# US 12,215,308 B2 · Charged particle beam apparatus and cell evaluation method

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- Number: US 12,215,308 B2
- Document ID: US12215308B2
- Status: Granted
- Kind: B2
- Application number: 16/604,908
- Filed: 2017-04-14
- Published: 2020-02-20
- Granted: 2025-02-04
- Earliest claimed: 2017-04-14
- Assignees: Hitachi High-Tech Corporation
- Applicants: Hitachi High-Technologies Corporation
- Inventors: Akira Ikeuchi; Shigeru Kawamata; Hiromi Mise; Akira Sawaguchi
- Web page: https://patentgrep.com/patent/US12215308B2

## CPC

- C12M 41/46: {of cellular or enzymatic activity or functionality, e.g. cell viability}
- C12Q 1/04: Determining presence or kind of microorganism; Use of selective media for testing antibiotics or bacteriocides; Compositions containing a chemical indicator therefor {(C12Q1/6897 takes precedence)}
- G01N 33/4833: {of solid biological material, e.g. tissue samples, cell cultures (tissue in vivo A61B5/00; cell suspensions G01N33/48735)}
- G06T 7/62: of area, perimeter, diameter or volume
- G06T 7/64: of convexity or concavity
- H01J 37/222: {Image processing arrangements associated with the tube}
- H01J 37/26: Electron or ion microscopes; Electron or ion diffraction tubes
- H01J 2237/221: Image processing
- C12M: APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; {APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS}
- 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
- 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)
- G06T: IMAGE DATA PROCESSING OR GENERATION, IN GENERAL
- H01J: ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS (spark-gaps H01T; electric arc lamps H05B31/00; particle accelerators H05H)

## Abstract

Provided is a charged particle beam apparatus capable of more objectively and highly accurately calculating a feature of a cell from an observation image of a cell and evaluating a cell. The charged particle beam apparatus includes an image acquisition unit 18 that acquires an image of a cell, a contour extraction unit 19 that extracts a contour of the image, a feature calculation unit 20 that calculates a morphological feature of the contour based on the contour and calculates the feature of an internal structure such as a cytoplasm contained in an internal area of the contour, and a determination unit 21 that determines quality and/or functionality of the cell based on the feature, and can objectively and highly accurately evaluate the quality and/or the functionality of the cell included in the captured image.

## Claims

### Claim 1

A charged particle beam apparatus comprising:
a computer processor; and
a memory storing a program that when executed by the computer processor causes the computer processor to:
acquire a cross-sectional image of a cell based on a signal, including a reflected electron or a secondary electron, detected by a detector of the charged particle beam apparatus;
determine a quality and/or a functionality of the cell based on a feature in the acquired image;
extract a contour of the cell based on the acquired image; and
calculate, as the feature, a morphological feature of the contour based on the extracted contour and a feature of an internal structure included in an internal area of the contour;
wherein the cell is a differentiated cell generated from undifferentiated cells;
wherein the differentiated cell is a platelet, the quality of the platelet shows a presence or absence of hemostatic ability, and the functionality of the platelet shows a size of the hemostatic ability; and
wherein the morphological feature of the contour shows roundness of the platelet outline, and the feature of the internal structure includes an area ratio of an open canalicular system of the platelet, an expansion degree of the open canalicular system, and an area ratio of a deep dyeing region of the platelet; and
wherein the computer processor determines the quality of the platelet and/or the functionality of the platelet based on the morphological feature and the feature of the internal structure.

### Claim 2 (depends on 1)

The charged particle beam apparatus according to claim 1, wherein
the computer processor calculates the morphological feature showing the roundness of the platelet outline from the area and the circumference of the platelet.

### Claim 3 (depends on 1)

The charged particle beam apparatus according to claim 1, wherein
the computer processor calculates as the feature, the area ratio of the open canalicular system, which is a proportion of a total area of the open canalicular system to the area of the platelet.

### Claim 4 (depends on 1)

The charged particle beam apparatus according to claim 1, wherein
the computer processor calculates as the feature, the expansion degree of the open canalicular system, which is the maximum diameter of the open canalicular system with respect to the diameter of the platelet.

### Claim 5 (depends on 1)

The charged particle beam apparatus according to claim 1, wherein
the computer processor calculates as the feature, the deep dyeing region, which is an area showing secretory granules and mitochondria of the platelets.