基于马赫泽德结构的差分干涉SPR传感系统与生物医学检测应用研究
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摘要
表面等离子体共振(Surface Plasmon Resonance, SPR)传感器是一种用于探测传感芯片表面折射率变化的传感器,它主要适用于对大分子结合反应的实时测量,自从上世纪80年代开始,SPR传感器已经广泛应用于生物医学领域,并有一系列商用传感器面世。SPR传感器最重要的性能指标是分辨率和动态范围,在SPR的四种检测方式(强度、角度、波长、相位)之中,相位检测方法具有最高的灵敏度,但由于其光路复杂、易受环境噪声影响以及动态范围较窄,限制了它的使用。本研究搭建的基于马赫泽德结构的差分干涉型SPR传感系统是一种新型的相位调制型SPR系统,它在拥有高灵敏度优点的同时,可大幅降低环境噪声,从而达到很高的分辨率,并且由于该系统从时间轴提取相位信息,在进行SPR成像传感时不损失空间分辨率,与传统的相位调制型SPR成像技术相比具有很大优势。
本文首先介绍了SPR技术的基本理论,并在该理论基础上分析了影响相位调制型SPR传感器灵敏度和动态范围的四大因素：金属介电常数、入射光波长、金膜厚度和入射角度,其中金膜厚度是一个易于调节的因素,可以在动态范围满足测量要求的基础上尽可能提高灵敏度,并进行了实验验证。
搭建了基于马赫泽德结构的差分干涉型SPR传感器,介绍了本系统提取相位信息的方法和差分干涉降低噪声的原理,编写了相位提取程序,在程序中使用非线性拟合及取平均的方法降低了系统噪声。制作了微流控系统,使用轮廓仪测量高真空镀膜机蒸镀所得金膜的厚度,从而选取厚度为45nm左右的金膜进行传感芯片的制作,将使用模塑法制作的PDMS基片和传感芯片进行氧离子键合以制成微流槽。通过精确调节入射角,尽可能减小入射角与SPR角的误差以发挥相位调制SPR传感器高灵敏度的优势,确定系统达到最高分辨率所需测量次数为15次,通过测量一系列折射率的NaCl溶液,确定了系统的分辨率为10(?)折射率单位。
进行了基于马赫泽德结构的差分干涉SPR成像传感器的研究工作,虽然差分干涉SPR传感器提取相位的方式不损失空间分辨率,但该方法需要将p光和s光两幅干涉图进行对准后提取相位,本研究使用光阑增加参考光图样的相似性,并进行互相关运算来优化对准效果。由于硬件性能的限制,系统中使用CCD采集图像数据的频率为30帧／s,在程序中采取局部多项式最小二乘曲线拟合法尽量减小由采集频率较低造成的误差。调节压电陶瓷的移动速度至0.6um／s,以弥补较低采集频率带来的误差,程序计算所得相变值的误差为±0.65,通过测量一系列折射率的NaCl溶液,确定了系统的分辨率为10-4叫折射率单位,系统的空间分辨率为9.77um×15.63um。
将本系统应用于生物医学检测的研究工作包括：传感芯片表面的活化、实时检测牛血清白蛋白与抗体的结合反应、检测低浓度乙肝表面抗原溶液、实时检测结肠癌细胞系与表皮生长因子的反应。本系统使用以硫醇体系为基础的自组装膜技术活化传感芯片,可以使生物分子定向结合在芯片表面。通过实验验证,本系统可以实时检测牛血清白蛋白与特异性抗体的结合反应,在整个测量过程中,一共增加了2.5×10-3折射率单位,对应IgG免疫球蛋白结合密度为160个／um2。从血清中检测乙肝表面抗原是否存在是判断乙肝感染的指标,因此使用高灵敏度的检测手段,进行准确的定性测量是具有重要意义的,使用本系统能够在30分钟之内测量出1-10ng/ml浓度的乙肝表面抗原,在检测分辨率上相当于目前常用的ELISA和RIA检测方法,而检测时间则短于上述两种方法。对三种具有不同表皮生长因子受体表达水平的结肠癌细胞系与表皮生长因子的结合过程以及接下来的信号转导过程进行了实时检测,结果表明,受体表达水平越高,两个信号转导过程所产生的信号峰越陡峭,使用本系统能够确定癌细胞某项肿瘤标志物或细胞表面受体的表达水平,并能够实时检测信号转导途径的进行。
Surface Plasmon Resonance (SPR) sensors can be used to detect change of refractive index near sensor chips. It is mainly applied to real-time measurement of macromolecules binding reactions. Since the1980s, SPR sensors have been widely used in the biomedical field and a series of commercial sensors have been produced. The most important performance index of SPR sensors are resolution and dynamic range. Among the four detection methods (intensity, angle, wavelength, phase) of SPR sensors, the phase modulation method has the highest sensitivity. However, phase modulation SPR sensors have a limited range of applications because its optical system is complicated, sensitive to environmental noise influence, and its dynamic range is narrow. A differential interference SPR sensing system based on Mach-Zehnder configuration in this study is a new kind of phase modulation SPR system. It not only has the advantage of high sensitivity, but also can significantly reduce the influence of enviromental noise to achieve a higher resolution. On the other hand, it has not loss of spatial resolution during SPR imaging because it extract phase information from the time axis. In this performance index, it has a great advantage compared with the conventional phase modulation SPR imaging.
This paper first introduces the basic theory of SPR technology. From this, the four factors which effect sensitivity and dynamic range of SPR sensors are analyzed: the dielectric constant of metal, the wavelength of incident light, the thickness of gold film and the incident angle. The thickness of gold film can be adjusted easily among these factors to meet the measurement requirements of the dynamic range on the basis of improving sensitivity as much as possible. The above has been verified by experiment.
A differential interference SPR sensor based on Mach-Zehnder configuration is set up. The method of extracting phase information and the principle of reduction noise by differential interference are described. The phase extraction procedures are programmed in which nonlinear fitting and averaging method are used to reduce the system noise. In the microfluidic system production, the profilometer is used to measure the gold membrane thickness vapor-deposited by the high vacuum coating machine in order to select film with about45nm thickness of gold membrane to make the sensor chip. Sensor chip and PDMS substrate made by molding method are used to make microfluid groove, which are produced by PDMS oxygen ions bonding method. The incident angle is adjusted precisely to minimize the error between the incident angle and the SPR angle to utilize high sensitivity advantage of phase modulation SPR sensors.15measurement times are needed to achieve the highest resolution of the system. The resolution of the system is determined to10'5refractive index units by measuring a series refractive index of NaCl solution.
The research work of the differential interference SPR imaging sensor based on Mach-Zehnder configuration is described. Although there is no loss of spatial resolution in the method of phase extraction of differential interference SPR sensors, but the method requires to align two interferogram of p-and s-polarization light to extract phase. Diaphragm is used to increase the similarity of the reference light pattern, and correlation algorithm is carried on to optimize the alignment effect. Due to the limitations of the hardware performance, acquisition frequency of the CCD used in the system is30frame/s. the method of local polynomial least squares curve fitting is applied to minimize the error caused by the low acquisition frequency of the CCD. The moving speed of the piezoelectric ceramic is adjusted to0.6μm/s in order to compensate the error caused by the lower acquisition frequency. The error of the phase change calculated by the program is±0.65°. The resolution of the system is determined to be10-4refractive index units and the spatial resolution is0.77μm×15.63μm by measuring a series refractive index of NaCl solution.
The system is applied to biomedical detection including the following research works:activation of the sensor chip surface, real-time detecting binding reaction between bovine serum albumin and antibody, detecting low concentration solution of hepatitis B surface antigen. Self assembled monolayer technology based on mercaptan system is used to activate sensor chip which can make biological moleculars coated to the chip surface directed. Verified by experiment, the system can real-time detect binding reaction between bovine serum albumin and its specific antibody. In the whole process, the increase of refractive index is2.5×10-3units which is corresponded to160number/μm2binding density of IgG immunoglobulin. Because hepatitis B surface antigen detected from serum is the indicator of hepatitis B infection, it has important significance to qualitative measure accurately by high sensitivity method. Concentration of hepatitis B surface antigen low to1-10ng/ml can be detected by the system in30minutes. The resolution of the system is equivalent to the currently used methods, such as enzyme linked immunosorbent and radioimmunoassay, while the detection time is shorter than the above two methods. The binding process between three colorectal cancer cell lines with different epidermal growth factor receptor expression level and epidermal growth factor are measured. Then the subsequent signal transduction process is detected in real-time. The results show that the signal peaks generated by two signal transduction process become steeper when the receptor expresstion level is higher. The system can determine expression level of a tumor marker or cell surface receptor in cancer cell and real-time detect signal transduction pathway progress.
本文首先介绍了SPR技术的基本理论,并在该理论基础上分析了影响相位调制型SPR传感器灵敏度和动态范围的四大因素：金属介电常数、入射光波长、金膜厚度和入射角度,其中金膜厚度是一个易于调节的因素,可以在动态范围满足测量要求的基础上尽可能提高灵敏度,并进行了实验验证。
搭建了基于马赫泽德结构的差分干涉型SPR传感器,介绍了本系统提取相位信息的方法和差分干涉降低噪声的原理,编写了相位提取程序,在程序中使用非线性拟合及取平均的方法降低了系统噪声。制作了微流控系统,使用轮廓仪测量高真空镀膜机蒸镀所得金膜的厚度,从而选取厚度为45nm左右的金膜进行传感芯片的制作,将使用模塑法制作的PDMS基片和传感芯片进行氧离子键合以制成微流槽。通过精确调节入射角,尽可能减小入射角与SPR角的误差以发挥相位调制SPR传感器高灵敏度的优势,确定系统达到最高分辨率所需测量次数为15次,通过测量一系列折射率的NaCl溶液,确定了系统的分辨率为10(?)折射率单位。
进行了基于马赫泽德结构的差分干涉SPR成像传感器的研究工作,虽然差分干涉SPR传感器提取相位的方式不损失空间分辨率,但该方法需要将p光和s光两幅干涉图进行对准后提取相位,本研究使用光阑增加参考光图样的相似性,并进行互相关运算来优化对准效果。由于硬件性能的限制,系统中使用CCD采集图像数据的频率为30帧／s,在程序中采取局部多项式最小二乘曲线拟合法尽量减小由采集频率较低造成的误差。调节压电陶瓷的移动速度至0.6um／s,以弥补较低采集频率带来的误差,程序计算所得相变值的误差为±0.65,通过测量一系列折射率的NaCl溶液,确定了系统的分辨率为10-4叫折射率单位,系统的空间分辨率为9.77um×15.63um。
将本系统应用于生物医学检测的研究工作包括：传感芯片表面的活化、实时检测牛血清白蛋白与抗体的结合反应、检测低浓度乙肝表面抗原溶液、实时检测结肠癌细胞系与表皮生长因子的反应。本系统使用以硫醇体系为基础的自组装膜技术活化传感芯片,可以使生物分子定向结合在芯片表面。通过实验验证,本系统可以实时检测牛血清白蛋白与特异性抗体的结合反应,在整个测量过程中,一共增加了2.5×10-3折射率单位,对应IgG免疫球蛋白结合密度为160个／um2。从血清中检测乙肝表面抗原是否存在是判断乙肝感染的指标,因此使用高灵敏度的检测手段,进行准确的定性测量是具有重要意义的,使用本系统能够在30分钟之内测量出1-10ng/ml浓度的乙肝表面抗原,在检测分辨率上相当于目前常用的ELISA和RIA检测方法,而检测时间则短于上述两种方法。对三种具有不同表皮生长因子受体表达水平的结肠癌细胞系与表皮生长因子的结合过程以及接下来的信号转导过程进行了实时检测,结果表明,受体表达水平越高,两个信号转导过程所产生的信号峰越陡峭,使用本系统能够确定癌细胞某项肿瘤标志物或细胞表面受体的表达水平,并能够实时检测信号转导途径的进行。
Surface Plasmon Resonance (SPR) sensors can be used to detect change of refractive index near sensor chips. It is mainly applied to real-time measurement of macromolecules binding reactions. Since the1980s, SPR sensors have been widely used in the biomedical field and a series of commercial sensors have been produced. The most important performance index of SPR sensors are resolution and dynamic range. Among the four detection methods (intensity, angle, wavelength, phase) of SPR sensors, the phase modulation method has the highest sensitivity. However, phase modulation SPR sensors have a limited range of applications because its optical system is complicated, sensitive to environmental noise influence, and its dynamic range is narrow. A differential interference SPR sensing system based on Mach-Zehnder configuration in this study is a new kind of phase modulation SPR system. It not only has the advantage of high sensitivity, but also can significantly reduce the influence of enviromental noise to achieve a higher resolution. On the other hand, it has not loss of spatial resolution during SPR imaging because it extract phase information from the time axis. In this performance index, it has a great advantage compared with the conventional phase modulation SPR imaging.
This paper first introduces the basic theory of SPR technology. From this, the four factors which effect sensitivity and dynamic range of SPR sensors are analyzed: the dielectric constant of metal, the wavelength of incident light, the thickness of gold film and the incident angle. The thickness of gold film can be adjusted easily among these factors to meet the measurement requirements of the dynamic range on the basis of improving sensitivity as much as possible. The above has been verified by experiment.
A differential interference SPR sensor based on Mach-Zehnder configuration is set up. The method of extracting phase information and the principle of reduction noise by differential interference are described. The phase extraction procedures are programmed in which nonlinear fitting and averaging method are used to reduce the system noise. In the microfluidic system production, the profilometer is used to measure the gold membrane thickness vapor-deposited by the high vacuum coating machine in order to select film with about45nm thickness of gold membrane to make the sensor chip. Sensor chip and PDMS substrate made by molding method are used to make microfluid groove, which are produced by PDMS oxygen ions bonding method. The incident angle is adjusted precisely to minimize the error between the incident angle and the SPR angle to utilize high sensitivity advantage of phase modulation SPR sensors.15measurement times are needed to achieve the highest resolution of the system. The resolution of the system is determined to10'5refractive index units by measuring a series refractive index of NaCl solution.
The research work of the differential interference SPR imaging sensor based on Mach-Zehnder configuration is described. Although there is no loss of spatial resolution in the method of phase extraction of differential interference SPR sensors, but the method requires to align two interferogram of p-and s-polarization light to extract phase. Diaphragm is used to increase the similarity of the reference light pattern, and correlation algorithm is carried on to optimize the alignment effect. Due to the limitations of the hardware performance, acquisition frequency of the CCD used in the system is30frame/s. the method of local polynomial least squares curve fitting is applied to minimize the error caused by the low acquisition frequency of the CCD. The moving speed of the piezoelectric ceramic is adjusted to0.6μm/s in order to compensate the error caused by the lower acquisition frequency. The error of the phase change calculated by the program is±0.65°. The resolution of the system is determined to be10-4refractive index units and the spatial resolution is0.77μm×15.63μm by measuring a series refractive index of NaCl solution.
The system is applied to biomedical detection including the following research works:activation of the sensor chip surface, real-time detecting binding reaction between bovine serum albumin and antibody, detecting low concentration solution of hepatitis B surface antigen. Self assembled monolayer technology based on mercaptan system is used to activate sensor chip which can make biological moleculars coated to the chip surface directed. Verified by experiment, the system can real-time detect binding reaction between bovine serum albumin and its specific antibody. In the whole process, the increase of refractive index is2.5×10-3units which is corresponded to160number/μm2binding density of IgG immunoglobulin. Because hepatitis B surface antigen detected from serum is the indicator of hepatitis B infection, it has important significance to qualitative measure accurately by high sensitivity method. Concentration of hepatitis B surface antigen low to1-10ng/ml can be detected by the system in30minutes. The resolution of the system is equivalent to the currently used methods, such as enzyme linked immunosorbent and radioimmunoassay, while the detection time is shorter than the above two methods. The binding process between three colorectal cancer cell lines with different epidermal growth factor receptor expression level and epidermal growth factor are measured. Then the subsequent signal transduction process is detected in real-time. The results show that the signal peaks generated by two signal transduction process become steeper when the receptor expresstion level is higher. The system can determine expression level of a tumor marker or cell surface receptor in cancer cell and real-time detect signal transduction pathway progress.
引文
[1]Huang, C.H. and Sedlak, D.L. Analysis of estrogenic hormones in municipal wastewater effluent and surface water using enzyme-linked immunosorbent assay and gas chromatography/tandem mass spectrometry. Environ Toxicol Chem,2001,20(1):133-139.
[2]Fedeniuk, R. W., Boison, J. O. and MacNeil, J. D. Validation of a gas chromatography-mass spectrometry method for the determination of pg/ml levels of 17 beta-estradiol and 17 beta-trenbolone in bovine serum. Chromatogr B,2004,802(2):307-315.
[3]Yang, L. H., Luan, T. G. and Lan, C. Y. Solid-phase microextraction with on-fiber silylation for simultaneous determinations of endocrine disrupting chemicals and steroid hormones by gas chromatography-mass spectrometry. Chromatogr A,2006,1104(1-2):23-32.
[4]Kelly, C. Analysis of steroids in environmental water samples using solid-phase extraction and ion-trap gas chromatography-mass spectrometry and gas chromatography-tandem mass spectrometry. Chromatogr A,2000,872(1-2):309-314.
[5]Watabe, Y., Kubo, T., Nishikawa, T. et al. Fully automated liquid chromatography-mass spectrometry determination of 17 beta-estradiol in river water. Chromatogr A,2006,1120(1-2): 252-259.
[6]Hu, J.Y., Zhang, H. F. and Chang, H. Improved method for analyzing estrogens in water by liquid chromatography-electrospray mass chromatography. Chromatogr A,2005,1070(1-2): 221-224.
[7]Lagana, A., Bacaloni, A., Fago, G. et al. Trace analysis of estrogenic chemicals in sewage effluent using liquid chromatography combined with tandem mass spectrometry. Rapid Commun Mass Sp,2000,14(6):401-407.
[8]Rothenhausler, B. and W. Knoll, Surface-plasmon microscopy. Nature,1988.332(6165): 615-617.
[9]Byun K M, Yoon S J, Kim D H, et al. Experimental study of. sensitivity enhancement in surface plasmon resonance biosensors by use of periodic metallic nanowires. Opt. Lett.,2007, 32(13):1902-1904.
[10]Chien F C. Direct determination of the refractive index and thickness of a biolayer based on coupled waveguide surface plasmon resonance mode. Opt. Lett.,2006,31(2):187-189.
[11]Patskovsky S, Kabashin A V, Meunier M, et al. Near-infrared surface plasmon resonance sensing on a silicon platform. Sensors and Actuators B,2004,97:409-414.
[12]Rich R L, Myszka D G. Survey of the year 2000 commercial optical biosensor literature. Journal of Molecular recognition,2001,14(6):273-294.
[13]Diaz-Cruz, M. S., de Alda, M. J. L., Lopez, R. et al. Determination of estrogens and progestogens by mass spectrometric techniques (GC/MS, LC/MS and LC/MS/MS). Mass Spectrom,2003,38(9):917-923.
[14]Matsumoto, Y., Kuramitz, H., Itoh, S. et al. New fluorometric enzyme immunoassay for 17 beta estradiol by homogeneous reaction using biotinylated estradiol. Talanta,2006,69(3): 663-668.
[15]Kokko, L., Johansson, N., Lovgren, T. et al. Enzyme inhibitor screening using a homogeneous proximity-based immunoassay for estradiol. Biomol Screen,2005,10(4): 348-354.
[16]Pemberton, R. M., Mottram, T. T. and Hart, J. P. Development of a screen printed carbon electrochemical immunosensor for picomolar concentrations of estradiol in human serum extracts. Biochem Bioph Meth,2005,63(3):201-212.
[17]www.biacore.com
[18]Natsume, T., Taoka, M., Manki, H. et al. Rapid analysis of protein interactions:On-chip micropurification of recombinant protein expressed in Esherichia coli. Proteomics,2002,2(9): 1247-1253.
[19]Spadavecchia, J., Manera, M. G, Quaranta, F. et al. Surface plasmon resonance imaging of DNA based biosensors for potential applications in food analysis. Biosens Bioelectron,2005, 21(6):894-900.
[20]Kanoh, N., Kyo, M., Inamori, K. et al. SPR imaging of photo cross linked small molecule arrays on gold. Anal Chem,2006,78(7):2226-2230.
[21]Forzani, E. S., Zhang, H. Q., Chen, W. et al. Detection of heavy metal ions in drinking water using a high resolution differential surface plasmon resonance sensor. Environ Sci Technol, 2005,39(5):1257-1262.
[22]Evans, A. G. and Charles, S. A. The application of a rapid, homogeneous biosensor gased on surface plasmon resonance to clinical chemistry, DNA probes and immunoassay, Abstract book. Biosensors'90,1990:223-224.
[23]张先恩编著.生物传感器.北京：化学工业出版社,2006：215-217.
[24]De Crescenzo, G., Pham, P. L., Durocher, Y. et al. Enhancement of the antagonistic potency of transforming growth factor alpha receptor extracellular domains by coiled coil induced homo-and heterodimerization. Biol Chem,2004,279(25):26013-26018.
[25]Casper, D., Bukhtiyarova, M. and Springman, E. B. A Biacore biosensor method for detailed kinetic binding analysis of small molecule inhibitors of p38 alpha mitogen activated protein kinase. Anal Biochem,2004,325(1):126-136.
[26]Nordin, H., Jungnelius, M., Karlsson, R. et al. Kinetic studies of small molecule interactions with protein kinases using biosensor thchnology. Anal Biochem,2005,340(2):359-368.
[27]波恩,沃尔夫张颖颖.表面等离子体共振(SPR)传感技术及在介质复折射率测量中的应用：[博士学位论文].南京理工大学,2009.,2005.
[28]张颖颖.表面等离子体共振(SPR)传感技术及在介质复折射率测量中的应用：[博士学位论文].南京理工大学,2009.
[29]Ordal M A, Bell R J, Alexander R W, et al. Optical properties of fourteen metals in the infrared and far infrared:Al, Co, Cu, Au, Fe, Pb, Mo, Ni, Pd, Pt, Ag, Ti, V, and W. Applied Optics,1985,24:4493-4499.
[30]Iwata T, Maeda S. Simulation of an absorption based surface plasmon resonance sensor by means of ellipsometry. Applied Optics,2007,46:1575-1582.
[31]Kurihara K, Suzuki K. Theoretical understanding of an absorption based surface plasmon resonance sensor based on Kretchmann's theory. Analytical Chemistry,2002,74:696-701.
[32]戚非,王晓秋.用波动理论计算古斯-汉辛距离.大连大学学报,2004,24(4)：21-24.
[33]Weng Cho Chew. Waves and fields in inhomogeneous media. New York:Van Nostrand Reinhold,1999:49-53.
[34]Matsubara K, Kawata S, Minami S. Optical chemical sensor based on surface plasmon measurement. Applied Optics,1988,27:1160-1163.
[35]Liedberg B, Lundstrom I, Stenberg E. Principles of biosensing with an extended coupling matrix and surface plasmon resonance. Sensors and Actuators B,1993,11:63-72.
[36]崔大付,周力夫.表面等离子体谐振测试仪.中国专利,专利号：98102366.5
[37]Jorgenson R C, Yee S S. A fiber-optic chemical sensor based on surface plasmon resonance. Sensors and Actuators B,1993,12:213-220.
[38]Zhang L M, Uttamchandani D. Optical chemical sensing employing surface plasmon resonance. Electronics Letters,1988,23:1469-1470.
[39]Vukusic P S, Bryan-Brown G P, Sambles J R. Surface plasmon resonance on grating as novel means for gas sensing. Sensors and Actuators B,1992,8:155-160.
[40]Vidal M M B, Lopez R, Aleggret S, et al. Determination of probable alcohol yield in musts by means of an SPR optical sensor. Sensors and Actuators B,1993,11:455-459.
[41]Nylander C, Liedberg B, Lind T. Gas detection by means of surface plasmons resonance. Sensors and Actuators,1982,3:79-88.
[42]Liedberg B, Nylander C, Lundstrom I. Surface plasmons resonance for gas detection and biosensing. Sensors and Actuators,1983,4:299-304.
[43]Homola J, Yee S S, Gauglitz G. Surface plasmon resonance sensors:review. Sensors and Actuators B,1999,54:3-15.
[44]Ho H P, Law W W. Application of differential phase measurement technique to surface plasmon resonance sensors. Sensors and Actuators B,2003, (96):554-559.
[45]Wu C, Jian Z, Joe S. High-sensitivity sensor based on surface plasmon resonance and heterodyne interferometry. Sensors and Actuators B,2003, (92):133-136.
[46]Nitikin P I, Grigorenko A N, Belogzelov A A. Surface plasmon resonance interferometry for micro-array biosensing. Sensors and Actuators B,2000,85:189-193.
[47]Naraoka R, Kajikawa K. Phase detection of surface plasmon resonance using rotating analyzer method. Sensors and Actuators B,2005,107:952-956.
[48]Kruchinin A A, Vlasov Y G. Surface plasmon resonance monitoring by means of polarization state measurement in reflected light as the basisi of a DNA-probe biosensor. Sensors and Actuators B,1996,30:77-80.
[49]Nitikin P I, Belogzelov A A, Kochergin V E. Surface plasmon resonance interferometry for biological and chemical sensing. Sensors and Actuators B,1999,54:43-50.
[50]Kochergin V E, Valeiko M V, Belogzelov A A. Visualiztion of the angular depandence of the reflected radiation phase under conditions of a surface plasmon resonance and its sensor application. Quantum Electronic,1998,28:835-839.
[51]Wu C M, Jian Z C, Joe S F. High-sensitivity sensor based on surfae plasmon resonance and heterodyne interferometry. Sensors and Actuators B,2003,92:133-136.
[52]Yu X L, Zhao L Q, Jiang H. Immunosensor based on optical heterodyne phase detection. Sensors and Actuators B,2001,76:199-202.
[53]Shen S, Liu T, Gua J. Optical phase-shift detection of surface plasmon resonance. Applied Optics,1998,37:1747-1751.
[54]Yu X L, Wang D, Wei X. A surface plasmon resonance imaging interferometry for protein micro-array detection. Sensors and Actuators B,2005,108:761-771.
[55]余兴龙,刘俊峰,定翔.基于SPR相位检测的蛋白质芯片信号获取与处理研究.生命科学仪器,2005,3：20-24.
[56]王弋嘉,张崇磊,王蓉等.差分干涉表面等离子体共振传感器的优化与验证.光学精密工程,2013,21(3)：2464-2471.
[57]郝鹏,吴一辉.基于噪声分析的波长表面等离子体共振分析仪的数据处理.光学精密工程,2009,17(9)：2159-2164.
[58]Siu-Pang Ng, Chi-Man Lawrence Wu, Shu-Yuen Wu, Ho-Pui Ho, S.K. Kong. Differential spectral phase interferometry for wide dynamic range surface plasmon resonance biosensing. Biosensors and Bioelectronics,2010,26:1593-1598.
[59]Kyoungsook Park, Junhyoung Ahn, So Yeon Yi, et al. SPR imaging-based monitoring of caspase-3 activation. Biochemical and Biophysical Research Communications,2008,368: 684-689.
[60]Takeshi Mori, Kazuki Inamori, Yusuke Inoue, et al. Evaluation of protein kinase activities of cell lysates using peptide microarrays based on surface plasmon resonance imaging. Analytical Biochemistry,2008,375:223-231.
[61]A.M.P.B. Seneviratne, Michael Burroughs, Ernest Giralt, et al. Direct-reversible binding of small molecules to G protein βγ subunits. Biochimica et Biophysica Acta 2011,1814: 1210-1218.
[62]Robert G. Hamilton, Sarbjit S. Saini, Donald MacGlashan. Surface plasmon resonance analysis of free IgE in allergic patients receiving omalizumab(Xolair). Journal of Immunological Methods 383,(2012):54-59.
[63]张兵心,陈淑芬,付雷,等.一种温控的可调表面等离子体光学器件.光学学报,2012,32(7)：723005-1.
[64]李娟,王冰艳,薛文瑞.基于MIM型表面等离子体光波导的Y形分束器的传输性能研究.光学学报,2012,32(1)：0124002-1.
[65]Yu Xinglong, Wang Dingxin, Yan Zibo. Simulation and analysis of surface plasmon resonance biosensor based on phase detection. Sensors and Actuators B, Chem.,2003,91:285-290.
[66]Ryo Naraoka, Kotaro Kajikawa. Phase detection of surface plasmon resonance using rotating analyzer method. Sensors and Actuators B,2005,107:952-956.
[67 H.P. Ho, W.C. Law, S.Y. Wu, et al. Phase-sensitive surface plasmon resonance biosensor using the photoelastic modulation technique. Sensors and Actuators B,2006,114:80-84.
[68]H. P. Ho, W. W. Lam, and S. Y. Wu. Surface plasmon resonance sensor based on the measurement of differential phase. Review of scientific instruments.2002,73:3534-3539.
[69]刘畅,邹正峰,陈淑芬,等.基于光盘光栅的表面等离子体共振传感器.中国激光,2012,39(3)：1-4.
[70]方肇伦,殷学锋,方群等.微流控分析芯片.第1版.北京：科学出版社,2003.
[71]殷学锋,方群,凌云扬等.微流控分析芯片的加工技术.现代科学仪器.2001,2(4)：9-14.
[72]金亚,罗国安,汤扬华等.集成毛细管电泳芯片系统的制作、测试及应用.分析科学学报.2001,17(2)：148-152.
[73]Wu D P, Luo Y, Zhou X M, Dai Z P, Lin B C. Multilayer POLY(vinyl alcohol)-absorbed coating on poly(polydimethyl siloxane) microfluidic chips for biopolymer separation. Electrophoresis,2005,26(1):211-218.
[74]林炳成,秦建华.图解微流控芯片实验室.北京：科学出版社.2008.
[75]Duffy D. C., McDonald J C, Schueller O. J. A. et al. Rapid prototyping of micro fluidic systems in poly(dimethylsiloxane). Anal. Chem.,1998,70(4):974-984.
[76]金鹏,谭久彬PDMS微小流路微加工技术的研究.微细加工技术,2001,3：31-40.
[77]D.布里格斯著,聚合物表面分析,北京：化学工业出版社,2001.
[78]David C Duffy, Olivier J A Schueller, Scott T Brittain and George M Whitesides. Rapid prototyping of microfluidic switches in poly(dimethyl siloxane) and their actuation by electro-osmotic flow. Journal of Micromechanics and Microengineering,1999.
[79]Yeatman E M, Ash E A. Surface plasmon microscopy. Electron. Lett.,1987,23:1091-1092.
[80]Hickel W, Knoll W. Surface plasmon microscopy of lipid layers. Thin Solid Films,1990,187: 349-356.
[81]Kooyman R P H, Krull U J. Surface plasmon microscopy of two crystalline domains in a lipid monolayer. Langmuir,1991,7:1506-1509.
[82]Notcovich A G, Zhuk V, Lipson S G Surface plasmon resonance phase imaging. Appl. Phys. Lett.,2000,76:1665-1667.
[83]Hutter E, Cha S, Liu J F, et al. Role of substrate metal in gold nanoparticle enhanced surface plasmon resonance imaging. J. Phys. Chem. B,2001,105:8-12.
[84]Chah S, Hutter E, Roy D, et al. The effect of substrate metal on 2-aminoethanethiol and nanoparticle enhanced surface plasmon resonance imaging. Chem. Phys.,2001,272:127-136.
[85]Berger C E H, Kooyman R P H, Greve J. Resolution in surface plasmon microscopy. Rev. Sci. Instrum.,1994,65:2829-2835.
[86]Kano H, Knoll W. A scanning microscope employing localized surface plasmon polaritons as a sensing probe. Opt. Commun.,2000,182:11-15.
[87]Giebel K F, Bechinger C, Herminghars S, et al. Imaging of cell/substrate contacts of living cells with surface plasmon resonance microscopy. Biophys. J,1999,76:509-516.
[88]De Bruijn H E, Kooyman R P H, Greve J. Surface plasmon resonance microscopy: improvement of the resolution by rotation of the object. Appl. Optic,1993,32:2426-2430.
[89]Okamoto T, Yamaguchi I. Surface plasmon microscope with and electrionic angular scanning. Opt. Commun.,1992,93:265-270.
[90]Grigorenko A N, Nikitin P I, Kabashin A V. Phase jumps and interferometric surface plasmon resonance imaging. Appl. Phys. Lett.,1999,75:3917-3919.
[91]Nikitin P I, Grigorenko A N, Beloglazov A A, et al. Surface plasmon resonance interferometry for micro array biosensing. Sensor Actuat. B,2000,85:189-193.
[92]Grigorenko A N, Beloglazov A A, Nikitin P I, et al. Dark field surface plasmon resonance microscopy. Opt. Commun.,2000,74:151-155.
[93]Hickel W, Knoll W. Surface plasmon microscopic imaging of ultrathin metal coatings. Acta Metall.,1989,37:2141-2144.
[94]Steiner G, Sablinskas V, Hubner A, et al. Surface plasmon resonance imaging of microstructred monolayers. J. Mol. Struct.,1999,509:265-273.
[95]Morgan H, Taylor D M. Surface plasmon resonance microscopy:Reconstructing a three dimensional image. Appl. Physo. Lett.,1994,64:1330-1331.
[96]Furuki M, Kameoka J, Craighead H G, et al. Surface plasmon resonance sensors utilizing microfabricated channels. Sensor Actuat. B,2001,79:63-69.
[97]Kano H, Mizuguchi S, Kawata S J. Excitation of surface plasmon polaritions by a focused laser beam. Opt. Soc. Am. B,1998,15:1381-1396.
[98]Somekh M G, Liu S G, Velinov T S, et al. Optical V(z) for high resolution 2 pi furface plasmon microscopy. Opt. Lett.,2000,25:823-825.
[99]Yeatman E, Ash E. Surface plasmon scanning microscopy. Proc. SPIE.1988,897:100-107.
[100]Yeatman E, Ash E. Computerised surface plasmon microscopy. Proc. SPIE,1988,1028: 231-236.
[101]Stabler G, Somekh M G, See C W. High resolution wide field surface plasmon microscopy. J. Microsc.,2004,214:328-333.
[102]Matsubara K, Kawata S, Minami S. A compact surface plasmon resonance sensor for measurement of water in process. Appl. Spectrosc.,1988,42:1375-1379.
[103]Lyon L A, Holliway W D, Natan M J. An improved surface plasmon resonance imaging apparatus. Rev. Sci. Instrum.,1999,70:2076-2081.
[104]Fu E, Chinowsky T, Foley J, et al. Rev. Sci. Instrum.,2004,75:2300-2304.
[105]Rothenhausler B, Knoll W. Surface plasmon microscopy. Nature,1988,332:615-617.
[106]Evans S D, Flynn T M, Ulman A. Self-Assembled Multilayer formation on predefined templates. Langmuir,1995,11:3811-3814.
[107]Sui S F, Zhou Y. Phase separation of supported membrane imaged by surface plasmon microscopy. Sensor Actuat. B,2000,66:146-148.
[108]Florin E L, Gaub H E. Painted supported lipid membranes. Biophys. J.,1993,64:375-383.
[109]Evans S D, Allinson H, Boden N, et al. Surface plasmon resonance imaging of liquid crystal anchoring on patterned self assembled monolayers. J. Phys. Chem. B,1997,101:2143-2148.
[110]Sawodny M, Stumpe J, Knoll W. Photovolatilization of thin polysilane films detected by surface plasmon spectroscopy. J. Appl. Phys.,1991,69:1927-1935.
[111]Hegner M, Dreier M, Wagner P, et al. Modified DNA immobilized on bioreactive self assembled monolayer on gold for dynamic force microscopy imaging in aqueous buffer solution. J. Vac. Sci.Technol. B.,1996,14:1418-1421.
[112]Piscevic D, Knoll W, Tarlov M J. Surface plasmon microscopy of biotin streptavidin binding reactions on UV photopatterned alkanethiol sefl assembled monolayers. Supramolecular Science,1995,2:99-106.
[113]Thiel A J, Frutos A G, Jorfan C E, et al. In situ surface plasmon resonance imaging detection of DNA hybridization to oligonucleotide arrays on gold surfaces. Anal. Chem.,1997,69: 4948-4956.
[114]Livache T, Maillart E, Lassalle N, et al. Polypyrrole based DNA hybridization assays:study of label free detection processes versus fluorescence on microchips. J. Pharmaceut. Biomed., 2003,32:687-696.
[115]Smith E A, Kyo M, Kumasawa H, et al. Chemically induced hairpin formation in DNA monolayers. J. Am. Chem. Soc.,2002,124:6810-6811.
[116]Chen S, Deng T, Wang T, et al. Visualization of high-throughput and label-free antibody-polypeptide binding for drug screening based on microarrays and surface plasmon resonance imaging. J Biomed Opt.2012,17(1):1-8.
[117]Yuhki Yanase, Takaaki Hiragun, Sakae Kaneko, et al. Detection of refractive index changes in individual living cells by means of surface plasmon resonance imaging. Biosensors and Bioelectronics,2010,26:674-681.
[118]Takeshi Mori, Kazuki Inamori, Yusuke Inoue, et al. Evaluation of protein kinase activities of cell lysates using peptide microarrays based on surface plasmon resonance imaging. Analytical Biochemistry,2008,375:223-231.
[119]Jordan C E, Frutos A G, Thiel A J, et al. Surface plasmon resonance imaging measurements of DNA hybridization adsorption and strptavidin/DNA multilayer formation at chemically modified gold surfaces. Anal. Chem.,1997,69:4939-4947.
[120]Goodrich T T, Lee H J, Corn R M, Direct detection of genomic DNA by enzymatically amplified SPR imaging measurements of RNA microarrays. J. Am. Chem. Soc.,2004,126: 4086-4087.
[121]Jennifer M. Brockman, Bryce P. Nelson, et al. Surface plasmon resonance imaging measurements of ultrathin organic films. Annu. Rev. Phys. Chem,2000,51:41-63.
[122]X.L. Yu, D.X. Wang, X. Wei, et al. A surface plasmon resonance imaging interferometry for protein micro-array detection, Sensors and Actuators B,2005,108:765-771.
[123]S. Y. Wu, H. P. Ho, W. C. Law, et al. Highly sensitive differential phase-sensitive surface plasmon resonance biosensor based on the Mach-Zehnder configuration. Optics letters,2004, 29(20):2378-2380.
[124]王弋嘉,张崇磊,王蓉等.表面等离子体共振成像系统相位提取.光学学报,2013,33(5)：0524001.
[125]C. D. Bain, E. B. Troughton, Y. Y. Tao, J. Evall, G. M. Whiteside, R. G Nuzzo, Formation of monolayer films by spontaneous assembly of organic thiols from solution onto gold, J. Am. Chem. Soc.111(1989)321.
[126]L. Bertilsson, B. Liedberg, Infrared study of thiol assemblies on gold:preparation, characterization, and functionalization of mixed monolayers, Langmuir 9 (1993):141-149.
[127]Ulman A. Formation and structure of self assembled monolayers. Chem Rev,1996,96(4): 1533-1554.
[128]J. Spinke, M. Liley, H. J. Gudder, L. Angermaier, W. Knoll. Molecular regnization at self assemblyed monolayers:the constructino of multicomponent layers, Langmuir 9 (1993): 1821-1825.
[129]S. Lofas, B. Johnsson, A. Edstron, A. Hansson, G Lindquist, R. M. M. Hillgren, L. Stigh. Methods for the site controlled coupling to carboxymethyldextran surfaces in SPR sensors. Biosensors Bioelectron,10(1995):813-822.
[130]Nabok A. V., Hassan A. K., Ray A. K., et al. Study of adsorption of some organic molecules in calyx resorcinolarene LB films by surface plasmon resonance. Sensors and Actuators B, 1997,45(2):115-121.
[131]Bain C D, Troughton E B, Tao Y T, et al. Formation of monolayer films by the spontaneous assembly of organic thiols form solution onto gold. J. Am Chem Soc,1989,111(1):321-335.
[132]Schreiber F. Structure and growth of self assembling monolayers. Prog Surf Sci,2000, 65(5-8):151-156.
[133]Wang J, Rivas G, Jiang M, et al. Electrochemically induced release of DNA form gold ultramicroelectrodes. Langmuir,1999,15(19):6541-6545.
[134]Kafer D, Witte G, Cyganik P, et al. A comprehensive study of self-assembled monolayers of anthracenethiol on gold:solvent effects, structure, and stability. J. Am. Chem. Soc.,2006, 128(5):1723-32.
[135]Marie-Therese Stockhausen, Helle Broholm, Mette Villingsh(?)j,et al. Maintenance of EGFR and EGFRvⅢ expressions in an in vivo and in vitro model of human glioblastoma multiforme. Experimental cell research,2011,317(11):1513-1526.
[136]Zora Baretta, Rodrigo Santa Cruz Guindalini, Galina Khramtsova, et al. Resistance to trastuzumab in Her2-positive mucinous invasive ductal breast carcinoma. Clinical breast cancer, 2013,13(2):156-158.
[137]Jean Faivre, Anne-Marie Bouvier, Claire Bonithon-Kopp. Epidemiology and screening of colorectal cancer. Best practice & research clinical gastroenterology,2002,16(2):187-199.
[2]Fedeniuk, R. W., Boison, J. O. and MacNeil, J. D. Validation of a gas chromatography-mass spectrometry method for the determination of pg/ml levels of 17 beta-estradiol and 17 beta-trenbolone in bovine serum. Chromatogr B,2004,802(2):307-315.
[3]Yang, L. H., Luan, T. G. and Lan, C. Y. Solid-phase microextraction with on-fiber silylation for simultaneous determinations of endocrine disrupting chemicals and steroid hormones by gas chromatography-mass spectrometry. Chromatogr A,2006,1104(1-2):23-32.
[4]Kelly, C. Analysis of steroids in environmental water samples using solid-phase extraction and ion-trap gas chromatography-mass spectrometry and gas chromatography-tandem mass spectrometry. Chromatogr A,2000,872(1-2):309-314.
[5]Watabe, Y., Kubo, T., Nishikawa, T. et al. Fully automated liquid chromatography-mass spectrometry determination of 17 beta-estradiol in river water. Chromatogr A,2006,1120(1-2): 252-259.
[6]Hu, J.Y., Zhang, H. F. and Chang, H. Improved method for analyzing estrogens in water by liquid chromatography-electrospray mass chromatography. Chromatogr A,2005,1070(1-2): 221-224.
[7]Lagana, A., Bacaloni, A., Fago, G. et al. Trace analysis of estrogenic chemicals in sewage effluent using liquid chromatography combined with tandem mass spectrometry. Rapid Commun Mass Sp,2000,14(6):401-407.
[8]Rothenhausler, B. and W. Knoll, Surface-plasmon microscopy. Nature,1988.332(6165): 615-617.
[9]Byun K M, Yoon S J, Kim D H, et al. Experimental study of. sensitivity enhancement in surface plasmon resonance biosensors by use of periodic metallic nanowires. Opt. Lett.,2007, 32(13):1902-1904.
[10]Chien F C. Direct determination of the refractive index and thickness of a biolayer based on coupled waveguide surface plasmon resonance mode. Opt. Lett.,2006,31(2):187-189.
[11]Patskovsky S, Kabashin A V, Meunier M, et al. Near-infrared surface plasmon resonance sensing on a silicon platform. Sensors and Actuators B,2004,97:409-414.
[12]Rich R L, Myszka D G. Survey of the year 2000 commercial optical biosensor literature. Journal of Molecular recognition,2001,14(6):273-294.
[13]Diaz-Cruz, M. S., de Alda, M. J. L., Lopez, R. et al. Determination of estrogens and progestogens by mass spectrometric techniques (GC/MS, LC/MS and LC/MS/MS). Mass Spectrom,2003,38(9):917-923.
[14]Matsumoto, Y., Kuramitz, H., Itoh, S. et al. New fluorometric enzyme immunoassay for 17 beta estradiol by homogeneous reaction using biotinylated estradiol. Talanta,2006,69(3): 663-668.
[15]Kokko, L., Johansson, N., Lovgren, T. et al. Enzyme inhibitor screening using a homogeneous proximity-based immunoassay for estradiol. Biomol Screen,2005,10(4): 348-354.
[16]Pemberton, R. M., Mottram, T. T. and Hart, J. P. Development of a screen printed carbon electrochemical immunosensor for picomolar concentrations of estradiol in human serum extracts. Biochem Bioph Meth,2005,63(3):201-212.
[17]www.biacore.com
[18]Natsume, T., Taoka, M., Manki, H. et al. Rapid analysis of protein interactions:On-chip micropurification of recombinant protein expressed in Esherichia coli. Proteomics,2002,2(9): 1247-1253.
[19]Spadavecchia, J., Manera, M. G, Quaranta, F. et al. Surface plasmon resonance imaging of DNA based biosensors for potential applications in food analysis. Biosens Bioelectron,2005, 21(6):894-900.
[20]Kanoh, N., Kyo, M., Inamori, K. et al. SPR imaging of photo cross linked small molecule arrays on gold. Anal Chem,2006,78(7):2226-2230.
[21]Forzani, E. S., Zhang, H. Q., Chen, W. et al. Detection of heavy metal ions in drinking water using a high resolution differential surface plasmon resonance sensor. Environ Sci Technol, 2005,39(5):1257-1262.
[22]Evans, A. G. and Charles, S. A. The application of a rapid, homogeneous biosensor gased on surface plasmon resonance to clinical chemistry, DNA probes and immunoassay, Abstract book. Biosensors'90,1990:223-224.
[23]张先恩编著.生物传感器.北京：化学工业出版社,2006：215-217.
[24]De Crescenzo, G., Pham, P. L., Durocher, Y. et al. Enhancement of the antagonistic potency of transforming growth factor alpha receptor extracellular domains by coiled coil induced homo-and heterodimerization. Biol Chem,2004,279(25):26013-26018.
[25]Casper, D., Bukhtiyarova, M. and Springman, E. B. A Biacore biosensor method for detailed kinetic binding analysis of small molecule inhibitors of p38 alpha mitogen activated protein kinase. Anal Biochem,2004,325(1):126-136.
[26]Nordin, H., Jungnelius, M., Karlsson, R. et al. Kinetic studies of small molecule interactions with protein kinases using biosensor thchnology. Anal Biochem,2005,340(2):359-368.
[27]波恩,沃尔夫张颖颖.表面等离子体共振(SPR)传感技术及在介质复折射率测量中的应用：[博士学位论文].南京理工大学,2009.,2005.
[28]张颖颖.表面等离子体共振(SPR)传感技术及在介质复折射率测量中的应用：[博士学位论文].南京理工大学,2009.
[29]Ordal M A, Bell R J, Alexander R W, et al. Optical properties of fourteen metals in the infrared and far infrared:Al, Co, Cu, Au, Fe, Pb, Mo, Ni, Pd, Pt, Ag, Ti, V, and W. Applied Optics,1985,24:4493-4499.
[30]Iwata T, Maeda S. Simulation of an absorption based surface plasmon resonance sensor by means of ellipsometry. Applied Optics,2007,46:1575-1582.
[31]Kurihara K, Suzuki K. Theoretical understanding of an absorption based surface plasmon resonance sensor based on Kretchmann's theory. Analytical Chemistry,2002,74:696-701.
[32]戚非,王晓秋.用波动理论计算古斯-汉辛距离.大连大学学报,2004,24(4)：21-24.
[33]Weng Cho Chew. Waves and fields in inhomogeneous media. New York:Van Nostrand Reinhold,1999:49-53.
[34]Matsubara K, Kawata S, Minami S. Optical chemical sensor based on surface plasmon measurement. Applied Optics,1988,27:1160-1163.
[35]Liedberg B, Lundstrom I, Stenberg E. Principles of biosensing with an extended coupling matrix and surface plasmon resonance. Sensors and Actuators B,1993,11:63-72.
[36]崔大付,周力夫.表面等离子体谐振测试仪.中国专利,专利号：98102366.5
[37]Jorgenson R C, Yee S S. A fiber-optic chemical sensor based on surface plasmon resonance. Sensors and Actuators B,1993,12:213-220.
[38]Zhang L M, Uttamchandani D. Optical chemical sensing employing surface plasmon resonance. Electronics Letters,1988,23:1469-1470.
[39]Vukusic P S, Bryan-Brown G P, Sambles J R. Surface plasmon resonance on grating as novel means for gas sensing. Sensors and Actuators B,1992,8:155-160.
[40]Vidal M M B, Lopez R, Aleggret S, et al. Determination of probable alcohol yield in musts by means of an SPR optical sensor. Sensors and Actuators B,1993,11:455-459.
[41]Nylander C, Liedberg B, Lind T. Gas detection by means of surface plasmons resonance. Sensors and Actuators,1982,3:79-88.
[42]Liedberg B, Nylander C, Lundstrom I. Surface plasmons resonance for gas detection and biosensing. Sensors and Actuators,1983,4:299-304.
[43]Homola J, Yee S S, Gauglitz G. Surface plasmon resonance sensors:review. Sensors and Actuators B,1999,54:3-15.
[44]Ho H P, Law W W. Application of differential phase measurement technique to surface plasmon resonance sensors. Sensors and Actuators B,2003, (96):554-559.
[45]Wu C, Jian Z, Joe S. High-sensitivity sensor based on surface plasmon resonance and heterodyne interferometry. Sensors and Actuators B,2003, (92):133-136.
[46]Nitikin P I, Grigorenko A N, Belogzelov A A. Surface plasmon resonance interferometry for micro-array biosensing. Sensors and Actuators B,2000,85:189-193.
[47]Naraoka R, Kajikawa K. Phase detection of surface plasmon resonance using rotating analyzer method. Sensors and Actuators B,2005,107:952-956.
[48]Kruchinin A A, Vlasov Y G. Surface plasmon resonance monitoring by means of polarization state measurement in reflected light as the basisi of a DNA-probe biosensor. Sensors and Actuators B,1996,30:77-80.
[49]Nitikin P I, Belogzelov A A, Kochergin V E. Surface plasmon resonance interferometry for biological and chemical sensing. Sensors and Actuators B,1999,54:43-50.
[50]Kochergin V E, Valeiko M V, Belogzelov A A. Visualiztion of the angular depandence of the reflected radiation phase under conditions of a surface plasmon resonance and its sensor application. Quantum Electronic,1998,28:835-839.
[51]Wu C M, Jian Z C, Joe S F. High-sensitivity sensor based on surfae plasmon resonance and heterodyne interferometry. Sensors and Actuators B,2003,92:133-136.
[52]Yu X L, Zhao L Q, Jiang H. Immunosensor based on optical heterodyne phase detection. Sensors and Actuators B,2001,76:199-202.
[53]Shen S, Liu T, Gua J. Optical phase-shift detection of surface plasmon resonance. Applied Optics,1998,37:1747-1751.
[54]Yu X L, Wang D, Wei X. A surface plasmon resonance imaging interferometry for protein micro-array detection. Sensors and Actuators B,2005,108:761-771.
[55]余兴龙,刘俊峰,定翔.基于SPR相位检测的蛋白质芯片信号获取与处理研究.生命科学仪器,2005,3：20-24.
[56]王弋嘉,张崇磊,王蓉等.差分干涉表面等离子体共振传感器的优化与验证.光学精密工程,2013,21(3)：2464-2471.
[57]郝鹏,吴一辉.基于噪声分析的波长表面等离子体共振分析仪的数据处理.光学精密工程,2009,17(9)：2159-2164.
[58]Siu-Pang Ng, Chi-Man Lawrence Wu, Shu-Yuen Wu, Ho-Pui Ho, S.K. Kong. Differential spectral phase interferometry for wide dynamic range surface plasmon resonance biosensing. Biosensors and Bioelectronics,2010,26:1593-1598.
[59]Kyoungsook Park, Junhyoung Ahn, So Yeon Yi, et al. SPR imaging-based monitoring of caspase-3 activation. Biochemical and Biophysical Research Communications,2008,368: 684-689.
[60]Takeshi Mori, Kazuki Inamori, Yusuke Inoue, et al. Evaluation of protein kinase activities of cell lysates using peptide microarrays based on surface plasmon resonance imaging. Analytical Biochemistry,2008,375:223-231.
[61]A.M.P.B. Seneviratne, Michael Burroughs, Ernest Giralt, et al. Direct-reversible binding of small molecules to G protein βγ subunits. Biochimica et Biophysica Acta 2011,1814: 1210-1218.
[62]Robert G. Hamilton, Sarbjit S. Saini, Donald MacGlashan. Surface plasmon resonance analysis of free IgE in allergic patients receiving omalizumab(Xolair). Journal of Immunological Methods 383,(2012):54-59.
[63]张兵心,陈淑芬,付雷,等.一种温控的可调表面等离子体光学器件.光学学报,2012,32(7)：723005-1.
[64]李娟,王冰艳,薛文瑞.基于MIM型表面等离子体光波导的Y形分束器的传输性能研究.光学学报,2012,32(1)：0124002-1.
[65]Yu Xinglong, Wang Dingxin, Yan Zibo. Simulation and analysis of surface plasmon resonance biosensor based on phase detection. Sensors and Actuators B, Chem.,2003,91:285-290.
[66]Ryo Naraoka, Kotaro Kajikawa. Phase detection of surface plasmon resonance using rotating analyzer method. Sensors and Actuators B,2005,107:952-956.
[67 H.P. Ho, W.C. Law, S.Y. Wu, et al. Phase-sensitive surface plasmon resonance biosensor using the photoelastic modulation technique. Sensors and Actuators B,2006,114:80-84.
[68]H. P. Ho, W. W. Lam, and S. Y. Wu. Surface plasmon resonance sensor based on the measurement of differential phase. Review of scientific instruments.2002,73:3534-3539.
[69]刘畅,邹正峰,陈淑芬,等.基于光盘光栅的表面等离子体共振传感器.中国激光,2012,39(3)：1-4.
[70]方肇伦,殷学锋,方群等.微流控分析芯片.第1版.北京：科学出版社,2003.
[71]殷学锋,方群,凌云扬等.微流控分析芯片的加工技术.现代科学仪器.2001,2(4)：9-14.
[72]金亚,罗国安,汤扬华等.集成毛细管电泳芯片系统的制作、测试及应用.分析科学学报.2001,17(2)：148-152.
[73]Wu D P, Luo Y, Zhou X M, Dai Z P, Lin B C. Multilayer POLY(vinyl alcohol)-absorbed coating on poly(polydimethyl siloxane) microfluidic chips for biopolymer separation. Electrophoresis,2005,26(1):211-218.
[74]林炳成,秦建华.图解微流控芯片实验室.北京：科学出版社.2008.
[75]Duffy D. C., McDonald J C, Schueller O. J. A. et al. Rapid prototyping of micro fluidic systems in poly(dimethylsiloxane). Anal. Chem.,1998,70(4):974-984.
[76]金鹏,谭久彬PDMS微小流路微加工技术的研究.微细加工技术,2001,3：31-40.
[77]D.布里格斯著,聚合物表面分析,北京：化学工业出版社,2001.
[78]David C Duffy, Olivier J A Schueller, Scott T Brittain and George M Whitesides. Rapid prototyping of microfluidic switches in poly(dimethyl siloxane) and their actuation by electro-osmotic flow. Journal of Micromechanics and Microengineering,1999.
[79]Yeatman E M, Ash E A. Surface plasmon microscopy. Electron. Lett.,1987,23:1091-1092.
[80]Hickel W, Knoll W. Surface plasmon microscopy of lipid layers. Thin Solid Films,1990,187: 349-356.
[81]Kooyman R P H, Krull U J. Surface plasmon microscopy of two crystalline domains in a lipid monolayer. Langmuir,1991,7:1506-1509.
[82]Notcovich A G, Zhuk V, Lipson S G Surface plasmon resonance phase imaging. Appl. Phys. Lett.,2000,76:1665-1667.
[83]Hutter E, Cha S, Liu J F, et al. Role of substrate metal in gold nanoparticle enhanced surface plasmon resonance imaging. J. Phys. Chem. B,2001,105:8-12.
[84]Chah S, Hutter E, Roy D, et al. The effect of substrate metal on 2-aminoethanethiol and nanoparticle enhanced surface plasmon resonance imaging. Chem. Phys.,2001,272:127-136.
[85]Berger C E H, Kooyman R P H, Greve J. Resolution in surface plasmon microscopy. Rev. Sci. Instrum.,1994,65:2829-2835.
[86]Kano H, Knoll W. A scanning microscope employing localized surface plasmon polaritons as a sensing probe. Opt. Commun.,2000,182:11-15.
[87]Giebel K F, Bechinger C, Herminghars S, et al. Imaging of cell/substrate contacts of living cells with surface plasmon resonance microscopy. Biophys. J,1999,76:509-516.
[88]De Bruijn H E, Kooyman R P H, Greve J. Surface plasmon resonance microscopy: improvement of the resolution by rotation of the object. Appl. Optic,1993,32:2426-2430.
[89]Okamoto T, Yamaguchi I. Surface plasmon microscope with and electrionic angular scanning. Opt. Commun.,1992,93:265-270.
[90]Grigorenko A N, Nikitin P I, Kabashin A V. Phase jumps and interferometric surface plasmon resonance imaging. Appl. Phys. Lett.,1999,75:3917-3919.
[91]Nikitin P I, Grigorenko A N, Beloglazov A A, et al. Surface plasmon resonance interferometry for micro array biosensing. Sensor Actuat. B,2000,85:189-193.
[92]Grigorenko A N, Beloglazov A A, Nikitin P I, et al. Dark field surface plasmon resonance microscopy. Opt. Commun.,2000,74:151-155.
[93]Hickel W, Knoll W. Surface plasmon microscopic imaging of ultrathin metal coatings. Acta Metall.,1989,37:2141-2144.
[94]Steiner G, Sablinskas V, Hubner A, et al. Surface plasmon resonance imaging of microstructred monolayers. J. Mol. Struct.,1999,509:265-273.
[95]Morgan H, Taylor D M. Surface plasmon resonance microscopy:Reconstructing a three dimensional image. Appl. Physo. Lett.,1994,64:1330-1331.
[96]Furuki M, Kameoka J, Craighead H G, et al. Surface plasmon resonance sensors utilizing microfabricated channels. Sensor Actuat. B,2001,79:63-69.
[97]Kano H, Mizuguchi S, Kawata S J. Excitation of surface plasmon polaritions by a focused laser beam. Opt. Soc. Am. B,1998,15:1381-1396.
[98]Somekh M G, Liu S G, Velinov T S, et al. Optical V(z) for high resolution 2 pi furface plasmon microscopy. Opt. Lett.,2000,25:823-825.
[99]Yeatman E, Ash E. Surface plasmon scanning microscopy. Proc. SPIE.1988,897:100-107.
[100]Yeatman E, Ash E. Computerised surface plasmon microscopy. Proc. SPIE,1988,1028: 231-236.
[101]Stabler G, Somekh M G, See C W. High resolution wide field surface plasmon microscopy. J. Microsc.,2004,214:328-333.
[102]Matsubara K, Kawata S, Minami S. A compact surface plasmon resonance sensor for measurement of water in process. Appl. Spectrosc.,1988,42:1375-1379.
[103]Lyon L A, Holliway W D, Natan M J. An improved surface plasmon resonance imaging apparatus. Rev. Sci. Instrum.,1999,70:2076-2081.
[104]Fu E, Chinowsky T, Foley J, et al. Rev. Sci. Instrum.,2004,75:2300-2304.
[105]Rothenhausler B, Knoll W. Surface plasmon microscopy. Nature,1988,332:615-617.
[106]Evans S D, Flynn T M, Ulman A. Self-Assembled Multilayer formation on predefined templates. Langmuir,1995,11:3811-3814.
[107]Sui S F, Zhou Y. Phase separation of supported membrane imaged by surface plasmon microscopy. Sensor Actuat. B,2000,66:146-148.
[108]Florin E L, Gaub H E. Painted supported lipid membranes. Biophys. J.,1993,64:375-383.
[109]Evans S D, Allinson H, Boden N, et al. Surface plasmon resonance imaging of liquid crystal anchoring on patterned self assembled monolayers. J. Phys. Chem. B,1997,101:2143-2148.
[110]Sawodny M, Stumpe J, Knoll W. Photovolatilization of thin polysilane films detected by surface plasmon spectroscopy. J. Appl. Phys.,1991,69:1927-1935.
[111]Hegner M, Dreier M, Wagner P, et al. Modified DNA immobilized on bioreactive self assembled monolayer on gold for dynamic force microscopy imaging in aqueous buffer solution. J. Vac. Sci.Technol. B.,1996,14:1418-1421.
[112]Piscevic D, Knoll W, Tarlov M J. Surface plasmon microscopy of biotin streptavidin binding reactions on UV photopatterned alkanethiol sefl assembled monolayers. Supramolecular Science,1995,2:99-106.
[113]Thiel A J, Frutos A G, Jorfan C E, et al. In situ surface plasmon resonance imaging detection of DNA hybridization to oligonucleotide arrays on gold surfaces. Anal. Chem.,1997,69: 4948-4956.
[114]Livache T, Maillart E, Lassalle N, et al. Polypyrrole based DNA hybridization assays:study of label free detection processes versus fluorescence on microchips. J. Pharmaceut. Biomed., 2003,32:687-696.
[115]Smith E A, Kyo M, Kumasawa H, et al. Chemically induced hairpin formation in DNA monolayers. J. Am. Chem. Soc.,2002,124:6810-6811.
[116]Chen S, Deng T, Wang T, et al. Visualization of high-throughput and label-free antibody-polypeptide binding for drug screening based on microarrays and surface plasmon resonance imaging. J Biomed Opt.2012,17(1):1-8.
[117]Yuhki Yanase, Takaaki Hiragun, Sakae Kaneko, et al. Detection of refractive index changes in individual living cells by means of surface plasmon resonance imaging. Biosensors and Bioelectronics,2010,26:674-681.
[118]Takeshi Mori, Kazuki Inamori, Yusuke Inoue, et al. Evaluation of protein kinase activities of cell lysates using peptide microarrays based on surface plasmon resonance imaging. Analytical Biochemistry,2008,375:223-231.
[119]Jordan C E, Frutos A G, Thiel A J, et al. Surface plasmon resonance imaging measurements of DNA hybridization adsorption and strptavidin/DNA multilayer formation at chemically modified gold surfaces. Anal. Chem.,1997,69:4939-4947.
[120]Goodrich T T, Lee H J, Corn R M, Direct detection of genomic DNA by enzymatically amplified SPR imaging measurements of RNA microarrays. J. Am. Chem. Soc.,2004,126: 4086-4087.
[121]Jennifer M. Brockman, Bryce P. Nelson, et al. Surface plasmon resonance imaging measurements of ultrathin organic films. Annu. Rev. Phys. Chem,2000,51:41-63.
[122]X.L. Yu, D.X. Wang, X. Wei, et al. A surface plasmon resonance imaging interferometry for protein micro-array detection, Sensors and Actuators B,2005,108:765-771.
[123]S. Y. Wu, H. P. Ho, W. C. Law, et al. Highly sensitive differential phase-sensitive surface plasmon resonance biosensor based on the Mach-Zehnder configuration. Optics letters,2004, 29(20):2378-2380.
[124]王弋嘉,张崇磊,王蓉等.表面等离子体共振成像系统相位提取.光学学报,2013,33(5)：0524001.
[125]C. D. Bain, E. B. Troughton, Y. Y. Tao, J. Evall, G. M. Whiteside, R. G Nuzzo, Formation of monolayer films by spontaneous assembly of organic thiols from solution onto gold, J. Am. Chem. Soc.111(1989)321.
[126]L. Bertilsson, B. Liedberg, Infrared study of thiol assemblies on gold:preparation, characterization, and functionalization of mixed monolayers, Langmuir 9 (1993):141-149.
[127]Ulman A. Formation and structure of self assembled monolayers. Chem Rev,1996,96(4): 1533-1554.
[128]J. Spinke, M. Liley, H. J. Gudder, L. Angermaier, W. Knoll. Molecular regnization at self assemblyed monolayers:the constructino of multicomponent layers, Langmuir 9 (1993): 1821-1825.
[129]S. Lofas, B. Johnsson, A. Edstron, A. Hansson, G Lindquist, R. M. M. Hillgren, L. Stigh. Methods for the site controlled coupling to carboxymethyldextran surfaces in SPR sensors. Biosensors Bioelectron,10(1995):813-822.
[130]Nabok A. V., Hassan A. K., Ray A. K., et al. Study of adsorption of some organic molecules in calyx resorcinolarene LB films by surface plasmon resonance. Sensors and Actuators B, 1997,45(2):115-121.
[131]Bain C D, Troughton E B, Tao Y T, et al. Formation of monolayer films by the spontaneous assembly of organic thiols form solution onto gold. J. Am Chem Soc,1989,111(1):321-335.
[132]Schreiber F. Structure and growth of self assembling monolayers. Prog Surf Sci,2000, 65(5-8):151-156.
[133]Wang J, Rivas G, Jiang M, et al. Electrochemically induced release of DNA form gold ultramicroelectrodes. Langmuir,1999,15(19):6541-6545.
[134]Kafer D, Witte G, Cyganik P, et al. A comprehensive study of self-assembled monolayers of anthracenethiol on gold:solvent effects, structure, and stability. J. Am. Chem. Soc.,2006, 128(5):1723-32.
[135]Marie-Therese Stockhausen, Helle Broholm, Mette Villingsh(?)j,et al. Maintenance of EGFR and EGFRvⅢ expressions in an in vivo and in vitro model of human glioblastoma multiforme. Experimental cell research,2011,317(11):1513-1526.
[136]Zora Baretta, Rodrigo Santa Cruz Guindalini, Galina Khramtsova, et al. Resistance to trastuzumab in Her2-positive mucinous invasive ductal breast carcinoma. Clinical breast cancer, 2013,13(2):156-158.
[137]Jean Faivre, Anne-Marie Bouvier, Claire Bonithon-Kopp. Epidemiology and screening of colorectal cancer. Best practice & research clinical gastroenterology,2002,16(2):187-199.