Particle analyzer classifying particles of various biological types using a correlation of measurements

• US 5,719,666 A
• Filed: 11/14/1995
• Issued: 02/17/1998
• Est. Priority Date: 11/14/1994
• Status: Expired due to Fees

• Current Assignee: Unarco Industries, LLC (Berkshire Hathaway Incorporated)
• Original Assignee: Toa Medical Electronics Co., Ltd.
• Inventors: Oka, Masaaki, Nakamoto, Hiroyuki, Fukuda, Masakazu
• Primary Examiner(s): Font, Frank G.
• Assistant Examiner(s): VIERRA EISENBERG, JASON D
• Application Number:
  US08/557,576
• Time in Patent Office: 826 Days
• Field of Search: 356/72, 356/73, 356/317-318, 356/335-343, 356/442, 324/73.1
• US Class Current: 356/72
• CPC Class Codes: G01N 15/1456 without spatial resolution of the texture or inner structure of the particle, e.g. processing of pulse signals
• CPC Class Codes: G01N 2015/1019 Associating Coulter-counter and optical flow cytometer [OFC]

Abstract

A particle analyzer includes a flow cell including first and second cells for containing an electrolyte with various types of biological particles floating therein. The first and second cells are connected to each other by a pore to allow the particles to flow from the first cell to the second cell through the pore. A first and a second electrode are provided in the electrolyte in the first and second cells respectively. A first detector detects an electric resistance between the first and second electrodes which changes according as the particle passes through the pore to generate an electric resistance signal representative of the electric resistance. A light source emits a beam of light to the flowing particle and a second detector detects scattered light from the particle receiving the beam of light to generate a scattered light signal representative of an intensity of the scattered light. A clock device clocks a period of time during which the scattered light signal is generated. An analyzer classifies the particle as a particular type of biological particle based on a correlation between the electric resistance signal and the clocked period of time.

Claims

1. A particle analyzer comprising:

a flow cell including first and second cells for containing electrolyte, the first and second cells being connected to each other by a pore to allow particles of various biological types to flow from the first cell to the second cell through the pore;

a first and second electrodes provided in the electrolyte in the first and second cells respectively;

first detecting means for detecting an electric resistance between the first and second electrodes which changes according as the particle passes through the pore to generate an electric resistance signal representative of the electric resistance;

a light source for emitting a beam of light to the flowing particle;

second detecting means for detecting scattered light from the particle receiving the beam of light to generate a scattered light signal representative of an intensity of the scattered light;

clock means for clocking a period of time during which the scattered light signal is generated; and

analysis means for classifying the particle as a particular type of the various biological types based on a correlation between the electric resistance signal and the clocked period of time.

2. The particle analyzer according to claim 1, further comprising:

comparison means for comparing the scattered light signal obtained by the second detecting means with a first reference value as well as a second reference value larger than the first reference value;

second clock means for clocking a first period of time during which the scattered light signal is larger than the first reference value and a second period of time during which the scattered light signal is larger than the second reference value; and

second analysis means for classifying the particle based on a correlation between the first and second periods of time.

3. The particle analyzer according to claim 2, further comprising means for eliminating particles identified by said second analysis means from consideration by said analysis means.

4. The particle analyzer according to claim 2, further comprising:

peak detecting means for detecting a maximum value of the scattered light signal obtained by the second detecting means; and

fourth analysis means for classifying the particle based on the obtained maximum value.

5. The particle analyzer according to claim 1, further comprising:

third detecting means for detecting fluorescence from the particle receiving the beam of light to generate a fluorescence signal representative of an intensity of the fluorescence;

second comparison means for comparing the fluorescence signal means with a third reference value;

third clock means for clocking a third period of time during which the fluorescence signal is larger than the third reference value; and

third analysis means for classifying the particle based on a correlation between the clocked third period of time and the scattered light signal generated period of time.

6. The particle analyzer according to claim 5, further comprising;

peak detecting means for detecting a maximum value of the fluorescence signal obtained by the third detecting means; and

fifth analysis means for classifying the particle based on the obtained maximum value.

7. The particle analyzer according to claim 5, further comprising means for eliminating particles identified by said third analysis means from consideration by said analysis means.

8. A particle analyzer comprising:

a flow cell including first and second cells for containing electrolyte, the first and second cells being connected to each other by a pore to allow particles of various biological types to flow from the first cell to the second cell through the pore;

a light source for emitting a beam of light to the flowing particle;

a detector for detecting scattered light from the particle receiving the beam of light to generate a scattered light signal representative of an intensity of the scattered light;

comparison means for comparing the scattered light signal obtained by the detector with a first reference value as well as a second reference value larger than the first reference value;

a clock for clocking a first period of time during which the scattered light signal is larger than the first reference value and a second period of time during which the scattered light signal is larger than the second reference value; and

analysis means for classifying the particle based on a correlation between the first and second periods of time.

9. The particle analyzer according to claim 8, further comprising:

peak detecting means for detecting a maximum value of the scattered light signal obtained by the second detecting means; and

fourth analysis means for classifying the particle based on the obtained maximum value.

10. A particle analyzer comprising:

a flow cell including first and second cells for containing electrolyte, the first and second cells being connected to each other by a pore to allow particles of various biological types to flow from the first cell to the second cell through the pore;

a light source for emitting a beam of light to the flowing particle;

a first detector for detecting scattered light from the particle receiving the beam of light to generate a scattered light signal representative of an intensity of the scattered light;

a clock for clocking a period of time during which the scattered light signal is generated;

a second detector for detecting fluorescence from the particle receiving the beam of light to generate a fluorescence signal representative of an intensity of the fluorescence;

a comparator for comparing the fluorescence signal means with a reference value;

another clock for clocking another period of time during which the fluorescence signal is larger than the reference value; and

analysis means for classifying the particle based on a correlation between the another clocked period of time and the scattered light signal generated period of time.

11. The particle analyzer according to claim 10, further comprising:

peak detecting means for detecting a maximum value of the fluorescence signal obtained by the second detector; and

second analysis means for classifying the particle based on the obtained maximum value.

12. A method for analyzing particles in an electrolyte comprising the steps of:

connecting first and second cells for containing electrolyte to each other to allow particles of various types to flow from the first cell to the second cell;

providing first and second electrodes in the electrolyte in the first and second cells respectively;

detecting an electric resistance between the first and second electrodes which changes according as the particle passes through the pore to generate an electric resistance signal representative of the electric resistance;

emitting a beam of light to the flowing particle;

sensing scattered light from the particle receiving the beam of light to generate a scattered light signal representative of an intensity of the scattered light;

clocking a period of time during which the scattered light signal is generated; and

classifying the particle as a particular type of the various types based on a correlation between the electric resistance signal and the clocked period of time.

13. The method according to claim 12, further comprising;

comparing the scattered light signal obtained during said sensing step with a first reference value as well as a second reference value larger than the first reference value; and

clocking a first period of time during which the scattered light signal is larger than the first reference value and a second period of time during which the scattered light signal is larger than the second reference value;

said classifying step further includes classifying the particle based on a correlation between the first and second periods of time.

14. The method according to claim 13, further comprising:

eliminating particles identified by the correlation between the first and second periods of time from consideration by classifying by the correlation between the electric resistance signal and the clocked period of time.

15. The according to claim 13, further comprising peak detecting a maximum value of the scattered light signal obtained by said sensing step, wherein said classifying step further includes classifying the particle based on the obtained maximum value.

16. The method according to claim 12, further comprising:

generating a fluorescence signal representative of an intensity of the fluorescence from the particle receiving the beam of light;

comparing the fluorescence signal means with a reference value; and

clocking another period of time during which the fluorescence signal is larger than the reference value;

said classifying step further including classifying the particle based on a correlation between the another clocked period of time and the scattered light signal generated period of time.

17. The method according to claim 16, further comprising:

eliminating particles identified by the correlation between the another clocked period of time and the scattered light signal generated period of time from consideration by classifying by the correlation between the electric resistance signal and the clocked period of time.

18. The method according to claim 16, further comprising peak detecting a maximum value of the fluorescence signal obtained by the generating step, wherein said classifying step includes classifying the particle based on the obtained maximum value.