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Virtual Journal for Biomedical Optics

Virtual Journal for Biomedical Optics

| EXPLORING THE INTERFACE OF LIGHT AND BIOMEDICINE

  • Editor: Gregory W. Faris
  • Vol. 4, Iss. 13 — Dec. 2, 2009
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Phase and amplitude sensitivities in surface plasmon resonance bio and chemical sensing

Andrei V. Kabashin, Sergiy Patskovsky, and Alexander N. Grigorenko  »View Author Affiliations


Optics Express, Vol. 17, Issue 23, pp. 21191-21204 (2009)
http://dx.doi.org/10.1364/OE.17.021191


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Abstract

We consider amplitude and phase characteristics of light reflected under the Surface Plasmon Resonance (SPR) conditions and study their sensitivities to refractive index changes associated with biological and chemical sensing. Our analysis shows that phase can provide at least two orders of magnitude better detection limit due to the following reasons: (i) Maximal phase changes occur in the very dip of the SPR curve where the vector of probing electric field is maximal, whereas maximal amplitude changes are observed on the resonance slopes: this provides a one order of magnitude larger sensitivity of phase to refractive index variations; (ii) Under a proper design of a detection scheme, phase noises can be orders of magnitude lower compared to amplitude ones, which results in a much better signal-to-noise ratio; (iii) Phase offers much better possibilities for signal averaging and filtering, as well as for image treatment. Applying a phase-sensitive SPR polarimetry scheme and using gas calibration model, we experimentally demonstrate the detection limit of 10−8 RIU, which is about two orders of magnitude better compared to amplitude-sensitive schemes. Finally, we show how phase can be employed for filtering and treatment of images in order to improve signal-to-noise ratio even in relatively noisy detection schemes. Combining a much better physical sensitivity and a possibility of imaging and sensing in micro-arrays, phase-sensitive methodologies promise a substantial upgrade of currently available SPR technology.

© 2009 OSA

1. Introduction

Over last 15 years Surface Plasmon Resonance (SPR) has become an undisputable leading technology for label-free detection and studies of biological binding events on the surface [1

1. B. Liedberg, C. Nylander, and I. Lundstrom, “Biosensing with surface plasmon resonance - how it all started,” Biosens. Bioelectron. 10(8), 1–9 ( 1995). [CrossRef]

3

3. R. B. M. Schasfoort, and A. J. Tudos, eds., Handbook of Surface Plasmon Resonance (Royal Society of Chemistry, 2008).

]. SPR biosensors take advantage of the phenomenon of surface plasmon polariton (SPP) excitation over metal/liquid interface. P-polarized light is directed through a glass prism and reflected from a gold covered prism facet in contact with liquid ambience, as shown in Fig. 1
Fig. 1 Schematics of SPR biosensor
. The SPR effect consists in a resonant transfer of energy from an incident photon to a surface plasmon polariton (kspp) over the metal/liquid interface, which is observed as a dip in angular (spectral) dependence of reflected intensity. Biomolecular binding events on gold lead to an increase of the refractive index (thickness) of an ultra-thin organic layer on the metal film (normally, 200-300 nm), resonantly changing conditions of SPR production and thus shifting angular [4

4. B. Liedberg, C. Nylander, and I. Lundstrum, “Surface plasmon resonance for gas detection and biosensing,” Sens. Actuators B Chem. 4(1), 299–304 ( 1983). [CrossRef]

,5

5. J. L. Melendez, R. Carr, D. U. Bartholomew, K. A. Kukanskis, J. Elkind, S. S. Yee, C. E. Furlong, and R. G. Woodbury, “A commercial solution for surface plasmon sensing,” Sens. Actuators B Chem. 35(1-3), 212–216 ( 1996). [CrossRef]

] or spectral [6

6. L. M. Zhang and D. Uttamchandani, “Optical chemical sensing employing surface plasmon resonance,” Electron. Lett. 24, 1469–1470 ( 1988). [CrossRef]

] position of the SPR dip. Such approach enables one to avoid time-consuming and impairing labeling step and thus obtain all reaction kinetics constants within minutes.

The detection limit of SPR technology is estimated as 1 pg∙mm−2 of biomaterial accumulating at the biosensor surface. This sensitivity is sufficient for studies of many interactions involving relatively large molecules such as e.g., antibody-antigen, protein-DNA, DNA-DNA etc [2

2. P. Schuck, “Use of surface plasmon resonance to probe the equilibrium and dynamic aspects of interactions between biological macromolecules,” Annu. Rev. Biophys. Biomol. Struct. 26(1), 541–566 ( 1997). [CrossRef] [PubMed]

,3

3. R. B. M. Schasfoort, and A. J. Tudos, eds., Handbook of Surface Plasmon Resonance (Royal Society of Chemistry, 2008).

,7

7. R. Karlsson, “SPR for molecular interaction analysis: a review of emerging application areas,” J. Mol. Recognit. 17(3), 151–161 ( 2004). [CrossRef] [PubMed]

]. However, the sensitivity still needs to be greatly improved for the detection of low molecular weight analytes (typically less than 500 Da) such as drugs, vitamins etc., as well as larger low copy number analytes such as e. g., antigens, viruses etc., which are deadly or pathogenic even in ultra-low quantities [3

3. R. B. M. Schasfoort, and A. J. Tudos, eds., Handbook of Surface Plasmon Resonance (Royal Society of Chemistry, 2008).

,7

7. R. Karlsson, “SPR for molecular interaction analysis: a review of emerging application areas,” J. Mol. Recognit. 17(3), 151–161 ( 2004). [CrossRef] [PubMed]

]. The main problem of current commercially available SPR technology is associated with the existence of a physical lower detection limit (LOD) of amplitude-sensitive schemes. This limit is conditioned by the level of noises in measurements and normally is estimated as 10−6 −10−5 Refractive Index Units (RIU) for various sensor implementations with angular, spectral or intensity interrogations [3

3. R. B. M. Schasfoort, and A. J. Tudos, eds., Handbook of Surface Plasmon Resonance (Royal Society of Chemistry, 2008).

].

The authors of a recent paper [58

58. B. Ran and S. G. Lipson, “Comparison between sensitivities of phase and intensity detection in surface plasmon resonance,” Opt. Express 14(12), 5641–5650 ( 2006). [CrossRef] [PubMed]

] disputed the statement on much higher phase sensitivity of SPR based techniques compared to the intensity one. As the main argument, they used the fact that up to the date of writing of their paper the projected LOD of 10−8 RIU has just been estimated and not confirmed by a direct experiment. Moreover, using a particular phase-step 4-detector polarimetry scheme and considering the shot noise of the detector as the main one, they came to a paradoxal conclusion that the intensity interrogation is better than the phase one and could provide the detection limit of the order of 10−9 RIU, which is far from what has been observed to date. This conclusion is in a direct contradiction with a widely accepted knowledge that phase techniques are far superior to intensity techniques for detection of small signals and often used to improve signal-to-noise ratio [15

15. M. Born, and E. Wolf, Principles of Optics, (Cambridge University Press, Cambridge, UK, 2002).

]. Surprisingly, this conclusion contrasts with results of an earlier paper on the same group [16

16. A. G. Notcovich, V. Zhuk, and S. G. Lipson, “Surface plasmon resonance phase imaging,” Appl. Phys. Lett. 76(13), 1665–1667 ( 2000). [CrossRef]

], in which a better resolution of phase measurements was obtained using Mach-Zehnder Interferometer-based SPR geometry. It seems therefore important to find the reasons for the dramatic conclusion of the Ref [58

58. B. Ran and S. G. Lipson, “Comparison between sensitivities of phase and intensity detection in surface plasmon resonance,” Opt. Express 14(12), 5641–5650 ( 2006). [CrossRef] [PubMed]

]. and reclaim the virtues of the phase technique which made it to become one of the most used techniques in radio, television, precision measurements (such as metrology and gravitation wave detection), etc.

It is also important to note that the discussion on detection limits of phase and amplitude measurements under SPR continued in many recent works, which appeared after [58

58. B. Ran and S. G. Lipson, “Comparison between sensitivities of phase and intensity detection in surface plasmon resonance,” Opt. Express 14(12), 5641–5650 ( 2006). [CrossRef] [PubMed]

], illustrating a persistent (and increasing) interest to this subject from photonics, analytical chemistry and biological communities. Some of the papers report progress in the improvement of the detection limit in both amplitude- and phase-sensitive schemes. We believe that we need to clearly distinguish three different types of works: (i) works, in which the low detection limit (LOD) is determined (and limited) by the level of instrumental and environmental (temperature and inertial drifts etc.) noises in a single amplitude or phase measurement; (ii) works reporting the LOD after the application of additional tools such as differential schemes, averaging, mathematical treatment of noises etc., which can significantly lower the LOD value in both phase- and amplitude-sensitive modalities; (iii) works, declaring unrealistic LOD values, which can only be explained by artificial facts taking into account the anticipated level of environmental noises. To avoid ambiguities in interpretation, in our analysis we will compare LODs in phase and amplitude measurements under the same level of instrumental noises without any additional signal treatment.

2. Phase and amplitude responses under SPR

Amplitude,E=|E0|, and phase, φ, represent two essential features of the vector of electric field of an electromagnetic wave E=E0cos(kxωt+φ). Amplitude is connected to the vector length, whereas phase describes an angular shift of the beginning of the oscillation cycle. Depending on geometry of light-medium interaction, the propagation or reflection of light from the medium can be accompanied by a change of amplitude, phase or amplitude and phase simultaneously. An example of a pure phase change includes light propagation in a transparent homogeneous media, whereas examples of pure amplitude changes include the light propagation in homogeneous absorbing media. It is important to note that both phase and amplitude of electromagnetic field carry information about the medium in which light propagates. As an example, the employment of phase information for image generation was used by Zernike to develop Nobel-prize winning phase contrast microscopy, while prominent examples of pure amplitude response include absorption-based gas sensing, light filters etc. Introducing a small change of the electric field produced by a tiny change in a medium asΔE, we can write the (relative) amplitude and phase responses as ΔE/E=(E0ΔE)/E2 and Δφ=|E0×ΔE|/E2 respectively. Thus, the maximal amplitude changes takes place when ΔE is parallel toE0, while the maximal phase change occurs when ΔE is perpendicular toE0. In other words it means that the maximal amplitude changes are observed at the condition of the absence of phase changes and, vice versa, the maximal phase change is observed at the minimum of the amplitude response.

Under SPR, we have a resonant phenomenon, consisting in a transfer of energy from a pumping photon to a plasmon under some angle of incidence and wavelength of incident light. This phenomenon is accompanied by simultaneous amplitude and phase changes for reflected light: a drastic drop of amplitude and a sharp phase jump considered as functions of either the incident angle or wavelength. Figure 2(a)
Fig. 2 (a) Schematics of electric vector changes under SPR; (b) Reflectivity (dashed) and phase (solid) as functions of the angle of incidence under the optimal thickness of the SPR-supporting gold
shows schematics of SPR measurements where a small change of the refractive index Δn of the analyzed medium produces a change of the reflected electromagnetic wave Er by ΔEr. It is clear that in the first approximation |ΔEr|αΔn|Espp|, where Espp is the electromagnetic field of the surface plasmon acting on the medium under study and α is a constant close to unity.

Due to properties the plasmon excitation, the surface plasmon field Espp is large which guarantees high sensitivity of the SPR techniques. This gives us the following estimate of the relative amplitude and phase responses: ΔEr/ErαΔn|Espp|/Er and ΔφαΔn|Espp|/Er. The maximum of the phase response is observed at the resonance minimum (where ErminΔEr) while the maximum of the amplitude signal is observed at the resonance slope (where ErslopeΔEr), see Fig. 2(b). Introducing a figure of merit (FOM) as a ratio of the phase response over the relative amplitude response, we get FOM=(|Esppmin|/|Esppslope|)(Erslope/Ermin). The physical meaning of FOM is as follows: it describes how much the phase signal will be larger than the amplitude one at the condition of the same intensity of light collected by the photodetector. Taking the formulae for the electric fields [59

59. H. Raether, Surface Plasmons on Smooth and Rough Surfaces and on Gratings, (Springer-Verlag, Berlin, 1988).

] and typical values for gold film of an optimal thickness at the wavelength of ~700nm, we obtain |Esppmin|/|Esppslope|1.5 and Erslope/Ermin6 and hence FOM9. Even larger FOM is obtained for SPR based on Ag films. Hence, the sensitivity of phase technique under SPR condition is at least an order of magnitude better than the amplitude sensitivity.

3. Phase and amplitude sensitivities in SPR schemes

We start our analysis by noting that any SPR technique requires three important ingredients: a source of light, SPR detection cell and a photodetector. Each of these elements contributes some noise into the system which ultimately defines the sensitivity and LOD of a SPR scheme. For the purpose of comparing phase and intensity modes of SPR measurements one needs to compare phase and intensity noises of these three elements.

Drifts of characteristics of light source and photodetector present instrumental noises. There most common source of light for SPR measurements are lasers. Lasers usually have excellent phase noise characteristics. The phase noise of a common laser can be evaluated as Δφ/φλ/lcΔfl/fl, where λ is the laser wavelength and lc is the coherence length, Δfl is the laser line width and fl is the laser frequency [15

15. M. Born, and E. Wolf, Principles of Optics, (Cambridge University Press, Cambridge, UK, 2002).

]. The coherence length of typical laser is well above 5 m which yields the magnitude of relative phase noise for a laser working at the wavelength of 500nm at the level of about Δφ/φ≈10−6. The single frequency solid state lasers can easily have even larger coherence length at the level of 10 km which makes phase noise of these lasers negligible [15

15. M. Born, and E. Wolf, Principles of Optics, (Cambridge University Press, Cambridge, UK, 2002).

]. At the same time, relative intensity noise of common lasers is significantly higher and is usually at the level of χ=ΔI/I≈10−2. There are several important factors which contribute to higher intensity noise of laser sources: instability in pumping, spot burning due to spatial distribution of laser modes, photon statistics during photon emission and absorption, beam pointing fluctuations, etc. All these factors result in considerable drift of laser intensity at low frequencies (1/f noise), a peak of the relaxation oscillation noise, quantum noise, etc. Figure 3
Fig. 3 Intensity noise of the (a) HeNe laser normalized to shot noise for different discharge currents [61]; (b) Nd laser for the pumping frequency of 1 mW [62]
shows the frequency dependence of the intensity noise of the most common gas and solid state lasers normalised on shot noiseS(f)=2Phf, where P is the laser power.

The Fig. 3 clearly demonstrates that in a large frequency range from 0 to 106 Hz the intensity noise of lasers is much larger than the shot noise and is governed by the factors others than the photon statistics. It is easy to check that a similar situation takes place for other types of lasers. In fact, it means that the fundamentally conditioned shot noise can dominate only in an idealized situation of the absence of “technological” noises arising during the lasing process, which never take place in practice. We can write the laser intensity noise as σnoise2=nm2I2+nsI+nb2, where I is average intensity, nm, ns, nb is the constant describing modulation, shot and background noise, respectively. The modulation noise (drift of laser intensity) is proportional to laser intensity I with coefficient nmχB where χ is the numerical coefficient χ ≈10−2 and B is the total bandwidth and the shot noise constant is ns2hf/A, where A is the size of the laser spot. From here we conclude that the modulation noise overcomes shot noise for a laser without an intensity stabilization scheme at relatively low powers of above P>2hfBχ21μW (at a generous bandwidth of 100MHz). Therefore the intensity modulation noise of the common lasers is the most important type of noise which limits operation of the SPR measurement techniques. (One needs to use different smart types of laser intensity stabilization in order to be in the limit of shot noise!).

Returning to results and conclusions of Ref [58

58. B. Ran and S. G. Lipson, “Comparison between sensitivities of phase and intensity detection in surface plasmon resonance,” Opt. Express 14(12), 5641–5650 ( 2006). [CrossRef] [PubMed]

], the authors of this work used a 4-detector polarimetry scheme to record changes of light phase. In this scheme, light of a mixed polarization is used to excite Surface Plasmons in the Kretschmann-Raether prism arrangement, while an automated polarizator is rotated using a step algorithm to provide four independent measurements of intensity corresponding to different light ellipticity states (0, π/2, π, 3π/2 for the reference wave). Phase is then extracted from these intensity measurements using standard formulae. The authors then compare signal-to-noise ratios for phase and amplitude measurements in such scheme considering the shot noise of the detector as the prime noise in the system. We believe that the authors employed a very ineffective phase scheme and used it in essentially incorrect regime, which could prevent the implementation of much higher phase sensitivity:

Furthermore, the authors of [58

58. B. Ran and S. G. Lipson, “Comparison between sensitivities of phase and intensity detection in surface plasmon resonance,” Opt. Express 14(12), 5641–5650 ( 2006). [CrossRef] [PubMed]

] compare the sensitivity of the phase technique with sensitivity of intensity measurements at a fixed intensity of the light source, which is obviously wrong. The phase and intensity measurements should be compared at a fixed intensity of light collected by the photodiode, since it is customary to adjust the power of laser source to a level where photodiode will be in the region of its maximal sensitivity (with the aim to avoid saturation). In this case, the shot noise of the phase scheme and the intensity schemes will be approximately the same, whilst the phase mode will have much better sensitivity due to a much stronger dependence of the light phase on the refractive index in the region of the phase jump than the light intensity. Therefore, even in the case of prevailing shot noise it is relatively easy to achieve much better sensitivity by the phase mode of SPR measurements simply by adjusting laser intensity. This conclusion is actually supported by the formulae presented in [58

58. B. Ran and S. G. Lipson, “Comparison between sensitivities of phase and intensity detection in surface plasmon resonance,” Opt. Express 14(12), 5641–5650 ( 2006). [CrossRef] [PubMed]

], provided the measurements are compared at a fixed intensity of light collected by the photodiode.

2. Even if the pumping intensity is increased, the achievement of superior phase sensitivity requires an employment of methodology, which somehow eliminates or subtracts amplitude noises. In contrast, the scheme and measurement procedure did not ensure amplitude noise-independent phase measurements. Recording the intensity of interferograms without any reference to laser intensity drifts, the authors collected all amplitude noises in their phase signal. Furthermore, they did four independent intensity measurements summarizing four intensity noises for the determination of a single phase value.

3. Experimental assessment of detection limit in phase-sensitive SPR schemes

To illustrate a feasibility of extremely low detection limit in practical conditions, we used a standard commercially available Biacore slide with a 50 nm gold film deposited on a glass substrate. The Biacore slide was in immersion contact with a glass prism (F10 glass). Together with a gas/liquid flow cell, they presented the sensing block. Light after the PEM was passed through the prism and reflected from the gold film, which was in contact with sample gas/liquid medium. Figure 5(b) shows experimentally measured angular dependences of reflectivity and phase of light for two pumping frequencies (632.8 and 670 nm) when gold was in contact with air. One can see that the SPR effect is accompanied by a drastic decrease of intensity of the p-polarized component and a sharp jump of its phase, changing the total polarization state of light. It is also visible that the slides were optimized for 670 nm with sharpest phase characteristics for this wavelength. Nevertheless, the characteristics of the SPR-supporting film were good enough even for 632.8 nm, which is the pumping wavelength in our scheme with a highly stabilized laser.

In our tests, we used a well-established gas methodology for tiny refractive index variations Δn [9

9. A. V. Kabashin and P. I. Nikitin, “Surface plasmon resonance interferometer for bio- and chemical-sensors,” Opt. Commun. 150(1-6), 5–8 ( 1998). [CrossRef]

,40

40. I. R. Hooper, J. R. Sambles, M. C. Pitter, and M. G. Somekh, “Phase sensitive array detection with polarization modulated differential sensing,” Sens. Actuators B Chem. 119(2), 651–655 ( 2006). [CrossRef]

,46

46. C. E. Stewart, I. R. Hooper, and J. R. Sambles, “Surface plasmon differential ellipsometry of aqueous solutions for bio-chemical sensing,” J. Phys. D Appl. Phys. 41(10), 105408–105415 ( 2008). [CrossRef]

]. This method consists in the comparison of the system response while two different inert gases with known refractive indices are brought into a contact with the gold film. In our experiments Ar and N2 were used, for which the refractive indices differ by Δn ≅1.5⋅10−5 RIU under the normal conditions [66]. The gases were passed to the cell through a long spiral copper tube to equalize their temperatures with a room one and then mixed in a mixer to provide a controlled ration of gases in the flow cell. The mixture of gases was then brought in contact with SPR-supporting gold film. The precision of gas mixing was better than 0.01%.

Figure 6
Fig. 6 Response of the system under the replacement of pure N2 by 2.5%Ar/97.5%N2 mixture
demonstrates the response of the system when 100% of N2 was replaced by a mixture of 2.5% of Ar and 97.5% of N2 (such replacement of gases corresponds to the change of the refractive index by 4.9*10−7 RIU). One can see that such a tiny RI change leads to a significant phase shift (almost 0.1 Deg.). Taking into account that the noise level did not exceed 0.006 Deg. (Fig. 6), we can conclude that the experimental detection limit of the system is better than 4⋅10−8 RIU, which is orders of magnitude better compared to amplitude-sensitive schemes. It is important that this value of the detection limit was obtained under non-optimal pumping wavelength (632.8 nm) for Biacore slides. Based on 4-times sharper phase characteristics, the use of the optimal wavelength (670 nm) is expected to provide the detection limit lower than 10−8 RIU. However, such measurements require highly stabilized source characteristics, which is not the case for laser diodes used in Biacore system. Another approach for a further improvement of the detection limit is based on the optimization of the film thickness for 632.8 nm pumping wavelength.

4. Phase sensitivity for interferometric SPR imaging

Thus, phase measurements offer additional powerful and flexible tools to improve signal-to-noise ratio even under a relatively high level of instrumental noises. In fact, such options are granted by nature of phase measurements. Indeed, phase control implies inherent relative measurement with respect to a reference beam or an unaffected component of the same beam. This makes possible spatial or temporal mapping, depending of geometry of phase-sensitive setup, and a subsequent filtering/averaging using the chosen map. In fact, similar mapping and subsequent filtering/averaging is possible in amplitude measurements under the involvement of an independent reference channel, unaffected by the SPR, but such arrangement is normally accompanied by an inevitable complication of the measurement system and increase of its cost. Notice that the latter approach has already been used to lower the measured LOD in some papers using amplitude-sensitive SPR systems.

Conclusions

We compared amplitude and phase characteristics of light reflected in conditions of Surface Plasmon Resonance bio- and chemical sensing. We showed that phase can provide at least two orders of magnitude lower LOD due to: (i) a much stronger response to refractive index variations as a result of probing of medium properties in the very dip of SPR dip where electric field is maximum; (ii) possibilities for a much lower level of phase noises compared to intensity ones under a proper design of phase-sensitive schemes; (iii) possibilities for additional filtering/averaging tools taking advantage of essentially relative nature of phase measurement. Providing a better sensitivity and offering imaging tools, phase-sensitive methodologies are expected to improve current SPR-based bio- and chemical sensing technology.

Finally, we are glad to state that the development of phase-sensitive SPR biosensors has recently resulted in the appearance of commercially available units (see, e.g. the system of BIOptics Inc., Ref. [68]), offering a better sensitivity and sensing in multi-channels.

Acknowledgements

We acknowledge the financial contribution from French National Research Agency (ANR) and EPSRC, grant EP/E01111X/1.

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W. Yuan, H. P. Ho, Y. K. Suen, S. K. Kong, and C. Lin, “Improving the sensitivity limit of surface plasmon resonance biosensors by detecting mixed interference signals,” Appl. Opt. 46(33), 8068–8073 ( 2007). [CrossRef] [PubMed]

32.

C. L. Wong, H. P. Ho, T. T. Yu, Y. K. Suen, W. W. Chow, S. Y. Wu, W. C. Law, W. Yuan, W. J. Li, S. K. Kong, and C. Lin, “Two-dimensional biosensor arrays based on surface plasmon resonance phase imaging,” Appl. Opt. 46(12), 2325–2332 ( 2007). [CrossRef] [PubMed]

33.

C. L. Wong, H. P. Ho, Y. K. Suen, S. K. Kong, Q. L. Chen, W. Yuan, and S. Y. Wu, “Real-time protein biosensor arrays based on surface plasmon resonance differential phase imaging,” Biosens. Bioelectron. 24(4), 606–612 ( 2008). [CrossRef] [PubMed]

34.

T. Konig, M. Weidemuller, and A. Hemmerich, “Real-time phase-shift detection of the surface plasmon resonance,” Appl. Phys. B 93(2-3), 545–549 ( 2008). [CrossRef]

35.

G. Nemova, A. V. Kabashin, and R. Kashyap, “Surface Plasmon Polariton Mach-Zehnder refractive index sensor,” J. Opt. Soc. Am. B 25(10), 1673–1677 ( 2008). [CrossRef]

36.

S. Y. Wu and H. P. Ho, “Single-beam self-referenced phase-sensitive surface plasmon resonance sensor with high detection resolution,” Chin. Opt. Lett. 6(3), 176–178 ( 2008). [CrossRef]

37.

I. R. Hooper and J. R. Sambles, “Differential ellipsometric surface plasmon resonance sensors with liquid crystal polarization modulators,” Appl. Phys. Lett. 85(15), 3017–3019 ( 2004). [CrossRef]

38.

H. P. Chiang, J. L. Lin, R. Chang, S. Y. Su, and P. T. Leung, “High-resolution angular measurement using surface-plasmon-resonance via phase interrogation at optimal incident wavelengths,” Opt. Lett. 30(20), 2727–2729 ( 2005). [CrossRef] [PubMed]

39.

R. Naraoka and K. Kajikawa, “Phase detection of surface plasmon resonance using rotating analyzer method,” Sens. Actuators B Chem. 107(2), 952–956 ( 2005). [CrossRef]

40.

I. R. Hooper, J. R. Sambles, M. C. Pitter, and M. G. Somekh, “Phase sensitive array detection with polarization modulated differential sensing,” Sens. Actuators B Chem. 119(2), 651–655 ( 2006). [CrossRef]

41.

H. P. Ho, W. C. Law, S. Y. Wu, X. H. Liu, S. P. Wong, C. Lin, and S. K. Kong, “Phase-sensitive surface plasmon resonance biosensor using the photo-elastic modulation technique,” Sens. Actuators B Chem. 114(1), 80–84 ( 2006). [CrossRef]

42.

P. P. Markowicz, W. C. Law, A. Baev, P. Prasad, S. Patskovsky, and A. V. Kabashin, “Phase-sensitive time-modulated SPR polarimetry for wide dynamic range biosensing,” Opt. Express 15, 1745 ( 2007). [CrossRef] [PubMed]

43.

W.-C. Law, P. Markowicz, K.-T. Yong, I. Roy, A. Baev, S. Patskovsky, A. V. Kabashin, H. P. Ho, and P. N. Prasad, “Wide dynamic range phase-sensitive surface plasmon resonance biosensor based on measuring the modulation harmonics,” Biosens. Bioelectron. 23(5), 627–632 ( 2007). [CrossRef] [PubMed]

44.

S. Patskovsky, R. Jacquemart, M. Meunier, G. De Crescenzo, and A. V. Kabashin, “Phase-sensitive spatially-modulated SPR Polarimetry for Detection of Biomolecular Interactions,” Sens. Actuators B Chem. 133, 628–631 ( 2008). [CrossRef]

45.

S. Patskovsky, M. Maisonneuve, M. Meunier, and A. V. Kabashin, “Mechanical modulation method for ultrasensitive phase measurements in photonics biosensing,” Opt. Express 16(26), 21305–21314 ( 2008). [CrossRef] [PubMed]

46.

C. E. Stewart, I. R. Hooper, and J. R. Sambles, “Surface plasmon differential ellipsometry of aqueous solutions for bio-chemical sensing,” J. Phys. D Appl. Phys. 41(10), 105408–105415 ( 2008). [CrossRef]

47.

W. Yuan, H. P. Ho, S. Y. Wu, Y. K. Suen, S. K. Kong c, H. P Ho, S. Y Wu, Y. K Suen, and S. K Kong,“Polarization-sensitive surface plasmon enhanced ellipsometry biosensor using the photoelastic modulation technique,” Sens. Actuators A Phys. 151(1), 23–28 ( 2009). [CrossRef]

48.

C. M. Wu, Z. C. Jian, S. F. Joe, and L. B. Chang, “High-sensitivity sensor based on surface Plasmon resonance and heterodyne interferometry,” Sens. Actuators B Chem. 92(1-2), 133–136 ( 2003). [CrossRef]

49.

W. C. Kuo, C. Chou, and H. T. Wu, “Optical heterodyne surface-plasmon resonance biosensor,” Opt. Lett. 28(15), 1329–1331 ( 2003). [CrossRef] [PubMed]

50.

C.-M. Wu and M.-C. Pao, “Sensitivity-tunable optical sensors based on surface plasmon resonance and phase detection,” Opt. Express 12(15), 3509–3514 ( 2004). [CrossRef] [PubMed]

51.

C. Chou, H.-T. Wu, Y.-C. Huang, W. C. Kuo, and Y. L. Chen, “Characteristics of a paired surface plasma waves biosensor,” Opt. Express 14(10), 4307–4315 ( 2006). [CrossRef] [PubMed]

52.

Y.-C. Li, Y.-F. Chang, L.-C. Su, and C. Chou, “Differential-phase surface plasmon resonance biosensor,” Anal. Chem. 80(14), 5590–5595 ( 2008). [CrossRef] [PubMed]

53.

S. Patskovsky, M. Meunier, and A. V. Kabashin, “Surface plasmon resonance polarizator for biosensing and imaging,” Opt. Commun. 281(21), 5492–5496 ( 2008). [CrossRef]

54.

A. V. Kabashin, V. E. Kochergin, A. A. Beloglazov, and P. I. Nikitin, “Phase-polarization contrast for SPR biosensors,” Biosens. Bioelectron. 13, 1263–1269 ( 1998). [CrossRef] [PubMed]

55.

J. Homola and S. S. Yee, “Novel polarization control scheme for spectral surface plasmon resonance sensors,” Sens. Actuators B Chem. 51(1-3), 331–339 ( 1998). [CrossRef]

56.

A. V. Kabashin, V. E. Kochergin, and P. I. Nikitin, “Surface plasmon resonance bio- and chemical sensors with phase-polarisation contrast,” Sens. Actuators B Chem. 54(1-2), 51–56 ( 1999). [CrossRef]

57.

M. Piliarik, H. Vaisocherová, and J. Homola, “A new surface plasmon resonance sensor for high-throughput screening applications,” Biosens. Bioelectron. 20(10), 2104–2110 ( 2005). [CrossRef] [PubMed]

58.

B. Ran and S. G. Lipson, “Comparison between sensitivities of phase and intensity detection in surface plasmon resonance,” Opt. Express 14(12), 5641–5650 ( 2006). [CrossRef] [PubMed]

59.

H. Raether, Surface Plasmons on Smooth and Rough Surfaces and on Gratings, (Springer-Verlag, Berlin, 1988).

60.

http://www.capovani.com/dp/cat/107/63160/iinfo.cfm?LCl=986&TVTID=0&TItemNo=0&ItemNo=422&q=2

61.

A. Waksberg and J. Wood, “Noise power spectrum characteristics for an HeNe laser operating under various discharge conditions,” Rev. Sci. Instrum. 40(10), 1306–1313 ( 1969). [CrossRef]

62.

K. G. Baigent, D. A. Shaddock, M. B. Gray, and D. E. McClelland, “Laser stabilisation for the measurement of thermal Noise,” Gen. Relativ. Gravit. 32(3), 399–409 ( 2000). [CrossRef]

63.

G. Keiser, Optical Communications Essentials, (McGraw-Hill, 2003).

64.

J. M. Liu, Photonic devices, (University press, Cambridge, 2005).

65.

M. W. Wang, F. H. Tsai, and Y. F. Chao, “In situ calibration technique for photoelastic modulator in ellipsometry,” Thin Solid Films 455–456, 78–83 ( 2004). [CrossRef]

66.

www.luxpop.com

67.

www.bioptics.com

OCIS Codes
(120.5050) Instrumentation, measurement, and metrology : Phase measurement
(240.6680) Optics at surfaces : Surface plasmons

ToC Category:
Optics at Surfaces

History
Original Manuscript: September 25, 2009
Revised Manuscript: October 27, 2009
Manuscript Accepted: October 27, 2009
Published: November 6, 2009

Virtual Issues
Vol. 4, Iss. 13 Virtual Journal for Biomedical Optics

Citation
Andrei V. Kabashin, Sergiy Patskovsky, and Alexander N. Grigorenko, "Phase and amplitude sensitivities in surface plasmon resonance bio and chemical sensing," Opt. Express 17, 21191-21204 (2009)
http://www.opticsinfobase.org/vjbo/abstract.cfm?URI=oe-17-23-21191


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  31. W. Yuan, H. P. Ho, Y. K. Suen, S. K. Kong, and C. Lin, “Improving the sensitivity limit of surface plasmon resonance biosensors by detecting mixed interference signals,” Appl. Opt. 46(33), 8068–8073 (2007). [CrossRef] [PubMed]
  32. C. L. Wong, H. P. Ho, T. T. Yu, Y. K. Suen, W. W. Chow, S. Y. Wu, W. C. Law, W. Yuan, W. J. Li, S. K. Kong, and C. Lin, “Two-dimensional biosensor arrays based on surface plasmon resonance phase imaging,” Appl. Opt. 46(12), 2325–2332 (2007). [CrossRef] [PubMed]
  33. C. L. Wong, H. P. Ho, Y. K. Suen, S. K. Kong, Q. L. Chen, W. Yuan, and S. Y. Wu, “Real-time protein biosensor arrays based on surface plasmon resonance differential phase imaging,” Biosens. Bioelectron. 24(4), 606–612 (2008). [CrossRef] [PubMed]
  34. T. Konig, M. Weidemuller, and A. Hemmerich, “Real-time phase-shift detection of the surface plasmon resonance,” Appl. Phys. B 93(2-3), 545–549 (2008). [CrossRef]
  35. G. Nemova, A. V. Kabashin, and R. Kashyap, “Surface Plasmon Polariton Mach-Zehnder refractive index sensor,” J. Opt. Soc. Am. B 25(10), 1673–1677 (2008). [CrossRef]
  36. S. Y. Wu and H. P. Ho, “Single-beam self-referenced phase-sensitive surface plasmon resonance sensor with high detection resolution,” Chin. Opt. Lett. 6(3), 176–178 (2008). [CrossRef]
  37. I. R. Hooper and J. R. Sambles, “Differential ellipsometric surface plasmon resonance sensors with liquid crystal polarization modulators,” Appl. Phys. Lett. 85(15), 3017–3019 (2004). [CrossRef]
  38. H. P. Chiang, J. L. Lin, R. Chang, S. Y. Su, and P. T. Leung, “High-resolution angular measurement using surface-plasmon-resonance via phase interrogation at optimal incident wavelengths,” Opt. Lett. 30(20), 2727–2729 (2005). [CrossRef] [PubMed]
  39. R. Naraoka and K. Kajikawa, “Phase detection of surface plasmon resonance using rotating analyzer method,” Sens. Actuators B Chem. 107(2), 952–956 (2005). [CrossRef]
  40. I. R. Hooper, J. R. Sambles, M. C. Pitter, and M. G. Somekh, “Phase sensitive array detection with polarization modulated differential sensing,” Sens. Actuators B Chem. 119(2), 651–655 (2006). [CrossRef]
  41. H. P. Ho, W. C. Law, S. Y. Wu, X. H. Liu, S. P. Wong, C. Lin, and S. K. Kong, “Phase-sensitive surface plasmon resonance biosensor using the photo-elastic modulation technique,” Sens. Actuators B Chem. 114(1), 80–84 (2006). [CrossRef]
  42. P. P. Markowicz, W. C. Law, A. Baev, P. Prasad, S. Patskovsky, and A. V. Kabashin, “Phase-sensitive time-modulated SPR polarimetry for wide dynamic range biosensing,” Opt. Express 15, 1745 (2007). [CrossRef] [PubMed]
  43. W.-C. Law, P. Markowicz, K.-T. Yong, I. Roy, A. Baev, S. Patskovsky, A. V. Kabashin, H. P. Ho, and P. N. Prasad, “Wide dynamic range phase-sensitive surface plasmon resonance biosensor based on measuring the modulation harmonics,” Biosens. Bioelectron. 23(5), 627–632 (2007). [CrossRef] [PubMed]
  44. S. Patskovsky, R. Jacquemart, M. Meunier, G. De Crescenzo, and A. V. Kabashin, “Phase-sensitive spatially-modulated SPR Polarimetry for Detection of Biomolecular Interactions,” Sens. Actuators B Chem. 133, 628–631 (2008). [CrossRef]
  45. S. Patskovsky, M. Maisonneuve, M. Meunier, and A. V. Kabashin, “Mechanical modulation method for ultrasensitive phase measurements in photonics biosensing,” Opt. Express 16(26), 21305–21314 (2008). [CrossRef] [PubMed]
  46. C. E. Stewart, I. R. Hooper, and J. R. Sambles, “Surface plasmon differential ellipsometry of aqueous solutions for bio-chemical sensing,” J. Phys. D Appl. Phys. 41(10), 105408–105415 (2008). [CrossRef]
  47. W. Yuan, H. P. Ho, S. Y. Wu, Y. K. Suen, S. K. Kong c, H. P Ho, S. Y Wu, Y. K Suen, and S. K Kong,“Polarization-sensitive surface plasmon enhanced ellipsometry biosensor using the photoelastic modulation technique,” Sens. Actuators A Phys. 151(1), 23–28 (2009). [CrossRef]
  48. C. M. Wu, Z. C. Jian, S. F. Joe, and L. B. Chang, “High-sensitivity sensor based on surface Plasmon resonance and heterodyne interferometry,” Sens. Actuators B Chem. 92(1-2), 133–136 (2003). [CrossRef]
  49. W. C. Kuo, C. Chou, and H. T. Wu, “Optical heterodyne surface-plasmon resonance biosensor,” Opt. Lett. 28(15), 1329–1331 (2003). [CrossRef] [PubMed]
  50. C.-M. Wu and M.-C. Pao, “Sensitivity-tunable optical sensors based on surface plasmon resonance and phase detection,” Opt. Express 12(15), 3509–3514 (2004). [CrossRef] [PubMed]
  51. C. Chou, H.-T. Wu, Y.-C. Huang, W. C. Kuo, and Y. L. Chen, “Characteristics of a paired surface plasma waves biosensor,” Opt. Express 14(10), 4307–4315 (2006). [CrossRef] [PubMed]
  52. Y.-C. Li, Y.-F. Chang, L.-C. Su, and C. Chou, “Differential-phase surface plasmon resonance biosensor,” Anal. Chem. 80(14), 5590–5595 (2008). [CrossRef] [PubMed]
  53. S. Patskovsky, M. Meunier, and A. V. Kabashin, “Surface plasmon resonance polarizator for biosensing and imaging,” Opt. Commun. 281(21), 5492–5496 (2008). [CrossRef]
  54. A. V. Kabashin, V. E. Kochergin, A. A. Beloglazov, and P. I. Nikitin, “Phase-polarization contrast for SPR biosensors,” Biosens. Bioelectron. 13, 1263–1269 (1998). [CrossRef] [PubMed]
  55. J. Homola and S. S. Yee, “Novel polarization control scheme for spectral surface plasmon resonance sensors,” Sens. Actuators B Chem. 51(1-3), 331–339 (1998). [CrossRef]
  56. A. V. Kabashin, V. E. Kochergin, and P. I. Nikitin, “Surface plasmon resonance bio- and chemical sensors with phase-polarisation contrast,” Sens. Actuators B Chem. 54(1-2), 51–56 (1999). [CrossRef]
  57. M. Piliarik, H. Vaisocherová, and J. Homola, “A new surface plasmon resonance sensor for high-throughput screening applications,” Biosens. Bioelectron. 20(10), 2104–2110 (2005). [CrossRef] [PubMed]
  58. B. Ran and S. G. Lipson, “Comparison between sensitivities of phase and intensity detection in surface plasmon resonance,” Opt. Express 14(12), 5641–5650 (2006). [CrossRef] [PubMed]
  59. H. Raether, Surface Plasmons on Smooth and Rough Surfaces and on Gratings, (Springer-Verlag, Berlin, 1988).
  60. http://www.capovani.com/dp/cat/107/63160/iinfo.cfm?LCl=986&TVTID=0&TItemNo=0&ItemNo=422&q=2
  61. A. Waksberg and J. Wood, “Noise power spectrum characteristics for an HeNe laser operating under various discharge conditions,” Rev. Sci. Instrum. 40(10), 1306–1313 (1969). [CrossRef]
  62. K. G. Baigent, D. A. Shaddock, M. B. Gray, and D. E. McClelland, “Laser stabilisation for the measurement of thermal Noise,” Gen. Relativ. Gravit. 32(3), 399–409 (2000). [CrossRef]
  63. G. Keiser, Optical Communications Essentials, (McGraw-Hill, 2003).
  64. J. M. Liu, Photonic devices, (University press, Cambridge, 2005).
  65. M. W. Wang, F. H. Tsai, and Y. F. Chao, “In situ calibration technique for photoelastic modulator in ellipsometry,” Thin Solid Films 455–456, 78–83 (2004). [CrossRef]
  66. www.luxpop.com
  67. www.bioptics.com

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