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，我们开发了关键设备，例如由压电薄膜驱动的用于增强细胞功能的生物微型设备本发明涉及通过对细胞施加机械刺激来实现细胞增殖（细胞增殖和基因转移）的纳米针阵列和能够将感兴趣的生物分子引入活细胞中并并行提取在细胞中表达的生物分子的纳米针阵列。我们使用有限元法（FEM）优化了生物微器件的设计。当PZT薄膜驱动器上施加10 V的电压时，氮化硅（Si_3N_4）膜片（尺寸大于100×100 μm^2）中心处的最大位移估计大于100 nm的目标值。此外，我们还采用溶胶-凝胶法制备了PZT薄膜作为驱动器，并对其晶体结构进行了表征。结果表明，在320℃热解1 min，然后在空气中600℃退火1 min，得到了（111）取向的PZT薄膜。具有圆形尖端形状的二氧化硅（SiO_2）针阵列（内径3.5 μm，采用各向异性深反应离子刻蚀（DRIE）工艺在Si衬底上形成通孔，然后进行湿法氧化，并结合各向同性XeF_（1-x）工艺，成功地制备了外径为6.0 μm，高度为45 μm的2刻蚀工艺，留下SiO_2纳米针结构。为了在玻璃基板中制造高纵横比的微通道和通孔，还开发了使用聚合物（PDMS）作为掩模材料的喷砂技术，该掩模材料使用厚光致抗蚀剂（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

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

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