JP4409530B2 - Particle measuring device - Google Patents

Description

  The present invention relates to a particle measuring apparatus, and more particularly to an apparatus for analyzing particles by nonlinearly converting a signal representing the characteristics of particles.

This type of conventional particle measuring apparatus includes a detection unit that converts particle characteristics into an analog particle signal, and an analog converter that performs nonlinear conversion, for example, logarithmic conversion, on the obtained analog particle signal. It is known that statistical processing is performed after conversion.
JP-A-62-112035

  However, the conventional particle measuring apparatus includes an analog non-linear converter, so that the circuit configuration of the apparatus becomes complicated, and the analog non-linear converter generally has a characteristic that the characteristic fluctuates sensitively to the ambient temperature, and an offset. There was a problem that calibration was not easy because of the large variation in quantity.

  The present invention has been made in consideration of such circumstances, and by performing nonlinear conversion processing after digitizing an analog particle signal, the particle configuration is simple and can be measured with high reproducibility. A measuring device is provided.

In view of the above problems, a particle measuring apparatus according to the present invention converts a particle characteristic into an analog particle signal and detects the particle signal, and converts the analog particle signal detected by the particle signal detection unit into a digital signal. An A / D conversion unit that converts and outputs, a storage unit that stores the digital particle signal x output from the A / D conversion unit, and a non-linear function y = f for the digital particle signal x stored in the storage unit A non-linear conversion unit that converts using (x), a calculation unit that calculates a particle characteristic parameter from the conversion value y generated by the non-linear conversion unit, an output unit that outputs a calculation result in the calculation unit, have a, the linear conversion unit, the digital particle signal x obtained from the storage unit multiplied by m (an integer), randomly obtained by adding any further from 0 (m-1) to the integer X And, to obtain a conversion value using a nonlinear function y = f (X / m) , characterized in that.

According to the present invention, it is possible to perform non-linear conversion of particle signals without using an analog non-linear converter, so that not only the circuit configuration becomes simple, but also the temperature change and input / output characteristics of the conversion characteristics of the analog non-linear converter It is possible to obtain particle data that is not affected by the variation of the particle size. In addition, if a frequency distribution diagram or a scattergram is created based on particle data subjected to nonlinear conversion, the distribution state can be easily grasped.

  The particles to be measured of the present invention include toner, graphite, silica, abrasive, ceramic powder, pigment, powder coating, cultured cells, yeast, plankton, magnetic powder, etc. The particle size ranges from submicron to several hundred microns.

  In the present invention, the particle signal detection unit that detects the characteristics of each particle for a plurality of particles and converts them into a particle signal, for example, allows a particle-containing liquid to flow through the sheath flow cell to detect optical information from the particles. Use an optical flow cytometer type detector or an electric resistance type detector that detects the change in the electrical impedance of the particle-containing liquid on both sides of the orifice by flowing the particle-containing liquid through the orifice (micropore). be able to.

  A commercially available high-speed A / D converter can be used for the A / D converter of the present invention. Further, the nonlinear conversion unit and the calculation unit can be integrally configured by a microcomputer or a personal computer. A CRT, a liquid crystal display panel, a printer, or the like can be used for the output unit.

  The reference table in the present invention includes a value X obtained by sequentially adding an integer from 0 to (m-1) to a value mx obtained by multiplying the particle signal x by m (integer), and a nonlinear function y = f (X / m). And a table (look-up table) that represents the value y calculated using and the nonlinear conversion unit multiplies the particle signal value x output from the A / D conversion unit by m, The table may be used by setting X as a value obtained by randomly adding any integer from 0 to (m−1). In the present invention, the non-linear function m is preferably set so that the maximum rate of change of y with respect to X is 1 or less. In the present invention, the nonlinear function may be a logarithmic function.

  Hereinafter, the present invention will be described in detail based on embodiments shown in the drawings. This does not limit the invention. FIG. 1 shows a block diagram of a flow cytometer according to an embodiment of the present invention. In the optical system 100, a suspension containing blood cells and cells is guided to the sheath flow cell 1, and laser light is irradiated from the laser light source 2 through the condenser lens 5 to the suspension flow narrowed by the sheath liquid flow.

  In this embodiment, the forward scattered light and the side fluorescence of each particle traversing the laser light irradiation area are captured through the condenser lenses 6 and 7, respectively, and the photodiode 3 and the photomultiplier tube 4 are respectively Photoelectric conversion. The respective particle signals obtained from the photodiode 3 and the photo multitube 4 are subjected to waveform processing by the signal processing system 200. In the signal processing system 200, the height, area, width, particle size, particle volume, and the like of each particle signal waveform corresponding to each particle are calculated as characteristic parameters.

  The signal processing system 200 samples A / D converters 8a and 8b for digitally converting analog particle signals output from the photodiode 3 and the photomultiplier tube 4, respectively, and samples each of the digitally converted particle signals to obtain a peak value thereof. And waveform processing units 9a and 9b for calculating particle data representing the pulse width, and 10a and 10b for storing the calculated particle data.

  A commercially available high-speed A / D converter is used for the A / D converters 8a and 8b, and the waveform processing units 9a and 9b are constituted by a known FPGA (Field Programmable Gate Array), and storage units 10a and 10b. RAM is used for.

  The signal processing system 200 further includes a CPU 11, a non-linear conversion unit 12 that converts particle data x using a non-linear function y = f (x), a calculation unit 13 that calculates particle characteristic parameters from the converted value y, and a calculation. The output part 14 which outputs a result is provided.

  The non-linear conversion unit 12 includes a storage unit 12a that stores in advance a reference table (lookup table) representing a value calculated from y = f (x) over a predetermined change region of x, and uses the reference table to perform non-linear conversion I do.

  The CPU 11, the non-linear conversion unit 12 and the calculation unit 13 can be integrally configured by a microcomputer or a personal computer, and the output unit 14 is configured by a CRT and a printer. It is also possible to provide the nonlinear conversion unit 12 in the waveform processing units 9a and 9b.

  Next, the operation of the signal processing system 200 having such a configuration will be described. When a sample liquid containing particles (cells, blood cells, etc.) to be measured is supplied to the sheath flow cell 1 and the laser light source 2 irradiates the sheath flow cell 1, the analog particle signals obtained from the photodiode 3 and the photomultiplier tube 4 respectively are It is converted into a digital particle signal by the A / D converters 8a and 8b.

  The waveform processing units 9a and 9b calculate particle data representing a peak value and a pulse width from the digital particle signal, respectively, and the calculated particle data is temporarily stored in the storage units 10a and 10b, respectively. When the particle measurement in the optical system 100 is completed, the particle data is read from the storage units 10a and 10b and nonlinearly converted by the nonlinear converter 12.

  The non-linearly converted particle data and the particle data directly read from the storage units 10a and 10b are converted into particle characteristic parameters such as particle size and particle volume by the calculation unit 13 and output as particle size distribution diagrams and scattergrams. Output from the unit 14.

Here, the operation of the nonlinear converter 12 will be described in further detail. The nonlinear conversion unit 12 converts the particle data x using the nonlinear function y = f (x). Specifically, the reference table (lookup table) stored in advance in the storage unit 12a, that is, a predetermined change in x. Conversion is performed using a reference table representing values calculated in advance from the function y = f (x) over the region. In this embodiment, the nonlinear function is a logarithmic function.
y = f (x) = a ・ Log (x + c) + b …… (1)
This will be described as an example.

  Now, when the particle data x is logarithmically converted with the function expressed by the equation (1), the reference table becomes, for example, as shown in Table 1, and when it is graphed, it becomes as shown in FIG. That is, in this case, there is no corresponding x value in 11 ≦ y ≦ 16, 18 ≦ y ≦ 22, and the like. This is because the maximum rate of change (slope) of the function with respect to x in this region is greater than 1. When feature parameters are calculated based on such converted values and are displayed as frequency distribution diagrams or scattergrams, partial stripes appear as shown in FIGS. 5 and 6, respectively, and the distribution state is correctly recognized from the diagrams. It becomes difficult.

Therefore, in the present invention, the calculation is performed using a value X obtained by sequentially adding an integer from 0 to (m-1) to a value mx obtained by multiplying the particle signal x by m (integer), and y = f (X / m). A reference table representing y in correspondence is created as shown in Table 2 and stored in advance in the storage unit 12a. In this embodiment, m = 2 ³ = 8. Although the output y is an integer in the reference table of this embodiment, it can be a real number depending on the purpose.

  When the reference table of Table 2 is graphed, the result is as shown in FIG. This is because m = 8 is determined so that the maximum change rate (slope) of the function with respect to X is 1 or less.

  Next, the particle data stored in the storage unit 10a or 10b is processed in the procedure shown in the flowchart of FIG. First, the total particle data number (total particle number) N is counted, and the particle data number i is initialized to 0 (step S1).

  Next, the i-th data D (i) is read (step S2), D (i) is multiplied by m (step S3), and then a random number β from 0 to (m−1) is added ( In step S4), the corresponding value y (i) is detected by referring to the value in the reference table (Table 2) (step S6). This operation is repeated for N particle data (steps S2 to S8). Thereby, the logarithmic conversion process of N particle data is completed.

  Since there is no missing portion in the value of y obtained in this way, even if a frequency distribution diagram or a scattergram is created based on logarithmically converted particle data, a striped pattern as shown in FIGS. Since it is not seen, it becomes easy to grasp the distribution state.

  The embodiment of the present invention is not limited to the above, and various modifications can be made as appropriate within the scope of the technical idea shown in the claims.

It is a block diagram which shows the Example of this invention. It is a graph explaining the comparative example of a reference table. It is a graph explaining the Example of a reference table. It is a flowchart which shows operation | movement of the principal part of an Example. It is a figure which shows the comparative example of a particle size distribution figure. It is a figure which shows the comparative example of a scattergram.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 Sheath flow cell 2 Laser light source 3 Photodiode 4 Photomultiplier tube 5 Condenser lens 6 Condensing lens 7 Condensing lens 8a A / D converter 8b A / D converter 9a Waveform processing part 9b Waveform processing part 10a Storage part 10b Storage part 11 CPU
DESCRIPTION OF SYMBOLS 12 Nonlinear conversion part 12a Storage part 13 Operation part 14 Output part 100 Optical system 200 Signal processing system

Claims (2)

A particle signal detector that detects and converts the characteristics of particles into an analog particle signal;
An A / D converter that converts the analog particle signal detected by the particle signal detector into a digital signal and outputs the digital signal;
A storage unit for storing the digital particle signal x output from the A / D conversion unit;
A non-linear conversion unit that converts the digital particle signal x stored in the storage unit using a non-linear function y = f (x);
A calculation unit for calculating the characteristic parameter of the particle from the conversion value y generated by the nonlinear conversion unit;
An output unit for outputting a calculation result in the calculation unit,
The non-linear conversion unit multiplies the digital particle signal x obtained from the storage unit by m (integer), and further randomly adds an integer from 0 to (m−1) as an X value. As a particle measuring apparatus, a converted value is acquired using a nonlinear function y = f (X / m). 2. The particle measuring apparatus according to claim 1, wherein the m is set so that a maximum change rate of the nonlinear function y with respect to X is 1 or less.

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