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首页> 外文学位 >Development of piezoresistive microcantilever based force feedback system for analysis of mechanosensation in Caenorhabditis elegans nematodes.
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Development of piezoresistive microcantilever based force feedback system for analysis of mechanosensation in Caenorhabditis elegans nematodes.

机译：基于压阻式微悬臂梁力反馈系统的开发，用于分析秀丽隐杆线虫线虫的机械感觉。

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摘要

Cellular mechanotransduction, or the conversion of a force into an electrochemical signal, is a fundamental process underlying our senses of hearing, touch and balance. While hearing and balance have been studied in detail, our sense of touch is only poorly understood. Caenorhabditis elegans, a nematode only about 1 mm in length, is a powerful model organism in which to analyze the mechanism of touch sensation and widely used in biology and medicine. However, few techniques exist to provide the minute forces and displacements appropriate for studies of touch sensation in C. elegans. To address this technological gap, we developed a metrology using piezoresistive cantilevers as force-displacement sensors coupled to a feedback system in order to apply and maintain defined load profiles in the nN-mN range. This thesis presents (1) the design and optimization of piezoresistive cantilevers, (2) integration and development of the force clamp system, and (3) direct application of the system to biological studies of C. elegans mechanotransduction.;Analytical modeling and optimization techniques are very useful in the design of piezoresistive devices with complex design constraints. We developed and validated a new analytical model for piezoresistive cantilevers. The model accurately predicted the force sensitivity and force resolution of a wide variety of piezoresistive cantilevers, as measured using laser doppler velocimetry. Using the analytical model, which also utilized doping profile results from TSUPREM simulations, we systemically analyzed the effect of process parameters on device sensitivity and force resolution. With this analytical model, we also developed an optimization approach for piezoresistive cantilever design. We evaluated the approach by fabricating and testing cantilevers designed using the optimization technique. The optimization technique was utilized to produce an optimal cantilever with a minimum force resolution of 69 pN over a 1-1000 Hz bandwidth.;We also conducted biological studies of C. elegans mechanotransduction by integrating the developed force probe with a force and displacement feedback control system. We measured body stiffness of wild type and mutant animals with altered body shape and cuticle proteins exposed to solutions of varying osmolarity. The results suggest that shell mechanics dominates C. elegans stiffness rather than hydrostatic pressure, which is contrary to common belief. We also studied the behavioral response of C. elegans to touch stimuli by utilizing the system in force-clamp mode. We applied a 100 nN to 10 mN step force to freely-moving wild type and mec-4 mutant animals, which lack touch receptor neurons. The behavioral result agrees with prior in-vivo work, which suggests that the physiological responses of wild type animals to touch saturate near a force threshold between 100 nN and 1 mN. These initial analyses provide new insights into the mechanism of touch sensation in C. elegans, and open the door to a wide variety of future experiments with C. elegans nematodes, from mechanics to electrophysiology.
机译：细胞机械转导，或将力转换为电化学信号，是我们听觉，触觉和平衡感的基础过程。虽然已详细研究了听力和平衡能力，但对触摸感的了解却很少。秀丽隐杆线虫（Caenorhabditis elegans）是一种仅约1 mm长的线虫，是一种功能强大的模型生物，可用于分析触感的机制，并广泛用于生物学和医学领域。但是，很少有技术可以提供适合研究秀丽隐杆线虫触摸感的微小力和位移。为了解决这一技术差距，我们开发了一种使用压阻悬臂作为与反馈系统耦合的力-位移传感器的度量衡技术，以便在nN-mN范围内施加并保持定义的载荷曲线。本文提出（1）压阻悬臂的设计和优化，（2）力钳系统的集成和开发，（3）该系统直接用于秀丽隐杆线虫机械转导的生物学研究。;分析建模和优化技术在具有复杂设计约束的压阻器件的设计中非常有用。我们开发并验证了压阻悬臂梁的新分析模型。该模型可准确预测各种压阻悬臂的力灵敏度和力分辨率，如使用激光多普勒测速仪测量的那样。使用分析模型，该模型还利用了TSUPREM模拟的掺杂轮廓结果，我们系统地分析了工艺参数对器件灵敏度和力分辨率的影响。利用该分析模型，我们还开发了压阻悬臂设计的优化方法。我们通过制造和测试使用优化技术设计的悬臂来评估该方法。该优化技术用于在1-1000 Hz带宽内产生最小悬臂力分辨率为69 pN的最佳悬臂梁。我们还通过将开发的力探头与力和位移反馈控制相集成来进行秀丽隐杆线虫机械转导的生物学研究。系统。我们测量了野生型和突变动物的身体刚度，这些动物的体型和表皮蛋白质暴露于不同的渗透压，其形态发生改变。结果表明，壳力学主导线虫的刚度而不是静水压力，这与普遍的看法相反。我们还研究了线虫在力钳模式下利用触觉刺激的行为反应。我们将100 nN到10 mN的阶跃力施加到自由移动的缺乏触摸受体神经元的野生型和mec-4突变动物上。该行为结果与先前的体内工作一致，这表明野生型动物触摸的生理反应在100 nN和1 mN之间的力阈值附近达到饱和。这些初步分析为秀丽隐杆线虫的触感机理提供了新的见解，并为今后从线虫到线虫的从机械到电生理的各种实验打开了大门。

著录项

  • 作者

    Park, Sung-Jin.;

  • 作者单位

    Stanford University.;

  • 授予单位 Stanford University.;
  • 学科 Engineering Mechanical.;Biophysics General.
  • 学位 Ph.D.
  • 年度 2009
  • 页码 140 p.
  • 总页数 140
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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