Abstract

In this work, we demonstrate in vitro detection of glucose by means of a lab-on-chip absorption spectroscopy approach. This optical method allows label-free and specific detection of glucose. We show glucose detection in aqueous glucose solutions in the clinically relevant concentration range with a silicon-based optofluidic chip. The sample interface is a spiral-shaped rib waveguide integrated on a silicon-on-insulator (SOI) photonic chip. This SOI chip is combined with micro-fluidics in poly(dimethylsiloxane) (PDMS). We apply aqueous glucose solutions with different concentrations and monitor continuously how the transmission spectrum changes due to glucose. Based on these measurements, we derived a linear regression model, to relate the measured glucose spectra with concentration with an error-of-fitting of only 1.14 mM. This paper explains the challenges involved and discusses the optimal configuration for on-chip evanescent absorption spectroscopy. In addition, the prospects for using this sensor for glucose detection in complex physiological media (e.g. serum) is briefly discussed.

© 2014 Optical Society of America

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2013 (5)

2012 (4)

2011 (5)

A. L. Washburn and R. C. Bailey, “Photonics-on-a-Chip: Recent advances in integrated waveguides as enabling detection elements for real-world, Lab-on-a-Chip biosensing applications,” Analyist136, 227–236 (2011).
[CrossRef]

W. Bogaerts and S. Selvaraja, “Compact single-mode silicon hybrid rib/strip waveguide with adiabatic bends,” IEEE Photon. J.3(3), 422–432 (2011)
[CrossRef]

J. Kasberger, T. Fromherz, A. Saeed, and B. Jakoby, “Miniaturized integrated evanescent field IR-absorption sensor: Design and experimental verification with deteriorated lubrication oil,” Vib. Spectrosc.56, 129–135 (2011).
[CrossRef]

C. Kopp, S. Bernabe, B. B. Bakir, J. M. Fedeli, R. Orobtchouk, F. Schrank, H. Porte, L. Zimmermann, and T. Tekin, “Silicon photonic circuits: on-CMOS integration, fiber optical coupling, and packaging,” IEEE J. Sel. Top. Quantum Electron.17(3), 498–509 (2011).
[CrossRef]

Z. Xia, A. A. Aftekhar, M. Soltani, B. Momeni, Q. Li, M. Chamanzar, S. Yegnanarayanan, and A. Adibi, “High resolution on-chip spectroscopy based on miniaturized microdonut resonators,” Opt. Express19(13), 12356–12364 (2011)
[CrossRef] [PubMed]

2010 (2)

W. Bogaerts, S. Selvaraja, P. Dumon, J. Brouckaert, K. De Vos, D. Van Thourhout, and R. Baets, “Silicon-on-insulator spectral filters fabricated with CMOS technology,” IEEE J. Sel. Top. Quantum Electron.16(1), 33–44 (2010)
[CrossRef]

F. Morichetti, A. Canciamilla, C. Ferrari, M. Torregiani, A. Melloni, and M. Martinelli, “Roughness induced backscattering in optical silicon waveguides,” Phys. Rev. Lett.104(3), 033902 (2010)
[CrossRef] [PubMed]

2009 (2)

2008 (1)

2007 (1)

2006 (1)

A. Densmore, D.-X. Xu, P. Waldron, S. Janz, P. Cheben, J. Lapointe, A. Delâge, B. Lamontagne, J. H. Schmid, and E. Post, “A silicon-on-insulator photonic wire based evanescent field sensor,” IEEE Photon. Technol. Lett.18(23), 2520–2522 (2006)
[CrossRef]

2005 (1)

C. Feng, C. Keong, Y. Hsueh, Y. Wang, and H. Sue, “Modeling of long-term creep behavior of structural epoxy adhesives,” Int. J. Adhes. Adhes.25(5), 427–436 (2005)
[CrossRef]

2004 (2)

2000 (2)

C. Z. Tan and J. Arndt, “Temperature dependence of refractive index of glassy SiO2 in the infrared wavelength range,” J. Phys. Chem. Solids61(8), 1315–1320 (2000)
[CrossRef]

J. C. McDonald, D. C. Duffy, J. R. Anderson, D. T. Chiu, H. Wu, O. J. Schueller, and G. M. Whitesides, “Fabrication of microfluidics systems in poly(dimethylsiloxane),” Electrophoresis21(1), 27–40 (2000)
[CrossRef] [PubMed]

1998 (2)

A. H. Harvey, J. S. Gallagher, and J. L. Sengers, “Revised formulation for the refractive index of water and steam as a function of wavelength, temperature and density,” J. Phys. Chem. Ref. Data27(4), 761–774 (1998)
[CrossRef]

K. H. Hazen, M. A. Arnold, and G. W. Small, “Measurement of Glucose and Other Analytes in Undiluted Human Serum with Near-Infrared Transmission Spectroscopy,” Anal. Chim. Acta.371(1–2), 255–267 (1998)
[CrossRef]

1993 (1)

L. A. Marquardt, M. A. Arnold, and G. W. Small, “Near-infrared spectroscopic measurement of glucose in a protein matrix,” Anal. Chem.65(22), 3271–3278, (1993)
[CrossRef] [PubMed]

1980 (1)

H. H. Li, “Refractive index of silicon and germanium and its wavelength and temperature derivatives,” J. Phys. Chem. Ref. Data9(3), 561–658 (1980)
[CrossRef]

Adibi, A.

Aftekhar, A. A.

Agarwal, A.

Amerov, A.

Anderson, J. R.

J. C. McDonald, D. C. Duffy, J. R. Anderson, D. T. Chiu, H. Wu, O. J. Schueller, and G. M. Whitesides, “Fabrication of microfluidics systems in poly(dimethylsiloxane),” Electrophoresis21(1), 27–40 (2000)
[CrossRef] [PubMed]

Arndt, J.

C. Z. Tan and J. Arndt, “Temperature dependence of refractive index of glassy SiO2 in the infrared wavelength range,” J. Phys. Chem. Solids61(8), 1315–1320 (2000)
[CrossRef]

Arnold, M.

Arnold, M. A.

K. H. Hazen, M. A. Arnold, and G. W. Small, “Measurement of Glucose and Other Analytes in Undiluted Human Serum with Near-Infrared Transmission Spectroscopy,” Anal. Chim. Acta.371(1–2), 255–267 (1998)
[CrossRef]

L. A. Marquardt, M. A. Arnold, and G. W. Small, “Near-infrared spectroscopic measurement of glucose in a protein matrix,” Anal. Chem.65(22), 3271–3278, (1993)
[CrossRef] [PubMed]

Baets, R.

E.M.P. Ryckeboer, A. Gassenq, M. Muneeb, N. Hattasan, S. Pathak, L. Cerutti, J.-B. Rodriguez, E. Tournie, W. Bogaerts, R. Baets, and G. Roelkens, “Silicon-on-insulator spectrometers with integrated GaInAsSb photodiodes for wide-band spectroscopy from 1510 to 2300 nm,” Opt. Express21(5), 6101–6108 (2013)
[CrossRef] [PubMed]

W. Bogaerts, S. Selvaraja, P. Dumon, J. Brouckaert, K. De Vos, D. Van Thourhout, and R. Baets, “Silicon-on-insulator spectral filters fabricated with CMOS technology,” IEEE J. Sel. Top. Quantum Electron.16(1), 33–44 (2010)
[CrossRef]

S. Selvaraja, P. Jaenen, W. Bogaerts, D. Van Thourhout, P. Dumon, and R. Baets, “Fabrication of photonic wire and crystal circuits in silicon-on-insulator using 193-nm optical lithography,” J. Lightwave Technol.27(18), 4076–7083 (2009)
[CrossRef]

D. Vermeulen, K. Van Acoleyen, S. Ghosh, S. Selvaraja, W. De Cort, N. Yebo, E. Hallynck, K. De Vos, P. Debackere, P. Dumon, W. Bogaerts, D. Van Thourhout, and R. Baets, “Efficient tapering to the fundamental quasi-TM mode in asymmetrical waveguides,” in European Conference on Integrated Optics (ECIO, 2010), paper WeP16.

Bailey, R. C.

A. L. Washburn and R. C. Bailey, “Photonics-on-a-Chip: Recent advances in integrated waveguides as enabling detection elements for real-world, Lab-on-a-Chip biosensing applications,” Analyist136, 227–236 (2011).
[CrossRef]

Bakir, B. B.

C. Kopp, S. Bernabe, B. B. Bakir, J. M. Fedeli, R. Orobtchouk, F. Schrank, H. Porte, L. Zimmermann, and T. Tekin, “Silicon photonic circuits: on-CMOS integration, fiber optical coupling, and packaging,” IEEE J. Sel. Top. Quantum Electron.17(3), 498–509 (2011).
[CrossRef]

Bernabe, S.

C. Kopp, S. Bernabe, B. B. Bakir, J. M. Fedeli, R. Orobtchouk, F. Schrank, H. Porte, L. Zimmermann, and T. Tekin, “Silicon photonic circuits: on-CMOS integration, fiber optical coupling, and packaging,” IEEE J. Sel. Top. Quantum Electron.17(3), 498–509 (2011).
[CrossRef]

Bock, P. J.

Bogaerts, W.

E.M.P. Ryckeboer, A. Gassenq, M. Muneeb, N. Hattasan, S. Pathak, L. Cerutti, J.-B. Rodriguez, E. Tournie, W. Bogaerts, R. Baets, and G. Roelkens, “Silicon-on-insulator spectrometers with integrated GaInAsSb photodiodes for wide-band spectroscopy from 1510 to 2300 nm,” Opt. Express21(5), 6101–6108 (2013)
[CrossRef] [PubMed]

W. Bogaerts and S. Selvaraja, “Compact single-mode silicon hybrid rib/strip waveguide with adiabatic bends,” IEEE Photon. J.3(3), 422–432 (2011)
[CrossRef]

W. Bogaerts, S. Selvaraja, P. Dumon, J. Brouckaert, K. De Vos, D. Van Thourhout, and R. Baets, “Silicon-on-insulator spectral filters fabricated with CMOS technology,” IEEE J. Sel. Top. Quantum Electron.16(1), 33–44 (2010)
[CrossRef]

S. Selvaraja, P. Jaenen, W. Bogaerts, D. Van Thourhout, P. Dumon, and R. Baets, “Fabrication of photonic wire and crystal circuits in silicon-on-insulator using 193-nm optical lithography,” J. Lightwave Technol.27(18), 4076–7083 (2009)
[CrossRef]

D. Vermeulen, K. Van Acoleyen, S. Ghosh, S. Selvaraja, W. De Cort, N. Yebo, E. Hallynck, K. De Vos, P. Debackere, P. Dumon, W. Bogaerts, D. Van Thourhout, and R. Baets, “Efficient tapering to the fundamental quasi-TM mode in asymmetrical waveguides,” in European Conference on Integrated Optics (ECIO, 2010), paper WeP16.

Bordel, D.

Brandily, M.

J. Charrier, M. Brandily, H. Lhermite, K. Michel, B. Bureau, F. Verger, and V. Nazabal, “Evanescent wave optical micro-sensor based on chalcogenide glass,” Sens. Actuator B-Chem.173, 468–476 (2012).
[CrossRef]

Brouckaert, J.

W. Bogaerts, S. Selvaraja, P. Dumon, J. Brouckaert, K. De Vos, D. Van Thourhout, and R. Baets, “Silicon-on-insulator spectral filters fabricated with CMOS technology,” IEEE J. Sel. Top. Quantum Electron.16(1), 33–44 (2010)
[CrossRef]

Bureau, B.

J. Charrier, M. Brandily, H. Lhermite, K. Michel, B. Bureau, F. Verger, and V. Nazabal, “Evanescent wave optical micro-sensor based on chalcogenide glass,” Sens. Actuator B-Chem.173, 468–476 (2012).
[CrossRef]

Calvo, M. L.

Canciamilla, A.

F. Morichetti, A. Canciamilla, C. Ferrari, M. Torregiani, A. Melloni, and M. Martinelli, “Roughness induced backscattering in optical silicon waveguides,” Phys. Rev. Lett.104(3), 033902 (2010)
[CrossRef] [PubMed]

Carlie, N.

Cerutti, L.

Chamanzar, M.

Charrier, J.

J. Charrier, M. Brandily, H. Lhermite, K. Michel, B. Bureau, F. Verger, and V. Nazabal, “Evanescent wave optical micro-sensor based on chalcogenide glass,” Sens. Actuator B-Chem.173, 468–476 (2012).
[CrossRef]

Cheben, P.

A. V. Velasco, P. Cheben, P. J. Bock, A. Delage, J. H. Schmid, J. Lapointe, S. Janz, M. L. Calvo, D. Xu, M. Florjanczyk, and M. Vachon, “High-resolution Fourier-transform spectrometer chipwith microphotonic silicon spiral waveguides,” Opt. Lett.38(5), 706–708 (2013)
[CrossRef] [PubMed]

A. Densmore, D.-X. Xu, P. Waldron, S. Janz, P. Cheben, J. Lapointe, A. Delâge, B. Lamontagne, J. H. Schmid, and E. Post, “A silicon-on-insulator photonic wire based evanescent field sensor,” IEEE Photon. Technol. Lett.18(23), 2520–2522 (2006)
[CrossRef]

Chen, J.

Chen, L.

Chiu, D. T.

J. C. McDonald, D. C. Duffy, J. R. Anderson, D. T. Chiu, H. Wu, O. J. Schueller, and G. M. Whitesides, “Fabrication of microfluidics systems in poly(dimethylsiloxane),” Electrophoresis21(1), 27–40 (2000)
[CrossRef] [PubMed]

Choi, D.

Ciriaco, V.

R. Feldman and V. Ciriaco, Applied Probability and Stochastic Processes (Springer, 2010)
[CrossRef]

De Cort, W.

D. Vermeulen, K. Van Acoleyen, S. Ghosh, S. Selvaraja, W. De Cort, N. Yebo, E. Hallynck, K. De Vos, P. Debackere, P. Dumon, W. Bogaerts, D. Van Thourhout, and R. Baets, “Efficient tapering to the fundamental quasi-TM mode in asymmetrical waveguides,” in European Conference on Integrated Optics (ECIO, 2010), paper WeP16.

De Vos, K.

W. Bogaerts, S. Selvaraja, P. Dumon, J. Brouckaert, K. De Vos, D. Van Thourhout, and R. Baets, “Silicon-on-insulator spectral filters fabricated with CMOS technology,” IEEE J. Sel. Top. Quantum Electron.16(1), 33–44 (2010)
[CrossRef]

D. Vermeulen, K. Van Acoleyen, S. Ghosh, S. Selvaraja, W. De Cort, N. Yebo, E. Hallynck, K. De Vos, P. Debackere, P. Dumon, W. Bogaerts, D. Van Thourhout, and R. Baets, “Efficient tapering to the fundamental quasi-TM mode in asymmetrical waveguides,” in European Conference on Integrated Optics (ECIO, 2010), paper WeP16.

Debackere, P.

D. Vermeulen, K. Van Acoleyen, S. Ghosh, S. Selvaraja, W. De Cort, N. Yebo, E. Hallynck, K. De Vos, P. Debackere, P. Dumon, W. Bogaerts, D. Van Thourhout, and R. Baets, “Efficient tapering to the fundamental quasi-TM mode in asymmetrical waveguides,” in European Conference on Integrated Optics (ECIO, 2010), paper WeP16.

Debbarma, S.

Delage, A.

Delâge, A.

A. Densmore, D.-X. Xu, P. Waldron, S. Janz, P. Cheben, J. Lapointe, A. Delâge, B. Lamontagne, J. H. Schmid, and E. Post, “A silicon-on-insulator photonic wire based evanescent field sensor,” IEEE Photon. Technol. Lett.18(23), 2520–2522 (2006)
[CrossRef]

Delanghe, J.

S. Sharma, M. Goodarzi, J. Delanghe, H. Ramon, and W. Saeys, “Using experimental data designs and multivariate modelling to assess the effect of glycated serum protein concentration on glucose prediction from near infrared spectra of human serum,” Appl. Spectrosc. (accepted).

Densmore, A.

A. Densmore, D.-X. Xu, P. Waldron, S. Janz, P. Cheben, J. Lapointe, A. Delâge, B. Lamontagne, J. H. Schmid, and E. Post, “A silicon-on-insulator photonic wire based evanescent field sensor,” IEEE Photon. Technol. Lett.18(23), 2520–2522 (2006)
[CrossRef]

DeVries, J.

M. Langendam, Y. Luijf, L. Hooft, J. DeVries, A. Mudde, and R. Scholten, “Continuous glucose monitoring systems for type I diabetes mellitus (Review),” The Cochrane Library2, (John Wiley & Sons, 2012)

Duan, G.

Duffy, D. C.

J. C. McDonald, D. C. Duffy, J. R. Anderson, D. T. Chiu, H. Wu, O. J. Schueller, and G. M. Whitesides, “Fabrication of microfluidics systems in poly(dimethylsiloxane),” Electrophoresis21(1), 27–40 (2000)
[CrossRef] [PubMed]

Dumon, P.

W. Bogaerts, S. Selvaraja, P. Dumon, J. Brouckaert, K. De Vos, D. Van Thourhout, and R. Baets, “Silicon-on-insulator spectral filters fabricated with CMOS technology,” IEEE J. Sel. Top. Quantum Electron.16(1), 33–44 (2010)
[CrossRef]

S. Selvaraja, P. Jaenen, W. Bogaerts, D. Van Thourhout, P. Dumon, and R. Baets, “Fabrication of photonic wire and crystal circuits in silicon-on-insulator using 193-nm optical lithography,” J. Lightwave Technol.27(18), 4076–7083 (2009)
[CrossRef]

D. Vermeulen, K. Van Acoleyen, S. Ghosh, S. Selvaraja, W. De Cort, N. Yebo, E. Hallynck, K. De Vos, P. Debackere, P. Dumon, W. Bogaerts, D. Van Thourhout, and R. Baets, “Efficient tapering to the fundamental quasi-TM mode in asymmetrical waveguides,” in European Conference on Integrated Optics (ECIO, 2010), paper WeP16.

Fedeli, J.

Fedeli, J. M.

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C. Feng, C. Keong, Y. Hsueh, Y. Wang, and H. Sue, “Modeling of long-term creep behavior of structural epoxy adhesives,” Int. J. Adhes. Adhes.25(5), 427–436 (2005)
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P. T. Lin, V. Singh, J. Hu, K. Richardson, J. D. Musgraves, I. Luzinov, J. Hensley, L. C. Kimerling, and A. Agarwal, “Chip-scale mid-infrared chemical sensors using air-clad pedestal silicon waveguides,” Lab Chip.13, 2161–2166 (2013).
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A. V. Velasco, P. Cheben, P. J. Bock, A. Delage, J. H. Schmid, J. Lapointe, S. Janz, M. L. Calvo, D. Xu, M. Florjanczyk, and M. Vachon, “High-resolution Fourier-transform spectrometer chipwith microphotonic silicon spiral waveguides,” Opt. Lett.38(5), 706–708 (2013)
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M. Langendam, Y. Luijf, L. Hooft, J. DeVries, A. Mudde, and R. Scholten, “Continuous glucose monitoring systems for type I diabetes mellitus (Review),” The Cochrane Library2, (John Wiley & Sons, 2012)

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C. Kopp, S. Bernabe, B. B. Bakir, J. M. Fedeli, R. Orobtchouk, F. Schrank, H. Porte, L. Zimmermann, and T. Tekin, “Silicon photonic circuits: on-CMOS integration, fiber optical coupling, and packaging,” IEEE J. Sel. Top. Quantum Electron.17(3), 498–509 (2011).
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A. H. Harvey, J. S. Gallagher, and J. L. Sengers, “Revised formulation for the refractive index of water and steam as a function of wavelength, temperature and density,” J. Phys. Chem. Ref. Data27(4), 761–774 (1998)
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P. T. Lin, V. Singh, J. Hu, K. Richardson, J. D. Musgraves, I. Luzinov, J. Hensley, L. C. Kimerling, and A. Agarwal, “Chip-scale mid-infrared chemical sensors using air-clad pedestal silicon waveguides,” Lab Chip.13, 2161–2166 (2013).
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S. Keyvaninia, G. Roelkens, D. Van Thourhout, C. Jany, M. Lamponi, A. Le Liepvre, F. Lelarge, D. Make, G. Duan, D. Bordel, and J. Fedeli, “Demonstration of a heterogeneously integrated III-V/SOI single wavelength tunable laser,” Opt. Express21(3), 3784–3792 (2013)
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Verger, F.

J. Charrier, M. Brandily, H. Lhermite, K. Michel, B. Bureau, F. Verger, and V. Nazabal, “Evanescent wave optical micro-sensor based on chalcogenide glass,” Sens. Actuator B-Chem.173, 468–476 (2012).
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A. Densmore, D.-X. Xu, P. Waldron, S. Janz, P. Cheben, J. Lapointe, A. Delâge, B. Lamontagne, J. H. Schmid, and E. Post, “A silicon-on-insulator photonic wire based evanescent field sensor,” IEEE Photon. Technol. Lett.18(23), 2520–2522 (2006)
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Figures (7)

Fig. 1
Fig. 1

Blue curve (with left y-axis): Transmission spectrum of a 1 cm long waveguide with a typical confinement factor of 0.1 and waveguide losses of 2 dB/cm, immersed in a 5.5 mM aqueous glucose solution. The other curves (with right y-axis) represents the change in transmission caused by glucose absorption for different glucose concentrations. This graph is based on reference data from [17].

Fig. 2
Fig. 2

(a) SOI chip design with indication of the microfluidic channels (b) design of the grating coupler and (c) rib waveguide design that is used in the sensor circuit. (d) contour plot of the amplitude of the dominant Ex field of the fundamental TE-mode of a 450 nm wide rib waveguide that is used for evanescent sensing.

Fig. 3
Fig. 3

(a) fabricated optofluidic chip (b) measurement set-up (the optical read-out instrumentation is not shown)

Fig. 4
Fig. 4

Measured water transmission spectrum (left y-axis), compared to the theoretically expected water transmission calculated from a reference measurement and simulated confinement factor (right y-axis)

Fig. 5
Fig. 5

Evolution of the detected power from the signal spiral at different wavelengths when (a) a 70mM glucose solution is applied three times and (b) when five different glucose solutions are applied. The switching moments are indicated by the black line.

Fig. 6
Fig. 6

(a) Procedure to create the virtual water reference spectrum. (b) Extracted absorption spectrum for the three 70 mM solution measurements with the theoretical fit.

Fig. 7
Fig. 7

(a) Extracted absorption spectrum for the different glucose solutions, compared to the theoretical fit that is obtained when using a linear regression model as shown in (b)

Equations (6)

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T = 10 ( Γ A s + A wg ) L
A s = ε gluc C gluc + ε H 2 O ( C H 2 O f w C gluc )
δ δ L ( δ Δ P δ C gluc ) = 0 L opt = 1 Γ ln ( 10 ) A s + ln ( 10 ) A wg
T measurement = P sig , water P ref , air 2 P sig , air P ref , air
E ^ = C pr 36 mM ( C ref C pr ) 2 6 = 1.14 mM
μ x [ x ¯ ± t n 1 , α / 2 s n ]

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