Development of Cell Surgery System on a Chip with Nanoneedle Array

纳米针阵列芯片上细胞手术系统的开发

• 批准号: 16300147
• 负责人: SHIBATA Takayuki
• 金额: $ 9.79万
• 依托单位: Toyohashi University of Technology (2005)Ibaraki University (2004)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16300147/
• 关键词: Cell surgery system; Nanoneedle; MEMS; BioMEMS; PZT thin film; Actuator; Gene transfer; Cell multiplication

In order to realize cell surgery on a chip-based system, we have developed key devices such as a bio-microdevice actuated by piezoelectric thin film for the enhancement of cell functions (cell multiplication and gene transfer) by applying mechanical stimulation to cells and a nanoneedle array capable of introducing biomolecules of interest into living cells and the parallel extracting biomolecules expressed in the cells.First, we optimized the design of the bio-microdevice using a finite element method (FEM). The maximum displacement at the center of a silicon nitride (Si_3N_4) diaphragm (with more than 100×100 μm^2 in size) was estimated to be more than the target value of 100 nm, when a voltage of 10 V was applied to the PZT thin film actuator. Moreover, we fabricated PZT thin film to be used as an actuator by a sol-gel method, and characterized its crystallographic structure. As a result, when pyrolysis at 320℃ for 1 min and then annealed at 600℃ for 1 min in air, PZT thin films with (111) orientation were obtained.In addition, we developed a novel and simple micromachining technique for the fabrication of out-of-plane, hollow nanoneedles in array. An array of silicon dioxide (SiO_2) needles with a circler tip shape (an inner diameter of 3.5 μm, an outer diameter of 6.0 μm and a height of 45 μm) were successfully fabricated by a combination of an anisotropic deep reactive ion etching (DRIE) process for producing thorough holes into a Si substrate as a needle mold followed by wet oxidation and an isotropic XeF_2 etching process for leaving SiO_2 nanoneedle structures. In order to fabricate high-aspect-ratio microchannels and through holes in a glass substrate, a sand blasting technique using a polymer (PDMS) as a mask material, which was patterned using a thick photoresist (SU-8) as a mold, was also developed.

为了在基于CHIP的系统上实现细胞手术，我们开发了关键设备，例如通过压电电离薄膜激活的生物 - 微观看息，以增强细胞功能（细胞繁殖和基因转移），通过将机械刺激应用于细胞和能够将生物元素引入生物元素的纳米型阵列中，并将生物元素用于生物元素，并将其引入生物元素，并将其引入生物元素，并将生物元素提取到活性单元格中，并将其排除在生物元素中，并将生物元素提取到活性细胞中使用结局元素方法（FEM）优化了Bio-Microdevice的设计。当将10 V电压施加到PZT薄膜执行器时，估计氮化硅（SI_3N_4）隔膜的最大位移（SI_3N_4）隔膜（尺寸大于100×100μm^2）的最大位移估计高于100 nm的目标值。此外，我们制造了PZT薄膜，可通过Sol-Gel方法用作执行器，并表征了其晶体学结构。结果，当在空气中以320℃进行热解，然后在空气中以600℃退火1分钟时，获得了带有（111）方向的PZT薄膜。此外，我们开发了一种新颖而简单的微机械技术，用于制造非平面外，空心的nanOneedles。 An array of silicon dioxide (SiO_2) needles with a circler tip shape (an inner diameter of 3.5 μm, an outer diameter of 6.0 μm and a height of 45 μm) were successfully fabricated by A combination of an anisotropic deep reactive ion etching (DRIE) process for producing thorough holes into a Si substrate as a needle mold followed by wet oxidation and an各向同性XEF_2蚀刻过程，用于离开sio_2纳米编结构。为了在玻璃基板的孔中构建高敏关系微通道，并通过使用聚合物（PDMS）作为掩模材料的砂爆炸技术，该技术也被开发为使用厚的光蛋白天（Su-8）作为模具进行图案化。

项目成果

Development of bio-microdevice actuated by piezoelectric thin film for enhancement of cell functions

开发压电薄膜驱动的生物微器件以增强细胞功能

• 发表时间: 2005
• 期刊: Proc.of the Japan Society for Precision Engineering (JSPE) Autumn Conference (in Japanese)
• 作者: N.Yoshida;T.Shibata;Y.Mizukami;O.Horiuchi;T.Masuzawa;T.Mineta;E.Makino
• 通讯作者: E.Makino

Accelerating system of cell multiplication with nanometer vibration

纳米振动细胞增殖加速系统

• 发表时间: 2004
• 期刊: Proc.of Ibaraki Distinct Conference of the Japan Society of Mechanical Engineers (in Japanese) No.040-3
• 作者: J.Kusama;M.Ishimaru;T.Masuzawa;T.Kimura;T.Shibata;A.Kishida
• 通讯作者: A.Kishida

オンチップ細胞サージェリーシステムのためのナノニードルアレイの開発-シリコンのドライエッチング特性の評価-

用于片上细胞手术系统的纳米针阵列的开发-硅干蚀刻特性的评价-

• 发表时间: 2005
• 期刊: 精密工学会秋季大会学術講演会講演論文集
• 作者: 伊藤圭介;柴田隆行;水上良明;堀内 宰;増澤 徹 ほか
• 通讯作者: 増澤 徹 ほか

細胞機能制御のためのMEMS細胞加振デバイスの開発

开发用于细胞功能控制的MEMS细胞振动装置

• 发表时间: 2005
• 期刊: 電気学会研究会資料(リニアドライブ研究会)
• 作者: 吉田典央;柴田隆行;堀内 宰;増澤 徹;岸田晶夫
• 通讯作者: 岸田晶夫

Development of Bio-Microdevice Actuated by Piezoelectric Thin Film for Cell Culture

压电薄膜驱动的细胞培养生物微器件的研制

• 发表时间: 2005
• 期刊: Proc. 5th Int. Conf. and 7th Annual General Meeting of the European Soc. for Precision Engineering and Nanotechnology
• 作者: T.Shibata;Y.Makita;T.Masuzawa;A.Kishida;E.Makino;T.Mineta
• 通讯作者: T.Mineta