WO2018158957A1 - Cell observation system - Google Patents

Cell observation system Download PDF

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Publication number
WO2018158957A1
WO2018158957A1 PCT/JP2017/008619 JP2017008619W WO2018158957A1 WO 2018158957 A1 WO2018158957 A1 WO 2018158957A1 JP 2017008619 W JP2017008619 W JP 2017008619W WO 2018158957 A1 WO2018158957 A1 WO 2018158957A1
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image
cell observation
data
observation system
unit
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PCT/JP2017/008619
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French (fr)
Japanese (ja)
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倫誉 山川
快彦 岩尾
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株式会社島津製作所
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Priority to PCT/JP2017/008619 priority Critical patent/WO2018158957A1/en
Publication of WO2018158957A1 publication Critical patent/WO2018158957A1/en

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    • GPHYSICS
    • G02OPTICS
    • G02BOPTICAL ELEMENTS, SYSTEMS OR APPARATUS
    • G02B21/00Microscopes
    • GPHYSICS
    • G06COMPUTING; CALCULATING OR COUNTING
    • G06TIMAGE DATA PROCESSING OR GENERATION, IN GENERAL
    • G06T1/00General purpose image data processing
    • HELECTRICITY
    • H04ELECTRIC COMMUNICATION TECHNIQUE
    • H04NPICTORIAL COMMUNICATION, e.g. TELEVISION
    • H04N1/00Scanning, transmission or reproduction of documents or the like, e.g. facsimile transmission; Details thereof

Definitions

  • the present invention relates to a cell observation system that observes cells using a holographic microscope.
  • a cell observation apparatus (holography observation apparatus) using a holographic microscope.
  • holographic observation apparatus an image of a cell accommodated in a culture plate is acquired while the cell is alive, and various measurements and analyzes are performed based on the image data.
  • a light beam with a uniform phase is divided into two parts, one of which is irradiated to the object to be passed or reflected, and the other is left as it is.
  • an image holographic image or hologram
  • the above-mentioned holographic image is measured by an image sensor for each region obtained by dividing the culture plate into a plurality, and a phase image and an intensity image are created by numerical calculation. Then, the phase images and intensity images of the plurality of divided regions are connected (also referred to as “tiling”) to obtain the phase image and intensity image of the entire culture plate.
  • the system of Patent Document 1 has a configuration in which a cell observation device and a display device are connected to a management server via a communication network.
  • the cell observation apparatus includes an optical microscope, an image sensor (CCD camera) that acquires an image of an object (specimen slide) located in an observation field of the optical microscope, and a tiling image acquired by the image sensor.
  • An image generation unit that generates an image of the entire object is provided.
  • the image data is sent to a management server via a communication network and stored in a database provided in the management server.
  • the management server creates an image (display image) to be displayed on the display device based on the image data of the object, and stores this data in the database. Then, in response to a transmission request from the display device, display image data is read from the database and transmitted to the display device.
  • the holography observation apparatus can observe the cells accommodated in the culture plate as they are alive, if the processing time related to the creation of the image in the cell observation apparatus is long, the culture plate is in a constant temperature culture chamber ( It takes a long time to leave outside the so-called “incubator”), which is not preferable.
  • the problem to be solved by the present invention is a cell observation system including a cell observation device and a management server connected by a communication network, and reduces the burden of processing executed in the cell observation device and creates an image of an observation target object Is to reduce the processing time required.
  • the present invention made to solve the above problems
  • the cell observation device is a) a light source that emits a coherent luminous flux; b) an irradiation optical system that irradiates the observation target object with the light beam emitted from the light source and interferes with the light beam transmitted or reflected at different positions of the observation target object; c) an image sensor for acquiring an interference image of a light beam transmitted or reflected by the observation object; d) a transmission unit that transmits data of an interference image acquired by the image sensor to the management server via the communication network, and
  • the management server is e) an image generation unit that generates an image based on the data transmitted from the transmission unit; f) a data storage unit for storing image information generated by the image generation unit; It is characterized by providing.
  • the irradiation optical system irradiates the light beam on the object to be observed and transmits or transmits the light at a different position of the object to be observed.
  • An interference image of the reflected light beam is formed.
  • the transmission unit transmits the interference image data as it is (in a so-called “raw data” state) to the management server through the communication network.
  • the image generation unit generates an image based on the interference image data transmitted from the transmission unit of the cell observation device, and stores the image information in the data storage unit.
  • the image generation unit of the management server may generate a phase image and a light intensity image of the observation target object based on the data transmitted from the transmission unit.
  • the data of the interference image transmitted from the transmission unit of the cell observation device to the management server is so-called hologram data. Therefore, in this configuration, the image generation unit of the management server configures the phase image and the light intensity image of the observation target object from the hologram data.
  • the cell observation system has a configuration in which one cell observation device is connected to one management server, and a plurality of cell observation devices are connected to one management server. be able to.
  • one or a plurality of display devices may be connected to the management server through a communication network.
  • the number of cell observation devices and the number of display devices may or may not be the same.
  • One of the cell observation devices and display devices connected to one management server may be one and the other may be a plurality.
  • the cell observation system includes a display device connected to the management server via the communication network
  • the management server In response to a request from the display device, the management server reads image information from the data storage unit, generates a display image from the image information, and transmits the display image data to the display device through the communication network. It is preferable to provide a display image generation unit. In this case, it is preferable that the display image generation unit reads out only the image information satisfying the request condition from the display device from the data storage unit.
  • the display image generation unit may include a processed image generation unit that generates the display image by processing the image generated by the image generation unit based on the image information read from the data storage unit. good.
  • processing refers to processing such as tiling, trimming, and resizing.
  • the display image generation unit generates a partial image that is an image of the whole or a part of the observation target object based on the image information read from the data storage unit.
  • a partial image generation unit may be provided.
  • the display image generation unit includes a magnification change image generation unit that generates an image in which an entire or a partial region of the observation target object is enlarged or reduced based on the image information read from the data storage unit. May be. According to this configuration, an image obtained by enlarging or reducing an image of an area to be measured or analyzed in the observation target object at an appropriate magnification can be displayed on the display device.
  • the image sensor when the image sensor cannot acquire an interference image of the entire observation object at once, the image sensor acquires an interference image for each region obtained by dividing the observation object into a plurality of parts, and manages the data. Will be sent to the server.
  • the data may be collectively transmitted to the management server. It is preferable that the transmission unit transmits the data to the management server via the communication network every time it is acquired.
  • the cell observation device includes a plurality of the image sensors, It is preferable that the transmission unit simultaneously transmits data acquired by each of the plurality of image sensors to the management server via the communication network.
  • a solid-state image sensor such as a CMOS image sensor or a CCD image sensor using a photodiode as a photoelectric conversion element can be used.
  • a solid-state image sensor such as a CMOS image sensor or a CCD image sensor using a photodiode as a photoelectric conversion element
  • the light source is configured to emit light beams having a plurality of different wavelengths, and includes a wavelength changing unit that changes the wavelength of the light beams emitted from the light source. According to this configuration, it is possible to emit a light beam having an appropriate wavelength according to the optical characteristics (absorption wavelength, transmission wavelength, etc.) of the observation target object and irradiate the observation target object.
  • the image sensor of the cell observation device acquires the interference image
  • the data is sent to the management server, and an image is generated there.
  • the burden can be reduced and the processing time for image generation can be shortened.
  • the whole block diagram of the cell observation system which is one Example of this invention.
  • FIG. 1 is a schematic diagram showing the overall configuration of the cell observation system according to the present example.
  • the communication network 1 such as the Internet includes a plurality of cell observation terminals 2A, 2B, 2C (hereinafter referred to as “2” unless the individual cell observation terminals need to be specified). Connected).
  • Each cell observation terminal 2 includes a microscope observation unit 21 and a personal computer (PC) 22 connected to the communication network 1.
  • the cell observation terminal 2 corresponds to the cell observation device of the present invention.
  • a management server 3 (hereinafter abbreviated as “server 3”) and a display device 4 are further connected to the communication network 1.
  • the server 3 is generally a high-performance computer, and includes a receiving unit 31 that receives data transmitted from the cell observation terminal 2, a data storage unit 32 that can store a large amount of data, and the computer.
  • a data processing unit 33 that is embodied by executing installed software is provided as a functional block.
  • the display device 4 includes a browsing computer 41, an input unit 42 such as a mouse and a keyboard attached to the browsing computer 41, and a display unit 43.
  • the browsing computer 41 is a general personal computer, and a standard OS as basic software and various software (for example, communication for performing bidirectional communication with the server 3) operating on the OS.
  • a control program, an input control program for controlling the operation of the input unit 42, and a display control program for controlling the operation of the display unit 43) are installed.
  • the browsing computer 41 includes a storage unit (not shown) that stores data such as a display image transmitted from the server 3.
  • the server 3 and the browsing computer 41 are connected to each other via an intranet (or the Internet) such as a LAN.
  • the connection between the server 3 and the browsing computer 41 is not limited to the intranet, and both may be connected via the communication network 1.
  • the microscopic observation unit 21 includes a holographic microscope made of IHM (In-line Holographic Microscopy). That is, as shown in FIG. 2, the microscopic observation unit 21 includes a light source unit 211, an image sensor 212, and a moving mechanism 214.
  • the light source unit 211 emits a laser diode 211a that emits a plurality of laser beams of different wavelengths, and irradiation that irradiates the culture plate 213 as an observation target object as a coherent light beam having a spread of a minute angle (about 10 degrees).
  • An optical system 211b is provided.
  • the image sensor 212 for example, a CMOS (Complementary Metal Oxide Semiconductor) image sensor is used.
  • the microscopic observation unit 21 may include one image sensor 212, but may include a plurality of image sensors 212. In the present embodiment, a total of four image sensors are provided, two on the front side and the back side in FIG. 2 (only two image sensors on the front side of the paper are shown in FIG. 2).
  • a coherent light beam emitted from the light source unit 211 is applied to a predetermined region of the culture plate 213. Then, the light (object light) in the coherent light beam transmitted through the cell S and the culture plate 213 reaches the image sensor 212 while interfering with the light (reference light) transmitted through the adjacent position of the cell S on the culture plate 213. .
  • an interference image (hologram) of the light transmitted through the cell S and the culture plate 213 and the light transmitted through the adjacent position of the cell S on the culture plate 213 is formed. Is done.
  • the light source unit 211 and the image sensor 212 are integrally moved in the XY direction (for example, the direction perpendicular to and parallel to the paper surface of FIG. 2) by the moving mechanism 214, for example. Thereby, the irradiation area (observation area
  • the PC 22 included in the cell observation terminal 2 is a general personal computer, which is equipped with a standard OS as basic software, and further installed with various software operating on the OS.
  • the PC 22 includes a storage unit 220, and controls the operation of the light source unit 211, such as changing the wavelength of the laser beam emitted from the laser diode 211a, as a functional block realized by executing installed software.
  • the data transmission unit 223 transmits the hologram data of the observation area acquired by the image sensor 212 (two-dimensional light intensity distribution data of the hologram formed on the detection surface of the image sensor 212) together with the identification information of the culture plate 213 to the server. 3 to send.
  • An input unit 23 and a display unit 24 are connected to the PC 22.
  • the receiving unit 31 included in the server 3 receives hologram data with identification information of the culture plate 213 sent from the cell observation terminal 2 for each cell observation terminal, and stores the data.
  • the data processing unit 33 includes an arithmetic processing unit 331 as a functional block, an image tiling unit 332, an image dividing unit 333, an instruction receiving unit 334, and an information reading unit 335.
  • the calculation processing unit 331 reads the hologram data from the data storage unit 32, executes predetermined calculation processing, and acquires phase information, intensity information, and pseudo phase information of each observation region from the hologram data. Based on these pieces of information, three types of observation images (phase image, intensity image, and pseudo phase image) are created. In addition, the arithmetic processing unit 331 executes general processing of image data (for example, image resolution change processing, image enlargement / reduction processing).
  • the image tiling unit 332 trims the observation image obtained by the arithmetic processing unit 331 based on the hologram data of the plurality of observation regions. Then, the trimmed observation images are pasted together (tiling) to create an observation image (tiling image) of the entire culture plate 213. Further, the image dividing unit 333 creates an observation image obtained for a part of the observation region of the culture plate 213 or a partial observation image obtained by dividing the observation image of the entire culture plate 213 into a plurality of pieces. The data of the tiling image created by the image tiling unit 332 and the partial observation image created by the image dividing unit 333 are stored in the data storage unit 32 together with the identification information of the culture plate 213.
  • the instruction receiving unit 334 receives a display image transmission request instruction coming from the browsing computer 41.
  • the information reading unit 335 accesses the data storage unit 32 and reads data and information that meet the conditions according to the instruction received by the instruction receiving unit 334.
  • FIG. 4 shows the flow of data and instructions in the operation when creating image data based on the hologram data obtained in the cell observation terminal 2 or creating display image data in response to an instruction from the browsing computer 41. It is a schematic diagram which shows.
  • the operator operates the input unit 23 to input identification information (measurement date, type of cultured cell, etc.) regarding the culture plate 213 and instruct to start the operation, a predetermined light emitted from the light source unit 211 is given.
  • a laser beam (coherent beam) having a wavelength and a coherent distance is irradiated onto the culture plate 213 set in the microscopic observation unit 21.
  • an interference image (hologram) of the light in the coherent light beam that has passed through the cells S and the culture plate 213 and the light that has passed through the adjacent position of the cells S on the culture plate 213 is formed on the detection surface of the image sensor 212.
  • the hologram two-dimensional light intensity distribution data (hologram data) measured by the image sensor 212 is stored in a data file with identification information of the culture plate 213 created in the storage unit 220 of the PC 22. Is done. Subsequently, the light source unit 211 and the image sensor 212 are moved by the moving mechanism 214, and hologram data of the next observation area is acquired by the image sensor 212 and stored in the data file of the storage unit 220.
  • the data transmission unit 223 reads the data file from the storage unit 220, and the identification information of the cell observation terminal 2 is obtained. Is sent to the server 3.
  • the PC 22 of the cell observation terminal 2 can transmit all data files stored in the storage unit 220 to the server 3, but only the data file of the culture plate 213 corresponding to specific identification information. It is of course possible to transmit to the server 3.
  • the operator can instruct what data file is transmitted from the cell observation terminal 2 to the server 3 by operating the input unit 23. Further, by operating the input unit 42 of the display device 4, the PC 22 of the cell observation terminal 2 may be instructed through the server 3 and the communication network 1.
  • the arithmetic processing unit 331 When the receiving unit 31 of the server 3 receives the data file from the cell observation terminal 2, in the data processing unit 33, the arithmetic processing unit 331 performs phase recovery processing, trimming processing, and tiling processing of the hologram data included in the data file. Execute. As a result, an image of each observation region (original image), an image of the entire culture plate 213, and other images obtained by dividing the culture plate 213 into an appropriate number (for example, 1/4 divided image and 1/2 divided image) are created. The The created image data is stored in the data storage unit 32 together with the identification information of the cell observation terminal 2 and the culture plate 213.
  • an operator who measures and analyzes the cultured cells accommodated in the culture plate 213 designates the types of the cell observation terminal 2 and the culture plate 213 from the input unit 42 of the display device 4, and then observes them.
  • the information reading unit 335 of the server 3 selects the entire observation image or partial observation image of the designated cell observation terminal 2 and culture plate 213 from the image data stored in the data storage unit 32.
  • the browsing computer 41 displays the transmitted image on the display unit 43.
  • the operator operates the input unit 42 of the browsing computer 41 to select a partial region of the image of the culture plate 213 displayed on the display unit 43 and information on the image (resolution, Specify the magnification, image type (phase image, intensity image, pseudo phase image, etc.) and request the creation of a display image.
  • the instruction receiving unit 334 determines information and image data to be read in response to a display image creation request from the browsing computer 41 and outputs the information and image data to the information reading unit 335.
  • the information reading unit 335 accesses the data storage unit 32 to read out necessary information and image data and sends them to the arithmetic processing unit 331.
  • the arithmetic processing unit 331 executes a predetermined process (trimming / enlargement / reduction process) based on the sent information and image data to create a display image.
  • the server 3 transmits the data of the display image to the browsing computer 41.
  • the browsing computer 41 that has received the display image displays the display image on the display unit 43.
  • FIG. 5 schematically shows a display image created by the arithmetic processing unit 331 of the server 3 based on the data acquired by the cell observation terminal 2.
  • the upper left diagram in FIG. 5 shows the relationship between the culture plate 213 and the observation areas of the four image sensors 212.
  • each of the four image sensors 212 acquires interference images of light beams that have passed through the quarter regions a1 to a4 of the entire culture plate 213. Therefore, when the culture plate 213 has six wells, observation images of 1.5 wells are created from the data acquired by one image sensor 212.
  • the image sensor 212 has 160 (12 ⁇ 14) pixels, an image obtained by dividing 1.5 wells into 160 sections is acquired by the image sensor 212 (see the lower left diagram in FIG. 5).
  • An observation image of 1.5 wells is created from the image data of 160 sections obtained in this way, and the observation image of one well is trimmed from the observation image of 1.5 wells. An image can be obtained.
  • An observation image of the entire culture plate 213 is created from the image data acquired by the four image sensors 212.
  • the center and the right part of FIG. 5 show examples of display images created by the arithmetic processing unit 331.
  • the center is an image (divided image) for one section, and the right part is an enlargement of a part of this divided image. An image is shown.
  • the server 3 since the data acquired by the image sensor 212 is transmitted to the server 3 as it is, the time required for data transmission can be shortened. Further, the server 3 processes the data acquired by the image sensor 212 to create an image, thereby reducing the burden of processing executed in the cell observation terminal 2 as compared to creating an image in the cell observation terminal 2. It is possible to shorten the processing time required for image creation.
  • the present invention is not limited to the above-described embodiments, and appropriate modifications and changes can be made.
  • the hologram data of the entire culture plate 213 is collectively transmitted to the server 3.
  • the hologram data may be transmitted to the server 3 as soon as the hologram data is acquired for each observation region.
  • the control unit light source control unit, moving mechanism control unit
  • storage unit of the microscopic observation unit 21 are realized by a personal computer 22 different from the microscopic observation unit 21.
  • a storage unit or a control unit may be incorporated.
  • the image dividing unit 333 divides the observation image of the culture plate 213 created by the image tiling unit 332 to create a partial observation image.
  • the image tiling unit 332 creates the image. May be. That is, the image tiling unit 332 can also create a partial observation image by pasting together hologram data of a plurality of observation regions that constitute a partial region of the culture plate 213.
  • the image dividing unit 333 can be omitted.
  • the cell observation unit 21 includes one image sensor that uses a partial region of the observation target object as an observation field, and moves the image sensor relative to the observation target object, so that the entire observation target object is displayed. You may make it acquire the image of.

Abstract

A cell observation system according to the present invention includes a cell observation device 2 and a management server 3 that is connected to the cell observation device 2 via a communication network 1, and is characterized in that: the cell observation device 2 is provided with a light source unit 211 that emits coherent beams of light, an irradiation optical system that irradiates an object 213 to be observed with the beams of light emitted from the light source unit 211, and causes interference with each other of the beams of light transmitted through or reflected at the different positions of the object, an image sensor 212 that acquires an interference image of the beams of light transmitted through or reflected on the object 213, and a transmission unit that transmits data of the interference image acquired by the image sensor 212 to the management sensor 3 via the communication network 1; and the management server 3 is provided with an image generation unit that generates an image on the basis of the data transmitted from the transmission unit, and a data storage unit that stores information about the image generated by the image generation unit.

Description

細胞観察システムCell observation system
 本発明は、ホログラフィ顕微鏡を用いて細胞を観察する細胞観察システムに関する。 The present invention relates to a cell observation system that observes cells using a holographic microscope.
 ES細胞やiPS細胞といった幹細胞を用いた再生医療技術の進展に伴い、培養細胞の生育状態や分化状態等を適切に管理するための装置が求められるようになっている。このような装置として、ホログラフィック顕微鏡を用いた細胞観察装置(ホログラフィ観察装置)がある。ホログラフィ観察装置では、培養プレートに収容された細胞の画像を該細胞が生きたままの状態で取得し、その画像データに基づいて様々な計測及び解析が行われる。 With the advancement of regenerative medical technology using stem cells such as ES cells and iPS cells, an apparatus for appropriately managing the growth state and differentiation state of cultured cells is required. As such an apparatus, there is a cell observation apparatus (holography observation apparatus) using a holographic microscope. In the holographic observation apparatus, an image of a cell accommodated in a culture plate is acquired while the cell is alive, and various measurements and analyzes are performed based on the image data.
 一般的なホログラフィ観察装置では、位相の揃った光束(コヒーレント光束)を2つに分割し、一方を対象物に照射して通過又は反射させ、他方をそのままにして、両光束を像面で干渉させることにより得られる像(ホログラフィ画像又はホログラム)を取得する。具体的には、培養プレートを複数に分割した領域毎に前述のホログラフィ像をイメージセンサによって測定し、数値演算により位相像や強度像を作成する。そして、複数の分割領域の位相像や強度像をつなぎ合わせて(「タイリング」ともいう)、培養プレート全体の位相像や強度像画像を取得する。 In a typical holographic observation device, a light beam with a uniform phase (coherent light beam) is divided into two parts, one of which is irradiated to the object to be passed or reflected, and the other is left as it is. To obtain an image (holographic image or hologram) obtained. Specifically, the above-mentioned holographic image is measured by an image sensor for each region obtained by dividing the culture plate into a plurality, and a phase image and an intensity image are created by numerical calculation. Then, the phase images and intensity images of the plurality of divided regions are connected (also referred to as “tiling”) to obtain the phase image and intensity image of the entire culture plate.
 最近の細胞観察装置では、多くの場合、装置の制御や得られた画像の処理にパーソナルコンピュータが利用されている。また、そうしたパーソナルコンピュータを通信ネットワークを介して管理サーバと接続し、細胞観察装置のデータを管理サーバで処理するようにしたシステムが開発されている。このようなシステムとして、特許文献1に記載のシステムがある。 In recent cell observation apparatuses, in many cases, a personal computer is used for controlling the apparatus and processing the obtained image. In addition, a system has been developed in which such a personal computer is connected to a management server via a communication network, and data of the cell observation apparatus is processed by the management server. As such a system, there is a system described in Patent Document 1.
 特許文献1のシステムは、細胞観察装置及び表示装置が通信ネットワークを介して管理サーバに接続された構成となっている。細胞観察装置は、光学顕微鏡と、該光学顕微鏡の観察視野に位置する対象物(標本スライド)の画像を取得するイメージセンサ(CCDカメラ)と、該イメージセンサが取得した画像をタイリングして対象物全体の画像を生成する画像生成部を備えている。このシステムでは、細胞観察装置において対象物の画像が得られると、その画像データが通信ネットワークを介して管理サーバに送られ、該管理サーバが備えるデータベースに格納される。また、管理サーバは、対象物の画像データに基づき表示装置に表示させるための画像(表示画像)を作成し、このデータをデータベースに格納する。そして、表示装置からの送信要求に応じて表示画像データをデータベースから読み出し、表示装置に送信する。 The system of Patent Document 1 has a configuration in which a cell observation device and a display device are connected to a management server via a communication network. The cell observation apparatus includes an optical microscope, an image sensor (CCD camera) that acquires an image of an object (specimen slide) located in an observation field of the optical microscope, and a tiling image acquired by the image sensor. An image generation unit that generates an image of the entire object is provided. In this system, when an image of an object is obtained in the cell observation device, the image data is sent to a management server via a communication network and stored in a database provided in the management server. The management server creates an image (display image) to be displayed on the display device based on the image data of the object, and stores this data in the database. Then, in response to a transmission request from the display device, display image data is read from the database and transmitted to the display device.
特開2005-117640号公報JP 2005-117640 A
 上述した特許文献1のシステムでは、細胞観察装置において光学顕微鏡による対象物全体の観察画像を作成し、管理サーバにおいて表示装置に表示させるための表示画像を作成する。このため、細胞観察装置において対象物の観察画像及び表示画像の両方を作成する構成に比べると、イメージセンサが取得した画像の処理時間を短縮することができる。しかしながら、ホログラフィ観察装置では、光学顕微鏡を用いた細胞観察装置に比べて高解像度のイメージセンサが用いられており、対象物の観察画像を生成するために必要な画像データの量が大きい。このため、特許文献1のシステムのように、管理サーバで表示画像を作成するようにしても、細胞観察装置の多くで利用されているパーソナルコンピュータのCPUの処理性能では、処理時間を十分に短縮することができない。 In the system of Patent Document 1 described above, an observation image of the entire object using an optical microscope is created in a cell observation device, and a display image for display on a display device is created in a management server. For this reason, compared with the structure which produces both the observation image and display image of a target object in a cell observation apparatus, the processing time of the image which the image sensor acquired can be shortened. However, in the holographic observation apparatus, a high-resolution image sensor is used as compared with a cell observation apparatus using an optical microscope, and the amount of image data necessary for generating an observation image of an object is large. For this reason, even if the display image is created by the management server as in the system of Patent Document 1, the processing time is sufficiently shortened in the processing performance of the CPU of the personal computer used in many cell observation apparatuses. Can not do it.
 また、ホログラフィ観察装置では、培養プレートに収容された細胞を生きたままの状態で観察できるため、細胞観察装置における画像の作成に係る処理時間が長いと、その分、培養プレートが恒温培養槽(いわゆる「インキュベータ」)の外に置かれる時間が長くなり、好ましくない。 In addition, since the holography observation apparatus can observe the cells accommodated in the culture plate as they are alive, if the processing time related to the creation of the image in the cell observation apparatus is long, the culture plate is in a constant temperature culture chamber ( It takes a long time to leave outside the so-called “incubator”), which is not preferable.
 本発明が解決しようとする課題は、通信ネットワークで接続された細胞観察装置及び管理サーバを含む細胞観察システムにおいて、細胞観察装置において実行される処理の負担を軽減するとともに、観察対象物体の画像作成にかかる処理時間を短縮することである。 The problem to be solved by the present invention is a cell observation system including a cell observation device and a management server connected by a communication network, and reduces the burden of processing executed in the cell observation device and creates an image of an observation target object Is to reduce the processing time required.
 上記課題を解決するために成された本発明は、
 細胞観察装置と、該細胞観察装置と通信ネットワークを介して接続された管理サーバとを含む細胞観察システムにおいて、
  前記細胞観察装置が、
 a)コヒーレント性を有する光束を射出する光源と、
 b)前記光源から射出された光束を観察対象物体に照射し、該観察対象物体の異なる位置で透過又は反射した光束を干渉させる照射光学系と、
 c)前記観察対象物体を透過又は反射した光束の干渉像を取得するイメージセンサと、
 d)前記イメージセンサが取得した干渉像のデータを前記通信ネットワークを介して前記管理サーバに送信する送信部と
 を備え、
  前記管理サーバが、
 e) 前記送信部から送信されてきたデータに基づき画像を生成する画像生成部と、
 f) 前記画像生成部により生成された画像情報を記憶するデータ記憶部と、
  を備えることを特徴とする。
The present invention made to solve the above problems
In a cell observation system including a cell observation device and a management server connected to the cell observation device via a communication network,
The cell observation device is
a) a light source that emits a coherent luminous flux;
b) an irradiation optical system that irradiates the observation target object with the light beam emitted from the light source and interferes with the light beam transmitted or reflected at different positions of the observation target object;
c) an image sensor for acquiring an interference image of a light beam transmitted or reflected by the observation object;
d) a transmission unit that transmits data of an interference image acquired by the image sensor to the management server via the communication network, and
The management server is
e) an image generation unit that generates an image based on the data transmitted from the transmission unit;
f) a data storage unit for storing image information generated by the image generation unit;
It is characterized by providing.
 本発明に係る細胞観察システムでは、細胞観察装置の光源からコヒーレント性を有する光束が射出されると、照射光学系によってその光束が観察対象物体に照射され、該観察対象物体の異なる位置で透過又は反射した光束の干渉像が形成される。そして、イメージセンサがこの干渉像を取得すると、送信部は、該干渉像のデータをそのままの状態で(いわゆる「生データ」の状態で)、通信ネットワークを通して管理サーバに送信する。管理サーバにおいては、細胞観察装置の送信部から送られてくる干渉像のデータに基づき画像生成部が画像を生成し、その画像情報をデータ記憶部に記憶する。 In the cell observation system according to the present invention, when a coherent light beam is emitted from the light source of the cell observation device, the irradiation optical system irradiates the light beam on the object to be observed and transmits or transmits the light at a different position of the object to be observed. An interference image of the reflected light beam is formed. When the image sensor acquires the interference image, the transmission unit transmits the interference image data as it is (in a so-called “raw data” state) to the management server through the communication network. In the management server, the image generation unit generates an image based on the interference image data transmitted from the transmission unit of the cell observation device, and stores the image information in the data storage unit.
 なお、前記管理サーバの前記画像生成部は、前記送信部から送信されてきたデータに基づき、前記観察対象物体の位相画像及び光強度画像を生成するようにしても良い。細胞観察装置の送信部から管理サーバに送られてくる干渉像のデータは、いわゆるホログラムデータである。従って、この構成においては、管理サーバの画像生成部は、ホログラムデータから、観察対象物体の位相画像及び光強度画像を構成することになる。 Note that the image generation unit of the management server may generate a phase image and a light intensity image of the observation target object based on the data transmitted from the transmission unit. The data of the interference image transmitted from the transmission unit of the cell observation device to the management server is so-called hologram data. Therefore, in this configuration, the image generation unit of the management server configures the phase image and the light intensity image of the observation target object from the hologram data.
 本発明に係る細胞観察システムは、1台の管理サーバに対して1台の細胞観察装置を接続する構成の他、1台の管理サーバに対して複数台の細胞観察装置を接続する構成とすることができる。また、細胞観察装置の他に1ないし複数台の表示装置が通信ネットワークを通して管理サーバに接続されていても良い。細胞観察装置及び表示装置が通信ネットワークを通して管理サーバに接続された構成の細胞観察システムでは、細胞観察装置と表示装置が同数であっても良く、同数でなくても良い。また、1台の管理サーバに接続される細胞観察装置及び表示装置の一方が1台、他方が複数台であっても良い。 The cell observation system according to the present invention has a configuration in which one cell observation device is connected to one management server, and a plurality of cell observation devices are connected to one management server. be able to. In addition to the cell observation device, one or a plurality of display devices may be connected to the management server through a communication network. In the cell observation system having a configuration in which the cell observation device and the display device are connected to the management server through the communication network, the number of cell observation devices and the number of display devices may or may not be the same. One of the cell observation devices and display devices connected to one management server may be one and the other may be a plurality.
 本発明に係る細胞観察システムが、前記管理サーバと前記通信ネットワークを介して接続された表示装置を備えている場合は、
 前記管理サーバが、前記表示装置からの要求に応じて、前記データ記憶部から画像情報を読み出して該画像情報から表示画像を生成し、該表示画像データを前記通信ネットワークを通して前記表示装置に送信する表示画像生成部を備えることが好ましい。
 この場合、前記表示画像生成部が、前記表示装置からの要求条件を満たした画像情報のみを前記データ記憶部から読み出すようにすることが好ましい。
When the cell observation system according to the present invention includes a display device connected to the management server via the communication network,
In response to a request from the display device, the management server reads image information from the data storage unit, generates a display image from the image information, and transmits the display image data to the display device through the communication network. It is preferable to provide a display image generation unit.
In this case, it is preferable that the display image generation unit reads out only the image information satisfying the request condition from the display device from the data storage unit.
 上記構成によれば、細胞観察装置で観察される画像を該細胞観察装置とは別に設けられた表示装置で閲覧する際に、該表示装置に表示させるための画像を管理サーバで生成することができるため、表示装置の負荷を低減することができる。 According to the above configuration, when an image observed by the cell observation device is viewed on a display device provided separately from the cell observation device, an image to be displayed on the display device can be generated by the management server. Therefore, the load on the display device can be reduced.
 ところで、観察対象物体の計測や解析を行う場合、該観察対象物の画像をそのまま表示するのではなく、該観察対象物の画像に何らかの加工を施した画像を用いた方が良い場合がある。 
 そこで、前記表示画像生成部が、前記データ記憶部から読み出した画像情報に基づき、前記画像生成部が生成した画像を加工することにより前記表示画像を生成する加工画像生成部を備えるようにしても良い。ここで、「加工」とは、タイリングやトリミング、リサイズ等の加工をいう。
By the way, when performing measurement or analysis of an observation target object, it may be better to use an image obtained by performing some processing on the image of the observation target object instead of displaying the image of the observation target object as it is.
Therefore, the display image generation unit may include a processed image generation unit that generates the display image by processing the image generated by the image generation unit based on the image information read from the data storage unit. good. Here, “processing” refers to processing such as tiling, trimming, and resizing.
 また、本発明に係る細胞観察システムでは、前記表示画像生成部が、前記データ記憶部から読み出した画像情報に基づき、前記観察対象物体の全体又は一部の領域の画像である部分画像を生成する部分画像生成部を備えるようにしても良い。 In the cell observation system according to the present invention, the display image generation unit generates a partial image that is an image of the whole or a part of the observation target object based on the image information read from the data storage unit. A partial image generation unit may be provided.
 さらに、前記表示画像生成部が、前記データ記憶部から読み出した画像情報に基づき、前記観察対象物体の全体又は一部の領域を拡大又は縮小した画像を生成する倍率変更画像生成部を備えるようにしても良い。この構成によれば、観察対象物体のうち計測又は解析したい領域の画像を適宜の倍率に拡大又は縮小した画像を表示装置に表示させることができる。 Further, the display image generation unit includes a magnification change image generation unit that generates an image in which an entire or a partial region of the observation target object is enlarged or reduced based on the image information read from the data storage unit. May be. According to this configuration, an image obtained by enlarging or reducing an image of an area to be measured or analyzed in the observation target object at an appropriate magnification can be displayed on the display device.
 細胞観察装置において、観察対象物全体の干渉像を一度にイメージセンサが取得することができない場合、該観察対象物を複数に分割した領域毎の干渉像をイメージセンサが取得し、そのデータを管理サーバに送ることになる。このような構成の細胞観察システムにおいては、観察対象物全体の干渉像のデータをイメージセンサが取得してから、該データをまとめて管理サーバに送信しても良いが、前記イメージセンサがデータを取得する毎に、前記送信部が当該データを前記通信ネットワークを介して前記管理サーバに送信することが好ましい。 In the cell observation device, when the image sensor cannot acquire an interference image of the entire observation object at once, the image sensor acquires an interference image for each region obtained by dividing the observation object into a plurality of parts, and manages the data. Will be sent to the server. In the cell observation system having such a configuration, after the image sensor acquires the interference image data of the entire observation object, the data may be collectively transmitted to the management server. It is preferable that the transmission unit transmits the data to the management server via the communication network every time it is acquired.
 また、前記細胞観察装置が、前記イメージセンサを複数備え、
 前記複数のイメージセンサの各々で取得されたデータを前記送信部が前記通信ネットワークを介して同時に前記管理サーバに送信することが好ましい。
The cell observation device includes a plurality of the image sensors,
It is preferable that the transmission unit simultaneously transmits data acquired by each of the plurality of image sensors to the management server via the communication network.
 前記イメージセンサとして、フォトダイオードを光電変換素子として使用したCMOSイメージセンサやCCDイメージセンサ等の固体撮像素子を利用することができる。この場合、複数のフォトダイオードを二次元に配置したエリアイメージセンサを用いることが好ましいが、フォトダイオードを一次元配置したラインイメージセンサを用いることも可能である。ラインイメージセンサを用いる場合は、フォトダイオードの配置方向と直交する方向にラインイメージセンサを移動させる移動手段を備えると良い。 As the image sensor, a solid-state image sensor such as a CMOS image sensor or a CCD image sensor using a photodiode as a photoelectric conversion element can be used. In this case, it is preferable to use an area image sensor in which a plurality of photodiodes are two-dimensionally arranged, but it is also possible to use a line image sensor in which photodiodes are one-dimensionally arranged. In the case of using a line image sensor, it is preferable to provide moving means for moving the line image sensor in a direction orthogonal to the arrangement direction of the photodiodes.
 また、本発明に係る細胞観察システムにおいては、
 前記光源が、異なる複数の波長の光束を出射可能に構成されており、該光源が出射する光束の波長を変化させる波長変更部を備えることが好ましい。
 この構成によれば、観察対象物体の光学特性(吸収波長、透過波長など)に応じた適宜の波長の光束を光源から出射して観察対象物体に照射することができる。
In the cell observation system according to the present invention,
It is preferable that the light source is configured to emit light beams having a plurality of different wavelengths, and includes a wavelength changing unit that changes the wavelength of the light beams emitted from the light source.
According to this configuration, it is possible to emit a light beam having an appropriate wavelength according to the optical characteristics (absorption wavelength, transmission wavelength, etc.) of the observation target object and irradiate the observation target object.
 本発明に係る細胞観察システムによれば、細胞観察装置のイメージセンサが干渉像を取得すると、そのデータが管理サーバに送られ、そこで画像が生成されるため、細胞観察装置において実行される処理の負担を軽減することができるとともに、画像生成の処理時間を短縮することができる。 According to the cell observation system of the present invention, when the image sensor of the cell observation device acquires the interference image, the data is sent to the management server, and an image is generated there. The burden can be reduced and the processing time for image generation can be shortened.
本発明の一実施例である細胞観察システムの全体構成図。BRIEF DESCRIPTION OF THE DRAWINGS The whole block diagram of the cell observation system which is one Example of this invention. 本実施例の細胞観察システムにおける細胞観察端末の概略構成図。The schematic block diagram of the cell observation terminal in the cell observation system of a present Example. 本実施例の細胞観察システムにおける管理装置の概略構成図。The schematic block diagram of the management apparatus in the cell observation system of a present Example. 本実施例の細胞観察システムにおけるデータや指示の流れを示す模式図。The schematic diagram which shows the flow of the data and instruction | indication in the cell observation system of a present Example. 本実施例の細胞観察システムにおいて作成される表示画像の例を示す図。The figure which shows the example of the display image produced in the cell observation system of a present Example.
 以下、本発明に係る細胞観察システムの一実施例を図面を参照して説明する。 Hereinafter, an embodiment of a cell observation system according to the present invention will be described with reference to the drawings.
 図1は、本実施例に係る細胞観察システムの全体構成を示す概略図である。インターネット等の通信ネットワーク1には複数の細胞観察端末2A、2B、2C・・・(以下、個々の細胞観察端末を特定する必要がある場合を除いて、細胞観察端末の符号を「2」とする)が接続されている。各細胞観察端末2は、顕微観察部21と、通信ネットワーク1に接続されたパーソナルコンピュータ(PC)22とを含む。細胞観察端末2が本発明の細胞観察装置に相当する。 FIG. 1 is a schematic diagram showing the overall configuration of the cell observation system according to the present example. The communication network 1 such as the Internet includes a plurality of cell observation terminals 2A, 2B, 2C (hereinafter referred to as “2” unless the individual cell observation terminals need to be specified). Connected). Each cell observation terminal 2 includes a microscope observation unit 21 and a personal computer (PC) 22 connected to the communication network 1. The cell observation terminal 2 corresponds to the cell observation device of the present invention.
 通信ネットワーク1にはさらに、管理サーバ3(以下、サーバ3と略記する)と表示装置4が接続されている。サーバ3は一般的には高性能なコンピュータであり、細胞観察端末2から送られてくるデータを受信する受信部31と、大容量のデータを格納可能であるデータ記憶部32と、該コンピュータにインストールされたソフトウエアを実行することで具現化されるデータ処理部33を機能ブロックとして備える。 A management server 3 (hereinafter abbreviated as “server 3”) and a display device 4 are further connected to the communication network 1. The server 3 is generally a high-performance computer, and includes a receiving unit 31 that receives data transmitted from the cell observation terminal 2, a data storage unit 32 that can store a large amount of data, and the computer. A data processing unit 33 that is embodied by executing installed software is provided as a functional block.
 表示装置4は、閲覧用コンピュータ41と、該閲覧用コンピュータ41に付設されたマウスやキーボード等の入力部42及び表示部43を備えている。閲覧用コンピュータ41は一般的なパーソナルコンピュータであって、基本ソフトウエアとして標準的なOSと、そのOS上で動作する様々なソフトウエア(例えばサーバ3との間で双方向通信を行うための通信制御プログラム、入力部42の動作を制御する入力制御プログラム、表示部43の動作を制御するための表示制御プログラム)がインストールされている。また、閲覧用コンピュータ41は、サーバ3から送信されてくる表示画像等のデータを格納する記憶部(図示せず)を備えている。サーバ3と閲覧用コンピュータ41とはLAN等のイントラネット(又はインターネット)で相互に接続されている。
 なお、サーバ3と閲覧用コンピュータ41の接続はイントラネットに限らず、通信ネットワーク1を介して両者を接続しても良い。
The display device 4 includes a browsing computer 41, an input unit 42 such as a mouse and a keyboard attached to the browsing computer 41, and a display unit 43. The browsing computer 41 is a general personal computer, and a standard OS as basic software and various software (for example, communication for performing bidirectional communication with the server 3) operating on the OS. A control program, an input control program for controlling the operation of the input unit 42, and a display control program for controlling the operation of the display unit 43) are installed. Further, the browsing computer 41 includes a storage unit (not shown) that stores data such as a display image transmitted from the server 3. The server 3 and the browsing computer 41 are connected to each other via an intranet (or the Internet) such as a LAN.
The connection between the server 3 and the browsing computer 41 is not limited to the intranet, and both may be connected via the communication network 1.
 本実施例では、顕微観察部21はIHM(In-line Holographic Microscopy)から成るホログラフィ顕微鏡を含む。すなわち、図2に示すように、顕微観察部21は、光源部211、イメージセンサ212及び移動機構214を備えている。光源部211は、複数の異なる波長のレーザ光を射出するレーザダイオード211aと、該レーザ光を微小角度(約10度)の拡がりを持つコヒーレント光束として観察対象物体としての培養プレート213に照射する照射光学系211bを備えている。イメージセンサ212は、例えばCMOS(Complementary metal oxide semiconductor)イメージセンサが用いられている。この場合、顕微観察部21は1個のイメージセンサ212を備えても良いが、複数個のイメージセンサ212を備えるようにしても良い。本実施例では、図2の紙面手前側と奥側にそれぞれ2個ずつ、計4個のイメージセンサが設けられている(図2では紙面手前側の2個のイメージセンサのみ示す)。 In the present embodiment, the microscopic observation unit 21 includes a holographic microscope made of IHM (In-line Holographic Microscopy). That is, as shown in FIG. 2, the microscopic observation unit 21 includes a light source unit 211, an image sensor 212, and a moving mechanism 214. The light source unit 211 emits a laser diode 211a that emits a plurality of laser beams of different wavelengths, and irradiation that irradiates the culture plate 213 as an observation target object as a coherent light beam having a spread of a minute angle (about 10 degrees). An optical system 211b is provided. As the image sensor 212, for example, a CMOS (Complementary Metal Oxide Semiconductor) image sensor is used. In this case, the microscopic observation unit 21 may include one image sensor 212, but may include a plurality of image sensors 212. In the present embodiment, a total of four image sensors are provided, two on the front side and the back side in FIG. 2 (only two image sensors on the front side of the paper are shown in FIG. 2).
 IHM光学系では、光源部211から発せられるコヒーレント光束は培養プレート213の所定の領域に照射される。そして、細胞S及び培養プレート213を透過したコヒーレント光束内の光(物体光)は、培養プレート213上の細胞Sの隣接位置を透過した光(参照光)と干渉しつつイメージセンサ212に到達する。この結果、イメージセンサ212の検出面(像面)上に、細胞S及び培養プレート213を透過した光と、培養プレート213上の細胞Sの隣接位置を透過した光の干渉像(ホログラム)が形成される。
 光源部211及びイメージセンサ212は例えば移動機構214によりXY方向(例えば図2の紙面に垂直及び平行な方向)に一体的に移動される。これにより、光源部211から発せられるコヒーレント光束の培養プレート213における照射領域(観察領域)を移動させて各観察領域のホログラムを取得することができる。
In the IHM optical system, a coherent light beam emitted from the light source unit 211 is applied to a predetermined region of the culture plate 213. Then, the light (object light) in the coherent light beam transmitted through the cell S and the culture plate 213 reaches the image sensor 212 while interfering with the light (reference light) transmitted through the adjacent position of the cell S on the culture plate 213. . As a result, on the detection surface (image surface) of the image sensor 212, an interference image (hologram) of the light transmitted through the cell S and the culture plate 213 and the light transmitted through the adjacent position of the cell S on the culture plate 213 is formed. Is done.
The light source unit 211 and the image sensor 212 are integrally moved in the XY direction (for example, the direction perpendicular to and parallel to the paper surface of FIG. 2) by the moving mechanism 214, for example. Thereby, the irradiation area (observation area | region) in the culture plate 213 of the coherent light beam emitted from the light source part 211 can be moved, and the hologram of each observation area | region can be acquired.
 細胞観察端末2に含まれるPC22は一般的なパーソナルコンピュータであって、基本ソフトウエアとして標準的なOSが搭載され、さらにそのOS上で動作する様々なソフトウエアがインストールされている。PC22は記憶部220を備え、また、インストールされているソフトウエアを実行することで実現される機能ブロックとして、レーザダイオード211aが出射するレーザ光の波長を変更する等、光源部211の動作を制御する光源制御部221と、移動機構214を制御する移動制御部222と、データ送信部223とを備えている。データ送信部223は、イメージセンサ212で取得された観察領域のホログラムデータ(イメージセンサ212の検出面で形成されたホログラムの2次元的な光強度分布データ)を、培養プレート213の識別情報とともにサーバ3に送信する。また、PC22には入力部23と表示部24が接続されている。 The PC 22 included in the cell observation terminal 2 is a general personal computer, which is equipped with a standard OS as basic software, and further installed with various software operating on the OS. The PC 22 includes a storage unit 220, and controls the operation of the light source unit 211, such as changing the wavelength of the laser beam emitted from the laser diode 211a, as a functional block realized by executing installed software. A light source control unit 221 that controls the movement mechanism 214, and a data transmission unit 223. The data transmission unit 223 transmits the hologram data of the observation area acquired by the image sensor 212 (two-dimensional light intensity distribution data of the hologram formed on the detection surface of the image sensor 212) together with the identification information of the culture plate 213 to the server. 3 to send. An input unit 23 and a display unit 24 are connected to the PC 22.
 図3に示すように、サーバ3に含まれる受信部31は、細胞観察端末2から送られてくる培養プレート213の識別情報が付されたホログラムデータを、細胞観察端末毎に受信し、データ記憶部32に格納する。また、データ処理部33は、機能ブロックとしての演算処理部331、画像タイリング部332、画像分割部333、指示受付部334、情報読出部335とを含む。 As shown in FIG. 3, the receiving unit 31 included in the server 3 receives hologram data with identification information of the culture plate 213 sent from the cell observation terminal 2 for each cell observation terminal, and stores the data. Stored in the unit 32. The data processing unit 33 includes an arithmetic processing unit 331 as a functional block, an image tiling unit 332, an image dividing unit 333, an instruction receiving unit 334, and an information reading unit 335.
 演算処理部331は、データ記憶部32からホログラムデータを読み出し、所定の演算処理を実行し、該ホログラムデータから各観察領域の位相情報、強度情報、擬似位相情報を取得する。そして、これらの情報に基づき3種類の観察画像(位相像、強度像、擬似位相像)を作成する。このほか、演算処理部331は、画像データの一般的な処理(例えば画像の解像度の変更処理、画像の拡大/縮小処理)を実行する。 The calculation processing unit 331 reads the hologram data from the data storage unit 32, executes predetermined calculation processing, and acquires phase information, intensity information, and pseudo phase information of each observation region from the hologram data. Based on these pieces of information, three types of observation images (phase image, intensity image, and pseudo phase image) are created. In addition, the arithmetic processing unit 331 executes general processing of image data (for example, image resolution change processing, image enlargement / reduction processing).
 画像タイリング部332は、1個の培養プレート213について複数の観察領域が設定された場合に、それら複数の観察領域のホログラムデータに基づき前記演算処理部331で得られた観察画像をトリミングするとともに、トリミングした観察画像を貼り合わせて(タイリング)、培養プレート213全体の観察画像(タイリング画像)を作成する。
 また、画像分割部333は、培養プレート213の一部の観察領域について得られた観察画像、又は培養プレート213全体の観察画像を複数に分割した部分観察画像を作成する。画像タイリング部332で作成されたタイリング画像、画像分割部333で作成された部分観察画像のデータは、培養プレート213の識別情報とともに前記データ記憶部32に記憶される。
When a plurality of observation regions are set for one culture plate 213, the image tiling unit 332 trims the observation image obtained by the arithmetic processing unit 331 based on the hologram data of the plurality of observation regions. Then, the trimmed observation images are pasted together (tiling) to create an observation image (tiling image) of the entire culture plate 213.
Further, the image dividing unit 333 creates an observation image obtained for a part of the observation region of the culture plate 213 or a partial observation image obtained by dividing the observation image of the entire culture plate 213 into a plurality of pieces. The data of the tiling image created by the image tiling unit 332 and the partial observation image created by the image dividing unit 333 are stored in the data storage unit 32 together with the identification information of the culture plate 213.
 指示受付部334は、閲覧用コンピュータ41から到来する表示画像の送信要求指示を受け付ける。情報読出部335は、データ記憶部32にアクセスして、指示受付部334が受け付けた指示に応じた条件に適合するデータや情報を読み出す。 The instruction receiving unit 334 receives a display image transmission request instruction coming from the browsing computer 41. The information reading unit 335 accesses the data storage unit 32 and reads data and information that meet the conditions according to the instruction received by the instruction receiving unit 334.
 次に、上記構成の細胞観察システムの特徴的な動作の一例を図4を参照しつつ説明する。図4は、細胞観察端末2において得られたホログラムデータに基づき画像データを作成したり、閲覧用コンピュータ41からの指示に応じて表示画像データを作成したりする際の動作におけるデータや指示の流れを示す模式図である。 Next, an example of a characteristic operation of the cell observation system having the above configuration will be described with reference to FIG. FIG. 4 shows the flow of data and instructions in the operation when creating image data based on the hologram data obtained in the cell observation terminal 2 or creating display image data in response to an instruction from the browsing computer 41. It is a schematic diagram which shows.
 細胞観察端末2において、作業者が入力部23を操作して培養プレート213に関する識別情報(測定日、培養細胞の種類等)を入力するとともに動作開始を指示すると、光源部211から発せられた所定の波長及び可干渉距離を有するレーザ光束(コヒーレント光束)が、顕微観察部21にセットされた培養プレート213上に照射される。その結果、イメージセンサ212の検出面に、細胞S及び培養プレート213を透過したコヒーレント光束内の光と、培養プレート213上の細胞Sの隣接位置を透過した光の干渉像(ホログラム)が形成される。イメージセンサ212において測定された、ホログラムの2次元的な光強度分布のデータ(ホログラムデータ)は、PC22の記憶部220内に作成された、培養プレート213の識別情報が付されたデータファイルに格納される。続いて、移動機構214によって光源部211及びイメージセンサ212が移動され、次の観察領域のホログラムデータがイメージセンサ212によって取得され、記憶部220のデータファイルに格納される。 In the cell observation terminal 2, when the operator operates the input unit 23 to input identification information (measurement date, type of cultured cell, etc.) regarding the culture plate 213 and instruct to start the operation, a predetermined light emitted from the light source unit 211 is given. A laser beam (coherent beam) having a wavelength and a coherent distance is irradiated onto the culture plate 213 set in the microscopic observation unit 21. As a result, an interference image (hologram) of the light in the coherent light beam that has passed through the cells S and the culture plate 213 and the light that has passed through the adjacent position of the cells S on the culture plate 213 is formed on the detection surface of the image sensor 212. The The hologram two-dimensional light intensity distribution data (hologram data) measured by the image sensor 212 is stored in a data file with identification information of the culture plate 213 created in the storage unit 220 of the PC 22. Is done. Subsequently, the light source unit 211 and the image sensor 212 are moved by the moving mechanism 214, and hologram data of the next observation area is acquired by the image sensor 212 and stored in the data file of the storage unit 220.
 培養プレート213全体のホログラムデータが記憶部220内のデータファイルに格納されると、細胞観察端末2のPC22では、データ送信部223が記憶部220からデータファイルを読み出し、細胞観察端末2の識別情報を付してサーバ3に送信する。この場合、細胞観察端末2のPC22は、記憶部220に格納されている全てのデータファイルをサーバ3に送信することも可能であるが、特定の識別情報に対応する培養プレート213のデータファイルのみをサーバ3に送信することももちろん可能である。どのようなデータファイルを細胞観察端末2からサーバ3に送信するかは、作業者が入力部23を操作して指示することができる。また、表示装置4の入力部42を操作することにより、サーバ3、通信ネットワーク1を通して細胞観察端末2のPC22に指示するようにしても良い。 When the hologram data of the entire culture plate 213 is stored in the data file in the storage unit 220, in the PC 22 of the cell observation terminal 2, the data transmission unit 223 reads the data file from the storage unit 220, and the identification information of the cell observation terminal 2 is obtained. Is sent to the server 3. In this case, the PC 22 of the cell observation terminal 2 can transmit all data files stored in the storage unit 220 to the server 3, but only the data file of the culture plate 213 corresponding to specific identification information. It is of course possible to transmit to the server 3. The operator can instruct what data file is transmitted from the cell observation terminal 2 to the server 3 by operating the input unit 23. Further, by operating the input unit 42 of the display device 4, the PC 22 of the cell observation terminal 2 may be instructed through the server 3 and the communication network 1.
 サーバ3の受信部31は、細胞観察端末2からのデータファイルを受信すると、データ処理部33において、演算処理部331がデータファイルに含まれるホログラムデータの位相回復処理、トリミング処理、タイリング処理を実行する。これにより、各観察領域の画像(オリジナル画像)、培養プレート213全体の画像、その他、適宜の数に培養プレート213を分割した画像(例えば1/4分割画像、1/2分割画像)が作成される。作成された画像のデータは、細胞観察端末2及び培養プレート213の識別情報とともにデータ記憶部32に格納される。 When the receiving unit 31 of the server 3 receives the data file from the cell observation terminal 2, in the data processing unit 33, the arithmetic processing unit 331 performs phase recovery processing, trimming processing, and tiling processing of the hologram data included in the data file. Execute. As a result, an image of each observation region (original image), an image of the entire culture plate 213, and other images obtained by dividing the culture plate 213 into an appropriate number (for example, 1/4 divided image and 1/2 divided image) are created. The The created image data is stored in the data storage unit 32 together with the identification information of the cell observation terminal 2 and the culture plate 213.
 一方、培養プレート213に収容されている培養細胞の計測及び解析を行う作業者が、表示装置4の入力部42から、細胞観察端末2及び培養プレート213の種類等を指定した上で、その観察画像の送信を要求すると、サーバ3の情報読出部335は、データ記憶部32に格納されている画像データの中から、指定された細胞観察端末2及び培養プレート213の全体観察画像又は部分観察画像のデータを抽出し、閲覧用コンピュータ41に送信する。この場合、画像データのサイズに応じて演算処理部331が解像度を低く変更する処理を行ってから、閲覧用コンピュータ41に送信しても良い。閲覧用コンピュータ41は、送信された画像を表示部43に表示する。 On the other hand, an operator who measures and analyzes the cultured cells accommodated in the culture plate 213 designates the types of the cell observation terminal 2 and the culture plate 213 from the input unit 42 of the display device 4, and then observes them. When requesting the transmission of the image, the information reading unit 335 of the server 3 selects the entire observation image or partial observation image of the designated cell observation terminal 2 and culture plate 213 from the image data stored in the data storage unit 32. Are extracted and transmitted to the browsing computer 41. In this case, the arithmetic processing unit 331 may perform processing for changing the resolution to be lower according to the size of the image data, and then may be transmitted to the browsing computer 41. The browsing computer 41 displays the transmitted image on the display unit 43.
 続いて、作業者が閲覧用コンピュータ41の入力部42を操作して、表示部43に表示されている培養プレート213の画像の一部の領域を選択するとともに、表示したい画像の情報(解像度、倍率、画像の種類(位相像、強度像、擬似位相像)等)を指定して、表示画像の作成を要求する。すると、サーバ3のデータ処理部33において、指示受付部334は、閲覧用コンピュータ41からの表示画像作成要求に応じて読み出すべき情報及び画像データを確定し、情報読出部335に出力する。情報読出部335は、データ記憶部32にアクセスして必要な情報及び画像データを読み出して演算処理部331に送る。演算処理部331では、送られてきた情報及び画像データに基づき、所定の処理(トリミング、拡大/縮小処理)を実行して表示画像を作成する。 Subsequently, the operator operates the input unit 42 of the browsing computer 41 to select a partial region of the image of the culture plate 213 displayed on the display unit 43 and information on the image (resolution, Specify the magnification, image type (phase image, intensity image, pseudo phase image, etc.) and request the creation of a display image. Then, in the data processing unit 33 of the server 3, the instruction receiving unit 334 determines information and image data to be read in response to a display image creation request from the browsing computer 41 and outputs the information and image data to the information reading unit 335. The information reading unit 335 accesses the data storage unit 32 to read out necessary information and image data and sends them to the arithmetic processing unit 331. The arithmetic processing unit 331 executes a predetermined process (trimming / enlargement / reduction process) based on the sent information and image data to create a display image.
 演算処理部331において表示画像の作成が終了すると、サーバ3は、その表示画像のデータを閲覧用コンピュータ41に送信する。表示画像を受信した閲覧用コンピュータ41は、その表示画像を表示部43に表示する。 When the creation of the display image is completed in the arithmetic processing unit 331, the server 3 transmits the data of the display image to the browsing computer 41. The browsing computer 41 that has received the display image displays the display image on the display unit 43.
 図5は、細胞観察端末2で取得されたデータに基づき、サーバ3の演算処理部331で作成された表示画像を模式的に示したものである。図5の左上の図は、培養プレート213と4個のイメージセンサ212の観察領域との関係を示している。この図に示すように、4個のイメージセンサ212は、それぞれ培養プレート213全体の1/4の領域a1~a4を透過した光束の干渉像を取得する。従って、培養プレート213が6個のウェルを有する場合、1個のイメージセンサ212が取得したデータから、1.5個分のウェルの観察画像が作成される。イメージセンサ212が160個(12×14)の画素を有する場合、1.5個分のウェルを160区画に分割した画像がイメージセンサ212によって取得される(図5の左下図参照)。このようにして得られた160区画分の画像データから1.5個分のウェルの観察画像を作成し、該1.5個分のウェルの観察画像をトリミングすることで1個のウェルの観察画像を得ることができる。また、4個のイメージセンサ212によって取得された画像データから、培養プレート213全体の観察画像が作成される。 FIG. 5 schematically shows a display image created by the arithmetic processing unit 331 of the server 3 based on the data acquired by the cell observation terminal 2. The upper left diagram in FIG. 5 shows the relationship between the culture plate 213 and the observation areas of the four image sensors 212. As shown in this figure, each of the four image sensors 212 acquires interference images of light beams that have passed through the quarter regions a1 to a4 of the entire culture plate 213. Therefore, when the culture plate 213 has six wells, observation images of 1.5 wells are created from the data acquired by one image sensor 212. When the image sensor 212 has 160 (12 × 14) pixels, an image obtained by dividing 1.5 wells into 160 sections is acquired by the image sensor 212 (see the lower left diagram in FIG. 5). An observation image of 1.5 wells is created from the image data of 160 sections obtained in this way, and the observation image of one well is trimmed from the observation image of 1.5 wells. An image can be obtained. An observation image of the entire culture plate 213 is created from the image data acquired by the four image sensors 212.
 図5の中央及び右部は、演算処理部331で作成された表示画像の例を示しており、中央は1区画分の画像(分割画像)を、右部はこの分割画像の一部の拡大画像を示している。 The center and the right part of FIG. 5 show examples of display images created by the arithmetic processing unit 331. The center is an image (divided image) for one section, and the right part is an enlargement of a part of this divided image. An image is shown.
 このように本実施例では、イメージセンサ212で取得されたデータをそのままサーバ3に送信するようにしたため、データ送信にかかる時間を短縮することができる。また、サーバ3において、イメージセンサ212で取得されたデータを処理して画像を作成することにより、細胞観察端末2において画像を作成するよりも、細胞観察端末2において実行される処理の負担を軽減することができるとともに、画像作成にかかる処理時間を短縮することができる。 Thus, in this embodiment, since the data acquired by the image sensor 212 is transmitted to the server 3 as it is, the time required for data transmission can be shortened. Further, the server 3 processes the data acquired by the image sensor 212 to create an image, thereby reducing the burden of processing executed in the cell observation terminal 2 as compared to creating an image in the cell observation terminal 2. It is possible to shorten the processing time required for image creation.
 なお、本発明は上記した実施例に限定されるものではなく、適宜の修正・変更が可能である。
 上記実施例では、培養プレート213全体のホログラムデータをまとめてサーバ3に送信するようにしたが、観察領域毎にホログラムデータを取得次第、そのホログラムデータをサーバ3に送信するようにしても良い。
 細胞観察端末2では、顕微観察部21とは別のパーソナルコンピュータ22によって顕微観察部21の制御部(光源制御部、移動機構制御部)や記憶部を実現するようにしたが、顕微観察部21が記憶部や制御部を内蔵するようにしても良い。
The present invention is not limited to the above-described embodiments, and appropriate modifications and changes can be made.
In the above embodiment, the hologram data of the entire culture plate 213 is collectively transmitted to the server 3. However, the hologram data may be transmitted to the server 3 as soon as the hologram data is acquired for each observation region.
In the cell observation terminal 2, the control unit (light source control unit, moving mechanism control unit) and storage unit of the microscopic observation unit 21 are realized by a personal computer 22 different from the microscopic observation unit 21. However, a storage unit or a control unit may be incorporated.
 上記実施例では、画像分割部333が、画像タイリング部332が作成した培養プレート213の観察画像を分割して部分観察画像を作成するようにしたが、画像タイリング部332が作成するようにしても良い。つまり、画像タイリング部332が、培養プレート213の一部の領域を構成する複数の観察領域のホログラムデータを貼り合わせることにより部分観察画像を作成することも可能である。この場合は、画像分割部333を省略することができる。
 細胞観察部21が、観察対象物体の一部の領域を観察視野とする1個のイメージセンサを備え、このイメージセンサを観察対象物体に対して相対的に移動させることにより、該観察対象物体全体の画像を取得するようにしても良い。
In the above embodiment, the image dividing unit 333 divides the observation image of the culture plate 213 created by the image tiling unit 332 to create a partial observation image. However, the image tiling unit 332 creates the image. May be. That is, the image tiling unit 332 can also create a partial observation image by pasting together hologram data of a plurality of observation regions that constitute a partial region of the culture plate 213. In this case, the image dividing unit 333 can be omitted.
The cell observation unit 21 includes one image sensor that uses a partial region of the observation target object as an observation field, and moves the image sensor relative to the observation target object, so that the entire observation target object is displayed. You may make it acquire the image of.
1…通信ネットワーク
2、2A、2B、2C…細胞観察端末(細胞観察装置)
 21…顕微観察部(細胞画像取得部、ホログラフィ顕微鏡)
  211…光源部
  212…イメージセンサ
  213…培養プレート(観察対象物体)
  214…移動機構
 22…パーソナルコンピュータ
  220…記憶部
  221…光源制御部
  222…移動制御部
  223…データ送信部
 23…入力部
 24…表示部
3…サーバ(管理サーバ)
 31…受信部
 32…データ記憶部
 33…データ処理部
  331…演算処理部
  332…画像タイリング部
  333…画像分割部
  334…指示受付部
  335…情報読出部
4…表示装置
 41…閲覧用コンピュータ
 42…入力部
 43…表示部
1 ... Communication network 2, 2A, 2B, 2C ... Cell observation terminal (cell observation device)
21 ... Microscopic observation part (cell image acquisition part, holographic microscope)
211: Light source 212: Image sensor 213: Culture plate (object to be observed)
DESCRIPTION OF SYMBOLS 214 ... Movement mechanism 22 ... Personal computer 220 ... Memory | storage part 221 ... Light source control part 222 ... Movement control part 223 ... Data transmission part 23 ... Input part 24 ... Display part 3 ... Server (management server)
DESCRIPTION OF SYMBOLS 31 ... Reception part 32 ... Data storage part 33 ... Data processing part 331 ... Arithmetic processing part 332 ... Image tiling part 333 ... Image division part 334 ... Instruction reception part 335 ... Information reading part 4 ... Display apparatus 41 ... Computer 42 for browsing 42 ... Input part 43 ... Display part

Claims (10)

  1.  細胞観察装置と、該細胞観察装置と通信ネットワークを介して接続された管理サーバとを含む細胞観察システムにおいて、
      前記細胞観察装置が、
     a)コヒーレント性を有する光束を射出する光源と、
     b)前記光源から射出された光束を観察対象物体に照射し、該観察対象物体の異なる位置で透過又は反射した光束を干渉させる照射光学系と、
     c)前記観察対象物体を透過又は反射した光束の干渉像を取得するイメージセンサと、
     d)前記イメージセンサが取得した干渉像のデータを前記通信ネットワークを介して前記管理サーバに送信する送信部と
     を備え、
      前記管理サーバが、
     e) 前記送信部から送信されてきたデータに基づき画像を生成する画像生成部と、
     f) 前記画像生成部により生成された画像情報を記憶するデータ記憶部と、
      を備えることを特徴とする細胞観察システム。
    In a cell observation system including a cell observation device and a management server connected to the cell observation device via a communication network,
    The cell observation device is
    a) a light source that emits a coherent luminous flux;
    b) an irradiation optical system that irradiates the observation target object with the light beam emitted from the light source and interferes with the light beam transmitted or reflected at different positions of the observation target object;
    c) an image sensor for acquiring an interference image of a light beam transmitted or reflected by the observation object;
    d) a transmission unit that transmits data of an interference image acquired by the image sensor to the management server via the communication network, and
    The management server is
    e) an image generation unit that generates an image based on the data transmitted from the transmission unit;
    f) a data storage unit for storing image information generated by the image generation unit;
    A cell observation system comprising:
  2.  請求項1の細胞観察システムにおいて、
     前記管理サーバの前記画像生成部が、前記送信部から送信されてきたデータに基づき前記観察対象物体の位相画像、光強度画像を生成することを特徴とする細胞観察システム。
    The cell observation system according to claim 1, wherein
    The cell observation system, wherein the image generation unit of the management server generates a phase image and a light intensity image of the observation object based on data transmitted from the transmission unit.
  3.  請求項1の細胞観察システムにおいて、
     前記管理サーバと前記通信ネットワークを介して接続された表示装置を備え、
     前記管理サーバが、前記表示装置からの要求に応じて、前記データ記憶部から画像情報を読み出して該画像情報から表示画像を生成し、該表示画像データを前記通信ネットワークを通して前記表示装置に送信する表示画像生成部を備えることを特徴とする細胞観察システム。
    The cell observation system according to claim 1, wherein
    A display device connected to the management server via the communication network;
    In response to a request from the display device, the management server reads image information from the data storage unit, generates a display image from the image information, and transmits the display image data to the display device through the communication network. A cell observation system comprising a display image generation unit.
  4.  請求項3の細胞観察システムにおいて、
     前記表示画像生成部が、前記表示装置の要求条件に合う所定の画像情報を前記データ記憶部から読み出すことを特徴とする細胞観察システム。 
    The cell observation system according to claim 3,
    The cell observation system, wherein the display image generation unit reads predetermined image information that meets a requirement condition of the display device from the data storage unit.
  5.  請求項3の細胞観察システムにおいて、
     前記表示画像生成部が、前記データ記憶部から読み出した画像情報に基づき、前記画像生成部により生成された画像を加工した加工画像を生成する加工画像生成部を備えることを特徴とする細胞観察システム。
    The cell observation system according to claim 3,
    The cell observation system, wherein the display image generation unit includes a processed image generation unit that generates a processed image obtained by processing the image generated by the image generation unit based on image information read from the data storage unit .
  6.  請求項3の細胞観察システムにおいて、
     前記表示画像生成部が、前記データ記憶部から読み出した画像情報に基づき、前記観察対象物体の全体又は一部の領域の画像である部分画像を生成する部分画像生成部を備えることを特徴とする細胞観察システム。
    The cell observation system according to claim 3,
    The display image generation unit includes a partial image generation unit that generates a partial image that is an image of the whole or a part of the observation target object based on image information read from the data storage unit. Cell observation system.
  7.  請求項3の細胞観察システムにおいて、
     前記表示画像生成部が、前記データ記憶部から読み出した画像情報に基づき、前記観察対象物体の全体又は一部の領域を拡大又は縮小した画像を生成する倍率変更画像生成部を備えることを特徴とする細胞観察システム。
    The cell observation system according to claim 3,
    The display image generation unit includes a magnification change image generation unit that generates an image obtained by enlarging or reducing the whole or a partial region of the observation target object based on image information read from the data storage unit. Cell observation system.
  8.  請求項1の細胞観察システムにおいて、
     前記イメージセンサがデータを取得する毎に、前記送信部が当該データを前記通信ネットワークを介して前記管理サーバに送信することを特徴とする細胞観察システム。
    The cell observation system according to claim 1, wherein
    Each time the image sensor acquires data, the transmission unit transmits the data to the management server via the communication network.
  9.  請求項1の細胞観察システムにおいて、
     前記細胞観察装置が、前記イメージセンサを複数備えおり、
     前記複数のイメージセンサの各々で取得されたデータを前記送信部が前記通信ネットワークを介して同時に前記管理サーバに送信することを特徴とする細胞観察システム。
    The cell observation system according to claim 1, wherein
    The cell observation device includes a plurality of the image sensors,
    The cell observation system, wherein the transmission unit simultaneously transmits data acquired by each of the plurality of image sensors to the management server via the communication network.
  10.  請求項1の細胞観察システムにおいて、
     前記光源が、異なる複数の波長の光束を出射可能に構成されており、該光源が出射する光束の波長を変化させる波長変更部を備えることを特徴とする細胞観察システム。
    The cell observation system according to claim 1, wherein
    The cell observation system, wherein the light source is configured to be able to emit light beams having a plurality of different wavelengths, and includes a wavelength changing unit that changes a wavelength of the light beams emitted from the light source.
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Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2005117640A (en) * 2003-09-16 2005-04-28 Sysmex Corp Method of displaying sample image and retrieval method employing the same, surveillance method, system of displaying sample image, program for displaying the sample image and recording medium recording with the program stored thereto
JP2015505983A (en) * 2011-12-02 2015-02-26 シー・エス・アイ・アールCsir Material analysis system, method and apparatus

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2005117640A (en) * 2003-09-16 2005-04-28 Sysmex Corp Method of displaying sample image and retrieval method employing the same, surveillance method, system of displaying sample image, program for displaying the sample image and recording medium recording with the program stored thereto
JP2015505983A (en) * 2011-12-02 2015-02-26 シー・エス・アイ・アールCsir Material analysis system, method and apparatus

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