细胞电旋转芯片的介电力场计算模型及系统构建
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摘要
生物芯片技术是90年代中期以来影响最深远的重大科技进展之一,是融微电子学、生物学、物理学、化学、计算机科学为一体的高度交叉的新技术,具有重大的基础研究价值,又具有明显的产业化前景。介电电泳芯片(Dielectrophoresis Chip, DEP Chip)技术作为一种重要的生物芯片技术,具有对生物体无损伤性以及快速、易与微系统合成等优点,迅速成为生命科学、分析化学等诸多领域中操控微系统内生物液体的主要手段。随着人们对该技术认识的不断深入,各种不同用途的采用了该技术的微系统器件被制作出来。其中,利用生物颗粒在旋转交流电场中电旋转频谱特性检测其电学参数的电旋转芯片己大量使用在生物细胞活性检测、细胞电导数及细胞膜电容的测量等筛选、监测和测量的研究领域。
本论文的研究工作主要包括：利用SCM方法对电旋转芯片的电场分布进行精确的解析解求解；对获得的介电力场分布进行误差分析,得到各区域的测量误差范围；对电旋转芯片实验中的测量误差进行相关分析并给出校正方案；对电旋转芯片中生物颗粒运动的成因及影响进行了研究；进而推导出了适用于介电电泳芯片设计的普适方程。在理论研究上,本文首次采用SCM方法和电场叠加的方法对电旋转芯片中处于不同电信号相位的电场分布作了解析求解,并通过解得的介电力场分析了生物颗粒在电旋转芯片中的运动成因,发现介电力场中两个介电力阱会随着电信号相位而周期改变位置是电旋转芯片中生物颗粒运动的主因。
本文进一步通过介电力场分布和电旋转转矩分布进行了电旋转芯片实验中测量误差的区域分析。通过测量误差的分析定义了一个适合电旋转测量的置信空间,该区域可定义为圆心在原点处、半径为环形电极的36%的一个圆形区域,区域内的电旋转转矩最大误差在5%以内。综合考虑介电力场对微粒摆动的影响后,该区域则可以定义为圆心在原点处、半径为环形电极的30%的圆形区域,在该区域内介电力场随着电信号相位的改变的波动幅度小于25%。该结果在本文中通过搭建的电旋转芯片实验平台进行了相关的实验验证。
由于本文中提出的基于SCM的电旋转芯片电场计算方法具有快速、精确和计算量小的特点,辅以图像处理技术,非常适合于电旋转芯片实验中的实时计算和校正。本文中根据研究结果给出了相关的可用于电旋转实验的实时计算校正方案。
本文中基于无源场拉普拉斯方程首次推导出了介电力普适方程,该普适方程的提出提高了对介电电泳中介电力场的认识,改变了以往介电电泳电极设计主要依靠经验的落后方法。针对该普适方程的求解,本文中提出了函数解析法和差分计算法两种方法。基于这两种方法,本文中提出了一种新型的介电电泳电极的设计方法。
Since the mid-90s, biochip technology is one of the most far-reaching strides in science and technology. Biochip is an interdisciplinary which integrated the financial microelectronics, biology, physics, chemistry, and computer science. Biochip has great value in basic research and significant industrial prospects. The dielectrophoresis chip (Dielectrophoresis Chip, DEP Chip) technology is one of the important bio-chip technologies. This technology has many advantages, such as without injury, fastly, and easily be integrated in micro-system. It becomes the mainly method to operate the bio-fluid in the micro-system within the life sciences, analysis chemistry and many other areas. With a deep understanding of this technology, many type micro-system components were studied. Among them, the electroration chip has been already widely applied on many areas including the measurement of the cell activity, the cell conductance and cell membrane capacitance. This chip measured these parameters using the spectrum of the biological particles in the chip.
The work in this paper mainly including solving analytical solution of the electric field distribution in the electroration chip using SCM method; analsising the measurement error of each area by the distribution of the dielectrophoretic force field in electroration chip; studying the reason and the effects of the biological particles'moving during the measurement; design the dielectrophoresis chip with the new universal equation which derived in this paper. In theory, the paper first solved analytical solution of the electric field distribution with different phase of the potential using the SCM method and the electric field superposition theorem. And the reason of the biological particles'moving were analyzed by the distribution of the dielectrophoretic force field solved. Based on the above, the main reason we found was that two dielectrophoretic force traps change their position with the potential phase changing.
The measurement errors within different areas were analysed by the distribution of the dielectrophoretic force field and the electic field in this paper. An area was defined base on the analysis of the measurement errors in wich the measurement on the biological particles has negligible error. This area can be defined as a circle area which the center is the origin point and the radius is 36% of the radius of the electrode. The maxium error in this area is less than 5%. Considering the biological particles' moving, this area is redefined as a circle area which radius is just 30% of the radius of the electrode. The fluctuations of the dielectrophoretic force at any position in this area are less than 25%. Related experiments described in this paper validated the theory above.
The SCM method given in this paper has many advantages, such as calculation rapidly, accurate result and using less computation resource. Combined with image processing technology, the SCM method is a best method to real-time compute and correct the measurement result. The detail of relevant method and algorithm is described below in this paper.
A new method to design the dielectrophoretic electrode was described in this paper. This method is based on the universal equation which is derived from Laplace equation. This universal equation raised the awareness of dielectrophoresis, changed the common design methods which mainly based on experience. For the universal equation, In this paper, two methods were metioned to solve the universal equation. The one is analytical method, and the other is the difference method.
本论文的研究工作主要包括：利用SCM方法对电旋转芯片的电场分布进行精确的解析解求解；对获得的介电力场分布进行误差分析,得到各区域的测量误差范围；对电旋转芯片实验中的测量误差进行相关分析并给出校正方案；对电旋转芯片中生物颗粒运动的成因及影响进行了研究；进而推导出了适用于介电电泳芯片设计的普适方程。在理论研究上,本文首次采用SCM方法和电场叠加的方法对电旋转芯片中处于不同电信号相位的电场分布作了解析求解,并通过解得的介电力场分析了生物颗粒在电旋转芯片中的运动成因,发现介电力场中两个介电力阱会随着电信号相位而周期改变位置是电旋转芯片中生物颗粒运动的主因。
本文进一步通过介电力场分布和电旋转转矩分布进行了电旋转芯片实验中测量误差的区域分析。通过测量误差的分析定义了一个适合电旋转测量的置信空间,该区域可定义为圆心在原点处、半径为环形电极的36%的一个圆形区域,区域内的电旋转转矩最大误差在5%以内。综合考虑介电力场对微粒摆动的影响后,该区域则可以定义为圆心在原点处、半径为环形电极的30%的圆形区域,在该区域内介电力场随着电信号相位的改变的波动幅度小于25%。该结果在本文中通过搭建的电旋转芯片实验平台进行了相关的实验验证。
由于本文中提出的基于SCM的电旋转芯片电场计算方法具有快速、精确和计算量小的特点,辅以图像处理技术,非常适合于电旋转芯片实验中的实时计算和校正。本文中根据研究结果给出了相关的可用于电旋转实验的实时计算校正方案。
本文中基于无源场拉普拉斯方程首次推导出了介电力普适方程,该普适方程的提出提高了对介电电泳中介电力场的认识,改变了以往介电电泳电极设计主要依靠经验的落后方法。针对该普适方程的求解,本文中提出了函数解析法和差分计算法两种方法。基于这两种方法,本文中提出了一种新型的介电电泳电极的设计方法。
Since the mid-90s, biochip technology is one of the most far-reaching strides in science and technology. Biochip is an interdisciplinary which integrated the financial microelectronics, biology, physics, chemistry, and computer science. Biochip has great value in basic research and significant industrial prospects. The dielectrophoresis chip (Dielectrophoresis Chip, DEP Chip) technology is one of the important bio-chip technologies. This technology has many advantages, such as without injury, fastly, and easily be integrated in micro-system. It becomes the mainly method to operate the bio-fluid in the micro-system within the life sciences, analysis chemistry and many other areas. With a deep understanding of this technology, many type micro-system components were studied. Among them, the electroration chip has been already widely applied on many areas including the measurement of the cell activity, the cell conductance and cell membrane capacitance. This chip measured these parameters using the spectrum of the biological particles in the chip.
The work in this paper mainly including solving analytical solution of the electric field distribution in the electroration chip using SCM method; analsising the measurement error of each area by the distribution of the dielectrophoretic force field in electroration chip; studying the reason and the effects of the biological particles'moving during the measurement; design the dielectrophoresis chip with the new universal equation which derived in this paper. In theory, the paper first solved analytical solution of the electric field distribution with different phase of the potential using the SCM method and the electric field superposition theorem. And the reason of the biological particles'moving were analyzed by the distribution of the dielectrophoretic force field solved. Based on the above, the main reason we found was that two dielectrophoretic force traps change their position with the potential phase changing.
The measurement errors within different areas were analysed by the distribution of the dielectrophoretic force field and the electic field in this paper. An area was defined base on the analysis of the measurement errors in wich the measurement on the biological particles has negligible error. This area can be defined as a circle area which the center is the origin point and the radius is 36% of the radius of the electrode. The maxium error in this area is less than 5%. Considering the biological particles' moving, this area is redefined as a circle area which radius is just 30% of the radius of the electrode. The fluctuations of the dielectrophoretic force at any position in this area are less than 25%. Related experiments described in this paper validated the theory above.
The SCM method given in this paper has many advantages, such as calculation rapidly, accurate result and using less computation resource. Combined with image processing technology, the SCM method is a best method to real-time compute and correct the measurement result. The detail of relevant method and algorithm is described below in this paper.
A new method to design the dielectrophoretic electrode was described in this paper. This method is based on the universal equation which is derived from Laplace equation. This universal equation raised the awareness of dielectrophoresis, changed the common design methods which mainly based on experience. For the universal equation, In this paper, two methods were metioned to solve the universal equation. The one is analytical method, and the other is the difference method.
引文
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