# US 2014/0154677 A1 · Cell analysis apparatus and cell analysis method

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- Number: US 2014/0154677 A1
- Document ID: US20140154677A1
- Status: Published application
- Kind: A1
- Application number: 14/164,773
- Filed: 2014-01-27
- Published: 2014-06-05
- Earliest claimed: 2007-10-29
- Assignees: Sysmex Corporation
- Applicants: Sysmex Corporation
- Inventors: Masaki ISHISAKA; Kazuki KISHI; Masakazu FUKUDA
- Web page: https://patentgrep.com/patent/US20140154677A1

## CPC

- G01N 21/6486: {Measuring fluorescence of biological material, e.g. DNA, RNA, cells (G01N21/6428 takes precedence)}
- G01N 15/147: {the analysis being performed on a sample stream}
- G01N 2015/0092: {Monitoring flocculation or agglomeration}
- G01N 2015/1497: {Particle shape}
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## Abstract

A cell analysis apparatus that can accurately distinguish between an aggregating cell and a non-aggregating cell is provided. The cell analysis apparatus (10) includes: an optical detection section (3) for flowing a measurement sample obtained from a biological sample and a pigment into a flow cell (51), irradiating the measurement sample flowing in the flow cell (51) with laser beam and detecting fluorescence from the measurement sample; a signal processing circuit (4) for acquiring, based on a fluorescence signal outputted from the detection section (3), a value reflecting the height of a waveform of the signal and a value reflecting the length of a ridge line of the waveform of the signal; and a system control section (13) for distinguishing between an aggregating cell formed by aggregation of a plurality of cells and a non-aggregating cell, based on the value reflecting the height of the waveform of the fluorescence signal and the value reflecting the length of the ridge line of the waveform of the fluorescence signal obtained by the signal processing circuit (4).

## Claims

### Claim 1

A cell analyzer comprising:
a detector configured to detect events associated with interrogation of cells and output a profile signal unique to a respective event, wherein the profile signal is representative of DNA amount of a nucleus of a respective cell; and
a computer programmed to:
quantize a profile signal of a respective detected event into a profile value, which is derived by integrating the profile signal; and
determine a relative number of events having profile values higher than a threshold value to thereby determine a relative number of cells having DNA amount greater than a threshold DNA amount.

### Claim 2 (depends on 1)

The cell analyzer according to claim 1, wherein the events are incidents of fluorescent light upon the detector from the cells dyed in preparation.

### Claim 3 (depends on 2)

The cell analyzer according to claim 2, wherein the profile signal is a function of an intensity of the fluorescent light incident upon the detector and time.

### Claim 4 (depends on 1)

The cell analyzer according to claim 1, wherein the computer is further programmed to map the detected events upon a function of a frequency of the events and the profile values of the events.

### Claim 5 (depends on 4)

The cell analyzer according to claim 4, wherein the computer is further programmed to:
determine a profile value of highest frequency of the events; and
selecting, as the threshold value, a profile value which is higher than the profile value of highest frequency of the events.

### Claim 6 (depends on 1)

The cell analyzer according to claim 1, wherein the threshold value is selected to distinguish cells with abnormally great DNA amount from cells with normal DNA amount.

### Claim 7 (depends on 1)

The cell analyzer according to claim 1, wherein the relative number is a ratio of a number of the events having the profile values higher than the threshold value to a number of the detected events.

### Claim 8 (depends on 1)

The cell analyzer according to claim 1, wherein the computer is further programmed to determine possibility of cancer based on the relative number.

### Claim 9 (depends on 1)

The cell analyzer according to claim 1, wherein the profile signal has a peak; and
the computer is further programmed to:
quantize a profile signal of a respective detected event into a second profile value which is a ratio between the peak of the respective profile signal and a sum of derivatives derived along the respective profile signal; and
identify events having second profile values higher than a second threshold value to thereby identify aggregating cells and non-aggregating cells.

### Claim 10 (depends on 1)

The cell analyzer according to claim 1, wherein the cells are epithelial cells.

### Claim 11

A cell analyzing method implemented by a computer of a cell analyzer, the method comprising:
detecting events associated with interrogation of cells and outputting a profile signal unique to a respective event, wherein the profile signal is representative of DNA amount of a nucleus of a respective cell;
quantizing a profile signal of a respective detected event into a profile value which is derived by integrating the profile signal; and
determining a relative number of events having profile values higher than a threshold value to thereby determine a relative number of cells having DNA amount greater than a threshold DNA amount.

### Claim 12 (depends on 11)

The method according to claim 11, wherein the events are incidents of fluorescent light from the cells dyed in preparation.

### Claim 13 (depends on 12)

The method according to claim 12, wherein the profile signal is a function of an intensity of the fluorescent light incidents and time.

### Claim 14 (depends on 11)

The method according to claim 11, further comprising mapping the detected events upon a function of a frequency of the events and the profile values of the events.

### Claim 15 (depends on 14)

The method according to claim 14, further comprising:
determining a profile value of highest frequency of the events; and
selecting, as the threshold value, a profile value which is higher than the profile value of highest frequency of the events.

### Claim 16 (depends on 11)

The method according to claim 11, wherein the threshold value is selected to distinguish cells with abnormally great DNA amount from cells with normal DNA amount.

### Claim 17

A cell analyzer comprising:
a measuring portion which measures cells that are nuclear stained;
a displaying portion which displays a histogram of a pulse area of fluorescence signal by using a result of the measurement by the measuring portion; and
a determining unit which obtains a number of cells that are distributed in an area where the pulse area of fluorescence signal is larger than normal cells, and which determines possibility of cancer based on the number of cells and the histogram.

### Claim 18 (depends on 17)

The cell analyzer according to claim 17, wherein the determining unit performs the determination based on a ratio of the number of cells to a number of cells obtained from the histogram.

### Claim 19

A cell analyzing method comprising:
measuring cells that are nuclear stained, to obtain a histogram of a pulse area of fluorescence signal;
detecting a peak of normal cells from data of the histogram;
obtaining a number of cells that are distributed in an area where the pulse area of fluorescence signal is larger than the peak of the normal cells; and
determining possibility of cancer based on the obtained number of cells and the histogram.

### Claim 20 (depends on 19)

The method according to claim 19, wherein the determination is performed based on a ratio of the number of cells to a total number of cells.
