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PHOTONIC SENSING A cutting-edge look at safety and security applications of photonic sensors With its many superior qualities, photonic sensing technology is increasingly used in early-detection and early-warning systems for biological hazards, structural flaws, and security threats. Photonic Sensing provides for the first time a comprehensive review of this exciting and rapidly evolving field, focusing on the development of cutting-edge applications in diverse areas of safety and security, from biodetection to biometrics. The book brings together contributions from leading experts in the field, fostering effective solutions for the development of specialized materials, novel optical devices, and networking algorithms and platforms. A number of specific areas of safety and security monitoring are covered, including background information, operation principles, analytical techniques, and applications. Topics include: * Document security and structural integrity monitoring, as well as the detection of food pathogens and bacteria * Surface plasmon sensors, micro-based cytometry, optofluidic techniques, and optical coherence tomography * Optic fiber sensors for explosive detection and photonic liquid crystal fiber sensors for security monitoring * Photonics-assisted frequency measurement with promising electronic warfare applications An invaluable, multidisciplinary resource for researchers and professionals in photonic sensing, as well as safety and security monitoring, this book will help readers jump-start their own research and development in areas of physics, chemistry, biology, medicine, mechanics, electronics, and defense.

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Table of Contents

Copyright

Half Title

Title Page

Preface

Contributors

Chapter 1: Surface Plasmons for Biodetection

1.1 Introduction

1.2 Principles of SPR Biosensors

1.3 Optical Platforms for SPR Sensors

1.4 Functionalization Methods for SPR Biosensors

1.5 Applications of SPR Biosensors

1.6 Summary

References

Chapter 2: Microchip-Based Flow Cytometry in Photonic Sensing: Principles and Applications for Safety and Security Monitoring

2.1 Introduction

2.2 Microchip-Based Flow Cytometry

2.3 Microchip-Based Flow Cytometry with Integrated Optics

2.4 Applications

2.5 Conclusion

References

Chapter 3: Optofluidic Techniques for the Manipulation of Micro Particles: Principles and Applications to Bioanalyses

3.1 Introduction

3.2 Optofluidic Techniques for the Manipulation of Particles

3.3 Enhancing Optical Manipulation with a Monolithically Integrated on-Chip Structure

3.4 Applications

3.5 Conclusion

Acknowledgments

References

Chapter 4: Optical Fiber Sensors and Their Applications for Explosive Detection

4.1 Introduction

4.2 A Brief Review of Existing Fiber-Optic-Based Explosive Detectors

4.3 High Performance Fiber-Optic Explosive Detector Based on the AFP Thin Film

4.4 Generating High Quality Polymer Film—Pretreatment with Adhesion Promoter

4.5 Effect of Photodegradation on AFP Polymer

4.6 Optimizing Polymer Concentration for Optimized AFP-Film Thickness

4.7 Explosive Vapor Preconcentration and Delivery

4.8 Future Directions and Conclusions

References

Chapter 5: Photonic Liquid Crystal Fiber Sensors for Safety and Security Monitoring

5.1 Introduction

5.2 Materials and Experimental Setups

5.3 Principle of Operation

5.4 Tuning Possibility

5.5 Photonic Devices

5.6 Photonic Liquid Crystal Fiber Sensors for Sensing and Security

5.7 Conclusion

Acknowledgments

Chapter 6: Miniaturized Fiber Bragg Grating Sensor Systems for Potential Air Vehicle Structural Health Monitoring Applications

6.1 Introduction

6.2 Spectrum Fixed AWG-Based FBG Sensor System

6.3 Spectrum Tuning AWG-/EDG-Based FBG Sensor Systems

6.4 Dual Function EDG-Based Interrogation Unit

6.5 Conclusion

Acknowledgments

References

Chapter 7: Optical Coherence Tomography for Document Security and Biometrics

7.1 Introduction

7.2 Principle of OCT

7.3 OCT Systems: Hardware and Software

7.4 Sensing Through Volume: Applications

7.5 Summary and Conclusion

References

Chapter 8: Photonics-Assisted Instantaneous Frequency Measurement

8.1 Introduction

8.2 Frequency Measurement Using an Optical Channelizer

8.3 Frequency Measurement Based on Power Monitoring

8.4 Other Methods for Frequency Measurement

8.5 Challenges and Future Prospects

8.6 Conclusion

References

Index

Bseries

Copyright © 2012 by John Wiley & Sons, Inc. All rights reserved.

Published by John Wiley & Sons, Inc., Hoboken, New Jersey.

Published simultaneously in Canada.

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Library of Congress Cataloging-in-Publication Data:

Xiao, Gaozhi.

Photonic sensing : principles and applications for safety and security monitoring / Gaozhi Xiao, Wojtek J. Bock.

p. cm.

Includes bibliographical references and index.

ISBN 978-0-470-62695-5 (hardback)

1. Optical fiber detectors. 2. Optical fiber detectors–Safety measures. 3. Optical fiber detectors–Security measures. I. Bock, Wojtek J. II. Title.

TA1815.X53 2012

681′.25–dc23

2011044215

Preface

Twenty-first century society places high priority on health, environment, and security; the threats of terrorism, climate change, and pollution are of increasing concern for both governments and citizens. While many of these threats can never be completely eliminated, their impact can be significantly mitigated by the presence of effective early-detection and early-warning systems. To provide such protection requires flexible, cost-effective sensing, and monitoring systems in areas such as structural integrity, environmental health, human security and health, and industrial process control. Photonics (the use of light) has the potential to provide highly effective solutions tailored to meet a broad range of specific sensing requirements, particularly, as it can leverage many of the technology platforms that were successfully developed for the communications industry. However, optimal sensing solutions require the development of specialized materials, novel optical devices, and new networking algorithms and platforms. As a sensor technology, photonics offers low power requirements, high sensitivity and selectivity, and immunity from electromagnetic interference. A single optical fiber can be used both to detect disturbances at multiple locations and to transit the information to a central point for data processing. Over the last two decades, we have seen the rapid development of photonic sensing technologies and their application in fields including food bacteria detection, oil/gas pipe structure health monitoring, bio chips, explosives detection, defense platform health monitoring, etc.

This book comprises a series of chapters contributed by leading experts in the field of photonic sensing, with target applications to safety and security. The objective is to provide a most comprehensive, though by no means complete, review of this exciting field. This book aims for multidisciplinary readership. The editors intend that the book serve as an invaluable reference that aids research and development of those areas that concern safety and security. Another aim of the book is to stimulate the interest of researchers from physics, chemistry, biology, medicine, mechanics, electronics, defense and others, and foster collaboration through multidisciplinary programs.

Each chapter of the book deals with a specific area of safety and security monitoring using the photonic technique. It provides discussions on background, operation principles, and applications. Chapter 1 is on surface plasmons and their applications to biodetection, in particular to food pathogen detection. Chapter 2 is on microchip-based flow cytometry and its application in bacteria detection and analysis. Chapter 3 is on optofluidic techniques and their application in bioanalysis. Chapter 4 is on optical fiber sensors and their application in explosives detection. Chapter 5 is on photonic liquid crystal fiber sensors and their application in safety and security monitoring. Chapter 6 is on optic fiber sensor systems targeting air vehicle structural health monitoring applications. Chapter 7 is on optical coherence tomography and its application in document security and biometrics. Chapter 8 is on photonics-assisted instantaneous frequency measurement and its potential for electronic warfare applications.

We are grateful to all the authors for their contributions. Without their assistance and cooperation, this book would not have been possible. We also like to thank Ms. Aleksandra Czapla for the cover design, Ms. Kari Capone and Ms. Lucy Hitz of Wiley for their continual support during the course of this book.

Gaozhi Xiao and Wojtek Bock

Contributors

Pavel Adam, Institute of Photonics and Electronics, Academy of Sciences of the Czech Republic, Prague, Czech Republic
Wojtek J. Bock, Centre de recherche en photonique, Département d'informatique et d'ingénierie, Université du Québec en Outaouais, Gatineau, Québec, Canada
Shoude Chang, Institute for Microstructural Sciences, National Research Council Canada, Ottawa, ON, Canada
Costel Flueraru, Institute for Microstructural Sciences, National Research Council Canada, Ottawa, ON, Canada
Honglei Guo, Microwave Photonics Research Laboratory, School of Information Technology and Engineering, University of Ottawa, Ottawa, ON, Canada
Jií Homola, Institute of Photonics and Electronics, Academy of Sciences of the Czech Republic, Prague, Czech Republic
Jianjun Ma, Centre de recherche en photonique, Département d'informatique et d'ingénierie, Université du Québec en Outaouais, Gatineau, Québec, Canada
Youxin Mao, Institute for Microstructural Sciences, National Research Council Canada, Ottawa, ON, Canada
Nezih Mrad, Air Vehicles Research Section, Defense R&D Canada, Department of National Defense, National Defense Headquarters, Ottawa, ON, Canada
Shilong Pan, Microwave Photonics Research Laboratory, School of Information Technology and Engineering, University of Ottawa, Ottawa, ON, Canada
Marek Piliarik, Institute of Photonics and Electronics, Academy of Sciences of the Czech Republic, Prague, Czech Republic
Hana Šípová, Institute of Photonics and Electronics, Academy of Sciences of the Czech Republic, Prague, Czech Republic
Tomáš Špringer, Institute of Photonics and Electronics, Academy of Sciences of the Czech Republic, Prague, Czech Republic
Milan Vala, Institute of Photonics and Electronics, Academy of Sciences of the Czech Republic, Prague, Czech Republic
Benjamin R. Watts, Department of Engineering Physics, McMaster University, Hamilton, ON, Canada
Tomasz Wolinski, Faculty of Physics, Warsaw University of Technology, Warszawa, Poland
Gaozhi Xiao, Institute for Microstructural Sciences, National Research Council Canada, Ottawa, ON, Canada
Chang-Qing Xu, Department of Engineering Physics, McMaster University, Hamilton, ON, Canada
Jianping Yao, Microwave Photonics Research Laboratory, School of Information Technology and Engineering, University of Ottawa, Ottawa, ON, Canada
Zhiyi Zhang, Institute for Microstructural Sciences, National Research Council of Canada, Ottawa, ON, Canada

Chapter 1

Surface Plasmons for Biodetection

Pavel Adam, Marek Piliarik, Hana Šípová, Tomáš Špringer, Milan Vala and Jií Homola

Institute of Photonics and Electronics, Academy of Sciences of the Czech Republic, Prague, Czech Republic

1.1 Introduction

The diffusion of inorganic and biological worlds represents an important paradigm of modern science and technology [1]. Biophotonics stands as an emerging field of research at the crossroads of physical, chemical, and life sciences. The integration of photonics, biology, and nanotechnology is leading to a new generation of devices that makes it possible to characterize chemical and other molecular properties and to discover novel phenomena and biological processes occurring at the molecular level. Biophotonics is widely regarded as the key science on which the next generation of clinical tools and biomedical research instruments will be based.

The last two decades have witnessed an increasing effort devoted to the research and development of optical biosensors and biochips worldwide. Recent scientific and technological advances have demonstrated that such devices hold tremendous potential for applications in areas such as genomics, proteomics, medical diagnostics, environmental monitoring, food analysis, agriculture, and security [2–4]. Label-free optical biosensors present a unique technology that enables the direct observation of molecular interaction in real-time and allows for the study of molecular systems, which cannot be labeled and studied by fluorescence spectroscopy [2]. Optical label-free biosensors measure binding-induced refractive index changes and are typically based on interferometric transducers, such as the integrated optical Mach–Zehnder interferometer [5], the integrated Young interferometer [6], and the white light interferometer [7], and transducers based on spectroscopy of guided modes of dielectric waveguides, such as the resonant mirror sensor [8] and the grating coupler sensor [9], or metal-dielectric waveguides, such as the surface plasmon resonance (SPR) sensor.

Since the first demonstration of the SPR method for the study of processes at the surfaces of metals [10] and sensing [11] in the early 1980s, SPR sensors have received a great deal of attention and allowed for great advances both in terms of technology and applications [12]. Thousands of research papers on SPR biosensors have been published and SPR biosensors have been extensively featured in books [1, 2, 4, 13] and reviews [3, 12, 14–18]. SPR biosensors have become a crucial tool for characterizing and quantifying biomolecular interactions. SPR biosensors have also been increasingly developed for the detection of chemical and biological species and numerous SPR biosensors for the detection of analytes related to medical diagnostics, environmental monitoring, food safety, and security have been reported as well.

This chapter describes the principles of SPR biosensors and discusses the advances that SPR biosensors have made both in terms of technology and applications over the last decade. The first part (Section 1.2) describes the fundamentals of SPR biosensors. Sections 1.3 and 1.4 are concerned with the optical configurations and immobilization methods used in current SPR sensors. The last part (Section 1.5) presents examples of applications of SPR biosensors for the detection of chemical and biological species with an emphasis on food safety and security applications.

1.2 Principles of SPR Biosensors

1.2.1 Surface Plasmons

Propagation constant of SP βSP at the metal–dielectric interface can be expressed as

1.1

where c is the speed of light in a vacuum, ω is the angular frequency, and nef is the effective index of the SP [20, 21]. If the structure is lossless , Equation 1.1 represents a guided mode only if the metal permittivity is negative and . Metals such as gold, silver, and aluminum exhibit a negative real part of permittivity in the visible and near-infrared region of the spectrum. Figure 1.1b depicts the wavelength dependence of the effective index of SP nef for the gold waveguide. The imaginary part of the propagation constant is associated with the imaginary part of the metal permittivity and determines attenuation of the SP in the direction of propagation [20].

A special example of the metallic waveguide is a symmetric dielectric–metal– dielectric planar structure. When the metal film thickness is much larger than the SP penetration depth into the metal, an independent SP may propagate at each metal–dielectric boundary. If the thickness of the metal film is decreased, coupling between the SPs at opposite sides of the metal film can occur, giving rise to mixed modes of electromagnetic field—symmetric and antisymmetric SPs [22, 23]. The profiles of magnetic intensity of symmetric and antisymmetric SPs are symmetric or antisymmetric with respect to the plane of symmetry of the structure. The field of the symmetric SP penetrates much deeper into the dielectric medium than the field of the antisymmetric SP or the field of a conventional SP at a single metal–dielectric interface. Moreover, the symmetric SP exhibits a lower attenuation than its antisymmetric counterpart and therefore it is referred to as a long-range surface plasmon (LRSP) while the antisymmetric mode is referred to as a short-range surface plasmon [22].

1.2.2 Excitation of Surface Plasmons

1.2.2.1 Prism Coupling

The most common approach to the excitation of SPs is by means of a prism coupler and the attenuated total reflection method (ATR). In the Kretschmann geometry of the ATR method [24], a high refractive index prism with refractive index np is interfaced with a metal–dielectric waveguide consisting of a metal film with permittivity ε m and a semi-infinite dielectric with a refractive index nd (nd < np), Figure 1.2.

Figure 1.2 Excitation of surface plasmons in the Kretschmann geometry of the attenuated total reflection (ATR) method.

When a light wave propagating in the prism totally reflects on the prism base, an evanescent electromagnetic wave decays exponentially in the direction perpendicular to the prism–metal interface [25]. If the metal film is sufficiently thin (less than 100 nm for light in the visible and near-infrared part of spectrum), the evanescent wave penetrates through the metal film and couples with an SP at the outer boundary of the metal film. In terms of the effective index, this coupling condition can be written as follows:

1.2

where nef is the effective index of the SP, and the perturbation in effective index , and the respective propagation constant of SP describe the effect of the presence of the prism.

Figure 1.3 shows the angular and wavelength spectra calculated using a rigorous Fresnel model of light reflection on a multilayer structure calculated at two different wavelengths and for two angles of incidence, respectively. The reflectivity spectra exhibit distinct dips in TM polarization, which are associated with the transfer of energy from the incident light wave into an SP and its subsequent dissipation in the metal film.

Figure 1.3 TM reflectivity as a function of the angle of incidence (a) and the wavelength (b) calculated for two different angles of incidence using the rigorous Fresnel reflection theory. Configuration: BK7 glass, gold film (thickness—48 nm for the wavelength of 650 nm and 50 nm for the wavelength of 850 nm), water.

The reflectivity spectra can be rigorously calculated using Maxwell equations and the boundary condition of the planar multilayer structure. Assuming that the permittivity of metal ε m obeys and , a Lorentzian (with respect to nef) approximation of the reflectivity can be used as follows [20]:

1.3

1.2.2.2 Grating Coupling

Another approach to optical excitation of SPs is based on the diffraction of light on a diffraction grating. In this method, a light wave is incident at an angle of incidence θ from a dielectric medium with the refractive index nd on a metal grating with the dielectric constant ε m, the grating period Λ, and the grating depth q (Fig. 1.4). The diffracted wave in m—the diffraction order can couple with SPs when their propagation constants are closely phase-matched. In terms of the effective index, the coupling condition can be written as

1.4

where accounts for the presence of the grating.

Figure 1.4 Excitation of surface plasmons by the diffraction of light on a diffraction grating.

The grating-moderated interaction between a light wave and an SP can be modeled by solving Maxwell's equations in differential form with a grating profile approximated by a stack of layers [27, 28], or in an integral form by solving the Helmholtz–Kirchhoff integral [29].

Figure 1.5 Reflectivity as a function of the angle of incidence (a) and the wavelength (b) calculated for two wavelengths and angles of incidence, respectively (denoted in the label). Configuration: gold–water interface; grating period 672 nm, grating depth 30 nm, angle of incidence taken in the air.

1.2.2.3 Waveguide Coupling

SP can also be excited by modes of dielectric waveguides, such as planar or channel-integrated optical waveguides and optical fibers. Typically, coupling between a dielectric waveguide mode and an SP propagating along a metal layer in the proximity of the dielectric waveguide is achieved by coupling the evanescent tails of the two waves. The evanescent wave of the dielectric waveguide mode can couple with SP when the propagation constant of the mode βM is equal to the real part of the propagation constant of the SP βSP:

1.5

As the coupling condition is fulfilled for only a narrow range of wavelengths, the excitation of SPs can be observed as a narrow dip in the spectrum of light transmitted through the waveguide structure.

1.2.3 Sensors Based on Surface Plasmons

A change in the refractive index of the dielectric medium produces a change in the propagation constant of SP at the interface of the metal and the dielectric. Thischange in propagation constant alters the coupling condition between the light wave and the SP, which can be observed as a change in the characteristics of the optical wave interacting with SP. The change in SP propagation is associated with the change in resonant coupling conditions, for example the resonant wavelength, the angle of incidence, or the strength of the SP coupling. Figure 1.6 illustrates the shift in the angular of wavelength SPR spectra because of the change in the refractive index of the dielectric medium nd. Depending on which characteristics of the reflected light wave are measured in the SPR sensor, SPR sensors are classified as (i) SPR sensors with wavelength modulation (the angle of incidence is fixed and the coupling wavelength serves as a sensor output); (ii) SPR sensors with angular modulation (the coupling wavelength is fixed and the coupling angle of incidence serves as a sensor output); (iii) SPR sensors with intensity modulation (both the angle of incidence and the wavelength of incident light are fixed at nearly resonant values and the light intensity serves as a sensor output); and (iv) SPR sensors with phase modulation (both the angle of incidence and the wavelength of incident light are fixed at nearly resonant values and the phase of the reflected light serves as a sensor output).

Figure 1.6 Change in the SPR spectra associated with the change in the refractive index of the dielectric media. Parameters , , and denote the shift in the resonant wavelength, the resonant angle of incidence, and the change in light intensity.

A change in the refractive index Δnd of the dielectric film with thickness h, produces a change in the effective index of the SP Δnef. If the thickness of the layer is much higher that the penetration depth Lpd of the SP field, the change in the effective refractive index of the SP can be calculated by differentiating the dispersion relation (1.1), which for the conventional SP yields [19]:

1.6

A change in the effective index of an SP owing to refractive index changes within a thin layer hLpd can be estimated using the perturbation theory [19] as

1.7

1.2.4 SPR Affinity Biosensors

SPR biosensors employ special biomolecules—referred to as biorecognition elements—that can recognize and capture target analytes. Such biorecognition elements are immobilized in the form of a sensitive layer on the surface of the SPR metallic waveguide. When a solution containing analyte molecules is brought into contact with the SPR sensor, analyte molecules in solution bind to the molecular recognition elements, producing an increase in the refractive index of the sensitive layer (Fig. 1.7).

Figure 1.7 Principle of SPR affinity biosensing.

The change in refractive index Δnd occurring within a layer of thickness h can be expressed as

1.8

1.9

where K is a constant.

1.2.5 Performance Characteristics of SPR Biosensors

The performance of SPR biosensors is usually characterized in terms of the sensitivity, resolution, limit of detection (LOD), linearity, accuracy, reproducibility, and dynamic range [19, 26].

The sensitivity of an SPR sensor is the ratio of the change in sensor output to the change in the quantity to be measured (e.g., the refractive index nd). The sensitivity of an SPR sensor to a refractive index S can be written as

1.10

where Y denotes the sensor output and depending on the modulation approach usually represents the resonant angle of incidence, or the resonant wavelength, or the reflectivity. Equation 1.10 describes the decomposition of the sensor sensitivity in two parts: (i) the sensitivity of the sensor output to the change in the effective index of an SP and (ii) the sensitivity of the effective index of an SP to the change in the refractive index [19, 26]. Therefore, the second term (ii) is independent of the modulation method and the method of excitation, and the first term (i) represents the instrumental factor which is independent of the measurand.

Analogously, the sensitivity of an SPR biosensor to a concentration of analyte c derives from the change in the refractive index of the sensitive layer nd caused by the analyte binding:

1.11

As with Equation 1.10, the first term is the instrumental factor and the second term characterizes the properties of SP mode. The third term in Equation 1.11 is derived from the relationship between the analyte concentration and the refractive index change described in Equation 1.8, the binding capabilities of biorecognition elements, and analyte transport to the sensor surface.

The instrumental factor ΔY/Δnef has been analyzed in detail for different combinations of the SPR couplers and modulation approaches in recent publications [26]. Clearly, the instrumental factor depends on which method of excitation of the SPs and modulation approach are used. For the most common sensors based on SPR spectroscopy with a prism coupler, the instrumental factor can be calculated by differentiating coupling conditions (1.2) as follows:

1.12

1.13

where λr and θr denote the resonant wavelength and angle of incidence respectively. Instrumental factors are thus determined by the geometry and material constants of the SPR coupler and dispersion of the SP mode. In similar manner, the instrumental factor ΔR/Δnef can be calculated for SPR sensors based on intensity modulation using the Lorentzian approximation Equation 1.3 as

1.14

Unlike instrumental factors calculated for SPR spectroscopy (Eqs. 1.12 and 1.13), Equation 1.14 suggests a significant dependence of the sensitivity on the strength of SPR coupling represented by the radiation coefficient γrad. This behavior is associated with the effect of γrad term on the shape of the SPR dip as discussed in Section 1.2.2.

The resolution of an SPR sensor is defined as the smallest change in the refractive index that produces a detectable change in the sensor output. The magnitude of the change in sensor output that can be detected depends on the level of uncertainty of the sensor output—the output noise. Resolution of an SPR sensor σn, is typically expressed in terms of the standard deviation of noise of the sensor output σY translated to the refractive index of the bulk medium:

1.15

The noise in the sensor output originates from the noise of individual light intensities involved in the calculation of the sensor output. The propagation of noise to the sensor output was investigated by Piliarik and Homola [26]. Their study revealed that, independent of the SPR coupling principle, the refractive index resolution of an SPR sensor can be expressed as follows:

1.16

As follows from the analysis presented above, the resolution of the SPR sensor depends on the noise of the used optoelectronic components, the strength of the coupling between the light wave and the SP, and material parameters of the metallic waveguide [26]. In contrast, although the sensitivity of SPR sensors depends strongly on the coupling principle and modulation, a comparable resolution can be achieved regardless of the SPR coupling principle and modulation.

The LOD of an SPR biosensor represents the ability of a biosensor to detect an analyte. LOD is defined as the concentration of analyte derived from the smallest measure of the sensor output Y, which can be distinguished from the sensor output corresponding to a blank sample. The value of the sensor output corresponding to the LOD, YLOD, can be expressed as

1.17

1.3 Optical Platforms for SPR Sensors

Since the first demonstration of SPR sensors in the early 1990s, optical platforms of SPR sensors have made substantial advances in terms of both performance [32–45] and new capabilities. SPR instruments have become compact enough to be used for routine bioanalytical tasks in the field [46–52] and have expanded to enable parallelized detection of hundreds of different analytes at a time [35, 53–56].

In this section, we present a brief overview of the advances in SPR optical platforms, in particular within the last decade. The section is organized into four subsections, based on the method of coupling of light to SPs (prism, grating, and waveguide). The last subsection presents examples of the available commercial SPR systems.

1.3.1 Prism-Based SPR Sensors

The use of prism couplers to couple light to SPs is straightforward, versatile, and does not require complex optical instrumentation. Therefore, SPR sensors based on the attenuated total reflection method and prism couplers have been the most widely used. All major types of modulation have been implemented in prism-based SPR sensors. In SPR sensors based on spectroscopy of SPs, the angular or wavelength spectrum of the optical wave coupled with the SP is measured. Alternatively, changes in the intensity or phase of the reflected wave can be measured at a fixed wavelength and an angle of incidence. While the spectroscopic SPR sensors usually offer higher resolution, they provide a rather limited number of sensing channels. By contrast, intensity or phase modulations can be adopted by SPR imaging configurations, where independent measurements are performed in as many as hundreds of sensing channels simultaneously.

1.3.1.1 Spectroscopic Prism-Based SPR Sensors

The use of angular modulation in SPR sensors has a long history. In 1991, Sjolander et al. reported an angular modulation-based SPR sensor utilizing a light-emitting diode (LED), a glass prism with a gold layer, and a detector array with imaging optics to detect the angular spectrum of light reflected from the gold layer (Fig. 1.8) [32]. A divergent beam emitted by the LED was collimated in the plane parallel to the gold layer and focused by a cylindrical lens in the perpendicular plane to produce a wedge-shaped beam illuminating a thin gold film. The imaging optics shaped the reflected beam in such a way that the angular spectrum of each sensor channel was projected on a separate row (or rows) of the array detector. This design has been further advanced by Biacore AB (Sweden) and has resulted in a variety of commercial SPR sensors (subsection 1.3.4).

Figure 1.8 (a) Side view and (b) top view of a prism-based SPR sensor in angular configuration with three parallel channels. a—light-emitting diode, b—lenses, c—sensor chip, d—microfluidic cartridge, e—coupling prism, f—polarizer, g—photodiode array detector.

Reprinted, by permission, from Reference 32

An interesting approach in the miniaturization of SPR sensors with angular modulation was reported by Thirstrup et al. [49]. They developed a polymeric exchangeable sensor chip containing two diffractive optical coupling elements (DOCEs). The DOCEs (chirped relief gratings) were used to focus an incident parallel beam to a sensing spot and project the reflected beam onto a detector array (Fig. 1.9). The sensor provided an angular sensitivity of 140°/RIU and a resolution of 5 × 10−7 RIU. The SPR chips with DOCEs were produced in plastic by injection molding, which provides a low-cost method for the mass production of SPR chips. However, the limited quality of the diffraction coupling elements caused background illumination, which had a negative influence on the performance of the sensor.

Figure 1.9 Scheme of the SPR sensor based on the diffractive optical coupling element (DOCE).

Reprinted, by permission, from Reference 49

Another compact SPR sensor based on angular modulation was proposed by the researchers at Texas Instruments and the University of Washington in the 1990s. In recent years, this design (referred to as Spreeta), has been further refined. Spreeta SPR sensor had specific dimensions of only 3 × 1.5 × 4 cm3 and consisted of a plastic prism molded to a printed circuit board (PCB). The PCB contained a microelectronic circuit containing an LED and a linear diode array detector. The divergent light beam emitted by the LED passed through a polarizer and hit the sensor surface at a range of angles above the critical angle. Therefore, different areas on the sensor chip were illuminated under different angles (Fig. 1.10). The light reflected from the mirror placed on the top of the sensor was captured by the detector. The sensor was showed to have a resolution of 1.8 × 10−7 RIU within a time interval of 0.8 s. However, the sensor exhibited deviations from a smooth response of 0.2% during the measurement of a change in the refractive index of 0.04 RIU, which corresponds to a resolution of 8 × 10−5 RIU [47]. Subsequently, Chinowsky et al. demonstrated a portable 24-channel SPR sensor integrating eight 3-channel Spreeta sensors into a single suitcase [48]. The sensor contained supporting electronics and a microfluidic system with a temperature-controlled flow cell and was demonstrated to provide a resolution of 1–3 × 10−6 RIU [48]. Currently, the Spreeta sensor is also commercially available from Sensata Technologies (Section 1.3.4).

Figure 1.10 Scheme of the Spreeta sensor from Texas Instruments.

Reprinted, by permission, from Reference 47

Kim et al. reported a portable SPR platform based on angular modulation of SPR in eight parallel sensing channels [50]. A special gold-coated replaceable prism served as a coupling prism and a sensing chip at the same time. This made it possible to avoid the use of refractive index matching oil. The system was reported to exhibit a baseline noise of 0.7 mdeg [50], which for a typical angular sensitivity of about 95°/RIU [19] corresponds to a resolution of 7 × 10−6 RIU.

In 2008, Feltis et al. reported a fully integrated handheld SPR device with a size of only 15 × 8 cm2 and a weight of 600 g [51] (Fig. 1.11). The sensor was based on angular modulation of SPR using a laser diode and a photodiode array as a light source and detector, respectively. The sensor only measured in a single channel and was demonstrated to achieve a resolution of about 3 × 10−6 RIU [51].

Figure 1.11 Photograph of a handheld SPR device based on a prism coupler and angular interrogation.

Reprinted, by permission, from Reference 51

In 2002, Song et al. reported an SPR sensor based on angular interrogation of SPR, which utilized a bi-cell detector instead of a photodiode array [57]. The intensity of the reflected light captured by the detector's two cells, A and B, was analyzed and the position of the SPR minimum was determined by dividing the differential and sum signals (A − B)/(A + B). The presented baseline noise of about corresponds to a resolution of 4 × 10−6 RIU (assuming an operating wavelength of 635 nm and a sensitivity of about 140°/RIU [19]). A similar approach was reported by Zhang et al. [36], who used a quadrant detector and thus were able to measure in two channels simultaneously. This sensor was reported to provide an angular resolution of 10−5, which corresponded to a refractive index resolution of about 10−7 RIU (assuming a sensitivity of 130°/RIU [19]).

In 2007, researchers from Agilent Technologies (USA) reported an SPR system, which offers both angular modulation and SPR imaging [35]. The sensor configuration with angular is depicted in Figure 1.12a. The light from a laser diode was collimated and passed through an acousto-optic deflector (AOD) where the direction of the beam was modulated within a defined angular span. The deflected light was then imaged by a two-lens telescope onto a sensing chip so that the illuminated region remained at the same place during the angular scanning. The surface of the sensing chip was then imaged onto a high-speed CMOS-based camera. In the performed experiment, the camera frame-rate was 1.1 kHz and scanning through the full angular range was done every 100 ms, which allowed for the acquisition of more than 100 spectra each second. The combination of a powerful light source and a high-speed camera allowed for massive averaging of angular spectra and therefore offered spectra with extremely low noise. The resulting performance of the sensor as a function of the number of imaged spots is shown in Figure 1.12b for two different values of dynamic range. For example, the sensor imaging 30 sensing spots and offering a dynamic range of 0.015 RIU provided a resolution of about 7 × 10−9 RIU [35].

Figure 1.12 (a) Configuration of the high-resolution and high-throughput SPR imaging sensor based on fast angular scanning. (b) System performance as a function of the number of cells and dynamic range. Black data (experimental datapoints and theoretical extrapolations) corresponds to a dynamic range of 0.06 RIU, while the gray data were obtained for a 0.015 RIU dynamic range.

Reprinted, by permission, from Reference 35

Wavelength modulation has also found its way to spectroscopic SPR sensors. For instance, a high-resolution prism-based SPR sensor with wavelength modulation was reported by Homola et al. (Fig. 1.13) [33, 58]. Light from a halogen lamp was transmitted through a multimode optical fiber and after collimation and polarization it was made incident on an SPR chip with a gold film interfaced with a coupling prism. The reflected polychromatic beam was then coupled to output optical fibers and transmitted to a multichannel spectrometer. With the use of an advanced data processing algorithm [34], a baseline noise as low as 1.5 × 10−3 nm was established. This low noise level makes it possible to achieve a refractive index resolution of 2 × 10−7 RIU (assuming an operating wavelength of 750 nm and sensor sensitivity of 7500 nm/RIU [19]).

Figure 1.13 Four-channel sensor based on a wavelength interrogation of SPR in a Kretschmann geometry.

Reprinted, by permission, from Reference 58

In order to increase the amount of information in SPR sensors with wavelength modulation, wavelength division multiplexing (WDM) was introduced to SPR sensors with wavelength modulation. Two different approaches to WDM were proposed by Homola's group [39, 40]. In the first approach, a sensing surface consisting of a thin gold film partly coated with a thin dielectric film was used. As the presence of the thin dielectric film red-shifted the resonant wavelength (compared to the bare gold), the reflected light exhibited two dips associated with the excitation of SPs in the area with and without the dielectric overlayer [39]. In the second configuration, a special skewed prism was used in which polychromatic light was sequentially made incident on two sensing channels under different angles [40]. This WDM approach was combined with the previously described 4-channel SPR sensor with four parallel beams yielding an 8-channel SPR sensor. The resolution was 1 × 10−6 RIU and 7 × 10−7 RIU for the short-wavelength (640 nm) channel and the long-wavelength (790 nm) channel, respectively [40].

Bardin et al. [41] reported an SPR sensor combining high resolution of spectroscopy of SPs with a high number of sensing channels. In this spectro-imaging SPR sensor, polychromatic light reflected from a linear array of sensing spots was dispersed by a diffraction grating and projected onto a 2D detector. The spectra of light reflected from individual channels appeared as narrow bands on the detector. The sensor was demonstrated to attain a resolution of 3.5 × 10−7 RIU in up to 20 channels [41].

More complex plasmonic modes, such as LRSPs, have also been exploited in spectroscopic SPR sensors. In 2001, Nenninger et al. [37] reported an SPR sensor utilizing LRSPs. LRSP is a guided mode of an optical structure consisting of a very thin metal film sandwiched between two dielectrics with similar refractive indices (Section 1.2.1). Nenninger et al. investigated LRSP sensing structures employing two dielectrics as a buffer layer—one with refractive indices slightly below (Teflon AF) and above (MgF2) that of water. In the wavelength-modulation-based SPR sensor, the MgF2 chips were found to perform better and to achieve a resolution of 2 × 10−7 RIU [37]. In 2007, Slavík and Homola improved the design and implementation of the LRSP-based sensor (with Teflon AF as a buffer layer) and achieved a resolution of 2.5 × 10−8 RIU [38].

1.3.1.2 Prism-Based Sensors with Intensity or Phase Modulation

Intensity modulation has been increasingly used in SPR sensors to enable spatially resolved measurements [59, 60]. In typical SPR imaging sensors, a parallel TM-polarized beam of monochromatic light is launched into a prism coupler and made incident on a thin metal film at an angle of incidence close to the coupling angle for the excitation of SPs. The intensity of reflected light depends on the strength of the coupling between the incident light and the SP and therefore can be correlated with the distribution of the refractive index along the metal film surface [61–63]. In order to increase the sensor stability and optimize the contrast of SPR images, Fu et al. proposed an SPR imaging employing a white light source and a bandpass interference filter [64]. This SPR sensor was demonstrated to provide a refractive index resolution of 3 × 10−5 RIU [61].

In 2007, Piliarik et al. [53] reported an SPR imaging sensor based on polarization contrast and an array of patterned multilayers. In this configuration, each sensing channel consisted of a pair of sensing spots (type I and II; Fig. 1.14) with different multilayers. The multilayers were designed in such a way that with an increasing refractive index at the sensor surface, the intensity of the reflected light increased for spot type I and decreased for spot type II. When the sensor response is defined as a ratio of the intensities of light reflected from the spots I and II, the sensitivity is higher than the sensitivity for each individual spot. In addition, the defined sensor output is therefore insensitive to light level fluctuations, which are correlated across the sensing area. The sensor was demonstrated to provide an extended dynamic range of 0.012 RIU and a resolution of 2 × 10−6 RIU. Later, the same group reported an SPR imaging sensor combining the polarization contrast with a different concept of internal referencing. This concept is based on two mirrors enabling real-time compensation of fluctuations of the dark current and intensity of incident light [54]. Resolution as low as 2 × 10−7 RIU in 120 sensing spots was achieved with this type of sensor [54].

Figure 1.14 Scheme of an SPR imaging device based on polarization contrast and internal referencing using two types of multilayer structures on each sensing channel.

Reprinted, by permission, from Reference 53

In 2007, Law et al. reported an SPR sensor with phase modulation and an extended dynamic range [65]. The sensor was based on temporal modulation of the phase and detection of the second and third modulation harmonics. While the detection of the third modulation harmonics resulted in a good resolution (3 × 10−7 RIU) and a limited operating range (0.004 RIU), detection of the second harmonic modulation offered a worse resolution (10−5 RIU) and a larger operating range (0.012 RIU) [65].

A high-resolution SPR sensor was demonstrated by Wu and Ho [42]. They demonstrated a single-beam self-referenced phase-sensitive SPR sensor with an ultrahigh resolution of 5 × 10−9 RIU. The sensor was based on a differential phase-detection scheme, in which the phase of the incident beam was periodically modulated using a liquid crystal modulator. The modulated beam was split into a TM-polarized probe beam passing through the sensor head and a TE-polarized reference beam. Signals from both arms were then compared using a digital oscilloscope. However, the sensor response was strongly nonlinear and this level of resolution was only available within a refractive index range of 6 × 10−5 RIU. In the linear portion of the operating range, the resolution of the sensor was much poorer (10−6 RIU) [42].

Another approach in the development of SPR sensors with phase modulation was proposed by Nikitin's group. In 2000, Nikitin et al. reported two novel approaches to SPR imaging based on interferometry [43]. In the first configuration, the Mach–Zehnder interferometer with TM-polarized beams in both the signal and reference arms was used. The second approach was based on the interference of the TM-polarized signal beam with the TE-polarized reference beam. This configuration was observed to be less sensitive to vibrations as both beams passed through the same optical elements. The second method was demonstrated in a “phase contrast mode” and in a “fringe mode” in which a small angle was introduced between the combined interfering beams resulting in a pattern of interference fringes superimposed over the image of the surface. The sensor operating in “fringe mode” was able to measure variations in the refractive index as small as 10−7 RIU. Expandability of this approach to high-throughput measurements was demonstrated by imaging multiple spots (diameter—50 μm) coated with a molecular monolayer [43].

An SPR sensor based on an interferometric approach allowing for multiple passes of the signal beam through the sensor was reported by Ho et al. [44]. In this sensor, a coupling prism with an SPR chip was placed inside one arm of the interferometer and phase variations induced by SPR were measured through the interference of the beams on a detector. The sensor was tested in three configurations based on Mach–Zehnder, Michelson, and Fabry–Perot interferometers, which resulted in single-pass, double-pass, and multiple-pass of the optical beam through the SPR sensor head, respectively. The resolution of the tested configurations were 1.5 × 10−6 RIU and about 8 × 10−7 RIU for single-pass and double-pass, respectively [44].

A high-throughput SPR sensor based on differential phase SPR imaging using the Mach–Zehnder interferometer was reported by Wong et al. [45]. In the reference arm of the interferometer, the optical path was periodically changed using a movable mirror mounted on a piezoelectric transducer (PZT). With the PZT continuously shifting the reference optical phase, intensity variations were captured by a detector pixel after recombining the beams from both arms of the interferometer, which followed a truncated sine function. The fast Fourier transform (FFT) was combined with appropriate signal processing, which then converted the raw data into a two-dimensional SPR phase map that has a direct correlation with the refractive index changes on the sensor surface. The sensor was demonstrated to achieve a resolution of 9 × 10−7 RIU in a 5 × 5 array of sensing spots [45].

1.3.2 SPR Sensors Based on Grating Couplers

Although grating couplers were initially used in SPR sensor much less than prism couplers, in the last decade, the popularity of grating couplers has grown substantially owing to several unique features and benefits. Replacing bulky and costly prism couplers with grating couplers formed on planar substrates allows for a reduction of the size and costs of SPR instruments. In addition, the use of grating couplers eliminates the need for refractive index matching fluids, which are needed in order to make an optical contact between the prism coupler and the SPR chip. Grating-based SPR sensors based on all the main modulation approaches have been developed. Nevertheless, the majority of grating-based SPR sensors are based on angular or wavelength spectroscopy of SPs.

1.3.2.1 Spectroscopic Grating-Coupled SPR Sensors

Various SPR sensors based on the classical approach to spectroscopy of SPs have been developed. In this approach, light is made incident on several areas of a coupler and angular or wavelength spectrum of light coupled to SPs in these distinct areas is measured in parallel. For instance, recently, Vala et al. reported a mobile SPR sensor based on angular spectroscopy of SPs in 10 independent sensing channels [52]. In this sensor, a light from a narrow band laser diode is shaped by special lens optics to a wedge beam and made incident on a disposable SPR cartridge incorporating a grating coupler. SPs were excited through the − 1 diffraction order of the grating and the reflected light was projected on a CCD detector. A resolution as low as 6 × 10−7 RIU was observed.

A high-throughput SPR sensor based on angular spectroscopy of SPs was reported by Dostálek et al. [55]. In this sensor, a TM-polarized monochromatic light was focused on a sensor chip cartridge (Fig. 1.15) and the back-reflected light was imaged on a CCD detector. The cartridge consisted of a two-dimensional array of SPR diffraction gratings and a microfluidic system with six independent flow-chambers. The imaging optics was motorized, which made scanning of the grating array possible. The design of the sensor was further optimized with respect to the operating wavelength, the parameters of the diffraction grating coupler, and the supporting optical system, which altogether yielded a resolution of 5 × 10−7 RIU in more than a hundred sensing channels [66]. However, the motorization and large size of some of the components limited the measurement speed and potential for miniaturization of the sensor.

Figure 1.15 High-throughput grating-based SPR sensor with angular modulation.

Reprinted, by permission, from Reference 55

Another interesting approach to high-throughput SPR sensing was reported by Kastl et al. [56]. Their sensor was based on scanning multiple variably shaped (bar-coded) microgratings. These grating particles were settled at the bottom of a polydimethylsiloxane (PDMS) flow cell and their type and orientation were identified by optical imaging. Simultaneously, SPs were excited on the gratings and the angular distribution of monochromatic light coupled to the SPs was measured. The readout time was 6 s per grating and the resolution was 3 × 10−5 RIU. The main advantage of this approach is that it allows for the convenient introduction of different functionalizations and biorecognition elements into the measurement area.

Recently, Piliarik et al. [46] demonstrated a compact high-resolution SPR sensor based on a new approach to spectroscopy of SPs on a special diffraction grating referred to as a surface plasmon resonance coupler and disperser (SPRCD). In this sensor, polychromatic light was made incident on the SPRCD element and while one of the diffraction orders of the grating was used to excite SPs, the light diffracted away from the grating is dispersed across a CMOS detector (Fig. 1.16). The SPRCD element was integrated into a miniature cartridge with six independent microfluidic channels. The size of the sensor unit was 15 × 15 cm2. A resolution as low as 3 × 10−7 RIU was observed with this type of sensor [46].

Figure 1.16 Principle of operation of the surface plasmon resonance coupler and disperser.

Reprinted, by permission, from Reference 46

Advanced diffractive structures allow for the simultaneous excitation of multiple SPs by different spectral components of a polychromatic light, making multiple SP spectroscopy possible. These structures include, for instance, multidiffractive gratings on which SPs can be excited through diffraction on different harmonics of the multidiffractive grating [67], a diffraction grating with extremely thin metal film supporting short-range and long-range SPs [68], and bi-diffractive structures supporting Bragg-scattered SPs [69]. As SPs excited at different wavelengths exhibit different field profiles, probing the same binding event with multiple plasmons can reveal more information about the system under study, for instance, in discriminating surface refractive index changes due to the binding from background refractive index variations. However, this process requires accurate calibration and sophisticated data processing [70].

1.3.2.2 Grating-Based Sensors with Intensity Modulation

Brockman and Fernandez [71] demonstrated a grating-based SPR imaging device. In this sensor, a collimated beam of monochromatic light was made incident onto a plastic chip with a gold-coated grating (Fig. 1.17). The reflected light with spatially distributed SPR information was projected onto a CCD detector. The system was demonstrated to perform simultaneous measurements in 400 sensing spots with a resolution in the order of 10−6 RIU. This design was commercialized by HTS Biosystems (Germany) as a FLEX-chip system and later acquired by Biacore [72].

Figure 1.17 Concept of an SPR sensor based on a grating coupling and intensity modulation.

1.3.3 SPR Sensors Based on Optical Waveguides

Optical waveguides have been exploited in SPR sensors to miniaturize the sensing element and to create a connection between the SPR instrument and the sensing element. The waveguide-based SPR sensors can be divided into two groups on the basis of whether they are based on optical fibers or integrated optical waveguides.

1.3.3.1 Fiber Optic SPR Sensors

There are several configurations of fiber optic SPR sensors. A fiber-based SPR sensor can be, for example, fabricated by locally removing the cladding (e.g., by side-polishing) and coating the exposed area of the fiber with a thin metal film. Recently, an SPR spectroscopic sensor based on a side-polished multimode optical fiber was reported with a resolution in the order of 10−6 RIU [73]. Pollet et al. [74] presented a compact SPR sensor based on SPR spectroscopy employing a reusable SPR multimode fiber sensing element. In this sensor design, the sensing area was produced at the tip of an optical fiber and light reflected by the metal-coated end of the fiber was interrogated by a spectrometer. However, the performance of SPR sensors based on multimode fibers is limited by modal and polarization noise owing to perturbations of the fiber (deformations, thermal effect, etc.). To overcome this limitation, fibers guiding only a few modes [75] or a single mode [73, 76] were demonstrated with resolutions as low as 5 × 10−7 RIU [76]. However, the performance of even single-mode optical-fiber-based SPR sensors could be negatively affected by deformations of the fiber. To suppress sensitivity of the SPR fiber optic sensor, Piliarik et al. developed a wavelength modulation-based fiber optic SPR sensor using a polarization-maintaining fiber [77]. The sensor was demonstrated to achieve a resolution better than 4 × 10−6 RIU under moderate deformations of the fiber.

Another approach to the development of SPR sensors is based on tapered fibers. Chang et al. developed an SPR sensor based on intensity modulation and a single-mode optical fiber, the tip of which was tapered and coated with a metal film around the tip of the fiber [78]. Another SPR sensor was reported by Monzon-Hernandez et al. who developed a sensing element based on a uniform-tapered asymmetrically metal-coated fiber supporting hybrid SP modes. A light transmitted through the sensing element exhibited multiple resonance peaks observed in the spectrum of transmitted light. The resolution of the sensor was estimated to be about 7 × 10−7 RIU [79]. A similar uniform-tapered sensing probe was described by Diaz-Herrera et al. [80]. The sensing element was illuminated by a polychromatic light. Two different fiber Bragg gratings (FBGs) located behind the sensing area reflected light of two selected wavelengths and these were detected by two photodiodes. These two wavelengths were tuned to correspond with the slopes of the SPR dip. From the intensity changes of the light at these two wavelengths, the SPR position changes were deduced. The observed resolution was 2 × 10−5 RIU.

Recently, Bragg gratings inscribed in the fiber have been used to excite SPs coupled to cladding modes of the fiber. Špacková et al. proposed a fiber optic sensor with two different FBGs inscribed into two different regions of the sensing area. In this sensor, polychromatic light propagated in the fiber and through diffraction on the grating, the light of distinct spectral components excited different cladding modes including cladding modes coupled to SPs on the outer boundary of metal film deposited around the optical fiber. The coupling gave rise to narrow dips in the spectrum of transmitted light. As the response from two different gratings is encoded in different parts of the spectrum, the two gratings form two independent sensing channels. The resolution of the sensor was estimated to be around 2 × 10−6 RIU [81]. Shao et al. proposed an SPR sensor using an optical fiber with a tilted FBG in the core of the fiber [82]. In contrast to the cladding mode resonances, which are sensitive to fluctuations in the temperature outside the fiber structure, the core mode back reflection resonance is only sensitive to the temperature of the fiber. Therefore, such a structure can be used to compensate for fluctuations in the temperature of the sample.

1.3.3.2 Integrated Optical SPR Sensors

The first SPR sensors based on integrated optical waveguides were developed in the 1990s. The sensors typically consisted of a waveguide formed in a glass substrate and a thin metal layer deposited on the waveguide. The combination of materials and operating wavelengths in the visible and near infrared spectra determined the resonant refractive index of the medium under study above 1.4 RIU, which is much larger than the values of the refractive index of samples typically encountered in SPR biosensing. Several approaches have been proposed to shift the operating range of the sensor to an aqueous environment. Dostálek et al. used a high refractive index dielectric overlayer deposited on top of the metal film and demonstrated an integrated optical SPR sensor for aqueous environment with a resolution better than 2 × 10−6 RIU [83]. Other integrated optics SPR sensors were aimed at compact sensors as presented by Suzuki et al. [84]. In this sensor, monochromatic light emitted from two different LEDs was coupled to a waveguide with a sensing area. The intensity of output light modulated by SPR was measured by photodiodes. The reported sensor system was light and compact and powered by a 9 V battery. Another compact and integrated sensor was presented by Johnston et al. [85] who exploited a photodetection system that integrates optical computing with each pixel of the detector. An electro-optical SPR sensor was proposed by Wang et al. [86]. In this sensor, the SPR characteristics can be modulated by the applied voltage. Therefore, the SPR position can be changed. Such a feature can be used to cover a wide refractive index range, even when using a high-resolution spectrograph with a rather limited operating range. Jette-Charbonneau presented an integrated optical sensor utilizing LRSPs [87]. The sensor consists of a metal slab of a constant thickness with a periodic change of the width of the slab. This design allows the excitation of LRSPs with an extended field, which makes the sensor suitable for the detection of large analytes.

1.3.4 Commercial SPR Sensors

In the last two decades, rapid advances in SPR technology and a growing number of possible applications have led to the development of a number of commercial solutions to SPR biosensing. Nowadays, tens of companies produce SPR sensors, which range from portable SPR sensing devices to large laboratory SPR instruments offering high-resolution and/or high-throughput. This section presents examples of commercial SPR sensors.