An experimental correlation study between field–target overlap and sensitivity of surface plasmon resonance biosensors based on sandwiched immunoassays

In this report, we have studied the effectiveness of field–target overlap to evaluate detection sensitivity of surface plasmon resonance (SPR) biosensors. The investigation used theoretical analysis based on the transfer matrix method, which was experimentally confirmed by thin film-based detection in sandwich and reverse sandwich immunoglobulin G (IgG) assays. Both theoretical and experimental results show that strong correlation exists between the overlap and the sensitivity with the coefficient of correlation higher than 95% in all the cases that we have considered. We have also confirmed the correlation in diffraction grating-based SPR measurement of IgG/anti-IgG interactions. The correlation elucidates the mechanism behind the far-field detection sensitivity of SPR biosensors and can lead to the enhancement of SPR biosensing with molecular scale sensitivity.     

一种基于相位测量的角漂移自适应结构表面等离子体共振气体折射率测量系统

提出了一种可抑制角漂移的表面等离子体传感器结构,并结合相位测量设计了相应的气体折射率测量系统。分析表明激光入射角、金膜厚度以及反射光p、s分量的相位差与气体折射率之间的固有非线性是影响相位响应度与折射率测量精度的主要因素。计算表明所提出的自适应结构将角漂移引起的误差降低了一个数量级并很大程度提高了测量灵敏度。同时分析设计了金膜厚度参数,并评估了反射光p、s分量的相位差与气体折射率之间固有非线性带来的误差。应用于空气折射率的测量比对实验显示其测量精度达到了10-6量级。     

基于辐射度的光谱校正与自适应拟合相结合的SPR共振波长确定方法

表面等离子体共振(SPR)传感技术因其灵敏度高、无需标记、可原位实时监测的特点,被广泛应用在生物医学、化学检测、食品安全、环境监测等领域。对于波长调制型SPR传感器,由于光谱测量系统各部件对不同波长响应度不同,从而对光谱共振波长的实际位置产生干扰,影响到实验检测结果。为消除这种影响,提出了一种基于辐射度空间的SPR相对反射率校正方法,并使用阶数自适应拟合算法对共振波长进行精确测定。通过标定光谱测量系统的仪器响应曲线,将光谱仪得到的原始光谱转换成辐射光谱,进而计算出不依赖于光谱仪系统中任何部件的SPR相对反射率。相比于传统的反射率校正方式(以共振光谱除以非共振光谱的结果作为反射率光谱),此方法校正后的光谱在光谱形状上具备半峰宽更窄和共振峰更对称的优势,从而为精确确定共振波长提供了可靠的保障。随后基于拟合误差最小化的目标,对共振区域采用阶数自适应多项式拟合算法确定共振波长。实验测量了不同入射角度下的SPR共振光谱,使用此方法校正得到反射率光谱的半峰全宽保持在(100±10) nm,表明此方法的光谱峰形优势具备普适性;连续采集了4 000组光谱并计算共振波长,其相对标准偏差为0.007 8%,处理速度为每个光谱12 ms,表明此方法具备良好的抗噪声波动鲁棒性和光谱数据处理的实时性;测量了不同浓度下NaCl溶液的SPR共振光谱,其共振波长与溶液折射率线性相关系数为0.998 5,品质因数为传统校正方式的3倍,表明此方法具备良好的可靠性,并且从光谱的处理算法层面提高了传感性能,相比于从工艺制备上提高品质因数的传统方式,处理简便,效果更突出。结果表明,基于辐射度空间的相对反射率矫正与阶数自适应拟合相结合的SPR共振波长检测方法具备可靠性好、运算速度快、分辨率高、抗噪声、品质因数高等特点,能够有效提高SPR传感器的数据处理与传感性能。     

Highly sensitive differential phase-sensitive surface plasmon resonance biosensor based on the Mach-Zehnder configuration

A high-sensitivity surface plasmon resonance (SPR) biosensor based on the Mach-Zehnder interferometer design is presented. The novel feature of the new design is the use of a Wollaston prism through which the phase quantities of the p and s polarizations are interrogated simultaneously. Since SPR affects only the p polarization, the signal due to the s polarization can be used as the reference. Consequently, the differential phase between the two polarizations allows us to eliminate all common-path phase noise while keeping the phase change caused by the SPR effect. Experimental results obtained from glycerin-water mixtures indicate that the sensitivity limit of our scheme is 5.5 x 10(-8) refractive-index units per 0.01 degrees phase change. To our knowledge, this is a significant improvement over previously obtained results when gold was used as the sensor surface. Such an improvement in the sensitivity limit should allow SPR biosensors to become a possible replacement for conventional biosensing techniques based on fluorescence. Monitoring of the bovine serum albumin (BSA) binding reaction with BSA antibodies is also demonstrated.     

Phase-shift interferometry combined with surface plasmon resonance effect for two-dimensional bio-surface analysis

The phase-shift interferometry combined with surface plasmon resonance (SPR) effect has been studied as a novel technique used to analyze the bio-surface, which measures the spatial phase variation of SPR reflected light. The spatial sensitivity of the SPR imaging sensor is improved over the conventional SPR imaging systems based on optical intensity.     

Phase sensitive SPR sensor for wide dynamic range detection

Phase detection has been utilized to enhance the sensitivity of surface plasmon resonance (SPR) sensors for a long time. However, an inherent drawback for phase sensitive SPR sensors are their limited dynamic range, which has greatly hindered wide applications of such sensors. In this Letter, a design combining phase detection and angular interrogation has been proposed to provide an SPR sensor with both high sensitivity and wide dynamic range. As a result, a resolution of 2.2×10^-7?RIU with a dynamic range of over 0.06?RIU has been achieved simultaneously. An added advantage of this design is the flexibility for sensitivity and dynamic range adjustment.     

一种用于变压器局部放电在线监测的光纤声发射传感器实验研究

提出了一种光纤声发射传感器并构建传感系统实现变压器局部放电在线监测,利用传感光栅体积小,重量轻,灵敏度高和抗电磁干扰的特点,将传感器置于变压器内部实现局部放电声发射信号的测量。研究了传感光栅实现声发射应力波测量的机理,声发射信号引起传感光栅反射光谱发生漂移,导致特定频点处反射光强发生变化,通过反射光强的变化实现声发射信号的测量。构建声发射传感系统实验模型并提出了一种系统性能优化策略,使系统工作在传感光栅反射光谱上升或下降沿的半峰值频点处,从而保障传感系统具有良好的线性输出特性;研究传感系统工作点稳定技术,设计信号反馈回路自动跟踪反射光谱的漂移,保证系统稳定工作在传感光栅半峰值频点处,消除温度变化对传感系统测量精度的影响。将封装好的传感器用于变压器局部放电现场检测,结果表明,光纤光栅声发射传感器与压电传感器相比具有灵敏度高、动态范围宽等优点,可以实现变压器局部放电在线监测。     

Optical cavity coupled surface plasmon resonance sensing for enhanced sensitivity

A surface plasmon resonance (SPR) sensing system based on the optical cavity enhanced detection tech-nique is experimentally demonstrated. A fiber-optic laser cavity is built with a SPR sensor inside. By measuring the laser output power when the cavity is biased near the threshold point, the sensitivity, defined as the dependence of the output optical intensity on the sample variations, can be increased by about one order of magnitude compared to that of the SPR sensor alone under the intensity interrogation scheme. This could facilitate ultra-high sensitivity SPR biosensing applications. Further system miniaturization is possible by using integrated optical components and waveguide SPR sensors.     

Measurement of small differences in refractive indices of solutions with interferometric optical method

Based on the principles of both surface plasmon resonance (SPR) and heterodyne interferometry, an optical method for measuring small differences in refractive indices of solutions was proposed. On a specially designed probe, two light beams are incident on both reference and test solutions. The phase differences between the p- and s-polarizations of each reflected light under SPR condition are measured simultaneously with heterodyne interferometric technique. The phase values are substituted into special equations derived from Fresnel's equations. Finally, the difference between the refractive indices of these two solutions can be estimated. The feasibility of this method was demonstrated and the measurement sensitivity of refractive index can reach a value of at least 8.57×10⁻⁷. This method should bear the merits of a simple structure, easy operation, high sensitivity and rapid measurement.     

光纤SPR湿敏传感器及其共振光谱特性研究

提出并研制了基于光纤SPR传感探针的新型湿敏传感器。首先研究了光纤SPR传感探针对环境湿度变化的敏感特性,在此基础上提出在光纤SPR传感探针表面增覆不同厚度且具有水分子吸附功能的PVA薄膜来实现环境相对湿度的监测。研究结果表明,增覆双层PVA薄膜的光纤SPR传感探针在高湿区具有较好监测效果,其共振强度对应的相对湿度测量灵敏度达到1.59%/%RH,较光纤SPR探针呈现显著提高。而增覆单层PVA薄膜的光纤SPR传感探针在高湿区共振波长对应的相对湿度监测灵敏度达到2.411nm/%RH。此外所提出的新型光纤SPR湿敏探针在PVA薄膜失效后经过特殊工艺处理仍可重复镀膜使用。     

准晶体结构光纤表面等离子体共振传感器特性研究

光纤表面等离子体共振传感器在高灵敏度传感和在线实时监测等领域具有重要意义. 设计了一种六重准晶体结构环形通道光纤表面等离子体共振传感器, 基于有限元法对该传感器的传感特性进行了数值模拟. 研究了光纤各结构参量对传感器特性的影响规律. 研究结果表明: 待测液折射率的有效监测范围为1.25–1.331, 最高灵敏度可达26400 nm·RIU^-1, 传感器具有损耗谱杂峰少、探测范围广、灵敏度高、设计灵活性高和光路可弯曲等特点, 在生化检测、公共安全、环境污染监测以及高灵敏度传感等领域具有广泛的应用前景.     

波长调制型表面等离子体共振的传感特性研究

表面等离子体共振(SPR)光学传感器能实现生物医学的快速、 无标记、 高精度检测,是生物化学分析的重要方法。 研制了基于波长调制型的Kretschmann结构表面等离子体共振(SPR)生物传感系统,研究了在体溶液传感方式下的传感性能。 利用不同浓度的乙醇和乙二醇溶液进行体溶液传感测试。 实验结果表明,在折射率低时共振波长对折射率变化响应的灵敏度低,但响应的线性度高;随着折射率增大,共振波长对折射率的响应变化的灵敏度提高。 在1.407 0～1.430 RIU折射率范围内,灵敏度高达11 487 nm·RIU-1。 传感器的共振波长的稳定性为0.213 8 nm,可分辨最小折射率趋近10-6 RIU。 所研制的波长调制型表面等离子共振传感器操作简单、 灵敏度高、 检测范围大,可实现浓度极低生物标记物的有效检测,在化学、 生物传感领域有重要的应用。     

Optical fiber SPR biosensor with sandwich assay for the detection of prostate specific antigen

We present a new, sensitive, few mode fiber (FMF) surface plasmon resonance (SPR) biosensor with a sandwich assay for the detection of PSA. The side-polished FMF biosensor does not need a polarizer and a thin high-index overlayer. The optical sensitivity of the SPR sensor was determined as 2.5 × 10⁻⁶ RIU. In the SPR PSA sensor, the SPR signals were amplified by a factor of 6 in average over no secondary antibody, using the sandwich assay. The proposed FMF SPR biosensor has great potential for real-time analysis of immune reaction between biomolecules and the advantages of high-sensitivity and label-free detection.     

基于全相位滤波技术的光纤表面等离子体共振传感解调算法

基于生物样品检测对折射率传感的迫切需求,构建一种全光纤表面等离子体共振(surface plasmon resonance,SPR)系统,并针对其设计了基于全相位滤波技术的SPR特征波长传感解调算法.基于系统仿真,理论计算了光纤SPR传感器的折射率传感灵敏度.采用全相位滤波技术提取光纤SPR传感器透射光谱的特征波长,理论推导了全相位滤波器的解析表达式.实验结果表明,使用本算法的光纤SPR传感器折射率传感灵敏度为1640.4 nm/RIU,折射率检测的分辨率是7.36×10~(-4)RIU,与传统方法相比,有效提高了系统的检测精度和抗光源扰动性能,降低了实验成本.     

表面等离子体共振传感技术应用于小分子检测

人体内的生物小分子对维持生命体健康具有重要影响,此类分子参与生命体的血液循环及免疫系统,因此检测生命体中生物小分子对研究小分子在生命体中的生理功能有着重要的意义。傅里叶变换-表面等离子体共振（Fourier transform-surface plasmon resonance,FT-SPR）光谱技术具有操作简便、灵敏度高、所需样品少、可实时检测等优点,近年越来越多应用于分子的检测。对于部分分子尤其是分子量非常小的生物小分子,FT-SPR直接检测法存在信号稳定性差、灵敏度不高等缺点,因此可以针对不同的检测目标构建系列SPR小分子生物传感器通过信号扩增弥补以上缺点。该研究分类并列举了用于小分子检测的SPR免疫传感器（直接检测法、“三明治”法、竞争检测法以及抑制检测法）、SPR分子印迹传感器以及其他基于SPR传感器,系统综述了SPR技术检测小分子的研究进展,并对其发展远景进行了展望。     

Enhanced surface plasmon resonance detection using porous ITO–gold hybrid substrates

We demonstrated enhanced surface plasmon resonance (SPR) detection by incorporating an indium tin oxide (ITO) layer on a thin gold film. Porous ITO layers were fabricated by e-beam evaporation and slanted deposition at room temperature and the ITO structure was optimized in terms of the surface roughness and the SPR curve characteristics. In sensing experiments, the results obtained by ethanol–water mixture test showed that SPR substrates with a porous ITO layer provided a notable sensitivity improvement compared to a conventional bare gold film, which is attributed to the nonlinear dispersion characteristic of surface plasmons. Our approach is intended to show the feasibility and extend the applicability of the porous ITO-mediated SPR biosensor to diverse biomolecular binding events.     

Surface plasmon resonance device with imaging processing detector for refractive index measurements

This work presents a new surface plasmon resonance (SPR) instrument based on Kretschmann configuration. This device acquires and processes the reflected SPR image of the sample by using a webcam together with an image processing algorithm that transforms the RGB image in numeric values and correlates the integrated intensity with the refractive index of the solution. Experimental signals were compared with theoretical values and it was found an excellent agreement. In addition, the applicability of the instrument was tested by measuring the refractive index of solutions in a continuous flow mode. Excellent stability and sensitivity of the signal were found in the presence of small changes of the refractive index.     

Sensitivity‐enhancement methods for surface plasmon sensors

Surface plasmon resonance (SPR) sensors have been a mature technology for more than two decades now, however, recent investigations show continuous enhancement of their sensitivity and their lower detection limit. Together with the recent investigations in localized SPR phenomena, extraordinary optical transmission through nanoapertures in metals, and surface‐enhanced spectroscopies, drastic developments are expected to revolutionize the field of optical biosensing. Sensitivity‐enhancement (SE) techniques are reviewed focusing both on the physical transduction mechanisms and the system performance. In the majority of cases the SE is associated with the enhancement of the electromagnetic field overlap integral describing the interaction energy within the analyte. Other important mechanisms are the interaction between plasmons and excitons and between the analyte molecules and the metal surface. The lower detection limit can be reduced significantly if systems with high signal‐to‐noise ratio are used such as common‐path interferometry, ellipsometry or polarimetry systems.     

Cascaded dual-channel fiber SPR temperature sensor based on liquid and solid encapsulations

In order to control the working wavelength range of the fiber surface plasmon resonance(SPR) temperature sensor and realize the wavelength division multiplexing type multi-channel fiber SPR temperature sensor, by comprehensively investigating the influence of liquids with different thermal-optical coefficients and solid packaging materials on the performance of fiber SPR temperature sensor, a dual-channel fiber SPR temperature sensor based on liquid–solid cascade encapsulation was designed and fabricated. The liquid temperature sensing stage encapsulated in capillary worked in 616.03 nm–639.05 nm band, the solid sensing stage coated with pouring sealant worked in 719.37 nm–825.27 nm band, and the two stages were cascaded to form a fiber dual-channel temperature sensor. The testing results indicated that when the temperature range was 35℃–95℃, the sensitivity of two-stage temperature detection was -0.384 nm/℃and -1.765 nm/℃ respectively. The proposed fiber sensor has simple fabrication and excellent performance which can be widely used in various fields of dual-channel temperature measurement and temperature compensation.     

Investigation of dual-channel fiber-optic surface plasmon resonance sensing for biological applications

A dual-channel fiber-optic sensor based on surface plasmon resonance (SPR) for self-referencing refractive-index measurements has been proposed. Most applications of fiber-optic SPR sensors are designed to measure the refractive index of a liquid or gas sample by measuring the signal from a single surface, the sensitivity and stability of which is easily affected by the fluctuation of external environmental conditions. We have designed a dual-channel fiber-optic surface sensor with two independent SPR signals from two areas of the same probe. A prototype sensor was fabricated and characterized. The preliminary experimental results demonstrate the characteristic responses of both SPR signals from two channels that independently correspond to the refractive index changes in the liquid samples with which they are in contact. The design could be extended to a multichannel sensor with further developments. The experimental results confirmed that one channel can be used as a reference sensor that could compensate for unexpected changes in bulk refraction or temperature and develop this sensor as a practicable high-sensitivity biosensing device.