JP2022511527A - 3dバイオプリンタ用のプリントヘッドアセンブリ - Google Patents
3dバイオプリンタ用のプリントヘッドアセンブリ Download PDFInfo
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Abstract
Description
本願は、2018年12月6日に出願され、本願に援用されているオーストラリア仮特許出願第2018904641号に対して優先権を主張するものである。
(a)データ収集のための非侵襲的医用画像技術(例:コンピュータ断層撮影(CT)や磁気共鳴画像(MRI))、並びに
(b)情報のデジタル化、3Dレンダリングされたモデルの生成、2D断面画像の生成に用いられるコンピュータ支援設計・コンピュータ支援製造(CAD-CAM)ツール及び数学的モデリング、に基づいている。
リザーバ、
リザーバと流体連通し、流体をリザーバに誘導するように構成されたサンプルローディングシステム、及び
リザーバと流体連通し、リザーバから流体を分配するように構成された分配口を有する分配システム、を含む、プリントヘッドアセンブリを提供する。
リザーバは複数のリザーバの一つである。
サンプルローディングシステムは、各リザーバと流体連通し、流体を複数のリザーバのいずれか一つに誘導するように構成される。
分配口は、複数の分配口の一つである。
各分配口は、前記複数のリザーバの一つと流体連通し、各リザーバから流体を分配するように構成される。
各リザーバは、リザーバ出口とリザーバ入口とを有し、
各分配口は、複数のリザーバの一つにおけるリザーバ出口と流体連通し、
各プライミング流体ラインは、マニホールド、及び複数のリザーバの一つにおけるリザーバ入口と流体連通している。
流体がマニホールドから各リザーバに流れることを可能にする開放構成と、
流体がマニホールドから各リザーバに流れるのを防ぐ閉鎖構成と、を有する弁を含む。
流体がマニホールドの入口を通ってマニホールドに流入することを可能にする開放構成と、
流体がマニホールドの入口を通ってマニホールドに流入することを防止する閉鎖構成と、を有する。
各リザーバから流体を分配することを可能にする開放構成と、
流体が各リザーバから分配されるのを防ぐ閉鎖構成と、を有するノズルである。
第1の態様によるプリントヘッドアセンブリ、
3D細胞構造を制作できる基板を配置する印刷ステージ、及び
カートリッジレセプタクルを含む、バイオプリンタを提供する。
第1の態様によるプリントヘッドアセンブリ、
3D細胞構造を制作できる基板を配置する印刷ステージ、
カートリッジレセプタクル、及び
サンプルローディングシステムと流体連通し、流体をサンプルローディングシステムに引き込み、流体をサンプルローディングシステムからリザーバのいずれか一つにポンプで送り込むように構成されたポンプ、を含む。
定義
プリントヘッドアセンブリの第2の例示的実施形態
プリントヘッドアセンブリの第3の例示的な実施形態
プリントヘッドアセンブリの第4の例示的実施形態
細胞の動き及び攪拌/再懸濁プロセス
バイオインク
・フルクトース、スクロース、又はグルコース官能基を含むポリマーなどの多糖類。
・ポリ(エチレングリコール)(PEG)、ポリ(ヒドロキシエチルメタクリレート(PHEMA)、ポリ(ε-カプロラクトン)(PCL)、ポリ(ビニルアルコール)(PVA)、ポリ(ビニルピロリドン)(PVP)、ポリ(NIPAAM)、ポリ(プロピレンフマレート)(PPF)などの非イオン性ポリマー、並びに誘導体。
・高分子電解質:正又は負の電荷を帯びたポリマー、両性及び双性イオン性ポリマー。
・ポリペプチド:多くのアミノ酸(最低2アミノ酸)の単一の直鎖で、アミド結合によって結合されている。
・合成ポリマーを含む核酸塩基:核酸塩基(アデニン、チミン、グアニン、又はシトシン)の繰り返し単位を持つポリマー。
・アルギン酸塩、キトサン、ジェランガム、ヒアルロン酸、アガロース、グリコサミノグリカンなどの多糖類。
・ゼラチン、フィブリン、コラーゲンなどのタンパク質。
・一本鎖DNA(ssDNA)、二本鎖DNA(dsDNA)DNAzyme及びアプタマーなどのDNA及びオリゴヌクレオチド。
・基底膜抽出物。
活性剤
・炭酸カルシウム、塩化カルシウム、塩化ナトリウム、硫酸マグネシウム、水酸化ナトリウム、塩化バリウムなどの無機塩。
・2,2-ジメトキシ-2-フェニルアセトフェノン(DMPA)やイルガキュアなどの光開始剤。
・高分子電解質:バイオインクの高分子とは反対の電荷を帯びるポリマー。陽イオン性、陰イオン性、両性及び双性イオン性であってもよい。
・ポリペプチド:多くのアミノ酸(最低2アミノ酸)の単一の直鎖で、アミド結合によって結合されている。
・DNAリンカー:バイオインクの高分子に存在するものを補完するヌクレオチド又はDNA配列を運ぶ高分子。
・天然又は化学修飾により、アミン又はチオール基を持つ天然又は合成高分子。
架橋又はゲル化
・イオン架橋:高分子と活性剤に存在する反対の電荷の相互作用を介した架橋。活性剤は、荷電オリゴマー、イオン性塩及びイオン性分子を含んでもよい。
・水素結合:極性分子の静電引力による架橋。この場合、高分子と活性剤は極性機能を持っている。
・温度架橋:温度変化(加熱又は冷却)への応答としての高分子鎖の再配列による架橋。
・疎水性相互作用又はファンデルワールス力。
・UV又は光照射によって架橋反応が促進される光架橋。
・水性媒体中でのチオールとビニル運搬高分子間のマイケル型付加反応。
・アミノ基とアルデヒド基の間のシッフ塩基反応。
・ディールスアルダー反応。
・クリックケミストリー。
・活性エステル基へのアミノリシス反応。
・酵素の架橋。
・グリセロールなどの小分子
・Ficoll(商標)、デキストラン、アルギン酸塩、ジェランガム、メチルセルロースなどの高分子、及びポリ(ビニルピロリドン)(PVP)
細胞培養溶液
・ダルベッコ改変イーグル培地(DMEM)、イーグル最小必須培地(MEM)、イスコフ改変ダルベッコ培地(IMDM)、Media199、HamF10、HamF12、McCoy5A、ロズウェルパーク記念研究所(RPMI)培地などの細胞培養培地。
・胎児子牛血清(FCS)、上皮成長因子(EGF)、塩基性線維芽細胞成長因子(bFBF)、線維芽細胞成長因子(FBF)、内皮細胞成長因子(ECGF)、インスリン様成長因子1(IGF-1)、血小板由来成長因子(PDGF)などの成長サプリメント。
・PBS、HEPES、CHESなどの生物学的バッファー。
・キレート化及び安定化液。
・滅菌されたMilliQ水。
細胞培養条件
ユーティリティ液
・正しい濃度のエタノール
・滅菌MilliQ水
・細胞培養培地
・洗剤
・過酸化水素溶液(最大濃度2w/v%)
バイオインクの調製
細胞の調製
活性剤の調製
細胞インクの準備
細胞採取
ヒドロゲル型の印刷
細胞型
Claims (26)
- 3Dバイオプリンタに適するプリントヘッドアセンブリであって、
リザーバ、
前記リザーバと流体連通し、流体を前記リザーバに誘導するように構成されたサンプルローディングシステム、及び
前記リザーバと流体連通し、前記リザーバから流体を分配するように構成された分配口を有する分配システム、を含む、プリントヘッドアセンブリ。 - 前記リザーバは複数のリザーバの一つであり、
前記サンプルローディングシステムは、各リザーバと流体連通し、流体を前記複数のリザーバのいずれか一つに誘導するように構成され、
前記分配口は、複数の分配口の一つであり、
各分配口は、前記複数のリザーバの一つと流体連通し、各リザーバから流体を分配するように構成される、請求項1に記載のプリントヘッドアセンブリ。 - 前記サンプルローディングシステムは、容器から流体を引き出し、前記流体で前記複数のリザーバのいずれか一つをプライミングするように構成される、請求項2に記載のプリントヘッドアセンブリ。
- 前記サンプルローディングシステムは、前記複数のリザーバと流体連通するマニホールドを含み、前記マニホールドは、流体を前記複数のリザーバのいずれか一つに誘導するように構成される、請求項2又は3に記載のプリントヘッドアセンブリ。
- 前記サンプルローディングシステムは、複数のプライミング流体ラインを更に含み、各プライミング流体ラインは、流体連通している一つのリザーバを前記マニホールドに結合する、請求項4に記載のプリントヘッドアセンブリ。
- 各リザーバは、リザーバ出口とリザーバ入口とを有し、
各分配口は、前記複数のリザーバの一つにおける前記リザーバ出口と流体連通し、
各プライミング流体ラインは、前記マニホールド、及び前記複数のリザーバの一つにおける前記リザーバ入口と流体連通している、
請求項5に記載のプリントヘッドアセンブリ。 - 前記各分配口は、分配流体ラインにより前記複数のリザーバの一つにおける前記リザーバ出口に流体連通で結合される、請求項6に記載のプリントヘッドアセンブリ。
- 前記各分配流体ラインは、粒子が前記各分配口に沈降することを低減するように構成された粒子トラップを含む、請求項7に記載のプリントヘッドアセンブリ。
- 前記粒子トラップは、前記分配流体ラインにおける一つ以上のループである、請求項8に記載のプリントヘッドアセンブリ。
- 前記各プライミング流体ラインは、流体が前記マニホールドから前記各リザーバに流れることを可能にする開放構成と、流体が前記マニホールドから前記各リザーバに流れるのを防ぐ閉鎖構成と、を有する弁を含む、請求項5~9のいずれか1項に記載のプリントヘッドアセンブリ。
- 前記サンプルローディングシステムは、前記マニホールドの入口と流体連通で結合され、流体を前記サンプルローディングシステムに引き込み、流体を前記サンプルローディングシステムから前記リザーバのいずれか一つにポンプで送り込むように構成されたポンプを含む、請求項3~10のいずれか1項に記載のプリントヘッドアセンブリ。
- 前記サンプルローディングシステムは、前記マニホールドの前記入口と流体連通し、容器から流体を引き出すために前記容器に挿入されるように構成されるニードルを更に含む、請求項11に記載のプリントヘッドアセンブリ。
- 前記サンプルローディングシステムは、前記ニードルを前記容器に挿入して前記容器から流体を引き出し、前記ニードルを前記容器から引き抜くように構成されたアクチュエータを更に含む、請求項12に記載のプリントヘッドアセンブリ。
- 前記各リザーバは、加圧ガス源に流体連通で結合され、前記各リザーバを加圧するように構成される、請求項1~13のいずれか1項に記載のプリントヘッドアセンブリ。
- 前記各リザーバは、圧力調整器に結合され、各リザーバ内の圧力を調整するように構成される、請求項14に記載のプリントヘッドアセンブリ。
- 前記各分配口は、各リザーバから流体を分配することを可能にする開放構成と、流体が各リザーバから分配されるのを防ぐ閉鎖構成と、を有するノズルである、請求項2~15のいずれか1項に記載のプリントヘッドアセンブリ。
- 細胞を印刷する3Dバイオプリンタであって、
請求項1~16のいずれか1項に記載のプリントヘッドアセンブリ、
3D細胞構造を制作できる基板を配置する印刷ステージ、及び
カートリッジレセプタクル、を含む、バイオプリンタ。 - 前記プリントヘッドアセンブリ、前記印刷ステージ、及び前記カートリッジレセプタクルが配置されるハウジングを更に含む、請求項17に記載のバイオプリンタ。
- 前記ハウジングは、前記バイオプリンタの内部へのアクセスを可能にする開放位置と、前記バイオプリンタの内部へのアクセスを防止する閉鎖位置とを有するアクセスドアを含む、請求項18に記載のバイオプリンタ。
- 各リザーバ内の圧力を調整するために各リザーバに流体連通で結合され、各リザーバを加圧するための加圧ガス源に流体連通で結合されるように構成された圧力調整システムを更に含む、請求項17~19のいずれか1項に記載のバイオプリンタ。
- 前記ハウジング内に配置され、前記ハウジング内に気流を引導するように構成された気流システムを更に含む、請求項18~20のいずれか1項に記載のバイオプリンタ。
- 前記カートリッジレセプタクルと前記印刷ステージとが配置されるホルダを更に含む、請求項17~21のいずれか1項に記載のバイオプリンタ。
- 軌道を有する第1位置決め部を更に含み、前記第1位置決め部は、前記ホルダに結合され、その軌道に沿って前記ホルダの位置決めを行うように構成される、請求項22に記載のバイオプリンタ。
- 軌道を有する第2位置決め部を更に含み、前記第2位置決め部は、前記プリントヘッドアセンブリに結合され、その軌道に沿って前記プリントヘッドアセンブリの位置決めを行うように構成される、請求項17~23のいずれか1項に記載のバイオプリンタ。
- 請求項1~17のいずれか1項に記載のプリントヘッドの分配システムから複数の流体液滴を分配することにより三次元(3D)細胞構造を印刷する方法。
- 請求項17~24のいずれか1項に記載のバイオプリンタの分配システムから複数の流体液滴を基板上に分配することにより三次元(3D)細胞構造を制作する方法。
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