Particle analyzer

• US 5,548,395 A
• Filed: 08/31/1992
• Issued: 08/20/1996
• Est. Priority Date: 09/20/1991
• Status: Expired due to Fees

• Current Assignee: Toa Medical Electronics Co., Ltd.
• Original Assignee: Toa Medical Electronics Co., Ltd.
• Inventors: Kosaka, Tokihiro
• Primary Examiner(s): McGraw, Vincent P.
• Assistant Examiner(s): HANTIS, KAREN
• Application Number:
  US07/937,340
• Time in Patent Office: 1,450 Days
• Field of Search: 356/39, 356/73, 356/23, 356/417, 382/6, 382/133
• US Class Current: 356/73
• CPC Class Codes: G01N 15/1433 using image recognition
• CPC Class Codes: G01N 15/1434 Optical arrangements
• CPC Class Codes: G01N 15/147 the analysis being performed on a sample stream
• CPC Class Codes: G01N 2015/1497 Particle shape
• CPC Class Codes: G01N 2021/058 Flat flow cell

Abstract

A particle analyzer comprising a one-dimensional image sensor for producing imaging signals by scanning a particle in a flow of specimen containing particle components such as blood and urine in a flat sheath flow thin in thickness in the light emitting direction and broad in the direction orthogonal to the light emitting direction, and a signal processing device for processing the signals and operating on the basis of the imaging signals from the one-dimensional image sensor. A particle analyzer excellent in analyzing capability for obtaining morphological information of particles in the liquid specimen flowing in a flow cell in real time is presented. Besides, by emitting light to a flowing particle, the transmitted light image is focused on the one-dimensional image sensor (line sensor), and the detected image signal from the line sensor is further processed in detail in the signal processing device. The signal processing device comprises a background correction processing circuit, a binarizing processing circuit, a binary signal processing circuit, a particle region division processing circuit and an arithmetic circuit. A particle analyzer high in analyzing capability for obtaining the absorption quantity and morphological information of individual particles in the liquid specimen flowing in a flow cell in real time is presented.

Claims

1. A particle analyzer for analyzing particles by passing a sheath liquid around a liquid specimen containing particles to be analyzed, and means for emitting light to the liquid specimen flow,

the liquid specimen flow being a flat flow which is thin in thickness and broad in width,

a one-dimensional image sensor disposed to extend in a direction vertical to the particle flow direction, and producing a signal at every scanning cycle for the particle, and

signal processing means for processing the signal from the one-dimensional image sensor, wherein

the signal processing means obtains feature parameters of individual particles on the basis of the signal from said one-dimensional image sensor, by processing the signal from the one dimensional image sensor, thereby analyzing the particles on the basis of the difference of the feature parameters of each particles, said feature parameters containing at least one of particle morphological information and absorption information,

said signal processing means comprises:

background correction processing means for obtaining correction data Sc(i), by calculating the difference between background data Sa obtained from the signal from the one-dimensional image sensor in the absence of a particle, and measured data Sb(i) obtained from the signal from the one-dimensional image sensor when a particle is passing through the imaging region,

binarizing processing means for obtaining binary signal Sd(i) for detecting the specified portion of the particle by comparing the correction data Sc(i) from the background correction processing means with specified threshold data,

binary signal processing means for logical operation for the binary signal from the binarizing processing means, and

arithmetic means for calculating said feature parameters by using the binary signal from said binary signal processing means.

2. A particle analyzer of claim 1, further comprising a second light source, and second imaging means for capturing the two-dimensional still image of the particle, wherein

a one-dimensional imaging region of the one-dimensional image sensor is formed so as to cross the flow of particle, in a two-dimensional imaging region of the second imaging means in the liquid specimen flow, and

the signal processing means detects the arrival of particle on the basis of the imaging signal at least from the one-dimensional image sensor, thereby controlling to illuminate the second light source for capturing two-dimensional still image.

3. A particle analyzer of claim 1, further comprising means for detecting scattered light or fluorescent light emitted from a passing particle, so that the data concerning the scattered light or fluorescent light are ignored when plural particles pass simultaneously and are detected by the one-dimensional image sensor.

4. A particle analyzer of claim 1, wherein the morphological information is at least one selected from cell area, cell circumferential length, cell nucleus area, cell width, cell complicatedness, cell roundness, and nucleus area rate, and wherein the absorption information is at least one selected from absorption quantity and absorptive degree of the particles being analyzed.

5. A particle analyzer of claim 1, further comprising first processing means for obtaining an AND signal S3(i) by a logical AND operation between a binary signal S2(i) of a scan cycle (i) and a binary signal S2(i-1) of one scan cycle before (i-1), and

means for obtaining the sum of widths of AND signal pulses corresponding to one particle, means for setting particle moving extent data L in one scanning period, and arithmetic means for multiplying the sum of the widths of the AND signal pulses by particle moving extent data L, whereby

area data of the particle being analyzed is obtained.

6. A particle analyzer of claim 1, further comprising second processing means for obtaining EXOR signal S6(i) by exclusive-or operation between the binary signal S2(i) of scan cycle i and binary signal S2(i-1) of one scan cycle before i-1,

means for obtaining the width of each EXOR signal pulse corresponding to one particle, means for setting the particle moving extent data L in one scanning period, arithmetic means for calculating the square root of the sum of the squared width of each EXOR signal pulse and squared particle moving extent data L in every EXOR signal pulse, and arithmetic means for obtaining the cumulative sum of same particle of the square root data from the arithmetic means, whereby

circumferential length data of the particle being analyzed is obtained.

7. A particle analyzer of claim 1, further comprising second processing means for obtaining EXOR signal S6(i) by exclusive-or operation between the binary signal S2(i) of scan cycle i and binary signal S2(i-1) of one scan cycle before i-1,

means for obtaining the sum of widths of EXOR signal pulses corresponding to one particle, and

arithmetic means for dividing the sum of widths of EXOR signal pulses by 2, whereby

the width data of the particle being analyzed in the direction vertical to the moving direction is obtained.

8. A particle analyzer of claim 1, further comprising arithmetic means for obtaining the cumulative sum of the corrected data corresponding to one particle, thereby obtaining absorption quantity data of said corresponding one particle.

9. A particle analyzer of claim 1, further comprising third processing means for obtaining AND signal S3(i) in scan cycle i by logical AND operation between the binary signal S2(i) of scan cycle i and binary signal S2(i-1) of one scan cycle before i-1, and obtaining EXOR signal S7(i) by exclusive-or operation between the AND signal S3(i) of scan cycle i and AND signal S3(i-1) of one scan cycle before i-1, and

means for obtaining the width for obtaining the EXOR signal pulse, means for setting the particle moving extent data L in one scanning period, arithmetic means for calculating the square root of the sum of the squared width of each EXOR signal pulse and squared particle moving extent data L in every EXOR signal pulse, and arithmetic means for obtaining cumulative sum for one particle of square root data from the arithmetic means, whereby circumferential length data is obtained.

10. A particle analyzer of claim 1, further comprising third processing means for obtaining AND signal S3(i) in scan cycle i by logical AND operation between the binary signal S2(i) of scan cycle i and binary signal S2(i-1) of one scan cycle before i-1, and obtaining EXOR signal S7(i) by exclusive-or operation between the AND signal S3(i) of scan cycle i and AND signal S3(i-1) of one scan cycle before i-1,

means for obtaining the sum of widths of EXOR signal pulses corresponding to one particle, and

arithmetic means for dividing the sum of widths of EXOR signal pulses by 2, whereby

the width data of the particle being analyzed in the direction vertical to the moving direction is obtained.

11. A particle analyzer of claim 1, further comprising two signal processing means for obtaining binary signals by two different threshold data Th1, Th2, obtaining binary signal S2(i) for the entire particle and the binary signal S4(i) for detecting the nucleus portion of particle, and obtaining AND signals S3(i), S5(i) by logical AND operation between binary signals S2(i), S4(i) of scan cycle i, and binary signals S2(i-1), S4(i-1) of one scan cycle before i-1, corresponding to these two kinds of signals, and

means for obtaining the sum of the widths of AND signal pulses corresponding to one particle as the particle area data and nucleus area data, and arithmetic means for dividing the nucleus area data by the particle area data, whereby

the nucleus area rate data is obtained.

12. A particle analyzer of claim 1, further comprising arithmetic means for obtaining the cumulative sum of the portion of the nucleus of the individual particles of the correction data, thereby obtaining the absorption quantity data of the nucleus portion.

13. A particle analyzer of claim 5, further comprising differentiating means for obtaining the difference of the adjacent data of each A-D converted data, said A-D converted data is obtained by sampling the corrected data by clocks, and by A-D converting said sampling data,

means for obtaining the sum of the differential data of the portion corresponding to one particle, or the sum of the square of the differential data as the complicated quantity data, and

arithmetic means for dividing the complicated quantity data by the area data from the arithmetic means for obtaining the area data, thereby obtaining the complicated degree data per unit area.

14. A particle analyzer of claim 6, further comprising arithmetic means for squaring the circumferential length data from the arithmetic means for obtaining the circumferential length and dividing by the area data from the arithmetic means for obtaining the area, thereby obtaining roundness data of the particle being analyzed.

15. A particle analyzer of claim 1, further comprising plural sets of arithmetic means so that feature parameters of particles may be calculated simultaneously if plural particles simultaneously cross the imaging area of the one-dimensional image sensor.

16. A particle analyzer of claim 9, further comprising arithmetic means for squaring the circumferential length data from the arithmetic means for obtaining the circumferential length and dividing by the area data from the arithmetic means for obtaining the area, thereby obtaining roundness data of the particle being analyzed.

17. A particle analyzer of claim 11, further comprising plural sets of arithmetic means so that feature parameters of particles may be calculated simultaneously if plural particles simultaneously cross the imaging area of the one-dimensional image sensor.