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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. 2, Iss. 11 — Nov. 26, 2007
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Optical characterization of extremely small volumes of liquid in sub-micro-holes by simultaneous reflectivity, ellipsometry and spectrometry

M. Holgado, R. Casquel, B. Sánchez, C. Molpeceres, M. Morales, and J. L. Ocaña  »View Author Affiliations


Optics Express, Vol. 15, Issue 20, pp. 13318-13329 (2007)
http://dx.doi.org/10.1364/OE.15.013318


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Abstract

We have fabricated and characterized a lattice of submicron cone-shaped holes on a SiO2/Si wafer. Reflectivity profiles as a function of angle of incidence and polarization, phase shift and spectrometry are obtained for several fluids with different refractive indexes filling the holes. The optical setup allows measuring in the center of a single hole and collecting all data simultaneously, which can be applied for measuring extremely low volumes of fluid (in the order of 0.1 femtolitres) and label-free immunoassays, as it works as a refractive index sensor. A three layer film stack model is defined to perform theoretical calculations.

© 2007 Optical Society of America

1. Introduction

Technology for nano-scale integration is achieving promising results for the development of novel sensors systems to explore its application to important medical, biopharmaceutical and environmental applications such as drug development and immunoassays.

Integrated devices used for sensing purposes are particularly attractive for many reasons: optical or photonic integrated chips can be implemented by using the planar technology that facilitates fabrication employing standard lithographic techniques, which permits mass production and the integration of compact devices on a single-chip for the simultaneous detection of several analytes. In addition, the use of mature silicon-based materials and processes for the fabrication of these sensors adds the important advantage of low cost. However, they need complex optical coupling systems, such as inverted taper and grating couplers [1

1. D. Van Thourhout, W. Bogaerts, P. Dumon, G. Roelkens, J. Van Campenhout, and R. Baets, “Functional Silicon Wire Waveguides,” Proceedings from the conference “Integrated Photonics Research and Application, Nanophotonics, OSA Topical Meetings” (2006).

].

Relevant attempts to implement planar photonic sensors to prove interactions of biomolecular binding (molecular recognition) employ the evanescent field of guided modes in high-index core waveguides within well-known optical structures such as those using waveguide surface plasmon resonance (SPR) [2–4

2. M. Shinn and W. M. Robertson. “Surface-Plasmon like sensor based on surface electromagnetic waves in a photonic band-gap material,” Sens. Actuators B 105, 360–364 (2005). [CrossRef]

], Mach-Zehnder (M-Z) interferometers [5–7

5. B. J. Luff, J. S. Wilkinson, J. Piehler, U. Hollenbach, J. Ingenhoff, and N. Fabricius. “Integrated optical Mach-Zehnder Biosensor,” J. Lightwave Technol. 16, 583 (1998). [CrossRef]

], directional couplers [8

8. B. J. Luff, R. D. Harris, J. S. Wilkinson, R. Wilson, and D. J. Schiffrin. ”Integrated-optical directional coupler biosensor,” Opt. Lett. 21, 618–620 (1996). [CrossRef] [PubMed]

], two-mode waveguide interferometry [9

9. G. H. Cross, A. A. Reeves, S. Brand, J. F. Popplewell, L. L. Peel, M. J. Swann, and N. J. Freeman. “A new quantitative optical biosensor for protein characterization,” Biosens. Bioelectron. 19, 383–390 (2003). [CrossRef] [PubMed]

,10

10. A. Ymeti, J. S. Kanger, J. Greve, P. V. Lambeck, R. Wijn, and R. G. Heideman, “Realization of a multichannel integrated Young interferometer chemical sensor,” Appl. Opt. 42, 5649–5660 (2003). [CrossRef] [PubMed]

], waveguide grating couplers [11

11. M. Nellen, K. Tiefenthaler, and W. Lukosz. “Integrated optical input grating couplers as biochemical sensors,” Sens. Actuators 15, 285–295 (1988). [CrossRef]

], anti resonant reflecting optical waveguides (ARROW) [12

12. S. Campopiano, R. Bernini, L. Zeni, and P. M. Sarro. “Microfluidic sensor based on integrated optical hollow waveguides,” Opt. Lett. 29, 1894–1896 (2004). [CrossRef] [PubMed]

] and photonic crystal waveguides [13

13. N. Skivesen, A. Têtu, M. Kristensen, J. Kjems, L. H. Frandsen, and P. I. Borel. “Photonic crystal waveguide biosensor,” Opt. Express 15, 3169–3176 (2007). [CrossRef] [PubMed]

] and micro-cavities [14

14. E. Chow, A. Grot, L. W. M. Mirkarimi, M. Sigalas, and G. Girolami. “Ultracompact biochemical sensor built with two-dimensional photonic crystal microcavity,” Opt. Lett. 29, 1093–1095 (2004). [CrossRef] [PubMed]

].

The integration between microfluidics and optics is a new emerging research field, with promising high impact applications in the area of optical lab-on-chip devices [15

15. C. Monat, P. Domachuck, and B. J. Eggleton. “Integrated Optofluidics: A new river of light,” Nat. Photonics 1, 106–114 (2007). [CrossRef]

, 16

16. D. Psaltis, S. R. Quake, and C. Yang. “Developing optofluidic technology through the fusion of microfluidics and optics,” Nature 442, 381–386 (2006). [CrossRef] [PubMed]

]. This is the case of tunable Mach-Zehnder interferometers [17

17. C. Grillet, P. Domachuk, V. Táeed, E. Mägi, J. A. Bolger, and B. J. Eggleton. “Compact tunable microfluidic interferometer,” Opt. Express 12, 5440–5447 (2004). [CrossRef] [PubMed]

], photonic crystal [18

18. P. Domachuck, H. C. Nguyen, B. J. Eggleton, M. Straub, and M. Gu. “Microfluidic tunable photonic band-gap device,” Appl. Phys. Lett. 84, 1838–1840 (2004). [CrossRef]

] and ring resonators [19

19. U. Levy, K. Campbell, A. Groisman, S. Mookherjea, and Y. Fainman. “On-chip microfluidic tuning of an optical microring resonator,” Appl. Phys. Lett. 88, 111107–111109 (2006). [CrossRef]

], which have been demonstrated recently. The capability of characterizing optically small volumes of fluid can be applied to improve performance of optofluidic devices, and has clearly potential in bioapplications such as drug delivery [20

20. K. B. Neeves, C. T. Lo, C. P. Foley, W. M. Saltzman, and W. L. Olbricht. “Fabrication and characterization of microfluidic probes for convection enhanced drug delivery,” J. Control. Release 111, 252–262 (2006). [CrossRef] [PubMed]

] and label-free immunoassays.

In this work we demonstrate a sensing system based on sub-micron structures as refractive index sensors with potential application to be used as label free biosensors and in optical evaluation of small volumes of fluid. It is based on the observation of external reflectivity profiles. The structure consists of a 2D-periodic structure working as photonic sensitive cell, measured simultaneously with reflectometry [21

21. V. S-Y. Lin, K. Motesharei, K-P. S. Dancil, M. J. Sailor, and M. R. Ghadir. “A porous silicon-based optical interferometric biosensor,” Science 278, 840 (1997). [CrossRef] [PubMed]

], ellipsometry [22

22. R. M. Ostroff, D. Maul, G. R. Bogart, S. Yang, J. Christian, D. Hopkins, D. Clark, B. Trotter, and G. Moddel. “Fixed polarizer ellipsometry for simple and sensitive detection of thin films generated by specific molecular interactions: applications in immunoassays and DNA sequence detection,” Clin. Chem. 44, 2031–2035 (1998). [PubMed]

, 23

23. H. Arwin. “Ellipsometry on thin organic layers of biological interest: characterization and applications,” Thin Solid Films 377–378, 48–56 (2000). [CrossRef]

] and spectrometry [24

24. O. Levi, M. M. Lee, J. Zhang, V. Lousse, S. R. J. Brueck, S. Fan, and J. S. Harris. “Sensitivity analysis of a photonic crystal structure for index-of-refraction sensing,” Proc. SPIE 6447, 2–9 (2007).

] based techniques. To check out that the device works properly as refractive index sensor, the holes are filled with extremely small volumes of fluids with several refractive indexes. The experimental and theoretical results of the simultaneous reflectivity, ellipsometry and spectrometry measurements ensure sensitive, accurate and reliable optical sensing detection.

The optical sensing system proposed uses a tightly focused beam laser which provides a spot size of 0.9 μm. This allows characterizing optically a single submicrometric hole. As each hole fabricated has a volume in the order of 0.1 femtolitres, we are able to characterize extremely small volumes of fluid. Furthermore, it overcomes the need for using complex systems for light coupling because the sensor evaluation is measured vertically collecting the reflected light of the sub-micron structure, and the sub-micron spot permit to measure in situ of sub-micron size geometries directly on wafers. It also might makes routine screening more cost-effective and suitable to perform hundreds of measurements on a single or several samples.

2. Optical techniques description and sensing system design

The proposed structure has been fabricated using conventional microfabrication technologies, and consists of a triangular lattice of sub-micron cone-shaped holes of 650 nm in top diameter and 396 nm at the bottom, fabricated on a wafer with a 3.01 μm thick silicon oxide layer, over a silicon substrate, and 1.38 μm in depth, with a lattice parameter of 800 nm, over a silicon substrate (Fig. 1).

Fig. 1. SEM micrographs of the sensing structure. (a) Cross section. (b) Top view.

We have measured reflectivity as a function of angle of incidence and polarization, reflectivity as a function of wavelength, as well as phase change of elliptically polarized light.

The experiments have been carried out using a commercial available Therma Wave Optiprobe 5220, which has the advantages of integrating different measurement techniques, performing them simultaneously and allowing to measure in submicrometric areas. Using a laser diode operating at 675 nm as light source, it provides a spot of 0.9 μm in size. This allows measuring the reflectivity of a single submicrometric hole of the fabricated sensing structure. This laser is the source used for the Beam Profile Reflectometry (BPR) and Beam Profile Ellipsometry (BPE) optical techniques. BPR has been described in detailed [25

25. A. Rosencwaig, J. Opsal, D. L. Willenborg, S. M. Kelso, and J. T. Fanton. “Beam profile reflectometry: A new technique for dielectric film measurements,” Appl. Phys. Lett. 60, 1301–1303 (1992). [CrossRef]

, 26

26. J. T. Fanton, J. Opsal, D. L. Willenborg, S. M. Kelso, and A. Rosencwaig. “Multiparameter measurements of thin films using beam-profile reflectometry,” J. Appl. Phys. 73, 7036–7040 (1993). [CrossRef]

, 27

27. J. M. Leng, J. Chen, J. Fanton, M. Senko, K. Ritz, and J. Opsal. “Characterization of titanium nitride TiN films on various substrates using spectrophotometry, beam profile reflectometry, beam profile ellipsometry and spectroscopic beam profile ellipsometry,” Thin Solid Films 313–314, 308–313 (1998). [CrossRef]

], and gives reflected light profiles as a function of angle of incidence from - 64° to 64°, for both s (Rs profile) and p (Rp profile) polarizations, and using a quarter wave plate and a polarizer, BPE technique [27

27. J. M. Leng, J. Chen, J. Fanton, M. Senko, K. Ritz, and J. Opsal. “Characterization of titanium nitride TiN films on various substrates using spectrophotometry, beam profile reflectometry, beam profile ellipsometry and spectroscopic beam profile ellipsometry,” Thin Solid Films 313–314, 308–313 (1998). [CrossRef]

] allows obtaining a result (Rdiff) similar to conventional ellipsometry parameter ∆ (phase shift) [27

27. J. M. Leng, J. Chen, J. Fanton, M. Senko, K. Ritz, and J. Opsal. “Characterization of titanium nitride TiN films on various substrates using spectrophotometry, beam profile reflectometry, beam profile ellipsometry and spectroscopic beam profile ellipsometry,” Thin Solid Films 313–314, 308–313 (1998). [CrossRef]

,28

28. R. M. A. Azzam and N. M. Bashara, Ellipsometry and Polarized Light (North-Holland, Amsterdam, 1977).

]. Moreover, a white light source allows measuring normal incidence reflectivity as a function of wavelength from 470 to 870 nm (Spectrometry), but with larger spot size (2.5 μm).

To perform the measurement, first step is focusing on the centre of a single hole (Fig. 2). A 100x microscope objective and a camera ensure a X-Y positioning precision of 0.1 μm. The autofocus system positions the focusing lens in its proper height. Then BPR and BPE measurement are performed. Consecutively the spectrometry data is obtained. It must be checked out that both sides of Rp and Rs reflectivity profiles (from -64° to 0° and 0° to 64) are symmetrical. Non-symmetry reveal that the beam is not positioned on the center of the hole, and the measurement must be repeated, as it will be described later.

Fig. 2. Proposed sub-micron sensing structure and a schematic representation of the optical techniques employed. When the laser beam is focused in the center of a sub-micro-hole, each half of the reflectivity profiles must be symmetrical.

To estimate the optical response theoretically, a three layers and substrate film stack model is proposed (Fig. 3). The substrate is silicon, the first layer is the non-etched SiO2, the second represents a combination of SiO2 and the fluid inside the holes, and a third layer is an extra layer of fluid which remained and covered the sensing structure. This layer was characterized with optical and confocal microscopy, as well as measured with the optical techniques on the wafer where no holes had been etched, but close to them, evaluating this thickness in the order of tens of nanometers. Furthermore, the theoretical model fitted properly with the experimental results when considering this layer. Refractive index of SiO2, Silicon and fluids indices are well known [29

29. M. J. Weber. Handbook of optical materials (C.R.C. Press L.L.C., 2003).

], and for layer 2 it has been calculated an effective index (neff), as it will be explained later.

Depending on the optical technique considered, parameters of the layer stack change, as seen in Fig. 3. For spectrometry spot size is 2.5 μm, the effective index where the beam is propagating is different from BPR and BPE, with a spot size of 0.9 μm. This must be taken into account when calculating neff. We have considered that the fluid layer is not homogeneous on the top of the submicron structure, due to the fact that the surface tension and the sub-micro-patterned topology of the surface may imply a different thickness on the top of the sub-micron structure [30

30. O. Gang, K. J. Alvine, M. Fukuto, P. S. Pershan, C. T. Black, and B. M. Ocko. “Liquids on topologically nanopatterned surfaces,” Phys. Rev. Lett. 95, 217801-1-4 (2005). [CrossRef] [PubMed]

]. Thus, for spectrometry we have an average thickness holes-no holes estimated in 50 nm, and in BPE/BPR the thickness obtained has been 100nm (see Fig. 3).

Fig. 3. Film stack model for theoretical calculations. (a). Theoretical model applied for BPE and BPR. (b). Theoretical model for Spectrometry. (c) Three layer model film stack.

To estimate neff of layer 2, we have simulated a Gaussian beam propagating trough the holes by finite difference beam propagation method [31

31. R. Scarmozzino, A. Gopinath, R. Pregla, and S. Helfert. “Numerical techniques for Modeling Guided-Wave Photonic Devices,” J. Sel. Top. Quantum Electron. 6, 150–162 (2000). [CrossRef]

]. It has been simulated the same conical structure as fabricated, considering both index for fluids and for silicon oxide. Two different calculations have been performed, one for Spectrometry and other for BPE and BPR, with their corresponding beam spot sizes (Fig. 4). Results are shown in Table 1. It must be noted that for BPR/BPE wavelength corresponds with laser diode wavelength, whereas for Spectrometry it has been consider the wavelength corresponding with the dip that has been analyzed (675 nm in both cases).

Fig. 4. Calculation of neff. (a) Laser spot size of 0.9 μm and field distribution at 1.38 μm in depth for BPE and BPR. (b) White light spot size of 2.5 μm and field distribution. A gausian beam with different width is simulated in both cases. The holes lattice confine the field around the center hole by photonic crystal effect. To ensure a good confinement there must be a minimum of three rings of holes surrounding the centre hole.

Table 1. Results for layer 2 (SiO2-fluid neff calculations). BPE/BPR and Spectrometry neff are different. In BPR/BPE is lower because the fraction of liquid volume is higher.

table-icon
View This Table

Reflectivity profiles Rp, Rs and spectrometry for this three layer model can be easily calculated, using multilayer model equations [25

25. A. Rosencwaig, J. Opsal, D. L. Willenborg, S. M. Kelso, and J. T. Fanton. “Beam profile reflectometry: A new technique for dielectric film measurements,” Appl. Phys. Lett. 60, 1301–1303 (1992). [CrossRef]

, 26

26. J. T. Fanton, J. Opsal, D. L. Willenborg, S. M. Kelso, and A. Rosencwaig. “Multiparameter measurements of thin films using beam-profile reflectometry,” J. Appl. Phys. 73, 7036–7040 (1993). [CrossRef]

, 27

27. J. M. Leng, J. Chen, J. Fanton, M. Senko, K. Ritz, and J. Opsal. “Characterization of titanium nitride TiN films on various substrates using spectrophotometry, beam profile reflectometry, beam profile ellipsometry and spectroscopic beam profile ellipsometry,” Thin Solid Films 313–314, 308–313 (1998). [CrossRef]

, 32

32. E. Hecht and A. Zajac. Optics, (Addisson-Westley Publishing Company, 1974).

]. As a result, we obtain different profiles for each fluid used. BPE is also theoretically calculated using analytical equations [27

27. J. M. Leng, J. Chen, J. Fanton, M. Senko, K. Ritz, and J. Opsal. “Characterization of titanium nitride TiN films on various substrates using spectrophotometry, beam profile reflectometry, beam profile ellipsometry and spectroscopic beam profile ellipsometry,” Thin Solid Films 313–314, 308–313 (1998). [CrossRef]

], and it is demonstrated that Rdiff is roughly similar to ellipsometric parameter ∆ [28

28. R. M. A. Azzam and N. M. Bashara, Ellipsometry and Polarized Light (North-Holland, Amsterdam, 1977).

, 33

33. H. G. Tompkins and E. A. Irene. Handbook of Ellipsometry (William Andrew Inc., 2005). [CrossRef]

]. Both theoretical and experimental data are obtained and compared.

2.1. Experimental liquid filling procedure and measurement process

It was applied both hydrostatic pressure on the sample and temperature on the fluid to ensure the fluid had totally filled the hole. Then, the samples were optically characterized, repeating the measurements 5 times to ensure repetitiveness, and the fluid was removed by heating up to 600 ° C during 4 hours. Finally, the sample was re-characterized to check out that the measurement at the end of the process was exactly the same than the reference data. The whole process was repeated for each fluid.

3. Results and discussion

3.1 BPR results

Figure 5 shows calculated Rs and Rp spectra for the different fluids. As it can be seen in the figures, as neff increases when introducing fluids dips and peaks position move to higher absolute value of reflected angle.

Figure 6 shows the experimental BPR spectra for both s and p polarizations with different fluids inside the holes. Dips and peaks move to a higher absolute value of angle of incidence as the refractive index of the fluids increases. The reflectivity of light normally incident on the sample also gets reduced. .The quasi-symmetrical shape of the spectra ensures that the measurement has been done just in the centre of a hole, as the reflected signal is measured from -64° to 64°; otherwise both sides of the spectra would be drastically different. We have chosen dip positioned between 20 and 30 degrees to compare. Figure 7 shows theoretical and experimental dip position for each polarization as a function of the introduced fluid.

Fig. 5. Theoretical BPR Spectra profiles. (a) s-polarization. (b) p-polarization
Fig. 6. BPR experimental spectra profiles. (a) s-polarized. (b) p-polarized.

We have estimated the detection limit using Eq. (1), in which θresolution is the minimum angle variation which can be detected, and the derivative has been calculated using the linear fit from the experimental data, shown in Fig. 7. In the optical setup used for the accomplishment of the measurements the angle resolution depend on the resolution and size of the linear array detector for each polarization, which it is a θresolution=0.5 °. With this data, ∆nmin= 0.005 (s-polarization) and 0.008 (p-polarization). This resolution can be improved by using a setup with a higher resolution. The current technology offer linear arrays integrated in hundreds of detectors per inch. Thus, ∆nmin may be reduced to values in the order of 10-5 R.I.U. with a θresolution=0.01°, which is easily feasible.

Fig. 7. Dip position experimental and theoretical. (a) s polarization. (b) p polarization.
Δnmin=θresolutionxdnfluiddθdipposition
(1)

3.2 BPE

We have measured and theoretically calculated Rdiff as a function of the refractive index of the filling fluid. Figure 8 shows theoretical curve compared with experimental data. It is also shown theoretical phase shift calculated for incident angle= 26°, which is roughly similar to Rdiff curve. To estimate the detection limit for this technique, we have used Eq. (2). The value of the derivative depends on the range of values chosen. We have calculated the slope of the curve from n = 1.33 to 1.38, where it is similar to a linear function. With this data, ∆nmin= 10-6 R.I.U by using a setup with a detector with a Rdiff resolution of 1 μV.

Δnmin=RdiffresolutionxdnfluiddRdiff
(2)
Fig. 8. (a). Theoretical and experimental data for Rdiff. (b) Ellipsometric theoretical ∆ for angle of incidence of 26°.

4. Spectrometry results

Figure 9 shows both theoretical and experimental reflectivity profiles for the different fluids used. The position of dips and peaks moves to a higher value of wavelength as the refractive index of the introduced fluid increases. We have used dip positioned between 690 and 710 nm to compare. Figure 10 shows dip position for theoretical and experimental data.

Fig. 9. Spectrometry profiles. (a) Experimental. (b) Theoretical
Fig. 10. Dip position for VIS. Experimental, theoretical and linearly fitted data.

In order to estimate detection limit with this technique, we have used Eq. (3), in which λresolution is the wavelength resolution of the measurement setup, and the derivative is calculated using the linear fit for the experimental data. The detection limit with this optical technique significantly depends on the spectrum analyzer resolution. In our optical setup the spectrum resolution is 2 nm, which is quite poor, and therefore the calculated limit detection is 0.02 R.I.U. This resolution can be improved drastically with higher spectrum analyzer resolution. Several technologies nowadays easily permit to obtain spectra resolution in the order of 0.02 nm or even better. As a result, the estimated limit detection may be reduced to values in the order of 10-5 R.I.U.

Δnmin=λresolutionxdnfluiddλdipposition
(3)

5. Conclusions

In this work we have described a new concept of high sensitive system based on inexpensive devices. It has been demonstrated that the proposed optical sensing system works as a refractive index sensor, and therefore has clearly potential application in chemical, biochemical, pharmaceutical and clinical chemistry sectors as the index of refraction of the common biomolecular layers is in the range of indexes that have been measured (1.329 to 1.420). Preliminary simulations indicate that a biological monolayer on the holes surfaces will be easily detected. The simultaneous use of three different techniques makes the system much more reliable, and removes ambiguities. The model proposed for theoretical calculations has performed properly for the three techniques. Moreover, we have demonstrated the capability of measuring extremely small small-volume of fluid (of the order of 0.1 femtolitres per hole). The fabrication of the sensing structure has been based on well-known CMOS techniques, ensuring low cost and fabrication reliability. Finally, the possibility of integrating hundred of sensing structures per wafer may allow performing multi-single or multi-parameter measurements with high throughput and monitoring directly on wafers.

Further research could include improvement of the optical setup, such as high resolution spectrometer and linear arrays as well as optimizing design for different submicron optofluidic structures. These improvements may allow achieving detection limits around the level of 10-6 / 10-7 R.I.U., which is competitive compared with nowadays state of the art [34

34. R. Ince and R. Narayanaswamy, “Analysis of the performance of interferometry, surface plasmon resonance and luminescence as biosensors and chemosensors. Review,” Anal. Chim. Acta 569, 1–20 (2006). [CrossRef]

].

Acknowledgment

We acknowledge useful and valuable discussions with Prof. J. Sanchez-Dehesa, Dr. L. Lechuga and Dr. C. A. Barrios. We would also thank the Nanophotonics Technology Center-UPV and I. Rodriguez at the Centro Tecnológico de Ondas – UPV for the support in the device fabrication. This work has been partially founded by FPU program of the Universidad Politécnica de Madrid.

References and links

1.

D. Van Thourhout, W. Bogaerts, P. Dumon, G. Roelkens, J. Van Campenhout, and R. Baets, “Functional Silicon Wire Waveguides,” Proceedings from the conference “Integrated Photonics Research and Application, Nanophotonics, OSA Topical Meetings” (2006).

2.

M. Shinn and W. M. Robertson. “Surface-Plasmon like sensor based on surface electromagnetic waves in a photonic band-gap material,” Sens. Actuators B 105, 360–364 (2005). [CrossRef]

3.

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

4.

J. Homola, S. Yee, and G. Gauglitz “Surface plasmon resonance sensors: review,” Sens. Actuators B 54, 3–15 (1999). [CrossRef]

5.

B. J. Luff, J. S. Wilkinson, J. Piehler, U. Hollenbach, J. Ingenhoff, and N. Fabricius. “Integrated optical Mach-Zehnder Biosensor,” J. Lightwave Technol. 16, 583 (1998). [CrossRef]

6.

F. Prieto, B. Sepúlveda, A. Calle, A. Llobera, C. Domínguez, A. Abad, A. Montoya, and L. M. Lechuga. “An integrated optical interferometric nanodevice based on silicon technology for biosensor applications,” Nanotechnology 14, 907–912 (2003). [CrossRef]

7.

D. H. Luo, R. A. Levy, Y. F. Hor, J. F. Federici, and R. M. Pafchek. “An integrated photonic sensor for in situ monitoring of hazardous organics,” Sens. actuators B 92, 121–126 (2003). [CrossRef]

8.

B. J. Luff, R. D. Harris, J. S. Wilkinson, R. Wilson, and D. J. Schiffrin. ”Integrated-optical directional coupler biosensor,” Opt. Lett. 21, 618–620 (1996). [CrossRef] [PubMed]

9.

G. H. Cross, A. A. Reeves, S. Brand, J. F. Popplewell, L. L. Peel, M. J. Swann, and N. J. Freeman. “A new quantitative optical biosensor for protein characterization,” Biosens. Bioelectron. 19, 383–390 (2003). [CrossRef] [PubMed]

10.

A. Ymeti, J. S. Kanger, J. Greve, P. V. Lambeck, R. Wijn, and R. G. Heideman, “Realization of a multichannel integrated Young interferometer chemical sensor,” Appl. Opt. 42, 5649–5660 (2003). [CrossRef] [PubMed]

11.

M. Nellen, K. Tiefenthaler, and W. Lukosz. “Integrated optical input grating couplers as biochemical sensors,” Sens. Actuators 15, 285–295 (1988). [CrossRef]

12.

S. Campopiano, R. Bernini, L. Zeni, and P. M. Sarro. “Microfluidic sensor based on integrated optical hollow waveguides,” Opt. Lett. 29, 1894–1896 (2004). [CrossRef] [PubMed]

13.

N. Skivesen, A. Têtu, M. Kristensen, J. Kjems, L. H. Frandsen, and P. I. Borel. “Photonic crystal waveguide biosensor,” Opt. Express 15, 3169–3176 (2007). [CrossRef] [PubMed]

14.

E. Chow, A. Grot, L. W. M. Mirkarimi, M. Sigalas, and G. Girolami. “Ultracompact biochemical sensor built with two-dimensional photonic crystal microcavity,” Opt. Lett. 29, 1093–1095 (2004). [CrossRef] [PubMed]

15.

C. Monat, P. Domachuck, and B. J. Eggleton. “Integrated Optofluidics: A new river of light,” Nat. Photonics 1, 106–114 (2007). [CrossRef]

16.

D. Psaltis, S. R. Quake, and C. Yang. “Developing optofluidic technology through the fusion of microfluidics and optics,” Nature 442, 381–386 (2006). [CrossRef] [PubMed]

17.

C. Grillet, P. Domachuk, V. Táeed, E. Mägi, J. A. Bolger, and B. J. Eggleton. “Compact tunable microfluidic interferometer,” Opt. Express 12, 5440–5447 (2004). [CrossRef] [PubMed]

18.

P. Domachuck, H. C. Nguyen, B. J. Eggleton, M. Straub, and M. Gu. “Microfluidic tunable photonic band-gap device,” Appl. Phys. Lett. 84, 1838–1840 (2004). [CrossRef]

19.

U. Levy, K. Campbell, A. Groisman, S. Mookherjea, and Y. Fainman. “On-chip microfluidic tuning of an optical microring resonator,” Appl. Phys. Lett. 88, 111107–111109 (2006). [CrossRef]

20.

K. B. Neeves, C. T. Lo, C. P. Foley, W. M. Saltzman, and W. L. Olbricht. “Fabrication and characterization of microfluidic probes for convection enhanced drug delivery,” J. Control. Release 111, 252–262 (2006). [CrossRef] [PubMed]

21.

V. S-Y. Lin, K. Motesharei, K-P. S. Dancil, M. J. Sailor, and M. R. Ghadir. “A porous silicon-based optical interferometric biosensor,” Science 278, 840 (1997). [CrossRef] [PubMed]

22.

R. M. Ostroff, D. Maul, G. R. Bogart, S. Yang, J. Christian, D. Hopkins, D. Clark, B. Trotter, and G. Moddel. “Fixed polarizer ellipsometry for simple and sensitive detection of thin films generated by specific molecular interactions: applications in immunoassays and DNA sequence detection,” Clin. Chem. 44, 2031–2035 (1998). [PubMed]

23.

H. Arwin. “Ellipsometry on thin organic layers of biological interest: characterization and applications,” Thin Solid Films 377–378, 48–56 (2000). [CrossRef]

24.

O. Levi, M. M. Lee, J. Zhang, V. Lousse, S. R. J. Brueck, S. Fan, and J. S. Harris. “Sensitivity analysis of a photonic crystal structure for index-of-refraction sensing,” Proc. SPIE 6447, 2–9 (2007).

25.

A. Rosencwaig, J. Opsal, D. L. Willenborg, S. M. Kelso, and J. T. Fanton. “Beam profile reflectometry: A new technique for dielectric film measurements,” Appl. Phys. Lett. 60, 1301–1303 (1992). [CrossRef]

26.

J. T. Fanton, J. Opsal, D. L. Willenborg, S. M. Kelso, and A. Rosencwaig. “Multiparameter measurements of thin films using beam-profile reflectometry,” J. Appl. Phys. 73, 7036–7040 (1993). [CrossRef]

27.

J. M. Leng, J. Chen, J. Fanton, M. Senko, K. Ritz, and J. Opsal. “Characterization of titanium nitride TiN films on various substrates using spectrophotometry, beam profile reflectometry, beam profile ellipsometry and spectroscopic beam profile ellipsometry,” Thin Solid Films 313–314, 308–313 (1998). [CrossRef]

28.

R. M. A. Azzam and N. M. Bashara, Ellipsometry and Polarized Light (North-Holland, Amsterdam, 1977).

29.

M. J. Weber. Handbook of optical materials (C.R.C. Press L.L.C., 2003).

30.

O. Gang, K. J. Alvine, M. Fukuto, P. S. Pershan, C. T. Black, and B. M. Ocko. “Liquids on topologically nanopatterned surfaces,” Phys. Rev. Lett. 95, 217801-1-4 (2005). [CrossRef] [PubMed]

31.

R. Scarmozzino, A. Gopinath, R. Pregla, and S. Helfert. “Numerical techniques for Modeling Guided-Wave Photonic Devices,” J. Sel. Top. Quantum Electron. 6, 150–162 (2000). [CrossRef]

32.

E. Hecht and A. Zajac. Optics, (Addisson-Westley Publishing Company, 1974).

33.

H. G. Tompkins and E. A. Irene. Handbook of Ellipsometry (William Andrew Inc., 2005). [CrossRef]

34.

R. Ince and R. Narayanaswamy, “Analysis of the performance of interferometry, surface plasmon resonance and luminescence as biosensors and chemosensors. Review,” Anal. Chim. Acta 569, 1–20 (2006). [CrossRef]

OCIS Codes
(120.2130) Instrumentation, measurement, and metrology : Ellipsometry and polarimetry
(130.0130) Integrated optics : Integrated optics
(130.6010) Integrated optics : Sensors
(310.6860) Thin films : Thin films, optical properties

ToC Category:
Instrumentation, Measurement, and Metrology

History
Original Manuscript: June 11, 2007
Revised Manuscript: July 31, 2007
Manuscript Accepted: August 1, 2007
Published: September 28, 2007

Virtual Issues
Vol. 2, Iss. 11 Virtual Journal for Biomedical Optics

Citation
M. Holgado, R. Casquel, B. Sánchez, C. Molpeceres, M. Morales, and J. L. Ocaña, "Optical characterization of extremely small volumes of liquid in sub-micro-holes by simultaneous reflectivity, ellipsometry and spectrometry," Opt. Express 15, 13318-13329 (2007)
http://www.opticsinfobase.org/vjbo/abstract.cfm?URI=oe-15-20-13318


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References

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  18. P. Domachuck, H. C. Nguyen, B. J. Eggleton, M. Straub, and M. Gu. "Microfluidic tunable photonic band-gap device," Appl. Phys. Lett. 84, 1838-1840 (2004). [CrossRef]
  19. U. Levy, K. Campbell, A. Groisman, S. Mookherjea, and Y. Fainman. "On-chip microfluidic tuning of an optical microring resonator," Appl. Phys. Lett. 88, 111107-111109 (2006). [CrossRef]
  20. K. B. Neeves, C. T. Lo, C. P. Foley, W. M. Saltzman, and W. L. Olbricht. "Fabrication and characterization of microfluidic probes for convection enhanced drug delivery," J. Control. Release 111,252-262 (2006). [CrossRef] [PubMed]
  21. V. S-Y. Lin, K. Motesharei, K-P. S. Dancil, M. J. Sailor, and M. R. Ghadir. "A porous silicon-based optical interferometric biosensor," Science 278, 840 (1997). [CrossRef] [PubMed]
  22. R. M. Ostroff, D. Maul. G. R. Bogart, S. Yang, J. Christian, D. Hopkins, D. Clark, B. Trotter, and G. Moddel. "Fixed polarizer ellipsometry for simple and sensitive detection of thin films generated by specific molecular interactions: applications in immunoassays and DNA sequence detection," Clin. Chem. 44, 2031-2035 (1998). [PubMed]
  23. H. Arwin. "Ellipsometry on thin organic layers of biological interest: characterization and applications," Thin Solid Films 377-378, 48-56 (2000). [CrossRef]
  24. O. Levi, M. M. Lee, J. Zhang, V. Lousse, S. R. J. Brueck, S. Fan, J. S. Harris. "Sensitivity analysis of a photonic crystal structure for index-of-refraction sensing," Proc. SPIE 6447, 2-9 (2007).
  25. A. Rosencwaig, J. Opsal, D. L. Willenborg, S. M. Kelso and J. T. Fanton. "Beam profile reflectometry: A new technique for dielectric film measurements," Appl. Phys. Lett. 60, 1301-1303 (1992). [CrossRef]
  26. J. T. Fanton, J. Opsal, D. L. Willenborg, S. M. Kelso, and A. Rosencwaig. "Multiparameter measurements of thin films using beam-profile reflectometry," J. Appl. Phys. 73, 7036-7040 (1993). [CrossRef]
  27. J. M. Leng, J. Chen, J. Fanton, M. Senko, K. Ritz, and J. Opsal. "Characterization of titanium nitride TiN films on various substrates using spectrophotometry, beam profile reflectometry, beam profile ellipsometry and spectroscopic beam profile ellipsometry," Thin Solid Films 313-314, 308-313 (1998). [CrossRef]
  28. R. M. A. Azzam and N. M. Bashara, Ellipsometry and Polarized Light (North-Holland, Amsterdam, 1977).
  29. M. J. Weber. Handbook of optical materials (C.R.C. Press L.L.C., 2003).
  30. O. Gang, K. J. Alvine, M. Fukuto, P. S. Pershan, C. T. Black, and B. M. Ocko. "Liquids on topologically nanopatterned surfaces," Phys. Rev. Lett. 95, 217801-1-4 (2005). [CrossRef] [PubMed]
  31. R. Scarmozzino, A. Gopinath, R. Pregla, and S. Helfert. "Numerical techniques for Modeling Guided-Wave Photonic Devices," J. Sel. Top. Quantum Electron. 6, 150-162 (2000). [CrossRef]
  32. E. Hecht and A. Zajac. Optics, (Addisson-Westley Publishing Company, 1974).
  33. H. G. Tompkins and E. A. Irene. Handbook of Ellipsometry (William Andrew Inc., 2005). [CrossRef]
  34. R. Ince and R. Narayanaswamy, "Analysis of the performance of interferometry, surface plasmon resonance and luminescence as biosensors and chemosensors. Review," Anal. Chim. Acta 569,1-20 (2006). [CrossRef]

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