JP2008092811A - Cell culture apparatus - Google Patents

Cell culture apparatus Download PDF

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JP2008092811A
JP2008092811A JP2006274874A JP2006274874A JP2008092811A JP 2008092811 A JP2008092811 A JP 2008092811A JP 2006274874 A JP2006274874 A JP 2006274874A JP 2006274874 A JP2006274874 A JP 2006274874A JP 2008092811 A JP2008092811 A JP 2008092811A
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microscope
light source
cells
culture
light
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JP2008092811A5 (en
JP5148854B2 (en
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Daisuke Ieshima
大輔 家島
Tsutomu Suzuki
力 鈴木
Masayuki Kobayashi
正幸 小林
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Hitachi Healthcare Manufacturing Ltd
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Hitachi Medical Corp
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    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • 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
    • C12M41/00—Means for regulation, monitoring, measurement or control, e.g. flow regulation
    • C12M41/30—Means for regulation, monitoring, measurement or control, e.g. flow regulation of concentration
    • C12M41/36—Means for regulation, monitoring, measurement or control, e.g. flow regulation of concentration of biomass, e.g. colony counters or by turbidity measurements

Abstract

<P>PROBLEM TO BE SOLVED: To provide a cell culture apparatus capable of ensuring constant and stable light quantity from a light source, when a culturing vessel is photographed in a microscope mounted on the culturing apparatus. <P>SOLUTION: The cell culture apparatus comprises a culture vessel 4 for culturing cells, the microscope 5 for imaging the cells in the culture vessel 4 and a light source means 12 for irradiating the cells with light for imaging the cells. In the cell culture apparatus, a moving means 6 for moving the microscope 5 is installed and the light source means 12 lights the light source, at a position corresponding to the position of the microscope 5. <P>COPYRIGHT: (C)2008,JPO&INPIT

Description

この発明は、細胞培養容器内の細胞の培養状態を培養容器内の全面に渉って鮮明に観察するための観察技術およびそれを用いた細胞培養装置に関する。   The present invention relates to an observation technique for clearly observing a culture state of a cell in a cell culture container over the entire surface of the culture container, and a cell culture apparatus using the observation technique.

細胞培養装置において細胞を培養する場合、培養過程にある細胞の状態を観察することが必要となる。そのため、細胞培養装置には培養容器内の細胞の可視光像を撮像する撮像装置が設けられている。この撮像装置は、個々の細胞レベルの解像力が必要とされるため、顕微鏡方式のものや、レンズとカメラを組み合わせて必要な解像力を得るものが知られている。以下、これらの撮像装置を顕微鏡と称す。   When culturing cells in a cell culture device, it is necessary to observe the state of cells in the culturing process. For this reason, the cell culture device is provided with an imaging device that captures a visible light image of the cells in the culture vessel. Since this imaging device requires a resolution at the level of individual cells, a microscope type and a device that obtains a necessary resolution by combining a lens and a camera are known. Hereinafter, these imaging devices are referred to as a microscope.

可視光を対象物に対して直交するように照らし出す光学顕微鏡の種類については、型式の分類として、試料の上方から観察を行うタイプの正立顕微鏡、試料の下方から観察を行うタイプの倒立顕微鏡がある。正立顕微鏡は、プレパラートなどの固定された試料を観察するのに適しており、倒立顕微鏡は、シャーレに入った培養試料などを観察するのに適していることから、細胞培養装置に付属の顕微鏡は、生きた試料を観察するのに適した倒立型の形式をとることが多い。   As for the types of optical microscopes that illuminate visible light so as to be orthogonal to the object, the type classification is an upright microscope that observes from above the sample and an inverted microscope that observes from below the sample. There is. The upright microscope is suitable for observing a fixed sample such as a preparation, and the inverted microscope is suitable for observing a culture sample in a petri dish. Often takes the inverted form suitable for observing live samples.

上記の如き顕微鏡は、解像力に重きを置くがゆえに撮影領域が狭く、1回の撮影では培養容器の培養面全域を撮像することができない。よって、複数回の撮影で培養面全域を撮影する方法を用いる。   The microscope as described above places importance on the resolving power, so the imaging area is narrow, and the entire culture surface of the culture vessel cannot be imaged with one imaging. Therefore, a method of photographing the entire culture surface by a plurality of photographing is used.

自動撮影が可能な細胞培養装置に搭載されている顕微鏡の多くは、一般の倒立顕微鏡同様に、培養器下方に顕微鏡を、上方に光源を固定し、観察対象となる培養器を支えるトレーを、顕微鏡と光源の間で稼動させるタイプがある(例えば特許文献1)。また、スキャナー方式で、培養器下方から顕微鏡を走査させて細胞画像を取得するタイプがある(例えば特許文献2)。また、顕微鏡の移動にあわせて、光源ランプも移動させる構造をとっているタイプがある(例えば特許文献3)。
特開2006-187206号公報 特開2002-85054号公報 特開2005-295818号公報 Many of the microscopes mounted on cell culture devices that can be automatically photographed, like a general inverted microscope, have a microscope below the incubator, a light source above the incubator, and a tray that supports the incubator to be observed. There is a type that operates between a microscope and a light source (for example, Patent Document 1). In addition, there is a scanner type that acquires a cell image by scanning a microscope from below the incubator (for example, Patent Document 2). In addition, there is a type in which the light source lamp is also moved in accordance with the movement of the microscope (for example, Patent Document 3).
JP 2006-187206 A JP 2002-85054 A JP 2005-295818

しかし、顕微鏡と光源を固定し培養器を動かすタイプのものでは、ある程度の培養器の可動領域を確保する必要があることから、装置が大型化しやすい、あるいは、培養面積を小型化しなくてはならないという問題があり、また、スキャナー方式では、観察毎に培養器をスキャンしなくてはならないため、ライブ画像の観察などには不向きである。
また、顕微鏡の移動にあわせて、光源ランプを移動させる構造をとっているタイプの場合、装置構成が大掛かりで複雑になるため、コスト面、装置制御面等で課題が残っている。 However, with the type that moves the incubator while fixing the microscope and light source, it is necessary to secure a certain range of the incubator, so the device tends to be large or the culture area must be reduced. In addition, the scanner method is not suitable for observing live images because the incubator must be scanned for each observation.
Further, in the case of a type that has a structure in which the light source lamp is moved in accordance with the movement of the microscope, the apparatus configuration is large and complicated, so that there remain problems in terms of cost, apparatus control, and the like.

本発明の目的は、構造が簡単で且つその制御も容易な培養観察装置を備えた細胞培養装置を提供することに或る。   An object of the present invention is to provide a cell culture apparatus having a culture observation apparatus that is simple in structure and easy to control.

前記課題を解決するために、本発明は以下の様に構成される。細胞を培養する培養容器と、前記培養容器の細胞を撮像する撮像装置と、前記細胞を撮像する時に前記細胞に光を照射する光源手段と、前記顕微鏡を移動する移動手段とを備える細胞培養装置において、前記光源手段は、複数の光源を有しており、前記顕微鏡の位置に対応する前記光源を点灯させる。   In order to solve the above problems, the present invention is configured as follows. A cell culture device comprising: a culture vessel for culturing cells; an imaging device for imaging the cells in the culture vessel; light source means for irradiating the cells with light when imaging the cells; and moving means for moving the microscope The light source means has a plurality of light sources, and turns on the light sources corresponding to the position of the microscope.

培養装置に搭載される顕微鏡において、培養器を撮影する際、光源から一定で安定した光量を確保することができる。   In a microscope mounted on a culture apparatus, when photographing an incubator, a constant and stable light quantity can be secured from a light source.

本発明に係る培養装置は、図1に示すような構成をもつ。
細胞培養装置1は、細胞を培養する培養容器4と、細胞を撮像するための顕微鏡5と、顕微鏡5を移動させるための顕微鏡駆動装置6と、顕微鏡駆動装置6を制御するドライバ10と、顕微鏡5の位置情報に基いて光源基板に設けられた複数の光源3の特定光源に対する電源をオン状態にする切換え器7と、切り換え器7と光源3とを接続する光源配線9と、光源3を配列させた光源基板2と、これらを制御するコントローラ8とから構成される。また、培養装置は、コントローラ8に接続され、トラックボール又はキーボードからなる入力部20を備えている。 The culture apparatus according to the present invention has a configuration as shown in FIG.
The cell culture device 1 includes a culture vessel 4 for culturing cells, a microscope 5 for imaging cells, a microscope driving device 6 for moving the microscope 5, a driver 10 for controlling the microscope driving device 6, a microscope A switch 7 that turns on the power to a specific light source of a plurality of light sources 3 provided on the light source board based on the position information of 5, a light source wiring 9 that connects the switch 7 and the light source 3, and a light source 3 The light source substrate 2 is arranged and a controller 8 for controlling them. The culture apparatus is connected to the controller 8 and includes an input unit 20 formed of a trackball or a keyboard.

顕微鏡駆動装置6は、モータとボールねじ機構を有する駆動機構が備えられており、ボールねじ機構を介して顕微鏡5を2次元的に移動させることができる。また、ボールねじ機構には、ボールねじの回転量を検出し、それを顕微鏡5の位置情報に変換して検出するロータリーエンコーダなどからなる位置センサを有している。位置センサはボールねじの回転量を検出することにより、顕微鏡5の位置を2次元的に特定することができる。この顕微鏡5の位置情報は、ドライバ10を介してコントローラ8に伝達される。   The microscope driving device 6 includes a driving mechanism having a motor and a ball screw mechanism, and can move the microscope 5 two-dimensionally via the ball screw mechanism. Further, the ball screw mechanism has a position sensor including a rotary encoder that detects the amount of rotation of the ball screw, converts it into position information of the microscope 5, and detects it. The position sensor can specify the position of the microscope 2 two-dimensionally by detecting the rotation amount of the ball screw. The position information of the microscope 5 is transmitted to the controller 8 via the driver 10.

ボールねじ機構は、らせん状の溝を有するボールねじと、その溝に沿って移動するスリーブとからなる。そのスリーブには顕微鏡5が設置されている。ボールねじを回転させることによりスリーブ及び顕微鏡5を直線的に移動させることができる。2つボールねじ機構をそれぞれ直角になるように備えることにより、スリーブ及び顕微鏡5を2次元的に移動させることができる。   The ball screw mechanism includes a ball screw having a spiral groove and a sleeve moving along the groove. A microscope 5 is installed on the sleeve. The sleeve and the microscope 5 can be moved linearly by rotating the ball screw. By providing the two ball screw mechanisms at right angles, the sleeve and the microscope 5 can be moved two-dimensionally.

図2〜図4は、図1内の顕微鏡装置11、光源装置12、および培養容器4を示した図である。 以下、顕微鏡装置11、光源装置12を詳細に説明する。
図2の平面図に示すように光源装置12は、光源3と光源基板2とを有している。具体的には、複数の光源3が2次元的に配置されるよう、光源基板2に並設されている。図2では横方向に5つ、縦方向に4つの光源3が均等に並設されている。 2 to 4 are diagrams showing the microscope device 11, the light source device 12, and the culture vessel 4 in FIG. Hereinafter, the microscope apparatus 11 and the light source apparatus 12 will be described in detail.
As shown in the plan view of FIG. 2, the light source device 12 includes a light source 3 and a light source substrate 2. Specifically, the plurality of light sources 3 are arranged side by side on the light source substrate 2 so as to be two-dimensionally arranged. In FIG. 2, five light sources 3 are arranged in parallel in the horizontal direction and four light sources 3 in the vertical direction.

光源3は、培養する細胞にとって有害な波長成分を有さないものがよい。たとえば、紫外線は細胞のDNAに損傷を与えたり、紫外線誘発アポトーシスを惹起し、結果的に細胞の癌化の原因になるといわれている。したがって、通常の細胞を培養するときは、光源3としてそのような成分を含むことは避けなければならない。
また、赤外線は熱を生じるために細胞にとってストレスとなりうる。逆に、特定の波長の光が細胞を活性化させることもあるので、積極的に光源3の波長が培養に有利なものとなるよう制御することもできる。光源3の波長やその成分比は、培養する細胞やその目的に合わせて変更できるようにしておくことが望ましい。 The light source 3 preferably does not have a wavelength component harmful to cells to be cultured. For example, ultraviolet rays are said to damage cell DNA or induce ultraviolet-induced apoptosis, resulting in cell canceration. Therefore, when culturing normal cells, it should be avoided to include such components as the light source 3.
Infrared rays can also cause stress for cells because they generate heat. On the contrary, since light of a specific wavelength may activate cells, it is possible to positively control the wavelength of the light source 3 to be advantageous for culture. It is desirable that the wavelength of the light source 3 and the component ratio thereof can be changed according to the cell to be cultured and its purpose.

光源3の種類としては特に定めるものはないが、好ましくは、単色性の強いLEDなどの光源素子を用いるか、目的用途に応じて、水銀ランプ、キセノンランプ、タングステンランプ、ハロゲンランプなどの種類の光源3を用いることが望ましい。また、目的の波長を得るために、光源3と培養容器4の間に任意のフィルタを介在させてもよい。   The type of the light source 3 is not particularly defined, but preferably, a light source element such as a highly monochromatic LED is used, or the type of a mercury lamp, a xenon lamp, a tungsten lamp, a halogen lamp, etc. It is desirable to use the light source 3. In addition, an arbitrary filter may be interposed between the light source 3 and the culture vessel 4 in order to obtain a target wavelength.

光源3間の距離については、撮像した際に光のムラができない距離であればよい。好ましくは1mm〜10mm程度である。また光源3の個数については、培養容器4全体がカバーできるよう、１mm〜10mm間隔で、使用する光源基板2全面に光源3が配置できるだけの個数が必要である。また、光源基板2の大きさは、使用する培養容器4と同等以上の大きさである。   The distance between the light sources 3 may be a distance that does not cause unevenness of light when taking an image. Preferably, it is about 1 mm to 10 mm. As for the number of light sources 3, it is necessary to arrange the light sources 3 on the entire surface of the light source substrate 2 to be used at intervals of 1 to 10 mm so that the entire culture vessel 4 can be covered. Further, the size of the light source substrate 2 is equal to or larger than that of the culture vessel 4 to be used.

図3に示すように、顕微鏡5が移動するに伴い、光源3が駆動する形態を説明する。顕微鏡装置11は、顕微鏡5と、顕微鏡駆動装置6とを有している。その構成は、図3(A)のように2方向に動作可能なもので図3(B)のように、1方向に動作可能な顕微鏡駆動装置6を複数組み合わせて、動作可能なものでよい。   As shown in FIG. 3, a mode in which the light source 3 is driven as the microscope 5 moves will be described. The microscope device 11 includes a microscope 5 and a microscope driving device 6. The configuration is operable in two directions as shown in FIG. 3 (A), and can be operated by combining a plurality of microscope driving devices 6 operable in one direction as shown in FIG. .

ここで、顕微鏡装置11と光源装置12の組み合わせとしては、顕微鏡5の可動領域をカバーする形態の光源装置12を用いることが好ましい。また、顕微鏡装置11および光源装置12を用いる場合、顕微鏡駆動装置6の動きと直交する方向に、培養容器4を直線的あるいは放物線的あるいは円弧状に培養器を動かして、顕微鏡5の動きと培養容器4の動作を併せることで、培養容器4全面を観察できるようにしてもよい。光源基板2を用いる場合は、基板2の長さは、使用する培養容器4の直径以上の長さであることが好ましい。   Here, as a combination of the microscope apparatus 11 and the light source apparatus 12, it is preferable to use the light source apparatus 12 that covers the movable region of the microscope 5. Further, when using the microscope apparatus 11 and the light source apparatus 12, the culture vessel 4 is moved linearly, parabolically or arcuately in a direction orthogonal to the movement of the microscope driving apparatus 6, and the movement and culture of the microscope 5 are moved. By combining the operation of the container 4, the entire surface of the culture container 4 may be observed. When the light source substrate 2 is used, the length of the substrate 2 is preferably equal to or longer than the diameter of the culture vessel 4 to be used.

次に顕微鏡駆動装置6と光源3との動作関係を説明する。操作者がある特定の位置の培養状態を観察するために、入力部20から位置情報を入力すると、コントローラ8からドライバ10へ入力された位置情報に対応した駆動制御信号が出力され、モータによってボールねじ機構が駆動され、入力部20から入力された位置に顕微鏡5が移動される。位置センサは、ボールねじの回転による顕微鏡5の位置を読み取り、その位置情報をコントローラ8に伝達する。コントローラ8は、切り替え器7を介して複数の光源3のうち顕微鏡5の真上の光源3が点灯するように、複数の光源3を制御する。   Next, the operational relationship between the microscope driving device 6 and the light source 3 will be described. When the operator inputs position information from the input unit 20 to observe the culture state at a specific position, a drive control signal corresponding to the position information input from the controller 8 to the driver 10 is output, and the ball is moved by the motor. The screw mechanism is driven, and the microscope 5 is moved to the position input from the input unit 20. The position sensor reads the position of the microscope 5 due to the rotation of the ball screw and transmits the position information to the controller 8. The controller 8 controls the plurality of light sources 3 so that the light source 3 directly above the microscope 5 among the plurality of light sources 3 is turned on via the switch 7.

ここで、光源基板2の大きさを、例えば縦40mm、横70mmとする。光源基板2には、10mm間隔で光源3が配置されているとする。また、顕微鏡5は光源基板2の大きさに対応して縦方向40mm、横方向70mmの駆動範囲を持っている。顕微鏡5を座標(50，20)の位置に移動させ細胞の状態を観察したい場合、顕微鏡5の中心位置を座標(50，20)の位置になるように、顕微鏡5を顕微鏡駆動装置6により移動させる。なお、この座標の原点は、顕微鏡駆動装置6の左下の光源3の位置である。そして、ドライバ10は、顕微鏡駆動装置6の位置センサから取得される座標の位置をコントローラ8に伝達する。コントローラ8は、切り換え器7を介して座標(50，20)に対応する複数の光源3のうち右から6個目、下から3個目の光源3を点灯させる。よって、顕微鏡5の真上の光源3を点灯させることができる。   Here, the size of the light source substrate 2 is, for example, 40 mm long and 70 mm wide. It is assumed that the light source 3 is arranged on the light source substrate 2 at intervals of 10 mm. The microscope 5 has a driving range of 40 mm in the vertical direction and 70 mm in the horizontal direction corresponding to the size of the light source substrate 2. If you want to move the microscope 5 to the coordinates (50, 20) and observe the state of the cells, move the microscope 5 with the microscope drive 6 so that the center position of the microscope 5 is the coordinates (50, 20). Let The origin of the coordinates is the position of the light source 3 at the lower left of the microscope driving device 6. Then, the driver 10 transmits the coordinate position acquired from the position sensor of the microscope driving device 6 to the controller 8. The controller 8 turns on the sixth light source 3 from the right and the third light source 3 from the bottom among the plurality of light sources 3 corresponding to the coordinates (50, 20) via the switch 7. Therefore, the light source 3 directly above the microscope 5 can be turned on.

また、顕微鏡5を座標(39，12)の位置に移動させ細胞の状態を観察したい場合、顕微鏡5の中心位置を座標(39，12)の位置になるように、顕微鏡5を顕微鏡駆動装置6により移動させる。そして、ドライバ10は、顕微鏡駆動装置6の位置センサから取得される座標の位置をコントローラ8に伝達する。コントローラ8は、切り換え器7を介して座標(39，12)に対応する複数の光源3のうち右から5個目、下から2個目の光源3を点灯させる。よって、顕微鏡5に最も近い光源3を点灯させることができる。   When the microscope 5 is moved to the position of coordinates (39, 12) and the state of the cells is to be observed, the microscope 5 is moved to the microscope driving device 6 so that the center position of the microscope 5 becomes the position of coordinates (39, 12). To move. Then, the driver 10 transmits the coordinate position acquired from the position sensor of the microscope driving device 6 to the controller 8. The controller 8 turns on the fifth light source 3 from the right and the second light source 3 from the bottom among the plurality of light sources 3 corresponding to the coordinates (39, 12) via the switch 7. Therefore, the light source 3 closest to the microscope 5 can be turned on.

また、図4に示すように、光源3を1方向に配列させ、顕微鏡5を1方向に動作可能なものでもよい。ここで、光源基板2の長さを、例えば50mmとする。光源基板2には、10mm間隔で光源3が配置されている。また、顕微鏡5は光源基板2の大きさに対応して横方向50mm以上の駆動範囲を持っている。顕微鏡5を座標(20)の位置に移動させ細胞の状態を観察したい場合、顕微鏡5の中心位置を座標(20)の位置になるように、顕微鏡5を顕微鏡駆動装置6により移動させる。そして、ドライバ10は、顕微鏡駆動装置6の位置センサから取得される座標の位置をコントローラ8に伝達する。コントローラ8は、座標(20)に対応する複数の光源3のうち右から3個目の光源3を点灯させる。よって、顕微鏡5の真上の光源3を点灯させることができる。   Further, as shown in FIG. 4, the light source 3 may be arranged in one direction and the microscope 5 may be operable in one direction. Here, the length of the light source substrate 2 is, for example, 50 mm. Light sources 3 are arranged on the light source substrate 2 at intervals of 10 mm. The microscope 5 has a driving range of 50 mm or more in the lateral direction corresponding to the size of the light source substrate 2. When the microscope 5 is moved to the position of the coordinate (20) and the state of the cell is to be observed, the microscope 5 is moved by the microscope driving device 6 so that the center position of the microscope 5 becomes the position of the coordinate (20). Then, the driver 10 transmits the coordinate position acquired from the position sensor of the microscope driving device 6 to the controller 8. The controller 8 turns on the third light source 3 from the right among the plurality of light sources 3 corresponding to the coordinates (20). Therefore, the light source 3 directly above the microscope 5 can be turned on.

さらに、図4(C)に示すように、培養容器4を顕微鏡5の移動方向と直交する方向に移動させる機構を有していてもよい。培養容器4の下部には、例えば複数の車輪が設けられており、レール41とレール42上に複数の車輪が嵌め込まれている。また、培養容器4には複数の車輪を回転させるためのモータが設けられており、コントローラ8はこのモータを制御する。これにより、培養容器4を顕微鏡5の移動方向と直交する方向に移動させることができる。なお、培養容器4には、上述したモータとボールねじ機構を有する駆動機構を有していてもよい。コントローラ8は、培養容器4及び顕微鏡5を移動させることにより、培養容器4内の細胞の様子を把握することができる。   Further, as shown in FIG. 4C, a mechanism for moving the culture vessel 4 in a direction orthogonal to the moving direction of the microscope 5 may be provided. For example, a plurality of wheels are provided in the lower part of the culture vessel 4, and the plurality of wheels are fitted on the rail 41 and the rail 42. The culture vessel 4 is provided with a motor for rotating a plurality of wheels, and the controller 8 controls the motor. Thereby, the culture vessel 4 can be moved in a direction orthogonal to the moving direction of the microscope 5. The culture vessel 4 may have a drive mechanism having the motor and the ball screw mechanism described above. The controller 8 can grasp the state of the cells in the culture container 4 by moving the culture container 4 and the microscope 5.

図5は、図1の光源基板2及び顕微鏡駆動装置6であり、光源3の点灯例を示した図である。光源3の点灯方法については、図5に示すように、顕微鏡が5aの位置にあるときには3bは消灯し、顕微鏡5aの真上にある光源3aが点灯し、顕微鏡が5aから5bの位置に移動したとき、光源3aが消灯し、顕微鏡5bの真上にある光源3bが点灯する。
光源3の点灯のタイミングについては、図5において、顕微鏡が5aの位置に存在するときは、光源3aを点灯させ、顕微鏡が5aから5bの位置に移動する際、その中間点13を含む中間点付近を通過した時点で、光源3bが点灯し、光源3aが消灯する。 FIG. 5 is a diagram showing a lighting example of the light source 3, which is the light source substrate 2 and the microscope driving device 6 of FIG. Regarding the lighting method of the light source 3, as shown in FIG. 5, when the microscope is at the position of 5a, 3b is turned off, the light source 3a immediately above the microscope 5a is turned on, and the microscope is moved from the position of 5a to 5b. Then, the light source 3a is turned off, and the light source 3b directly above the microscope 5b is turned on.
Regarding the lighting timing of the light source 3, in FIG. 5, when the microscope exists at the position 5a, when the light source 3a is turned on and the microscope moves from the position 5a to 5b, the intermediate point including the intermediate point 13 is included. When passing through the vicinity, the light source 3b is turned on and the light source 3a is turned off.

また、光源3の点灯形式については、前述の点灯方法に従い、図6(A)のように顕微鏡5の真上の光源3のみを、顕微鏡5の動作にあわせて光源を点灯させてもよいし、図6(B)のように、顕微鏡5の真上にある光源3を中心に複数個、顕微鏡5の動きにあわせて点灯させてもよい。
具体的には、顕微鏡5を座標(30，20)の位置に移動させ細胞の状態を観察したい場合、顕微鏡5の中心位置を座標(30，20)の位置になるように、顕微鏡5を顕微鏡駆動装置6により移動させる。なお、この座標の原点は、顕微鏡駆動装置6の左下の光源3の位置である。そして、ドライバ10は、顕微鏡駆動装置6の位置センサから取得される座標の位置をコントローラ8に伝達する。コントローラ8は、切り換え器7を介して座標(30，20)に対応する複数の光源3のうち右から2〜6個目、下から1〜5個目の光源3を点灯させる。よって、顕微鏡5の真上にある光源3を中心に複数個点灯させることができる。 As for the lighting type of the light source 3, only the light source 3 directly above the microscope 5 may be turned on according to the operation of the microscope 5, as shown in FIG. As shown in FIG. 6 (B), a plurality of light sources 3 directly above the microscope 5 may be turned on in accordance with the movement of the microscope 5.
Specifically, when the microscope 5 is moved to the position of coordinates (30, 20) and the state of the cell is to be observed, the microscope 5 is moved to the position of coordinates (30, 20) so that the center position of the microscope 5 becomes the position of coordinates (30, 20). It is moved by the driving device 6. The origin of the coordinates is the position of the light source 3 at the lower left of the microscope driving device 6. Then, the driver 10 transmits the coordinate position acquired from the position sensor of the microscope driving device 6 to the controller 8. The controller 8 turns on the second to sixth light sources 3 from the right and the first to fifth light sources 3 from the bottom among the plurality of light sources 3 corresponding to the coordinates (30, 20) via the switch 7. Therefore, a plurality of light sources 3 can be turned on around the light source 3 directly above the microscope 5.

顕微鏡5を用いて撮像した画像の処理方法については特に定めるものはないが、好ましくは、顕微鏡5にCCDカメラ、画像処理ユニットなどを付属させて、顕微鏡5より取得した画像をリアルタイムで直接観察したり、写真やビデオ画像として保存できるようにしておくことが望ましい。
また、観察の対象となる培養容器4の材質については、光を透過する材質であれば特に限定はないが、好ましくは、ポリスチレン、ポリエチレンテレフタラート樹脂、ガラスなどがよい。使用する顕微鏡5および撮像装置の倍率については特に定めるものはないが、望ましくは、細胞を明瞭に観察可能な、40〜1000倍程度の拡大倍率が好ましい。 Although there is no specific method for processing the image captured using the microscope 5, it is preferable to attach a CCD camera, an image processing unit, etc. to the microscope 5 and directly observe the image acquired from the microscope 5 in real time. It is desirable to be able to save as photos or video images.
Further, the material of the culture vessel 4 to be observed is not particularly limited as long as it is a material that transmits light, but preferably, polystyrene, polyethylene terephthalate resin, glass or the like is used. The magnification of the microscope 5 and the imaging device to be used is not particularly defined, but desirably an enlargement magnification of about 40 to 1000 times that can clearly observe cells is preferable.

本発明の培養装置の各構成手段の配置の概略を示す図。The figure which shows the outline of arrangement | positioning of each structural means of the culture apparatus of this invention. 本発明の光源装置および顕微鏡装置の概略を示す図。The figure which shows the outline of the light source device and microscope apparatus of this invention. 本発明の光源装置および顕微鏡装置の概略を示す図。The figure which shows the outline of the light source device and microscope apparatus of this invention. 本発明の光源装置および顕微鏡装置の概略を示す図。The figure which shows the outline of the light source device and microscope apparatus of this invention. 本発明の顕微鏡の動きに伴う光源の点灯方法を示す図。The figure which shows the lighting method of the light source accompanying the movement of the microscope of this invention. 本発明の顕微鏡の動きに応じた光源の点灯形式を示す図。The figure which shows the lighting format of the light source according to the motion of the microscope of this invention.

符号の説明Explanation of symbols

１ 培養装置
２ 光源基板
３ 光源
４ 培養容器
５ 顕微鏡
６ 顕微鏡駆動装置
７ 切り換え器
８ コントローラ
９ 光源配線
１０ ドライバ
１１ 顕微鏡装置
１２ 光源装置
１３ 光源中間点 DESCRIPTION OF SYMBOLS 1 Culture apparatus 2 Light source board 3 Light source 4 Culture container 5 Microscope 6 Microscope drive apparatus 7 Switch 8 Controller 9 Light source wiring 10 Driver 11 Microscope apparatus 12 Light source apparatus 13 Light source intermediate point

Claims (1)

細胞を培養する培養容器と、前記培養容器の細胞を撮像する撮像装置と、前記細胞を撮像する時に前記細胞に光を照射する光源手段と、前記顕微鏡を移動する移動手段とを備える細胞培養装置において、前記光源手段は、複数の光源を有しており、前記顕微鏡の位置に対応する前記光源を点灯させることを特徴とする細胞培養装置。   A cell culture device comprising: a culture vessel for culturing cells; an imaging device for imaging the cells in the culture vessel; light source means for irradiating the cells with light when imaging the cells; and moving means for moving the microscope And the light source means has a plurality of light sources, and lights up the light sources corresponding to the position of the microscope.
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