area) and hole length of the orifice 11, the electric conductivity of the sample liquid, and the diameter of the flow of the sample liquid. Depends on

By passing a constant current from the DC constant current source 15 between the electrodes 12 and 13, a DC voltage determined by the electric resistance between the electrodes 12 and 13 and the current value is generated. Further, when particles pass through the orifice 11, the electric resistance at both ends of the orifice 11 changes, so that the electric resistance changes between the electrodes 12 and 13 only during the passage of the particles in a pulse-like manner. The maximum value (peak value of the pulse) is proportional to the size of the particle passing through the orifice 11. This change is amplified by the amplifier 16 and output as a resistance signal 29 (pulse analog signal).

On the other hand, the sample liquid flow 2 flowing through the orifice 11
The laser light oscillated from the laser 17 is squeezed into an ellipse by the condenser lens 18 and emitted to 6. The size of the ellipse is approximately the same as the test particle diameter in the direction of sample flow,
For example, it is about 10 μm, and is sufficiently larger than the test particle diameter in a direction orthogonal to the sample flow direction, for example, 100 to 4 μm.
It is about 00 μm.

The laser light that has passed through the flow cell 5 without colliding with the particles in the sample liquid is shielded by the beam stopper 19. The forward scattered light emitted from the particles that have received the laser beam is collected by the collector lens 20 and the light shielding plate 30
Through the pinhole 21. The scattered light is received by the photodiode 25 and output as a scattered light signal 28 (pulse analog signal).

Therefore, the analysis control unit 50 processes the resistance signal 29 and the scattered light signal 28 obtained during the driving time T of the syringe 4 in the following manner, and discriminates what is formed in the sample. .

For example, since the epithelial cells, mucus filaments, and casts contained in urine each have a morphology as shown in FIG. 3, the ratio to the length of each volume, that is, (volume) / (length) Has a relationship of epithelial cell>column> mucus thread.

On the other hand, the signal 29 output from the amplifier 16 is
When the particles pass through the pores, they have a mountain-like pulse waveform,
As is well known, the pulse height (resistance peak value) is substantially proportional to the particle volume.

The generation period (scattered light pulse width) of the scattered light signal 28 of one particle reflects the length information of the particle in the flow direction. Therefore, when the correlation between the maximum value of the signal 29 and the generation period of the scattered light signal 28 is obtained for each particle sequentially passing through the pores, the result is as shown in FIG. 4, and the analysis control unit 50 determines the correlation based on this correlation. The type of particles.
Then, the discrimination result is output to the output unit 52.

When the analysis step is completed in this way, a cleaning step is executed as described below. First, the manipulator 43 moves the chamber 36 and moves the nozzle 36a.
And the nozzle 3 are inserted into the waste liquid container 41. Next, the valves 2, 33, 34 are opened for a time T. As a result, the cleaning liquid in the container 35 is (1) the valve 33-the diaphragm pump 42-the chamber 36-the waste liquid container 40,
(2) valve 34-suction nozzle 3-waste liquid container 40,
(3) Valve 34-valve 2-sample nozzle 6-cell 5
The liquid is supplied to each flow path of the drain port 14 and is washed for a time T.

If the turbidity A detected in the turbidity detecting step is smaller than C1, the analysis control unit 50 sets T =
The cleaning time is controlled in accordance with the turbidity by setting 6 seconds and T = 10 seconds in the case of C1 or more. In this way, the washing step is completed, and preparations are made for the next analysis of the sample liquid.

[0039]

According to the present invention, the sample channel of the urine analyzer is efficiently washed in accordance with the turbidity of the sample, and the analysis accuracy is improved.

[Brief description of the drawings]

FIG. 1 is a configuration explanatory view showing a fluid system and an optical system according to an embodiment of the present invention.

FIG. 2 is a block diagram showing a control system according to the embodiment of the present invention.

FIG. 3 is a side view of epithelial cells, mucus, and casts contained in urine.

FIG. 4 is a graph showing a relationship between a scattered light pulse width and a resistance peak value in an example.

[Explanation of symbols]

 Reference Signs List 1 valve 2 valve 3 suction nozzle 4 syringe 4a motor 5 flow cell 6 sample nozzle 7a first cell 7b second cell 8 valve 9 sheath liquid container 10 supply port 11 orifice (pore) 12 electrode 13 electrode 14 drain port 15 DC constant Current power supply 16 Amplifier 17 Laser light source 18 Condenser lens 19 Beam stopper 20 Collector lens 21 Pinhole 25 Photodiode 26 Sample liquid flow 30 Shield plate 31 Valve 32 Valve 33 Valve 34 Valve 35 Cleaning liquid container 36 Chamber 36a Nozzle 37 Light emitting diode 39 Photodiode 40 Sample Liquid container 41 Waste liquid container 42 Diaphragm pump 43 Manipulator

Claims (2)

[Claims] 1. A turbidity measurement unit for measuring turbidity of a sample, a particle analysis unit for analyzing the form and number of particles in the sample, and a sample through a flow path to the turbidity measurement unit and the particle analysis unit. A sample analyzer with a washing control function, comprising: a sample supply unit for supplying the sample, a washing unit for washing a flow path through which the sample flows, and a control unit for controlling the operation of the washing unit according to the turbidity of the sample. 2. The sample analyzer with a washing control function according to claim 1, wherein the control unit further has a function of stopping the sample supply operation of the sample supply unit according to the detected turbidity.