聚合酶链式反应生物芯片系统的设计研究
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摘要
聚合酶链式反应(Polymerase Chain Reaction, PCR)广泛应用于生命科学的各个领域。集成化的PCR生物芯片充分利用芯片热容量小、比表面积大、节省珍贵样品的优点使得该项技术应用更加方便快捷、高效可靠。
本文的研究内容包括:首先针对PCR反应所需的温度均衡性,应用有限元分析方法优化加热电极形状及微腔反应室的高度。采用基于微加工技术的研究方法,在0.2mm厚的玻璃基片集成Pt加热电极及温度传感器,针对高分子聚合物聚碳酸酯(PC)热模压工艺参数进行了研究并制作出芯片微反应室的腔体。其次对于Pt传感器温度电阻公式进行分析测得所制作的Pt传感器的电阻温度系数。之后对传感器微信号的获取进行了深入研究并采用了以精准恒流源LM336-2.5、AD620以及OP07为基础的高精度放大电路。最后采用以FPGA为核心的控制系统,用VHDL硬件描述语言实现包括AMP、AD、PID、PWM和LCD等模块,用ISE软件完成编译下载实现系统功能。该系统有利于PCR系统的升级并能有效集成到微全分析系统中。
基于玻璃基片和聚碳酸酯实现的PCR芯片集成了DNA反应室、Pt加热电极及温度传感器等功能组件。微腔反应室容积约为5微升。通过简化芯片的微结构、微加工工艺和微加工设备,制作出较低成本PCR芯片。同时对芯片的控制系统进行了研究,构建了以FPGA为核心的控制系统。
Polymerase Chain Reaction (PCR) is widely used in every field of life sciences. Integrated PCR biochip has the advantages of small heat capacity, high specific surface areas and saving Precious samples, which made its application more convenient, faster, efficient and reliable.
The research contents of this thesis focus on the temperature proportionality of PCR reaction, to optimize heating electrode shape and the height of micro-cavity Chamber by Finite element analysis. Using Micro-processing technology, Platinum electrode and temperature sensor is integrated into Glass Substrate of 0.2mm. What’s more, polycarbonate hot molding process Parameters is studied and the biochip chamber is made. And then we got Temperature Coefficient of Resistance of platinum sensor that has been made by analyzing Temperature resistance formula of platinum sensor. Later on signal acquisition was studied by applying Amplifying Circuit of High Precision of Precision current source focus on LM336-2.5, AD620 and OP07. Finally control system focused on FPGA was applied; using VHDL Hardware Description Language to implement AMP, AD, PID, PWM, LCD and so on, Compiling and downloading was finished by a software named ISE so as to implement system function. The system can help PCR to upgrade and integrate into Micro-Total Analysis System efficiently.
The PCR biochip on Glass Substrate and polycarbonate (PC) integrated into functional unit such as DNA chamber, platinum electrode temperature sensor, etc. The Volume of micro-cavity Chamber is about 5 ul. We can lower the PCR biochip cost by simplifying the micro-structure of biochip, Micro-machining process and equipments. Meanwhile the biochip control system was studied and constructed on FPGA .
本文的研究内容包括:首先针对PCR反应所需的温度均衡性,应用有限元分析方法优化加热电极形状及微腔反应室的高度。采用基于微加工技术的研究方法,在0.2mm厚的玻璃基片集成Pt加热电极及温度传感器,针对高分子聚合物聚碳酸酯(PC)热模压工艺参数进行了研究并制作出芯片微反应室的腔体。其次对于Pt传感器温度电阻公式进行分析测得所制作的Pt传感器的电阻温度系数。之后对传感器微信号的获取进行了深入研究并采用了以精准恒流源LM336-2.5、AD620以及OP07为基础的高精度放大电路。最后采用以FPGA为核心的控制系统,用VHDL硬件描述语言实现包括AMP、AD、PID、PWM和LCD等模块,用ISE软件完成编译下载实现系统功能。该系统有利于PCR系统的升级并能有效集成到微全分析系统中。
基于玻璃基片和聚碳酸酯实现的PCR芯片集成了DNA反应室、Pt加热电极及温度传感器等功能组件。微腔反应室容积约为5微升。通过简化芯片的微结构、微加工工艺和微加工设备,制作出较低成本PCR芯片。同时对芯片的控制系统进行了研究,构建了以FPGA为核心的控制系统。
Polymerase Chain Reaction (PCR) is widely used in every field of life sciences. Integrated PCR biochip has the advantages of small heat capacity, high specific surface areas and saving Precious samples, which made its application more convenient, faster, efficient and reliable.
The research contents of this thesis focus on the temperature proportionality of PCR reaction, to optimize heating electrode shape and the height of micro-cavity Chamber by Finite element analysis. Using Micro-processing technology, Platinum electrode and temperature sensor is integrated into Glass Substrate of 0.2mm. What’s more, polycarbonate hot molding process Parameters is studied and the biochip chamber is made. And then we got Temperature Coefficient of Resistance of platinum sensor that has been made by analyzing Temperature resistance formula of platinum sensor. Later on signal acquisition was studied by applying Amplifying Circuit of High Precision of Precision current source focus on LM336-2.5, AD620 and OP07. Finally control system focused on FPGA was applied; using VHDL Hardware Description Language to implement AMP, AD, PID, PWM, LCD and so on, Compiling and downloading was finished by a software named ISE so as to implement system function. The system can help PCR to upgrade and integrate into Micro-Total Analysis System efficiently.
The PCR biochip on Glass Substrate and polycarbonate (PC) integrated into functional unit such as DNA chamber, platinum electrode temperature sensor, etc. The Volume of micro-cavity Chamber is about 5 ul. We can lower the PCR biochip cost by simplifying the micro-structure of biochip, Micro-machining process and equipments. Meanwhile the biochip control system was studied and constructed on FPGA .
引文
[1] Xia Y., Whitesides G. M. Soft Lithography. Angew. Chem. Int. Ed., 1998, 37: 550-575
[2]程京.生物芯片技术与应用,中国科学技术前沿.北京:高等教育出版社, 2000
[3] Lagally ET, Scherer JR, Blazej RG, Mathies RA. Genetic analysis using a portable PCR-CE microsystem. Micro Total Analysis System, California USA; 2003: 1283–6
[4] Liu CN, Toriello NM, Mathies RA. Multichannel PCR-CE microdevice for genetic analysis. Anal Chem, 2006, 78(15): 5474-9
[5] Huang FC, Liao CS, Lee GB. An integrated microfluidic chip for DNA/RNA amplification, electrophoresis separation and on-line oPtical detection. Electrophoresis, 2006, 27: 3297-305
[6] P. J. Obeid, T. K. Christopoulos, H. J. Crabtree, et al. Microfabricated device for DNA and RNA amplification by continuousflow polymerase chain reaction and reverse transcriPtion-polymerase chain reaction with cycle nμmber selection, Anal. Chem, 2003, 75: 288-295
[7] L. J. Kricka, P. Wilding, Microchip PCR, Anal. Bioanal. Chem, 2003, 377: 820-825
[8] Toriello NM, Liu CN, Mathies RA. Multichannel reverse transcriPtionpolymerase chain reaction microdevice for rapid gene expression and biomarker analysis. Anal Chem, 2006, 78(23): 7997-8003
[9] Jing Cheng, Larry J. Kricka. Biochip Technology. Harwood Academic Publishers, 2001
[10] Auroux P-A, Iossifidis D, Reyes DR, Manz A. Micro total analysis systems: 2. Analytical standard operations and applications. Anal Chem, 2002, 74: 2637-52
[11] Dittrich PS, Tachikawa K, Manz A. Micro total analysis systems. Latest advancements and trends. Anal Chem, 2006, 78: 3887-908
[12] Manz A, Graber N, Widmer HM. miniaturized total analysis systems: a novel concePt for chemical sensing. Sens Actuators B Chem, 1990, 1(1): 244-8
[13] Vilkner T, Janasek D, Manz A. Micro total analysis systems: recent developments. Anal Chem, 2004, 76: 3373-86
[14] Reyes DR, Iossifidis D, Auroux P-A, Manz A. Micro total analysis systems: 1. Introduction, theory, and technology. Anal Chem, 2002, 74: 2623-36
[15] Y. C. Lin, M. Y. Huang, K. C. Young, et al. A rapid micropolymerasechain reaction system for hepatitis C virus amplification. Sens. Actuators, 2000, B 71: 2-8
[16] E. T. Lagally, C. A. Emrich, R. A. Mathies, Fullyintegrated PCR-capillaryelectrophoresis microsystem for DNA analysis, Lab. Chip, 2001, 1(2): 102-107
[17] M. Bu, T. Melvin, G. Ensell, et al. Design and theoretical evaluation of a novel microfluidic device to be used for PCR, J. Micromech. Microeng, 2003, 13: S125-S130
[18] C. G. J. Schabmueller, J. R. Pollard, A. G. R. Evans, J. S. Wilkinson, G. Ensell, A. Brunnschweiler, Integrated diode detector and oPtical fibres for in situ detection within micromachined polymerase chain reaction chips, J. Micromech. Microeng, 1990, 11: 329-333
[19] M. A. Northrup, B. Benett, D. Hadley, et al. A miniature analytical instrμment for nucleic acids based onmicromachined silicon reaction chambers, Anal. Chem, 1998, 70: 918-922
[20] M. U. Kopp, A. Manz. Chemical amplification: continuous-flow PCR on achip. Science, 1998, 280: 1046-1048
[21] Pavel Neuzil Chunyan Zhang Juergen Pipper, Ultra fast miniaturized real-time PCR: 40 cycles in less than six minutes Nucleic Acids Research, 2006, 34: e77
[22] Lagally ET, Scherer JR, Blazej RG, et al. Integrated portable genetic analysis microsystem for pathogen/infectious disease detection. Anal Chem 2004;76(11): 3162-70
[23] Liu CN, Toriello NM, Mathies RA. Multichannel PCR-CE microdevicefor genetic analysis. Anal Chem, 2006, 78(15): 5474-9
[24] P, Seo TS, Beyor N, Shin K, et al. Integrated portable PCR-capillary electrophoresis microsystem for rapid forensic short tandem repeat typing. Anal Chem, 2007, 79(5): 1881-9
[25] Kaigala GV, Huskins RJ, Preiksaitis J, et al. Automated screening using microfluidic chipbased PCR and product detection to assess risk of BK virusassociated nephropathy in renal transplant recipients. Electrophoresis, 2006, 27: 3753-63
[26] Oh KW, Park C, Namkoong K, et al. World-tochip microfluidic interface with built-in valves for multichamber chip-based PCR assays. Lab Chip 2005a, 5: 845-50
[27] Lien KY, Lee WC, Lei HY, Lee GB. Integrated reverse transcriPtion polymerase chain reaction systems for virus detection. Biosens Bioelectron, 2007, 22: 1739-48
[28] J. N. Yang, Y. J. Liu, C. B. Rauch, et al. Grodzinski, High sensitivity PCR assay in plastic micro reactors, Lab on a Chip, 2002, 2: 179-187
[29] B. C. Giordano, J. Ferrance, S. Swedberg, et al. Polymerase chain reaction in polymeric microchips: DNA amplificationin less than 240 s, Anal. Biochem, 2001, 291: 124-132
[30] P. Sethu, C. H. Mastrangelo. Cast epoxy-based microfluidic systems and their application in biotechnology, Sens. Actuators B: Chem, 2004, 98: 337-346
[31] J. W. Hong, T. Fujii, M. Seki, et al. Integration of gene amplification and capillary gel electrophoresis on a polydimethylsiloxane-glass hybrid microchip. Electrophoresis, 22
[32] E. T. Lagally, P. C. Simpson, R. A. Mathies. Monolithic integrated microfluidic DNA amplification and capillary electrophoresis analysis system. Sens. Actuators B: Chem, 2000, 63: 138-146
[33] H. Nagai, Y. Murakami, Y. Morita, et al. Development of a microchamber array for picoliter PCR. Anal. Chem, 2001, 73: 1043-1047
[34] J. Kim, M. K. Chaudhury, M. J. Owen. Hydrophobicity loss and recovery of silicone HV insulation. IEEE Trans. Dielectr. Electr. Insul, 1999, 6: 695-702
[35] H. Hillborg, U. W. Gedde. Hydrophobicity changes in silicone rubbers. IEEE Trans. Dielectr. Electr. Insul, 1999, 6: 703-717
[36] J. C. Lotters, W. Olthuis, P. H. Veltink, et al. Polydimethylsiloxane, a photocurable rubberelastic polymer used as spring materialin micromechanical sensors. Microsyst. Technol, 1997, 3: 64-67
[37] Y. S. Shin, K. Cho, S. H. Lim, et al. PDMS-based micro PCR chip with parylene coating. J. Micromech. Microeng, 2003, 13: 768-774
[38] X. M. Yu, D. C. Zhang, T. Li, et al. 3-D microarrays biochip for DNA amplification in polydimethylsiloxane (PDMS) elastomer. Sens. Actuators A: Phys, 2003, 108: 103-107
[39] J. Liu, M. Enzelberger, S. Quake. A nanoliter rotary device for polymerase chain reaction. Electrophoresis, 2002, 23: 1531-1536
[40] J. Liu, C. Hansen, S. R. Quake. Solving the“world-to-chip”interface problem with a microfluidic matrix. Anal. Chem, 2003, 75: 4718-4723
[41] J. C. McDonald, G. M. Whitesides. Poly(dimethylsiloxane) as a material for fabricating microfluidic devices. Acc. Chem. Res., 2002, 35: 491-499
[42] B. D. Gates, G. M. Whitesides. Replication of vertical features smaller than 2 nm by soft lithography. J. Am. Chem. Soc., 2003, 125: 14986-14987
[43]方擎伦.微流控分析芯片的制作及应用.北京:化学工业出版社, 2005
[44] Pilarski PM, Adamia S, Backhouse CJ. An adaPtable microvalving system for on-chip polymerase chain reactions. J Immunol Methods, 2005, 305: 48-58
[45] Prakash R, Kaler KVIS. An integrated genetic analysis microfluidic platform with valves and a PCR chip reusability method to avoid contamination. Microfluid Nanofluid, 2007, 3: 177-87
[46]高尚通.跨世纪的微电子封装.半导体情报, 2000, 37(6): 1-7
[47]张朝晖. ANSYS8. 0热分析教程与实例解析.北京:中国铁道出版社, 2005
[48]章熙民,任泽霈.传热学.北京:中国建筑工业出版社, 2001
[49]孔祥谦,有限单元法在传热学中的应用.北京:科学出版社, 1981
[50]博弈创作室. APDL参数化在限元分析技术及其应用实例.北京:中国水利水电出版社, 2004
[51]龚曙光. ANSYS操作命令与参数数化编程.北京:机械工业出版社, 2004
[52]邓凡平. ANSYS10. 0有限元分析自学手册.北京:人民邮电出版社, 2007
[53]康华光.电子技术基础(模拟部分).北京:高等教育出版社, 1999
[54]谢自美.电子电路设计实验测试.武汉:华中科技大学出版社, 2002
[55]孙航. Xilinx可编程逻辑器件的高级应用与设计技巧.北京:电子工业出版社, 2004
[56] http: //www. xilinx. com/products/boards/s3estarter/reference_designs. htm
[57]侯伯亨. VHDL硬件描述语言与数字逻辑电路设计.西安:西安电子科技大学出版社, 1997
[58]周润景.基于QuartusⅡ的FPGA/CPLD数字系统设计实例.北京:电子工业出版社, 2007
[59] John L Hennessy, David A Patterson. Computer Architecrure, a Quantitative Approach[M].北京:机械工业出版社, 2002
[60]胡寿松.自动控制原理.北京:科学出版社, 2001
[61]刘金琨.先进PID控制及其MATLAB仿真.北京:电子工业出版社, 2003
[62] http: //www. atmel. com/atmel/products/prod102. htm
[2]程京.生物芯片技术与应用,中国科学技术前沿.北京:高等教育出版社, 2000
[3] Lagally ET, Scherer JR, Blazej RG, Mathies RA. Genetic analysis using a portable PCR-CE microsystem. Micro Total Analysis System, California USA; 2003: 1283–6
[4] Liu CN, Toriello NM, Mathies RA. Multichannel PCR-CE microdevice for genetic analysis. Anal Chem, 2006, 78(15): 5474-9
[5] Huang FC, Liao CS, Lee GB. An integrated microfluidic chip for DNA/RNA amplification, electrophoresis separation and on-line oPtical detection. Electrophoresis, 2006, 27: 3297-305
[6] P. J. Obeid, T. K. Christopoulos, H. J. Crabtree, et al. Microfabricated device for DNA and RNA amplification by continuousflow polymerase chain reaction and reverse transcriPtion-polymerase chain reaction with cycle nμmber selection, Anal. Chem, 2003, 75: 288-295
[7] L. J. Kricka, P. Wilding, Microchip PCR, Anal. Bioanal. Chem, 2003, 377: 820-825
[8] Toriello NM, Liu CN, Mathies RA. Multichannel reverse transcriPtionpolymerase chain reaction microdevice for rapid gene expression and biomarker analysis. Anal Chem, 2006, 78(23): 7997-8003
[9] Jing Cheng, Larry J. Kricka. Biochip Technology. Harwood Academic Publishers, 2001
[10] Auroux P-A, Iossifidis D, Reyes DR, Manz A. Micro total analysis systems: 2. Analytical standard operations and applications. Anal Chem, 2002, 74: 2637-52
[11] Dittrich PS, Tachikawa K, Manz A. Micro total analysis systems. Latest advancements and trends. Anal Chem, 2006, 78: 3887-908
[12] Manz A, Graber N, Widmer HM. miniaturized total analysis systems: a novel concePt for chemical sensing. Sens Actuators B Chem, 1990, 1(1): 244-8
[13] Vilkner T, Janasek D, Manz A. Micro total analysis systems: recent developments. Anal Chem, 2004, 76: 3373-86
[14] Reyes DR, Iossifidis D, Auroux P-A, Manz A. Micro total analysis systems: 1. Introduction, theory, and technology. Anal Chem, 2002, 74: 2623-36
[15] Y. C. Lin, M. Y. Huang, K. C. Young, et al. A rapid micropolymerasechain reaction system for hepatitis C virus amplification. Sens. Actuators, 2000, B 71: 2-8
[16] E. T. Lagally, C. A. Emrich, R. A. Mathies, Fullyintegrated PCR-capillaryelectrophoresis microsystem for DNA analysis, Lab. Chip, 2001, 1(2): 102-107
[17] M. Bu, T. Melvin, G. Ensell, et al. Design and theoretical evaluation of a novel microfluidic device to be used for PCR, J. Micromech. Microeng, 2003, 13: S125-S130
[18] C. G. J. Schabmueller, J. R. Pollard, A. G. R. Evans, J. S. Wilkinson, G. Ensell, A. Brunnschweiler, Integrated diode detector and oPtical fibres for in situ detection within micromachined polymerase chain reaction chips, J. Micromech. Microeng, 1990, 11: 329-333
[19] M. A. Northrup, B. Benett, D. Hadley, et al. A miniature analytical instrμment for nucleic acids based onmicromachined silicon reaction chambers, Anal. Chem, 1998, 70: 918-922
[20] M. U. Kopp, A. Manz. Chemical amplification: continuous-flow PCR on achip. Science, 1998, 280: 1046-1048
[21] Pavel Neuzil Chunyan Zhang Juergen Pipper, Ultra fast miniaturized real-time PCR: 40 cycles in less than six minutes Nucleic Acids Research, 2006, 34: e77
[22] Lagally ET, Scherer JR, Blazej RG, et al. Integrated portable genetic analysis microsystem for pathogen/infectious disease detection. Anal Chem 2004;76(11): 3162-70
[23] Liu CN, Toriello NM, Mathies RA. Multichannel PCR-CE microdevicefor genetic analysis. Anal Chem, 2006, 78(15): 5474-9
[24] P, Seo TS, Beyor N, Shin K, et al. Integrated portable PCR-capillary electrophoresis microsystem for rapid forensic short tandem repeat typing. Anal Chem, 2007, 79(5): 1881-9
[25] Kaigala GV, Huskins RJ, Preiksaitis J, et al. Automated screening using microfluidic chipbased PCR and product detection to assess risk of BK virusassociated nephropathy in renal transplant recipients. Electrophoresis, 2006, 27: 3753-63
[26] Oh KW, Park C, Namkoong K, et al. World-tochip microfluidic interface with built-in valves for multichamber chip-based PCR assays. Lab Chip 2005a, 5: 845-50
[27] Lien KY, Lee WC, Lei HY, Lee GB. Integrated reverse transcriPtion polymerase chain reaction systems for virus detection. Biosens Bioelectron, 2007, 22: 1739-48
[28] J. N. Yang, Y. J. Liu, C. B. Rauch, et al. Grodzinski, High sensitivity PCR assay in plastic micro reactors, Lab on a Chip, 2002, 2: 179-187
[29] B. C. Giordano, J. Ferrance, S. Swedberg, et al. Polymerase chain reaction in polymeric microchips: DNA amplificationin less than 240 s, Anal. Biochem, 2001, 291: 124-132
[30] P. Sethu, C. H. Mastrangelo. Cast epoxy-based microfluidic systems and their application in biotechnology, Sens. Actuators B: Chem, 2004, 98: 337-346
[31] J. W. Hong, T. Fujii, M. Seki, et al. Integration of gene amplification and capillary gel electrophoresis on a polydimethylsiloxane-glass hybrid microchip. Electrophoresis, 22
[32] E. T. Lagally, P. C. Simpson, R. A. Mathies. Monolithic integrated microfluidic DNA amplification and capillary electrophoresis analysis system. Sens. Actuators B: Chem, 2000, 63: 138-146
[33] H. Nagai, Y. Murakami, Y. Morita, et al. Development of a microchamber array for picoliter PCR. Anal. Chem, 2001, 73: 1043-1047
[34] J. Kim, M. K. Chaudhury, M. J. Owen. Hydrophobicity loss and recovery of silicone HV insulation. IEEE Trans. Dielectr. Electr. Insul, 1999, 6: 695-702
[35] H. Hillborg, U. W. Gedde. Hydrophobicity changes in silicone rubbers. IEEE Trans. Dielectr. Electr. Insul, 1999, 6: 703-717
[36] J. C. Lotters, W. Olthuis, P. H. Veltink, et al. Polydimethylsiloxane, a photocurable rubberelastic polymer used as spring materialin micromechanical sensors. Microsyst. Technol, 1997, 3: 64-67
[37] Y. S. Shin, K. Cho, S. H. Lim, et al. PDMS-based micro PCR chip with parylene coating. J. Micromech. Microeng, 2003, 13: 768-774
[38] X. M. Yu, D. C. Zhang, T. Li, et al. 3-D microarrays biochip for DNA amplification in polydimethylsiloxane (PDMS) elastomer. Sens. Actuators A: Phys, 2003, 108: 103-107
[39] J. Liu, M. Enzelberger, S. Quake. A nanoliter rotary device for polymerase chain reaction. Electrophoresis, 2002, 23: 1531-1536
[40] J. Liu, C. Hansen, S. R. Quake. Solving the“world-to-chip”interface problem with a microfluidic matrix. Anal. Chem, 2003, 75: 4718-4723
[41] J. C. McDonald, G. M. Whitesides. Poly(dimethylsiloxane) as a material for fabricating microfluidic devices. Acc. Chem. Res., 2002, 35: 491-499
[42] B. D. Gates, G. M. Whitesides. Replication of vertical features smaller than 2 nm by soft lithography. J. Am. Chem. Soc., 2003, 125: 14986-14987
[43]方擎伦.微流控分析芯片的制作及应用.北京:化学工业出版社, 2005
[44] Pilarski PM, Adamia S, Backhouse CJ. An adaPtable microvalving system for on-chip polymerase chain reactions. J Immunol Methods, 2005, 305: 48-58
[45] Prakash R, Kaler KVIS. An integrated genetic analysis microfluidic platform with valves and a PCR chip reusability method to avoid contamination. Microfluid Nanofluid, 2007, 3: 177-87
[46]高尚通.跨世纪的微电子封装.半导体情报, 2000, 37(6): 1-7
[47]张朝晖. ANSYS8. 0热分析教程与实例解析.北京:中国铁道出版社, 2005
[48]章熙民,任泽霈.传热学.北京:中国建筑工业出版社, 2001
[49]孔祥谦,有限单元法在传热学中的应用.北京:科学出版社, 1981
[50]博弈创作室. APDL参数化在限元分析技术及其应用实例.北京:中国水利水电出版社, 2004
[51]龚曙光. ANSYS操作命令与参数数化编程.北京:机械工业出版社, 2004
[52]邓凡平. ANSYS10. 0有限元分析自学手册.北京:人民邮电出版社, 2007
[53]康华光.电子技术基础(模拟部分).北京:高等教育出版社, 1999
[54]谢自美.电子电路设计实验测试.武汉:华中科技大学出版社, 2002
[55]孙航. Xilinx可编程逻辑器件的高级应用与设计技巧.北京:电子工业出版社, 2004
[56] http: //www. xilinx. com/products/boards/s3estarter/reference_designs. htm
[57]侯伯亨. VHDL硬件描述语言与数字逻辑电路设计.西安:西安电子科技大学出版社, 1997
[58]周润景.基于QuartusⅡ的FPGA/CPLD数字系统设计实例.北京:电子工业出版社, 2007
[59] John L Hennessy, David A Patterson. Computer Architecrure, a Quantitative Approach[M].北京:机械工业出版社, 2002
[60]胡寿松.自动控制原理.北京:科学出版社, 2001
[61]刘金琨.先进PID控制及其MATLAB仿真.北京:电子工业出版社, 2003
[62] http: //www. atmel. com/atmel/products/prod102. htm