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.

为了在基于芯片的系统上实现细胞手术，我们开发了关键器件，例如由压电薄膜驱动的生物微型器件，通过对细胞施加机械刺激来增强细胞功能（细胞增殖和基因转移），以及纳米针阵列能够将感兴趣的生物分子引入活细胞中并并行提取细胞中表达的生物分子。首先，我们使用有限元方法（FEM）优化了生物微器件的设计。当对 PZT 薄膜致动器施加 10 V 的电压时，氮化硅（Si_3N_4）隔膜（尺寸超过 100×100 μm^2）估计超过 100 nm 的目标值。通过溶胶-凝胶方法制备了用作致动器的 PZT 薄膜，并表征了其在 100 ℃热解时的晶体结构。 320℃ 1 min，然后在空气中 600℃ 退火 1 min，得到具有（111）取向的 PZT 薄膜。此外，我们开发了一种新颖且简单的微加工技术，用于制造面外、空心薄膜。纳米针阵列，具有圆形尖端形状（内径为 3.5 μm，外径为 6.0 μm，直径为 6.0 μm）。通过结合各向异性深反应离子蚀刻（DRIE）工艺在硅基板上形成通孔作为针模，然后进行湿氧化和各向同性 XeF_2 蚀刻工艺留下 SiO_2 纳米针结构，成功制备了高度为 45 μm）。为了在玻璃基板上制造高深宽比的微通道和通孔，采用喷砂技术，使用聚合物（PDMS）作为掩模材料，将其图案化还开发了使用厚光刻胶（SU-8）作为模具的技术。

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