JP2022105173A - 3d細胞凝集体の生成及び培養のための装置及び方法 - Google Patents
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Abstract
Description
実施形態に従った基材を、図12に示されるエンボス加工法を使用して製造した。図12は、ポリマーフィルムにおけるマイクロウェル形成の熱エンボス/熱成形法を示している。ホットプレート1を提供する。ホットプレートを130℃まで予備加熱した。所望のウェルプロファイルを反映する、エンボス加工の鋳型2を提供した。ポリマーフィルム3の層を提供し、シリコーンマット4をポリマーフィルムの後ろに提供した。ホットプレートを加熱し、シリコーン層で支えられたポリマーフィルムに対して押圧した。ホットプレートを取り外したときに、その内部で型押しされた所望のウェルプロファイルを有するマイクロウェルのアレイを有するポリマーフィルムを得た。
本明細書に記載の実施形態の開発中に行われた実験は、例えば、3D細胞凝集体の所望の直径の約1~3倍の直径(D)を有する、各々が半球形の円形底部及び丸みを帯びた上部を有する、個別の空間的に離間されたマイクロウェルのアレイにおいて、均一な直径の3D細胞培養凝集体が形成及び培養されることを実証するものである。マイクロウェル高さ(H)は、円形の底部部分の直径の約0.7~1.3倍に等しく、マイクロウェルの上部開口部の直径(D上部)は、円形の底部の直径の約1.5~2.5倍に等しい。
少なくとも1つの毛管構造と、スフェロイドを誘発する幾何学形状とを含むマイクロウェルのアレイを有する細胞培養基材。
前記少なくとも1つの毛管構造が、リッジ、割れ目、ピラー、不連続な壁、波形状の壁、口部、放物面又は正弦波のウェル形状、若しくは組合せからなる群より選択されることを特徴とする、実施形態1に記載の細胞培養基材。
前記リッジが、円形状、角形状、針状、又は六角形の形状であることを特徴とする、実施形態2に記載の細胞培養基材。
前記割れ目が、円形状、角形状、針状、又は六角形の形状であることを特徴とする、実施形態2に記載の細胞培養基材。
前記スフェロイドを誘発する幾何学形状が、ピラー、不連続な壁、波形状の壁、丸みを帯びたセル底部、くぼみのあるウェル底部、凹み、ペン先領域、不連続な壁、又は組合せを含むことを特徴とする、実施形態1~4のいずれかに記載の細胞培養基材。
前記基材が、前記細胞培養基材の表面1平方センチメートル当たり、前記マイクロウェルを2~10000個含むことを特徴とする、実施形態1~5のいずれかに記載の細胞培養基材。
前記マイクロウェルの少なくとも前記底部が、非接着性の表面を含むことを特徴とする、実施形態1~6のいずれかに記載の細胞培養基材。
前記マイクロウェルの少なくとも前記底部が、ガス透過性材料を含むことを特徴とする、実施形態1~7のいずれかに記載の細胞培養基材。
前記基材が、前記細胞培養基材の表面1平方センチメートル当たり、前記マイクロウェルを2~10000個含むことを特徴とする、実施形態1~8のいずれかに記載の細胞培養基材。
前記細胞培養基材が、細胞培養容器の少なくとも一部を含むことを特徴とする、実施形態1~9のいずれかに記載の細胞培養基材。
前記細胞培養容器が、マルチウェルプレート、皿、フラスコ、管、多層フラスコ、側部軟質性のフラスコ及びバッグからなる群より選択されることを特徴とする、実施形態10に記載の細胞培養基材。
前記細胞培養容器が、透過性の膜によって互いに分離された少なくとも2つの細胞培養チャンバを備えていることを特徴とする、実施形態10に記載の細胞培養基材。
前記マイクロウェルが、該マイクロウェルの少なくとも1つと単一の液体貯槽との間の流体連通を可能にするように構成されることを特徴とする、実施形態1~12のいずれかに記載の細胞培養基材。
前記細胞培養容器が、前記マイクロウェルの上部に配置されたメッシュを備えていることを特徴とする、実施形態1~10のいずれかに記載の細胞培養基材。
各マイクロウェルが、上部開口、ウェル底部、及び、1つ以上の側壁を備えており、
前記上部開口が有効直径D上部を有し、前記1つ以上の側壁が前記ウェル底部から前記上部開口まで延びる高さHを有し、前記マイクロウェルが前記上部開口とウェル底部との間の有効直径の中間点D中間を有し、D上部:D中間の比が1.5:2.5である
ことを特徴とする、実施形態1~14のいずれかに記載の細胞培養基材。
D上部=1.5~2.5D中間であることを特徴とする、実施形態15に記載の細胞培養基材。
H=0.7~1.3D中間であることを特徴とする、実施形態15に記載の細胞培養基材。
D中間が200~1000μmであることを特徴とする、実施形態15に記載の細胞培養基材。
実施形態10~12のいずれかに記載の細胞培養容器に培養培地を充填する工程;及び、
スフェロイド形成細胞を前記培養培地に加える工程
を含む、スフェロイドを培養する方法。
前記培養培地を置換又は交換する工程をさらに含むことを特徴とする、実施形態19に記載の方法。
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4. J. Friedrich, C. Seidel, R. Ebner. Spheroid ‐based drug screen: considerations and practical approach. Nature protocols, 2009, vol4 no3, 309-323
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110 口部
111 上部開口部/口部の上部
112 口部の底部
113 側壁
115 ウェル
116 ウェルの底部
170 リッジ
270 割れ目
401 マイクロウェル
402 フレーム
403 側壁
500 スフェロイド
501 ピラー
505 空間
510 上部
515 ウェル
800 フラスコ
815 上面
820 側壁
850 細胞培養チャンバ
860 ポート
861 ねじぶた
1110 基材
1114 基材
1300 細胞培養培地
1400 細胞培養装置
1410A~C 細胞培養コンパートメント
1415 トレイ
1420 通気マニホルド
1422 キャップ
1425 開口部
1426 開口部
1427 フィルタ
1429 通気カラム
1430 充填マニホルド
1432 キャップ
1435 開口部
1439 列
1440 側壁
1441 上部空間
1442 通気開口
1443 充填開口
1450 上部内面/上面
1460A~C 通路/導管空間
1500 スペーサ
1510 プレート
1601 六角形のウェル
2100 細胞培養装置
2110 基材
2115 ウェル
2120 側壁
2152 培養チャンバ
2154 第2のチャンバ
2162 第1のポート
2164 第2のポート
2202 スフェロイド細胞
3100 細胞培養装置
3110 基材
3111 プレート
3113 フレーム
3115 ウェル
3116 ペン先領域
3118 上部開口
3120 側壁表面
3121 変曲点
3122 下部側壁表面
3123 点
3124 上部側壁表面
3130 スフェロイド
3140 細胞培養容積
3142 高さ
3144 直径寸法
3145 第2の容積
3150 基材
3600 細胞培養組立体
3610 底部プレート
3611 主面
3615 マイクロウェル/ウェル
3620 側壁
3650 細胞培養装置
3670 メッシュ
4100 細胞培養装置
4110 底部プレート
4115 マイクロウェル/ウェル
4120 側壁
4140 入口
4145 出口
4200 細胞培養組立体
4560 フレーム
4570 メッシュ
Claims (1)
- マイクロウェルのアレイを含む細胞培養基材であって、各マイクロウェルが、上部ウェルエッジ、波形状のマイクロウェルの側壁、及び、丸みを帯びたウェル底部によって画成された前記マイクロウェル内への開口部を備え、
複数の前記波形状の側壁の間の間隙に、複数の前記マイクロウェルが生成されるように、複数の前記波形状の側壁が位置合わせされている、細胞培養基材。
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CN107109341A (zh) | 2017-08-29 |
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JP2017532974A (ja) | 2017-11-09 |
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