# US 12,110,480 B2 · Observation device

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- Number: US 12,110,480 B2
- Document ID: US12110480B2
- Status: Granted
- Kind: B2
- Application number: 17/256,362
- Filed: 2019-07-04
- Published: 2021-09-02
- Granted: 2024-10-08
- Earliest claimed: 2018-07-06
- Assignees: Nipro Corporation; Sapporo Medical University
- Applicants: Nipro Corporation; Sapporo Medical University
- Inventors: Osamu Honmou; Daiki Tateyama; Kosuke Takahashi; Kosei Tateyama; Yoshihiro Yoshikawa
- Web page: https://patentgrep.com/patent/US12110480B2

## CPC

- C12M 41/36: {of biomass, e.g. colony counters or by turbidity measurements (electrooptical investigation of individual particles G01N15/14, flow cytometers G01N15/1404)}
- C12M 23/22: {Transparent or translucent parts (glassware for laboratory use B01L3/00)}
- C12M 23/34: {Internal compartments or partitions}
- C12M 41/12: {of temperature (controlling the temperature of chemical or physical processes B01J19/0013, heating or cooling apparatus for laboratory use B01L7/00)}
- G02B 21/0088: {Inverse microscopes}
- G02B 21/082: {for incident illumination only}
- G02B 21/14: affording illumination for phase-contrast observation
- G02B 21/26: Stages; Adjusting means therefor
- G02B 21/34: Microscope slides, e.g. mounting specimens on microscope slides
- G02B 21/362: {Mechanical details, e.g. mountings for the camera or image sensor, housings (G02B21/364 takes precedence)}
- G02B 21/365: {Control or image processing arrangements for digital or video microscopes (G02B21/361, G02B21/362 take precedence)}
- G06V 20/693: {Acquisition}
- G06V 20/695: {Preprocessing, e.g. image segmentation}
- 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}
- G02B: OPTICAL ELEMENTS, SYSTEMS OR APPARATUS
- G06V: IMAGE OR VIDEO RECOGNITION OR UNDERSTANDING

## Abstract

An observation device includes a microscope. The microscope includes an illumination light beam source, an illumination optical system, and an observation optical system forming an optical image of an observation target from reflected light beams obtained by reflection of illumination light beams by the observation target. The observation optical system includes a phase plate changing the phase of directly reflected light beams reflected on a reflection surface among the reflected light beams. Both the illumination optical system and the observation optical system are arranged under the observation target. The observation device includes an image pickup device photoelectrically converting the optical image obtained by the observation optical system to create image data of the observation target and a display device displaying the image data. The illumination light beam emitted from the illumination optical system is a collimated light beam.

## Claims

### Claim 1

An observation device comprising:
an epi-illumination phase contrast microscope including an illumination light beam source, an illumination optical system emitting an illumination light beam from the illumination light beam source to an observation target which is a biological cell, and an observation optical system forming an optical image of the observation target from one or more reflected light beams obtained by reflection of the illumination light beam after passing through the observation target;
a moving device moving the epi-illumination phase contrast microscope relative to the observation target, the illumination optical system and the observation optical system being configured to be moved integrally by the moving device;
the observation optical system including a phase plate changing a phase of a directly reflected light beam reflected on a reflection surface among the reflected light beams;
both the illumination optical system and the observation optical system being arranged under the observation target;
an image pickup device photoelectrically converting the optical image obtained by the observation optical system to create image data of the observation target;
a display device displaying the image data,
wherein the illumination light beam emitted from the illumination optical system and passing through the observation target is a collimated light beam which is parallel to optical axes of the illumination optical system and the observation optical system; and
an incubator including a chassis having an opening, a lid body capable of opening/closing the opening, and a partition wall partitioning an internal space defined by the chassis and the lid body into a culture chamber in an upper portion of the internal space and a machine chamber in a lower portion of the internal space, wherein
the observation target is arranged in the culture chamber,
the illumination light beam source, the illumination optical system and the observation optical system, including a first objective lens, a second objective lens, the phase plate, and a half mirror, along with the image pickup device, and the moving device are arranged in the machine chamber,
the partition wall is fixed to the chassis such that the culture chamber maintains airtightness and watertightness against the machine chamber, and
at least one part of the partition wall is formed of a transparent material transmitting the illumination light beam.

### Claim 2 (depends on 1)

The observation device according to claim 1, wherein
the illumination light beam source is configured to be able to switch a wavelength of the illumination light beam among a plurality of different wavelengths.

### Claim 3 (depends on 2)

The observation device according to claim 2 comprising:
an image processing portion correcting the image data, wherein
in the image data, one or more pixels containing a luminance value as color information are arranged in two-dimensional coordinates, and
the image processing portion includes:
a calculation portion calculating a difference between the luminance values for each of the pixels of a same coordinate with respect to two image data of the image data obtained by the illumination light beams of two different wavelengths among the wavelengths;
a recognition portion recognizing the pixel having the difference smaller than a predetermined value as a noise pixel containing incorrect information; and
a creation portion deleting the noise pixel from each of the two image data to create two corrected image data.

### Claim 4 (depends on 2)

The observation device according to claim 2, further comprising a computer for image processing to determine whether image data of the obtained optical image is a part of the observation target or is formed by foreign substances by comparing image data for different wavelengths of the illumination light beams.

### Claim 5 (depends on 1)

The observation device according to claim 1, comprising:
a reflector arranged above the observation target.

### Claim 6 (depends on 5)

The observation device according to claim 5 comprising:
a petri dish containing a lower dish and an upper dish formed of a translucent material and housing the biological cell, wherein
the reflector is fixed to the upper dish.

### Claim 7 (depends on 5)

The observation device according to claim 5, comprising:
a petri dish containing a lower dish and an upper dish formed of a translucent material and housing the biological cell, and
wherein the reflector is distinct from the petri dish, is attached to an upper outer surface of the upper dish, and reflects the illumination light beam after passing through the observation target to provide the reflected light beams.

### Claim 8 (depends on 1)

The observation device according to claim 1, wherein
the illumination optical system includes a half mirror reflecting the illumination light beam from the illumination light beam source and a first objective lens and a second objective lens refracting the illumination light beam reflected on the half mirror, and
the observation optical system includes the first objective lens and the second objective lens refracting the reflected light beam from the observation target and the half mirror transmitting the refracted reflected light beam to the image pickup device via only a phase film region of the phase plate.

### Claim 9 (depends on 1)

The observation device according to claim 1,
wherein a half mirror common to the illumination optical system and observation optical system receives the illumination light beam and the one or more reflected light beams; and
wherein the directly reflected light beam exiting the half mirror toward the phase plate has a light path consisting of only the phase plate and open space before impinging on the image pickup device.

### Claim 10 (depends on 1)

The observation device according to claim 1, wherein the moving device is configured to move the illumination optical system and the observation optical system in only two dimensions, so as to be moved horizontally relative to the partition wall.

### Claim 11 (depends on 1)

The observation device according to claim 1, wherein the one or more reflected light beams obtained by the reflection of the illumination light beam after passing through the observation target and entering the observation optical system include, as the directly reflected light beam, another collimated light beam which is parallel to the optical axes of the illumination optical system and the observation optical system.
