Abstract

Current optical fiber probes for fluorescence spectroscopy struggle with large luminescence background and low detection sensitivities that challenge the detection of fluorescent molecules at sub-micromolar concentration. Here we report the demonstration of a hollow-core photonic crystal fiber (HC-PCF) probe for remote fluorescence sensing with single molecule sensitivity down to nanomolar concentrations, where both the excitation and fluorescence beams are counter-propagating through the same fiber. A 20 μm polystyrene microsphere is used to efficiently excite and collect the fluorescence from the sample solution thanks to a photonic nanojet effect. Compared to earlier work with silica fibers, the new HC-PCF-microsphere probe achieves a 200x improvement of the signal-to-noise ratio for a single molecule detection event, and a 1000x reduction of the minimum detectable concentration. The device is implemented with fluorescence correlation spectroscopy to distinguish between molecules of similar fluorescence spectra based on the analysis of their translational diffusion properties, and provides similar performance as conventional confocal microscopes.

© 2012 OSA

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2012 (1)

2011 (2)

N. K. Singh, J. V. Chacko, V. K. A. Sreenivasan, S. Nag, and S. Maiti, “Ultracompact alignment-free single molecule fluorescence device with a foldable light path,” J. Biomed. Opt. 16, 025004 (2011).
[Crossref] [PubMed]

A. Darafsheh, A. Fardad, N. M. Fried, A. N. Antoszyk, H. S. Ying, and V. N. Astratov, “Contact focusing multimodal microprobes for ultraprecise laser tissue surgery,” Opt. Express 19, 3440–3448 (2011).
[Crossref] [PubMed]

2010 (2)

N. Ma, P. C. Ashok, D. J. Stevenson, F. J. Gunn-Moore, and K. Dholakia, “Integrated optical transfection system using a microlens fiber combined with microfluidic gene delivery,” Biomed. Opt. Express 1, 694–705 (2010).
[Crossref]

P. Haas, P. Then, A. Wild, W. Grange, S. Zorman, M. Hegner, M. Calame, U. Aebi, J. Flammer, and B. Hecht, “Fast Quantitative Single-Molecule Detection at Ultralow Concentrations,” Anal. Chem. 82, 6299–6302 (2010).
[Crossref] [PubMed]

2009 (2)

2008 (5)

2007 (2)

K. Garai, R. Sureka, and S. Maiti, “Detecting amyloid-beta aggregation with fiber-based fluorescence correlation spectroscopy,” Biophys. J. 92, L55–L57 (2007).
[Crossref] [PubMed]

F. H. C. Wong, D. S. Banks, A. Abu-Arish, and C. Fradin, “A Molecular Thermometer Based on Fluorescent Protein Blinking,” J. Am. Chem. Soc. 129, 10302–10303 (2007).
[Crossref] [PubMed]

2006 (5)

2005 (2)

2004 (2)

2003 (3)

J. R. Epstein and D. R. Walt, “Fluorescence-based fibre optic arrays: a universal platform for sensing,” Chem. Soc. Rev. 32, 203–214 (2003).
[Crossref] [PubMed]

U. Utzinger and R. R. Richards-Kortum, “Fiber optic probes for biomedical optical spectroscopy,” J. Biomed. Opt. 8, 121–147 (2003).
[Crossref] [PubMed]

N. Opitz, P. J. Rothwell, B. Oeke, and P. Schwille, “Single molecule FCS-based oxygen sensor (O2-FCSensor): a new intrinsically calibrated oxygen sensor utilizing fluorescence correlation spectroscopy (FCS) with single fluorescent molecule detection sensitivity,” Sensors and Actuators B 96, 460–467 (2003).
[Crossref]

2002 (2)

V. Gerke and S. E. Moss, “Annexins: from structure to function,” Physiol. Rev. 82, 331–371 (2002).
[PubMed]

F. Helmchen, “Miniaturization of fluorescence microscopes using fibre optics,” Exp. Physiol. 87, 737–745 (2002).
[Crossref] [PubMed]

1999 (1)

R. F. Cregan, B. J. Mangan, J. C. Knight, T. A. Birks, P. St. J. Russell, P. J. Roberts, and D. C. Allan, “Single-Mode Photonic Band Gap Guidance of Light in Air,” Science 285, 1537–1539 (1999).
[Crossref] [PubMed]

1998 (1)

M. Pitschke, R. Prior, M. Haupt, and D. Riesner, “Detection of single amyloid β-protein aggregates in the cerebrospinal fluid of Alzheimer’s patients by fluorescence correlation spectroscopy,” Nature Medicine 4, 832–834 (1998).
[Crossref] [PubMed]

1997 (1)

S. Maiti, U. Haupts, and W. W. Webb, “Fluorescence correlation spectroscopy: diagnostics for sparse molecules,” Proc. Natl. Acad. Sci. U.S.A. 94, 11753–11757 (1997).
[Crossref] [PubMed]

1996 (1)

Abu-Arish, A.

F. H. C. Wong, D. S. Banks, A. Abu-Arish, and C. Fradin, “A Molecular Thermometer Based on Fluorescent Protein Blinking,” J. Am. Chem. Soc. 129, 10302–10303 (2007).
[Crossref] [PubMed]

Addison, C. J.

Aebi, U.

P. Haas, P. Then, A. Wild, W. Grange, S. Zorman, M. Hegner, M. Calame, U. Aebi, J. Flammer, and B. Hecht, “Fast Quantitative Single-Molecule Detection at Ultralow Concentrations,” Anal. Chem. 82, 6299–6302 (2010).
[Crossref] [PubMed]

Allan, D. C.

R. F. Cregan, B. J. Mangan, J. C. Knight, T. A. Birks, P. St. J. Russell, P. J. Roberts, and D. C. Allan, “Single-Mode Photonic Band Gap Guidance of Light in Air,” Science 285, 1537–1539 (1999).
[Crossref] [PubMed]

Antoszyk, A. N.

Aouani, H.

H. Aouani, F. Deiss, J. Wenger, P. Ferrand, N. Sojic, and H. Rigneault, “Optical-fiber-microsphere for remote fluorescence correlation spectroscopy,” Opt. Express 17, 19085–19092 (2009).
[Crossref]

J. Wenger, D. Gérard, H. Aouani, and H. Rigneault, “Disposable microscope objective lenses for fluorescence correlation spectroscopy using latex microspheres,” Anal. Chem. 80, 6800–6804 (2008).
[Crossref] [PubMed]

Ashok, P. C.

Astratov, V. N.

Backman, V.

Baker, J. R.

Banks, D. S.

F. H. C. Wong, D. S. Banks, A. Abu-Arish, and C. Fradin, “A Molecular Thermometer Based on Fluorescent Protein Blinking,” J. Am. Chem. Soc. 129, 10302–10303 (2007).
[Crossref] [PubMed]

Birks, T. A.

R. F. Cregan, B. J. Mangan, J. C. Knight, T. A. Birks, P. St. J. Russell, P. J. Roberts, and D. C. Allan, “Single-Mode Photonic Band Gap Guidance of Light in Air,” Science 285, 1537–1539 (1999).
[Crossref] [PubMed]

Blades, M. W.

Boned, A.

Bonod, N.

Calame, M.

P. Haas, P. Then, A. Wild, W. Grange, S. Zorman, M. Hegner, M. Calame, U. Aebi, J. Flammer, and B. Hecht, “Fast Quantitative Single-Molecule Detection at Ultralow Concentrations,” Anal. Chem. 82, 6299–6302 (2010).
[Crossref] [PubMed]

Chacko, J. V.

N. K. Singh, J. V. Chacko, V. K. A. Sreenivasan, S. Nag, and S. Maiti, “Ultracompact alignment-free single molecule fluorescence device with a foldable light path,” J. Biomed. Opt. 16, 025004 (2011).
[Crossref] [PubMed]

Chang, Y.-C.

Chen, Y.

Chen, Z.

Conchonaud, F.

Cregan, R. F.

R. F. Cregan, B. J. Mangan, J. C. Knight, T. A. Birks, P. St. J. Russell, P. J. Roberts, and D. C. Allan, “Single-Mode Photonic Band Gap Guidance of Light in Air,” Science 285, 1537–1539 (1999).
[Crossref] [PubMed]

Darafsheh, A.

Deiss, F.

Devilez, A.

Dholakia, K.

Dintinger, J.

Ebbesen, T. W.

Enderlein, J.

C.B. Müller, A. Loman, V. Pacheco, F. Koberling, D. Willbold, W. Richtering, and J. Enderlein, “Precise measurement of diffusion by multi-color dual-focus fluorescence correlation spectroscopy,” EPL 83, 46001 (2008).
[Crossref]

Epstein, J. R.

J. R. Epstein and D. R. Walt, “Fluorescence-based fibre optic arrays: a universal platform for sensing,” Chem. Soc. Rev. 32, 203–214 (2003).
[Crossref] [PubMed]

Fardad, A.

Ferrand, P.

Flammer, J.

P. Haas, P. Then, A. Wild, W. Grange, S. Zorman, M. Hegner, M. Calame, U. Aebi, J. Flammer, and B. Hecht, “Fast Quantitative Single-Molecule Detection at Ultralow Concentrations,” Anal. Chem. 82, 6299–6302 (2010).
[Crossref] [PubMed]

Fradin, C.

F. H. C. Wong, D. S. Banks, A. Abu-Arish, and C. Fradin, “A Molecular Thermometer Based on Fluorescent Protein Blinking,” J. Am. Chem. Soc. 129, 10302–10303 (2007).
[Crossref] [PubMed]

Fried, N. M.

Frosz, M.

Gachet, D.

Garai, K.

K. Garai, R. Sureka, and S. Maiti, “Detecting amyloid-beta aggregation with fiber-based fluorescence correlation spectroscopy,” Biophys. J. 92, L55–L57 (2007).
[Crossref] [PubMed]

K. Garai, M. Muralidhar, and S. Maiti, “Fiber-optic fluorescence correlation spectrometer,” Appl. Opt. 45, 7538–7542 (2006).
[Crossref] [PubMed]

Gérard, D.

Gerke, V.

V. Gerke and S. E. Moss, “Annexins: from structure to function,” Physiol. Rev. 82, 331–371 (2002).
[PubMed]

Ghenuche, P.

Grange, W.

P. Haas, P. Then, A. Wild, W. Grange, S. Zorman, M. Hegner, M. Calame, U. Aebi, J. Flammer, and B. Hecht, “Fast Quantitative Single-Molecule Detection at Ultralow Concentrations,” Anal. Chem. 82, 6299–6302 (2010).
[Crossref] [PubMed]

Gunn-Moore, F. J.

Haas, P.

P. Haas, P. Then, A. Wild, W. Grange, S. Zorman, M. Hegner, M. Calame, U. Aebi, J. Flammer, and B. Hecht, “Fast Quantitative Single-Molecule Detection at Ultralow Concentrations,” Anal. Chem. 82, 6299–6302 (2010).
[Crossref] [PubMed]

Haupt, M.

M. Pitschke, R. Prior, M. Haupt, and D. Riesner, “Detection of single amyloid β-protein aggregates in the cerebrospinal fluid of Alzheimer’s patients by fluorescence correlation spectroscopy,” Nature Medicine 4, 832–834 (1998).
[Crossref] [PubMed]

Haupts, U.

S. Maiti, U. Haupts, and W. W. Webb, “Fluorescence correlation spectroscopy: diagnostics for sparse molecules,” Proc. Natl. Acad. Sci. U.S.A. 94, 11753–11757 (1997).
[Crossref] [PubMed]

Haustein, E.

E. Haustein and P. Schwille, “Single-molecule spectroscopic methods,” Curr. Opinion Struct. Biol. 14, 531–540 (2004).
[Crossref]

Hecht, B.

P. Haas, P. Then, A. Wild, W. Grange, S. Zorman, M. Hegner, M. Calame, U. Aebi, J. Flammer, and B. Hecht, “Fast Quantitative Single-Molecule Detection at Ultralow Concentrations,” Anal. Chem. 82, 6299–6302 (2010).
[Crossref] [PubMed]

Hegner, M.

P. Haas, P. Then, A. Wild, W. Grange, S. Zorman, M. Hegner, M. Calame, U. Aebi, J. Flammer, and B. Hecht, “Fast Quantitative Single-Molecule Detection at Ultralow Concentrations,” Anal. Chem. 82, 6299–6302 (2010).
[Crossref] [PubMed]

Heifetz, A.

A. Heifetz, S. C. Kong, A. V. Sahakian, A. Taflove, and V. Backman, “Photonic Nanojets,” J. Comput. Theor. Nanosci. 6, 1979–1992 (2009).
[Crossref] [PubMed]

Helmchen, F.

F. Helmchen, “Miniaturization of fluorescence microscopes using fibre optics,” Exp. Physiol. 87, 737–745 (2002).
[Crossref] [PubMed]

Joly, N. Y.

Knight, J. C.

R. F. Cregan, B. J. Mangan, J. C. Knight, T. A. Birks, P. St. J. Russell, P. J. Roberts, and D. C. Allan, “Single-Mode Photonic Band Gap Guidance of Light in Air,” Science 285, 1537–1539 (1999).
[Crossref] [PubMed]

Koberling, F.

C.B. Müller, A. Loman, V. Pacheco, F. Koberling, D. Willbold, W. Richtering, and J. Enderlein, “Precise measurement of diffusion by multi-color dual-focus fluorescence correlation spectroscopy,” EPL 83, 46001 (2008).
[Crossref]

Kong, S. C.

A. Heifetz, S. C. Kong, A. V. Sahakian, A. Taflove, and V. Backman, “Photonic Nanojets,” J. Comput. Theor. Nanosci. 6, 1979–1992 (2009).
[Crossref] [PubMed]

Konorov, S. O.

Lenne, P.-F.

Li, X.

Li, Y.-S.

Loman, A.

C.B. Müller, A. Loman, V. Pacheco, F. Koberling, D. Willbold, W. Richtering, and J. Enderlein, “Precise measurement of diffusion by multi-color dual-focus fluorescence correlation spectroscopy,” EPL 83, 46001 (2008).
[Crossref]

Ma, J.

Ma, N.

Maiti, S.

N. K. Singh, J. V. Chacko, V. K. A. Sreenivasan, S. Nag, and S. Maiti, “Ultracompact alignment-free single molecule fluorescence device with a foldable light path,” J. Biomed. Opt. 16, 025004 (2011).
[Crossref] [PubMed]

K. Garai, R. Sureka, and S. Maiti, “Detecting amyloid-beta aggregation with fiber-based fluorescence correlation spectroscopy,” Biophys. J. 92, L55–L57 (2007).
[Crossref] [PubMed]

K. Garai, M. Muralidhar, and S. Maiti, “Fiber-optic fluorescence correlation spectrometer,” Appl. Opt. 45, 7538–7542 (2006).
[Crossref] [PubMed]

S. Maiti, U. Haupts, and W. W. Webb, “Fluorescence correlation spectroscopy: diagnostics for sparse molecules,” Proc. Natl. Acad. Sci. U.S.A. 94, 11753–11757 (1997).
[Crossref] [PubMed]

Mangan, B. J.

R. F. Cregan, B. J. Mangan, J. C. Knight, T. A. Birks, P. St. J. Russell, P. J. Roberts, and D. C. Allan, “Single-Mode Photonic Band Gap Guidance of Light in Air,” Science 285, 1537–1539 (1999).
[Crossref] [PubMed]

Marguet, D.

Moss, S. E.

V. Gerke and S. E. Moss, “Annexins: from structure to function,” Physiol. Rev. 82, 331–371 (2002).
[PubMed]

Müller, C.B.

C.B. Müller, A. Loman, V. Pacheco, F. Koberling, D. Willbold, W. Richtering, and J. Enderlein, “Precise measurement of diffusion by multi-color dual-focus fluorescence correlation spectroscopy,” EPL 83, 46001 (2008).
[Crossref]

Muralidhar, M.

Nag, S.

N. K. Singh, J. V. Chacko, V. K. A. Sreenivasan, S. Nag, and S. Maiti, “Ultracompact alignment-free single molecule fluorescence device with a foldable light path,” J. Biomed. Opt. 16, 025004 (2011).
[Crossref] [PubMed]

Norris, T. B.

Oeke, B.

N. Opitz, P. J. Rothwell, B. Oeke, and P. Schwille, “Single molecule FCS-based oxygen sensor (O2-FCSensor): a new intrinsically calibrated oxygen sensor utilizing fluorescence correlation spectroscopy (FCS) with single fluorescent molecule detection sensitivity,” Sensors and Actuators B 96, 460–467 (2003).
[Crossref]

Opitz, N.

N. Opitz, P. J. Rothwell, B. Oeke, and P. Schwille, “Single molecule FCS-based oxygen sensor (O2-FCSensor): a new intrinsically calibrated oxygen sensor utilizing fluorescence correlation spectroscopy (FCS) with single fluorescent molecule detection sensitivity,” Sensors and Actuators B 96, 460–467 (2003).
[Crossref]

Pacheco, V.

C.B. Müller, A. Loman, V. Pacheco, F. Koberling, D. Willbold, W. Richtering, and J. Enderlein, “Precise measurement of diffusion by multi-color dual-focus fluorescence correlation spectroscopy,” EPL 83, 46001 (2008).
[Crossref]

Pianta, M.

Pitschke, M.

M. Pitschke, R. Prior, M. Haupt, and D. Riesner, “Detection of single amyloid β-protein aggregates in the cerebrospinal fluid of Alzheimer’s patients by fluorescence correlation spectroscopy,” Nature Medicine 4, 832–834 (1998).
[Crossref] [PubMed]

Popov, E.

Prior, R.

M. Pitschke, R. Prior, M. Haupt, and D. Riesner, “Detection of single amyloid β-protein aggregates in the cerebrospinal fluid of Alzheimer’s patients by fluorescence correlation spectroscopy,” Nature Medicine 4, 832–834 (1998).
[Crossref] [PubMed]

Rammler, S.

Richards-Kortum, R. R.

U. Utzinger and R. R. Richards-Kortum, “Fiber optic probes for biomedical optical spectroscopy,” J. Biomed. Opt. 8, 121–147 (2003).
[Crossref] [PubMed]

Richtering, W.

C.B. Müller, A. Loman, V. Pacheco, F. Koberling, D. Willbold, W. Richtering, and J. Enderlein, “Precise measurement of diffusion by multi-color dual-focus fluorescence correlation spectroscopy,” EPL 83, 46001 (2008).
[Crossref]

Riesner, D.

M. Pitschke, R. Prior, M. Haupt, and D. Riesner, “Detection of single amyloid β-protein aggregates in the cerebrospinal fluid of Alzheimer’s patients by fluorescence correlation spectroscopy,” Nature Medicine 4, 832–834 (1998).
[Crossref] [PubMed]

Rigneault, H.

Roberts, P. J.

R. F. Cregan, B. J. Mangan, J. C. Knight, T. A. Birks, P. St. J. Russell, P. J. Roberts, and D. C. Allan, “Single-Mode Photonic Band Gap Guidance of Light in Air,” Science 285, 1537–1539 (1999).
[Crossref] [PubMed]

Rothwell, P. J.

N. Opitz, P. J. Rothwell, B. Oeke, and P. Schwille, “Single molecule FCS-based oxygen sensor (O2-FCSensor): a new intrinsically calibrated oxygen sensor utilizing fluorescence correlation spectroscopy (FCS) with single fluorescent molecule detection sensitivity,” Sensors and Actuators B 96, 460–467 (2003).
[Crossref]

Russell, P. St. J.

P. Ghenuche, S. Rammler, N. Y. Joly, M. Scharrer, M. Frosz, J. Wenger, P. St. J. Russell, and H. Rigneault, “Kagome hollow-core photonic crystal fiber probe for Raman spectroscopy,” Opt. Lett. 37, 4371–4373 (2012).
[Crossref] [PubMed]

P. St. J. Russell, “Photonic crystal fibers,” J. Ligthwave Technol. 24, 4729–4749 (2006).
[Crossref]

R. F. Cregan, B. J. Mangan, J. C. Knight, T. A. Birks, P. St. J. Russell, P. J. Roberts, and D. C. Allan, “Single-Mode Photonic Band Gap Guidance of Light in Air,” Science 285, 1537–1539 (1999).
[Crossref] [PubMed]

Sahakian, A. V.

A. Heifetz, S. C. Kong, A. V. Sahakian, A. Taflove, and V. Backman, “Photonic Nanojets,” J. Comput. Theor. Nanosci. 6, 1979–1992 (2009).
[Crossref] [PubMed]

Scalora, M.

Scharrer, M.

Schulze, H. G.

Schwille, P.

E. Haustein and P. Schwille, “Single-molecule spectroscopic methods,” Curr. Opinion Struct. Biol. 14, 531–540 (2004).
[Crossref]

N. Opitz, P. J. Rothwell, B. Oeke, and P. Schwille, “Single molecule FCS-based oxygen sensor (O2-FCSensor): a new intrinsically calibrated oxygen sensor utilizing fluorescence correlation spectroscopy (FCS) with single fluorescent molecule detection sensitivity,” Sensors and Actuators B 96, 460–467 (2003).
[Crossref]

Singh, N. K.

N. K. Singh, J. V. Chacko, V. K. A. Sreenivasan, S. Nag, and S. Maiti, “Ultracompact alignment-free single molecule fluorescence device with a foldable light path,” J. Biomed. Opt. 16, 025004 (2011).
[Crossref] [PubMed]

Sojic, N.

Sreenivasan, V. K. A.

N. K. Singh, J. V. Chacko, V. K. A. Sreenivasan, S. Nag, and S. Maiti, “Ultracompact alignment-free single molecule fluorescence device with a foldable light path,” J. Biomed. Opt. 16, 025004 (2011).
[Crossref] [PubMed]

Stevenson, D. J.

Stout, B.

Sureka, R.

K. Garai, R. Sureka, and S. Maiti, “Detecting amyloid-beta aggregation with fiber-based fluorescence correlation spectroscopy,” Biophys. J. 92, L55–L57 (2007).
[Crossref] [PubMed]

Taflove, A.

Then, P.

P. Haas, P. Then, A. Wild, W. Grange, S. Zorman, M. Hegner, M. Calame, U. Aebi, J. Flammer, and B. Hecht, “Fast Quantitative Single-Molecule Detection at Ultralow Concentrations,” Anal. Chem. 82, 6299–6302 (2010).
[Crossref] [PubMed]

Thomas, T.

Turner, R. F. B.

Utzinger, U.

U. Utzinger and R. R. Richards-Kortum, “Fiber optic probes for biomedical optical spectroscopy,” J. Biomed. Opt. 8, 121–147 (2003).
[Crossref] [PubMed]

Walt, D. R.

J. R. Epstein and D. R. Walt, “Fluorescence-based fibre optic arrays: a universal platform for sensing,” Chem. Soc. Rev. 32, 203–214 (2003).
[Crossref] [PubMed]

Webb, W. W.

S. Maiti, U. Haupts, and W. W. Webb, “Fluorescence correlation spectroscopy: diagnostics for sparse molecules,” Proc. Natl. Acad. Sci. U.S.A. 94, 11753–11757 (1997).
[Crossref] [PubMed]

Wenger, J.

Wild, A.

P. Haas, P. Then, A. Wild, W. Grange, S. Zorman, M. Hegner, M. Calame, U. Aebi, J. Flammer, and B. Hecht, “Fast Quantitative Single-Molecule Detection at Ultralow Concentrations,” Anal. Chem. 82, 6299–6302 (2010).
[Crossref] [PubMed]

Willbold, D.

C.B. Müller, A. Loman, V. Pacheco, F. Koberling, D. Willbold, W. Richtering, and J. Enderlein, “Precise measurement of diffusion by multi-color dual-focus fluorescence correlation spectroscopy,” EPL 83, 46001 (2008).
[Crossref]

Wolfbeis, O. S.

O. S. Wolfbeis, “Fiber-optic chemical sensors and biosensors,” Anal. Chem. 78, 3859–3873 (2006).
[Crossref] [PubMed]

Wong, F. H. C.

F. H. C. Wong, D. S. Banks, A. Abu-Arish, and C. Fradin, “A Molecular Thermometer Based on Fluorescent Protein Blinking,” J. Am. Chem. Soc. 129, 10302–10303 (2007).
[Crossref] [PubMed]

Ye, J. Y.

Ying, H. S.

Zheltikov, A.

Zorman, S.

P. Haas, P. Then, A. Wild, W. Grange, S. Zorman, M. Hegner, M. Calame, U. Aebi, J. Flammer, and B. Hecht, “Fast Quantitative Single-Molecule Detection at Ultralow Concentrations,” Anal. Chem. 82, 6299–6302 (2010).
[Crossref] [PubMed]

Anal. Chem. (3)

O. S. Wolfbeis, “Fiber-optic chemical sensors and biosensors,” Anal. Chem. 78, 3859–3873 (2006).
[Crossref] [PubMed]

P. Haas, P. Then, A. Wild, W. Grange, S. Zorman, M. Hegner, M. Calame, U. Aebi, J. Flammer, and B. Hecht, “Fast Quantitative Single-Molecule Detection at Ultralow Concentrations,” Anal. Chem. 82, 6299–6302 (2010).
[Crossref] [PubMed]

J. Wenger, D. Gérard, H. Aouani, and H. Rigneault, “Disposable microscope objective lenses for fluorescence correlation spectroscopy using latex microspheres,” Anal. Chem. 80, 6800–6804 (2008).
[Crossref] [PubMed]

Appl. Opt. (2)

Biomed. Opt. Express (1)

Biophys. J. (1)

K. Garai, R. Sureka, and S. Maiti, “Detecting amyloid-beta aggregation with fiber-based fluorescence correlation spectroscopy,” Biophys. J. 92, L55–L57 (2007).
[Crossref] [PubMed]

Chem. Soc. Rev. (1)

J. R. Epstein and D. R. Walt, “Fluorescence-based fibre optic arrays: a universal platform for sensing,” Chem. Soc. Rev. 32, 203–214 (2003).
[Crossref] [PubMed]

Curr. Opinion Struct. Biol. (1)

E. Haustein and P. Schwille, “Single-molecule spectroscopic methods,” Curr. Opinion Struct. Biol. 14, 531–540 (2004).
[Crossref]

EPL (1)

C.B. Müller, A. Loman, V. Pacheco, F. Koberling, D. Willbold, W. Richtering, and J. Enderlein, “Precise measurement of diffusion by multi-color dual-focus fluorescence correlation spectroscopy,” EPL 83, 46001 (2008).
[Crossref]

Exp. Physiol. (1)

F. Helmchen, “Miniaturization of fluorescence microscopes using fibre optics,” Exp. Physiol. 87, 737–745 (2002).
[Crossref] [PubMed]

J. Am. Chem. Soc. (1)

F. H. C. Wong, D. S. Banks, A. Abu-Arish, and C. Fradin, “A Molecular Thermometer Based on Fluorescent Protein Blinking,” J. Am. Chem. Soc. 129, 10302–10303 (2007).
[Crossref] [PubMed]

J. Biomed. Opt. (2)

N. K. Singh, J. V. Chacko, V. K. A. Sreenivasan, S. Nag, and S. Maiti, “Ultracompact alignment-free single molecule fluorescence device with a foldable light path,” J. Biomed. Opt. 16, 025004 (2011).
[Crossref] [PubMed]

U. Utzinger and R. R. Richards-Kortum, “Fiber optic probes for biomedical optical spectroscopy,” J. Biomed. Opt. 8, 121–147 (2003).
[Crossref] [PubMed]

J. Comput. Theor. Nanosci. (1)

A. Heifetz, S. C. Kong, A. V. Sahakian, A. Taflove, and V. Backman, “Photonic Nanojets,” J. Comput. Theor. Nanosci. 6, 1979–1992 (2009).
[Crossref] [PubMed]

J. Ligthwave Technol. (1)

P. St. J. Russell, “Photonic crystal fibers,” J. Ligthwave Technol. 24, 4729–4749 (2006).
[Crossref]

Nature Medicine (1)

M. Pitschke, R. Prior, M. Haupt, and D. Riesner, “Detection of single amyloid β-protein aggregates in the cerebrospinal fluid of Alzheimer’s patients by fluorescence correlation spectroscopy,” Nature Medicine 4, 832–834 (1998).
[Crossref] [PubMed]

Opt. Express (9)

D. Gérard, J. Wenger, A. Devilez, D. Gachet, B. Stout, N. Bonod, E. Popov, and H. Rigneault, “Strong electromagnetic confinement near dielectric microspheres to enhance single-molecule fluorescence,” Opt. Express 16, 15297–15303 (2008).
[Crossref] [PubMed]

A. Darafsheh, A. Fardad, N. M. Fried, A. N. Antoszyk, H. S. Ying, and V. N. Astratov, “Contact focusing multimodal microprobes for ultraprecise laser tissue surgery,” Opt. Express 19, 3440–3448 (2011).
[Crossref] [PubMed]

J. Wenger, D. Gérard, P.-F. Lenne, H. Rigneault, J. Dintinger, T. W. Ebbesen, A. Boned, F. Conchonaud, and D. Marguet, “Dual-color fluorescence cross-correlation spectroscopy in a single nanoaperture : towards rapid multicomponent screening at high concentrations,” Opt. Express 14, 12206–12216 (2006).
[Crossref] [PubMed]

S. O. Konorov, A. Zheltikov, and M. Scalora, “Photonic-crystal fiber as a multifunctional optical sensor and sample collector,” Opt. Express 13, 3454–3459 (2005).
[Crossref] [PubMed]

Z. Chen, A. Taflove, and V. Backman, “Photonic nanojet enhancement of backscattering of light by nanoparticles: a potential novel visible-light ultramicroscopy technique,” Opt. Express 12, 1214–1220 (2004).
[Crossref] [PubMed]

X. Li, Z. Chen, A. Taflove, and V. Backman, “Optical analysis of nanoparticles via enhanced backscattering facilitated by 3-D photonic nanojets,” Opt. Express 13, 526–533 (2005).
[Crossref] [PubMed]

P. Ferrand, J. Wenger, M. Pianta, H. Rigneault, A. Devilez, B. Stout, N. Bonod, and E. Popov, “Direct imaging of photonic nanojets,” Opt. Express 16, 6930–6940 (2008).
[Crossref] [PubMed]

Y.-C. Chang, J. Y. Ye, T. Thomas, Y. Chen, J. R. Baker, and T. B. Norris, “Two-photon fluorescence correlation spectroscopy through dual-clad optical fiber,” Opt. Express 16, 12640–12649 (2008).
[Crossref] [PubMed]

H. Aouani, F. Deiss, J. Wenger, P. Ferrand, N. Sojic, and H. Rigneault, “Optical-fiber-microsphere for remote fluorescence correlation spectroscopy,” Opt. Express 17, 19085–19092 (2009).
[Crossref]

Opt. Lett. (2)

Physiol. Rev. (1)

V. Gerke and S. E. Moss, “Annexins: from structure to function,” Physiol. Rev. 82, 331–371 (2002).
[PubMed]

Proc. Natl. Acad. Sci. U.S.A. (1)

S. Maiti, U. Haupts, and W. W. Webb, “Fluorescence correlation spectroscopy: diagnostics for sparse molecules,” Proc. Natl. Acad. Sci. U.S.A. 94, 11753–11757 (1997).
[Crossref] [PubMed]

Science (1)

R. F. Cregan, B. J. Mangan, J. C. Knight, T. A. Birks, P. St. J. Russell, P. J. Roberts, and D. C. Allan, “Single-Mode Photonic Band Gap Guidance of Light in Air,” Science 285, 1537–1539 (1999).
[Crossref] [PubMed]

Sensors and Actuators B (1)

N. Opitz, P. J. Rothwell, B. Oeke, and P. Schwille, “Single molecule FCS-based oxygen sensor (O2-FCSensor): a new intrinsically calibrated oxygen sensor utilizing fluorescence correlation spectroscopy (FCS) with single fluorescent molecule detection sensitivity,” Sensors and Actuators B 96, 460–467 (2003).
[Crossref]

Other (1)

P. Kapusta, “Absolute diffusion coefficients: compilation of reference data for FCS calibration,” http://www.picoquant.com/technotes/appnotediffusioncoefficients.pdf

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Figures (5)

Fig. 1
Fig. 1

(a) Scanning electron micrograph of the Kagome-lattice HC-PCF. (b) Transmission losses. The red line indicates the 633 nm wavelength used for excitation and the orange shaded region is the spectral range used for fluorescence collection.(c) Luminescence background spectrum (red) with maximum 11 mW input power and 10 s integration time. The black line is the background noise of the spectrometer. (d) Experimental setup. (e) Computed electric field intensity with a 20 μm polystyrene sphere illuminated by the fundamental Gaussian-shaped fiber mode at λ = 633 nm. (f) Horizontal cut at the best focus plane. (g) Vertical cut along the microsphere center.

Fig. 2
Fig. 2

Fluorescence intensity time trace (a) and correlation function (b) obtained with the HC-PCF and the 20 μm sphere (excitation power 750 μW at the fiber input). The curves in (c) and (d) are for a conventional confocal microscope with a 63x 1.2NA water-immersion objective (excitation power 40 μW). Black lines in (b), (d) are numerical fits using Eq. (1). For both cases, the Alexa Fluor 647 concentration is 3 nM.

Fig. 3
Fig. 3

(a) Number of molecules in the FCS detection volume versus the molecular concentration. The inset shows the corresponding fluorescence correlation functions. (b) Fluorescence count rate computed back to per molecule (red) and background noise (gray) versus the excitation power.

Fig. 4
Fig. 4

Fluorescence correlation functions for the cellular protein Annexin A5b labelled with Cyanine-5 obtained with the HC-PCF-microsphere (a) and the 1.2NA objective (b). the dashed lines are the reference correlation functions for the Alexa Fluor 647 free dye. For all cases, the dye concentration is 13.6 nM.

Fig. 5
Fig. 5

(a) Experimental setup with the HC-PCF combined with a 10x 0.3NA objective and a 2 μm diameter polystyrene microsphere. The inset shows the electric field intensity computed for a 2 μm polystyrene sphere set at the focus of the 0.3NA objective. (b) Fluorescence intensity time trace and correlation function (c) obtained with the HC-PCF (excitation power 500 μW at the fiber input). The curves in (d) and (e) are for a conventional confocal microscope with a 63x 1.2NA water-immersion objective (excitation power 40 μW). For both cases, the Alexa Fluor 647 concentration is 30 nM.

Equations (1)

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g ( 2 ) ( τ ) = 1 + 1 N ( 1 B F ) 2 [ 1 + n T exp ( τ τ T ) ] 1 ( 1 + τ / τ d ) 1 + s 2 τ / τ d

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