# US 2018/0024148 A1 · Blood analyzer and blood analyzing method

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- Number: US 2018/0024148 A1
- Document ID: US20180024148A1
- Status: Published application
- Kind: A1
- Application number: 15/657,962
- Filed: 2017-07-24
- Published: 2018-01-25
- Earliest claimed: 2016-07-25
- Assignees: Sysmex Corporation
- Applicants: Sysmex Corporation
- Inventors: Yuhgi SUZUKI; Takuma WATANABE
- Web page: https://patentgrep.com/patent/US20180024148A1

## CPC

- G01N 33/80: involving blood groups or blood types {or red blood cells (white blood cells G01N33/56972)}
- C12Q 1/06: Quantitative determination
- G01N 1/30: Staining; Impregnating {; Fixation; Dehydration; Multistep processes for preparing samples of tissue, cell or nucleic acid material and the like for analysis}
- G01N 15/1429: Signal processing
- G01N 15/1456: {without spatial resolution of the texture or inner structure of the particle, e.g. processing of pulse signals}
- G01N 15/1459: {the analysis being performed on a sample stream}
- G01N 21/6428: {Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" (in vivo A61B5/00; immunoassay G01N33/53)}
- G01N 33/56905: {Protozoa}
- G01N 2015/012: {Red blood cells}
- G01N 2015/1006: {for cytology}
- G01N 2015/1402: {Data analysis by thresholding or gating operations performed on the acquired signals or stored data}
- G01N 2015/1497: {Particle shape}
- G01N 2021/6439: {with indicators, stains, dyes, tags, labels, marks}
- G01N 2333/445: Plasmodium
- Y02A 50/30: Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
- 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)
- C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE

## Abstract

Disclosed is a blood analyzer that includes: a sample preparation unit configured to mix a blood specimen and a fluorescent dye for staining nucleic acid to prepare a measurement sample; a light receiver configured to receive fluorescence and scattered light that are generated by light being applied to the measurement sample prepared by the sample preparation unit; and a controller programmed to determine whether or not infection with Plasmodium has occurred, on the basis of a value representing variation of a distribution of first particles in a range where single-ring form of red blood cells appear, the range where single-ring form of red blood cells appear being identified according to fluorescence intensities and scattered light intensities obtained by processing of signals from the light receiver.

## Claims

### Claim 1

A blood analyzer comprising:
a sample preparation unit configured to mix a blood specimen and a fluorescent dye for staining nucleic acid to prepare a measurement sample;
a light receiver configured to receive fluorescence and scattered light that are generated by light being applied to the measurement sample prepared by the sample preparation unit; and
a controller programmed to determine whether or not infection with Plasmodium has occurred, on the basis of a value representing variation of a distribution of first particles in a range where single-ring form of red blood cells appear, the range where single-ring form of red blood cells appear being identified according to fluorescence intensities and scattered light intensities obtained by processing of signals from the light receiver.

### Claim 2 (depends on 1)

The blood analyzer of claim 1, wherein the controller is programmed to identify the first particles separately from second particles in a range where multi-ring form of red blood cells appear.

### Claim 3 (depends on 1)

The blood analyzer of claim 1, wherein the value representing the variation is a value that represents variation of a frequency distribution with respect to the fluorescence intensities of the first particles.

### Claim 4 (depends on 1)

The blood analyzer of claim 1, wherein the value representing the variation is a coefficient of variation, a standard deviation, or a half-value width in a frequency distribution chart.

### Claim 5 (depends on 1)

The blood analyzer of claim 1, wherein the sample preparation unit further mixes a diluent that causes red blood cells to contract, to prepare the measurement sample.

### Claim 6 (depends on 1)

The blood analyzer of claim 1, wherein the controller is programmed to determine whether or not infection with Plasmodium has occurred, on the basis of the value representing the variation, and the number of third particles in a range where red blood cells infected with Plasmodium appear.

### Claim 7 (depends on 6)

The blood analyzer of claim 6, wherein the controller is programmed to determine that the blood specimen is infected with Plasmodium when the number of the third particles is greater than or equal to a first threshold value, and the value representing the variation is less than a second threshold value.

### Claim 8 (depends on 6)

The blood analyzer of claim 6, wherein the controller is programed to determine that the blood specimen is infected with Plasmodium when the number of the third particles is greater than or equal to a first threshold value, the value representing the variation is less than a second threshold value, and the number of the first particles is greater than or equal to a third threshold value.

### Claim 9 (depends on 1)

The blood analyzer of claim 1, further comprising:
an output unit configured to output information, wherein
the controller is programmed to cause the output unit to output a determination result as to infection with Plasmodium.

### Claim 10 (depends on 9)

The blood analyzer of claim 9, wherein the controller is programed to cause the output unit to output information representing a reliability of a determination result as to infection with Plasmodium, in a case where the value representing the variation is greater than or equal to a predetermined threshold value.

### Claim 11 (depends on 10)

The blood analyzer of claim 10, wherein the output unit comprises a display unit for displaying information, wherein the controller is programmed to cause the display unit to display both the information representing the reliability and a determination result as to infection with Plasmodium.

### Claim 12 (depends on 11)

The blood analyzer of claim 11, wherein the controller is programmed to cause the display unit to further display a frequency distribution chart with respect to the fluorescence intensities of the first particles.

### Claim 13 (depends on 11)

The blood analyzer of claim 11, wherein the controller is programmed to cause the display unit to further display a scattergram based on the fluorescence intensities and the scattered light intensities.

### Claim 14 (depends on 1)

The blood analyzer of claim 1, comprising:
a flow cell configured to allow the measurement sample prepared by the sample preparation unit to flow therethrough; and
a light source configured to apply the light to the measurement sample that flows through the flow cell, wherein
the light receiver receives the scattered light and the fluorescence generated, by application of the light, from a particle included in the measurement sample.

### Claim 15 (depends on 14)

The blood analyzer of claim 14, wherein the light source emits light in a blue-violet wavelength band.

### Claim 16

A blood analyzing method comprising determining whether or not infection with Plasmodium has occurred, on the basis of a value representing variation of a distribution of first particles in a range where single-ring form of red blood cells appear, the range where single-ring form of red blood cells appear being identified according to fluorescence and scattered light generated by light being applied to a measurement sample, the measurement sample being prepared by mixing a blood specimen and a fluorescent dye for staining nucleic acid.

### Claim 17

A blood analyzer comprising:
a sample preparation unit configured to mix a blood specimen and a fluorescent dye for staining nucleic acid to prepare a measurement sample; and
a light receiver configured to receive fluorescence generated by light being applied to the measurement sample prepared by the sample preparation unit; and
a controller programmed to determine whether at least one of a red blood cell including an inclusion body of nucleic acid; and an extracellular vesicle is present or absent, on the basis of fluorescence intensities obtained by processing of signals from the light receiver.

### Claim 18 (depends on 17)

The blood analyzer of claim 17, wherein the controller is programmed to identify particles in a range where the fluorescence intensities are lower than those of white blood cells, and determine, on the basis of the identified particles, whether at least one of a red blood cell including an inclusion body of nucleic acid, and an extracellular vesicle is present or absent.

### Claim 19 (depends on 17)

The blood analyzer of claim 17, wherein the sample preparation unit further mixes a diluent that causes red blood cells to contract, to prepare the measurement sample.

### Claim 20 (depends on 19)

The blood analyzer of claim 19, wherein the controller is programmed to identify particles in a range where the fluorescence intensities are higher than those of red blood cells that are contracted by the diluent, and are lower than those of white blood cells, and determine, on the basis of the identified particles, whether at least one of a red blood cell including an inclusion body of nucleic acid, and an extracellular vesicle is present or absent.
