CN116481982B

CN116481982B - Particle detection method based on Coulter particle size detector and detector

Info

Publication number: CN116481982B
Application number: CN202310425109.9A
Authority: CN
Inventors: 张国强; 熊贵; 王荣
Original assignee: Ruixin Zhizao Shenzhen Technology Co ltd
Current assignee: Ruixin Zhizao Shenzhen Technology Co ltd
Priority date: 2023-04-20
Filing date: 2023-04-20
Publication date: 2024-09-20
Anticipated expiration: 2043-04-20
Also published as: CN116481982A

Abstract

The particle detection method based on the Coulter particle size detector comprises a host machine and a detection module which is fixedly connected or detachably connected with the host machine, wherein the detection module comprises two solution tanks for containing liquid, an electrode for connecting an excitation source is arranged in each solution tank, the two solution tanks are communicated through micropores, and the micropores are used for allowing particles to be detected to pass through along with single particles of electrolyte; acquiring a parameter value of a first electrical characteristic signal applied to the electrode by an excitation source; acquiring a sampling value of a second electrical characteristic signal on the electrode; judging whether the detection environment condition is abnormal or not according to the sampling value of the second electrical characteristic signal so as to further determine the validity of the data of the final detection report or correct the detection environment condition in time to obtain valid particle detection data.

Description

Particle detection method based on Coulter particle size detector and detector

Technical Field

The invention relates to the field of particle detection, in particular to a particle detection method based on a Coulter particle size detector and the detector.

Background

Particle detection (such as particle concentration detection, particle size detection, charge data detection and the like) is a very important basic work, is widely applied to cells, bacteria, foods, additives, pesticides, graphite, photosensitive materials, fuels, ink, metal and nonmetal powders and other powdery materials, and has definite regulation on the range of each parameter of particles in industry standards such as medicines, semiconductors, coating ink, filtration and the like.

Common methods for particle concentration detection are colorimetry, fluorescence, chemiluminescence and nanoparticle tracking analysis based on the nano youcoulter principle. Colorimetry is a test of the principle that absorbance of suspended particles in solution is proportional to concentration by lambert-beer law. Fluorescence and chemiluminescence methods, both of which label target particles with specific luminescent groups and detect the concentration of target particles by luminescence intensity. The nanoparticle tracking analysis is to collect scattered light signals of an exosome through an optical microscope, observe images of brownian motion of the particles in a solution within a period of time, track and analyze each particle, and calculate the hydrodynamic size and concentration of the exosome through an Einstein equation.

Besides the particle detection method, the method also comprises a detection method based on the nano Coulter principle, as shown in figure 1, when single particles suspended in the electrolyte pass through small holes (micropores) along with the electrolyte, the same volume of electrolyte is replaced, the electric resistance between the inner electrode and the outer electrode of the small hole tube is instantaneously changed in a constant current or constant voltage designed circuit, and correspondingly, electric potential or current pulses are generated, and the size and the number of pulse signals are proportional to the size and the number of the particles, so that the particle size distribution, the number and the concentration of the particles are measured.

However, none of the above detection methods makes a judgment as to whether or not there is a problem in the detection environmental condition in the particle detection, and thus cannot make a judgment as to the accuracy of the detection data of the detection report.

Disclosure of Invention

The invention provides a particle detection method based on a Coulter particle size detector and the detector, which have the characteristic of judging the detection environment condition in particle detection.

According to a first aspect, in one embodiment, a particle detection method based on a coulter particle size detector is provided, the coulter particle size detector includes a host machine and a detection module fixedly connected or detachably connected with the host machine, the detection module includes two solution tanks for holding liquid, an electrode for connecting an excitation source is arranged in each of the two solution tanks, the two solution tanks are communicated through micropores, and the micropores are used for allowing particles to be detected to pass through along with single particles of electrolyte; the method may include the steps of,

Acquiring a parameter value of a first electrical characteristic signal applied to the electrode by an excitation source;

acquiring a sampling value of a second electrical characteristic signal on the electrode;

and judging whether the detected environmental condition is abnormal or not according to the sampling value of the second electrical characteristic signal.

According to a second aspect, a particle detection method based on a coulter particle size detector, the coulter particle size detector comprises a host and a detection module fixedly connected or detachably connected with the host, the detection module comprises two solution tanks for containing liquid, an electrode for connecting an excitation source is arranged in each of the two solution tanks, the two solution tanks are communicated through micropores, and the micropores are used for allowing particles to be detected to pass through along with single particles of electrolyte; the method comprises a particle measurement step comprising:

Applying a constant first electrical characteristic signal to the two electrodes by an excitation source;

Detecting a second electrical characteristic signal on the electrode as the particle to be detected passes through the microwell with the electrolyte;

Calculating parameters of the particles to be detected and/or carrying out statistical analysis on the particles to be detected according to the sampling value of the second electrical characteristic signal;

The method further comprises a measurement anomaly monitoring step comprising:

In a specific embodiment, the first electrical characteristic signal is a voltage signal and the second electrical characteristic signal is a current signal; or, the first electrical characteristic signal is a current signal, and the second electrical characteristic parameter is a voltage signal.

In one embodiment, the determining whether the detected environmental condition is abnormal based on the sampled value of the second electrical characteristic signal includes:

judging a particle detection stage where the current operation is located;

Acquiring a normal parameter range of a second electrical characteristic signal in the current particle detection stage;

judging whether the sampling value of the current second electrical characteristic signal exceeds a preset range, and if so, considering that the current detection environment condition is abnormal.

In one embodiment, the host includes a measurement seat, and the detection module is a detection card detachably connected with the measurement seat; the particle detection stage comprises a first detection stage before starting a particle measurement step, wherein in the first detection stage, a detection card loaded with a diluent and a sample mixed solution to be detected is loaded into a measurement seat of a Coulter particle size detector, and measurement parameters are set; when the current operation is in the first detection stage, judging whether the sampling value of the current second electrical characteristic signal exceeds a preset range, and if so, considering that the current detection environment condition is abnormal, wherein the method comprises the following steps:

judging whether the sampling value of the second electric characteristic signal is stable or not, specifically comprising: and in a preset first time interval, calculating the times that the fluctuation amplitude of the sampling value of the second electrical characteristic signal exceeds a preset first amplitude threshold value, judging whether the times exceed the first time threshold value, if not, considering that the sampling value of the second electrical characteristic signal is stable, and if so, considering that the detection card is abnormal.

In one embodiment, the host includes a measurement seat, and the detection module is a detection card detachably connected with the measurement seat; the particle detection stage comprises a first detection stage before starting detection, wherein in the first detection stage, a detection card loaded with a diluent and a sample mixed solution to be detected is arranged in a measurement seat of a Coulter particle size detector, and measurement parameters are set; when the current operation is in the first detection stage, judging whether the sampling value of the current second electrical characteristic signal exceeds a preset range, and if so, considering that the current detection environment condition is abnormal, wherein the method comprises the following steps:

Determining an offset of a sample value of the second electrical characteristic signal, comprising: judging whether the sampling value of the second electrical characteristic signal exceeds a preset first deviation range threshold value or not in a preset second time interval, if not, judging that the sampling value is normal, and if so, judging that the loading operation is abnormal.

Judging symmetry of sampling values of the second electrical characteristic signal, specifically comprising: acquiring sampling values of two second electrical characteristic signals detected under positive and negative first electrical characteristic signals respectively; judging whether a level line drawn by sampling values of the two second electric characteristic signals exceeds a symmetrical range relative to a 0-value reference line, wherein the symmetrical range is a relative symmetrical range within a preset error threshold range relative to the 0-value reference line; if the detection chip is not exceeded, the detection chip is considered to be normal, and if the detection chip is exceeded, the detection chip of the detection card is considered to be abnormal.

Judging whether the sampling value of the second electric characteristic signal is stable or not, specifically comprising: in a preset first time interval, calculating the times that the fluctuation amplitude of the sampling value of the second electric characteristic signal exceeds a preset first amplitude threshold value, judging whether the times exceed the first time threshold value, if not, considering that the sampling value of the second electric characteristic signal is stable, and if so, considering that the detection card is abnormal;

when the sampling value of the second electrical characteristic signal is stable, determining the deviation of the sampling value of the second electrical characteristic signal specifically includes: judging whether the sampling value of the second electrical characteristic signal exceeds a preset first offset range threshold value or not in a preset second time interval, if not, considering that the sampling value of the second electrical characteristic signal is normal, and if so, considering that the loading operation is abnormal;

when the sampling value of the second electrical characteristic signal is normal, judging the symmetry of the sampling value of the second electrical characteristic signal, specifically comprising: acquiring sampling values of two second electrical characteristic signals detected under positive and negative first electrical characteristic signals respectively; judging whether a level line drawn by sampling values of the two second electric characteristic signals exceeds a symmetrical range relative to a 0-value reference line, wherein the symmetrical range is a relative symmetrical range within a preset error threshold range relative to the 0-value reference line; if the detection chip is not exceeded, the detection chip is considered to be normal, and if the detection chip is exceeded, the detection chip of the detection card is considered to be abnormal.

In one embodiment, in the first detection stage, in the case that it is determined that the level line drawn by the sampling values of the two second electrical characteristic signals does not exceed the symmetry range with respect to the 0-value reference line, the particle detection method further includes:

And entering a second detection stage after the start detection, when the current operation is judged to be in the second detection stage, judging whether the sampling value of the current second electric characteristic signal exceeds a preset range, and if so, judging that the current detection environment condition is abnormal, wherein the method comprises the following steps of:

Judging whether abnormal pulse appears in the sampling curve of the second electrical characteristic signal, specifically comprising: judging whether the fluctuation amplitude of the second electrical characteristic parameter exceeds a preset second amplitude threshold value, wherein the second amplitude threshold value is a hole blocking value, and if so, considering that micropores are blocked in the test process;

When the fluctuation amplitude of the second electrical characteristic parameter does not exceed a preset second amplitude threshold, judging whether the sampling value of the current second electrical characteristic signal exceeds a preset range, and if so, judging that the current detection environmental condition is abnormal, wherein the method comprises the following steps:

Judging whether the sampling curve of the second electrical characteristic signal has abnormal deviation or not, specifically comprising: determining a noise value according to the sampling curve of the second electrical characteristic signal; judging whether the noise value exceeds a preset noise threshold value, and if so, considering that micropores are polluted in the detection process;

When the noise value does not exceed the preset noise threshold value, judging whether the sampling value of the current second electric characteristic signal exceeds the preset range, and if so, judging that the current detection environment condition is abnormal, wherein the method comprises the following steps: judging whether the pulse number on the sampling curve of the second electrical characteristic signal is abnormal or not, specifically comprising: and calculating the pulse number according to the sampling value of the second electrical characteristic signal, judging whether the pulse number is linearly increased along with time, and if not, judging that the dispersion uniformity of the sample to be detected is poor.

In one embodiment, the particle detection stage includes a second detection stage after the start of detection, when the current operation is determined to be in the second detection stage, determining whether the sampling value of the current second electrical characteristic signal is out of a preset range, and if so, considering that the current detection environmental condition is abnormal, including:

Judging whether abnormal pulse appears in the sampling curve of the second electrical characteristic signal, specifically comprising: judging whether the fluctuation amplitude of the second electrical characteristic parameter exceeds a preset second amplitude threshold value, wherein the second amplitude threshold value is a hole blocking value, and if so, considering that micropores are blocked in the testing process.

In one embodiment, the current particle detection stage includes a second detection stage after the start of detection, when the current operation is determined to be in the second detection stage, the determining whether the sampling value of the current second electrical characteristic signal is beyond a preset range, and if so, considering that the current detection environmental condition is abnormal includes:

Judging whether the sampling curve of the second electrical characteristic signal has abnormal deviation or not, specifically comprising: determining a noise value according to the sampling curve of the second electrical characteristic signal; judging whether the noise value exceeds a preset noise threshold value, and if so, considering that micropores are polluted in the testing process.

judging whether the pulse number on the sampling curve of the second electrical characteristic signal is abnormal or not, specifically comprising: and calculating the pulse number according to the sampling value of the second electrical characteristic signal, judging whether the pulse number is linearly increased along with time, and if not, judging that the dispersion uniformity of the sample to be detected is poor.

In one embodiment, the method further includes outputting corresponding abnormality prompt information according to the corresponding abnormality judgment, where the abnormality prompt information includes at least one of a voice alarm, a light alarm and a display screen prompt information alarm.

In one embodiment, the method further includes outputting a corresponding abnormality removal operation prompt based on the corresponding abnormality determination.

According to a third aspect, there is provided in one embodiment a coulter particle size detector comprising,

The detection module comprises two solution tanks for containing liquid, an electrode for connecting an excitation source is arranged in each of the two solution tanks, the two solution tanks are communicated through micropores, and the micropores are used for allowing particles to be detected to pass through along with single particles of the electrolyte;

a memory for storing programs and/or data;

a processor for implementing the method of any one of the above by executing the program stored in the memory.

According to a fourth aspect, an embodiment provides a computer readable storage medium having stored thereon a program executable by a processor to implement the method of any one of the above.

According to the particle detection method of the embodiment, due to the acquisition of the parameter value of the first electrical characteristic signal and the sampling value of the second electrical characteristic signal on the counter electrode in particle detection, whether the detection environmental condition in particle detection is abnormal or not can be judged according to the sampling value of the second electrical characteristic signal, so that the accuracy of the data of a final detection report can be further determined or the detection environmental condition can be corrected in time to obtain more accurate particle detection data.

Drawings

FIG. 1 is a schematic diagram of a detection module according to an embodiment;

FIG. 2 is a flow chart of a particle detection method according to an embodiment;

FIG. 3 is a flow chart of a particle measurement method according to an embodiment;

FIG. 4 is a flowchart illustrating an embodiment of determining whether an abnormality exists in a detected environmental condition;

FIG. 5 is a plot of sample current signal values for an embodiment under ideal conditions of a constant voltage source applied to the electrodes of the detection module during a first detection phase;

FIG. 6 is a plot of current signal samples for detecting card anomalies in a first detection stage of an embodiment;

FIG. 7 is a plot of current signal samples for abnormal loading operations in a first detection phase according to an embodiment;

FIG. 8 is a plot of sample values of two current signals for detecting the presence of an anomaly in a chip under a constant positive and negative voltage source during a first detection phase of an embodiment;

FIG. 9 is a flowchart illustrating a method for determining whether an abnormality exists in a current detected environmental condition in a first detection stage according to an embodiment;

FIG. 10 is a plot of a normal second electrical characteristic signal sample during a second detection phase of an embodiment;

FIG. 11 is a plot of sampled values of a current signal for an embodiment in which micropores are considered to be plugged during a second detection phase;

FIG. 12 is a plot of sampled values of a current signal that is indicative of microporous contamination during particle detection in a second detection phase of an embodiment;

FIG. 13 is a plot of sampled values of a current signal for which sample dispersion is considered non-uniform during a second detection phase of an embodiment;

fig. 14 is a block diagram of a coulter granularity meter according to an embodiment.

Detailed Description

The application will be described in further detail below with reference to the drawings by means of specific embodiments. Wherein like elements in different embodiments are numbered alike in association. In the following embodiments, numerous specific details are set forth in order to provide a better understanding of the present application. However, one skilled in the art will readily recognize that some of the features may be omitted, or replaced by other elements, materials, or methods in different situations. In some instances, related operations of the present application have not been shown or described in the specification in order to avoid obscuring the core portions of the present application, and may be unnecessary to persons skilled in the art from a detailed description of the related operations, which may be presented in the description and general knowledge of one skilled in the art.

Furthermore, the described features, operations, or characteristics of the description may be combined in any suitable manner in various embodiments. Also, various steps or acts in the method descriptions may be interchanged or modified in a manner apparent to those of ordinary skill in the art. Thus, the various orders in the description and drawings are for clarity of description of only certain embodiments, and are not meant to be required orders unless otherwise indicated.

The numbering of the components itself, e.g. "first", "second", etc., is used herein merely to distinguish between the described objects and does not have any sequential or technical meaning.

In order to accurately understand the technical scheme and the inventive concept of the present application, some coulter granularity detection techniques will be briefly described herein.

The detection principle of the coulter particle size detector is that when particles suspended in electrolyte pass through micropores along with the electrolyte, the electrolyte with the same volume is replaced, and the resistance between two electrodes at two sides of the micropores is instantaneously changed in a circuit designed by applying constant voltage or constant current, so that corresponding current pulses or potential pulses are generated. The size and number of pulses is proportional to the size and number of particles.

Based on the coulter particle size detector, parameter calculation and/or statistical analysis of the particles to be detected can be realized, however, researchers find that when the detection environment is abnormal, such as abnormality of the detection module, poor dispersion state of the sample, abnormal loading operation and the like, the accuracy of the data of the particle detection report can be influenced, so that how to judge the accuracy of the data of the retrieval report becomes a problem to be solved.

Researchers have also found in research that when an abnormality occurs in the detection environment, it is possible to reflect to some extent on the electrical characteristic signal sampled at the time of detection. Based on this, the following describes specific technical solutions of the present application.

The coulter particle size detector generally includes a host and a detection module that is fixedly or removably connected to the host. The host computer includes casing, application of sample portion, liquid way system, data processing portion, display portion and electrical portion. The sample adding part is used for collecting a sample and adding the sample into the detection module, and the liquid path system is used for providing diluent for the detection module and recovering waste liquid released by the detection module. The electrical section includes an excitation source for providing a constant electrical signal, such as a voltage signal or a current signal, to the detection module, and a signal processing circuit. The data processing part comprises a memory and a processor, the memory is used for storing programs and/or data, the processor is used for reading and writing the memory and executing the programs stored in the memory, the programs comprise measurement, statistics and analysis algorithms for particles, and the processor notifies execution of corresponding programs according to the received electric signals to measure, statistics and analysis for the particles.

The detection module is used for providing a place for containing the sample solution and the diluent, and micropores are arranged between the sample solution and the diluent, so that particles in the sample solution pass through the micropores under the action of pressure or electric field force, and the change of an electric signal caused when the particles pass through the micropores is detected.

Referring to fig. 1, in one embodiment, the detection module includes two solution tanks (a first solution tank 1 and a second solution tank 2 in fig. 1) for holding a liquid, one electrode (an anode electrode 3 and a cathode electrode 4 in fig. 1) is respectively disposed in each of the two solution tanks, the two electrodes are respectively connected to two output ends of an excitation source, the two solution tanks are communicated through a micropore 5, and the micropore 5 is used for allowing particles to be detected to pass through along with single particles of the electrolyte. In one embodiment, the sample addition portion adds a sample to the first solution tank 1 of the detection module, the fluid path system adds a diluent to the first solution tank 1 and the second solution tank 2, and the sample and the diluent are mixed to form a sample solution. After applying a constant voltage/current signal to the two electrodes, the particles in the sample solution pass through the microwells 5 one by one under the influence of pressure or electric field forces. The detection module outputs the current/voltage signal on the electrode to the signal processing circuit, the signal processing circuit can amplify and/or filter the current/voltage signal, perform A/D conversion and other processes, and the processed signal is operated by the processor to obtain the detection result of the target particles.

For the detection module, in one embodiment, the detection module is fixedly connected to the host of the coulter particle size detector. In one embodiment, the detection module is removably coupled to a host computer of the coulter particle size detector.

When the detection module is detachably connected to the host, in one embodiment, the detection module is a detection card, and the coulter particle size detector includes a measurement seat, and the detection card is detachably connected to the measurement seat.

In one embodiment, the detection card comprises a detection chip which is fixedly or detachably connected, and micropores for communicating the two solution tanks are arranged on the detection chip. When the detection chip is detachably connected, a detection chip card slot is arranged between the communication areas of the two solution tanks of the detection card, the detection chip is detachably connected with the detection chip card slot, and the specific structure can be seen in the patent application with the publication number of CN216208448U, and the whole content of the patent application is incorporated into the application and is not repeated here.

In the embodiment of the present application, the particle detection method includes a particle measurement step and a measurement anomaly monitoring step, referring to fig. 2, the measurement anomaly monitoring step includes:

in step S01, a parameter value of a first electrical characteristic signal applied to the electrode by the excitation source is obtained.

If the excitation source is a constant voltage source, the voltage value of the voltage source is obtained, and if the excitation source is a constant current source, the current value of the current source is obtained.

Step S02, a sampling value of the second electrical characteristic signal on the electrode is obtained.

In one embodiment, the first electrical characteristic signal is a voltage signal, i.e. a constant voltage source is applied to the electrode, the second electrical characteristic signal is a current signal, and the current value under the constant voltage signal is collected as a sampling value.

In one embodiment, the first electrical characteristic signal is a current signal, i.e. a constant current source is applied to the electrode, the second electrical characteristic signal is a voltage signal, and the voltage value under the constant current signal is collected as a sampling value.

Step S03, judging whether the detected environmental condition is abnormal or not according to the sampling value of the second electrical characteristic signal.

Under normal detection environmental conditions, the sampling value of the second electrical characteristic signal and its variation under the excitation source generally follow a normal range, and when the sampling value of the second electrical characteristic signal and/or its variation exceeds the normal range, an abnormality of the detection environmental condition may exist. Therefore, the parameter value of the first electrical characteristic signal and the sampling value of the second electrical characteristic signal on the counter electrode in particle detection can be obtained, so that whether the detection environment condition in particle detection is abnormal or not can be judged according to the sampling value of the second electrical characteristic signal, and the validity of the data of a final detection report can be further determined or the detection environment condition can be corrected in time to obtain valid particle detection data.

Referring to fig. 3, in one embodiment, the particle measurement step of the particle detection method includes,

Step S11, applying a constant first electrical characteristic signal to the two electrodes through the excitation source.

Step S12, detecting a second electrical characteristic signal on the electrode when the particles to be detected pass through the micropores with the electrolyte.

And step S13, calculating parameters of the particles to be detected and/or carrying out statistical analysis on the particles to be detected according to the sampling value of the second electrical characteristic signal, wherein the parameters comprise one or more of the number of the particles, the concentration of the particles, the particle size value of the particles, the charge data of the particles and the like.

The measurement abnormality monitoring step may be started before the particle measurement step, or may be performed simultaneously with the particle measurement step.

The following description will be made mainly by taking an example of applying a constant voltage to an electrode, sampling a current signal, and judging whether or not abnormality exists in a detection environment condition based on the sampled value of the current signal.

The size of the excitation source for particle detection is determined by the size of the micro-pores. In the embodiment shown in fig. 3, the excitation source used in the particle detection and the excitation source used in the particle measurement step are the same excitation source. In other embodiments, a different excitation source is also possible.

In one embodiment, referring to fig. 4, determining whether an abnormality exists in the detected environmental condition according to the sampled value of the second electrical characteristic signal includes:

Step S031, judging the particle detection stage in which the current operation is performed.

In one embodiment of the application, the particle detection phase comprises a first detection phase before the particle measurement is initiated and a second detection phase after the particle measurement is initiated.

Step S032, obtaining the normal parameter range of the second electrical characteristic signal in the current particle detection stage.

Taking the example of applying a constant voltage, the normal parameter range of the sampling current signal in the present particle detection phase is obtained. If a constant current source is applied, the normal parameter range of the sampled voltage signal in the current particle detection phase is obtained. The normal parameter range is determined by the micropore size of the detection module and the electrical characteristic parameters (such as resistivity) of the detection particles in the current experiment.

Step S033, judging whether the sampling value of the current second electrical characteristic signal exceeds a preset range, and if so, considering that the current detection environmental condition is abnormal.

Researchers find that a certain normal parameter range exists in electrical characteristic signal sampling values sampled by normal particle detection environments in different particle detection stages, and when the electrical characteristic signal sampling values exceed the normal parameter range, the possibility that the current detection environment conditions are abnormal is high.

The abnormality determination in the first detection stage will be described below.

In one embodiment, a test card loaded with a mixture of diluent and sample to be tested is loaded into the measurement station of the coulter analyzer and the measurement parameters are set. The parameter setting can be performed by setting the parameter related to the current experiment through an input box of software, and the information of the detection card, such as the size of the micro-hole, is obtained by scanning the information code (two-dimensional code or one-dimensional code) on the detection card. In the first detection stage before starting the particle measurement step, referring to fig. 5, in the case of applying a constant voltage source, the sampled normal current signal is ideally the sampled current value I corresponding to the vertical axis is unchanged with the increase of the time T of the horizontal axis, and in the actual particle detection, a relatively stable range exists in the sampled value, and a preset range is set according to the relatively stable range as a basis for judging whether the sampled value is stable, so as to judge whether the sampled current value is stable.

Researchers found that in the first detection stage, if the sampled value of the sampled second electrical characteristic signal always fluctuates greatly, the detection module may have problems, such as poor electrode contact, pollution of the inner wall of the solution tank affecting the flow of the electrolyte through hole, quality problems of the electrode itself, and the like.

In one embodiment of the present application, the method for determining whether an abnormality exists in a current detected environmental condition includes determining whether a sampled current value is stable, including: and in a preset first time interval, calculating the times that the fluctuation amplitude of the sampling value of the second electrical characteristic signal exceeds a preset first amplitude threshold value, judging whether the times exceed the first time threshold value, if not, considering that the sampling value of the second electrical characteristic signal is stable, and if so, considering that the detection card is abnormal. The preset first time interval, the first amplitude threshold and the first time number threshold are determined by the stability requirement of the sampled current value, and specifically, the micropore size of the detection module and the electrical characteristic parameters (such as resistivity) of the detection particles in the current experiment. In one embodiment, referring to fig. 6, the absolute value of the first amplitude threshold is i1, and the total number of times that the amplitude of the upward fluctuation and the amplitude of the downward fluctuation of the sampled value of the collected current signal exceed i1 are calculated in any preset first time interval, if the total number of times exceeds the preset first number of times threshold, the sampled value of the current signal is considered to be greatly fluctuated all the time, and the detection card may have abnormality, such as poor contact of the electrode, pollution of the inner wall of the solution tank affects the flow of the electrolyte through hole, quality problems of the electrode itself, and the like.

Researchers have found that during the first detection phase, if the sampled value of the sampled second electrical characteristic signal deviates from a normal range, this may indicate that the loading operation may be problematic, such as bubbles in the electrolyte, uneven sample dispersion, etc.

In one embodiment, the method for judging whether the current detection environment condition is abnormal comprises judging the deviation of the sampling value of the current signal, and specifically comprises the following steps: judging whether the sampling value of the second electrical characteristic signal exceeds a preset first deviation range threshold value or not in a preset second time interval, if not, judging that the sampling value is normal, and if so, judging that the loading operation is abnormal. The preset second time interval and the first deviation range threshold are determined by the deviation allowable range of the sampled current value, specifically, the micropore size of the detection module and the electrical characteristic parameters (such as resistivity) of the detection particles in the current experiment. In one embodiment, referring to fig. 7, in fig. 7, i2 to i3 are preset first offset range thresholds, and if the sampling value of the current signal exceeds the preset first offset range threshold, the loading operation is considered to be abnormal.

Researchers found that in the first detection stage, under the condition of positive and negative excitation sources, if the sampled values of the two sampled second electrical characteristic signals are not symmetrical, the detection chip may have problems, such as mismatching of the size of the micropores with detection particles, blockage of foreign matters, and the like.

In one embodiment, the method for determining whether the current detected environmental condition is abnormal includes determining symmetry of a sampling value of the second electrical characteristic signal, and specifically includes: acquiring sampling values of two second electrical characteristic signals detected under positive and negative first electrical characteristic signals respectively; judging whether a level line drawn by sampling values of the two second electrical characteristic signals exceeds a symmetrical range relative to a 0-value reference line, wherein the symmetrical range is a relative symmetrical range within a preset error threshold range relative to the 0-value reference line, and specifically, the level line is determined by the micropore size of a detection module of the current experiment and the electrical characteristic parameters (such as resistivity) of detection particles; if the detection chip is not exceeded, the detection chip is considered to be normal, and if the detection chip is exceeded, the detection chip of the detection card is considered to be abnormal.

Taking the first electric characteristic signal as a voltage signal, taking the voltage value of 200mV as an example, acquiring a first sampling value level line of a current signal under +200mV voltage, acquiring a second sampling value level line of the current signal under-200 mV voltage, and judging whether two sampling value curves acquired under positive and negative voltage signals are symmetrical relative to a 0 value reference line. In one embodiment, a relative symmetric range within a preset error threshold range is determined, whether two sampling value curves obtained under positive and negative voltage signals are within the relative symmetric range is determined, if yes, the detection chip of the detection card is considered to be normal, and if exceeding, the detection chip of the detection card is considered to be abnormal. The 0 value line may be a direct 0 value line, a relative reference line, or a 0 value line obtained by integrally adjusting the sampling value.

Referring to fig. 8, the current sampling value level line above the 0-line is the first sampling value level line obtained at +200mV voltage, the current sampling value level line below the 0-line is the second sampling value level line obtained at-200 mV voltage, the preset error threshold range is i4 to i5, and the second sampling value level line exceeds the relative symmetry range of the preset error threshold range, so that at this time, it is considered that the detecting chip of the detecting card has an abnormality, such as the detecting chip has no pairs of micropore sizes, the detecting chip micropores have foreign matter blockage, and the like. The preset error threshold range is determined by the requirement of the relative symmetry of the sampled current value, and specifically, the micropore size of the detection module and the electrical characteristic parameters (such as resistivity) of the detection particles in the current experiment.

In one embodiment, referring to fig. 9, in a first detection stage, a method for determining that an abnormality exists in a current detection environment condition includes:

Step S041, judging whether the sampling value of the second electrical characteristic signal is stable or not, specifically comprising: and in a preset first time interval, calculating the times that the fluctuation amplitude of the sampling value of the second electrical characteristic signal exceeds a preset first amplitude threshold value, judging whether the times exceed the first time threshold value, if not, considering that the sampling value of the second electrical characteristic signal is stable, and if so, considering that the detection card is abnormal. The preset first time interval and the first time threshold are determined by the stability requirement of the sampling value of the second electrical characteristic signal, and specifically, the micropore size of the detection module and the electrical characteristic parameter (such as resistivity) of the detection particle in the current experiment.

Step S042, when the sampling value of the second electrical characteristic signal is stable, of determining the offset of the sampling value of the second electrical characteristic signal, specifically includes: judging whether the sampling value of the second electrical characteristic signal exceeds a preset first deviation range threshold value or not in a preset second time interval, if not, considering that the sampling value of the second electrical characteristic signal is normal, and if so, considering that the loading operation is abnormal. The preset second time interval and the first deviation range threshold are determined by the normal deviation requirement of the sampling value of the second electrical characteristic signal, specifically, the micropore size of the detection module and the electrical characteristic parameter (such as resistivity) of the detection particle in the current experiment.

Step S043, when the sampling value of the second electrical characteristic signal is normal, determining symmetry of the sampling value of the second electrical characteristic signal specifically includes: acquiring sampling values of two second electrical characteristic signals detected under positive and negative first electrical characteristic signals respectively; judging whether a level line drawn by sampling values of the two second electric characteristic signals exceeds a symmetrical range relative to a 0-value reference line, wherein the symmetrical range is a relative symmetrical range within a preset error threshold range relative to the 0-value reference line; if the detection chip is not exceeded, the detection chip is considered to be normal, and if the detection chip is exceeded, the detection chip of the detection card is considered to be abnormal. The preset error threshold range is determined by the relative symmetrical requirement of the two second electrical characteristic signals under the positive and negative first electrical characteristic signals, and specifically, the micropore size of the detection module and the electrical characteristic parameters (such as resistivity) of the detection particles in the current experiment.

The abnormality determination in the second detection stage will be described below.

Referring to fig. 10, a sampling curve of a normal second electrical characteristic signal in a second detection phase according to an embodiment of the present application is shown, wherein the pulse is a pulse in which particles are detected.

And when the current operation is in the second detection stage, judging whether the sampling value of the current second electric characteristic signal exceeds a preset range, and if so, considering that the current detection environment condition is abnormal.

In one embodiment, in the second detection stage, determining whether an abnormality exists in the current detection environment includes determining whether an abnormal pulse occurs in a sampling curve of the second electrical characteristic signal, and specifically includes: judging whether the fluctuation amplitude of the second electrical characteristic parameter exceeds a preset second amplitude threshold, wherein the second amplitude threshold is a hole blocking value, and if so, considering that the micropores are blocked in the test process.

Researchers have found that in the second detection phase, when the detected particle cannot pass through the microwell due to the microwell being blocked, the fluctuation amplitude of the pulse of the sampled second electrical characteristic signal is relatively large, and therefore, if the amplitude of the fluctuation pulse of the second electrical characteristic signal exceeds a certain normal amplitude value, the microwell is highly likely to be blocked. Referring to fig. 11, a second amplitude threshold is preset according to the normal range of the pulse amplitude of the current signal, and it is determined whether the amplitude of the fluctuation pulse of the sampled current signal exceeds the preset second amplitude threshold, in fig. 11, after a period of normal testing, the amplitudes of the fluctuation pulses exceed the second amplitude threshold, and then the phenomenon that micropores are blocked occurs in the testing process of the second detection stage is considered. Since the sizes of the micropores of different detection chips may be different, the values of the applied excitation sources may also be different, so that the blockage Kong Shuzhi which may be abnormal is set as a second amplitude threshold according to the normal amplitude requirement of the fluctuation pulse of the second electrical characteristic parameter under the first electrical characteristic signal of the micropores with different sizes; specifically, the size of the micropores of the detection module in the current experiment and the electrical characteristic parameters (such as resistivity) of the detection particles are determined.

In one embodiment, in the second detection stage, determining whether an abnormality exists in the current detection environment includes determining whether an abnormal shift occurs in a sampling curve of the second electrical characteristic signal, and specifically includes: determining a noise value according to the sampling curve of the second electrical characteristic signal; judging whether the noise value exceeds a preset noise threshold value, and if so, considering that micropores are polluted in the detection process.

Referring to fig. 12, in the second detection stage, researchers find that, when micropores are contaminated due to adhesion of some impurities but not blocked, a specific noise value obtained by the discrete degree and standard deviation of the sampling curve data of the second electrical characteristic signal exceeds a normal noise threshold value, so that we can obtain a specific noise value according to the discrete degree and standard deviation of the sampling curve data of the second electrical characteristic signal, preset a normal noise threshold value as the noise threshold value, determine whether micropores are contaminated by judging whether the noise value exceeds the preset noise threshold value, and if yes, consider that micropores are contaminated in the particle detection process. Since the sizes of the micropores of different detection chips may be different, the values of the applied excitation sources may also be different, and therefore, the noise threshold value which may be abnormal needs to be set according to the normal noise value requirement of the second electrical characteristic parameters of the micropores with different sizes under the first electrical characteristic signals; specifically, the size of the micropores of the detection module in the current experiment and the electrical characteristic parameters (such as resistivity) of the detection particles are determined.

In one embodiment, in the second detection stage, determining whether the current detection environment has an abnormality includes determining whether the number of pulses on the sampling curve of the second electrical characteristic signal is abnormal, including: and calculating the pulse number according to the sampling value of the second electrical characteristic signal, judging whether the pulse number is linearly increased along with time, and if not, judging that the dispersion uniformity of the sample to be detected is poor. Specifically, referring to fig. 13, in one embodiment, in any two adjacent time period thresholds, there is no fluctuation of the fluctuation amplitude of the second electrical characteristic signal within the preset third fluctuation amplitude range threshold. The third fluctuation range threshold can be determined by detecting the general fluctuation range of the particles passing through the micropores, and thus, the third fluctuation range threshold is determined by the size of the micropores, the second electrical characteristic signal down-sampled by the first electrical characteristic signal, and the electrical characteristic parameter (such as resistivity) and dilution degree of the particles to be detected.

In one embodiment, step S043 further comprises:

Step S044, entering a second detection stage after starting detection, when judging that the current operation is in the second detection stage, judging whether the sampling value of the current second electric characteristic signal exceeds a preset range, if so, judging that the current detection environmental condition is abnormal, and comprising the following steps:

step S045, when the fluctuation range of the second electrical characteristic parameter does not exceed the preset second amplitude threshold, determining whether the sampling value of the current second electrical characteristic signal exceeds the preset range, if so, determining that the current detection environmental condition is abnormal, including:

Step S045, when the noise value does not exceed the preset noise threshold value, determining whether the sampling value of the current second electrical characteristic signal exceeds the preset range, if so, determining that the current detection environmental condition is abnormal, including: judging whether the pulse number on the sampling curve of the second electrical characteristic signal is abnormal or not, specifically comprising: and calculating the pulse number according to the sampling value of the second electrical characteristic signal, judging whether the pulse number is linearly increased along with time, and if not, judging that the dispersion uniformity of the sample to be detected is poor.

It should be noted that, the above embodiments are described by taking the case of applying a constant voltage source and sampling a current signal as an example, and those skilled in the art can adaptively change the case of applying a constant current source and sampling a voltage signal according to the above description, without affecting the protection scope of the present application.

In one embodiment, the corresponding abnormality prompt information is output according to the corresponding abnormality judgment, and the abnormality prompt information comprises at least one of a voice alarm, a light alarm and a display screen prompt information alarm. The voice alarm may only prompt the existence of an abnormality, or may prompt the type of abnormality. For the lamplight alarm, only one lamplight can be used for prompting the existence of an abnormality, and the lamplight alarm can also be used for prompting the existence of the abnormal type by combining a plurality of lamplights. The display screen prompts information, which can prompt the existence of abnormality only or prompt the type of abnormality. The combined abnormality prompt can also be performed, for example, the lamplight alarm has abnormality, the display screen prompts the type of information prompt abnormality, or other combined abnormality prompts.

In one embodiment, the particle detection method further includes outputting a corresponding abnormality removal operation prompt according to the corresponding abnormality determination. If the abnormality judges that the micropores are polluted, the cleaning condition of the micropores can be prompted to be checked and/or the micropores can be cleaned; when the abnormality is judged that the detecting chip is abnormal, the detecting chip for detecting whether the size of the micro-hole meets the requirement or not, whether the micro-hole is blocked by foreign matters or not, and/or replacing the detecting chip with the correct micro-hole size or the like can be prompted.

In one embodiment, the present application provides a coulter particle size detector, see fig. 14, comprising,

The detection module 10 comprises two solution tanks for containing liquid, wherein an electrode for connecting an excitation source is arranged in each solution tank, the two solution tanks are communicated through micropores, and the micropores are used for allowing particles to be detected to pass through along with single particles of the electrolyte.

Memory 20 for storing programs and/or data.

A processor 30 for implementing the particle detection method of any one of the above embodiments by executing a program stored in the memory.

In one embodiment, the present application provides a computer readable storage medium having stored thereon a program executable by a processor to implement any of the particle detection methods described above.

Those skilled in the art will appreciate that all or part of the functions of the various methods in the above embodiments may be implemented by hardware, or may be implemented by a computer program. When all or part of the functions in the above embodiments are implemented by means of a computer program, the program may be stored in a computer readable storage medium, and the storage medium may include: read-only memory, random access memory, magnetic disk, optical disk, hard disk, etc., and the program is executed by a computer to realize the above-mentioned functions. For example, the program is stored in the memory of the device, and when the program in the memory is executed by the processor, all or part of the functions described above can be realized. In addition, when all or part of the functions in the above embodiments are implemented by means of a computer program, the program may be stored in a storage medium such as a server, another computer, a magnetic disk, an optical disk, a flash disk, or a removable hard disk, and the program in the above embodiments may be implemented by downloading or copying the program into a memory of a local device or updating a version of a system of the local device, and when the program in the memory is executed by a processor.

The foregoing description of the invention has been presented for purposes of illustration and description, and is not intended to be limiting. Several simple deductions, modifications or substitutions may also be made by a person skilled in the art to which the invention pertains, based on the idea of the invention.

Claims

1. The particle detection method based on the Coulter particle size detector comprises a host machine and a detection module detachably connected with the host machine, wherein the detection module comprises two solution tanks for containing liquid, an electrode for connecting an excitation source is arranged in each of the two solution tanks, the two solution tanks are communicated through micropores, and the micropores are used for allowing particles to be detected to pass through along with single particles of electrolyte; characterized in that the method comprises the steps of,

judging whether the detected environmental condition is abnormal or not according to the sampling value of the second electrical characteristic signal;

The judging whether the detected environmental condition is abnormal or not according to the sampling value of the second electric characteristic signal comprises the following steps:

judging a particle detection stage where the current operation is located;

Judging whether the sampling value of the current second electrical characteristic signal exceeds a preset range, and if so, considering that the current detection environment condition is abnormal;

The host comprises a measuring seat, and the detection module is a detection card detachably connected with the measuring seat; the particle detection stage comprises a first detection stage before starting a particle measurement step, wherein in the first detection stage, a detection card loaded with a diluent and a sample mixed solution to be detected is loaded into a measurement seat of a Coulter particle size detector, and measurement parameters are set; when the current operation is in the first detection stage, judging whether the sampling value of the current second electrical characteristic signal exceeds a preset range, and if so, considering that the current detection environment condition is abnormal, wherein the method comprises the following steps:

judging whether the sampling value of the second electric characteristic signal is stable or not, specifically comprising: in a preset first time interval, calculating the times that the fluctuation amplitude of the sampling value of the second electric characteristic signal exceeds a preset first amplitude threshold value, judging whether the times exceed the first time threshold value, if not, considering that the sampling value of the second electric characteristic signal is stable, and if so, considering that the detection card is abnormal; and/or

Judging whether the sampling value of the current second electrical characteristic signal exceeds a preset range, if so, considering that the current detection environment condition is abnormal, and comprising the following steps: determining an offset of a sample value of the second electrical characteristic signal, comprising: judging whether the sampling value of the second electrical characteristic signal exceeds a preset first deviation range threshold value or not in a preset second time interval, if not, judging that the sampling value is normal, and if so, judging that the loading operation is abnormal; and/or

Judging whether the sampling value of the current second electrical characteristic signal exceeds a preset range, if so, considering that the current detection environment condition is abnormal, and comprising the following steps:

2. The particle detection method based on the Coulter particle size detector comprises a host machine and a detection module detachably connected with the host machine, wherein the detection module comprises two solution tanks for containing liquid, an electrode for connecting an excitation source is arranged in each of the two solution tanks, the two solution tanks are communicated through micropores, and the micropores are used for allowing particles to be detected to pass through along with single particles of electrolyte; the method comprises a particle measurement step comprising:

detecting a second electrical characteristic signal on the electrode as particles to be detected pass through the microwells with an electrolyte;

The method is characterized by further comprising a measurement anomaly monitoring step, wherein the measurement anomaly monitoring step comprises the following steps:

judging a particle detection stage where the current operation is located;

3. The particle detection method of claim 1 or 2, wherein the first electrical characteristic signal is a voltage signal and the second electrical characteristic signal is a current signal; or, the first electrical characteristic signal is a current signal and the second electrical characteristic signal is a voltage signal.

4. The particle detection method of claim 1 or 2, wherein the host computer comprises a measurement seat, and the detection module is a detection card detachably connected with the measurement seat; the particle detection stage comprises a first detection stage before starting detection, wherein in the first detection stage, a detection card loaded with a diluent and a sample mixed solution to be detected is arranged in a measurement seat of a Coulter particle size detector, and measurement parameters are set; when the current operation is in the first detection stage, judging whether the sampling value of the current second electrical characteristic signal exceeds a preset range, and if so, considering that the current detection environment condition is abnormal, wherein the method comprises the following steps:

5. The particle detection method of claim 1 or 2, wherein the particle detection phase includes a second detection phase after the start of detection, and when the current operation is determined to be in the second detection phase, determining whether the sampling value of the current second electrical characteristic signal is out of a preset range, and if so, determining that the current detection environmental condition is abnormal includes:

judging whether abnormal pulse appears in the sampling curve of the second electrical characteristic signal, specifically comprising: judging whether the fluctuation amplitude of the second electrical characteristic parameter exceeds a preset second amplitude threshold value, wherein the second amplitude threshold value is a hole blocking value, and if so, considering that micropores are blocked in the test process; and/or

Judging whether the sampling curve of the second electrical characteristic signal has abnormal deviation or not, specifically comprising: determining a noise value according to the sampling curve of the second electrical characteristic signal; judging whether the noise value exceeds a preset noise threshold value, and if so, considering that micropores are polluted in the detection process; and/or

Judging whether the sampling value of the current second electrical characteristic signal exceeds a preset range, if so, considering that the current detection environment condition is abnormal, and comprising the following steps: judging whether the pulse number on the sampling curve of the second electrical characteristic signal is abnormal or not, specifically comprising: and calculating the pulse number according to the sampling value of the second electrical characteristic signal, judging whether the pulse number is linearly increased along with time, and if not, judging that the dispersion uniformity of the sample to be detected is poor.

6. The particle detection method according to claim 4, wherein in the first detection stage, in the case where it is judged that the level line drawn by the sampling values of the two second electric characteristic signals does not exceed the symmetry range with respect to the 0-value reference line, the particle detection method further comprises:

7. The particle detection method of claim 1 or 2, further comprising outputting a corresponding abnormality alert message based on the corresponding abnormality determination, the abnormality alert message including at least one of a voice alert, a light alert, and a display alert message alert.

8. The particle detection method according to claim 1 or 2, further comprising outputting a corresponding abnormality removal operation prompt in accordance with the corresponding abnormality determination.

9. A Coulter particle size detector is characterized by comprising,

a memory for storing programs and/or data;

a processor for implementing the method of any one of claims 1 to 8 by executing a program stored in said memory.

10. A computer readable storage medium, characterized in that the medium has stored thereon a program executable by a processor to implement the method of any of claims 1-8.