嵌入式早期肿瘤检测子系统的研究
摘要
研究发现TK1在异常增殖的肿瘤细胞中出现较早，含量或活性增高幅度明显。因此，检测出TK1活性或含量，对于肿瘤早期诊断具有特别重要的临床意义。由于正常成年肿瘤患者人体中，肿瘤标志物的绝对含量非常少，所以准确可靠得测量出TK1／Hpank的含量非常重要。
目前利用放射性酶法可测定出TK1／Hpank蛋白的活性和含量，但是长期采用放射性酶法，存在一定的放射性污染，重复性和稳定性较差，操作繁琐，且无法进行临床的早期诊断。利用压电石英晶体测量微质量物质精度高，稳定性好，设备操作简单，容易携带，而且无放射污染。在对各种检测方法做了比较之后，为了准确检测出TK1／Hpank的含量，本文选用了压电石英晶体作为微质量检测传感器。
论文首先验证了压电石英晶体传感器的频率测量精度可以满足要求之后，然后进行了嵌入式肿瘤早期检测子系统的开发。整个系统设计由硬件设计和软件开发两大部分组成。硬件检测电路设计包括由压电石英晶体传感器和振荡电路组成的系统前端数据采集模块、由CPLD和50MHZ的基准晶振组成的频率计数模块。嵌入式系统的外围接口电路设计包括SDRAM、FLASH、USB、IDE、串口、网卡、触摸液晶屏等；软件设计部分包括uboot的移植，μClinux操作系统的移植，μClinux操作系统驱动程序开发，嵌入式图形界面MiniGUI的开发。
最后完成了系统的硬件及软件开发后，对系统进行了软硬件调试以及实际测试，结果满足了我们的精度要求，证明整个系统在实际运行过程中是稳定可靠的。在本文中，不仅介绍了嵌入式系统的硬件以及软件的详细开发过程，还为以后在相关领域进行嵌入式系统医疗设备的开发提供了一个很好的参考。
It is studied that TK1 appears in the tumor cells very early,it's content and activity also increases very obvious.So measuring the TK1's content and activity are very important for early tumor diagnose.Because the tumor symbol in the adult tumor sufferer is very few,so measuring the the TK1's content exactly and dependable is very important.
At present,using radioactivity enzyme can measure the content of TK1.But using this way for a long time have some radioactivity pollution, the repetition and stability are not good,the operation is very complexity,and can't do the early clinical diagnose.Using OCM to measure the tiny mass has a very high precision and stability, the equipment's operation is very easy,and has no radioactivity pollution.After compareing some ways of measuring TK1,in order to measuring the content of TK1 exactly,we choice the OCM as our sensor.
The thesis first proves that the precision of frequency measurement can meet the system demands, and recommends an embedded measurement subsystem's development. The whole system is divided into two parts of hardware and software. The measurement hardware design includes circuits of data acquisition and frequency counting; The embeded hardware design includes systematic power circuit,peripheral interface circuits such as SDRAM、FLASH、USB、IDE、Netcard、touched LCD. The software design includes the process of porting uboot to hardware、the process of portingμClinux to hardware, the program of the drivers and applications of the uClinux OS、the development of MiniGui which is the graphics interface system of embedded OS and the program of applications of the miniGUI.
At last,after completing the development of hardware and software, we debuged and tested the system, and have proved the system is stable.This thesis not only introduce the detailed process of hardware and software development of embedded system, but also have provided a kind of beneficial reference for other medical equipments development in the correlative field.
目前利用放射性酶法可测定出TK1／Hpank蛋白的活性和含量，但是长期采用放射性酶法，存在一定的放射性污染，重复性和稳定性较差，操作繁琐，且无法进行临床的早期诊断。利用压电石英晶体测量微质量物质精度高，稳定性好，设备操作简单，容易携带，而且无放射污染。在对各种检测方法做了比较之后，为了准确检测出TK1／Hpank的含量，本文选用了压电石英晶体作为微质量检测传感器。
论文首先验证了压电石英晶体传感器的频率测量精度可以满足要求之后，然后进行了嵌入式肿瘤早期检测子系统的开发。整个系统设计由硬件设计和软件开发两大部分组成。硬件检测电路设计包括由压电石英晶体传感器和振荡电路组成的系统前端数据采集模块、由CPLD和50MHZ的基准晶振组成的频率计数模块。嵌入式系统的外围接口电路设计包括SDRAM、FLASH、USB、IDE、串口、网卡、触摸液晶屏等；软件设计部分包括uboot的移植，μClinux操作系统的移植，μClinux操作系统驱动程序开发，嵌入式图形界面MiniGUI的开发。
最后完成了系统的硬件及软件开发后，对系统进行了软硬件调试以及实际测试，结果满足了我们的精度要求，证明整个系统在实际运行过程中是稳定可靠的。在本文中，不仅介绍了嵌入式系统的硬件以及软件的详细开发过程，还为以后在相关领域进行嵌入式系统医疗设备的开发提供了一个很好的参考。
It is studied that TK1 appears in the tumor cells very early,it's content and activity also increases very obvious.So measuring the TK1's content and activity are very important for early tumor diagnose.Because the tumor symbol in the adult tumor sufferer is very few,so measuring the the TK1's content exactly and dependable is very important.
At present,using radioactivity enzyme can measure the content of TK1.But using this way for a long time have some radioactivity pollution, the repetition and stability are not good,the operation is very complexity,and can't do the early clinical diagnose.Using OCM to measure the tiny mass has a very high precision and stability, the equipment's operation is very easy,and has no radioactivity pollution.After compareing some ways of measuring TK1,in order to measuring the content of TK1 exactly,we choice the OCM as our sensor.
The thesis first proves that the precision of frequency measurement can meet the system demands, and recommends an embedded measurement subsystem's development. The whole system is divided into two parts of hardware and software. The measurement hardware design includes circuits of data acquisition and frequency counting; The embeded hardware design includes systematic power circuit,peripheral interface circuits such as SDRAM、FLASH、USB、IDE、Netcard、touched LCD. The software design includes the process of porting uboot to hardware、the process of portingμClinux to hardware, the program of the drivers and applications of the uClinux OS、the development of MiniGui which is the graphics interface system of embedded OS and the program of applications of the miniGUI.
At last,after completing the development of hardware and software, we debuged and tested the system, and have proved the system is stable.This thesis not only introduce the detailed process of hardware and software development of embedded system, but also have provided a kind of beneficial reference for other medical equipments development in the correlative field.
引文
[1] 任凤梅，张晓春等．中医药治疗肝癌的试验研究进展 医药导报 2007．3 26-3，42-43
[2] 丁克祥HTK1／Hpank基因重组、蛋白纯化和免疫传感器智能化肝癌诊断系统的研究．老年学．2004 12-15
[3] 张超，冯冠平，陈森芳．液体介质石英晶体谐振传感器．传感器技术，1995．5，26-28
[4] 楚霞，林朝晖，沈国励等．石英微天平用于免疫球蛋白M免疫反应的动力学研究．高等学校化学学报，1996．17 20-22
[5] 谢青季，姚守拙，聂利华．石英微天平测定抗坏血酸．湖南师范大学自然科学学报1997．6．71—73
[6] Park IS Lin N. Thiolated Salmonella antibody immobilization onto the gold surface of piezoelectric quartz crystal Biosens Bioelectron, 1998,13.45-47
[7] Jens Schroder, R alf Borngader Advanced interface electronics and method for QCM.Sensors and Actuators A 97-98(2002)543-547
[8] BURR-BROWN.user manual OPA660—Wide Bandwidth Operational Transconductance Amplifier and Buffer Burr-Brown Corporation, 1990. 25-27
[9] Chao zhang, Guanping Feng, Zhixian Gao.development of a new kind of dua modulated QCM biosensors biosensors and bioelectrics, 1997.12. 19-22
[10] Shij Koike,Takuya,Fujieda Noboru,Wakabayashi Shunichi,Higuchi. Electrochemical and quartz microbalance techinique studies of anode material for secondary batteries. Journal of Power Source 1997.68.48-51
[11] ALTRA. Emp7000 serial user manual, 1999. 21-22
[12] Michael D．Ciletti著，张雅绮 李锵等译．Verilog HDL高级数字设计．电子工业出版社2005．1．41-42
[13] HYNIX HY29LV160 Data Manual,1996. 14-15
[14] HYNIX HY57v641620 Data Manual,1996. 25-26
[15] 范振宇，程昱．ADS7843在嵌入式系统中的应用．煤炭科学技术2005．12．35-36
[16] 胡冰，吴升艳，岳春生．ADS7843触摸屏接口．国外电子元器件2002．7．10-12
[17] 蒋伟平．浅析IDE硬盘与SCSI硬盘．视听界广播电视技术2004．2．32-33
[18] 李家星，苗长云，李鸿强．基于单片机的IDE硬盘控制的研究与设计．微计算机信息2004．10．21—23
[19] 骆震波．基于D12的USB接口设计．内江科技2006．7．15-17
[20] SAMSUNG.User Manual S3c44b0x Risc Microprocessor,2000.34-35
[21] 张蓬鹤，王群，张东辉．RTL8019型控制器与高速数字信号处理器的接口设计及编程技巧．国外电子元器件 2006．8．52-53
[22] 何剑锋，李宏穆，庄阿龙。基于三星S3C44BOX目标板在μClinux系统上bootloader．石河子大学学报 2006．6．71-73
[23] 李兰英，刘洋，姜秀丽。嵌入式系统bootloader的设计与实现。电脑学习2006．6．10-12
[24] The DENX U-Boot and Linux Guide (DULG) for TQM8xxL 2000.6. 110-112
[25] 王东，李哲英。U-boot在S3C4480上的移植方法。北京交通大学学报 2005．2．15-18
[26] Hongxia zhou, Boot Process and Boot Code Analysis of Embedded Linux System.Computer Development & Applications 2005.2. 56-57
[27] 李岩，荣盘祥．基于S3C44BOX嵌入式μClinux系统原理及应用，北京：清华大学出版社，2002．42-43
[28] 庞丽萍．操作系统原理，武汉：华中理工大学出版社 1988．50-52
[29] Moshe[美]．天宏工作室译Linux文件系统，北京：清华大学出版社 2003．153-155
[30] 王学龙著．嵌入式Linux系统设计与应用，北京：清华大学出版社 2001．98-100
[31] Rick Grehan,Robert Moote，hugo Cyliax 著，许汝峰译．32位嵌入式系统编程。北京：中国电力出版社 2001．3．231-232
[32] Alessandro Rubini Jonathan Corbet，魏永明等译．LINUX设备驱动程序，北京：中国电力出版社 2002．10．24-25
[33] 杜春雷．ARM体系结构与编程，北京：清华大学出版社，1999．310-311
[34] 周立功．PDIUSBD12 USB固件编程与驱动开发．北京：航空航天大学出版社 1998．63-64
[35] 施威铭研究室．Linux C语言务实入式μClinux，北京：机械工业出版社．2002．45-46
[36] 郑军，郝久玉．翟霄翔；嵌入式图形用户界面的研究与移植．电子测量技术 2006．2．10-11
[37] 王聪，张殉，．基于嵌入式linux的GUI的设计方案．杭州电子科技大学学报 2006．3．31-32
[38] 肖寅．嵌入式系统上的图形界面输入引擎的研究．科学技术与工程 2006．8．32-33
[39] Xue En JIA; Zhi Wei ZHANG. QCM Detection of Adhesion, Spreading and Proliferation of Human Breast Cancer Calls (MCF-7) on a Gold Surface. Chinese Chemical Letters.2006.4 21-23
[40] Nie lihua,Lv rixin. Technical Elements And Prospects Of Piezoelectric Quartz Crystal Biosensors. Sensor World.2006.10.43-45
[41] Yao chunyan,Fu weiling. Piezoelectric Immunoglobulin Microarray Immunosensor.Chinese Journal of Nosocomiology,2006.11.12-13
[2] 丁克祥HTK1／Hpank基因重组、蛋白纯化和免疫传感器智能化肝癌诊断系统的研究．老年学．2004 12-15
[3] 张超，冯冠平，陈森芳．液体介质石英晶体谐振传感器．传感器技术，1995．5，26-28
[4] 楚霞，林朝晖，沈国励等．石英微天平用于免疫球蛋白M免疫反应的动力学研究．高等学校化学学报，1996．17 20-22
[5] 谢青季，姚守拙，聂利华．石英微天平测定抗坏血酸．湖南师范大学自然科学学报1997．6．71—73
[6] Park IS Lin N. Thiolated Salmonella antibody immobilization onto the gold surface of piezoelectric quartz crystal Biosens Bioelectron, 1998,13.45-47
[7] Jens Schroder, R alf Borngader Advanced interface electronics and method for QCM.Sensors and Actuators A 97-98(2002)543-547
[8] BURR-BROWN.user manual OPA660—Wide Bandwidth Operational Transconductance Amplifier and Buffer Burr-Brown Corporation, 1990. 25-27
[9] Chao zhang, Guanping Feng, Zhixian Gao.development of a new kind of dua modulated QCM biosensors biosensors and bioelectrics, 1997.12. 19-22
[10] Shij Koike,Takuya,Fujieda Noboru,Wakabayashi Shunichi,Higuchi. Electrochemical and quartz microbalance techinique studies of anode material for secondary batteries. Journal of Power Source 1997.68.48-51
[11] ALTRA. Emp7000 serial user manual, 1999. 21-22
[12] Michael D．Ciletti著，张雅绮 李锵等译．Verilog HDL高级数字设计．电子工业出版社2005．1．41-42
[13] HYNIX HY29LV160 Data Manual,1996. 14-15
[14] HYNIX HY57v641620 Data Manual,1996. 25-26
[15] 范振宇，程昱．ADS7843在嵌入式系统中的应用．煤炭科学技术2005．12．35-36
[16] 胡冰，吴升艳，岳春生．ADS7843触摸屏接口．国外电子元器件2002．7．10-12
[17] 蒋伟平．浅析IDE硬盘与SCSI硬盘．视听界广播电视技术2004．2．32-33
[18] 李家星，苗长云，李鸿强．基于单片机的IDE硬盘控制的研究与设计．微计算机信息2004．10．21—23
[19] 骆震波．基于D12的USB接口设计．内江科技2006．7．15-17
[20] SAMSUNG.User Manual S3c44b0x Risc Microprocessor,2000.34-35
[21] 张蓬鹤，王群，张东辉．RTL8019型控制器与高速数字信号处理器的接口设计及编程技巧．国外电子元器件 2006．8．52-53
[22] 何剑锋，李宏穆，庄阿龙。基于三星S3C44BOX目标板在μClinux系统上bootloader．石河子大学学报 2006．6．71-73
[23] 李兰英，刘洋，姜秀丽。嵌入式系统bootloader的设计与实现。电脑学习2006．6．10-12
[24] The DENX U-Boot and Linux Guide (DULG) for TQM8xxL 2000.6. 110-112
[25] 王东，李哲英。U-boot在S3C4480上的移植方法。北京交通大学学报 2005．2．15-18
[26] Hongxia zhou, Boot Process and Boot Code Analysis of Embedded Linux System.Computer Development & Applications 2005.2. 56-57
[27] 李岩，荣盘祥．基于S3C44BOX嵌入式μClinux系统原理及应用，北京：清华大学出版社，2002．42-43
[28] 庞丽萍．操作系统原理，武汉：华中理工大学出版社 1988．50-52
[29] Moshe[美]．天宏工作室译Linux文件系统，北京：清华大学出版社 2003．153-155
[30] 王学龙著．嵌入式Linux系统设计与应用，北京：清华大学出版社 2001．98-100
[31] Rick Grehan,Robert Moote，hugo Cyliax 著，许汝峰译．32位嵌入式系统编程。北京：中国电力出版社 2001．3．231-232
[32] Alessandro Rubini Jonathan Corbet，魏永明等译．LINUX设备驱动程序，北京：中国电力出版社 2002．10．24-25
[33] 杜春雷．ARM体系结构与编程，北京：清华大学出版社，1999．310-311
[34] 周立功．PDIUSBD12 USB固件编程与驱动开发．北京：航空航天大学出版社 1998．63-64
[35] 施威铭研究室．Linux C语言务实入式μClinux，北京：机械工业出版社．2002．45-46
[36] 郑军，郝久玉．翟霄翔；嵌入式图形用户界面的研究与移植．电子测量技术 2006．2．10-11
[37] 王聪，张殉，．基于嵌入式linux的GUI的设计方案．杭州电子科技大学学报 2006．3．31-32
[38] 肖寅．嵌入式系统上的图形界面输入引擎的研究．科学技术与工程 2006．8．32-33
[39] Xue En JIA; Zhi Wei ZHANG. QCM Detection of Adhesion, Spreading and Proliferation of Human Breast Cancer Calls (MCF-7) on a Gold Surface. Chinese Chemical Letters.2006.4 21-23
[40] Nie lihua,Lv rixin. Technical Elements And Prospects Of Piezoelectric Quartz Crystal Biosensors. Sensor World.2006.10.43-45
[41] Yao chunyan,Fu weiling. Piezoelectric Immunoglobulin Microarray Immunosensor.Chinese Journal of Nosocomiology,2006.11.12-13