JP5750102B2 - 生物細胞の特性又は挙動を特徴づけるためにバイオセンシングするマイクロプレートの振動 - Google Patents
生物細胞の特性又は挙動を特徴づけるためにバイオセンシングするマイクロプレートの振動 Download PDFInfo
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Description
実験結果
1.メンブレンバイオセンシングデバイスの組立て
2.生物学的実験
1.最初に、シリコンマイクロメンブレンが洗浄され、そして洗浄液(エタノール及びアセトン混合物)、オートクレーブ処理、及びUV光照射を用いて滅菌された。
2.マイクロメンブレン上に細胞を播種する前に、継代プロセス期間中に懸濁液の細胞密度が規定された。生存細胞数が、細胞懸濁液20μlを取り出し、そしてこれをトリパンブルー20μlと混合することにより見積もられた。次に、細胞数の計測が改良されたNeubauer血球計算器を用いて、この新しい混合物について実施された。細胞密度が規定されたら、密度が既知のEA.hy926細胞からなる細胞懸濁液5mlが、培地を用いて調製された。インキュベーション時間を制御することにより、メンブレン表面上に様々な細胞密度及び分布を実現することができる。
3.メンブレンセンシング表面上の細胞分布がLSM(レーザースキャン顕微鏡検査)画像を用いて記録された。細胞の密度又は分布は、このLSM画像に基づき定量可能である。
4.接着細胞を伴うメンブレンの動力学は、図6の基礎励起装置により測定された。細胞情報を推測するために、細胞を伴う及び細胞を伴わない個々のマイクロメンブレンそれぞれに関するFRFデータが比較され、その情報はLSMスキャン画像に記録された。
5.最終的に、細胞はマイクロメンブレン表面から除去され、そしてステップ1の洗浄プロセスを繰り返した後、再滅菌されたマイクロメンブレンは次の実験に用いられた。
3.ニューラルネットワーク法
1.最初に、FRFマトリックス[H(ω)]M×Nに基づき、相関マトリックス[C]MXMが構築される。
2.次に、マトリックス[C]の固有値及び対応する固有ベクトルを計算して、それから主要成分が得られる。
[CIX]=λ[X](3)
3.最終的に、M個の抽出された固有値が調べられ、そして最初の数個の最大固有値が取り出される。次に、これらの最大固有値に関連した固有ベクトルが主要な成分であると考えられ、またオリジナルのFRFデータセットの最も重要な情報に該当し得るとみなされる。
Claims (14)
- 少なくとも1つの生物細胞の特性又は挙動を特徴づける方法であって、
マイクロプレートを提供するステップと、
特徴づけの対象となる少なくとも1つの生物細胞が前記マイクロプレートと接触した状態になるように、前記マイクロプレートの少なくとも1つの表面を液体中に水没させるステップと、
前記マイクロプレートを振動させるステップと、
前記マイクロプレートに取り付けられた、相互に隔てられた複数のセンサーを提供するステップと、
前記マイクロプレートが振動している間に、各センサーからそれぞれの時系列センサーデータを取得するステップであって、前記取得された時系列センサーデータが互いに独立しないように、前記マイクロプレート及び前記センサーが配置されている前記ステップと、
少なくとも1つの生物細胞の特性又は挙動を特徴づけるように前記時系列センサーデータを処理するステップと、
を含む方法。 - 前記処理ステップが、
細胞の動的挙動分類を規定するステップと、
前記少なくとも1つの細胞の動的挙動が、前記規定された細胞の動的挙動分類に該当するかどうか決定するように、前記時系列センサーデータを処理するステップと、
を含む、請求項1に記載の方法。 - 前記処理ステップが、
細胞特性を規定するステップと、
前記少なくとも1つの細胞の前記規定された特性を測定するかどうか決定するように前記時系列センサーデータを処理するステップと、
を含む、請求項1に記載の方法。 - 前記処理ステップが、時間ドメイン、周波数ドメイン、及びウェーブレットドメインの1つ又は複数における前記時系列センサーデータを解析するステップを含む、請求項1から3のいずれかに記載の方法。
- 前記処理ステップが、周波数応答関数(FRF)を解析するステップを含む、請求項1から4のいずれかに記載の方法。
- 前記処理ステップが、1つ又は複数のニューラルネットワーク及びカルーネン・レーベ分解を用いるステップを含む、請求項1から5のいずれかに記載の方法。
- 前記マイクロプレートを振動させるステップが、前記マイクロプレートを定期的に振動させるステップを含む、請求項1から6のいずれかに記載の方法。
- 前記マイクロプレートを振動させるステップが、前記マイクロプレートをランダムに振動させるステップを含む、請求項1から6のいずれかに記載の方法。
- 少なくとも1つの生物細胞の特性又は挙動を特徴づけるためのシステムであって、
液体用のコンテナーと、
前記コンテナーが少なくとも部分的に液体で満たされるときに、マイクロプレートの少なくとも1つの表面が、前記液体中に水没するように、前記コンテナー内に置かれた前記マイクロプレートと、
前記マイクロプレートを振動させるように作動可能な少なくとも1つのアクチュエーターと、
前記マイクロプレートに取り付けられた、相互に隔てられた複数のセンサーであって、各センサーが、前記マイクロプレートが振動している間、それぞれの時系列センサーデータを提供するように作動可能であり、前記マイクロプレート及び前記センサーが、前記提供された時系列センサーデータが互いに独立しないように配置されている前記センサーと、
前記センサーから前記時系列センサーデータを受け取るように、及び前記マイクロプレートに接触している少なくとも1つの生物細胞の特性又は挙動を特徴づけるために、受け取った前記時系列センサーデータを処理するように作動可能なプロセッサーと、
を備えるシステム。 - 前記マイクロプレートの境界の状態が、クランプで固定された状態、カンチレバー、非固定状態、及び点支持状態から選択される、請求項9に記載のシステム。
- 前記センサーが、ピエゾ抵抗素子ゲージセンサー、光学センサー、歪みセンサー、及び加速度センサーから選択される、請求項9又は請求項10に記載のシステム。
- 前記少なくとも1つのアクチュエーターが、圧電トランスデューサーを備える、請求項9から11のいずれかに記載のシステム。
- 前記少なくとも1つのアクチュエーターが、音波アクチュエーターを備える、請求項9から11のいずれかに記載のシステム。
- 前記コンテナーがペトリ皿である、請求項9から13のいずれかに記載のシステム。
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