Temperature-Dependent Refractive Index Determination from Critical Angle Measurements: Implications for Quantitative SPR Sensing

Temperature-dependent measurements of surface coverage and interfacial kinetics remain relatively unexploited in thin-film sensing applications that rely on optical surface-sensitive techniques such as surface plasmon resonance spectroscopy (SPR). These techniques are inherently sensitive to the optical properties of the bulk solution in contact with the thin film; therefore, quantitative thin-film sensing requires accurate refractive index data for bulk solutions at the conditions of interest. The refractive index for bulk solutions depends strongly on temperature, solution composition, and optical excitation wavelength. In this paper, we demonstrate the use of critical angle measurements for accurate, independent determination of the refractive index of bulk solutions and present results for different experimental conditions of solution temperature, solution concentration, and excitation wavelength. We also examine the implications of incorrect accounting of the bulk solution for the case of two-color SPR sensing of ultrathin organic films. This sensing technique, which depends inherently on the contrast in the dispersion of the refractive index of the film and the bulk solution, can be over 1 order of magnitude more sensitive than single-color SPR measurements. Critical angle measurements can be implemented in conjunction with SPR measurements and will be invaluable for thin film sensing application in which the bulk refractive index varies during the experiment, for example, in temperature-dependent SPR measurements, or for applications in which the solution refractive index is not known.     

采用虚拟仪器技术的表面等离子体共振传感器

针对表面等离子体共振(SPR)传感器对精度和数据处理能力的要求,利用虚拟仪器技术,自行设计了一套基于角度扫描的Kretschmann结构SPR测试系统。为了提高折射率的测量分辨力,系统采用了高精度步进电机控制的旋转平台。软件中使用巴特沃思低通滤波器消除出射光干涉噪声引起的高频干扰。同时,提出了一种双棱镜自适应结构对出射光路进行实时调整,实现角度扫描过程中光探测器固定不动。实验测得空气和蒸馏水样品的折射率分别为1.00293和1.33432,结果与理论值基本吻合,且具有良好的重复性和达到10-5RIU(RefractiveIndexUnit)的分辨力。     

Planar antiresonant reflecting optical waveguides as integrated optical refractometer

This paper reports on an integrated refractometer sensor, useful for measuring chemical quantities, based on antiresonant reflecting optical waveguides (ARROWs). We show that, by a suitable design, the attenuation in ARROW waveguides can strongly depend on the refractive index of the superstrate layer. We use this property to design and realize an integrated refractometer. The proposed sensor structure is unique in that it consists in the ARROW waveguide itself acting like a vertical interferometer. The device is fabricated using standard silicon technology fully compatible with bipolar and CMOS integrated circuit process. The measurement results show a sensing resolution of /spl Delta/n = 6e - 4 when used in a solution with a refractive index of 1.4600.     

Silicon-based surface plasmon resonance sensing with two surface plasmon polariton modes

Surface plasmon resonance (SPR) sensing on a silicon-based platform is considered. We have studied properties of SPR in a combined silicon-dielectric layer-gold film-sample medium structure and established conditions of the simultaneous excitation of two plasmon polariton modes that provide narrow and well-separated minima of the reflected intensity. It has been shown that the external mode over the gold-sample medium interface demonstrates a highly sensitive response to a change in the refractive index of the sample medium, whereas the internal mode over the dielectric-gold interface is almost insensitive to medium parameters. We propose that the internal mode can be used as an effective reference zero point for miniature and portable SPR-based systems designed for field and multichannel sensing.     

Side-polished multimode fiber biosensor based on surface plasmon resonance with halogen light

A side-polished multimode fiber sensor based on surface plasmon resonance (SPR) as the transducing element with a halogen light source is proposed. The SPR fiber sensor is side polished until half the core is closed and coated with a 37 nm gold thin film by dc sputtering. The SPR curve on the optical spectrum is described by an optical spectrum analyzer and can sense a range of widths in wavelengths of SPR effects. The measurement system using the halogen light source is constructed for several real-time detections that are carried out for the measurement of the index liquid detections for the sensitivity analysis. The sensing fiber is demonstrated with a series of refractive index (RI) liquids and set for several experiments, including the stability, repeatability, and resolution calibration. The results for the halogen light source with the resolution of the measurement based on wavelength interrogation were 3 x 10(-6) refractive index units (RIUs). The SPR dip shifted in wavelength is used as a measure of the RI change at a surface, and this RI change varies directly with the number of biomolecules at the surface. The SPR dip shift in wavelength, which was hybridized at 0.1 microM of the target DNA to the probe DNA, was 8.66 nm. The all-fiber multimode SPR sensor, which has the advantages of being low cost, being disposable, having high stability and linearity, being free of labeling, and having potential for real-time detection, permit the sensor and system to be used in biochemical sensing and environmental monitoring.     

System-on-Chip Circuit Architecture for Eliminating Interferents in Surface Plasmon Resonance Sensing Systems

This paper presents a system-on-chip circuit architecture that enables the extraction of concentration information directly from a surface plasmon resonance (SPR) probe, independent of ambient fluctuations in the reference medium, temperature, and background light. Compensation for these baseline (bulk) interferences is embedded into the baseline integration state of the photodetectors in the optical path, creating a ldquoflat linerdquo for the baseline [no analyte present/bulk refractive index (RI)] condition and the characteristic SPR dips for the measurement (analyte present) condition. A resolution of 2 times 10^-4 RI units is possible with this system, comparable to the 5 times 10^-4 RI unit resolution of conventional signal processing (software-based) approaches to processing the same data using a similar framework. This approach demonstrates experimentally the capability of the dip-based SPR probe in a portable footprint for detecting RI at resolution levels suitable for practical applications of these probes to field environments.     

Quantitative methods for spatially resolved adsorption/desorption measurements in real time by surface plasmon resonance microscopy

A simple method for converting local reflectivity changes measured in surface plasmon resonance (SPR) microscopy to effective adlayer thicknesses and absolute surface coverages of adsorbed species is presented. For a range of high-contrast angles near the SPR resonance where the local metal surface's reflectivity changes linearly with angle, the change in reflectivity at fixed angle is proportional to the change in effective refractive index (eta(eff)) near the surface. This change in eta(eff) can be converted to absolute adsorbate coverage using methods developed for quantitative SPR spectroscopy. A measurement of the change in reflectivity due to changes in refractive index of bulk solutions, i.e., percent reflectivity change per refractive index unit (RIU), is the only calibration required. Application of this method is demonstrated for protein adsorption onto protein/DNA arrays on gold from aqueous solution using an SPR microscope operating at 633 nm. A detection limit of 0.072% change in absolute reflectivity is found for simultaneous measurements of all 200 microm x 200 microm areas within the 24-mm(2) light beam with 1-s time averaging. This corresponds to a change in effective refractive index of 1.8 x 10(-5) and a detection limit for protein adsorption of 1.2 ng/cm(2) (approximately 0.5 pg in a 200-microm spot). The linear dynamic range is Deltaeta(eff) = approximately 0.011 RIU or approximately 720 ng/cm(2) of adsorbed protein. Using a nearby spot as a reference channel, one can correct for instrumental drift and changes in refractive index of the solutions in the flow cell.     

On-chip surface-based detection with nanohole arrays

A microfluidic device with integrated surface plasmon resonance (SPR) chemical and biological sensors based on arrays of nanoholes in gold films is demonstrated. Widespread use of SPR for surface analysis in laboratories has not translated to microfluidic analytical chip platforms, in part due to challenges associated with scaling down the optics and the surface area required for common reflection mode operation. The resonant enhancement of light transmission through subwavelength apertures in a metallic film suggests the use of nanohole arrays as miniaturized SPR-based sensing elements. The device presented here takes advantage of the unique properties of nanohole arrays: surface-based sensitivity; transmission mode operation; a relatively small footprint; and repeatability. Proof-of-concept measurements performed on-chip indicated a response to small changes in refractive index at the array surfaces. A sensitivity of 333 nm per refractive index unit was demonstrated with the integrated device. The device was also applied to detect spatial microfluidic concentration gradients and to monitor a biochemical affinity process involving the biotin-streptavidin system. Results indicate the efficacy of nanohole arrays as surface plasmon-based sensing elements in a microfluidic platform, adding unique surface-sensitive diagnostic capabilities to the existing suite of microfluidic-based analytical tools.     

Sensitivity and detection limit of concentration and adsorption measurements by laser-induced surface-plasmon resonance

The shot noise limitation as well as other factors that influence the sensitivity of measurements with a surface plasmon resonance (SPR) sensor are considered. It is demonstrated that minute changes in the refractive index of a medium close to the surface of a metal film can be detected owing to a shift in the resonance angle. In particular, changes in the adsorption layer of only a fraction of a biomolecular monolayer could be measured. Data for SPR are presented with adjacent media of air, water, as well as aqueous solutions of ethanol and sodium chloride at different concentrations. The immobilization of the protein bovine serum albumin to a specially prepared surface was monitored with the SPR technique. Specific responses to changes in the concentration and thickness of the adsorption layer were determined. The angular resolution of the present apparatus is approximately 1 millidegree, corresponding to a detection limit for an adsorbed protein layer of 15 pg/mm(2), which is still 2 to 3 orders of magnitude larger than the shot-noise limit, and therefore a further improvement in sensitivity is possible.     

Surface plasmon resonance spectroscopic study of UV-addressable phenylalanine sensing based on a self-assembled spirooxazine derivative monolayer

Light-addressable compounds are very interesting due to the possibilities of their practical use such as optical switches and memories or variable transmission materials. For example, transportation of phenylalanine across liposomal bilayers mediated by a photoresponsive carrier like spirooxazine through electrostatic interaction between phenylalanine and spirooxazine derivative. Thus, the spirooxazine is expected to form a UV-addressable phenylalanine sensing interface.In this study, we prepared phenylalanine sensing interface of a spirooxazine derivative by self-assembly technique and evaluated interaction between a spirooxazine moiety and phenylalanine with a surface plasmon resonance (SPR). The refractive index change of monolayer caused by interaction between a spirooxazine derivative and phenylalanine led to the SPR angle shifts upon UV irradiation. The SPR angle shift increased with increasing the concentration of phenylalanine solution. These results indicated that the spirooxazine derivative self-assembled monolayer (SAM) has an application potential for UV-addressable phenylalanine sensing.     

Bloch surface wave structures for high sensitivity detection and compact waveguiding

Resonant propagating waves created on the surface of a dielectric multilayer stack, called Bloch surface waves (BSW), can be designed for high sensitivity monitoring of the adjacent refractive index as an alternative platform to the metal-based surface plasmon resonance (SPR) sensing. The resonant wavelength and polarization can be designed by engineering of the dielectric layers unlike the fixed resonance of SPR, while the wide bandwidth low loss of dielectrics permits sharper resonances, longer propagation lengths and thus their use in waveguiding devices. The transparency of the dielectrics allows the excitation and monitoring of surface-bound fluorescent molecules. We review the recent developments in this technology. We show the advantages that can be obtained by using high index contrast layered structures. Operating at 1550 nm wavelengths will allow the BSW sensors to be implemented in the silicon photonics platform where active waveguiding can be used in the realization of compact planar integrated circuits for multi-parameter sensing.     

Plasmonic Sensing of Biological Analytes Through Nanoholes

A transmission-based surface plasmon resonance (SPR) sensor for label-free detection of protein–carbohydrate and protein–protein binding proximate to a perforated gold surface is demonstrated. An SPR instrument makes real-time measurements of the resonant wavelength and/or the resonant angle of incidence of transmitted light; both are influenced by the presence of proteins at the gold surface-liquid interface. Ethylene glycol solutions with known refractive indexes were used to calibrate the instrument. A paired polarization-sensitive detector achieved an overall detection resolution of $sim {hbox{6.6}}times {hbox{10}}^{-5}$ refractive index units (RIU). Proof of principle experiments was performed with concanavalin A (Con A) binding to gold-adsorbed ovomucoid and anti-bovine serum albumin (BSA) binding to gold-adsorbed BSA.      

Simulation on wavelength-dependent complex refractive index of liquids obtained by phase retrieval from reflectance dip due to surface plasmon resonance

A method for the calculation of the wavelength-dependent complex refractive index of absorbing liquid from reflectance in the vicinity of surface plasmon resonance (SPR) is presented. The calculation is based on the maximum entropy method (MEM). As an example, phase retrieval from a simulated SPR reflectance of a red colored liquid solution is carried out. It is proposed that MEM can be applied to wavelength-dependent complex refractive index assessment from reflectance of absorbing liquids in SPR measurement in wavelength scanning mode.     

Nanohole-based surface plasmon resonance instruments with improved spectral resolution quantify a broad range of antibody-ligand binding kinetics

We demonstrate an affordable low-noise surface plasmon resonance (SPR) instrument based on extraordinary optical transmission (EOT) in metallic nanohole arrays and quantify a broad range of antibody-ligand binding kinetics with equilibrium dissociation constants ranging from 200 pM to 40 nM. This nanohole-based SPR instrument is straightforward to construct, align, and operate, since it is built around a standard microscope and a portable fiber-optic spectrometer. The measured refractive index resolution of this platform is 3.1 × 10(-6) without on-chip cooling, which is among the lowest reported for SPR sensors based on EOT. This is accomplished via rapid full-spectrum acquisition in 10 ms followed by frame averaging of the EOT spectra, which is made possible by the production of template-stripped gold nanohole arrays with homogeneous optical properties over centimeter-sized areas. Sequential SPR measurements are performed using a 12-channel microfluidic flow cell after optimizing surface modification protocols and antibody injection conditions to minimize mass-transport artifacts. The immobilization of a model ligand, the protective antigen of anthrax on the gold surface, is monitored in real-time with a signal-to-noise ratio of ~860. Subsequently, real-time binding kinetic curves were measured quantitatively between the antigen and a panel of small, 25 kDa single-chain antibodies at concentrations down to 1 nM. These results indicate that nanohole-based SPR instruments have potential for quantitative antibody screening and as a general-purpose platform for integrating SPR sensors with other bioanalytical tools.     

Parallel scan spectral surface plasmon resonance imaging

We describe a parallel scan spectral surface plasmon resonance (SPR) imaging technique. We demonstrate experimentally, with a line-shaped light illumination, that an image acquired with an area CCD detector provides both SPR wavelength information and one-dimensional spatial distribution. Thus two-dimensional distribution of the refractive index of the entire sensing plane can be obtained with a one-dimensional optical line parallel scan. The technique offers advantages of both high sensitivity and high throughput, and could have potential applications in biochips analysis.     

Surface plasmon resonance sensor based on polarization interferometry and angle modulation

A surface plasmon resonance (SPR) sensing technique based on polarization interferometry and angle modulation is presented. Its sensitivity is not a direct function of variation of reflection intensity, nor of phase shift. Rather, it is a function of the complex reflection coefficient. A three times standard deviation detection limit of 5.1 x 10(-7) refractive index units in a 2 Hz bandwidth is obtained with our experimental setup. A theoretical analysis shows that this technique can provide a wide linear measurement range. Moreover, the sensitivity is insensitive to the thickness of gold films over approximately 5 nm. This SPR sensing technique is suitable for physical, chemical, and biological research.     

Determination of the refractive index and the chiral parameter of a chiral solution based on chiral reflection equations and heterodyne interferometry

This study develops a method for determining the chiral parameter and the refractive index of an isotropic chiral medium using chiral reflection equations and critical angle phenomena. Linearly polarized light propagates back and forth in a parallelogram prism between two parallel compartments with chiral solutions. A beam splitter then divides the light that emerges from the prism into a reflected light beam and a transmitted light beam. The two beams pass through a compensator and an analyzer, respectively, to cause phase compensation and interference of s and p polarizations. The phase difference between the two interference signals are initially optimized by a suitable optical arrangement and subsequently measured by heterodyne interferometry. Additionally, the refractive index of the solution is determined from the critical angle that occurred at the discontinuity of the phase difference between the two interference signals. These results are substituted into derived equations to calculate the chiral parameter. The approach has the merits of both common-path interferometry and heterodyne interferometry.     

Superimposed noninterfering probes to extend the capabilities of phase Doppler anemometry

We propose using multiple superimposed noninterfering probes (SNIPs) of the same wavelength but different beam angles to extend the capabilities of phase Doppler anemometry. When a particle is moving in a SNIP the Doppler signals that are produced exhibit multiple Doppler frequencies and phase shifts. The resolution of the measurements of particle size (i.e., by fringe spacing and Doppler frequency) increases with beam angle. Then, with the solution proposed, even with only two detectors several measurements of size can be obtained for the same particle with increasing resolution if we consider higher frequencies in the signal. Several optical solutions to produce SNIPs as well as a signal-processing algorithm to treat the multiple-frequency Doppler signals are proposed. Experimental validations of the sizing of spherical and cylindrical particles demonstrate the applicability of this technique for particle measurement. We believe that this new technique can be of great interest when high resolution of size, velocity, and even refractive index is required.     

Chemical sensors for portable, handheld field instruments

A review of three commonly used classes of chemical sensor technologies as applicable to implementation in portable, handheld field instruments is presented. Solid-state gas and chemical sensors have long been heralded as the solution to a wide variety of portable chemical sensing system applications. However, advances in optical sensing technology have reduced the size of supporting infrastructure to be competitive with their solid-state counterparts. Optical, solid-state, and hybrid arrays of sensors have application for portable instruments, but issues of insufficient selectivity and sensitivity continue to hamper the widespread introduction of these miniaturized sensors for solving chemical sensing problems in environments outside the laboratory. In this article, we evaluate three of the major classes of compact chemical sensors for portable applications: (solid-state) chemiresistors, (solid-state) CHEMFETs, and (optical) surface plasmon resonance sensors (SPR). These sensors are evaluated and reviewed, according to the current state of research, in terms of their ability to operate at low-power, small-size, and relatively low-cost in environments, with numerous interferents and variable ambient conditions     

Postcolumn renewal of sensor surfaces for high-performance liquid chromatography-surface plasmon resonance detection

The combination of high-performance liquid chromatography (HPLC) with surface plasmon resonance (SPR) for continuous separation and label-free detection of protein samples is described. The detection was realized by electrostatic adsorption of proteins bearing positive and negative charges onto chemically modified SPR sensors in two separate SPR channels. One SPR channel is coated with carboxymethylated dextran which facilitates the detection of positively charged proteins, whereas the other, devoted to the monitoring of negatively charged proteins, is covered with ethylenediamine molecules attached onto a dextran surface. Renewal of the sensor surface in the channels can be accomplished by introducing regeneration solutions through two six-port valves. The coupled technique (HPLC-SPR) was assessed for its analytical figures of merit and applied to the quantification of lysozyme in human milk samples. Unlike the SPR detection of bulk solution refractive index changes during chromatographic peak elutions, the highest sensitivity of SPR is retained in this work since the measurement is performed at the SPR sensor surface where the evanescent field is the strongest. The renewable SPR detection of continuous separations is reproducible and versatile and does not require the separated proteins to contain chromophores or to be prelabeled with a tag (e.g., a redox-active or fluorescent molecule). Such generality makes SPR complementary to other types of chromatographic detectors.