肺癌呼吸诊断电子鼻仪器设计
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摘要
肺癌严重威胁着人类的健康和生命,已成为人类因肿瘤致死的首位病因。肺癌的早期诊断是降低肺癌死亡率的关键。目前临床尚缺乏常规简易的肺癌早期诊断方法与仪器。呼吸诊断通过检测人体呼吸气体中的挥发性有机化合物,反映相应组织细胞代谢改变,是一种新型的、无创的诊断技术。电子鼻技术方便快捷。论文设计了基于声表面波检测技术和毛细管分离技术的肺癌呼吸诊断电子鼻仪器,实现了肺癌的快速、无创诊断,为肺癌早期诊断开辟了一条新的途径。本论文的主要研究内容:
根据国内外的研究,肺癌病人呼吸气体中具有肺癌特征的挥发性有机气体成分,选用了对此类气体敏感的声表面波传感器,设计了声表面波检测器电路,灵敏度达到1KHz/ng。
对基于声表面波检测技术和毛细管分离技术的肺癌呼吸诊断电子鼻仪器进行了总体设计。整个仪器主要分为:气体采集与预处理系统、气体分离系统、气体检测系统、数据分析和通讯系统、软件诊断系统等。并对各个系统进行了论证,设计了仪器的气路结构。
设计并实现了仪器的硬件和软件部分。利用最小二乘法拟合的方法解决了Pt100铂电阻测温时带来的非线性误差;采用PID算法实现精确控温。对仪器的各个电路模块进行了标定。整个仪器实现了自动化,在上位机操作界面中完成仪器的控制。MSP430作为下位机的控制核心,执行上位机发送的指令。C51完成检测信号的采集和处理。上位机软件实时显示仪器的工作状态,并且可以发出控制信号调整仪器的工作状态,初步建立了诊断系统。
完成仪器的标定和临床应用研究。针对与肺癌相关的几种挥发性有机气体,仪器进行了标定,利用仪器对几例肺癌病人和正常人进行了诊断,诊断结果良好。
我们研制的肺癌呼吸诊断电子鼻仪器可以作为一种肺癌诊断的辅助手段,为医师提供参考依据,将来还可以应用到其它与呼吸有关的病症诊断。
Lung cancer is the leading cause of cancer death in both men and women, and badly threatens the health of human .The diagnosis in the early stage is the key to decrease the rate of death caused by lung cancer .Presently, there is no routine and simple instrument to diagnose early lung cancer in the clinic .Breath diagnosis is a novel and non-invasive technology and reflects the metabolism change of tissue by detecting the VOCs in the patient's breath gas. The e-nose is convenient. In this dissertation we propose a novel e-nose based on a kind of virtual array of surface acoustic wave (SAW) gas sensors and an imaging recognition method to diagnose lung cancer.
The main research content of this work:
According to the foreign research, the breath gas of lung cancer patient contains the marker VOCs .We choose the SAW gas sensor and design the detecting circuit. Its sensitivity to mass change can reach 1 KHz/ng .
We propose a novel e-nose based on a kind of virtual array of surface acoustic wave (SAW) gas sensors and an imaging recognition method, and design the structure of the instrument, which contain several parts, such as collection and pretreatment system, separation system, detecting system, data analysis and communication system, diagnosis software .We demonstrate every system and design the gas path.
We design and implement the hardware and software of this instrument, resolve the nonlinearity of Pt100 resistance using least square fitting method , accurately control temperature using PID arithmetic . The circuit of the e-nose was calibrated by standard methods and the calibration components. MSP430 is the controlling core in the lower computer and the instrument is controlled by manipulating the upper computer's software. We study and design a diagnosis system.
This instrument is used in the clinical application. Using the e-nose to detect lung cancer patients and healthy persons, the results is fine.
The research produces a relatively noninvasive tool effective in diagnosing lung cancer at an early and potentially curable stage. These breath biomarkers may eliminate the need for additional and often more invasive diagnostic tests that are costly, incur risk, and prolong the diagnostic evaluation of people with suspicion of lung cancer and can provide public health benefit by saving lives.
根据国内外的研究,肺癌病人呼吸气体中具有肺癌特征的挥发性有机气体成分,选用了对此类气体敏感的声表面波传感器,设计了声表面波检测器电路,灵敏度达到1KHz/ng。
对基于声表面波检测技术和毛细管分离技术的肺癌呼吸诊断电子鼻仪器进行了总体设计。整个仪器主要分为:气体采集与预处理系统、气体分离系统、气体检测系统、数据分析和通讯系统、软件诊断系统等。并对各个系统进行了论证,设计了仪器的气路结构。
设计并实现了仪器的硬件和软件部分。利用最小二乘法拟合的方法解决了Pt100铂电阻测温时带来的非线性误差;采用PID算法实现精确控温。对仪器的各个电路模块进行了标定。整个仪器实现了自动化,在上位机操作界面中完成仪器的控制。MSP430作为下位机的控制核心,执行上位机发送的指令。C51完成检测信号的采集和处理。上位机软件实时显示仪器的工作状态,并且可以发出控制信号调整仪器的工作状态,初步建立了诊断系统。
完成仪器的标定和临床应用研究。针对与肺癌相关的几种挥发性有机气体,仪器进行了标定,利用仪器对几例肺癌病人和正常人进行了诊断,诊断结果良好。
我们研制的肺癌呼吸诊断电子鼻仪器可以作为一种肺癌诊断的辅助手段,为医师提供参考依据,将来还可以应用到其它与呼吸有关的病症诊断。
Lung cancer is the leading cause of cancer death in both men and women, and badly threatens the health of human .The diagnosis in the early stage is the key to decrease the rate of death caused by lung cancer .Presently, there is no routine and simple instrument to diagnose early lung cancer in the clinic .Breath diagnosis is a novel and non-invasive technology and reflects the metabolism change of tissue by detecting the VOCs in the patient's breath gas. The e-nose is convenient. In this dissertation we propose a novel e-nose based on a kind of virtual array of surface acoustic wave (SAW) gas sensors and an imaging recognition method to diagnose lung cancer.
The main research content of this work:
According to the foreign research, the breath gas of lung cancer patient contains the marker VOCs .We choose the SAW gas sensor and design the detecting circuit. Its sensitivity to mass change can reach 1 KHz/ng .
We propose a novel e-nose based on a kind of virtual array of surface acoustic wave (SAW) gas sensors and an imaging recognition method, and design the structure of the instrument, which contain several parts, such as collection and pretreatment system, separation system, detecting system, data analysis and communication system, diagnosis software .We demonstrate every system and design the gas path.
We design and implement the hardware and software of this instrument, resolve the nonlinearity of Pt100 resistance using least square fitting method , accurately control temperature using PID arithmetic . The circuit of the e-nose was calibrated by standard methods and the calibration components. MSP430 is the controlling core in the lower computer and the instrument is controlled by manipulating the upper computer's software. We study and design a diagnosis system.
This instrument is used in the clinical application. Using the e-nose to detect lung cancer patients and healthy persons, the results is fine.
The research produces a relatively noninvasive tool effective in diagnosing lung cancer at an early and potentially curable stage. These breath biomarkers may eliminate the need for additional and often more invasive diagnostic tests that are costly, incur risk, and prolong the diagnostic evaluation of people with suspicion of lung cancer and can provide public health benefit by saving lives.
引文
[1]吴小和.肺癌.江西科学技术出版社,2000年6月第一版.
[2]卫生部.第三次全国死因调查主要情况.http://www.moh.gov.cn/newshtml/21702.htm.
[3]国际卫生组织.2007年世界卫生统计报告.
[4]林关福.PET/CT在肺癌诊断中的应用.上海医学影像,2007,Vol.16,No.309-311.
[5]蒲敬泽,蒋华庭,钟洪伟.肺癌MRI的临床应用比较.实用医技杂志,2007,14(22).
[6]丁翠敏,杨书芳,金普乐,王平.痰液中survivin、p53蛋白检测对肺癌的诊断价值.国际呼吸杂志,2007,27(20)1535-1537.
[7]杨艳,潘秦镜等.纤维支气管镜ThinPrep刷片细胞病理诊断在肺癌分型中的应用.中国肿瘤临床,2007,34(23)1358-1361.
[8]Matthias Lechner.Hpylori Infection Increases Levels of Exhaled Nitrate HELICOBACTER,2005 10(5)385-390.
[9]M.Phillips,K.Gleeson,W.Patrick,M.Vay,Volatile organic compounds in breath as markers of lung cancer:a cross-sectional study,Lancet 353(1999)1930-1932.
[10]M.Phillips,R.N.Cataneo,R.C.Andrew,D.M.Cummin,Detection of Lung Cancer With Volatile Markers in the Breath,CHEST 123(2003)2115.
[11]Michael Phillips,et al.Prediction of lung cancer using volatile biomarkers in breath,Cancer Biomarkers 3(2007)95 109.
[12]Wang ping,Tan yi,et al,A novel method for diabetes diagnosis based on electronic nose,Biosensors & Bioelectronics,Vol 12,No.9-10,1997,1031-1036.
[13]武以立,邓盛刚.声表面波原理及其在电子技术中的应用.国防工业出版社,1983年8月第一版.
[14]Michael J,Vellekoop,Acoustic wave sensors and their technology,Ultrasonics,Vol.36,1998,7-14.
[15]应可净,黄强.呼吸气体检测在肺癌早期诊断中的应用.国际呼吸杂志,2006年,第26卷第2期.
[16]Wang P,Tan Y,Li R.A novel method for diagnosis diabetes using an electronic nose.Biosens Bioelectron.1997;12:1031-1036.
[17]Zhang Q,Wang P,Li J,Gao X.Diagnosis of diabetes by imaging detection of breath using gas-sensitive LAPS.Biosens Bioelectron.2000;15:249-256.
[18]Chen X,Cao M F,Yi LI,Hu W J,Wang P Ying K J,Pan H M "A study of an electronic nose for detection of lung cancer based on a virtual SAW gas sensors array and imaging recognition method" Meas.Sci.Technol.16 1535 1546,2005.
[19]Chen X,Cao M F,Hao Y,Yi LI,Wang P "A Non-invasive Detection of Lung Cancer Combined Virtual Gas Sensors Array with Imaging Recognition Technique" Proceedings of the 2005 IEEE Engineering in Medicine and Biology 27th Annual Conference Shanghai,China,Paper ID 1652,2005.
[20]Jin F,Wang Z,Kishimoto K,Basic properties of Rayleigh surface wave propagation along curved surfaces,International Journal of Engineering Science,Vol.43,Issue:3-4,2005,250-261.
[21]Chen Weizhong,Wu junru,Reflectometry using longitudinal,shear and Rayleigh waves,Ultrasonics,Vol.38,Issue:9,2000,909-913.
[22]Jakoby B,Vellekoop MJ,Substrates for zero temperature coefficient Love wave sensors,IEEE Transactions on Ultrasonics,Ferroelectrics and Frequency Control,Vol.47,Issue 3,2000,701-705.
[23]徐恭勤,朱文章.声表面波传感器及其应用.传感器世界,1996年8月.
[24]苟永明.声表面波传感器原理及应用.传感嚣世界 1998 10.
[25]Lb.Yakoviun,Yun.Vlassov,A.Sxozu V,Smrpsky,"Highly Sensitive Saw Sensors" IEEE International Frequency Control Symposium,1994:395-400.
[26]Wohltjen H.;Dessy R."Surface acoustic wave probe for chemical analysis Ⅰ:Introduction and instrument design "Anal.Chem.,Vol.51,No.9,1979:1458 1475.
[27]Roh Y.R.;Kim H.B.;Lee,Y.J.;Cho.H.M.;" Development of SAW Gas Sensor for Monitoring SOX Gas",IEEE Ultrasonics Symposium,1995:473-476.
[28]陈星.呼吸检测电子鼻及其在肺癌诊断应用中的研究[学位论文博],浙江大学.
[29]Becker H,Schickfus MV,Hunklinger S "A new sensor principle based on the reflection of surface acoustic waves" Transducers' 95 -Conf.on Solid-State Sensors and Actuators 1995:720-723.
[30]徐良.新型气体传感器及呼吸诊断电子鼻设计[学位论文硕],浙江大学.
[31]Krotozynski,B.K.;Gabriel,G.;O' Neill,H.J.Chromatogr.Sci.1977,15:239-244.
[32]董希林.铂电阻测温中的线性校正,江南大学学报(自然科学版).2003年12月,第2卷第6期.
[33]王俊杰,张伟.最小二乘法在铂热电阻测温中的应用.仪表技术与传感器.1999年第5期.
[34 张迎春,高文红.热敏电阻不平衡电桥的简单设计技巧.山东轻工业学院学报,1997年3月,第11卷第1期.
[35]立宇电子.DH950新型超精密恒流管器件.http://www.ly-dz.com/news/ArticleShow.asp?ArticleID=1601
[36]李挺,朱金刚,赵良熙.热电阻测温仪导线电阻补偿新方法.电子测量技术,2003年9月.
[37]朱延钊.AD7705/AD7706的原理与应用.国外电子元器件,2002年6月,第6期.
[38]肖衡.PID温度控制装置的电路设计.计量与测试技术,2003年,No.1.
[39]刘升.二相步进电机驱动芯片TA8435H及其应用.国外电子元器,2005年第3期.
[40]王磊,艾晓庸.基于LMD18200组件的直流电机驱动器的设计.自动化与仪蓑2004年第1期.
[41]王俊杰,张伟.最小二乘法在铂热电阻测温中的应用.仪表技术与传感器,1999年第1期.
[42]杨振营 宗有弟.周期PID温度控制的原理及实现.信息与控自,1990年第1期.
[43]皮红梅,黄刚.加热炉自动温度控制系统改造.辽宁化工,2003年3月,第32卷第3期.
[44]夏春梅,王金胜.用可编程调节器实现程序升温控制.2003年12月,第12卷第4期.
[45]曹明富.肺癌呼吸气体检测电子鼻及诊断方法的研究[学位论文硕],浙江大学.
[2]卫生部.第三次全国死因调查主要情况.http://www.moh.gov.cn/newshtml/21702.htm.
[3]国际卫生组织.2007年世界卫生统计报告.
[4]林关福.PET/CT在肺癌诊断中的应用.上海医学影像,2007,Vol.16,No.309-311.
[5]蒲敬泽,蒋华庭,钟洪伟.肺癌MRI的临床应用比较.实用医技杂志,2007,14(22).
[6]丁翠敏,杨书芳,金普乐,王平.痰液中survivin、p53蛋白检测对肺癌的诊断价值.国际呼吸杂志,2007,27(20)1535-1537.
[7]杨艳,潘秦镜等.纤维支气管镜ThinPrep刷片细胞病理诊断在肺癌分型中的应用.中国肿瘤临床,2007,34(23)1358-1361.
[8]Matthias Lechner.Hpylori Infection Increases Levels of Exhaled Nitrate HELICOBACTER,2005 10(5)385-390.
[9]M.Phillips,K.Gleeson,W.Patrick,M.Vay,Volatile organic compounds in breath as markers of lung cancer:a cross-sectional study,Lancet 353(1999)1930-1932.
[10]M.Phillips,R.N.Cataneo,R.C.Andrew,D.M.Cummin,Detection of Lung Cancer With Volatile Markers in the Breath,CHEST 123(2003)2115.
[11]Michael Phillips,et al.Prediction of lung cancer using volatile biomarkers in breath,Cancer Biomarkers 3(2007)95 109.
[12]Wang ping,Tan yi,et al,A novel method for diabetes diagnosis based on electronic nose,Biosensors & Bioelectronics,Vol 12,No.9-10,1997,1031-1036.
[13]武以立,邓盛刚.声表面波原理及其在电子技术中的应用.国防工业出版社,1983年8月第一版.
[14]Michael J,Vellekoop,Acoustic wave sensors and their technology,Ultrasonics,Vol.36,1998,7-14.
[15]应可净,黄强.呼吸气体检测在肺癌早期诊断中的应用.国际呼吸杂志,2006年,第26卷第2期.
[16]Wang P,Tan Y,Li R.A novel method for diagnosis diabetes using an electronic nose.Biosens Bioelectron.1997;12:1031-1036.
[17]Zhang Q,Wang P,Li J,Gao X.Diagnosis of diabetes by imaging detection of breath using gas-sensitive LAPS.Biosens Bioelectron.2000;15:249-256.
[18]Chen X,Cao M F,Yi LI,Hu W J,Wang P Ying K J,Pan H M "A study of an electronic nose for detection of lung cancer based on a virtual SAW gas sensors array and imaging recognition method" Meas.Sci.Technol.16 1535 1546,2005.
[19]Chen X,Cao M F,Hao Y,Yi LI,Wang P "A Non-invasive Detection of Lung Cancer Combined Virtual Gas Sensors Array with Imaging Recognition Technique" Proceedings of the 2005 IEEE Engineering in Medicine and Biology 27th Annual Conference Shanghai,China,Paper ID 1652,2005.
[20]Jin F,Wang Z,Kishimoto K,Basic properties of Rayleigh surface wave propagation along curved surfaces,International Journal of Engineering Science,Vol.43,Issue:3-4,2005,250-261.
[21]Chen Weizhong,Wu junru,Reflectometry using longitudinal,shear and Rayleigh waves,Ultrasonics,Vol.38,Issue:9,2000,909-913.
[22]Jakoby B,Vellekoop MJ,Substrates for zero temperature coefficient Love wave sensors,IEEE Transactions on Ultrasonics,Ferroelectrics and Frequency Control,Vol.47,Issue 3,2000,701-705.
[23]徐恭勤,朱文章.声表面波传感器及其应用.传感器世界,1996年8月.
[24]苟永明.声表面波传感器原理及应用.传感嚣世界 1998 10.
[25]Lb.Yakoviun,Yun.Vlassov,A.Sxozu V,Smrpsky,"Highly Sensitive Saw Sensors" IEEE International Frequency Control Symposium,1994:395-400.
[26]Wohltjen H.;Dessy R."Surface acoustic wave probe for chemical analysis Ⅰ:Introduction and instrument design "Anal.Chem.,Vol.51,No.9,1979:1458 1475.
[27]Roh Y.R.;Kim H.B.;Lee,Y.J.;Cho.H.M.;" Development of SAW Gas Sensor for Monitoring SOX Gas",IEEE Ultrasonics Symposium,1995:473-476.
[28]陈星.呼吸检测电子鼻及其在肺癌诊断应用中的研究[学位论文博],浙江大学.
[29]Becker H,Schickfus MV,Hunklinger S "A new sensor principle based on the reflection of surface acoustic waves" Transducers' 95 -Conf.on Solid-State Sensors and Actuators 1995:720-723.
[30]徐良.新型气体传感器及呼吸诊断电子鼻设计[学位论文硕],浙江大学.
[31]Krotozynski,B.K.;Gabriel,G.;O' Neill,H.J.Chromatogr.Sci.1977,15:239-244.
[32]董希林.铂电阻测温中的线性校正,江南大学学报(自然科学版).2003年12月,第2卷第6期.
[33]王俊杰,张伟.最小二乘法在铂热电阻测温中的应用.仪表技术与传感器.1999年第5期.
[34 张迎春,高文红.热敏电阻不平衡电桥的简单设计技巧.山东轻工业学院学报,1997年3月,第11卷第1期.
[35]立宇电子.DH950新型超精密恒流管器件.http://www.ly-dz.com/news/ArticleShow.asp?ArticleID=1601
[36]李挺,朱金刚,赵良熙.热电阻测温仪导线电阻补偿新方法.电子测量技术,2003年9月.
[37]朱延钊.AD7705/AD7706的原理与应用.国外电子元器件,2002年6月,第6期.
[38]肖衡.PID温度控制装置的电路设计.计量与测试技术,2003年,No.1.
[39]刘升.二相步进电机驱动芯片TA8435H及其应用.国外电子元器,2005年第3期.
[40]王磊,艾晓庸.基于LMD18200组件的直流电机驱动器的设计.自动化与仪蓑2004年第1期.
[41]王俊杰,张伟.最小二乘法在铂热电阻测温中的应用.仪表技术与传感器,1999年第1期.
[42]杨振营 宗有弟.周期PID温度控制的原理及实现.信息与控自,1990年第1期.
[43]皮红梅,黄刚.加热炉自动温度控制系统改造.辽宁化工,2003年3月,第32卷第3期.
[44]夏春梅,王金胜.用可编程调节器实现程序升温控制.2003年12月,第12卷第4期.
[45]曹明富.肺癌呼吸气体检测电子鼻及诊断方法的研究[学位论文硕],浙江大学.